Novel Quaternary Chalcogenide/Reduced Graphene Oxide-Based Asymmetric Supercapacitor with High Energy Density.

In this work we have synthesized quaternary chalcogenide Cu2NiSnS4 (QC) nanoparticles grown in situ on 2D reduced graphene oxide (rGO) for application as anode material of solid-state asymmetric supercapacitors (ASCs). Thorough characterization of the synthesized composite validates the proper phase, stoichiometry, and morphology. Detailed electrochemical study of the electrode materials and ASCs has been performed. The as-fabricated device delivers an exceptionally high areal capacitance (655.1 mF cm-2), which is much superior to that of commercial micro-supercapacitors. Furthermore, a remarkable volumetric capacitance of 16.38 F cm-3 is obtained at a current density of 5 mA cm-2 combined with a very high energy density of 5.68 mW h cm-3, which is comparable to that of commercially available lithium thin film batteries. The device retains 89.2% of the initial capacitance after running for 2000 cycles, suggesting its long-term capability. Consequently, the enhanced areal and volumetric capacitances combined with decent cycle stability and impressive energy density endow the uniquely decorated QC/rGO composite material as a promising candidate in the arena of energy storage devices. Moreover, Cu2NiSnS4 being a narrow band gap photovoltaic material, this work offers a novel protocol for the development of self-charging supercapacitors in the days to come.

Genetic analysis of river, swamp and hybrid buffaloes of north-east India throw new light on phylogeography of water buffalo (Bubalus bubalis).

This study analysed buffaloes from north-east India and compared their nuclear and mitochondrial DNA variations with buffaloes of mainland India, China, Mediterranean and South-East Asia. Microsatellite genotypes of 338 buffaloes including 210 from six north-east Indian buffalo populations and three mainland Indian breeds were analysed to evaluate their genetic structure and evolutionary relationships. Phylogenetic analysis and multidimensional scaling plot of pairwise FST revealed the clustering of all swamp-type buffaloes of north-east India with Lower Assamese (significantly hybrid type) buffaloes in one plane and all the mainland river buffaloes in another plane while the upper Assamese buffaloes being distinct from both these clusters. Analysis of mtDNA D-loop region of 530-bp length was performed on 345 sequences belonging to 23 buffalo populations from various geographical regions to establish the phylogeography of Indian water buffalo. The swamp buffaloes of north-east India clustered with both the lineages of Chinese swamp buffalo. Multidimensional scaling display of pairwise FST derived from mitochondrial DNA data showed clustering of upper Assamese, Chilika and Mediterranean buffaloes distinctly from all the other Indian buffalo populations. Median-joining network analysis further confirmed the distinctness and ancestral nature of these buffaloes. The study revealed north-east region of India forming part of the wider hybrid zone of water buffalo that may probably extend from north-east India to South-East Asia.

Outcome of sepsis-associated acute kidney injury in an intensive care unit: an experience from a tertiary care center of central Nepal.

Acute kidney injury (AKI) is a common and major complication of sepsis. Sepsis-induced AKI is associated with higher morbidity and mortality. A prospective study was designed to include all the patients with a provisional diagnosis of sepsis with AKI admitted in our intensive care unit from August 2009 to September 2010. Detailed demographic data including various clinical parameters, co-morbidities, investigations, complications and outcome were entered in a designated proforman and were analyzed. A total of 53 subjects with the provisional diagnosis of sepsis with AKI were included in the study. The majority of patients (60.37%) were female. The mean age of the study population was 45.84 ± 20.5 years. Forty-nine percent of the subjects were <45 years old and 26.4% patients were >65 years. Among the co-morbid conditions, 9.4% subjects had diabetes mellitus type 2. Among the primary causes of AKI, 72% of the cases were due to medical causes, in which pneumonia was the major cause, and 28% were due to surgical causes, in which cholecystitis was the major cause. 47.1% cases expired, 11.3% subjects left against medical advice and 41.5% cases had favorable outcome. Among the expired cases, 20.7% subjects expired within 24 h; for others, the median hospital stay was four days. This prospective study showed that the major causes of AKI were medical illness and pneumonia. Mortality in sepsis-induced AKI is significantly high. This highlights the importance of prevention of AKI in sepsis by early and renal-friendly aggressive treatment of sepsis and the need for improvement in the management of such AKI cases.

Intradialytic Muscle Cramp and its Association with Peripheral Arterial Disease in End Stage Renal Disease Patients on Hemodialysis.

INTRODUCTION:  Muscle cramp is a common intradialytic complication observed in hemodialysis patients. Similarly Peripheral arterial disease is a common condition in the hemodialysis population. METHODS:  Fifty patients with a diagnosis of End Stage Renal Disease who were on hemodialysis were studied over a period of one year. Muscle cramp was defined clinically as contractions of a large muscle group and Peripheral arterial disease was diagnosed on the basis of the ankle -brachial index (ABI). RESULTS:  A total of 50 End Stage Renal Disease patients were analyzed. The major causes of End Stage Renal Disease in the study population was Chronic Glomerulonephritis 40 % (n=20). Muscle cramps were present in 26% (n=13) cases. Peripheral arterial disease was present in 30% (n=15) of patients. However there was no statistically significant association between the presence of Intradialytic Muscle cramps and peripheral arterial disease (p value =0.18) CONCLUSIONS: Intradialytic Muscle cramps and peripheral arterial disease were common occurrence in end stage renal disease patients on hemodialysis patients, however there was no association between the presence of intradialytic Muscle cramps and peripheral arterial disease.

Prevalence of Peripheral Arterial Disease (PAD) in End Stage Renal Disease (ESRD) Patients on Hemodialysis: a study from central Nepal.

BACKGROUND: Peripheral arterial disease is a common condition in the hemodialysis population with an estimated prevalence ranging from 17-48%. Many studies have been conducted to know the prevalence of peripheral vascular disease in hemodialysis population. However no such study has been conducted so far in Nepal. OBJECTIVE: This study was carried out with an objective to assess the prevalence of Peripheral Arterial Disease in End Stage Renal Disease Patients on Hemodialysis. METHOD: Fifty patients with a diagnosis of End Stage Renal Disease (irrespective of the underlying cause), and those who were on hemodialytic support for more than 3 months were studied over a period of one year. Peripheral arterial disease was diagnosed on the basis of the ankle -brachial index, which was the ratio of the resting systolic blood pressure in the arteries of the ankle to that of the brachial artery, measured by using a standard mercury manometer with a cuff of appropriate size and the Doppler ultrasound. Patients with ankle -brachial index ≤0.9 were considered positive for peripheral arterial disease. RESULT: A total of 50 End Stage Renal Disease patients were analyzed. The mean age of the patient was 49.81±12.63 years. The age range was from 18- 79 years. Majority of them were males 64% (n=32). Peripheral arterial disease defined by ankle -brachial index ≤ 0.9 was present in 30% (n=15) of patients. The three major cause of End Stage Renal Disease in the study population was Chronic Glomerulonephritis 40 % (n=20), Type 2 Diabetes Mellitus 28 % (n=14) and Hypertension 24 % (n=12). Type 2 Diabetes Mellitus was the commonest cause 53% (n=8) of End Stage Renal Disease in patients with peripheral arterial disease followed by hypertension 33% (n=5). On univariate analysis, peripheral arterial disease was found to be significantly associated with age > 40 years (p value= 0.003; OR=14.8; CI=1.75-125.27), Type 2 Diabetes Mellitus (p value= 0.009; OR=5.4; CI=1.44-21.14), parasthesia of lower limbs (p value= 0.001; OR=10; CI-2.31-43.16), and intact PTH >300 ng/ml (p value =0.006; OR=5.7; CI=1.55-21.50). However on multivariate analysis only parasthesia of lower limbs and intact PTH >300 ng/ml were significantly and independently associated with peripheral arterial disease, while other variables were not significant. CONCLUSION: Peripheral arterial disease was common occurrence in End Stage Renal Disease patients on hemodialysis. Ankle -brachial index needs to be included as a routine assessment in End Stage Renal Disease patients to detect peripheral arterial disease at its earliest.

Acute renal failure in falciparum malaria: clinical characteristics, demonstration of oxidative stress, and prognostication.

In this prospective study, we aimed to assess the clinical characteristics of acute renal failure (ARF), determine oxidative stress, as well as to predict the outcome in patients with severe falciparum malaria (FM). The study included a total of 75 subjects; there were 25 adult patients with acute severe FM and ARF, 25 adult patients with uncomplicated FM without ARF, and 25 age- and sex-matched healthy subjects who served as controls. In patients with severe FM and ARF (n = 25), renal failure was non-oliguric in 28% and oliguric in 72%. The average duration of renal failure was 10.53 ± 4.0 days. Sixty percent recovered and 40% died. All patients with non-oliguric presentation recovered. The mean serum malondialdehyde (MDA) levels were 0.82 ± 0.43 µmol/L, 2.97 ± 1.11 µmol/L, and 6.86 ± 2.62 µmol/L, respectively, in healthy controls, in patients with uncomplicated FM, and in those with severe FM with ARF. The Acute Physiology Age and Chronic Health Evaluation II (APACHE II) score, Sequential Organ Failure Assessment (SOFA) score, and the Acute Tubular Necrosis-Individual Severity Index (ATN-ISI) score were all significantly higher in the expired group (19 ± 5.49) when compared to the survivor group (14.4 ± 3.15) (P = 0.014). Kaplan-Meier survival analysis showed that survival was low in patients with delayed hospitalization and longer duration of symptoms. Also, we observed a high occurrence of acute respiratory distress syndrome and central nervous system involvement among the patients who expired.

Carotid intima-media thickness in patients with end-stage renal disease.

Accelerated atherosclerosis and cardiovascular disease are major causes of morbidity and mortality in patients of end-stage renal disease. Carotid intima media thickness is taken as a useful surrogate marker of atherosclerosis. Thirty end-stage renal disease (ESRD) patients were subjected to ultrasonography to study CIMT before the initiation of dialysis. CIMT was found to be higher in ESRD patients than in controls. Levels of a serum marker of oxidative stress were also found to be higher in patients than in the controls. CIMT is an easy, noninvasive, reproducible, and cost-effective investigation in patients with chronic renal failure.

Lattice resistance to dislocation motion at the nanoscale.

In this Letter, we propose a model that demonstrates the effect of a free surface on the lattice resistance experienced by a moving dislocation in nanodimensional systems. This effect manifests in an enhanced velocity of dislocation due to the proximity of the dislocation line to the surface. To verify this finding, molecular dynamics simulations for an edge dislocation in bcc molybdenum are performed, and the results are found to be in agreement with the numerical implementations of this model. The reduction in this effect at higher stresses and temperatures, as revealed by the simulations, confirms the role of lattice resistance behind the observed change in the dislocation velocity.

A giant vesical calculus.

Massive or giant vesical calculus is a rare entity in the recent urological practice. Males are affected more than the females. Vesical calculi are usually secondary to bladder outlet obstruction. These patients present with recurrent urinary tract infection, haematuria or with retention of urine. We report a young male patient who presented with defaecatory problems along with other urinary symptoms. The patient having an average built, non diabetic but hypertensive. The stone could be palpated by physical examination. His urea levels were within normal limits but urine examination shows infection. USG reveals bilateral hydronephrosis with multiple stones in both kidneys along with a giant vesical calculus. After controlling urinary infection and hypertention he underwent an open cystolithotomy. During operation digital rectal help was needed to remove the stone as it was adherent with bladder mucosa. Post operative period was uneventful. His urinary output was quite normal and had no defaecatory problems. Patient left the hospital 10 days after operation.

Lack of detectable shedding of Cryptosporidium parvum oocysts by periparturient dairy cattle.

We examined whether periparturient dairy cattle shed Cryptosporidium parvum oocysts within 12 hr of calving on 3 commercial dairy farms endemic for calfhood cryptosporidiosis. Using a diagnostic method that can detect as few as 1 oocyst per gram of feces, we found no evidence of C. parvum oocysts in 86 fecal samples collected within 12 hr of calving from 43 dairy cows.

Taxol-induced cell cycle arrest and apoptosis: dose-response relationship in lung cancer cells of different wild-type p53 status and under isogenic condition.

The effective dose, schedule, molecular basis of the cytotoxicity of taxol and their dependence on the genetic background in tumor cells are still not well understood. Here, we examined how the dose-response relationship for taxol varies in lung cancer cells with different p53 status and under isogenic conditions. DNA content analyses in A 549 (p53, +/+) and H 1299 (p53, -/-) cells, showed that taxol progressively induced G2/M arrest in both cell lines in a concentration-dependent manner, which was accompanied by a parallel decrease in the G1 population. G2/M arrest, however, occurred at a lower concentration in A 549 cell lines than in H 1299 cells. The S-phase population in A 549 cells was not significantly changed up to 0.025 microM, but dropped by six-fold at 1.0 microM taxol, in contrast to that in H 1299 cells. A sub-G1 apoptotic population was present at 24 h, even at 0.002 microM taxol, when G2/M arrest was not appreciably detected. In both cell lines, the maximum apoptosis of about 28% was achieved at 0.025 microM taxol, implicating that wild-type p53 does not modulate the level of taxol-induced apoptosis. When we examined the role of the wild-type p53 in isogenic cell lines developed in a H 1299 background, the maximum level of apoptosis was in the range of 28-34% at a drug concentration around 0.03 microM, not significantly different from that observed in parental H 1299 cells. We conclude that taxol is effective in inducing apoptosis at very low doses (0.020-0.035 microM), and that the presence or absence of the wild-type p53 does not make a statistically significant difference in the level of apoptotic cell death in these lung cancer cell lines, but the maximum is attained at a lower drug concentration in the presence of p53.

Activation of the insulin-like growth factor II transcription by aflatoxin B1 induced p53 mutant 249 is caused by activation of transcription complexes; implications for a gain-of-function during the formation of hepatocellular carcinoma.

Aflatoxin B1 (AFB1) induced mutation of the p53 gene at codon 249 (p53mt249) is critical during the formation of hepatocellular carcinoma (HCC) following hepatitis B virus (HBV) infection. p53mt249 markedly increases insulin-like growth factor II (IGF-II) transcription largely from promoter 4, accumulating the fetal form of IGF-II. Modulation of the transcription factor binding to IGF-II P4 by wild-type p53 and p53mt249 was identified. Wild-type p53 inhibited binding of transcription factors Sp1 and TBP on the P4 promoter, while p53mt249 enhanced the formation of transcriptional complexes through enhanced DNA-protein (Sp1 or TBP) and protein-protein (Sp1 and TBP) interactions. p53mt249 stimulates transcription factor Sp1 phosphorylation which might be a cause of increased transcription factor binding on the P4 promoter while wild-type p53 does not. Transfection of hepatocytes with p53mt249 impaired induction of apoptosis by the HBV-X protein and TNF-alpha. Therefore, the blocking of apoptosis through enhanced production of IGF-II should provide a favorable opportunity for the selection of transformed hepatocytes. These results explain the molecular basis for the genesis of HCC by p53mt249 which was found to be induced by a potent mutagen, AFB1.

The A enhancer of polyomavirus: protein-protein interactions for the differential early and late promoter function under nonreplicating conditions.

The A enhancer of the polyomavirus early promoter is a 110-bp domain located in the late region and it contains the major late RNA initiation site. The 'core' of this enhancer binds several cellular proteins, including proteins PEA1, PEA2 and PEA3. Another element, NF-D/YY1, is also located in this enhancer. The A enhancer is known to stimulate the early promoter, contains auxiliary elements for replication and serves as the initiator for late transcription. It may also be involved in early-to-late switch. We were interested in investigating how the A-core- and NF-D-binding proteins regulate early and late promoter activity under nonreplicating conditions and how the protein-protein interactions affect the function of the individual elements. By point mutational analysis, we show that, except for PEA1, all other proteins activate the early and late promoters differentially under nonreplicating conditions. All three core-binding proteins, and the protein bound to the NF-D site, are activators and have a combinatorial effect on early promoter activity. On late transcription, only PEA1 acts positively and inactivation of the NF-D site is without any effect. In contrast, PEA2 and PEA3 have a repressor-like activity under nonreplicating conditions, indicating that these two proteins might be involved in repressing late transcription, probably early in infection. By increasing the spacing between two consecutive elements, we further show that protein-protein interaction is important for enhancer function. Transactivation of the early promoter was affected by mutations in all four protein-binding sites. Responsiveness of these factors in regard to the late promoter was parallel to their intrinsic promoter strength. The effects of middle and large T antigens are parallel for both the early and the late promoter, suggesting that the pathway(s) for transactivation function of these oncoproteins may overlap downstream. This study with cloned viral promoter will be reflective of situations in vivo, at least partially, under nonreplicating conditions.

Interaction of human polyomavirus BK with the tumor-suppressor protein p53.

We have been studying the interaction of the oncogenic human polyomavirus BK (BKV) with the tumor-suppressor protein p53 to understand the biology of this virus as well as to understand the basic mechanisms of p53 transactivation. We here demonstrate that p53 binds specifically to the viral promoter at two different sites, S-I (np 361-383) and S-II (np 314-336) in the late region. Site S-I is a 23 bp domain comprising an unique combination of a 10 bp consensus monomer binding site (Pu Pu Pu C (A/T) (T/A) G Py Py Py) which is contiguous with a GC-rich Sp-1 motif that binds p53 in the SV40 promoter. Site S-II also spans a 23 bp sequence containing two tandem consensus binding sites with three base pair mismatches in each and a one base pair deletion. A dimer of a 100 bp region spanning both the binding sites or the site S-I alone induced p53 responsiveness to a basal promoter when cloned upstream from the TATA box, but a similar construct using S-II did not. One tumor-derived mutant protein, p53-175 H, which is defective in DNA binding, also failed to transactivate the reporter gene. We further show that p53 binding-dependent transactivation is abrogated by BKV large T antigen, thereby suggesting an interaction between these two proteins in vivo. In contrast to the isolated p53 binding site, viral early promoter is repressed by p53 in H 1299 cells and the mutants are defective in this function to varying extent. This is suggestive of an involvement of cellular factors in modulating p53's function in the context of the whole promoter. p53 binding sites in BKV are flanked by the binding sites for transcription factors Sp-1 and NF-1 and we show that these transcription factors are present in the immunocomplex with purified p53, implicating modification of p53's transactivation function by protein-protein interaction. Thus, oncoprotein synthesis in this virus might be modulated by p53 in vivo by a complex mechanism other than simple DNA binding and sequestration of the TATA binding protein. Together with SV40 and polyomavirus, which also harbor p53 binding sites, this viral system will serve as a model to understand the role of p53 in viral infection.

Cell-specific modulation of the papovavirus promoters by tumor-suppressor protein p53 in the absence of large T-antigen.

The oncoproteins from several DNA tumor viruses form a complex with p53 and inactivate its function. Wild-type p53 is a transcription factor and can regulate eukaryotic promoters both positively and negatively. To elucidate the basis of the opposing functions and to understand whether and how oncoprotein synthesis in papovaviruses is regulated by p53, we studied modulation of the early promoters of SV40, polyomavirus and BK virus in the absence of the interfering effect of viral large T antigens. We here show that murine p53 can regulate the viral promoters either positively or negatively depending on the cell type. A temperature-sensitive mutant p53, 135 Val, at 37 degrees C also showed a cell-specific effect. These results suggest that promoter activation by p53 is not solely determined by p53 binding site, but host factors modulate p53's transactivation function. A TATA-less polyomavirus late promoter was also repressed in HeLa cells and the level of repression was much less in the presence of active early promoter. As p53 and 135 Val were overexpressed to similar extent in different transfected cell lines, variation in transactivation function is not due to the difference in the level of expressed protein. Our observations thus suggest that p53 interactions with cellular factors in addition to the TATA binding protein (TBP) are important for activator and repressor functions of p53. Well-defined viral promoters could thus provide us with an important tool for the identification and characterization of cellular factors that modulate p53-binding dependent gene regulation in animal cells.

Acute renal failure associated with freshwater fish toxin.

Clinical observations on toxicity after ingestion of gall bladder of Labeo rohita, a freshwater fish found commonly in India, were recorded from 22 patients between 1985 to 1990. The gall bladder in raw, cooked or desiccated form was swallowed as a traditional method of treatment for various chronic diseases. Patients generally presented with gastrointestinal symptoms such as cramping pain, nausea and vomiting within 12 hours (mean 4.6 +/- 3.7 hours) after ingestion. Subsequently renal failure was observed in all and hepatic dysfunction in some (36.3%) patients. The outcome in general is good. From the clinical course the role of toxic substance(s) is presumed as the causative factor(s), which needs further evaluation.

Biochemical and mutational analysis of the polyomavirus core promoter: involvement of nuclear factor-1 in early promoter function.

The polyomavirus enhancer is separated from the early RNA initiation sites by a 120 bp promoter region. To identify the core promoter elements, we introduced base-substitution mutations within the potential elements in the vicinity of the RNA initiation site. Three of these mutants, two with mutations within a putative nuclear factor-1 (NF-1) binding site and the other within the TATA box, exhibited reduced promoter activity by about threefold in the mouse NIH 3T3 cell line. The activity of the other three mutants was either little affected or remained unchanged. Mobility shift assays using specific competitors and antibodies against NF-1 demonstrated the binding of a protein of the NF-1 family at a site adjacent to the TATA box, suggesting a role for NF-1 binding in early promoter function. The effect of these mutations was also evaluated in undifferentiated mouse embryonal carcinoma (F9) cells in the presence of an additional mutation (F441) at nucleotide position 5233. This additional mutation creates a strong binding site for a transcription factor, TEF-1, and helps the virus to grow in this cell line. While the TATA box and the GC box mutants behaved qualitatively in a similar fashion, the NF-1 motif now played a minor role in F9 cells. Western blot experiments demonstrated low levels of NF-1 protein in this cell line. The NF-1 motif partially overlaps a T-antigen binding motif and this motif is not involved in T-antigen-mediated regulation of the early promoter. Our results suggest that a protein of the NF-1 family binds to the core promoter and is important for early transcription in vivo. We further demonstrate that undifferentiated F9 cells contain a very low level of NF-1 and the F441 mutant possibly follows a different mechanism for promoter function in these cells.

Identification of proteins binding to the F441 locus of polyomavirus B enhancer that are required for its activity in embryonic carcinoma cells.

A point mutation at nucleotide 5233 of the polyomavirus (A2 strain) enables it to overcome growth restriction in undifferentiated embryonal carcinoma cells. We analysed the binding of nuclear proteins from F9 cells to a 38 bp region that spans this site of mutation and encompasses two copies of the bovine papillomavirus core sequence, CCACCC, and characterized this domain by mutational analysis. Our results showed that the F441 mutation creates a sequence motif which binds TEF-1 or a TEF-1-like protein from F9 cells more strongly than its wild-type counterpart and increases its activity by about 10-fold. Another protein identified as CP1 binds with increased affinity in the presence of the F441 mutation to the CAT box-like sequences which is contiguous with the downstream CCACCC box. Point mutations within these two motifs that abolished binding in vitro also impaired the activity of the F441 locus in vivo. As neither the wild-type sequence without the F441 mutation, nor the F441 template without the CAT box has appreciable activity in vivo, interaction between these two elements is required for function. At a higher level of organization, this interaction is probably extended to factors bound to other domains in the A and B enhancer.