Controlled inter-state switching between quantized conductance states in resistive devices for multilevel memory

A detailed understanding of quantization conductance (QC), their correlation with resistive switching phenomena and controlled manipulation of quantized states is crucial for realizing atomic-scale multilevel memory elements. Here, we demonstrate highly stable and reproducible quantized conductance states (QC-states) in Al/Niobium oxide/Pt resistive switching devices. Three levels of control over the QC-states, required for multilevel quantized state memories, like, switching ON to different quantized states, switching OFF from quantized states, and controlled inter-state switching among one QC states to another has been demonstrated by imposing limiting conditions of stop-voltage and current compliance. The well defined multiple QC-states along with a working principle for switching among various states show promise for implementation of multilevel memory devices

Genetic variation and heritability estimation in Jatropha curcas L. progenies for seed yield and vegetative traits

In this study, experiment was conducted on sandy loam soils poor in organic carbon and water holding capacity in southern Haryana, India to determine the best progenies of Jatropha curcas for bio-diesel production. Fifty progenies raised from seed sources collected from nine states of India were evaluated after five years of plantation for growth, seed and oil content traits. The progenies showed significant (P> 0.05) differences for all the traits studied. Maximum seed yield/plant (879.37 g), number of capsules/plant (522.67) and plant height (408.33 cm) was recorded in P-44. Maximum oil content observed in P-37 (36.08%) followed by P-5 (35.64%). The magnitude of phenotypic coefficient of variation (PCV) was higher than the corresponding genotypic coefficient of variation (GCV) for all the characters studied. Heritability was highest for oil content (95.49%) and 100-seed weight (87.75%) followed by seed yield (75.54%). Total capsules/plant exhibited highest genetic advance (92.69%) followed by number of branches per plant (64.32%). Hierarchical Euclidean cluster analysis of all 50 progenies using D2 statistics was done where the D2 analysis grouped the progenies into five clusters. The intra cluster distances ranged from 1.33 to 2.72. The maximum inter-cluster distance was observed between cluster II and V (6.43) followed by I and V indicating greater divergence among progenies belonging to these clusters and an attempt to cross the progenies in these clusters should bring out desirable gene combinations. These progenies showed considerable potential which can be tapped for planting and selecting the improved varieties

SWI/SNF regulates a transcriptional programme that induces senescence to prevent liver cancer

Oncogene-induced senescence (OIS) is a potent tumour suppressor mechanism. To identify senescence regulators relevant to cancer, we screened an shRNA library targeting genes deleted in hepatocellular carcinoma (HCC). Here, we describe how knockdown of the SWI/SNF component ARID1B prevents OIS and cooperates with RAS to induce liver tumours. ARID1B controls p16INK4a and p21CIP1a transcription but also regulates DNA damage, oxidative stress and p53 induction, suggesting that SWI/SNF uses additional mechanisms to regulate senescence. To systematically identify SWI/SNF targets regulating senescence, we carried out a focused shRNA screen. We discovered several new senescence regulators including ENTPD7, an enzyme that hydrolyses nucleotides. ENTPD7 affects oxidative stress, DNA damage and senescence. Importantly, expression of ENTPD7 or inhibition of nucleotide synthesis in ARID1B-depleted cells results in re-establishment of senescence. Our results identify novel mechanisms by which epigenetic regulators can affect tumor progression and suggest that pro-senescence therapies could be employed against SWI/SNF-mutated cancers

Research into the effect Of SGLT2 inhibition on left ventricular remodelling in patients with heart failure and diabetes mellitus (REFORM) trial rationale and design

Background Heart failure (HF) and diabetes (DM) are a lethal combination. The current armamentarium of anti-diabetic agents has been shown to be less efficacious and sometimes even harmful in diabetic patients with concomitant cardiovascular disease, especially HF. Sodium glucose linked co-transporter type 2 (SGLT2) inhibitors are a new class of anti-diabetic agent that has shown potentially beneficial cardiovascular effects such as pre-load and after load reduction through osmotic diuresis, blood pressure reduction, reduced arterial stiffness and weight loss. This has been supported by the recently published EMPA-REG trial which showed a striking 38 and 35 % reduction in cardiovascular death and HF hospitalisation respectively. Methods The REFORM trial is a novel, phase IV randomised, double blind, placebo controlled clinical trial that has been ongoing since March 2015. It is designed specifically to test the safety and efficacy of the SLGT2 inhibitor, dapagliflozin, on diabetic patients with known HF. We utilise cardiac-MRI, cardio-pulmonary exercise testing, body composition analysis and other tests to quantify the cardiovascular and systemic effects of dapagliflozin 10 mg once daily against standard of care over a 1 year observation period. The primary outcome is to detect the change in left ventricular (LV) end systolic and LV end diastolic volumes. The secondary outcome measures include LV ejection fraction, LV mass index, exercise tolerance, fluid status, quality of life measures and others. Conclusions This trial will be able to determine if SGLT2 inhibitor therapy produces potentially beneficial effects in patients with DM and HF, thereby replacing current medications as the drug of choice when treating patients with both DM and HF

Harnessing the potential of ligninolytic enzymes for lignocellulosic biomass pretreatment

Abundant lignocellulosic biomass from various industries provides a great potential feedstock for the production of value-added products such as biofuel, animal feed, and paper pulping. However, low yield of sugar obtained from lignocellulosic hydrolysate is usually due to the presence of lignin that acts as a protective barrier for cellulose and thus restricts the accessibility of the enzyme to work on the cellulosic component. This review focuses on the significance of biological pretreatment specifically using ligninolytic enzymes as an alternative method apart from the conventional physical and chemical pretreatment. Different modes of biological pretreatment are discussed in this paper which is based on (i) fungal pretreatment where fungi mycelia colonise and directly attack the substrate by releasing ligninolytic enzymes and (ii) enzymatic pretreatment using ligninolytic enzymes to counter the drawbacks of fungal pretreatment. This review also discusses the important factors of biological pretreatment using ligninolytic enzymes such as nature of the lignocellulosic biomass, pH, temperature, presence of mediator, oxygen, and surfactant during the biodelignification process

Substitution of lead with tin suppresses ionic transport in halide perovskite optoelectronics.

Despite the rapid rise in the performance of a variety of perovskite optoelectronic devices with vertical charge transport, the effects of ion migration remain a common and longstanding Achilles' heel limiting the long-term operational stability of lead halide perovskite devices. However, there is still limited understanding of the impact of tin (Sn) substitution on the ion dynamics of lead (Pb) halide perovskites. Here, we employ scan-rate-dependent current-voltage measurements on Pb and mixed Pb-Sn perovskite solar cells to show that short circuit current losses at lower scan rates, which can be traced to the presence of mobile ions, are present in both kinds of perovskites. To understand the kinetics of ion migration, we carry out scan-rate-dependent hysteresis analyses and temperature-dependent impedance spectroscopy measurements, which demonstrate suppressed ion migration in Pb-Sn devices compared to their Pb-only analogues. By linking these experimental observations to first-principles calculations on mixed Pb-Sn perovskites, we reveal the key role played by Sn vacancies in increasing the iodide ion migration barrier due to local structural distortions. These results highlight the beneficial effect of Sn substitution in mitigating undesirable ion migration in halide perovskites, with potential implications for future device development

Association of cytokines with endothelium dependent flow mediated vasodilation (FMD) of systemic arteries in patients with non-ischemic cardiomyopathy

<p>Abstract</p> <p>Background</p> <p>Aim of this study was to elucidate the relation between localised inflammatory heart disease and endothelial dysfunction in the peripheral circulation, considering circulating cytokines as a potential link.</p> <p>Methods</p> <p>In 38 patients with non-ischemic heart disease, myocardial biopsies were examined for myocardial inflammation (immunohistology) and virus persistence (PCR). Cytokines (sIL-4, IFN-g, IFN-b, IFN-a, sIL-12p7, TNF-a) were measured by ELISA in venous serum. Endothelial function of the radial artery was examined by ultrasound, measuring diameter changes in response to reactive hyperemia (FMD), compared to glyceroltrinitrate (GTN-MD). Patients with EF < 35% were excluded.</p> <p>Results</p> <p>Age 44 ± 14 years, 19 male, 19 female, EF 63.5[16]%. FMD 4.38 [4.82]%. 30 patients had myocardial inflammation (8 not), 23 virus persistence (15 not). FMD correlated significantly with sIL-12p7 (p = 0.024, r = -0.365), but not with other cytokines. sIL-12p7 levels were significantly higher in patients with severely impaired FMD (n = 17), compared with normal FMD (n = 21): 10.70 [10.72] vs. 4.33 [7.81] pg/ml (p = 0.002). Endothelium independent vasodilation (GTN-MD 23.67 [8.21]%) was not impaired.</p> <p>Conclusion</p> <p>Endothelial dysfunction of peripheral arteries in patients with non-ischemic cardiomyopathy is associated with elevated serum concentrations of sIL-12p7, but not of other cytokines. Circulating sIL-12p7 may partly explain, that endothelial dysfunction is not restricted to the coronary circulation, but involves systemic arteries.</p

Glutathione Deficiency in Cardiac Patients Is Related to the Functional Status and Structural Cardiac Abnormalities

International audienceBACKGROUND: The tripeptide glutathione (L-gamma-glutamyl-cysteinyl-glycine) is essential to cell survival, and deficiency in cardiac and systemic glutathione relates to heart failure progression and cardiac remodelling in animal models. Accordingly, we investigated cardiac and blood glutathione levels in patients of different functional classes and with different structural heart diseases. METHODS: Glutathione was measured using standard enzymatic recycling method in venous blood samples obtained from 91 individuals, including 15 healthy volunteers and 76 patients of New York Heart Association (NYHA) functional class I to IV, undergoing cardiac surgery for coronary artery disease, aortic stenosis or terminal cardiomyopathy. Glutathione was also quantified in right atrial appendages obtained at the time of surgery. RESULTS: In atrial tissue, glutathione was severely depleted (-58%) in NYHA class IV patients compared to NYHA class I patients (P = 0.002). In patients with coronary artery disease, this depletion was related to the severity of left ventricular dysfunction (P = 0.006). Compared to healthy controls, blood glutathione was decreased by 21% in NYHA class I patients with structural cardiac disease (P<0.01), and by 40% in symptomatic patients of NYHA class II to IV (P<0.0001). According to the functional NYHA class, significant depletion in blood glutathione occurred before detectable elevation in blood sTNFR1, a marker of symptomatic heart failure severity, as shown by the exponential relationship between these two parameters in the whole cohort of patients (r = 0.88). CONCLUSIONS: This study provides evidence that cardiac and systemic glutathione deficiency is related to the functional status and structural cardiac abnormalities of patients with cardiac diseases. These data also suggest that blood glutathione test may be an interesting new biomarker to detect asymptomatic patients with structural cardiac abnormalities

Cardiovascular Safety in Oncology Clinical Trials:JACC: CardioOncology Primer

The development of novel treatments has improved cancer outcomes but may result in cardiovascular toxicities. Traditional approaches to clinical trial safety evaluation have limitations in their ability to detect signals of cardiovascular risk. Mechanisms to increase power and specificity to clarify cardiovascular safety are required. However, implications include increased costs and slower development. The Cardiovascular Safety Research Consortium facilitated stakeholder discussions with representation from academia, industry, and regulators. A think tank was assembled with the aim of providing recommendations for improved collection and reporting of cardiovascular safety signals in oncology trials. Two working groups were formed. The first focuses on incorporation of consensus definitions of cardiovascular disease into the Common Terminology Criteria for Adverse Events used in oncology trial reporting. The second group considers methods for ascertainment and adjudication of cardiovascular events in cancer trials. The overarching aim of this primer is to improve understanding of the potential cardiovascular toxicities of cancer therapies.</p

Neutrophil to Lymphocyte Ratio and Outcomes in Patients with New-Onset or Worsening Heart Failure with Reduced and Preserved Ejection Fraction

Inflammation is thought to play a role in heart failure (HF) pathophysiology. Neutrophil-to-lymphocyte ratio (NLR) is a simple, routinely available measure of inflammation. Its relationship with other inflammatory biomarkers and its association with clinical outcomes in addition to other risk markers have not been comprehensively evaluated in HF patients. Methods We evaluated patients with worsening or new-onset HF from the BIOlogy Study to Tailored Treatment in Chronic Heart Failure (BIOSTAT-CHF) study who had available NLR at baseline. The primary outcome was time to all-cause mortality or HF hospitalization. Outcomes were validated in a separate HF population. Results 1622 patients were evaluated (including 523 ventricular ejection fraction [LVEF] < 40% and 662 LVEF ≥ 40%). NLR was significantly correlated with biomarkers related to inflammation as well as NT-proBNP. NLR was significantly associated with the primary outcome in patients irrespective of LVEF (hazard ratio [HR] 1.18 per standard deviation increase; 95% confidence interval [CI] 1.11–1.26, P < 0.001). Patients with NLR in the highest tertile had significantly worse outcome than those in the lowest independent of LVEF (<40%: HR 2.75; 95% CI 1.84–4.09, P < 0.001; LVEF ≥ 40%: HR 1.51; 95% CI 1.05–2.16, P = 0.026). When NLR was added to the BIOSTAT-CHF risk score, there were improvements in integrated discrimination index (IDI) and net reclassification index (NRI) for occurrence of the primary outcome (IDI + 0.009; 95% CI 0.00–0.019, P = 0.030; continuous NRI + 0.112, 95% CI 0.012–0.176, P = 0.040). Elevated NLR was similarly associated with adverse outcome in the validation cohort. Decrease in NLR at 6 months was associated with reduced incidence of the primary outcome (HR 0.75; 95% CI 0.57–0.98, P = 0.036). Conclusions Elevated NLR is significantly associated with elevated markers of inflammation in HF patients and is associated with worse outcome. Elevated NLR might potentially be useful in identifying high-risk HF patients and may represent a treatment target