Early Release Science of the exoplanet WASP-39b with JWST NIRSpec PRISM.

Transmission spectroscopy1-3 of exoplanets has revealed signatures of water vapour, aerosols and alkali metals in a few dozen exoplanet atmospheres4,5. However, these previous inferences with the Hubble and Spitzer Space Telescopes were hindered by the observations' relatively narrow wavelength range and spectral resolving power, which precluded the unambiguous identification of other chemical species-in particular the primary carbon-bearing molecules6,7. Here we report a broad-wavelength 0.5-5.5 µm atmospheric transmission spectrum of WASP-39b8, a 1,200 K, roughly Saturn-mass, Jupiter-radius exoplanet, measured with the JWST NIRSpec's PRISM mode9 as part of the JWST Transiting Exoplanet Community Early Release Science Team Program10-12. We robustly detect several chemical species at high significance, including Na (19σ), H2O (33σ), CO2 (28σ) and CO (7σ). The non-detection of CH4, combined with a strong CO2 feature, favours atmospheric models with a super-solar atmospheric metallicity. An unanticipated absorption feature at 4 µm is best explained by SO2 (2.7σ), which could be a tracer of atmospheric photochemistry. These observations demonstrate JWST's sensitivity to a rich diversity of exoplanet compositions and chemical processes.

CHARIOT: a phase I study of berzosertib with chemoradiotherapy in oesophageal and other solid cancers using time to event continual reassessment method.

BACKGROUND: Berzosertib (M6620) is a highly potent (IC50 = 19 nM) and selective, first-in-class ataxia telangiectasia-mutated and Rad3-related protein kinase (ATR) inhibitor. This trial assessed the safety, preliminary efficacy, and tolerance of berzosertib in oesophageal cancer (A1 cohort) with RT and advanced solid tumours (A2 cohort) with cisplatin and capecitabine. METHODS: Single-arm, open-label dose-escalation (Time-to-Event Continual Reassessment Method) trial with 16 patients in A1 and 18 in A2. A1 tested six dose levels of berzosertib with RT (35 Gy over 15 fractions in 3 weeks). RESULTS: No dose-limiting toxicities (DLTs) in A1. Eight grade 3 treatment-related AEs occurred in five patients, with rash being the most common. The highest dose (240 mg/m2) was determined as the recommended phase II dose (RP2D) for A1. Seven DLTs in two patients in A2. The RP2D of berzosertib was 140 mg/m2 once weekly. The most common grade ≥3 treatment-related AEs were neutropenia and thrombocytopenia. No treatment-related deaths were reported. CONCLUSIONS: Berzosertib combined with RT is feasible and well tolerated in oesophageal cancer patients at high palliative doses. Berzosertib with cisplatin and capecitabine was well tolerated in advanced cancer. Further investigation is warranted in a phase 2 setting. CLINICAL TRIALS IDENTIFIER: EU Clinical Trials Register (EudraCT) - 2015-003965-27 ClinicalTrials.gov - NCT03641547.

First principle studies on structural, elastic, electronic, optical, and thermoelectric properties of new perovskite TlTaO3: For renewable energy applications.

The structural, optoelectronics, and transport properties of TlTaO3 compounds were determined utilizing the full potential augmented plane wave approach using first-principle method. We have considered the generalized gradient approximation for structural optimization and modified Becke-Johnson for electronic properties. The electronic properties reveal that the studied TlTaO3 possesses direct bandgap of magnitude 1.52 eV. Between 0 and 12 eV, optical spectra calculations are made, taking into account the real and imaginary parts of the dielectric function, refractive index, and loss function. The transport properties are estimated considering Boltzmann transport theory. The Seebeck coefficient, electrical conductivity, thermal conductivity, and power factor are all assessed using the Boltzmann transport theory. The optimized thermoelectric response of the examined TlTaO3 is produced by the improved carrier mobility, which also improves the thermoelectric efficiency of the TlTaO3. The obtained results will act as a theoretical road map for upcoming experimental and commercial TlTaO3 applications.

Platelet lysate can support the development of a 3D-engineered skin for clinical application.

Safety concerns associated with foetal bovine serum (FBS) have restricted its translation into clinics. We hypothesised that platelet lysate (PL) can be utilised as a safe alternative to produce serum-free 3D-engineered skin. PL supported a short-term expansion of fibroblasts, with negligible replication-induced senescence and directed epidermal stratification. PL-expanded fibroblasts were phenotypically separated into three subpopulations of CD90+FAP+, CD90+FAP- and CD90-FAP+, based on CD90 (reticular marker) and FAP (papillary marker) expression profile. PL drove the expansion of the intermediate CD90+ FAP+ subpopulation in expense of reticular CD90+FAP-, which may be less fibrotic once grafted. The 3D-engineered skin cultured in PL was analysed by immunofluorescence using specific markers. Detection of ColIV and LMN-511 confirmed basement membrane. K10 confirmed near native differentiation pattern of neo-epidermis. CD29- and K5-positive interfollicular stem cells were also sustained. Transmission and scanning electron microscopies detailed the ultrastructure of the neo-dermis and neo-epidermis. To elucidate the underlying mechanism of the effect of PL on skin maturation, growth factor contents in PL were measured, and TGF-ß1 was identified as one of the most abundant. TGF-ß1 neutralising antibody reduced the number of Ki67-positive proliferative cells, suggesting TGF-ß1 plays a role in skin maturation. Moreover, the 3D-engineered skin was exposed to lucifer yellow on days 1, 3 and 5. Penetration of lucifer yellow into the skin was used as a semi-quantitative measure of improved barrier function over time. Our findings support the concept of PL as a safe and effective serum alternative for bioengineering skin for cell therapies.

Phase switching phenomenon in a system of three coupled DC glow discharge plasmas.

We report the first experimental observations of phase switching in a system of three coupled plasma sources. Two of the plasma sources are inductively coupled to each other while the third one is directly coupled to one of them. The coupled system acquires a frequency pulling synchronized state following which a transition occurs to a frequency entrainment state with an increase in the frequency of the directly coupled system. We also observe a sudden jump from a lower to a higher frequency entrainment state and a concomitant phase switching between the oscillations of the two directly coupled sources while the phase difference between the inductively coupled sources remains constant. These experimental findings are established using various diagnostic tools, such as the Fourier spectra, frequency bifurcation plots, Lissajous plots, and Hilbert transforms of the data. The experimental results are qualitatively modeled using three coupled van der Pol equations, in which two of them are environmentally coupled while the third one is directly coupled with one of them.

Clinical perspectives, immunohematologic insights, and transfusion management in IgA-associated autoimmune hemolytic anemia.

Autoimmune hemolytic anemia (AIHA) due to warm-reacting IgA autoantibodies is rare. Here, we explored the clinical and immunohematologic characteristics of patients suffering from IgA-associated warm AIHA (WAIHA) and their transfusion management. The 9-year study included 214 patients with WAIHA who were further classified into two groups: (1) IgA-associated WAIHA and (2) non-IgA-associated WAIHA. Clinical and laboratory details were obtained from patient files and the Hospital Information System. All immunohematologic investigations were performed following standard operating procedures and established protocols. Among the 214 patients with WAIHA, 17 (7.9%) belonged to the IgA-associated group; of these, two IgA-only WAIHA cases were found. The mean hemoglobin in this group was 5.58 g/dL, and 15 (88.2%) of these patients received a total of 32 units of packed red blood cell (RBC) transfusions. In vivo hemolytic markers were significantly abnormal in the IgA-associated WAIHA group when compared with the non-IgA group. Secondary WAIHA was found in 11 (64.7%) patients with IgA-associated WAIHA. Patients with IgA-associated WAIHA received more blood transfusions than individuals in the non-IgA group (p = 0.0004). A total of 17 (7.9%) patients with WAIHA experienced adverse events to blood transfusion. Detailed characterization of WAIHA with particular emphasis on IgA-associated and non-IgA-associated WAIHA is essential to evaluate the disease characteristics, access the degree of hemolysis, understand the immunohematologic behaviors of the antibodies, and manage blood transfusions.

Fracture risk in hypoparathyroidism: a systematic review and meta-analysis.

In this meta-analysis, we analyzed 7 observational studies for assessing the fracture risk in patients with hypoparathyroidism (hypoPT). We found that the risk of vertebral fractures is increased by almost 2-fold, especially those with nonsurgical hypoPT. PURPOSE: Patients with hypoPT have higher bone mineral density than age- and sex-matched controls. This would theoretically translate into a lower risk of fractures, although available clinical evidence is contradictory. Hence, the present systematic review and meta-analysis was undertaken to collate and provide a precise summary of fracture risk in hypoPT. METHODS: PubMed, Scopus, and Web of Science databases were systematically searched using appropriate keywords till March 8, 2021, to identify observational studies reporting the rate of occurrence of fractures among hypoPT patients (nonsurgical and/or postsurgical) compared to non-hypoPT subjects (controls). Study quality was assessed using Newcastle-Ottawa Scale. Pooled odds ratio (OR) with 95% confidence intervals (CI) was calculated. Subgroup analyses of nonsurgical and postsurgical hypoPT patients were also conducted. RESULTS: We identified 7 observational studies of high-quality pooling data retrieved from 1470 patients with hypoPT. When stratified based on the skeletal site, pooled analyses showed that hypoPT patients were at an increased risk of vertebral fractures compared to non-hypoPT controls (OR 2.22, 95% CI: 1.23, 4.03, p = 0.009, I2 = 49%, random-effects model). The increased risk of vertebral fractures was seen only in patients with nonsurgical hypoPT (OR 2.31, 95% CI: 1.32, 4.03, p = 0.003, I2 = 3%, random-effects model) but not in those with postsurgical hypoPT. hypoPT patients were not at an increased or decreased risk of any, humerus, or proximal femur/hip fractures than controls. CONCLUSIONS: Nonsurgical hypoPT patients are at an almost 2-fold increased risk of vertebral fractures and thus need to be actively screened irrespective of the underlying BMD.

Blood group discrepancy in Ah para-Bombay phenotype: a rare blood group variant and its clinical significance.

Individuals with the rare para-Bombay phenotype have inherited defects in producing H associated with FUT1 and/or FUT2 genes. We report a case of blood group discrepancy in a para-Bombay patient from a tertiary care hospital of eastern India. A 31-year-old woman with rheumatic heart disease presented with fatigue and breathlessness and was then scheduled for valvuloplasty, for which a blood transfusion request was sent to the blood center. During pre-transfusion testing, red blood cell (RBC) testing showed group O, and serum testing showed strong reactivity with group B RBCs, weak reactivity with group O RBCs, and very weak reactivity with group A RBCs. Saliva inhibition testing and enzyme treatment of RBCs concluded the patient to be of "Ah para-Bombay" phenotype. The patient's Lewis phenotype was Le(a-b+). This patient's serum also had cold-reacting anti-IH along with anti-B. This case report highlights the importance of performing an advanced immunohematologic workup, including adsorption, elution, enzyme treatment, and saliva inhibition testing for identification of weak A or B subgroups as well as the rare para-Bombay blood group, when routine ABO typing, using forward and reverse grouping, is inconclusive. Accurate identification of blood group helps in preventing transfusion-related adverse events and encouraging safe transfusion practice.Individuals with the rare para-Bombay phenotype have inherited defects in producing H associated with FUT1 and/or FUT2 genes. We report a case of blood group discrepancy in a para-Bombay patient from a tertiary care hospital of eastern India. A 31-year-old woman with rheumatic heart disease presented with fatigue and breathlessness and was then scheduled for valvuloplasty, for which a blood transfusion request was sent to the blood center. During pre-transfusion testing, red blood cell (RBC) testing showed group O, and serum testing showed strong reactivity with group B RBCs, weak reactivity with group O RBCs, and very weak reactivity with group A RBCs. Saliva inhibition testing and enzyme treatment of RBCs concluded the patient to be of "Ah para-Bombay" phenotype. The patient's Lewis phenotype was Le(a­b+). This patient's serum also had cold-reacting anti-IH along with anti-B. This case report highlights the importance of performing an advanced immunohematologic workup, including adsorption, elution, enzyme treatment, and saliva inhibition testing for identification of weak A or B subgroups as well as the rare para-Bombay blood group, when routine ABO typing, using forward and reverse grouping, is inconclusive. Accurate identification of blood group helps in preventing transfusion-related adverse events and encouraging safe transfusion practice.

Observational study to compare the effect of altitude on cardiopulmonary reserves of different individuals staying more than 6 weeks at 10,000 ft and 15,000 ft.

BACKGROUND: The variation in heights beyond high altitude has different effects on the cardiorespiratory profile of individuals because of variation in oxygen density with every thousand feet. This study was planned to analyze and compare the effects of difference in altitudes on cardiorespiratory profile from anesthesiologist's point of view. METHODS: A multicenter observational study was done involving two different groups of 600 patients at 10,000 ft (Group A) and 15,000 ft (Group B). Observation and comparison of oxygen saturation, 6-min walk test, and breath holding time was carried out. RESULTS: Fifty-five percent of subjects in Group A had oxygen saturation of more than 93% in comparison to 5.5% in Group B. This was statistically significant (P < 0.001). Two percent of subjects in Group A in comparison to 63.5% of Group B had oxygen saturation of less than 88% (P < 0.001). Percentage increase of more than 15% of heart rate was found to be statistically significant in all the age groups. Overall, 3.8% of individuals in Group A had breath holding time less than 15 s in comparison to 16.6% of individuals in Group B (P value < 0.001). CONCLUSION: The study demonstrates that there is a significant fall in oxygen saturation, significant rise in the heart rate in 6-min walk test, and significant fall in the breath holding time in the group located at 15,000 ft. Heights beyond 10,000 ft should be restricted to life and limb saving surgeries, and logistics should be focused more on "scoop and run" than "stay and play" policy.

Correction: Feasibility of attenuated total reflection-fourier transform infrared (ATR-FTIR) chemical imaging and partial least squares regression (PLSR) to predict protein adhesion on polymeric surfaces.

Correction for 'Feasibility of attenuated total reflection-fourier transform infrared (ATR-FTIR) chemical imaging and partial least squares regression (PLSR) to predict protein adhesion on polymeric surfaces' by S. Mukherjee et al., Analyst, 2019, 144, 1535-1545. DOI.

Susceptibility to neurofibrillary tangles: role of the PTPRD locus and limited pleiotropy with other neuropathologies.

Tauopathies, including Alzheimer's disease (AD) and other neurodegenerative conditions, are defined by a pathological hallmark: neurofibrillary tangles (NFTs). NFT accumulation is thought to be closely linked to cognitive decline in AD. Here, we perform a genome-wide association study for NFT pathologic burden and report the association of the PTPRD locus (rs560380, P=3.8 × 10-8) in 909 prospective autopsies. The association is replicated in an independent data set of 369 autopsies. The association of PTPRD with NFT is not dependent on the accumulation of amyloid pathology. In contrast, we found that the ZCWPW1 AD susceptibility variant influences NFT accumulation and that this effect is mediated by an accumulation of amyloid ß plaques. We also performed complementary analyses to identify common pathways that influence multiple neuropathologies that coexist with NFT and found suggestive evidence that certain loci may influence multiple different neuropathological traits, including tau, amyloid ß plaques, vascular injury and Lewy bodies. Overall, these analyses offer an evaluation of genetic susceptibility to NFT, a common end point for multiple different pathologic processes.

Feasibility of attenuated total reflection-fourier transform infrared (ATR-FTIR) chemical imaging and partial least squares regression (PLSR) to predict protein adhesion on polymeric surfaces.

Predicting the degree to which proteins adhere to a polymeric surface is an ongoing challenge in the scientific community to prevent non-specific protein adhesion and drive favourable protein - surface interactions. This work explores the potential of multivariate PLSR modelling in conjunction with Attenuated Total Reflection - Fourier Transform Infrared (ATR-FTIR) chemical imaging to investigate whether experimentally characterised surface chemistry can be used to predict surface protein adhesion. ATR-FTIR spectra were collected on dry and wetted polymeric surfaces, followed by evaluation of adhered fibrinogen on surfaces using the micro bicinchoninic (BCA) protein assay as a reference method. Partial Least Squares Regression (PLSR) models were built using IR spectra as the predictor variable. Overall the models built with 'wetted polymer' IR spectra performed better as compared to the models built using 'dry polymer' IR spectra (average coefficient of determination, R2P 0.998, 0.996 respectively), with the lowest error in prediction (4 ± 0.6 µg) for ultra-high molecular weight polyethylene (UHMPE) as a test surface. This indicates the potential of this method to predict the degree to which protein adhesion occurs on polymeric surfaces using experimentally determined surface chemistry.

Effect of Si substitution in ferromagnetic Pr2Fe17: a magnetocaloric material with zero thermal expansion operative at high temperature.

This article deals with the magnetic and thermal expansion properties of Pr2Fe16Si. This compound has been well characterized from the structural point of view by analysing X-ray diffraction (XRD) patterns. The temperature dependent behaviour of magnetization (M) and the structural parameters (lattice parameters, unit cell volume) suggest that the compound undergoes a second order phase transition from a paramagnetic to a ferromagnetic state at TC = 390 K, driven by an increase in bond length between iron atoms at 6c sites. The field-dependent behaviour of M below TC, and comparatively lower value of coercivity (Hc) have been explained by the role of Si atoms as pinning centres. In the ferromagnetic phase, the system is found to behave like an inhomogenous mean field system. The study of thermal expansion properties establishes that the compound is a zero thermal expansion material (αv = 5.3 × 10-6 K-1) operative in the temperature range T = 200-340 K. As a magnetocaloric material, Pr2Fe16Si possesses high RCP (87 J kg-1 at µ0H = 1.5 T), high operating temperature (390 K) and moderate |ΔSM|max.

Reduction of Thermal Conductivity in Nanowires by Combined Engineering of Crystal Phase and Isotope Disorder.

Nanowires are a versatile platform to investigate and harness phonon and thermal transport phenomena in nanoscale systems. With this perspective, we demonstrate herein the use of crystal phase and mass disorder as effective degrees of freedom to manipulate the behavior of phonons and control the flow of local heat in silicon nanowires. The investigated nanowires consist of isotopically pure and isotopically mixed nanowires bearing either a pure diamond cubic or a cubic-rhombohedral polytypic crystal phase. The nanowires with tailor-made isotopic compositions were grown using isotopically enriched silane precursors 28SiH4, 29SiH4, and 30SiH4 with purities better than 99.9%. The analysis of polytypic nanowires revealed ordered and modulated inclusions of lamellar rhombohedral silicon phases toward the center in otherwise diamond-cubic lattice with negligible interphase biaxial strain. Raman nanothermometry was employed to investigate the rate at which the local temperature of single suspended nanowires evolves in response to locally generated heat. Our analysis shows that the lattice thermal conductivity in nanowires can be tuned over a broad range by combining the effects of isotope disorder and the nature and degree of polytypism on phonon scattering. We found that the thermal conductivity can be reduced by up to ∼40% relative to that of isotopically pure nanowires, with the lowest value being recorded for the rhombohedral phase in isotopically mixed 28Si x30Si1- x nanowires with composition close to the highest mass disorder ( x ∼ 0.5). These results shed new light on the fundamentals of nanoscale thermal transport and lay the groundwork to design innovative phononic devices.

An in vitro study to compare the influence of different all-ceramic systems on the polymerization of dual-cure resin cement.

AIM: The aim of the study is to compare the effect of composition of three different all-ceramic systems on the polymerization of dual-cure resin cement, using different curing cycles and evaluated immediately within 15 min and after 24 h. MATERIALS AND METHODS: Resin cement disc samples were fabricated by polymerization through three different all-ceramic disc, namely: lithium disilicate discs - IPS e.max (Group B), leucitereinforced discs - IPS Empress (Group C), zirconia discs - Cercon (Group D), and without an intervening ceramic disc, as control (Group A). A total of 80 resin cement disc samples were fabricated for fur groups (n = 20). Each group further consisted of two subgroups (n = 10), t10 and t20 according to two different exposure times of 10 and 20 s, respectively. Each of the 80 resin disc samples was evaluated for their degree of polymerization achieved, by measuring the microhardness(Vickers hardness number) of the samples immediately within 15 min and after 24 h, giving us a total of 160 readings. Oneway analysis of variance test, ttest, and paired ttest were used for multiple group comparisons followed by Tukey's post hoc for groupwise comparison. RESULTS: Direct activation of the resin cement samples of control (Group A) showed statistically significant higher mean microhardness values followed by Groups C then B and D, both immediately and after 24 h. The mean microhardness for immediate post-activation was always inferior to the 24 h post-activation test. For both 10 and 20 s curing cycle, there was a significant increase in the microhardness of the resin cement discs cured for 20 s through the different ceramics. CONCLUSION: Ceramic composition affected the polymerization of dual cured resin cement. Doubling the light irradiation time or curing cycle significantly increased mean microhardness value. Greater degree of conversion leading to an increase in hardness was observed when the resin cement discs were evaluated after 24 h.

Cloning and Expression of Novel Aminoglycoside Phosphotransferase Genes from Campylobacter and Their Role in the Resistance to Six Aminoglycosides.

Nine aph genes, including aph(2″)-Ib, aph(2″)-Ic, aph(2″)-Ig, aph(2″)-If, aph(2″)-If1, aph(2″)-If3, aph(2″)-Ih, aac(6')-Ie-aph(2″)-Ia, and aac(6')-Ie-aph(2″)-If2, were previously identified in Campylobacter To measure the contribution of these alleles to aminoglycoside resistance, we cloned nine genes into the pBluescript and expressed them in Escherichia coli DH5α. The nine aph expressed in E. coli showed various levels of resistance to gentamicin, kanamycin, and tobramycin. Three genes, aac(6″)-Ie-aph(2″)-Ia, aph2″-If1, and aph2″-Ig, showed increased MICs to amikacin, and five aph genes were transferrable.

An IL-10 dominant polarization of monocytes is a feature of Indian Visceral Leishmaniasis.

Leishmania donovani, the causative parasite of Visceral Leishmaniasis (VL), deviously manipulates host monocytes/macrophages to ensure its survival. Although monocytes/macrophages from patients with VL have demonstrated an impaired oxidative burst and antigen presentation, an unanswered yet pertinent question remains as to whether they are deactivated or alternatively activated. The significantly raised plasma levels of IL-4/IL-13 and IL-10 in VL patients suggested a microenvironment conducive for alternative activation of monocytes/macrophages. Accordingly, the classical markers for IL-4-driven monocytes/macrophages [M(IL-4)] were studied namely intramonocytic CD206+ , circulating CCL22 and CCL17, and were unchanged. Furthermore, the mRNA expression of Kruppel-like factor 4 (KLF4), peroxisome proliferator-activated receptors (PPAR)-γ and arginase-I (ARG-I) in peripheral blood mononuclear cells was unaltered. However, markers for IL-10-driven monocytes/macrophages [M(IL-10)], namely soluble CD163, intramonocytic IL-10, and circulating CXCL13 were significantly increased. Monocytes/macrophages of patients with VL demonstrated an increased expression of markers for M(IL-10), along with the absence of markers for M(IL-4). Taken together, in human VL, manipulation of these IL-10 polarized monocytes-macrophages may pave the way for improved therapeutic outcomes.

Predictive modelling of the water contact angle of surfaces using attenuated total reflection - Fourier transform infrared (ATR-FTIR) chemical imaging and partial least squares regression (PLSR).

The static water contact angle (CA) quantifies the degree of wetting that occurs when a surface encounters a liquid, e.g. water. This property is a result of factors such as surface chemistry and local roughness and is an important analytical parameter linked to the suitability of a surface for a given bioanalytical process. Monitoring the spatial variation in wettability over surfaces is increasingly critical to analysts and manufacturers for improved quality control. However, CA acquisition is often time-consuming because it involves measurements over multiple spatial locations, independent sampling and the need for a single instrument operator. Furthermore, surfaces exposed to local environments specific to an intended application may affect the surface chemistry thereby modifying the surface properties. In this study, Attenuated Total Reflection-Fourier Transform Infrared (ATR-FTIR) chemical imaging data acquired from wet and dry polymer surfaces were used to develop multivariate predictive models for CA prediction. Partial Least Squares Regression (PLSR) models were built using IR spectra from surfaces presenting differences in the experimentally measured CA in the range 16°-141°. The best performing PLSR models were locally developed and combined to make a global model utilising wet IR spectra which performed well (R2p = 0.98, RMSECV ∼ 5°) when tested on an independent experimental set. This model was subsequently applied to IR spectra acquired from a surface exhibiting spatial differences in surface chemistry and the CA with a reasonable confidence and precision (prediction error within 10°), demonstrating the potential of this method for prediction of the spatially varying CA as a non-destructive in-line process monitoring technique.

An empirical model for magnetic field dependent resistivity and magnetoresistance in manganites: application on polycrystalline charge-ordered La0.4Gd0.1Ca0.5MnO3.

In this paper, we have investigated the electrical and magnetic response of a La0.4Gd0.1Ca0.5MnO3 polycrystalline sample. This sample seems to exhibit fascinating phenomena like charge ordering, magnetic phase separation, training effects and kinetic arrest. It also shows colossal values of negative magnetoresistance (∼91.7% at 96 K under 1 T applied magnetic field), which raises the possibility of using this sample for technological applications. We have also proposed, in this work, a new empirical model to describe the evolution of resistivity and magnetoresistance as a function of magnetic field. This model was successfully tested on the La0.4Gd0.1Ca0.5MnO3 sample in spite of its complicated magnetic behavior, which suggests the use of this model for other magnetic samples in order to check its validity.

Effect of non-ß-lactams on stable variants of inhibitor-resistant TEM ß-lactamase in uropathogenic Escherichia coli: implication for alternative therapy.

AIMS: ß-lactamase inhibitor resistance (BLIR) among the uropathogenic Escherichia coli (UPEC) minimizes treatment options. This study aimed to identify inhibitor-resistant TEM (IRT) ß-lactamase that impart BLIR phenotype and explore non-ß-lactams as alternative therapeutics. METHODS AND RESULTS: Thirty BLIR UPEC isolates were detected by Kirby-Bauer disc diffusion technique using ß-lactam-ß-lactamase inhibitor combination. Conjugal transfer of BLIR was successful from 17 isolates. PCR and sequencing of the TEM ß-lactamases from the transconjugants indicated 14 TEM-84 (IRT) and three novel IRT variants (pUE184TEM, pUE203TEM, pUE210TEM). Three-dimensional models of the latter were predicted and validated. Molecular docking of selected non-ß-lactams (morin, catechin, naringenin triacetate) with the variants using AutoDock 4.2 showed comparable docking scores with significant hydrogen bond and hydrophobic interactions. Molecular dynamics simulation study confirmed stability of the non-ß-lactams inside the catalytic pocket of the enzymes. Moreover, all three non-ß-lactams were found to inhibit the purified TEM ß-lactamase variants in vitro. Microbroth dilution method indicated naringenin triacetate 64 µg ml-1 in combination with ceftazidime (CAZ) 30 µg ml-1 to be most effective against the BLIR transconjugants. CONCLUSIONS: BLIR phenotypes were primarily attributed to the production of IRT ß-lactamases. Administration of the non-ß-lactams with CAZ demonstrated an alternative therapeutic strategy against the IRT ß-lactamase producers. SIGNIFICANCE AND IMPACT OF THE STUDY: This study indicates high risk of transmission of IRT ß-lactamases and suggests ß-lactam-non-ß-lactam combination therapy to combat BLIR.