Quality control by a mobile molecular workshop: quality versus quantity

Ribosome is a molecular machine that moves on a mRNA track while, simultaneously, polymerizing a protein using the mRNA also as the corresponding template. We define, and analytically calculate, two different measures of the efficiency of this machine. However, we arugue that its performance is evaluated better in terms of the translational fidelity and the speed with which it polymerizes a protein. We define both these quantities and calculate these analytically. Fidelity is a measure of the quality of the products while the total quantity of products synthesized in a given interval depends on the speed of polymerization. We show that for synthesizing a large quantity of proteins, it is not necessary to sacrifice the quality. We also explore the effects of the quality control mechanism on the strength of mechano-chemical coupling. We suggest experiments for testing some of the ideas presented here.Comment: Final version published in Physical Review

Distribution of lifetimes of kinetochore-microtubule attachments: interplay of energy landscape, molecular motors and microtubule (de-)polymerization

Before a cell divides into two daughter cells, chromosomes are replicated resulting in two sister chromosomes embracing each other. Each sister chromosome is bound to a separate proteinous structure, called kinetochore (kt), that captures the tip of a filamentous protein, called microtubule (MT). Two oppositely oriented MTs pull the two kts attached to two sister chromosomes thereby pulling the two sisters away from each other. Here we theoretically study an even simpler system, namely an isolated kt coupled to a single MT; this system mimics an {\it in-vitro} experiment where a single kt-MT attachment is reconstituted using purified extracts from budding yeast. Our models not only account for the experimentally observed "catch-bond-like" behavior of the kt-MT coupling, but also make new predictions on the probability distribution of the lifetimes of the attachments. In principle, our new predictions can be tested by analyzing the data collected in the {\it in-vitro} experiments provided the experiment is repeated sufficiently large number of times. Our theory provides a deep insight into the effects of (a) size, (b) energetics, and (c) stochastic kinetics of the kt-MT coupling on the distribution of the lifetimes of these attachments.Comment: This is an author-created, un-copyedited version of an article accepted for publication in "Physical Biology" (IOP). IOP Publishing Ltd is not responsible for any errors or omissions in this version of the manuscript or any version derived from i

Low use of statins and other coronary secondary prevention therapies in primary and secondary care in India.

ObjectiveTo determine the frequency of use of pharmacotherapy with aspirin, beta blocker, statin, and angiotensin-converting enzyme (ACE) inhibitor in patients with stable coronary heart disease (CHD) among physicians at different levels of health care in Rajasthan state, India.MethodsPhysicians practicing at tertiary hospitals and clinics at tertiary, secondary and primary levels were contacted. Prescriptions of CHD patients were audited and descriptive statistics reported.ResultsWe evaluated 2,993 prescriptions (tertiary hospital discharge 711, tertiary 688, secondary 1,306, and primary 288). Use of aspirin was in 2,713 (91%) of prescriptions, beta blockers 2,057 (69%), ACE inhibitors or angiotensin receptor blockers (ARBs) 2,471 (82%), and statins 2,059 (69%). Any one of these drugs was prescribed in 2,991 (100%), any two in 2,880 (96%), any three in 1,740 (58%), and all four in 1,062 (35.5%) (P < 0.001). As compared to tertiary hospital, prescriptions at tertiary, secondary, and primary levels were lower: aspirin (96% vs 95%, 91%, 67%), beta blockers (80% vs 62%, 66%, 70%), statins (87% vs 82%, 62%, 21%): two drugs (98% vs 96%, 98%, 85%), three drugs (75% vs 58%, 55%, 28%), or four drugs (54% vs 44%, 28%, 7%) (P < 0.01). Use of ACE inhibitors/ARBs was similar while nitrates (43% vs 23%, 43%, 70%), dihydropyridine calcium channel blockers (12% vs 15%, 30%, 47%), and multivitamins (6% vs 26%, 37%, 47%) use was more in secondary and primary care.ConclusionsThere is suboptimal use of various evidence-based drugs (aspirin, beta blockers, ACE inhibitors, and statins) for secondary prevention of CHD in India

Stroke mortality: predictive value of simple laboratory tests and acute physiology, age, chronic health evaluation III scoring system: a hospital based study

Background: Acute stroke is a heterogeneous condition with respect to prognosis. This study was undertaken with the aim to evaluate the significance of routine simple blood parameters and APACHE (acute physiology, age, chronic health evaluation) III scoring system as methods of prediction of 1-month mortality in stroke patients and to assess the sensitivity and specificity of APACHE III scoring system in predicting short term outcome in critically ill patients having stroke.Methods: Patients of stroke presenting within 48 hours of onset were included in the study irrespective of age, sex or type of stroke. The clinical evaluation, neuroimaging and blood investigations were performed. APACHE III scoring system was applied for each patient to calculate the score for each one. The outcome of the patients at the end of one month was determined as survivors and expired.Results: Among the total 120 cases in the study, 54.16% (n=65) patients survived at the end of one month. The mean APAPCHE III Score among the survivors was 45.3 and in expired patients it was 88.6. Taking a cut-off value of 50, APACHE III Score was significantly associated in predicting the mortality in stroke patients (P-value<0.0001).Conclusions: The study concluded that a low GCS at the time of admission and increased serum creatinine were independent predictors of mortality among patients presenting to the hospital within 48 hours with first time acute stroke.  APACHE III scoring system was found to be sensitive and reasonably specific in predicting short term outcome in patients having cerebral stroke.

Work Function Engineered Charge Plasma-Germanium Double Gate Tunnel Field Effect Transistor for Low-Power Switching Applications

Here, we propose a Charge Plasma (CP)-based Germanium Double Gate Tunnel Field-Effect Transistor (Ge-DGTFET) device structure, where a CP is induced in the heavily doped source region using the work function engineering of source electrode. The CP enables creation of electrical metallurgical junction and converts n-p-n to p-n-p-n structure of TFET and enhances the drain current, reliability, eliminate additional pocket ion-implantation. The proposed CP-Ge-DGTFET device structure revealed excellent electrical DC performance as compared to the conventional Ge-DGTFET device structure such as high ON current (ION), excellent ION/IOFF ratio, and low sub-threshold swing of ~4.7E-4 A/um, ~1.8E9, and ~5.23 mV/dec, respectively. Furthermore, analog/RF analyses revealed high transconductance, upright cut-off frequency, low overall capacitance, transit time, and power delay product. Therefore, the proposed CP-Ge-DGTFET device structure with alternate channel material Ge, High-\k{appa} Al2O3, and work function engineered CP in source region furnishes high performance and cost-effective solution for next-generation energy-efficient switching applications.Comment: 7 pages, 10 figure

Lightning generated sferics: diagnostics tools to study upper atmosphere

Atmospherics or sferics that originate from lightning discharges on propagating large distances in the Earth-ionosphere waveguide or in the dispersive regions of ionosphere and magnetosphere form dispersed sferics called tweeks and whistlers respectively. Tweeks are novel diagnostic tool to monitor the nighttime D-region ionosphere. In this paper the lightning sferics (tweeks) recorded at a low latitude station, Suva (18.2o S,178.3oE, geomag. lat. 22.2o S, L = 1.17)) Fiji, in the South Pacific region and Allahabad (geomag. lat. 16.490 N, L=1.09) in India, will be presented and shown how they could be used to probe the night time D-region of the ionosphere. The computed D-region electron density is then compared with the electron density profile obtained from International Reference Ionosphere (IRI) 2007 model. Typical records of whistlers observed in Fiji and in India are presented