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The water quality of Sutlej river in Indian Punjab is getting deteriorated due to expansion of agricultural, industrial and recreational activities in the region. Many studies have evaluated the water quality of Sutlej river around the stretches of contaminated drains confluence with the river, but there are very few studies in which hydrochemistry of surface water of the river has been studied from the entry point of Sutlej river in Indian Punjab to its tail end when it leaves the country. Surface water samples (n = 97) were collected from the river during May 2019 and analyzed for pH, electrical conductivity, carbonate, bicarbonate, chloride, calcium, magnesium, sodium, potassium, nitrate and sulfate in the laboratory using the standard protocols. Results showed that total alkalinity, total hardness, sodium, potassium, chloride and nitrate were higher along the transboundary of the river. Water samples of the river are mainly Ca–Mg–HCO3 and Ca–Mg–Cl–SO4 types. Spatial distribution of all the parameters showed higher concentration of cations and anions along transboundary of the river. Principal component analysis, Heat map analysis and non-metric multidimensional scaling showed that water quality along the transboundary of the river are having different signature from the other zones of the river due to variations in chloride, sodium, total alkalinity and total hardness in water. Health risk assessment due to nitrate in water also showed that possibility of hazard was higher in the areas along transboundary of the river and children are more prone to health risks followed by women and men. Water quality along transboundary of the river followed by the area from the confluence of contaminated drain with river to transboundary along with localized spots in the river are not suitable for irrigation and drinking purposes. These results suggest that management of anthropogenic pressure, implementation of wastewater management and other strategies are required to improve the water quality of river.

Metabolic reprogramming is a newly emerged hallmark of cancer attaining a recent consideration as an essential factor for the progression and endurance of cancer cells. A prime event of this altered metabolism is increased glucose uptake and discharge of lactate into the cells surrounding constructing a favorable tumor niche. Several oncogenic factors help in promoting this consequence including, pyruvate kinase M2 (PKM2) a rate-limiting enzyme of glycolysis in tumor metabolism via exhibiting its low pyruvate kinase activity and nuclear moon-lightening functions to increase the synthesis of lactate and macromolecules for tumor proliferation. Not only its role in cancer cells but also its role in the tumor microenvironment cells has to be understood for developing the small molecules against it which is lacking with the literature till date. Therefore, in this present review, the role of PKM2 with respect to various tumor niche cells will be clarified. Further, it highlights the updated list of therapeutics targeting PKM2 pre-clinically and clinically with their added limitations. This upgraded understanding of PKM2 may provide a pace for the reader in developing chemotherapeutic strategies for better clinical survival with limited resistance.

This paper provides a description of the transmission function of an XPS instrument operating with exchangeable Al Kα (1486.6 eV) and Ag Lα (2984.3 eV) sources. Both sources use the same quartz crystal monochromator and illuminate the same area of the sample. The transmission-function-corrected data from sputter cleaned gold provides a useful reference material to calibrate other instruments of the same type. Sensitivity factors for Ag Lα and Al Kα are calculated from photoionisation cross sections and electron effective attenuation lengths. These compare well to previous experimental values and data acquired from ionic liquids. The intensity of the Ag Lα source is found to be approximately 50 times lower than the Al Kα source. This, coupled with generally lower photoemission efficiencies, results in noisier data or extended acquisition times. However, there are clear advantages to using the Ag Lα source to analyse certain elements where additional core levels can be accessed and for many technologically important elements where interference from Auger electron peaks can be eliminated. The combination of calibrated data from both sources provides direct and easily interpreted insight into the depth distribution of chemical species. This could be particularly important for topographic samples, where angle resolved experiments are not always helpful. We also demonstrate, using thin coatings of chromium and carbon, that the inelastic background in Ag Lα wide-scan spectra has a significantly increased information depth compared to Al Kα.

The non-analytic growth bound of a $$C_{0}$$-semigroup measures the extent to which the semigroup may be approximated via holomorphic functions and may be thought of as a non-analytic analogue of the exponential growth bound. In this paper, we study the non-analytic growth bound $$ \zeta (\mathcal {T}) $$ of the delay semigroup $$ \{\mathcal {T}(t)\}_{t\ge 0} $$ associated with the delay equation $$ u^{\prime }(t) = Bu(t) + \Phi u_{t} $$, where $$ u_{t} $$ is the history function, $$ \Phi \in \mathcal {L}(W^{1,p}([-1,0],X),X) $$ is the delay operator, and (B, D(B)) is the generator of a $$ C_{0} $$-semigroup $$ \{T(t)\}_{t\ge 0} $$ on Banach space X. In particular, we obtain conditions under which $$\zeta (T) < \alpha $$ implies that $$ \zeta (\mathcal {T}) < \alpha $$.

We describe a method for the intensity calibration of XPS instruments using polyethylene as the reference material. Previous methods for have employed noble metals, such as gold, silver and copper. Polyethylene has a number of advantages over these. It has far fewer photoelectron and Auger electron peaks than such metals, i.e. the spectrum largely comprises inelastic background over a wide and continuous range of kinetic energies. The XPS spectrum can be described by a mathematical function enabling simple and noise-free implementation of the reference spectrum. Polyethylene can be cleaned ex-situ using a sharp knife or razor blade to remove trace oxygen and, due to its chemical composition, should not be affected by adventitious carbon contamination. Thus, an ion source for sputter cleaning is not required, although an electron flood source for charge compensation is required. The drawback to using polyethylene is that the photoelectron yield is far lower than gold or silver and this necessitates longer acquisition times and removal of dark noise. Longer acquisition times carry the risk of damaging the polyethylene surface and we show that, even if damage does occur, it has negligible effect on the XPS background intensity. The reference spectrum is valid for monochromated Al Kα XPS instruments with a monochromator-sample-analyser angle close to 60°.

Gliomas are lethal and aggressive form of brain tumors with resistance to conventional radiation and cytotoxic chemotherapies; inviting continuous efforts for drug discovery and drug delivery. Interestingly, small molecule hybrids are one such pharmacophore that continues to capture interest owing to their pluripotent medicinal effects. Accordingly, we earlier reported synthesis of potent Styryl-cinnamate hybrids (analogues of Salvianolic acid F) along with its plausible mode of action (MOA). We explored iTRAQ-LC/MS-MS technique to deduce differentially expressed landscape of native & phospho-proteins in treated glioma cells. Based on this, Protein-Protein Interactome (PPI) was looked into by employing computational tools and further validated in vitro. We hereby report that the Styryl-cinnamate hybrid, an analogue of natural Salvianolic acid F, alters key regulatory proteins involved in translation, cytoskeleton development, bioenergetics, DNA repair, angiogenesis and ubiquitination. Cell cycle analysis dictates arrest at G0/G1 stage along with reduced levels of cyclin D; involved in G1 progression. We discovered that Styryl-cinnamate hybrid targets glioma by intrinsically triggering metabolite-mediated stress. Various oncological circuits alleviated by the potential drug candidate strongly supports the role of such pharmacophores as anticancer drugs. Although, further analysis of SC hybrid in treating xenografts or solid tumors is yet to be explored but their candidature has gained huge impetus through this study. This study equips us better in understanding the shift in proteomic landscape after treating glioma cells with SC hybrid. It also allows us to elicit molecular targets of this potential drug before progressing to preclinical studies.

Quantum circuits show unprecedented sensitivity to external fluctuations compared to their classical counterparts, and it can take as little as a single atomic defect somewhere in a mm-sized area to completely spoil device performance. For improved device coherence it is thus essential to find ways to reduce the number of defects, thereby lowering the hardware threshold for achieving fault-tolerant large-scale error-corrected quantum computing. Given the evasive nature of these defects, the materials science required to understand them is at present in uncharted territories, and new techniques must be developed to bridge existing capabilities from materials science with the needs identified by the superconducting quantum circuit community. In this paper, we give an overview of methods for characterising the chemical and structural properties of defects in materials relevant for superconducting quantum circuits. We cover recent developments from in-operation techniques, where quantum circuits are used as probes of the defects themselves, toin situanalysis techniques and well-establishedex situmaterials analysis techniques. The latter is now increasingly explored by the quantum circuits community to correlate specific material properties with qubit performance. We highlight specific techniques which, given further development, look especially promising and will contribute towards a future toolbox of material analysis techniques for quantum.

Hard X-ray Photoelectron Spectroscopy (HAXPES) provides minimally destructive depth profiling into the bulk, extending the photoelectron sampling depth. Detection of deeply buried layers beyond the elastic limit is enabled through inelastic background analysis. To test the robustness of this technique, we present results on a thin (18 nm) layer of metal–organic complex buried up to 200 nm beneath organic material. Overlayers with thicknesses 25–140 nm were measured using photon energies ranging 6–10 keV at the I09 end station at Diamond Light Source, and a new fixed energy Ga Kα (9.25 keV) laboratory-based HAXPES spectrometer was also used to measure samples with overlayers up to 200 nm thick. The sampling depth was varied: at Diamond Light Source by changing the photon energy, and in the lab system by performing angle-resolved measurements. For all the different overlayers and sampling depths, inelastic background modelling consistently provided thicknesses which agreed, within reasonable error, with the ellipsometric thickness. Relative sensitivity factors were calculated, and these factors consistently provided reasonable agreement with the expected nominal stoichiometry, suggesting the calculation method can be extended to any element. These results demonstrate the potential for the characterisation of deeply buried layers using synchrotron and laboratory-based HAXPES.

IMID-2, a newly identified piperazine-based anticancer molecule, has been shown to be cytotoxic against various cancer cell lines. The primary aim of this research was to identify and characterize possible metabolites of the molecule formed during biotransformation. A metabolite identification study was first executed using an in silico tool to predict the possible metabolism sites of IMID-2. Thereafter, metabolites generated in vitro (rat liver microsomes, rat S9 fractions and human liver microsomes) and in vivo (rat plasma, urine and feces) were identified and characterized employing UPLC-QTOF-MS/MS. A total of eight metabolites, among which were six in phase I and two in phase II reactions, were recognized. The plausible structure of the metabolites and probable metabolic pathway have been established based on the mass fragmentation pattern, mass ppm error, ring double bond calculation and nitrogen rule. The majority of phase I metabolites were generated by N-oxidation, hydroxylation, oxidative deamination followed by reduction, oxidative dechlorination, N-dearylation, and N-dealkylation. Glucuronidation played a significant role in the formation of phase II metabolites of the molecule.

Pyruvate kinase M2 (PKM2) catalyzes the conversion of phosphoenolpyruvate (PEP) to pyruvate. It plays a central role in the metabolic reprogramming of cancer cells and is expressed in most human tumors. It is essential in indiscriminate proliferation, survival, and tackling apoptosis in cancer cells. This positions PKM2 as a hot target in cancer therapy. Despite its well-known structure and several reported modulators targeting PKM2 as activators or inhibitors, a comprehensive review focusing on such modulators is lacking. Herein we summarize modulators of PKM2, the assays used to detect their potential, the preferable tense (T) and relaxed (R) states in which the enzyme resides, lacunae in existing modulators, and several strategies that may lead to effective anticancer drug development targeting PKM2.

We introduce a technique for the directed transfer of molecules from an adjacent reservoir onto a sample surface inside the vacuum chamber of a ToF-SIMS instrument using gas cluster ion beam (GCIB) sputtering. An example application for

The Andean bear is the only extant member of the Tremarctine subfamily and the only extant ursid species to inhabit South America. Here, we present an annotated de novo assembly of a nuclear genome from a captive-born female Andean bear, Mischief, generated using a combination of short and long DNA and RNA reads. Our final assembly has a length of 2.23 Gb, and a scaffold N50 of 21.12 Mb, contig N50 of 23.5 kb, and BUSCO score of 88%. The Andean bear genome will be a useful resource for exploring the complex phylogenetic history of extinct and extant bear species and for future population genetics studies of Andean bears.

Chronic inflammation (CI) is a primary contributing factor involved in multiple diseases like cancer, stroke, diabetes, Alzheimer's disease, allergy, asthma, autoimmune diseases, coeliac disease, glomerulonephritis, sepsis, hepatitis, inflammatory bowel disease, reperfusion injury, and transplant rejections. Despite several expansions in our understanding of inflammatory disorders and their mediators, it seems clear that numerous proteins participate in the onset of CI. One crucial protein pyruvate kinase M2 (PKM2) much studied in cancer is also found to be inextricably woven in the onset of several CI's. It has been found that PKM2 plays a significant role in several disorders using a network of proteins that interact in multiple ways. For instance, PKM2 forms a close association with epidermal growth factor receptors (EGFRs) for uncontrolled growth and proliferation of tumor cells. In neurodegeneration, PKM2 interacts with apurinic/apyrimidinic endodeoxyribonuclease 1 (APE1) to onset Alzheimer's disease pathogenesis. The cross-talk of protein tyrosine phosphatase 1B (PTP1B) and PKM2 acts as stepping stones for the commencement of diabetes. Perhaps PKM2 stores the potential to unlock the pathophysiology of several diseases. Here we provide an overview of the notoriously convoluted biology of CI's and PKM2. The cross-talk of PKM2 with several proteins involved in stroke, Alzheimer's, cancer, and other diseases has also been discussed. We believe that considering the importance of PKM2 in inflammation-related diseases, new options for treating various disorders with the development of more selective agents targeting PKM2 may appear.

Label-free protein characterization at surfaces is commonly achieved using digestion and/or matrix application prior to mass spectrometry. We report the assignment of undigested proteins at surfaces in situ using secondary ion mass spectrometry (SIMS). Ballistic fragmentation of proteins induced by a gas cluster ion beam (GCIB) leads to peptide cleavage producing fragments for subsequent OrbitrapTM analysis. In this work we annotate 16 example proteins (up to 272 kDa) by de novo peptide sequencing and illustrate the advantages of this approach by characterizing a protein monolayer biochip and the depth distribution of proteins in human skin., Label-free protein characterization at surfaces requires digestion or matrix application prior to mass spectrometry. Here, the authors report the assignment of undigested proteins at surfaces by de novo sequencing and apply the methodology to a protein monolayer biochip and for in situ depth profiling of proteins through human skin.

We report on the electromagnetic properties of Co2+ substituted spinel MgCuZn ferrites developed via a facile molten salt synthesis (MSS) route. The choice of synthesis route in combination with cobalt substitution led to strong electromagnetic properties such as high saturation magnetization (i.e., 63 emu/g), high coercivity (17.86 gauss), and high initial permeability (2730), which are beneficial for the multilayer chip inductor (MLCI) application. In a typical process, the planned ferrites were synthesized at 800 &deg, C using sodium chloride as a growth inhibitor, with dense morphology and irregularity in the monolithicity of the grains. The compositional analysis of as-prepared ferrite confirms the presence of desired elements with their proportion. The crystallite size (using X-ray diffraction (XRD) analysis) for different samples varies in the range of 49&ndash, 51 nm. The scanning electron microscopy (SEM) and transmission electron microscopy (TEM) analysis showcases the compact morphology of the developed samples, which is typical in the ferrite system. The dielectric properties (dielectric-loss and dielectric-constant) in the frequency range of 100Hz&ndash, 1MHz suggest normal dielectric distribution according to interfacial polarization from Maxwell&ndash, Wagner. From the developed ferrites, upon comparison with a low dielectric loss with high permeability value, Mg-Cu-Zn ferrite with Co = 0.05 substitution proved to be a stronger material for MLCIs with high-performance applications.

PKM2is considered a desirable target as its enzymatic activation is expected to cause a diminution in tumorigenesis and prevent limitless replication in cancerous cells. However, considering the functional consequences of kinase inhibitors, the design of PKM2 activators has been an attractive strategy that has yielded potent anticancer molecules like DASA-58. Therefore, a new class of boronic acid derivate was developed to elucidate the possible mechanistic link between PKM2 activation and TPI1 activity, which has a significant role in the redox balance in cancer. The present in vitro study revealed that treatment with boronic acid-based compound 1 and DASA-58 was found to activate PKM2 with an AC