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Background Few studies have explored factors affecting preference of medical students towards general practice as a career choice. We conducted a survey in Karachi across various public and private sector medical colleges to examine factors associated with students' general practice career aspirations in Karachi, Pakistan. Methods From January to March 2018, we distributed a 21-item questionnaire to final year medical students in eight medical schools. The survey asked students about their top three career preferences from 19 specialty fields, their demographics and their career priorities. Multivariable logistic regression was used to determine the effect of each item. Results A total of 1400 responses were obtained. The top five specialty fields chosen by students with their numbers were: internal medicine, 898 (64.2%); general practice, 337 (24.1%); pediatrics, 449 (32.1%); surgery, 380 (27.2%); and emergency medicine, 243 (17.4%). The \"intent to inherit existing practice\" and \"other academic or professional experiences prior to medical school\" had a positive association with choosing general practice while \"having a physician parent'' had a negative association among the medical students demographics after adjusting for other covariates in the multivariable logistic regression. Medical students who ranked \"clinical diagnostic reasoning\", \"community-oriented practice\", \"involvement in preventive medicine\", and \"frequent patient communication\" as highly important were more likely to choose general practice, whereas, \"access to advanced medical fields\", \"mastering advanced procedures\", and \"depth rather than breadth of practice\" were less likely to be associated with general practice aspiration. Conclusion The study's results depicted limited interest of family medicine as a career option in graduating students, and pointed out the factors that likely influence the choice of general practice as a career are clinical diagnostic reasoning, community-oriented practice and preventive medicine.

ABSTRACT Lathyrol, a natural diterpenoid molecule is one of the major components of Semen Euphorbiae, a famous traditional Chinese medicine with a long history of clinical use in China. Very recently, lathyrol has been reported to inhibit the growth and induce apoptosis in lung cancer cells. However, the anticancer activity of lathyrol remains largely unknown in various human cancers. The present study was designed to evaluate lathyrol for its broad-spectrum anticancer activity and binding affinity with STAT3 DNA binding domain. Using CCK-8 assay kit, we showed that lathyrol reduced the cell viability of Hep-3B, MHCC97-L, A2780 and taxol resistant Hey-T30 cells in a dose-dependent fashion. Using Molecular docking study, we found that lathyrol exhibits strong binding interactions with STAT3 DNA binding domain through hydrogen bonding and hydrophobic interactions with various amino acid residues of STAT3. Using immunoblotting, we found that lathyrol did not inhibit STAT3 phosphorylation and dimerization. Moreover, we showed that lathyrol induces apoptosis as evident from a remarkably increased expression of cleaved caspase-3 in all four cancer cell lines. Taken together, our findings suggest that lathyrol is a potent STAT3 DNA binding domain inhibitor and exhibits a broadspectrum anticancer activity.

PIDD1 encodes p53-Induced Death Domain protein 1, which acts as a sensor surveilling centrosome numbers and p53 activity in mammalian cells. Early results also suggest a role in DNA damage response where PIDD1 may act as a cell-fate switch, through interaction with RIP1 and NEMO/IKKg, activating NF-κB signaling for survival, or as an apoptosis-inducing protein by activating caspase-2. Biallelic truncating mutations in CRADD—the protein bridging PIDD1 and caspase-2—have been reported in intellectual disability (ID), and in a form of lissencephaly. Here, we identified five families with ID from Iran, Pakistan, and India, with four different biallelic mutations in PIDD1, all disrupting the Death Domain (DD), through which PIDD1 interacts with CRADD or RIP1. Nonsense mutations Gln863* and Arg637* directly disrupt the DD, as does a missense mutation, Arg815Trp. A homozygous splice mutation in the fifth family is predicted to disrupt splicing upstream of the DD, as confirmed using an exon trap. In HEK293 cells, we show that both Gln863* and Arg815Trp mutants fail to co-localize with CRADD, leading to its aggregation and mis-localization, and fail to co-precipitate CRADD. Using genome-edited cell lines, we show that these three PIDD1 mutations all cause loss of PIDDosome function. Pidd1 null mice show decreased anxiety, but no motor abnormalities. Together this indicates that PIDD1 mutations in humans may cause ID (and possibly lissencephaly) either through gain of function or secondarily, due to altered scaffolding properties, while complete loss of PIDD1, as modeled in mice, may be well tolerated or is compensated for.

The study aimed to determine the effect of two aphid species; Lipaphis erysimi (Kaltenbach) and Aphis gossypii Glover (Hemiptera: Aphididae) on life table and demographic parameters of Hippodamia convergens Gu`erin-M´eneville (Coleoptera: Coccinellidae). The developmental period of all life stages of H. convergens was shorter when fed on L. erysimi . Net reproductive rate ( R o ) was higher (159.85 offspring/individual) on L. erysimi , while it was 87.85 offspring/individual on A. gossypii . Mean generation time (T) was shorter (30.49 d) on L. erysimi than on A. gossypii (45.1 days). Values of the intrinsic rate of increase (r) and finite rate of increase (λ) were calculated as 0.166 days −1 and 1.181 days −1 , respectively, on L. erysimi that were higher than on A. gossypii (0.099 days −1 and 1.104 days −1 , respectively). Similarly, the survival rate was also higher when the predator was fed on L. erysimi . Overall, the findings suggest using L. erysimi as a better source of prey than A. gossypii for rearing H. convergens.

Severe acute respiratory syndrome virus 2 (SARS-CoV-2) belongs to the single-stranded positive-sense RNA family. The virus contains a large genome that encodes four structural proteins, small envelope (E), matrix (M), nucleocapsid phosphoprotein (N), spike (S), and 16 nonstructural proteins (nsp1-16) that together, ensure replication of the virus in the host cell. Among these proteins, the interactions of N and Nsp3 are essential that links the viral genome for processing. The N proteins reside at CoV RNA synthesis sites known as the replication–transcription complexes (RTCs). The N-terminal of N has RNA-binding domain (N-NTD), capturing the RNA genome while the C-terminal domain (N-CTD) anchors the viral Nsp3, a component of RTCs. Although the structural information has been recently released, the residues involved in contacts between N-CTD with Nsp3 are still unknown. To find the residues involved in interactions between two proteins, three-dimensional structures of both proteins were retrieved and docked using HADDOCK. Residues at N-CTD were detected in interaction with L499, R500, K501, V502, P503, T504, D505, N506, Y507, I508, T509, K529, K530K532, S533 of Nsp3 and N-NTD to synthesize SARS-CoV-2 RNA. The interaction between Nsp3 and CTD of N protein may be a potential drug target. The current study provides information for better understanding the interaction between N protein and Nsp3 that could be a possible target for future inhibitors.Graphic abstract

The performance of visual SLAM and localization methods is generally reported on famous datasets. These datasets are generally captured under human supervision and hence, are prone to human biases. In this work we expose two such biases (capture bias and negative world bias) in well-known SLAM datasets. Photo-realistic simulators provide a platform for gathering data without human supervision and hence human bias. However, not every simulator is suited for benchmarking visual localization methods. This is due to the difficulty of calibrating the first-view camera of these simulators. The calibration parameters (both intrinsic and extrinsic), while routinely provided with the datasets, are not generally available for simulators and virtual worlds. We propose a novel and user-friendly method to calibrate these simulators which is an essential requirement for using them for visual navigation. We demonstrate our method on a well-known simulator (MINOS), as well as a highly popular open world game (GTA-V). Finally, we also analyze the simulation-to-reality gap of these virtual platforms and propose a method to reduce this gap. We show that the performance of visual navigation algorithms (e.g., simultaneous localization and mapping: SLAM) significantly degrades when tested on novel situations available in virtual worlds.

Lead-free ceramics are promising candidates for replacing lead-based piezoelectric materials such as lead-zirconate-titanate (PZT) if they can compete in dielectric and ferroelectric characteristics. In this work, for lead-free piezoelectric ceramic, 0.74(Bi0.5Na0.5TiO3)-0.26(SrTiO3) (BNT-ST26) and niobium-substituted (Nb-BNT–ST26) ceramics were synthesized by solid-state reactions. The evolution of niobium substitution to the perovskite phase structure of BNT-ST26 ceramics was confirmed by X-ray diffraction (XRD) analysis and Raman spectra. Electromechanical properties of Nb-BNT-ST26 ceramics initially increased with the addition of niobium up to 0.5% and decreased with a further increase in Nb content. Temperature-dependent dielectric curves showed that the depolarization temperature (Td) decreased below room temperature because of Nb substitution. The composition with 0.5% Nb yielded a maximum bipolar strain (Smax) of 0.265% and normalized strain of d33* ~ 576 pm/V under an electric field of 4.6 kV/mm at room temperature. At this critical concentration of 0.5% Nb, maximum saturation polarization of 26 μC/cm2 was achieved. The dielectric constant with temperature peaks became more diffused and the depolarization temperature decreased with the increasing Nb content. The study concludes that Nb-doped BNT-ST26 is an excellent material for high-temperature, stable, frequency-dependent, lead-free piezoelectric devices.

The zinc finger-containing transcription factor Gli3 is a key mediator of Hedgehog (Hh) signaling pathway. In vertebrates, Gli3 has widespread expression pattern during early embryonic development. Along the anteroposterior axes of the central nervous system (CNS), dorsoventral neural pattern elaboration is achieved through Hh mediated spatio-temporal deployment of Gli3 transcripts. Previously, we and others uncovered a set of enhancers that mediate many of the known aspects of Gli3 expression during neurogenesis. However, the potential role of Gli3 associated enhancers in trait evolution has not yet received any significant attention. Here, we investigate the evolutionary patterns of Gli3 associated CNS-specific enhancers that have been reported so far. A subset of these enhancers has undergone an accelerated rate of molecular evolution in the human lineage in comparison to other primates/mammals. These fast-evolving enhancers have acquired human-specific changes in transcription factor binding sites (TFBSs). These human-unique changes within subset of Gli3 associated CNS-specific enhancers were further validated as single nucleotide polymorphisms through 1000 Genome Project Phase 3 data. This work not only infers the molecular evolutionary patterns of Gli3 associated enhancers but also provides clues for putative genetic basis of the population-specificity of gene expression regulation.

In a recent study, La +3 substituted T-type hexagonal ferrites S r 2 − x L a x F e 8 O 14 with concentration of (0.0 ≤ x ≤ 0.2) with increment of 0.05 step length was fabricated by sol–gel auto-combustion route. XRD results revealed that with the increment in the substitution of La +3 ions, the lattice parameters (a) and (c) decreased, and hence the unit cell volume decreased. The crystallite size was observed to vary in the range of 20.21–29.30 nm. The dielectric constant was observed to decrease as a function of frequency mean while the dielectric constant values declined with La 3+ ions substitutions. The ac conductivity of samples enhanced with the increase in applied frequency. The FTIR spectra exhibited the absorption bands at different wave numbers (447, 570, and 1532 cm −1 ) indicating the stretching vibration of carbon-oxygen and metal-Oxygen ions within material. In the P-E graphs, the samples divulged the lossy behavior and this lossy behavior varied inversely with doping concentration. The decrease in lossy behavior was observed with the La 3+ contents which unveiled the enhancement in resistivity of the samples. The saturation magnetization decreased with the substitution of La 3+ contents which was reasoned to the spin canting effect of rare earth ions. The law of approach to saturation magnetization (LAS) was applied for fitting the magnetic curves and the results showed coincidence between the experimental and theoretical results. The coercivity of the samples increased drastically with La 3+ ions substitution and the samples converted from soft magnetic materials to hard magnetic materials. The samples with high coercivity values might be suitable for high-density storage devices. Graphical Abstract Highlights A series of T-hexaferrites was prepared by sol-gel auto combustion method. The XRD analysis confirmed the single phase for all samples. The c/a ratio of these samples falls in the range of Hexaferrites. The dielectric properties changes with the increase of La 3+ contents. Magnetic properties varies with La 3+ contents.

ABSTRACT Tannase has significant importance due to its various industrial applications. Tannase production using pure tannic acid as substrate is very expensive especially at industrial level. In present study, various physical parameters and medium components were optimized for maximum tannase production employing Raoultella ornithinolytica in solid state fermentation (SSF) using corn (Zea mays) leaves as substrate to reduce its production cost. The maximum tannase production was obtained with 60% initial substrate moisture contents, tap water as enzyme extraction medium with 2 mL volume, 45°C incubation temperature, pH 7, 300 µL inoculum size, 24 h incubation period in agitated condition with substrate particle size of 4mm during one factor at a time optimization. Concentrations of medium components (3.75% tannic acid, 0.75% K HPO and 1.25% yeast extract) were optimized with central composite design of response surface methodology. Tannase characterization data revealed that 5.0 pH, 30°C temperature, 60 minutes incubation and 0.45% of substrate concentration showed highest tannase activity. The results depict utilization potential of low cost substrate (corn leaves) to reduce the production cost of tannase.