What is Muscle physiology

·        Voluntary muscles (supplied by somatic nerves)

o       Skeletal muscle: for locomotion, positional change & convection of respiratory gases.

·        Involuntary muscles: (supplied by autonomic nerves)

o       Cardiac muscle: for pumping the blood

o       Smooth muscle: motor of internal organs & blood vessels. 

Feature	Smooth	Cardiac	Skeletal
Myofibrils	Absent	Present	Present
T tubules	Absent	Short & broad	Long & thin
Depolarization	Spontaneous	Spontaneous	Upon stimulation
Summation	Possible	Not possible	Possible
RMP	Unstable	Stable	Stable
Source of Ca	Extracellular	SR	SR
Neuromuscular junction	Not well defined	Not well defined	Well defined

SKELETAL MUSCLE

·        The muscle mass is separated from neighbouring tissues by à fascia

·        Beneath the fascia, the muscle is covered by à epimysium

·        Muscle fiber bundle or fascicule is covered by à perimysium

·        Each muscle fiber is covered by à endomysium

·        Muscle cell or fibers are à multinucleated with peripheral nuclei located just beneath the sarcolemma.

·        Each striated muscle fiber is invested by a cell membrane à the sarcolemma, which surrounds the sarcoplasm, several mitochondria (sarcosomes) & myofibrils.

Structure of a myofibril

Each myofibril consists of a number of two alternating bands:

Light band: I band - Isotropic in nature (contain only actin filaments)

Dark band: A band - Anisotropic in nature (actin & myosin filaments overlap in this region)

(Isotropic: when polarized light is passed thru the muscle fiber, the light rays are refracted at the same angle)

Z lines or Z plates (plate-like proteins) subdivide each myofibril into striated compartments called sarcomeres (2μm long).

Sarcomere:

The portion of myofibril in btwn two Z lines.

It is the structural & functional unit of skeletal muscle.

H zone: lies in the middle of A band. Contains only myosin filaments.

M line: situated in the middle of H zone. It is formed by myosin binding proteins.

Sarcomere consists of myofilaments à action & myosin filaments

Actin Filaments: Thin filaments, Extend to z line, I band & upto H zone of A band.

Myosin Filaments: Thick filaments, Situated in A band, including the H zone.

During contraction: H zone & I band are shortened and the Z lines come closer.

Types of Skeletal Muscle proteins

Contractile proteins: Actin, Myosin

Regulatory proteins:

·        Skeletal & cardiac muscle – tropomyosin, troponin

·        Smooth muscle - Calmodulin

Nebulin: responsible for positioning of action.

Titin (connectin)

Contractile protein connected with Z disc: Actin

Contractile protein connected with M disc: Myosin

Titin is connected with z disc & M disc

MYOSIN

Myosin I – present in sperms

Myosin II - present in sarcomere (skeletal muscles)

·        Each myosin filament consists of a bundle of myosin-II molecules.

·        Each myosin molecule is made up of 6 polypeptide chains: 2 heavy chains & 4 light chains

·        At one end, the 2 heavy chains twist around each other to form a double helix – the tail.

·        At the other end, both the chains turn away in opposite directions & form – globular head.

·        Each myosin head is attached with 2 light chains (one regulatory & one essential).

·        Each myosin head has 2 sites: an actin binding site & a motor domain with a nucleotide binding pocket (for ATP or ADP + Pi)

·        Conformational changes in the head–neck segment allow the myosin head to “tilt” when interacting with actin (sliding filaments).

·        In the central part of myosin filament (H zone) à Myosin head is absent.

ACTIN

·        Each actin molecule is called F actin & it is a polymer of a small protein called G actin.

·        Actin molecules in actin filament are also arranged in the form of a double helix, which is positioned by the equally long protein nebulin.

·        Each F actin molecule has an active site for the attachment of myosin head.

During rest, Actin is detached from myosin by relaxing (inhibitory) proteins:

·        Tropomyosin: covers the myosin binding sites on F-actin molecules.

·        Troponin which is formed of 3 subunits:

o       Troponin T: binds to tropomyosin

o       Troponin I: binds with actin & prevents the filaments from sliding when at rest

o       Troponin C: has two regulatory bindings sites for Ca2+ at the amino end

Other proteins of the muscle:

·        Actinin: Attaches actin filament to Z line.

·        Desmin: binds Z line with sarcolemma.

·        Nebulin: runs parallel to actin filaments.

·        Titin (connectin): Connected to M line (at its carboxyl end) & Z line (at its amino end). Provides elasticity to the muscle.

Longest known polypeptide chain & comprises 10% of the total muscle mass.

[when the muscle is stretched, titin unfolds itself.

If the stretching is more, it offers resistance & protects the sarcomere from overstretching.]

·        Dystrophin: connects actin filament to to the membrane of muscle cell. It is connected to sarcoglycans of the sarcolemma.

·        Merosin binds the sarcoglycans to the collagen fibrils of the extracellular matrix.

Mutation of these proteins leads to muscular dystrophy (Duchenne muscular dystrophy, limb-girdle dystrophy, congenital muscular dystrophy) implying the degeneration of muscle fibers with increasing muscular weakness.

Sarcotubular System

Formed by: T tubules & L tubules (sarcoplasmic reticulum)

T tubules: Formed by transverse invaginations of the sarcolemma.

Function:

They act as the inward pathway for action potential.

It contains DHPR which are volt sensitive receptors.

Sarcoplasmic Retiuculum (L tubules)

The ER is modified as longitudinal tubules with terminal expansion called – cisternae which store Ca ions & contain RYR1.

Triad of skeletal muscle: T tubule along with terminal cisternae on either side.

They are situated at the junction btwn A band & I band.

When AP reaches DHPR on T tubules, it opens RYR1 on the cisternae à Ca efflux from the cisternae into sarcoplasm.

The released Ca binds with troponin C & uncovers the active sites for myosin on actin.

               

Skeletal muscle formed of:

·        Central contractile part – contains sk. Muscle fibers

·        Peripheral non-contractile ends – elastic non-contractile stretchable tissues

Contraction of sk muscle à shortening of central contractile part (In the form of shortening of sarcomeres.

Types of sk muscle contraction:

Isometric contraction	Isotonic contraction
Shortening of central contractile part = lengthening of peripheral non-contractile parts	Shortening of central contractile part as well as shortening & stretching of peripheral ends.
Total length is constant	Total tension is constant.
Eg: During upright position in lower sk muscles to maintain the body posture.	Could be associated with shortening or lengthening (Lifting or placing down of object with a constant tension (eg: picking of precious objects very slowly).
No external work done.	External work done
In cardiac muscle, this represents isovolumetric contraction, bcoz the muscle length determines the atrial or ventricular volume.)	In cardiac muscle, this represents isobaric contraction, bcoz the muscle force determines the atrial or ventricular pressure.

Auxotonic contractions: muscle length & force both vary simultaneously.

Afterloaded contraction: An isotonic or auxotonic contraction that builds on an isometric one.

                     

Types of skeletal muscle fibers depending on myosin ATPase activity:

Type I or slow twitch fibers – have small diameter

Type II or fast twitch fibers – have large diameter. Have two subtypes, FR (2 A) & FF (2 B).

Each motor unit contains only one type of fiber, this classification also applies to the motor unit.

Based on contraction time, skeletal muscles are classified into two types:

Feature	Red (slow) muscles	Pale (fast muscles)
Fiber type	Type I fibers are more	Type II fibers are more
Myoglobin content	High, so it is red ( for short-term O2 storage)	Less  (FF<< FR)
Blood supply	Rich	Relatively Less
Mitochondria	Rich	Relatively Less
Sarcoplasmic retiuculum	Less extensive	More extensive
Latent period	Long	Short
Power of Contraction	Less powerful	More powerful
Duration of contraction	Sustained contraction (longer contraction time)	Brief and rapid contractions.
Fatigue	Occurs slowly	Occurs quickly (FF > FR)
Energy source	Depends on cellular respiration (aerobic)  Have ­ conc. of fat droplets (high-energy substrate reserves) Rich in oxidative enzymes	Depends on glycolysis (anaerobic) Rich in glycogen (FF > FR)
Examples	Back muscles & gastrocnemius	Soleus (for upright position), Hand muscles & ocular muscles

Each fiber type can also be converted to the other type.

If, prolonged activation of fast-twitch fibers leads to a chronic ­ in cytosolic Ca2+ conc. fast-twitch fibers will be converted to slow-twitch fibers & vice versa.

Motor End-plate (MEP)

It is a type of chemical synapse where transmission of stimuli from a motor axon to a skeletal muscle fiber occurs.

Neurotransmitter à ACh

Receptors at the subsynaptic muscle membrane: N_M(nicotinergic)-ionotropic cholinoceptors

The N-cholinoceptor of the MEP (TypeN_M) has 5 subunits: (2α, 1β,1γ, 1δ), each containing 4 membrane spanning α-helices.

Unlike voltage-gated Na+-channels, the open probability po of the N_M-cholinoceptor is not increased by depolarization, but is determined by the ACh conc. in the synaptic cleft.

Endplate potential:

It is the change in the RMP (-90mV) when an impulse reaches the NMJ. It is a graded potential.

At RMP, binding of ACh molecule to the two α-subunits à brief opening of channel (specific to cations such as Na+, K+, Ca2+) à influx of Na+ ions mainly (& a much lower outflow of K+) à Depolarization of the subsynaptic membrane à endplate potential (EPP)

Miniature end plate current:

Release of a small quantity of Ach from the axon terminal à Single-channel currents à that are summated à yielding miniature end-plate current when spontaneous exocytosis occurs & a vesicle releases a quantum of ACh activating thousands of N_M-cholinoceptors.

Miniature end plate current: May occur spontaneously due to rupture & release of few Ach into synaptic cleft due to muscular contraction.

Can be described as fibrillation – can’t be seen with naked eye.

If they can be seen with naked eye – they are called twitches.

But generation of a postsynaptic action potential requires a motor neuron that triggers exocytosis of a 100 vesicles à opening of 200,000 channels at the same time à neurally induced end-plate current (IEP)

End-plate current (IEP) is dependent on:

·        No. of open channels = total number of channels (n) x the open-probability (po)

[po is determined by the conc. of ACh in the synaptic cleft (up to 1 mmol/L)]

·        Single-channel conductance γ

·        Membrane potential, Em, since the electrical driving “force” (= Em–ENa,K) becomes smaller when Em is less -ve.

[ENa,K = common equilibrium potential for Na+ & K+ (@ 0mV).

It is also called the reversal potential bcoz the direction of IEP (= INa + IK), which enters the cell when Em is -ve (Na+ influx > K+ outflow), reverses when Em is positive (K+ outflow > Na+ influx).

IEP = n . po . γ . (Em – ENa, K)

Because neurally induced EPPs in skeletal muscle are much larger (depolarization by 70 mV) than neuronal EPSPs (only a few mV), single motor axon action potentials are above threshold.

The EPP is transmitted electrotonically to the adjacent sarcolemma, where muscle AP’s are generated by means of voltage-gated Na+ channels à muscle contraction.

Termination of synaptic transmission in MEPs occurs by

(1) Rapid degradation of ACh in the synaptic cleft by acetylcholinesterase localized at the subsynaptic basal membrane, and

(2) Diffusion of ACh out of the synaptic cleft

Neuromuscular blockers

A motor end-plate can be blocked by certain poisons & drugsà muscular weakness & paralysis.

Botulinum neurotoxin: inhibits the discharge of NT’s from the vesicles.

α-bungarotoxin in snake venom: blocks the opening of ion channels.

Receptor blocker:

·        Competitive inhibitors to ACh: Curare-like substances such as (+)-tubocurarine à used as muscle relaxants in surgical operations. Displace ACh from its binding site but do not have a depolarizing effect of their own.

·        ACh-like substances: suxamethonium, succinylcholine or carbamylcholine act like Ach & keep the muscle in a depolarized state.

·        Since they are not destroyed by acetylcholinesterase, the muscle remains in a depolarized state for a long time à paralysis bcoz permanent depolarization also permanently inactivates Na+ channels near the motor end-plate on the sarcolemma.

Drugs stimulating Neuromuscular Junction:

·        Decurarinization: The inhibitory effect of curare can be reversed by cholinesterase inhibitors such as neostigmine.

·        These agents ­Ach conc. in the synaptic cleft, thereby displacing curare.

·        Entry of anticholinesterase agents into intact synapses à ­Ach conc. à paralysis due to permanent depolarization.

Motility and Muscle Types

Active motility is due to either:

·        Interaction of energy-consuming motor proteins (fueled by ATPase) such as myosin, kinesin & dynein with other proteins such as actin or

·        Polymerization & depolymerization of actin & tubulin.

Motor Unit of Skeletal Muscle

Smooth muscle (single unit type) & cardiac muscle fibers pass electric stimuli to each other thru gap junctions or nexus, while

Skeletal muscle fibers are not stimulated by adjacent muscle fibers, but by motor neurons.

[In fact, muscle paralysis occurs if the nerve is severed].

Motor unit (MU): One motor neuron together with all muscle fibers innervated by it.

To supply its muscle fibers, a motor neuron splits into collaterals with terminal branches.

A given motor neuron may supply only 25 muscle fibers (mimetic muscle) or well over 1000 (temporal muscle).

Motor pool: all ant. horn cells & the innervated muscle fibers for one sk. Muscle.

Not all the ant. horn cells are active at the same time i.e not all sk. Muscle fibers contracting at the same moment. There is alternative activity to avoid fatigue.

Recruitment of motor units: gradation of sk. Muscle contraction.

­stimulus strength à activation of more motor units à ­ force of contraction.

­ Frequency of action potential generated by motor cortex.

Graded muscle activity:

·        It is possible because a variable number of motor units can be recruited as needed.

·        The more motor units a muscle has, the more finely graded its contractions.

·        Contractions are much finer in the external eye muscles (2000 motor units), than in the lumbrical muscles (100 motor units).

·        Larger the number of motor units recruited, the stronger the contraction.

·        The no. & type of motor units recruited depends on the type of movement involved (fine or coarse, intermittent or persistent contraction etc.).

·        Strength of each motor unit can be increased by à ­ the frequency of neuronal impulses, as in the tetanization of skeletal muscle.

Stimulation of muscle fibers

Release of Ach at the MEP of sk. muscle à end-plate current that spreads electrotonically à  activation of fast voltage-gated Na+ channels in the sarcolemma à firing of an AP that travels rapidly along the sarcolemma of the entire muscle fiber & penetrates deep into it thru T tubules

[C:N - Genetic defects of these Na+ channels slow down their deactivation à hyperexcitability à extended contraction & delayed muscle relaxation (myotonia).]

The extended muscular activity à ­ K+ efflux to ECF à hyperkalemia à ¯ muscular resting potential à inactivation of Na+ à temporary muscle paralysis (familial hyperkalemic periodic paralysis)

Electromechanical coupling

The conversion of excitation of a muscle into a contraction.

In the skeletal muscle:

·        This process begins with the AP that excites the voltage- sensitive dihydropyridine receptors (DHPR) of the sarcolemma in the region of the triads.

·        The DHPR are arranged in rows & directly opposite them in the adjacent membrane of the SR are rows of Ca2+ channels called ryanodine receptors (RYR1 in sk. muscle).

·        Every other RYR1 is associated with a DHPR.

·        RYR1 open when they directly “sense” by mechanical means an AP-related conformational change in the DHPR.

·        In skeletal muscle, DHPR stimulation at a single site is enough to trigger the coordinated opening of an entire group of RYR1 à ­ reliability of impulse transmission.

In the myocardium:

·        Each DHPR is part of a voltage-gated Ca2+ channel (L-type) of the sarcolemma that opens in response to an action potential.

·        Small quantities of EC Ca2+ enter the cell thru this channel à opening of myocardial RYR2 (trigger effect of Ca2+ or Ca2+ spark).

Ca2+ ions stored in the SR now flow thru the opened RYR1 or RYR2 channels into the cytosol à ­ [Ca2+]i à saturation of the Ca2+ binding sites on troponin-C à canceling of the troponin-mediated inhibitory effect of tropomyosin on filament sliding à strong (high affinity) actin-myosin-II binding.

[C:N - In patients with genetic defects of RYR1, general anesthesia à massive release of Ca2+ à intense muscle contractions à rapid & life threatening increase of body temperature: malignant hyperthermia.]

Sliding filament mechanism of muscle contraction

ATP: essential for filament sliding & hence, for muscle contraction.

Myosin heads act as the motors (motor proteins) of this process à due to their ATPase activity. 

·        Myosin heads connect with actin filaments at a particular angle forming à cross-bridges.

·        Conformational change in the region of nucleotide binding site of myosin, (the spatial extent of which is increased by concerted movement of the neck region) à tilting down of myosin head à power stroke (drawing the thin filament a length of 4–12nm).

·        The head then detaches & “tenses” in preparation for the next “oarstroke” when it binds to actin anew.

·        Kinesin independently advances on the microtubule by incremental movement of its 2 heads, as in tug-of-war. In this case, 50% of the cycle time is “work time” (duty ratio = 0.5).

·        Btwn two consecutive interactions with actin in skeletal muscle, myosin-II “jumps” 36nm (or multiples of 36) to reach the next suitably located actin binding site (C3, jump from a to b).

·        Meanwhile, the other myosin heads working on this particular actin filament must make at least another 10 to 100 oarstrokes of around 4–12nm each.

·        The duty ratio of a myosin head is therefore à 0.1 to 0.01.

·        This division of labor by the myosin heads ensures that a certain percentage of the heads will always be ready to generate rapid contractions.

When filament sliding occurs:

·        Z plates approach each other à shortening of I band

·        Overlap region of thick & thin filaments becomes larger à shortening of H zone

·        Length of the filaments remains unchanged.

Max. muscle shortening occurs à When the ends of thick filaments bump against the Z plate à overlapping of the ends of thin filaments.

Shortening of the sarcomere therefore occurs at both ends of the myosin bundle, but in opposite directions.

Contraction cycle

Binding of ATP to each of the 2 myosin heads (with the aid of Mg2+) à M-ATP complex lying at 45° angle to the rest of the myosin filament à weak affinity of myosin for actin binding.

Influence of ­ cytosolic Ca2+ conc. on the troponin–tropomyosin complex à activation of myosin’s ATPase by actin à hydrolysis of ATP (ATP à ADP + Pi) à formation of A-M-ADP-Pi complex à lifting of myosin heads (conformational change) à ­actin-myosin association constant by 10⁴.

1^st step of power stroke: Detachment of Pi from the complex à 40° tilt of the myosin heads à sliding of actin & myosin filaments past each other.

2^nd step of power stroke: Release of ADP initiates à final positioning of the myosin heads

The remaining A-M complex (rigor complex) is stable & can again be transformed into a much weaker bond when the myosin heads bind ATP anew (“softening effect” of ATP,D4).

­ flexibility of muscle at rest is important for: processes such as cardiac filling or the relaxing of the extensor muscles during rapid bending movement.

If the cytosolic Ca2+ conc. remains high, the D1 to D4 cycle will begin anew. This depends mainly on whether subsequent AP’s arrive. Only a portion of the myosin heads that pull actin filaments are “on duty” (low duty ratio) to ensure the smoothness of contractions.

The Ca2+ ions released from the sarcoplasmic reticulum (SR): continuously pumped back to the SR actively by Ca2+-ATPase (SERCA).

If the RYR-mediated release of Ca2+ from the SR is interrupted, the cytosolic Ca2+ conc. rapidly drops & filament sliding ceases (resting position).

Parvalbumin:

·        It is a protein occuring in the cytosol of fast-twitch muscle fibers (type F).

·        Accelerates muscle relaxation after short contractions by binding cytosolic Ca2+ in exchange for Mg2+.

·        Its binding affinity for Ca2+ is higher than that of troponin, but lower than that of SR’s Ca2+-ATPase.

·        It therefore functions as a “slow” Ca2+ buffer.

During isotonic contractions (where muscle shortening occurs): The course of the filament sliding cycle as described above takes place.

During strictly isometric contractions (tension increases but length remains unchanged): tilting of the myosin heads & the filament sliding cannot take place.

Instead, the isometric force is created thru the deformation of myosin heads.

Skeletal muscle cramp: no ATP

For the myosin head to return back to its resting state, it needs to be energized.

Lack of ATP à sk. muscle cramps

May occur due to ischemia as decreased blood supply à decreased ATP supply.

If it occurs during death à rigor morse.

Muscle fibers of a dead body do not produce any ATP. So, after death:

·        Ca2+ is no longer pumped back into SR

·        ATP reserves needed to break down stable A-M complexes are depleted.

This results in stiffening of the dead body or rigor (firmness) mortis, which passes only after the actin & myosin molecules in the muscle fibers decompose.

Sk. Muscle relaxation is active due to two factors:

·        Energization of myosin head: binding of ATP to myosin head to bring it back to resting state.

·        Active Ca reuptake by longitudinal tubules (by Ca2+ ATPase).

Mechanical Features of Skeletal Muscle

AP’s generated in muscle fibers à ­[Ca2+]i à triggering of contraction

In skeletal muscles, gradation of contraction force is achieved by:

·        Variable recruitment of motor units

·        Changing the AP frequency

Single stimulus always à max. Ca2+ release à max. single twitch of sk. muscle fiber if above threshold (all-or-none response).

But a single stimulus does not induce max. shortening of muscle fiber: bcoz it is too brief to keep the sliding filaments in motion long enough for the end position to be reached.

Muscle shortening continues only if à a 2^nd stimulus arrives before the muscle has completely relaxed after the first stimulus.

Effects of two successive stimuli:

3 different effects are noticed depending upon the interval btwn the two stimuli:

Beneficial effect: when the 2^nd stimulus falls after the relaxation period of 1^st twitch, 2 separate curves are obtained but the force of 2^nd twitch is greater due to ­ temp. à ¯viscosity of muscle after 1^st twitch.

Superposition: if the 2^nd stimulus falls during relaxation period of 1^st twitch, 1^st curve is superimposed by the 2^nd curve.

Summation: If 2^nd stimulus is applied during contraction period, 2 contractions are summed up & single curve is obtained with an amplitude gr8r than the simple muscle curve.

Treppe or Staircase Phenomenon

Gradual increasein force of contraction of muscle when it is stimulated repeatedly with a maximal strength at a low frequency. It is different from summation & tetanus.

Tetanus: summation of contraction without relaxation due to marked ­ in the frequency of excitation.

Tetany: ­ neuromuscular excitability due to hypocalcemia caused by hypoparathyroidism etc

Tetanus

·        It is the sustained maximum contraction of the motor units.

·        It occurs if the frequency of stimulation becomes so high that the muscle can no longer relax at all btwn stimuli.

[It occurs at 20 Hz in slow-twitch muscles & at 60–100 Hz in fast-twitch muscles].

·        Muscle force during tetanus is as much as 4 times larger than that of single twitches.

·        The Ca2+ conc., which decreases to some extent btwn superpositioned stimuli, remains high in tetanus.

Contracture: Not caused by AP’s, but by persistent local depolarization due to:

·        ­[K+]o (K+ contracture) or

·        Drug-induced intracellular Ca2+ release, e.g., in response to caffeine.

The contraction of tonus fibers (specific fibers in external eye muscles & in muscle spindles) is also a form of contracture.

·        Tonus fibers do not respond to stimuli acc. to the all-or-none law, but contract in proportion with the magnitude of depolarization.

·        Magnitude of contraction of tonus fibers regulated by à variation of the cytosolic Ca2+ conc. (not by action potentials!)

·        The individual contractions cannot be detected bcoz the motor units are alternately (asynchronously) stimulated.  

[When apparently at rest, muscles such as the postural muscles are in this involuntary state of tension]

Resting muscle tone:

Continuous & partial contraction of muscles with certain degree of tension. It is maintained by different mechanisms:

·        In skeletal muscle: Regulated by reflexes (reflex tone). It is neurogenic i.e due to the arrival of normal AP’s at the individual motor units. It increases as the state of attentiveness increases.

·        In Smooth & cardiac muscle: It is myogenic i.e muscle themselves control the tone. It depends upon Ca2+ level & no. of cross bridges.

Muscle extensibility

A resting muscle containing ATP can be stretched like a rubber band.

The force required to start the stretching action (extension force at rest) is very small, but increases exponentially when the muscle is under high elastic strain.

Musscle’s resistance to stretch à keeps the sliding filaments in the sarcomeres from separating.

It is due to 2 factors:

·        Fascia (fibrous tissue) – to a small extent

·        Titin (connectin): giant filamentous elastic molecule incorporated in the sarcomere (6 titin molecules per myosin filament).

In the A band: Titin lies adjacent to a myosin filament & helps to keep it in the center of the sarcomere.

In the I band: Titin molecules are flexible & function as “elastic bands” that counteract passive stretching of a muscle & influence its shortening velocity.

Extensibility of titin molecules:

·         Titin molecules can stretch up to 10 times their normal length in sk. muscle & somewhat less in cardiac muscle.

·         It is mainly due to frequent repetition of the PEVK motif (proline-glutamate-valine-lysine).

·         In very strong muscle extension, which represents the steepest part of the resting extensibility curve (_D), globular chain elements called Ig C2 domains also unfold.

·         The quicker the muscle stretches, the more sudden & crude this type of “shock absorber” action will be.

Types of tension in sk. Muscle:

During rest: passive tension – minimal binding btwn actin & myosin, minimal baseline contraction. Sk. Muscle length is shorter than the distance btwn origin & insertion. This leads to their minimal stretching.

During voluntary movement: active tension + passive tension = total tension

[Active force is determined by the magnitude of all potential actin myosin interactions. Hence it varies in accordance with the initial sarcomere length]

Vmax: Maximal velocity of shortening of sarcomere after loading.

Lmax = 2 to 2.2 μm

Maximal length of sarcomere at which maximal tension will be developed.

It is the max. active (isometric) force (F₀) that a skeletal muscle can develop from its resting length.

When (L< Lmax):

Sarcomeres shorten & part of thin filaments overlap à so only forces smaller than F₀ develop.

When L = 70% of Lmax (sarcomere length: 1.65 μm): Thick filaments make contact with the Z disks & F becomes even smaller.

When L > Lmax:

The muscle is greatly pre-extended & can develop only restricted force bcoz à no. of potentially available actin–myosin bridges is reduced.

When extended to 130% or more of Lmax, the extension force at rest becomes a major part of the total muscle force.

Functional differences btwn cardiac muscle & skeletal muscle:

Skeletal muscle	Cardiac muscle
More extensible	Less extensible, so the passive extension force at rest is greater.
Functions in the plateau region of its length–force curve.	Operates in the ascending limb (below Lmax) of its length–force curve without a plateau. So, the ventricle responds to ­ diastolic filling loads by ­ its force development (Frank–Starling mechanism).
	Extension also affects troponin’s sensitivity to Ca2+ à steeper curve
AP’s are of shorter duration. Uses IC Ca2+, so no plateau phase.	AP’s are of much longer duration bcoz  gK¯ & gCa­ temporarily after rapid inactivation of Na+ channels à slow influx of EC Ca2+ à plateau phase of AP. As a result, the refractory period does not end until a contraction has almost subsided. So, tetanus cannot be evoked in cardiac muscle.
Contains motor units.	Has no motor units. The stimulus spreads across all myocardial fibers of the atria & ventricles à all-or-none contraction of both atria & thereafter, both ventricles.
No change	Duration of AP can change the force of contraction (which is controlled by the variable influx of Ca2+ into the cell).

If shortening does not occur à Maximal force & small amount of heat develops.

Greater the force (load) à lower the velocity of an (isotonic) contraction.

Without a stress load à Max. velocity & a lot of heat develops. So, light loads can be picked up more quickly than heavy loads.

The total amount of energy consumed for work & heat is greater in isotonic contractions than in isometric ones.

Muscle power: product of force & shortening velocity.

N· m · s–1 = W

Frank Starling Law

Force of contraction is directly proportional to the initial length of muscle fibers within physiological limits.

Energy Supply for Muscle Contraction

Direct source of chemical energy for muscle contraction à ATP

A muscle cell contains only a limited amount of ATP– only enough to take a sprinter.

So, spent ATP is continuously regenerated to keep the [ATP]i constant, even when large quantities of it are needed.

The three routes of ATP regeneration are:

1. Dephosphorylation of creatine phosphate (for short term peak performance)

2. Anaerobic glycolysis (for medium term high performance, occurs in cytoplasm, faster, produces few molecules of ATP)

3. Aerobic oxdn of glucose & fatty acids (for long term performance, occurs in mitochondria, needs O2, slower, produces large no. of ATP)

Creatine phosphate (CrP):

·        Provides chemical energy needed for rapid ATP regeneration (as routes 2 & 3 are relatively slow)

·        CrP reserve of the muscle is sufficient for short-term high-performance bursts of 10–20 s (e.g., for a 100-m sprint).

              mitochondrial creatine kinase

ADP -------------------------------------- > ATP & Cr

Anaerobic glycolysis

Occurs later than CrP dephosphorylation (after a max. of 30 s).

                                     glucose-6-phosphate

Muscle glycogen -----------------------> Lactic acid (lactate + H+)

Yields 3 ATP molecules for each glucose residue

Aerobic oxidation of glucose & fatty acids

·        Takes place @ 1 min after less productive anaerobic form of ATP regeneration.

·        Glucose must be imported from the liver where it is formed by glycogenolysis & gluconeogenesis.

·        Imported glucose yields only 2 ATP for each molecule of glucose, bcoz one ATP is required for 6-phosphorylation of glucose.

During light exercise: lactate is broken down in the heart & liver whereby H+ ions are used up.

During strenuous exercise: Anaerobic glycolysis must be continued along with aerobic oxdn if it does not supply sufficient quantities of ATP.

For sustained exercise: Aerobic regeneration of ATP from glucose (about 32 ATP per glucose residue) or fatty acids is required.

Cardiac output = HR x stroke volume

·        Total ventilation must be ­ to meet the ­ metabolic requirements of the muscle; the HR then becomes constant.

·        The several minutes that pass before this steady state is achieved are bridged by:

o       Anaerobic energy production

o       ­O2 extraction from the blood

o       Depletion of short-term O2 reserves in the muscle (myoglobin).

·        The interim (short term) btwn the 2 phases is perceived as the “low point” of physical performance.

O2 affinity of myoglobin > Hb, but lower than that of respiratory chain enzymes.

Thus, myoglobin is normally saturated with O2 & can pass on its O2 to the mitochondria during brief arterial O2 supply deficits.

Endurance limit:

In top athletes = 370W (@0.5 HP)

Mainly dependent on the speed at which O2 is supplied & speed of aerobic oxdn.

When the endurance limit is exceeded à steady state cannot occur à continuous ­ in HR

The muscles can temporarily compensate for the energy deficit but the H+-consuming lactate metabolism cannot keep pace with the persistently high level of anaerobic ATP regeneration.

An excess of lactate & H+ ions à lacticacidosis

When endurance limit exceeds by 60%: it is equivalent to max. O2 consumption à sharp ­ in plasma lactate conc. à  anaerobic threshold at 4 mmol/L

No significant increase in performance can be expected after that point (as lactic acid inhibits myosin ATPase as it is very sensitive to acidic pH à Limits sk. Muscle endurance)

Plasma lactate

Aerobic threshold: 2mmol (can be tolerated for prolonged periods of exercise)

Anaerobic threshold: 4mmol (indicate that the performance limit will soon be reached)

Exercise must eventually be interrupted, not bcoz of ­lactate conc., but bcoz of ­ acidosis.

Systemic drop in pH à ­ inhibition of chemical rxns needed for muscle contraction à ATP deficit à rapid muscle fatigue à stoppage of muscle work

                                     

CrP metabolism & anaerobic glycolysis enable the body to achieve 3 times the performance possible with aerobic ATP regeneration, although for only about 40 s.

These processes à O2 deficit that must be compensated for in the post-exercise recovery phase (O2 debt)

The body “pays off” the O2 debt by:

·        Regenerating its energy reserves

·        Breaking down the excess lactate in the liver & heart.

The O2 debt after strenuous exercise is much larger (up to 20 L) than the O2 deficit for several reasons.

PhysicalWork

There are three types of muscle work:

+ve dynamic work: requires muscles involved to alternately contract & relax (e.g., going uphill).

-ve dynamic work: requires muscles involved to alternately extend while braking (braking work) & contract without a load (e.g., going downhill).

Static postural work: requires continuous contraction (e.g., standing upright).

Many activities involve a combination of 2 or 3 types of muscle work.

Outwardly directed mechanical work is produced in dynamic muscle activity, but not in purely postural work.

Purely postural work

Force x distance = 0

Chemical energy is still consumed & completely transformed into a form of heat called maintenance heat (= muscle force x duration of postural work).

­ in blood flow is prevented as the continuously contracted muscle squeezes its own vessels. The muscle then fatigues faster than in rhythmic dynamic work.

Light to moderate exercise: HR soon levels out at a new constant level, and no fatigue occurs.

Strenuous exercise:

·        Muscles require up to 500 times more O2 than when at rest.

·        At the same time, the muscle must rid itself of metabolic products such as H+, CO2 & lactate. Muscle work therefore requires drastic cardiovascular & respiratory changes.

·        In untrained subjects (UT): CO rises to a maximum of 15–20 L/min during exercise

·        Work-related activation of the sympathetic nervous system:

­ the HR up to 2.5 fold

­ the SV up to 1.2 fold

Very strenuous exercise:

·        Must soon be interrupted bcoz the heart cannot achieve the required long-term performance.

·        ­CO: provides more blood for the muscles & the skin (heat loss).

·        Blood flow in the kidney & intestine: reduced by the sympathetic tone below the resting value. Ps rises while Pd remains constant à moderate increase in the mean pressure.

Smaller the muscle mass involved in the work à higher the increase in B.P

Hence, the B.P increase in arm activity (cutting hedges) is higher than that in leg activity (cycling).

[C:N- In patients with coronary artery disease or cerebrovascular sclerosis, arm activity is therefore more dangerous than leg activity due to the risk of myocardial infarction or brain hemorrhage.]

Muscular blood flow

At the maximum work level, blood flow in 1 kg of active muscle rises to: 2.5 L/min @10% of the max. CO

Hence, no more than 10 kg of muscle (<1/3 the total muscle mass) can be fully active at any one time.

Vasodilatation (for ­blood flow) achieved thru: local chemical influences (PCO2­, PO2­, pH¯) or NO release.

During physical exercise:

Feature	Resting value	During exercise (max. value)
Ventilation (V.E)	7.5 L/min	90 to 120 L/min
Respiratory rate		40–60 min–1max
Tidal volume		2 L
O2 consumption (V.O2)	0.3 L/min	3 L/min (due to­O2 consumption in tissues)
Respiratory equivalent (V.E/V.O2)	25 (i.e 25 L of air has to be ventilated to take up 1 L of O2 at rest)	40–50
Pulmonary transit time (Minimal time sufficient for gas exchange)	0.75s	0.25s (Time less than 0.25s, no proper gas exchange)

¯pH & ­ temp. shift the O2 binding curve towards the right.

O2 consumption: calculated as the arteriovenous difference in O2 conc. =

avDO2 (L/L blood) x Blood flow (L/min)

Maximum O2 consumption (V.O2 max) is defined as:

V. O2 max = HRmax· SVmax · avDO2max

Ideal measure of physical exercise capacity: V.O2 max per body weight

Physical Fitness and Training

Physical exercise capacity can be measured by using à ergometry.

Ergometry: assesses the effects of exercise on physiological parameters such as V.O2, respiration rate, HR & plasma lactate conc.

Measured physical power (performance) is expressed in: watts(W) or W/kg body weight (BW).

In bicycle ergometry: a brake is used to adjust the watt level.

In “uphill” ergometry: a treadmill is set at an angle α.

Margaria step test: the test subject is required to run up a staircase as fast as possible after a certain starting distance.

Short-term performance tests (10–30 s): measure performance achieved thru rapidly available energy reserves (CrP, glycogen).

Medium-term performance tests: measure performance fueled by anaerobic glycolysis.

Longer term aerobic exercise performance:  measure performance fueled thru oxdn of glucose & FFA by measuring V.O2 max.

In strenuous exercise (2/3 the max. physical capacity or more), aerobic mechanisms do not produce enough energy, so anaerobic metabolism must continue as a parallel energy source à lactacidosis.

Physical training

Raises & maintains the physical exercise capacity.

There are 3 types of physical training strategies:

Motor learning	Endurance training	Strength training
­ rate & accuracy of motor skills	Improves submaximal long-term performance	Improves max. short-term performance level
e.g., typewriting	e.g., running a marathon	e.g., in weight lifting
These activities primarily involve the CNS	To ­ the oxidative capacity of slow-twitch motor units*	To ­ muscle mass by ­ the size of the muscle fibers (hypertrophy) & to ­ the glycolytic capacity of type F motor units.

*e.g., by ­ the mitochondrial density, ­CO à ­ V. O2 max à ­ heart weight à ­SV & ­ tidal volumes à very low resting HR & respiratory rates.

Trained athletes: can therefore achieve larger increases in CO & ventilation.

In individuals practicing endurance training, exercise-related rise in the lactate conc. is also lower & occurs later than in UT.

V.O2 max of a healthy individual is limited by à  the cardiovascular capacity & NOT the respiratory capacity.

Excessive physical exercise causes à muscle soreness & stiffness (not due to lactic acid accumulation), but sarcomere microtrauma à muscle swelling & pain.

During exercise: contraction of muscle squeezes the blood vessels.

Veins are squeezed à  impaired venous drainage à so the metabolites & lactic acid cannot escape.

[Exercise increases venous drainage for the veins in between the sk. Muscles.]

Since the arterial blood pressure is high, it can overcome the sk. Muscle pressure & flow thru them.

Accumulation of metabolites (due to protein breakdown & lactate production) in the sarcomere à ­ osmotic pressure à extraction of water from ECF à swelling à ¯ blood flow à reflex tension à pain

Muscle ache à sign of microinflammation.

Fatigue: decreased sk. Muscle contraction

Neuromuscular fatigue: repeated stimulation of sk. Muscle by motor nerve. It is due to ¯ time for Ach production.

Depression: ¯ descending motor signals from the brain (motor efferent impulses), despite no sk. muscle work being done.

Muscle fatigue: may be peripheral or central.

Peripheral fatigue: caused by the exhaustion of energy reserves & accumulation of metabolic products in the active muscle. This is particularly quick to occur during postural work.

Central fatigue: characterized by work-related pain in the involved muscles & joints that prevents the continuation of physical exercise or decrease the individual’s motivation to continue the exercise.

Myasthemia Gravis

My – muscle, Athemia – weakness, Grave – generalized

Autoimmune disease leading to formation of antibodies against Ach receptors.

Anticholinesterase is given to increase Ach conc. so that Ach can find the receptors.

·        Digitalis à blocks Na/K pump in the heart

·        Single action potential is called à Spike potential

·        All or none rule: nerve & cardiac muscle.

·        The Na channels have 2 gates: activation gate (outside) & inactivation gate (inside).

·        The cell membrane contains more K+ leaky channels than Na. So the inside of the membrane become –ve.

·        Ionic basis for depolarization: Decreased membrane potential due to Na+ influx.

·        Peak of ascending limb of depolarization at à 35mv

·        We are using ATP not immediately during the action potential.

·        But it is used later after the action potential and during the resting potential to stabilize the membrane.

·        Motor neuron – ant. (ventral) horn cell.

·        At the motor end plate: Voltage gated Ca+ chanels

·        ACh receptors in neuromuscular junction: Ionotropic, ligand gated, nicotinic cholinergic, Na+ channels

·        Partial depolarization depends on the amount of Ach released.

·        Threshold level = -ve 40 – 45mV

Thanks :medicalpptonline.blogspot.com

Cappadocia, Turkey

 

Lying in south central Turkey, the moonscaped region of Cappadocia, southeast of Ankara, is most famous for unique geological features called fairy chimneys. The large, cone-like formations were created over time by erosion of the relatively soft volcanic ash around them. Past cultures have dug into them to create dwellings, castles (like Uchisar) and even entire underground cities like Kaymakli and Derinkuyu, used as hiding places by early Christians. Nearby Kayseri is the gateway to the area.

Kovan islamic history song

Water jet cutting !!

A look inside the physics of achieving high-pressure water for waterjet cutting

The energy required for cutting materials is obtained by pressurizing water to ultra-high pressures and forming an intense cutting stream by focusing this high-speed water through a small, precious-stone orifice. There are two main steps involved in the waterjet cutting process.

1. The Electric Servo Pump generally pressurizes normal tap water at pressure levels above 50,000 psi; to produce the energy required for cutting.
2. Water is then focused through a small precious stone orifice to form an intense cutting stream. The stream moves at a velocity of up to 3 times the speed of sound, depending on how the water pressure is exerted.

The process is applicable to both water only and abrasive jets. For abrasive cutting applications, abrasive garnet is fed into the abrasive mixing chamber, which is part of the cutting head body, to produce a coherent and an extremely energetic abrasive jet stream.

To achieve these pressures, water is introduced into the unit by way of a booster pump and filter. This filtering process is very important as water must be clean before reaching ultra-high pressures in order to protect the high-pressure parts and provide a consistent cutting stream.

A water treatment system is sometimes needed to remove harmful minerals from the water. After being filtered, the water enters the high pressure cylinder where it is pressurized to the desired level.

The water is then carried to either an abrasive or straight-water cutting nozzle, depending on the application. The cutting nozzle can be stationary or integrated into motion equipment, which allows for intricate shapes and designs to be cut. Motion equipment can range from a simple cross-cutter to 2D systems and 3D machines as well as multiple axis robots. CAD/CAM software combined with CNC controllers translate drawings or commands into a digitally programmed path for the cutting head to follow.Cutting harder materials requires adding a fine mesh abrasive to the cutting stream. Various abrasive materials which can be used include olivine, garnet, and corundum with a particle size of between 50 to 120 mesh. When abrasive is required, TECHNI Waterjet provides an abrasive unit consisting primarily of an abrasive hopper, an abrasive feeder system, a pneumatically controlled on/off valve, and the abrasive cutting nozzle which contains the specialized mixing chamber.

The abrasive is first stored in the pressurized hopper and travels to a metering assembly, which controls the amount of particles fed to the nozzle. The abrasive is then introduced into the cutting stream in a special mixing chamber within the abrasive cutting head. Abrasive cutting allows harder materials to be cut at a faster rate by accelerating the erosion process. After the cut, residual energy from the cutting stream is dissipated in a catcher tank, which stores the kerf material and spent abrasive.

Relationship Between Increased Pressure and Cutting Speed

As pressure increases the power requirement increases proportionately and therefore with a given amount of available power the flow rate must be proportionately reduced, by using a smaller orifice, as shown in the commonly used formula P (Power) = p (pressure) x q (water flow rate).

For example, a 50% increase in pressure will require a 50% increase in power unless there is an equivalent reduction in flow rate (using a smaller orifice). Higher pressure gives an increase in cutting speed for a given amount of power, as higher pressures and lower volumes result in higher velocity of the water leaving the cutting head, which is a more efficient transfer of power to kinetic energy (the energy used in the cutting process).

This efficiency comes about because increasing velocity is a more efficient way of increasing the kinetic energy stored in the particles of abrasive hitting the work-piece. This is illustrated through another commonly used formula E=M V², where by increasing the velocity has a squared affect on the kinetic energy, compared to increasing the mass which has a linear affect. Therefore, in theory if we increase the pressure by 50%, but decrease the volume by 33% we use the same amount of power but get an increase in the velocity of 50%, which has the effect
of increasing the kinetic energy by 48.5%, as illustrated in the formula E=0.666 (33% reduction in water mass) x 1.5² (50% increase in velocity) therefore E = 1.485 (48.5% increase in kinetic energy). However, this illustration is only relevant for Water Only cutting, as the mass of the abrasive has not yet been taken into account.

Abrasive cutting dramatically increases the cutting capabilities of a waterjet by accelerating the abrasive particles at the work piece where each particle takes out a small gouge of the work piece material during impact. If all the abrasive particles were to hit the work piece in the same condition, but at the higher velocity, the same equation as above would be true. However, the major factor that affects what actually happens is that the abrasive particles get smashed to a very fine powder when hit by the high velocity water stream during the initial introduction of the abrasive to the stream, and more gets destroyed throughout the focussing tube 1 The intensity of the disintegration of the abrasive particles depends on the water pressure. The result is that at 60,000psi, only about 45% of the abrasive material reaches the work piece in an affective cutting condition. This % drops to about 22% (or less depending on the quality of abrasive) at 90,000 psi. The net result is that there is therefore only a very small net increase in cutting speed when pressure is increased, for an equivalent amount of power. This can be illustrated in simplified terms for 60,000psi as E=0.45 (45% effective garnet) x 1² therefore E=0.45, and 90,000psi as E=0.22 (22% effective garnet) x 1.5² (50% increase in velocity) therefore E=0.49, or a 9% increase in cutting speed for a 50% increase in pressure.

The Cost of Higher Pressures

Another important consideration before deciding to increase pressure is the significant increase in the capital cost, maintenance cost, consumable cost and increased machine downtime.

Pressure (also known as force or load) has a non-linear relationship with fatigue-related wear, and for many mechanical machine components, it has a cubed (x³) relationship. For example, the ISO formula for calculating bearing wear is

L = (C/P)3
L = life
C= rated load
P = actual load

That means that a 50% increase in pressure will reduce the design life of many mechanical components by about 70% or adversely by reducing pressure by 33%, say from 90,000psi to 60,000psi, the life of many components will increase by 330%.

As a result, in order to make pumps and cutting heads that last for reasonable amounts of time at extreme pressures like 90,000psi, manufacturers are forced to use very expensive exotic materials, because metal fatigue becomes the dominant failure mechanism.. The cost of components and consumables that experience high pressures over 66,000psi (such as dynamic and static seals, check valves, tubing and high- and low-pressure cylinders) are therefore typically 50-300% higher than standard waterjet components.

The other factor in the pricing of such components is competition, as only a few manufacturers are currently capable of producing those parts that are resistant to wear and failure at high pressures. As a consequence, the competition to bring down prices doesn’t yet exist.

For instance, a standard focussing tube rated to 60,000psi sells for approx. $100, while a 90,000psi rated tube sells for around $300. Moreover, even with the more exotic and expensive components designed for 90,000psi, their life remains well below that of traditional waterjet parts operating with up to 60,000psi. This means increased down time and higher maintenance labour costs, on top of the higher component prices and more frequent part replacements.

What is Lithium aluminium hydride

Lithium aluminium hydride, commonly abbreviated to LAH, is an inorganic compound with the chemical formula LiAlH4. It was discovered by Finholt, Bond and Schlesinger in 1947. This compound is used as a reducing agent in organic synthesis, especially for the reduction of esters, carboxylic acids, and amides. The solid is dangerously reactive toward water, releasing gaseous hydrogen (H2). Some related derivatives have been discussed for hydrogen storage.

LAH is a colorless solid, but commercial samples are usually gray due to contamination.This material can be purified by recrystallization from diethyl ether. Large-scale purifications employ a Soxhlet extractor. Commonly, the impure gray material is used in synthesis, since the impurities are innocuous and can be easily separated from the organic products. The pure powdered material is pyrophoric, but not its large crystals. Some commercial materials contain mineral oil to inhibit reactions with atmospheric moisture, but more commonly it is packed in moisture-proof plastic sacks.

LAH violently reacts with water, including atmospheric moisture. The reaction proceeds according to the following idealized equation:
  
LiAlH4 + 4 H2O → LiOH + Al(OH)3 + 4 H2

This reaction provides a useful method to generate hydrogen in the laboratory. Aged, air-exposed samples often appear white because they have absorbed enough moisture to generate a mixture of the white compounds lithium hydroxide and aluminium hydroxide.
LAH crystallizes in the monoclinic space group P21/c. The unit cell has the dimensions: a = 4.82, b = 7.81, and c = 7.92 Å, α = γ=90° and β=112°. In the structure, Li+ centers are surrounded by five AlH−4 tetrahedra. The Li+ centers are bonded to one hydrogen atom from each of the surrounding tetrahedra creating a bipyramid arrangement. At high pressures (>2.2 GPa) a phase transition may occur to give β-LAH.
X-ray powder diffraction pattern of as-received LiAlH4. The asterisk designates an impurity, possibly LiCl.
Preparation
LiAH was first prepared from the reaction between lithium hydride (LiH) and aluminium chloride:

4 LiH + AlCl3 → LiAlH4 + 3 LiCl

In addition to this method, the industrial synthesis entails the initial preparation of sodium aluminium hydride from the elements under high pressure and temperature:

Na + Al + 2 H2 → NaAlH4

LiAlH4 is then prepared by a salt metathesis reaction according to:

NaAlH4 + LiCl → LiAlH4 + NaCl

which proceeds in a high yield of LAH. LiCl is removed by filtration from an ethereal solution of LiAH, with subsequent precipitation of LiAH to yield a product containing around 1% w/w LiCl.

A History of Violence Movie

Tom Stall is living a happy and quiet life with his lawyer wife and their two children in the small town of Millbrook, Indiana, but one night their idyllic existence is shattered when Tom foils a vicious attempted robbery in his diner. Sensing danger, he takes action and saves his customers and friends in the self-defense killings of two-sought-after criminals. Heralded as a hero, Tom's life is changed overnight, attracting a national media circus, which forces him into the spotlight. Uncomfortable with his newfound celebrity, Tom tries to return to the normalcy of his ordinary life only to be confronted by a mysterious and threatening man who arrives in town believing Tom is the man who's wronged him in the past. As Tom and his family fight back against this case of mistaken identity and struggle to cope with their changed reality, they are forced to confront their relationships and the divisive issues which surface as a result.

• Rating:
  R (for strong brutal violence, graphic sexuality, nudity, language and some drug use)
• Genre:
  Action & Adventure, Drama, Mystery & Suspense
• Directed By:
  David Cronenberg
• Written By:
  Josh Olson, Josh Olsen
• On DVD:
  Mar 14, 2006
• Box Office:
  $31,500,000.00
• Runtime:
  96 minutes
• Studio:
  New Line Cinema
  
  

ஒரு அமைதியான குடும்பம்... கணவன் ஒரு உணவகம் நடத்துகிறார்... , 2 கொலைகாரர்கள் உணவகத்தில் புகுந்து கலாட்டா செய்கிறார்கள்... உணவகத்தில் வேலை செய்யும் பெண்ணை பலாத்காரம் செய்ய முயல்கையில் ஜஸ்ட் லைக் தட் அவர்கள் இருவரையும் போட்டு தள்ளுகிறார்...

ஊரே அவரை ஹீரோவாக பார்க்கிறது.. ஆனால் மீண்டும் பிரச்சனை வேறு ரூபத்தில் வருகிறது ஒரு டான் கும்பல் வந்து அவரை வேறு பெயர் சொல்லி அழைக்கிறது... வேறு ஒரு கடந்த காலம் அவருக்கு இருப்பதாக சொல்கிறது... அவரை அழைத்து போக முயற்சிக்கிறது.. அப்பொழுது நடக்கும் சண்டையில் மீண்டும் அந்த குழுவை சேர்ந்த 3 பேரை அசால்ட்டாக போட்டு தள்ளுகிறார்... அவரின் செயலை பார்த்து மனைவிக்கு சந்தேகம் வர... ,"நீங்க யாரு பாம்பேல.. த...சீ.. பிலடெல்பியாவில் நீங்க என்னவா இருந்தீங்கன்னு கேக்குறாங்க"...

உண்மையில் அந்த டான் குழுவின் 'தலை'களில் இவரும் ஒருவர்.. வன்முறை பிடிக்காமல் அடையாளம் மாற்றி இங்கு வந்து அமைதியான வாழ்க்கை வாழ்வதாக... உண்மையை சொல்கிறார்... இதனால் குடும்பத்தில் குழப்பம் நடுவில் அந்த குழுவில் இருந்து அழைப்பு.. 'நீ இங்க வர்றியா நான் அங்க வரவான்னு மிரட்டல்..' யார்கிட்டயும் சொல்லாமல் கிளம்பி போறார்...

அந்த குழுவை சந்திக்கிறார்... அமைதியை விரும்புவதாக சொல்கிறார்.. ஆனால் அவர்கள் இவரை கொல்ல முயற்சிக்க.. அவர்களுடனான சண்டையில் அவர்களாய் வென்றாரா... குடும்பம் என்ன ஆகிறது என்பதை படத்தில் பாருங்கள்.. ;) Interesting Movie.. :)

Movie Name : A history of violence.

Harvard scientists just turned hydrogen into metal

More than 80 years after it was first predicted scientists at Harvard turned hydrogen into metal, and it could revolutionize our planet.

They did it by subjecting hydrogen to extremely high pressures, which changed it from a liquid to a solid.

The resulting material could be used as a superconductor, which would work at room temperature.

This would save lots of energy and money because current superconductors only work at below -269°C.

It could also be used to make MRI scanners and power lines cheaper and more efficient too.

In 1935, scientists predicted that the element hydrogen could become a metal if subjected to enough pressure. Teams have been attempting to confirm the prediction ever since, but have not been able to construct a vise capable of squeezing the element enough without breaking the equipment.

But a team of scientists at Harvard University published a paper this week in the peer-reviewed journal Science saying they managed to squeeze hydrogen in a diamond vise to the point that the element became reflective, a key property of metals.

The study is not merely a parlor trick. Metallic hydrogen is thought to be a superconductor, meaning it could conduct electricity without any resistance. Electricity traveling through normal circuits loses energy to resistance over time, often in the form of heat. This is why it is harder to send electrical currents (say, through the electricity grid) over long distances than short ones. But a current traveling through a superconducting material loses nearly zero energy.

Superconductive metals are used to make the magnets for devices such as hospital MRI machines and particle accelerators such as CERN. The trouble with many superconductors is that the materials now used need to be cooled to extremely low temperatures in order to work, which is expensive.

It is also possible that metallic hydrogen material may be "metastable," according to Science Magazine. This means that, once formed, it may retain its metallic properties even at normal temperatures and pressure levels, like diamonds. If so, it could conduct electricity at nearly 100 percent efficiency in normal conditions. Again, this could dramatically reduce the costs of transferring electrical currents, meaning more powerful and efficient electric motors, and a far more efficient electrical grid.

Scientists have been searching for such a material almost as long as they have known about superconductivity.

Of course, the study has its critics. Eugene Gregoryanz, a physicist at the University of Edinburgh, told Science Magazine he sees a several problems with the experiment's procedures.

"The word garbage cannot really describe it," said Gregoryanz, of the experiment.

The video below, from Harvard, discusses the discovery in detail:

The actual size of the entrance at the Great Pyramid of Giza

 

The entrance to the Great Pyramid is on the north side, about 59 feet (18 metres) above ground level. A sloping corridor descends from it through the pyramid’s interior masonry, penetrates the rocky soil on which the structure rests, and ends in an unfinished underground chamber. From the descending corridor branches an ascending passageway that leads to a room known as the Queen’s Chamber and to a great slanting gallery that is 151 feet (46 metres) long. At the upper end of this gallery, a long and narrow passage gives access to the burial room proper, usually termed the King’s Chamber. This room is entirely lined and roofed with granite. From the chamber two narrow shafts run obliquely through the masonry to the exterior of the pyramid; it is not known whether they were designed for a religious purpose or were meant for ventilation. Above the King’s Chamber are five compartments separated by massive horizontal granite slabs; the likely purpose of these slabs was to shield the ceiling of the burial chamber by diverting the immense thrust exerted by the overlying masses of masonry.

Adi Sankaracharya’s Soundarya Lahari

Translated by P. R. Ramachander

Introduction

Soundarya Lahari meaning waves of beauty consists of two parts viz. Ananda Lahari meaning waves of happiness (first 41 stanzas) and Soundarya Lahari(the next 59 stanzas). It is believed that Lord Ganesha himself has etched the Ananda Lahari on Mount Meru(Some people believe that Sage Pushpa Dhantha did the etching).It was read from there by Sage Gouda Pada who taught it to Adhi Sankara. Adhi Sankara himself added the rest of the 59 stanzas and completed it.

These 100 stanzas are supposed to be the foremost among Manthra literature. It is also believed that by Making suitable Yanthras and reciting particular stanzas and worshipping the yantras almost anything can be obtained in the world .There are more thn 36 commentries to Soundarya Lahari written in Sanskrit itself.Of them the most famous is that written by Lakshmi Dhara alias Lalla,His commentary is used to understand the meaning of the different verses.Though there are large number of translations and commentaries of Soundraya Lahari available this is perhaps the first time an attempt is made by a mere novice to translate them in to English verse. The aim is to bring to the notice of the devotes who know English better than other languages , the majesty of the medium of worship called Soundarya Lahari.A transliteration in roman script is also given. May all those who read this be drenched forever by this “Wave of happiness”

Part I – Ananda Lahari (The waves of happiness)*

1
Shivah shakthya yukto yadi bhavati shaktah prabhavitum
Na chedevam devo na khalu kusalah spanditumapi;
Atas tvam aradhyam Hari-Hara-Virinchadibhir api
Pranantum stotum vaa katham akrta-punyah prabhavati

Lord Shiva, only becomes able.
To do creation in this world.
along with Shakthi
Without her,
Even an inch he cannot move,
And so how can, one who does not do good deeds,
Or one who does not sing your praise,
Become adequate to worship you
Oh , goddess mine,
Who is worshipped by the trinity.

2

(Attracting all the world)&
Taniyamsam pamsum tava carana-pankeruha-bhavam
Virincih sanchinvan virachayati lokan avikalam;
Vahaty evam Shaurih katham api sahasrena shirasaam
Harah samksudy’ainam bhajati bhajati bhasito’ddhalama-vidhim.
Lord Brahma ,the creator of yore,
Selects a dust from your feet,
And creates he this world,
The great Adisesha* with his thousand heads,
Some how carries a dust of your feet,
With effort great,
And the great Lord Rudra,
Takes it and powders it nice,
And uses it as the holy ash.

3
(Attainment of all knowledge)
Avidyanam antas-timira-mihira-dweeppa-nagari
Jadanam chaitanya-stabaka-makaranda-sruti jhari
Daridranam cinta-mani-gunanika janma-jaladhau
Nimadhanam damshtra mura-ripu-varahasya bhavati.

The dust under your feet, Oh Goddess great,
Is like the city of the rising sun,
That removes all darkness , unfortunate,
From the mind of the poor ignorant one,
Is like the honey that flows ,
From the flower bunch of vital action,
To the slow witted one,
Is like the heap of wish giving gems,
To the poorest of men,
And is like the teeth of Lord Vishnu
In the form of Varaha,
Who brought to surface,
The mother earth,
To those drowned in this sea of birth.

4
(Removal of all fears, Curing of diseases)
Tvad anyah paanibhyam abhaya-varado daivataganah
Tvam eka n’aivasi prakatita-var’abhityabhinaya;
Bhayat tratum datum phalam api cha vancha samadhikam
Saranye lokanam tava hi charanaveva nipunav..

Oh, She who is refuge to all this world,
All gods except you mother,
Give refuge and grants wishes,
Only by their hand.
But only you mother
Never show the world in detail,
The boons and refuge that you can give,
For even your holy feet will suffice,
To remove fear for ever,
And grant boons much more than asked.

5
(Attracting of sexes to each other)
Haris tvam aradhya pranata-jana-saubhagya-jananim
Pura nari bhutva Pura-ripum api ksobham anayat;
Smaro’pi tvam natva rati-nayana-lehyena vapusha
Muninam apyantah prabhavati hi mohaya mahatam.

You who grant all the good things,
To those who bow at your feet,
Was worshipped by the Lord Vishnu,
Who took the pretty lovable feminine form,
And could move the mind of he who burnt the cities,
And make him fall in love with him.
And the God of love , Manmatha,
Took the form which is like nectar,
Drunk by the eyes by Rathi his wife,
After venerating you,
Was able to create passion ,
Even in the mind of Sages the great.

6
(Getting sons as progeny)
Dhanun paushpam maurvi madhu-kara-mayi pancha visikha
Vasantaha samanto Malaya-marud ayodhana-rathah;
Tatha’py ekah sarvam Himagiri-suthe kam api kripaam
Apangat te labdhva jagadidam Anango vijayate

Oh ,daughter of the mountain of ice,
With a bow made of flowers,
Bow string made of honey bees,
Five arrows made of only tender flowers,
With spring as his minister,
And riding on the chariot of breeze from Malaya mountains
The god of love who does not have a body,
Gets the sideways glance of your holy eyes,
And is able to win all the world alone.

7
(Seeing the Goddess in person, Winning over enemies)
Kvanat-kanchi-dama kari-kalabha-kumbha-stana-nata
Pariksheena madhye parinata-sarachandra-vadana;
Dhanur banan pasam srinim api dadhana karatalaii
Purastad astam noh Pura-mathitur aho-purushika.

With a golden belt,
Adorned by tiny tingling bells,
Slightly bent by breasts like the two frontal globes
Of an elephant fine,
With a thin pretty form,
And with a face like the autumn moon,
Holding in her hands,
A bow of sugar cane , arrows made of flowers,
And the noose and goad,
She who has the wonderful form,
Of the ego of the God who burnt the three cities,
Should please come and appear before us.