We present a hierarchical approach that combines atomistic and mesoscopic simulations that can generally be applied to vinyl polymers. As a test case, the approach is applied to atactic polystyrene ...(PS). First, a specific model for atactic PS is chosen. The bonded parameters in the coarse-grained force field, based on data obtained from atomistic simulations of isolated PS dimers, are chosen in a way which allows to differentiate between meso and racemic dyads. This approach in principle allows to study isotactic and syndiotactic melts as well. Nonbonded interactions between coarse-grained beads were chosen as purely repulsive. The proposed mesoscopic model reproduces both the local structure and the chain dimensions properly. An explicit time mapping is performed, based on the atomistic and CG mean-square displacements of short chains, demonstrating an effective speed up of about 3 orders of magnitude compared to brute force atomistic simulations. Finally the equilibrated coarse-grained chains are back mapped onto the atomistic systems. This opens new routes for obtaining well equilibrated high molecular weight polymeric systems and also providing very long dynamic trajectories at the atomistic level for these polymers.
Summary
RNAIII is a 514 nt regulatory RNA that is the effector molecule of the staphylococcal agr quorum‐sensing system, regulating a large set of virulence and other accessory genes at the level of ...transcription. RNAIII was discovered nearly 20 years ago and we long ago hypothesized that it would function by regulating the synthesis or activity of one or more intermediary transcription factors. We have finally confirmed this hypothesis, showing that Staphylococcus aureus RNAIII regulates the synthesis of a major pleiotropic transcription factor, Rot, by blocking its translation. RNAIII has a complex secondary structure with several stable hairpins that have highly C‐rich end loops, unusual in an AT‐rich organism. We noted that these loops are complementary to two G‐rich stem loops of the rot mRNA translation initiation region (TIR). Pairing of the complementary RNAs would be predicted to occlude the rot Shine–Dalgarno (SD) site and to block rot translation. Through a combination of transcriptional and translational fusions and Northern and Western blot hybridization analyses, we show that RNAIII does, indeed, block rot translation. Through alterations in the C‐rich loops of RNAIII and the G‐rich loops of rot, we show that the sequences of these loops are critical for inhibition of rot translation and suggest that this inhibition is affected by pairing between the complementary stem loops, followed by the cleavage of rot mRNA. We propose that the RNAIII–rot mRNA interaction plays a key role in agr regulation of staphylococcal virulence.
DEAP-3600 is a single-phase liquid argon detector aiming to directly detect weakly interacting massive particles (WIMPs), located at SNOLAB (Sudbury, Canada). After analyzing data taken during the ...first year of operation, a null result was used to place an upper bound on the WIMP-nucleon, spin-independent, isoscalar cross section. This study reinterprets this result within a nonrelativistic effective field theory framework and further examines how various possible substructures in the local dark matter halo may affect these constraints. Such substructures are hinted at by kinematic structures in the local stellar distribution observed by the Gaia satellite and other recent astronomical surveys. These include the Gaia Sausage (or Enceladus), as well as a number of distinct streams identified in recent studies. Limits are presented for the coupling strength of the effective contact interaction operators O1, O3, O5, O8, and O11, considering isoscalar, isovector, and xenonphobic scenarios, as well as the specific operators corresponding to millicharge, magnetic dipole, electric dipole, and anapole interactions. The effects of halo substructures on each of these operators are explored as well, showing that the O5 and O8 operators are particularly sensitive to the velocity distribution, even at dark matter masses above 100 GeV / c2.
Real-time fine-scale data was collected along the Bagmati River, in Kathmandu Valley, using mobile and fixed sensor system during the winter season. The water quality parameters; pH, conductivity, ...total dissolved salt (TDS), salinity, oxygen reduction potential (ORP), dissolved oxygen (DO), and turbidity were measured in the space domain using a fixed sensor and mobile sensor (small rafting boat loaded with sensor) systems. The water quality parameters from the fixed sensor system revealed that the Bagmati River was comparatively less polluted upstream from Gokarna to Tilganga sites and molecular oxygen present in the water was enough to decompose organic pollutants. However, the water quality downstream from Tinkune to Balkhu sites was degraded drastically making it unfit for living organisms. Temporal variation of water quality attributes that human activity significantly enhanced pollutants which severely degraded the water quality in the daytime. The fine-scale space domain heat map data of the mobile sensor system also suggested that the water quality continuously deteriorated from Shankhamul to Sundarighat sites. The ORP value was always negative and decreased with downflow and becomes -263 mV near the Sundarighat Bridge. The mixing of tributaries and increment of solid waste and untreated sewer along the river enhanced pollutants excessively and decreased oxygen level to zero. The results attributed that decomposition of the sewer by microorganism consumed almost all oxygen which produced volatile compounds and generated malodorous odor downstream of Bagmati River.
An unusual presentation of liver abscess secondary to toxoplasmosis in Nepal
This is a case report on a case of liver abscess admitted in the hospital.
A 45-year old immunocompetent male presented to ...the emergency department with complaints of high-grade fever for ten days along with abdominal discomfort, anorexia, nausea and vomiting for 5 days. Clinically, he had fever, tachycardia, decreased breath sound on right chest & hepatomegaly. In labs, he had neutrophilic leukocytosis (22.7 K/microliter) and mildly elevated liver enzymes. The CT scan of chest, abdomen & pelvis reported hepatic abscess on the right lobe of liver (17.2 × 8.4 × 11.7 cm) which was drained under ultrasonography guidance. The patient was started empirically on IV antibiotics: Piperacillin-Tazobactam & Metronidazole. Blood, sputum & urine cultures were negative. The results of drained pus were negative for gram stain, culture, AFB stain, TB-PCR, fungal stain/culture, anaerobic culture, ova/parasites except for gram stain positive for possible trophozoites of Toxoplasma gondii, supported by strongly positive Toxoplasma IgG serology. The patient continued to have a fever. On further questioning, he mentioned cleaning the litter box of a postpartum cat weeks before he started having fever. On the fourth day of admission, oral Bactrim-DS(160 mg Trimethoprim and 800 mg Sulfamethoxazole) was added to the regimen, after which the patient became afebrile & clinically improved within 24 hours. The patient was discharged home on oral Bactrim-DS. There was complete resolution of liver abscess in ultrasonographic evaluation of the abdomen performed after 4 weeks, & oral antibiotic was stopped.
This is the only case of liver abscess caused by toxoplasmosis, reported from Nepal. Liver abscess is commonly caused by Entamoeba histolytica or Enterobacteriaceae. However, Nepal being endemic to Toxoplasma, initial differential diagnosis should also include toxoplasmosis. As part of work up for toxoplasmosis, the abscess should be drained and histopathology sent for special stains (Hematoxylin & Eosin, Wright's or Giemsa), serum sent for serology, and abscess material sent for PCR if available.
United Nations data shows that the number of global diaspora had reached 281 million in 2020, and it continues to grow. Diasporas have contributed significantly to the development of their native ...lands through remittance, technology and knowledge transfer, philanthropy, and diplomacy. Many countries have designed policies to engage the diaspora more deeply by providing concessional citizenship and visa regimes, and attractive investment opportunities. Yet, there is room for improvement in policies and programs to enhance these prospects. Since the 2010s, the size and expanse of Nepali diaspora has grown dramatically, the number of permanent expatriates in the more developed parts of the world reaching about 800,000 in 2022. In addition, at any time, there are 2-3 million temporary migrants from Nepal working in foreign countries outside of India. With the enhanced level of education and experience, and their growing economic prowess, the Nepali diaspora is in a strong position to become a significant partner in Nepal's development efforts. The diaspora's potential contribution to Nepal's development remains vastly underutilized for mainly two policy-related reasons. The Nepali government's supporting policies, regulations, and programs to effectively engage the diaspora are inadequate. The diaspora groups too have not been able to fully assess and chart out their capacities, and create proper institutional, and policy mechanisms to mobilize their resources. This paper reviews some examples of diaspora in development, and the current situation of the Nepali diaspora, and provide recommendations for improving the strategies, policies, and programs both for the diaspora, and the Nepali government, and for similar developing countries.
Drug naïve animals given a single dose of ethanol show changed responses to subsequent doses, including the development of ethanol tolerance and ethanol preference. These simple forms of behavioral ...plasticity are due in part to changes in gene expression and neuronal properties. Surprisingly little is known about how ethanol initiates changes in gene expression or what the changes do. Here we demonstrate a role in ethanol plasticity for Hr38, the sole Drosophila homolog of the mammalian Nr4a1/2/3 class of immediate early response transcription factors. Acute ethanol exposure induces transient expression of Hr38 and other immediate early neuronal activity genes. Ethanol activates the Mef2 transcriptional activator to induce Hr38, and the Sirt1 histone/protein deacetylase is required to terminate Hr38 induction. Loss of Hr38 decreases ethanol tolerance and causes precocious but short‐lasting ethanol preference. Similarly, reduced Mef2 activity in all neurons or specifically in the mushroom body α/β neurons decreases ethanol tolerance; Sirt1 promotes ethanol tolerance in these same neurons. Genetically decreasing Hr38 expression levels in Sirt1 null mutants restores ethanol tolerance, demonstrating that both induction and termination of Hr38 expression are important for behavioral plasticity to proceed. These data demonstrate that Hr38 functions as an immediate early transcription factor that promotes ethanol behavioral plasticity.
Timely termination of immediate early gene expression allows development of ethanol tolerance.
A search for inelastic boosted dark matter (IBDM) using the COSINE-100 detector with 59.5 days of data is presented. This relativistic dark matter is theorized to interact with the target material ...through inelastic scattering with electrons, creating a heavier state that subsequently produces standard model particles, such as an electron-positron pair. In this study, we search for this electron-positron pair in coincidence with the initially scattered electron as a signature for an IBDM interaction. No excess over the predicted background event rate is observed. Therefore, we present limits on IBDM interactions under various hypotheses, one of which allows us to explore an area of the dark photon parameter space that has not yet been covered by other experiments. This is the first experimental search for IBDM using a terrestrial detector.
S. aureus vaccine development has proven particularly difficult. The conventional approach to achieve sterile immunity through opsonophagocytic killing has been largely unsuccessful. S. aureus is ...highly toxigenic and a great body of evidence suggests that a successful future vaccine for this organism should target extracellular toxins which are responsible for host tissue destruction and immunosuppression. Major staphylococcal toxins are alpha toxin (a single subunit hemolysin) along with a group of bicomponent pore-forming toxins (BCPFT), namely Panton-Valentine leukocidin (PVL), gamma hemolysins (HlgCB and AB), LukAB and LukED. In our previous report, an attenuated mutant of LukS-PV (PVL- S subunit) named as "LukS-mut9" elicited high immunogenic response as well as provided a significant protection in a mouse sepsis model. Recent discovery of PVL receptors shows that mice lack receptors for this toxin, thus the reported protection of mice with the PVL vaccine may relate to cross protective responses against other homologous toxins. This manuscript addresses this issue by demonstrating that polyclonal antibody generated by LukS-mut9 can neutralize other canonical and non-canonical leukotoxin pairs. In this report, we also demonstrated that several potent toxins can be created by non-canonical pairing of subunits. Out of 5 pairs of canonical and 8 pairs of non-canonical toxins tested, anti-LukS-mut9 polyclonal antibodies neutralized all except for LukAB. We also studied the potential hemolytic activities of canonical and noncanonical pairs among biocomponent toxins and discovered that a novel non-canonical pair consisting of HlgA and LukD is a highly toxic combination. This pair can lyse RBC from different species including human blood far better than alpha hemolysin. Moreover, to follow-up our last report, we explored the correlation between the levels of pre-existing antibodies to new sets of leukotoxins subunits and clinical outcomes in adult patients with S. aureus bacteremia. We found that there is an inversed correlation between the antibody titer to sepsis for leukotoxins LukS-mut9, LukF-PV, HlgC, LukE and LukAB, suggesting the risk of sepsis was significantly lower in the patients with higher antibody titer against those toxins.
Abstract
SARS-CoV-2 virus is the serious health concern throughout the world. A comprehensive investigation of binding of SARS-CoV-2 active site with host receptor protein hACE2 is important in ...designing effective drugs. In the present work, the major amino acid binding partners between the virus CTD and host receptor have been studied and are compared with SARS-CoV RBD binding with hACE2. Our investigation show that some unique hydrogen bond pairs which were not reported in previous work. Along with hydrogen bonding, salt-bridges, hydrophobic interactions and contributions of electrostatic and van der Waals contacts play significant role in binding mechanism. The binding affinity of SARS-CoV-2 CTD/hACE2 is greater than SARS-CoV RBD/hACE2. This outcome is also verified from the free energy estimation by using umbrella sampling.
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