Conformational Spread in the Flagellar Motor Switch: A Model Study

The reliable response to weak biological signals requires that they be amplified with fidelity. In E. coli, the flagellar motors that control swimming can switch direction in response to very small changes in the concentration of the signaling protein CheY-P, but how this works is not well understood. A recently proposed allosteric model based on cooperative conformational spread in a ring of identical protomers seems promising as it is able to qualitatively reproduce switching, locked state behavior and Hill coefficient values measured for the rotary motor. In this paper we undertook a comprehensive simulation study to analyze the behavior of this model in detail and made predictions on three experimentally observable quantities: switch time distribution, locked state interval distribution, Hill coefficient of the switch response. We parameterized the model using experimental measurements, finding excellent agreement with published data on motor behavior. Analysis of the simulated switching dynamics revealed a mechanism for chemotactic ultrasensitivity, in which cooperativity is indispensable for realizing both coherent switching and effective amplification. These results showed how cells can combine elements of analog and digital control to produce switches that are simultaneously sensitive and reliable. © 2012 Ma et al.

Assessing the welfare effects of microfinance in Vietnam : empirical results from a quasi-experimental survey

This article analyses the effects of NGO microfinance programmes on household welfare in Vietnam. Data on 470 households across 25 villages were collected using a quasi-experimental survey approach to overcome any self-selection bias. The sample was designed so that member households of microfinance programmes were compared with non-member households with similar characteristics. The analysis shows no significant effects of participation in NGO microfinance on household welfare, proxied by income and consumption per adult equivalent.

A comparative risk assessment of burden of disease and injury attributable to 67 risk factors and risk factor clusters in 21 regions, 1990–2010: A systematic analysis for the Global Burden of Disease Study 2010

BACKGROUND Quantification of the disease burden caused by different risks informs prevention by providing an account of health loss different to that provided by a disease-by-disease analysis. No complete revision of global disease burden caused by risk factors has been done since a comparative risk assessment in 2000, and no previous analysis has assessed changes in burden attributable to risk factors over time. METHODS We estimated deaths and disability-adjusted life years (DALYs; sum of years lived with disability [YLD] and years of life lost [YLL]) attributable to the independent effects of 67 risk factors and clusters of risk factors for 21 regions in 1990 and 2010. We estimated exposure distributions for each year, region, sex, and age group, and relative risks per unit of exposure by systematically reviewing and synthesising published and unpublished data. We used these estimates, together with estimates of cause-specific deaths and DALYs from the Global Burden of Disease Study 2010, to calculate the burden attributable to each risk factor exposure compared with the theoretical-minimum-risk exposure. We incorporated uncertainty in disease burden, relative risks, and exposures into our estimates of attributable burden. FINDINGS In 2010, the three leading risk factors for global disease burden were high blood pressure (7·0% [95% uncertainty interval 6·2-7·7] of global DALYs), tobacco smoking including second-hand smoke (6·3% [5·5-7·0]), and alcohol use (5·5% [5·0-5·9]). In 1990, the leading risks were childhood underweight (7·9% [6·8-9·4]), household air pollution from solid fuels (HAP; 7·0% [5·6-8·3]), and tobacco smoking including second-hand smoke (6·1% [5·4-6·8]). Dietary risk factors and physical inactivity collectively accounted for 10·0% (95% UI 9·2-10·8) of global DALYs in 2010, with the most prominent dietary risks being diets low in fruits and those high in sodium. Several risks that primarily affect childhood communicable diseases, including unimproved water and sanitation and childhood micronutrient deficiencies, fell in rank between 1990 and 2010, with unimproved water and sanitation accounting for 0·9% (0·4-1·6) of global DALYs in 2010. However, in most of sub-Saharan Africa childhood underweight, HAP, and non-exclusive and discontinued breastfeeding were the leading risks in 2010, while HAP was the leading risk in south Asia. The leading risk factor in Eastern Europe, most of Latin America, and southern sub-Saharan Africa in 2010 was alcohol use; in most of Asia, North Africa and Middle East, and central Europe it was high blood pressure. Despite declines, tobacco smoking including second-hand smoke remained the leading risk in high-income north America and western Europe. High body-mass index has increased globally and it is the leading risk in Australasia and southern Latin America, and also ranks high in other high-income regions, North Africa and Middle East, and Oceania. INTERPRETATION Worldwide, the contribution of different risk factors to disease burden has changed substantially, with a shift away from risks for communicable diseases in children towards those for non-communicable diseases in adults. These changes are related to the ageing population, decreased mortality among children younger than 5 years, changes in cause-of-death composition, and changes in risk factor exposures. New evidence has led to changes in the magnitude of key risks including unimproved water and sanitation, vitamin A and zinc deficiencies, and ambient particulate matter pollution. The extent to which the epidemiological shift has occurred and what the leading risks currently are varies greatly across regions. In much of sub-Saharan Africa, the leading risks are still those associated with poverty and those that affect children.

An algorithm for constructing Hjelmslev planes

Projective Hjelmslev planes and affine Hjelmslev planes are generalisations of projective planes and affine planes. We present an algorithm for constructing projective Hjelmslev planes and affine Hjelmslev planes that uses projective planes, affine planes and orthogonal arrays. We show that all 2-uniform projective Hjelmslev planes, and all 2-uniform affine Hjelmslev planes can be constructed in this way. As a corollary it is shown that all $2$-uniform affine Hjelmslev planes are sub-geometries of $2$-uniform projective Hjelmslev planes.

Global, regional, and national comparative risk assessment of 79 behavioural, environmental and occupational, and metabolic risks or clusters of risks in 188 countries, 1990–2013: a systematic analysis for the Global Burden of Disease Study 2013

Background The Global Burden of Disease, Injuries, and Risk Factor study 2013 (GBD 2013) is the first of a series of annual updates of the GBD. Risk factor quantification, particularly of modifiable risk factors, can help to identify emerging threats to population health and opportunities for prevention. The GBD 2013 provides a timely opportunity to update the comparative risk assessment with new data for exposure, relative risks, and evidence on the appropriate counterfactual risk distribution. Methods Attributable deaths, years of life lost, years lived with disability, and disability-adjusted life-years (DALYs) have been estimated for 79 risks or clusters of risks using the GBD 2010 methods. Risk–outcome pairs meeting explicit evidence criteria were assessed for 188 countries for the period 1990–2013 by age and sex using three inputs: risk exposure, relative risks, and the theoretical minimum risk exposure level (TMREL). Risks are organised into a hierarchy with blocks of behavioural, environmental and occupational, and metabolic risks at the first level of the hierarchy. The next level in the hierarchy includes nine clusters of related risks and two individual risks, with more detail provided at levels 3 and 4 of the hierarchy. Compared with GBD 2010, six new risk factors have been added: handwashing practices, occupational exposure to trichloroethylene, childhood wasting, childhood stunting, unsafe sex, and low glomerular filtration rate. For most risks, data for exposure were synthesised with a Bayesian meta-regression method, DisMod-MR 2.0, or spatial-temporal Gaussian process regression. Relative risks were based on meta-regressions of published cohort and intervention studies. Attributable burden for clusters of risks and all risks combined took into account evidence on the mediation of some risks such as high body-mass index (BMI) through other risks such as high systolic blood pressure and high cholesterol. Findings All risks combined account for 57·2% (95% uncertainty interval [UI] 55·8–58·5) of deaths and 41·6% (40·1–43·0) of DALYs. Risks quantified account for 87·9% (86·5–89·3) of cardiovascular disease DALYs, ranging to a low of 0% for neonatal disorders and neglected tropical diseases and malaria. In terms of global DALYs in 2013, six risks or clusters of risks each caused more than 5% of DALYs: dietary risks accounting for 11·3 million deaths and 241·4 million DALYs, high systolic blood pressure for 10·4 million deaths and 208·1 million DALYs, child and maternal malnutrition for 1·7 million deaths and 176·9 million DALYs, tobacco smoke for 6·1 million deaths and 143·5 million DALYs, air pollution for 5·5 million deaths and 141·5 million DALYs, and high BMI for 4·4 million deaths and 134·0 million DALYs. Risk factor patterns vary across regions and countries and with time. In sub-Saharan Africa, the leading risk factors are child and maternal malnutrition, unsafe sex, and unsafe water, sanitation, and handwashing. In women, in nearly all countries in the Americas, north Africa, and the Middle East, and in many other high-income countries, high BMI is the leading risk factor, with high systolic blood pressure as the leading risk in most of Central and Eastern Europe and south and east Asia. For men, high systolic blood pressure or tobacco use are the leading risks in nearly all high-income countries, in north Africa and the Middle East, Europe, and Asia. For men and women, unsafe sex is the leading risk in a corridor from Kenya to South Africa. Interpretation Behavioural, environmental and occupational, and metabolic risks can explain half of global mortality and more than one-third of global DALYs providing many opportunities for prevention. Of the larger risks, the attributable burden of high BMI has increased in the past 23 years. In view of the prominence of behavioural risk factors, behavioural and social science research on interventions for these risks should be strengthened. Many prevention and primary care policy options are available now to act on key risks.

Binding of DNA Nucleobases and Nucleosides with Graphene

Interaction of two different samples of graphene with DNA nucleobases and nucleosides is investigated by isothermal titration calorimetry. The relative interaction energies of the nucleobases decrease in the order guanine (G) > adenine (A) > cytosine (C) > thy mine (T) in aqueous solutions, although the positions of C and T seem to be interchangeable. The same trend is found with the nucleosides. Interaction energies of the A-T and G-C pairs are somewhere between those of the constituent bases. Theoretical calculations including van der Wools interaction and solvation energies give the trend G > A similar to T > C. The magnitudes of the interaction energies of the nucleobases with graphene are similar to those found with single-walled carbon nonotubes.

Beta-Turn Conformations In Crystal-Structures Of Model Peptides Containing Alpha,Alpha-Di-N-Propylglycine And Alpha,Alpha-Di-N-Butylglycine

The crystal state conformations of three peptides containing the alpha, alpha-dialkylated residues, alpha,alpha-di-n-propylglycine (Dpg) and alpha,alpha-di-n-butylglycine (Dbg), have been established by x-ray diffraction. Boc-Ala-Dpg-Ala-OMe (I) and Boc-Ala-Dbg-Ala-OMe (III) adopt distorted type II beta-turn conformations with Ala (1) and Dpg/Dbg (2) as the corner residues. In both peptides the conformational angles at the Dxg residue (I: phi = 66.2 degrees, psi = 19.3 degrees; III: phi = 66.5 degrees, psi = 21.1 degrees) deviate appreciably from ideal values for the i + 2 residue in a type II beta-turn. In both peptides the observed (N...O) distances between the Boc CO and Ala(3) NH groups are far too long (I: 3.44 Angstrom; III: 3.63 Angstrom) for an intramolecular 4 --> 1 hydrogen bond. Boc-Ala-Dpg-Ala-NHMe (II) crystallizes with two independent molecules in the asymmetric unit. Both molecules IIA and IIB adopt consecutive beta-turn (type III-III in IIA and type III-I in IIB) or incipient 3(10)-helical structures, stabilized by two intramolecular 4 --> 1 hydrogen bonds. In all four molecules the bond angle N-C-alpha-C' (tau) at the Dxg residues are greater than or equal to 110 degrees. The observation of conformational angles in the helical region of phi,psi space at these residues is consistent with theoretical predictions.

An analysis of MONTBLEX data on heat and momentum flux at Jodhpur

Parameterization of sensible heat and momentum fluxes as inferred from an analysis of tower observations archived during MONTBLEX-90 at Jodhpur is proposed, both in terms of standard exchange coefficients C-H and C-D respectively and also according to free convection scaling. Both coefficients increase rapidly at low winds (the latter more strongly) and with increasing instability. All the sensible heat flux data at Jodhpur (wind speed at 10m <(U)over bar (10)>, < 8ms(-1)) also obey free convection scaling, with the flux proportional to the '4/3' power of an appropriate temperature difference such as that between 1 and 30 m. Furthermore, for <(U)over bar (10)> < 4 ms(-1) the momentum flux displays a linear dependence on wind speed.

Solvent effect in molecular recognition: Determining binding constants in different solvents following an extraction based protocol

Semi-rigid molecular tweezers 1, 3 and 4 bind picric acid with more than tenfold increment in tetrachloromethane as compared to chloroform.

Conformation-activity correlations for chemotactic tripeptide analogs incorporating dialkyl residues with linear and cyclic alkyl sidechains at position 2

Five stereochemically constrained analogs of the chemotactic tripeptide incorporating 1-aminocycloalkane-1-carboxylic acid (Ac(n)c) and alpha,alpha-dialkylglycines (Deg, diethylglycine; Dpg, n,n-dipropylglycine and Dbg, n,n-dibutylglycine) at position 2 have been synthesized. NMR studies of peptides For-Met-Xxx-Phe-OMe (Xxx = Ac(7)c, I; Ac(8)c, II; Deg, III; Dpg, IV and Dbg, V; For, formyl) establish that peptides with cycloalkyl residues, I and II, adopt folded beta-turn conformations in CDCl3 and (CD3)(2)SO. In contrast, analogs with linear alkyl sidechains, III-V, favour fully extended (C-5) conformations in solution. Peptides I-V exhibit high activity in inducing beta-glucosaminidase release from rabbit neutrophils, with ED(50) values ranging from 1.4-8.0 x 10(-11)M. In human neutrophils the Dxg peptides III-V have ED(50) values ranging from 2.3 x 10(-8) to 5.9 x 10(-10) M, with the activity order being V > IV > III. While peptides I-IV are less active than the parent. For-Met-Leu-Phe-OH, in stimulating histamine release from human basophils, the Dbg peptide V is appreciably more potent, suggesting its potential utility as a probe for formyl peptide receptors.

ELISA for the detection of venoms from four medically important snakes of India

A double antibody sandwich enzyme linked immunosorbent assay (ELISA) was developed to detect Echis carinatus venom in various organs (brain, heart, lungs, liver, spleen and kidneys) as well as tissue at the site of injection of mice, at various time intervals (1, 6, 12, 18, 24 h and 12 h intervals up to 72 h) after death. The assay could detect E. carinatus venom levels up to 2.5 ng/ml of tissue homogenate and the venom was detected up to 72 h after death. A highly sensitive and species-specific avidin-biotin microtitre ELISA was also developed to detect venoms of four medically important Indian snakes (Bungarus caeruleus, Naja naja, E. carinatus and Daboia russelli russelli) in autopsy specimens of human victims of snake bite. The assay could detect venom levels as low as 100 pg/ml of tissue homogenate. Venoms were detected in brain, heart, lungs, liver, spleen, kidneys, tissue at the bite area and postmortem blood. In all 12 human victim cadavers tested the culprit species were identified. As observed in mice, tissue at the site of bite area showed the highest concentration of venom and the brain showed the least. Moderate amounts of venoms were found in liver, spleen, kidneys, heart and lungs. Development of a simple, rapid and species-specific diagnostic kit based on this ELISA technique useful to clinicians is discussed.

Effect Of Administration Of Luteinizing-Hormone (Lh) And Deprivation Of Lh On The Proteins Of Smooth Endoplasmic-Reticulum Of Immature And Adult-Rat Leydig-Cells

Analysis of proteins of smooth endoplasmic reticulum (SER) of Leydig cells from immature and admit rats by two-dimensional polyacrylamide gel electrophoresis (SDS-PAGE) revealed the presence of several new proteins in the adult rats. Administration of human chorionic gonadotropin to immature rats for ten days also resulted in a significant increase as well as the appearance of several new proteins. The general pattern of SDS-PAGE analysis of the SER proteins of Leydig cells resembled that of the adult rat. SDS-PAGE analysis of the SER proteins of Leydig cells from adult rats following deprivation of endogenous luteinizing hormone by administration of antiserum to ovine luteinizing hormone resulted in a pattern which to certain extent resembled that of an immature I at. Western Blot analysis of luteinizing hormone antiserum treated rat Leydig cell proteins revealed a decrease in the 17-alpha-hydroxylase compared to the control. These results provide biochemical evidence for the suggestion that one of the main functions of luteinizing hormone is the control of biogenesis and/or turnover SER of Leydig cells in the rat.

Energetics of rare earth manganese perovskites A1-xA ' xMnO3 (A = La, Nd, Y and A ' = Sr, La) systems

High temperature reaction calorimetry using molten lead berate as solvent has been used to study the thermochemistry of NdMnO3, YMnO3, La1-xSrxMnO3 (with 0 < x < 0.5), and Ln(0.5)Ca(0.5)MnO(3) (with Ln = La, Nd, Y), The enthalpies of formation of these multicomponent oxides from their binary constituents have been calculated from the measured enthalpy of drop solution, The energetic stability of the perovskite depends on the size of the A cation, The enthalpy of formation of YMnO3 (smallest A cation) is more endothermic than those of NdMnO3 and LaMnO3. The energetics of the perovskite also depends on the oxidation state of the B site's ions. In the La1-xSrxMnO3 system, the energetic stability of the structure increases with the Mn4+/Mn3+ ratio, The new values of the enthalpies of oxidations, with reliable standard entropies, were used to plot the phase stability diagram of the lanthanum-manganese-oxygen system in the temperature range 300-1100 K, The LaMnO3/MnO phase boundary evaluated in this study agrees with the one published by Atsumi et nl. calculated from thermogravimetric and conductivity measurements.

Elastic Properties Of Sodium Borovanadate Glasses

The elastic properties of sodium borovanadate glasses have been studied over a wide range of composition using ultrasonic measurements. It is found that variation of different elastic moduli is very similar in any given series of composition. The bulk and shear moduli show a monotonic variation with the covalent bond energy densities calculated from the proposed structural model for these glasses. The bulk moduli also vary as a negative power function of the mean atomic volume. The Debye temperature varies linearly with the glass transition temperature. The implications of the observed behavior have been discussed.

Spectroscopic investigations of manganese ions in microwave-prepared NaPO3-PbO glasses

The EPR spectra of microwave-prepared 70NaPO(3):30PbO glasses containing different weight percentages of manganese ions have been studied. The EPR spectra exhibit a well-resolved hyperfine pattern at g(eff) approximate to 2.0. Optical absorption, fluorescent emission and excitation spectra of the glasses have been examined. The absorption spectrum exhibits a peak near 500 nm and this has been attributed to the spin-allowed E-5(g) --> T-5(2g) transition of Mn3+ ions. The emission spectrum shows a band at 595 nm which has been assigned to the T-4(1g)(G) --> (6)A(1g)(S) spin-forbidden transition of Mn2+ ions in octahedral coordination. Concentration quenching of fluorescence was found to occur above 0.75 wt% of Mn2+ ions. The excitation spectra exhibit four bands characteristic of Mn2+ ions in octahedral coordination. From the observed band positions of the excitation spectra, the crystal field parameter D-q and the Racah interelectronic repulsion parameters, B and C have been calculated. A structural model is proposed based on the IR, Raman and MASNMR studies according to which Mn2+ ions are likely to occupy sites similar to Na+ ions in these glasses.