Rotation Bounds for Hölder Continuous Homeomorphisms with Integrable Distortion.

We obtain sharp rotation bounds for the subclass of homeomorphisms f : C → C of finite distortion which have distortion function in L loc p , p > 1 , and for which a Hölder continuous inverse is available. The interest in this class is partially motivated by examples arising from fluid mechanics. Our rotation bounds hereby presented improve the existing ones, for which the Hölder continuity is not assumed. We also present examples proving sharpness.

Seasonal Transition in PM10 Exposure and Associated All-Cause Mortality Risks in India.

Lack of a consistent PM10 (particulate matter smaller than 10 µm) database at high spatial resolution hinders in assessing the environmental impact of PM10 in India. Here we propose an alternate approach to estimate the PM10 database. Aerosol extinction coefficients at the surface are calculated from midvisible aerosol optical depth from MERRA-2 reanalysis data using characteristics vertical profiles from CALIOP and then are converted to PM10 mass using aerosol property information and microphysical data. The retrieved PM10 are bias-corrected and evaluated ( R2 = 0.85) against coincident ground-based data maintained under the Central Pollution Control Board network. PM10 exposure exceeds Indian annual air quality standard in 72.3% districts. Transition in PM10 exposure from the monsoon (Jun-Sep) to postmonsoon season (Oct-Nov) translates to 1-2% higher all-cause mortality risk over the polluted Indo-Gangetic Basin (IGB). Mortality risk increases in the central to eastern IGB and central India and reduces in Delhi national capital region in the winter (Dec-Feb) relative to the postmonsoon season. Mortality risk decreases by 0.5-1.8% in most parts of India in the premonsoon season (Mar-May). Our results quantify the vulnerability in terms of seasonal transition in all-cause mortality risks due to PM10 exposure at district level for the first time in India.

Efficient gradient computation for dynamical models.

Data assimilation is a fundamental issue that arises across many scales in neuroscience - ranging from the study of single neurons using single electrode recordings to the interaction of thousands of neurons using fMRI. Data assimilation involves inverting a generative model that can not only explain observed data but also generate predictions. Typically, the model is inverted or fitted using conventional tools of (convex) optimization that invariably extremise some functional - norms, minimum descriptive length, variational free energy, etc. Generally, optimisation rests on evaluating the local gradients of the functional to be optimized. In this paper, we compare three different gradient estimation techniques that could be used for extremising any functional in time - (i) finite differences, (ii) forward sensitivities and a method based on (iii) the adjoint of the dynamical system. We demonstrate that the first-order gradients of a dynamical system, linear or non-linear, can be computed most efficiently using the adjoint method. This is particularly true for systems where the number of parameters is greater than the number of states. For such systems, integrating several sensitivity equations - as required with forward sensitivities - proves to be most expensive, while finite-difference approximations have an intermediate efficiency. In the context of neuroimaging, adjoint based inversion of dynamical causal models (DCMs) can, in principle, enable the study of models with large numbers of nodes and parameters.

Hepatocellular carcinoma: important biomarkers and their significance in molecular diagnostics and therapy.

The increasing incidence of hepatocellular carcinoma (HCC) is of great concern not only in the United States but throughout the world because of two major reasons: firstly, HCC is one of the most lethal form of malignancies with less than 10% survival rate and secondly, a lack of prudent diagnostics makes early detection of HCC nearly impossible. The poor prognosis of HCC accentuates the need to develop new diagnostic markers and therapeutic approaches. In this review we discuss recent advances made in the discovery of molecular biomarkers and their significance in the detection of HCC. We focus on three major classes of biomarkers: serological, tumor, peri-tumoral tissue and cancer stem cell markers. Considerable progress has been made recently in our understanding of HCC at the molecular level increasing the potential of molecular targeted therapy. A number of molecular targets have been identified that have been showing promising results. Of particular interest is Sorafenib, a multi-tyrosine kinase inhibitor that has been approved for the HCC treatment. Inhibitors of other molecular targets such as VEGF, EGFR, mTOR etc. are emerging as plausible therapeutic agents for the treatment of HCC and are discussed in this review.

Hyperactive EGF receptor, Jaks and Stat3 signaling promote enhanced colony-forming ability, motility and migration of cisplatin-resistant ovarian cancer cells.

We present evidence that the cisplatin-resistant human ovarian cancer lines, A2780S/CP1 (S/CP1), A2780S/CP3 (S/CP3) and A2780S/CP5 (S/CP5), derived by subjecting the sensitive A2780S ovarian cancer line to multiple rounds of cisplatin treatments followed by recovery and are resistant to 1, 3 and 5 µM cisplatin, respectively, have increased colony-forming ability and altered morphology that is consistent with enhanced motility, migration and invasiveness in vitro. The malignant phenotype progresses with increasing resistance and is associated with hyperactive epidermal growth factor receptor (EGFR)/extracellular signal-regulated kinase (Erk)1/2 and janus kinases (Jaks), aberrant signal transducer and activator of transcription (Stat) 3 activation promoted by EGFR and Jaks, and epithelial-mesenchymal transition (EMT) in vitro. Survivin and FLIP anti-apoptotic factors, vascular endothelial growth factor (VEGF) and matrix metalloproteinase activities are also elevated in the resistant cells. Accordingly, the ectopic expression of constitutively-active Stat3C in the sensitive A2780S cells diminished cisplatin sensitivity. The inhibition of EGFR or Stat3 activity repressed Survivin, VEGF and Vimentin expression and the colony-forming potential, viability, motility and migration of the resistant cells, and sensitized them to cisplatin. Analysis of human ovarian cancer patients' tumor tissues shows aberrantly-active EGFR and Stat3 that in certain cases correlate with Vimentin over-expression. Intra-peritoneal mouse xenograft studies revealed, compared with the sensitive A2780S line that had low tumor incidence restricted to the ovary, a high tumor incidence for the resistant S/CP3 and S/CP5 lines that formed tumor nodules at several locations on the small intestine and colon, and which responded poorly to cisplatin, but were sensitive to concurrent treatment with cisplatin and EGFR or Stat3 inhibitor. Hyperactive EGFR signaling through Stat3 and the Jak-Stat3 activity together promote ovarian cancer progression to cisplatin resistance and therefore represent targets for preventing the development of cisplatin resistance and the recurrent disease during cisplatin therapy in ovarian cancer.

Assessing seasonal and spatial trends of persistent organic pollutants (POPs) in Indian agricultural regions using PUF disk passive air samplers.

The first survey of persistent organic pollutant (POP) concentrations in air across several Indian agricultural regions was conducted in 2006-2007. Passive samplers comprising polyurethane foam (PUF) disks were deployed on a quarterly basis at seven stations in agricultural regions, one urban site and one background site. The project was conducted as a sub-project of the Global Atmospheric Passive Sampling (GAPS) Network. In addition to revealing new information on air concentrations of several organochlorine pesticides (OCPs) and polychlorinated biphenyls (PCBs), the study has demonstrated the feasibility of conducting regional-scale monitoring for POPs in India using PUF disk samplers. The following analytes were detected with relatively high concentrations in air (mean for 2006 and 2007, pg/m(3)): α- and γ-hexachlorocyclohexane (HCH) (292 and 812, respectively); endosulfan I and II (2770 and 902, respectively); p,p'-DDE and p,p'-DDT (247 and 931, respectively); and for the sum of 48 PCBs, 12,100 (including a site with extremely high air concentrations in 2007) and 972 (when excluding data for this site).

Comparison of Langevin and Markov channel noise models for neuronal signal generation.

The stochastic opening and closing of voltage-gated ion channels produce noise in neurons. The effect of this noise on the neuronal performance has been modeled using either an approximate or Langevin model based on stochastic differential equations or an exact model based on a Markov process model of channel gating. Yet whether the Langevin model accurately reproduces the channel noise produced by the Markov model remains unclear. Here we present a comparison between Langevin and Markov models of channel noise in neurons using single compartment Hodgkin-Huxley models containing either Na+ and K+, or only K+ voltage-gated ion channels. The performance of the Langevin and Markov models was quantified over a range of stimulus statistics, membrane areas, and channel numbers. We find that in comparison to the Markov model, the Langevin model underestimates the noise contributed by voltage-gated ion channels, overestimating information rates for both spiking and nonspiking membranes. Even with increasing numbers of channels, the difference between the two models persists. This suggests that the Langevin model may not be suitable for accurately simulating channel noise in neurons, even in simulations with large numbers of ion channels.

Airway inflammation and upregulation of beta2 Mac-1 integrin expression on circulating leukocytes of female ragpickers in India.

OBJECTIVES: Over one million ragpickers collect and sale recyclable materials from municipal solid wastes (MSW) in India for a living. Since MSW contains a host of pathogenic microorganisms, we investigated the occurrence of airway inflammation and its underlying mechanism in 52 non-smoking female ragpickers (median age 29 yr) and 42 control women matched for age, smoking habit and socioeconomic conditions in Kolkata, eastern India. METHODS: Spontaneously expectorated sputum were stained using the Papanicolau method for cytology, and flow cytometry was used for measurements of surface expression of beta(2) Mac-1 integrin (CD11b/CD18) on leukocytes and P-selectin on platelets. The concentrations of pro-inflammatory cytokine tumor necrosis factor-alpha (TNF-alpha) and chemokine interleukin-8 (IL-8) were measured in plasma by enzyme-linked immunosorbent assay. RESULTS: Compared with controls, sputum samples of ragpickers contained significantly increased numbers of alveolar macrophages, neutrophils, eosinophils and lymphocytes, suggesting airway inflammation. Circulating neutrophils and monocytes of the ragpickers overexpressed CD11b/CD18 and their platelets had upregulated surface expression of P-selectin, implying functional activation of these cells. In addition, plasma levels of IL-8 and TNF-alpha were significantly increased, indicating greater trafficking of leukocytes from circulation to the tissues. Multivariate logistic regression analysis demonstrated a positive association between the ragpicking profession and leukocyte activation after controlling for potential confounders. CONCLUSIONS: Ragpickers experience leukocyte and platelet activation and airway inflammation that could make them more vulnerable to tissue damage and cardiovascular diseases.

Lack of horizontal gene transfer of methicillin-resistance genetic determinants from PBP2a-positive, coagulase-negative staphylococci to methicillin-sensitive Staphylococcus aureus using transcutaneous electrical nerve stimulation (TENS).

Previous research shows that approximately half of the coagulase-negative staphylococci (CNS) isolated from patients in the intensive care unit (ICU) at Belfast City Hospital were resistant to methicillin. The presence of this relatively high proportion of methicillin-resistance genetic material gives rise to speculation that these organisms may act as potential reservoirs of methicillin-resistance genetic material to methicillin-sensitive Staphylococcus aureus (MSSA). Mechanisms of horizontal gene transfer from PBP2a-positive CNS to MSSA, potentially transforming MSSA to MRSA, aided by electroporation-type activities such as transcutaneous electrical nerve stimulation (TENS), should be considered. Methicillin-resistant CNS (MR-CNS) isolates are collected over a two-month period from a variety of clinical specimen types, particularly wound swabs. The species of all isolates are confirmed, as well as their resistance to oxacillin by standard disc diffusion assays. In addition, MSSA isolates are collected over the same period and confirmed as PBP2a-negative. Electroporation experiments are designed to mimic the time/voltage combinations used commonly in the clinical application of TENS. No transformed MRSA were isolated and all viable S. aureus cells remained susceptible to oxacillin and PBP2a-negative. Experiments using MSSA pre-exposed to sublethal concentrations of oxacillin (0.25 microg/mL) showed no evidence of methicillin gene transfer and the generation of an MRSA. The study showed no evidence of horizontal transfer of methicillin resistance genetic material from MR-CNS to MSSA. These data support the belief that TENS and the associated time/voltage combinations used do not increase conjugational transposons or facilitate horizontal gene transfer from MR-CNS to MSSA.

Response to high LET radiation 12C (LET, 295 keV/microm) in M5 cells, a radio resistant cell strain derived from Chinese hamster V79 cells.

PURPOSE: To study the effects of 12C-beam of 295 keV/microm (57.24 MeV) on M5 and Chinese hamster V79 cells by using cytogenetic assays like micronuclei (MN) induction, chromosomal aberrations (CA) and apoptosis. Additionally, the relative survival of these two cell lines was tested by the colony forming ability of the cells, with a view to understanding the mechanism of cellular damages that lead to difference in cell survival. MATERIALS AND METHODS: Confluent cells were irradiated with 12C-beam at various doses using 15UD Pelletron accelerator. Cell survival was studied by the colony forming ability of cells. MN assay was done by fluorescent staining. Different types of chromosomal aberrations in metaphase cells were scored at 12 h after irradiation. Apoptosis was measured at different post irradiation times as detected by nuclear fragmentation and DNA ladder was prepared after 48 h of incubation. RESULTS: Dose-dependent decrease in surviving fractions was found in both the cell lines. However, the surviving fractions were higher in M5 cells in comparison to V79 cells when exposed to the same radiation doses. On the other hand, induced MN frequencies, CA frequencies and apoptosis percentages were less in M5 cells than V79 cells. Very good correlations between surviving fractions and induced MN frequencies or induced total CA or induced apoptosis percentages were obtained in this study. CONCLUSIONS: The cell strain M5 showed relatively more radio-resistance to 12C-beam compared to Chinese hamster V79 cells in this study. As the MN formation, CA and apoptosis induction were less in M5 cells as compared to parental V79 cells, the higher cell survival in the former could possibly be attributed to their better repairing ability leading to higher cell survival.

Profile of pediatric dengue cases from a tertiary care hospital in Kolkata.

A study was conducted on the 52 serologically positive cases of dengue, admitted to the Dept. of Paediatrics, R.G. Kar Medical College & Hospital, from an outbreak in Kolkata. The most unusual feature observed in this study was that the rash in some cases was urticarial and intensely pruritic. The shock appeared early in the course of the disease and it was less commonly associated with bleeding (22%). One out of three dengue cases was a severe disease. It was not possible to predict a severe disease from the early symptomatology.

Source apportionment of ambient VOCs in Delhi City.

Source apportionment using chemical mass balance (CMB) model was carried using a data set of 360 four hourly samples collected at 15 locations of five categories namely residential, commercial, industrial, traffic intersections and petrol pumps during August 2001-July 2002 in Delhi. The results indicate that emissions from diesel internal combustion engines dominate in Delhi. Vehicular exhaust and evaporative emissions also contribute significantly to VOCs in ambient air. Emission of VOCs associated with sewage sludge was also found to contribute to VOCs in Delhi's air. This points to the fact that open defecation and leaking sewage manholes are a problem in all categories of locations.

Study of Drug Resistant Pulmonary Tuberculosis.

BACKGROUND: Drug resistance has emerged as a major problem in management of pulmonary tuberculosis (PT) with increase in its incidence. METHODS: Sixty patients who presented to a tertiary referral chest centre with drug resistant PT were included in the study out of 835 clinically diagnosed cases of PT treated between January 2000 and May 2002. They were studied to see the incidence, pattern of drug resistance and response to treatment. RESULTS: 7.2% of the clinically diagnosed cases of PT had drug resistance and 14.8% of the 403 strains of mycobacterium tuberculosis (MTB) tested were resistant to one or more antitubercular drugs (ATD). 40 cases (66.7%) had initial resistance and acquired resistance was seen in 20(33.3%) out of the 60 cases of drug resistant PT. Single drug resistance was observed in 21 cases (35%), two drug resistance in 19 (31.7%) and 20(33.3%) cases showed resistance to three or more drugs. Individual drug resistance breakup was: INH(H) - 36(8.9%), Rifampicin (R)-38(9.4%), Ethambutol (E) - 14(3.5%), Streptomycin (S) - 34(8.4%), Pyrazinamide (Z) - 2(0.5%), Ciprofloxacin (C) - 2(0.5%), Ethionamide (N) - 2(0.5%), Cycloserine - 1(0.3%) and Kanamycin - 1(0.3%). 98.3% showed sputum conversion after starting reserve drugs. Average period of sputum conversion was 10 weeks. 3.3% were HIV positive. CONCLUSION: Incidence of drug resistance was not as high as reported by some other workers and majority of the cases showed satisfactory outcome.

A study on the delivery practices in riverine & non-riverine blocks of the district of South 24-Parganas, West Bengal.

A cross sectional study was undertaken in three riverine and two non-riverine blocks of South 24 Parganas district, West Bengal to study the delivery practices and compare between two locality. During the reference period of one year, of 3073 total deliveries, 89.36% were home deliveries. Home deliveries were higher in the riverine blocks (95.07%) compared to non-riverine blocks (81.64%). 'Dai' conducted 58.36% and 90.62% of home deliveries in riverine and non-riverine blocks respectively. Only 18.4% of the 'Dai' were trained.

Single megadose vitamin A supplementation of Indian mothers and morbidity in breastfed young infants.

BACKGROUND AND OBJECTIVE: In developing countries low maternal vitamin A stores combined with increased demands of pregnancy and lactation may lead to its deficiency in breastfed infants. This study evaluates the effects of maternal supplementation with a high dose of vitamin A on the serum retinol levels of exclusively breastfed infants, and their morbidity in the first six months of life. SETTING: Hospital based. STUDY DESIGN: Randomised controlled trial. SUBJECTS AND METHODS: Mothers of the test group (n=150) were orally supplemented with a single dose of retinol (209 micro mol) soon after delivery and were advised exclusive breastfeeding for six months. Before supplementation retinol levels were estimated in the mothers' and newborns' blood, and in colostrum. On follow up, breastmilk and infants' serum retinol contents were assessed monthly for six months. Retinol level <0.7 micro mol/l indicated vitamin A deficiency. Morbidity patterns like vitamin A deficiency, diarrhoea, febrile illnesses, acute respiratory infection, measles, and ear infection were also studied and compared between the two groups. RESULTS: Presupplement mean maternal serum retinol levels were 0.98 and 0.92 micro mol/l and mean breastmilk levels were 3.85 and 3.92 micro mol/l in the test and control groups respectively (p>0.05). Mean cord blood retinol levels were also comparable (0.68 v 0.64 micro mol/l). After supplementation, the test group showed a rise in mean breastmilk retinol content (12.08 v 2.96 micro mol/l) which remained significantly higher for four months. The infants' mean serum retinol level, initially 322.06% of the baseline value, was significantly higher for five months. In the control group, significant numbers of mothers and infants showed deficient breastmilk and serum retinol throughout the follow up (p<0.01). Decreased incidence and duration of various diseases were also found in the test group suggesting lesser morbidity. CONCLUSION: Maternal supplementation with single megadose vitamin A is an effective strategy for vitamin A prophylaxis of exclusively breastfed infants of 0-6 months.

Protein-flavonol interaction: fluorescence spectroscopic study.

Recent studies have shown that various synthetic as well as therapeutically active naturally occurring flavonols possess novel luminescence properties that can potentially serve as highly sensitive monitors of their microenvironments in biologically relevant systems. We report a study on the interactions of bovine serum albumin (BSA) with the model flavonol 3-hydroxyflavone (3HF), using the excited-state proton-transfer (ESPT) luminescence of 3HF as a probe. Upon addition of BSA to the flavonoid solutions, we observe remarkable changes in the absorption, ESPT fluorescence emission and excitation profiles as well as anisotropy (r) values. Complexation of 3HF with protein results in a pronounced shift (20 nm) of the ESPT emission maximum of the probe (from lambda(max)(em) = 513 nm to lambda(max)(em) = 533 nm) accompanied by a significant increase in fluorescence intensity. The spectral data also suggest that, in addition to ESPT, the protein environment induces proton abstraction from 3HF leading to formation of anionic species in the ground state. Fairly high values of anisotropy are observed in the presence of BSA for the tautomer (r = 0.25) as well as anion (r = 0.35) species of 3HF, implying that both the species are located in motion-restricted environments of BSA molecules. Analysis of relevant spectroscopic data leads to the conclusions that two binding sites are involved in BSA-3HF interaction, and the interaction is slightly positively cooperative in nature with a similar binding constant of 1.1 - 1.3 x 10(5) M(-1) for both these sites. Proteins 2001;43:75-81.

Influence of reverse micellar environments on the fluorescence emission properties of tryptophan octyl ester.

A number of recent studies have presented perspectives on the hydrophobic fluorescence probe tryptophan octyl ester (TOE). This molecule has attracted notable attention as a suitable model for the natural fluorophore tryptophan, in case of membrane proteins. We report here, for the first time, the fluorescence emission behaviour of TOE in reverse micelles of aerosol-OT (AOT) in n-heptane, containing different amounts of water. Relevant studies in representative homogeneous solvent media are also included for comparison. The fluorescence emission parameters (especially emission maximum, relative intensity, and anisotropy) of TOE are found to exhibit significant variation upon changes in the water/surfactant molar ratio (w(0)) of the reverse micelles. Fluorescence decay studies on TOE which we have also performed, indicate biexponential decay kinetics in reverse micelles as well as in homogeneous solvent media. The implications of these findings are examined in relation to the potentialities of TOE as a novel fluorescence probe for membrane proteins present in water restricted environments prevailing at the interfaces of biomembranes (for which reverse micelles serve as ideal model systems).

Characterization of the fluorescence emission properties of prodan in different reverse micellar environments.

We have examined the steady state and time resolved fluorescence emission properties of the hydrophobic fluorescence probe, prodan, in three representative reverse micellar systems formed by the surfactants poly(oxyethylene) (tetramethylbutyl) phenylether (Triton X-100, neutral), cetyl trimethylammonium bromide (CTAB, cationic) and sodium bis-(2-ethylhexyl) sulfosuccinate (AOT, anionic) in organic solvent media containing different concentrations of water. The results obtained from the experiments indicate conspicuous dependence of the emission behaviour of prodan on the type of surfactant used and the water/surfactant molar ratio (w0). The nature of the emission profiles, along with relevant parameters namely emission maximum (lambda(em)max), anisotropy (r) and lifetime (tau) data are used to infer the distribution and microenvironments of the prodan molecules in the reverse micelles at different w0 values. Furthermore, quantitative estimates have been obtained for the polarities (in terms of the empirical polarity parameter E(T)(30)) of the sites of solubilization of the fluorophore in different reverse micellar systems.

Luminescence behaviour of 5-hydroxyindole in different environments.

Steady state fluorescence emission spectroscopic studies along with some lifetime measurements have been performed for 5-hydroxyindole (5HI) in different environments. 5HI merits particular attention, since it is the chromophoric moiety of the non-natural amino acid 5-hydroxytryptophan (5HT), which has come into significant, recent prominence as a novel intrinsic optical probe for protein structure, function and dynamics. Studies in representative homogeneous solvents and solvent-mixtures indicate that unlike other fluorophores of related interest like indole (I) and 7-azaindole (7AI), the fluorescence emission maximum (lambda(em)max) of 5HI is relatively insensitive to solvent polarity. This behaviour suggests the lack of appreciable solvent dipolar relaxation in 5HI, which is consistent with our low temperature (77 K) emission data. Notwithstanding such limitation, fluorescence anisotropy (r) and quenching studies are shown to be effective for exploring changes in the micro-environments of 5HI in sodium bis-(2-ethylhexyl)sulfosuccinate (AOT) reverse micellar assemblies (which serve as a biomembrane mimetic model system) with variation in water/surfactant molar ratio (w0).