Miracle-dz/UniFAR-FTUs huggingface dataset:
From loss of merlin to tumorigenesis: evidence for pathological integrin-dependent adhesion, altered migration and decreased apoptosis rates

Mutations in the tumor suppressor gene Neurofibromatosis type 2 (NF2) cause the cancer predisposition syndrome NF2 as well as sporadic schwannomas, meningiomas, and human malignant mesotheliomas. The NF2 gene product merlin, an ERM protein, acts as molecular linker between cytoskeleton and plasmamembrane. The aim of this study was to contribute to the understanding on how the loss of merlin gives rise to tumorigenesis. Morphological changes of schwannoma cells (greater cell size, increased numbers of lamellipodia and filopodia, membrane ruffles) have already been described. Accordingly adhesion assays revealed much stronger adherence of schwannoma cells. By comparative gene expression analysis of Schwann vs. schwannoma cells 65 differentially expressed genes such as adhesion and signaling molecules as well as transcription and growth factors could be identified. The integrin receptors alpha6/beta1 and alpha6/beta4 were extensively studied in this thesis, and upregulation was verified at protein level and also shown in immunohistochemical staining of schwannoma tissue vs. normal nerve. Moreover clustering was detected on schwannoma cell surface, indicating high levels of integrin activity. Thus the adhesive properties of the cells are suspected to be affected, which could explain the pseudomesaxon formation by NF2-/- Schwann cells in vivo. The enhanced adhesion was proved to be integrin dependent. By examination of the cytoskeleton clear rearrangements were found for GFAP. Moreover schwannoma cells were observed to show higher migrational activity and to be less sensitive to apoptosis. The data presented here shed light on the cellular responses to loss of merlin, and reveals some potential therapeutic targets. Furthermore the impairment of proliferation of NF2-/- cells by quinidine, previously reported for schwannoma cells, was confirmed in human malignant mesothelioma cell lines, thus divulging another therapeutic approach for tumors related to loss of merlin.
Confirmation of ALS inhibitor herbicide resistance in Echinochloa colonum

Herbicides resistance is emerging as an important trend in global farming and this problem is increasing significantly. Herbicide resistance is developed in plants with the passage of time through evolution. ALS (Acetolactate synthase) is enzyme naturally occurred in plants involves in synthesis of amino acid and involved to catalyze the initial process of synthesis of various proteins that are branched in character. Bispybribic sodium herbicide inhibits the protein synthesis and generally marked as vital herbicide against weeds infestation in rice. The present experiment was performed to evaluate the prospective of ALS inhibitor herbicides resistance on different accessions of Jungle rice (Echinochloa colonum L.) under CRD with factorial arrangement. Mortality %, Visual injury %, LD50, GR50, Resistance index and Biomass % decrease over control parameters were recorded features of proposed experiment. The date of recorded parameters were analyzed properly by applying Fisher’s analysis of variance method and average data of all treatments were associated by least significant difference (LSD) test having 5% level of probability. After the application of treatments, the plants were supplied adequate amounts of water and nutrients for 30 days. Plant death (live or dead counts) was recorded 30 d after treatment (DAT). The application of four different doses of the herbicide was performed after 15 days of germination, with seedlings at the stage of 2 to 3 leaves. Sprayer configuration and growth condition for all biotypes for same. Significant and high biomass was showed by ECFS-7 (76.5) and ECFS-4 (75.66) as compared to EC-FS-SS (31.007). Less injury rate was showed by ECFS-4 (50.12) and ECFS-7 (53.69%) as compared to EC-FS-SS which show maximum injury percentage (72.18%). Maximum mortality percentage was showed in EC-FS-SS (76.062) and less in EC-FS-7 (42.37 %). LD50 of Accessions at different levels was analyzed with PROC PROBIT. The highest LD50 values were observed in EC-FS-7 (1.60) which was followed by EC-FS-5. The lowest value of THE INTERNATIONAL JOURNAL OF BIOLOGICAL RESEARCH (TIJOBR) ISSN Print 2618-1436 ISSN Online 2618-1444 Volume 2, 2019 RESEARCH ARTICLE
Drug-drug Interactions in Kidney Transplant Patients with Coronavirus Disease 2019: A Report of Two Cases and Literature Review

On February 19, 2020, the first confirmed case of Coronavirus disease 2019, known as COVID-19, was identified in Iran. Afterward, the disease spread rapidly throughout the country. Some of the cases were asymptomatic, some had mild to severe symptoms, and some of them died. Transplant patients are highly at risk due to long-term immunosuppressive therapy, and precise treatment approaches are needed to not only cure the disease but also protect graft function. This study reports two kidney transplant patients with COVID-19 pneumonia, both of whom showed respiratory and gastrointestinal symptoms. High cyclosporine and tacrolimus trough levels were observed despite initial dose reduction. After a treatment program containing reduced immunosuppressant dose and the addition of pulsatile hydrocortisone, these patients recovered effectively. We also discuss the importance of drug-drug interactions related to COVID-19 treatment protocol medications, especially with immunosuppressants, in these patients. In conclusion, frequent monitoring of the trough levels of calcineurin and mammalian target of rapamycin inhibitors during hospitalization is recommended since it helps to determine the ideal treatment and prevent serious clinical toxicity.
Optimization of bloom filter using simulated annealing for spam filtering

Bloom Filter (BF) is a simple but powerful data structure that can check membership to a static set. The trade-off to use Bloom filter is a certain configurable risk of false positives. The odds of a false positive can be made very low if the hash bitmap is sufficiently large. Spam is an irrelevant or inappropriate message sent on the internet to a large number of newsgroups or users. A spam word is a list of well-known words that often appear in spam mails. The proposed system of Bin Bloom Filter (BBF) groups the words into number of bins with different false positive rates based on the weights of the spam words for spam filtering. Simulated Annealing (SA) is stimulated by an analogy to annealing in solids. It is used to search for feasible solutions and converge to an optimal solution. In this paper SA is applied to minimize the total membership invalidation cost of BBF. The experimental results are analyzed for various sizes of bins. The results show that, the BBF using SA with different false positive rate has lower total membership invalidation cost than the standard BF.
NBER WORKING PAPER SERIES STABILITY FIRST: REFLECTIONS INSPIRED BY OTMAR ISSING’S SUCCESS AT THE ECB’S CHIEF ECONOMIST

In this paper, we review Otmar Issing's career as the ECB's inaugural chief economist and we document many notable successes. We try to infer some general principles that contributed to these successes and draw some lessons. In doing so, we review the evidence using Woodford’s (2003) recent revival of the Wicksellian approach to monetary policy making. Suitably interpreted the baseline model can rationalize Issing’s three guiding principles for successful policymaking. This baseline model, however, fails to account for the important role that monetary and financial analysis played in the conduct of policy during Issing’s tenure. We propose an extension of the model to account for financial developments and show that this extended model substantially improves our understanding of ECB practice. We conclude by listing six open questions, relevant for the future of central banking in Europe that Issing may want to consider in case leisure allows. Vitor Gaspar Banco de Portugal 148, Rua do Comercio 1101 Lisbon Codex PORTUGAL vitor_r_gaspar@bportugal.pt Anil Kashyap Graduate School of Business The University of Chicago 5807 S. Woodlawn Avenue Chicago, IL 60637 and NBER anil.kashyap@chicagogsb.edu
Vacuum polarization in heavy atoms

We formulate the Hartree–Fock method using a functional integral approach. Then we consider a nonperturbative component of the vacuum polarization. For the Dirac– Coulomb operator the renormalization ﬂow of the vacuum polarization is calculated numerically. For the Hartree–Fock operator the polarization is obtained by integrating an appropriately rescaled ﬂow. The text includes an approximate calculation of the vacuum polarization in Uranium.
Sensory Coding of Limb Kinematics in Motor Cortex across a Key Developmental Transition

Primary motor cortex (M1) undergoes protracted development in mammals, functioning initially as a sensory structure. Throughout the first postnatal week in rats, M1 is strongly activated by self-generated forelimb movements—especially by the twitches that occur during active sleep. Here, we quantify the kinematic features of forelimb movements to reveal receptive-field properties of individual units within the forelimb region of M1. At postnatal day 8 (P8), nearly all units were strongly modulated by movement amplitude, especially during active sleep. By P12, only a minority of units continued to exhibit amplitude tuning, regardless of behavioral state. At both ages, movement direction also modulated M1 activity, though to a lesser extent. Finally, at P12, M1 population-level activity became more sparse and decorrelated, along with a substantial alteration in the statistical distribution of M1 responses to limb movements. These findings reveal a transition toward a more complex and informationally rich representation of movement long before M1 develops its motor functionality. SIGNIFICANCE STATEMENT Primary motor cortex (M1) plays a fundamental role in the generation of voluntary movements and motor learning in adults. In early development, however, M1 functions as a prototypical sensory structure. Here, we demonstrate in infant rats that M1 codes for the kinematics of self-generated limb movements long before M1 develops its capacity to drive movements themselves. Moreover, we identify a key transition during the second postnatal week in which M1 activity becomes more informationally complex. Together, these findings further delineate the complex developmental path by which M1 develops its sensory functions in support of its later-emerging motor capacities.
Epidemiology of Injuries in National Collegiate Athletic Association Men's Basketball: 2014-2015 Through 2018-2019.

CONTEXT Basketball has remained a popular sport for players and spectators in the United States since before the first National Collegiate Athletic Association men's championship tournament in 1939. BACKGROUND Routine examinations of men's basketball injuries are important for identifying emerging temporal patterns. METHODS Exposure and injury data collected in the National Collegiate Athletic Association Injury Surveillance Program during 2014-2015 through 2018-2019 athletic seasons were analyzed. Injury counts, rates, and proportions were used to describe injury characteristics, and injury rate ratios were used to examine differences in injury rates. RESULTS The overall injury rate was 7.28 per 1000 athlete exposures, with competition rates twice those of practices (injury rate ratio = 2.07; 95% CI = 1.93, 2.22). Injuries to the ankle (22.2%), knee (13.0%), head/face (11.3%), and hand/wrist (10.1%) accounted for most reported injuries, with sprains (30.4%), contusions (14.3%), and strains (13.9%) most commonly reported. Ankle sprain rates initially trended upward and decreased between 2017-2018 and 2018-2019; concussion rates remained relatively stable during 2014-2015 through 2018-2019. CONCLUSIONS Findings suggest that common injury rates are trending downward relative to previous study findings.
REAL-TIME RESCHEDULING OF PRODUCTION SYSTEMS USING RELATIONAL REINFORCEMENT LEARNING

Most scheduling methodologies developed until now have laid down good theoretical foundations, but there is still the need for real-time rescheduling methods that can work effectively in disruption management. In this work, a novel approach for automatic generation of rescheduling knowledge using Relational Reinforcement Learning (RRL) is presented. Relational representations of schedule states and repair operators enable to encode in a compact way and use in real-time rescheduling knowledge learned through intensive simulations of state transitions. An industrial example where a current schedule must be repaired following the arrival of a new order is discussed using a prototype application – SmartGantt ®- for interactive rescheduling in a reactive way . SmartGantt ® demonstrates the advantages of resorting to RRL and abstract states for real-time rescheduling. A small number of training episodes are required to define a repair policy which can handle on the fly events such as order insertion, resource break-down, raw material delay or shortage and rush order arrivals using a sequence of operators to achieve a selected goal.
Relationship between Prenatal or Postnatal Exposure to Pesticides and Obesity: A Systematic Review

In recent years, the worldwide prevalence of overweight and obesity among adults and children has dramatically increased. The conventional model regarding the onset of obesity is based on an imbalance between energy intake and expenditure. However, other possible environmental factors involved, such as the exposure to chemicals like pesticides, cannot be discarded. These compounds could act as endocrine-disrupting chemicals (EDC) that may interfere with hormone activity related to several mechanisms involved in body weight control. The main objective of this study was to systematically review the data provided in the scientific literature for a possible association between prenatal and postnatal exposure to pesticides and obesity in offspring. A total of 25 human and 9 animal studies were analyzed. The prenatal, perinatal, and postnatal exposure to organophosphate, organochlorine, pyrethroid, neonicotinoid, and carbamate, as well as a combined pesticide exposure was reviewed. This systematic review reveals that the effects of pesticide exposure on body weight are mostly inconclusive, finding conflicting results in both humans and experimental animals. The outcomes reviewed are dependent on many factors, including dosage and route of administration, species, sex, and treatment duration. More research is needed to effectively evaluate the impact of the combined effects of different pesticides on human health.
Tips and tricks in the endoscopic management of a complex biliary stone in Billroth II gastrectomy

Post-surgical anatomy may make traditional endoscopic retrograde cholangiopancreatography challenging for the endoscopist. In patients with Billroth II gastrectomy, challenges include selective entrance to the afferent loop and cannulation of the common bile duct (CBD) due to the inverted position [1]. Endoscopic management of CBD stones may be especially difficult in these patients, especially those with complex biliary stones [2]. We present a case of a 67-year-old gentleman with a previous Billroth II gastrectomy due to peptic ulcer disease who presented with jaundice (total bilirubin 9.72mg/dl, direct bilirubin 6.3mg/dl) and abdominal pain. Imaging at this time with magnetic resonance cholangiopancreatography demonstrated extrahepatic bile duct dilation and a large distal CDB stone (1.6 cm×1 cm). For this case, a standard gastroscope was chosen in favor of a duodenoscope to decrease potential adverse events such as perforation [3]. On initial endoscopy, the major papilla was found and the cannulation occurred without difficulty (▶Video 1, ▶Fig. 1). Fluoroscopy evaluation revealed a dilated CBD with a large biliary stone. The ideal position (5 o’clock) to perform sphincterotomy was not achieved. Therefore, a limited sphincterotomy was performed to guide the balloon dilation. Next, a large through-the-scope balloon dilation E-Videos
Managing Anemia across the Stages of Kidney Disease in Those Hyporesponsive to Erythropoiesis-Stimulating Agents

Background: Patients with CKD frequently have anemia that results from iron-restricted erythropoiesis and inflammation. Anemia of CKD is currently managed with iron supplements and erythropoiesis-stimulating agents (ESAs) to promote erythropoiesis and with RBC transfusion in severe cases. Hyporesponse to ESAs, or the need for larger than usual doses to attain a given hemoglobin (Hb) level, is associated with increased morbidity and mortality and presents a pressing clinical challenge, particularly for patients on dialysis. This paper reviews ESA hyporesponse and potential new therapeutic options in the management of anemia of CKD. Summary: The most common causes of ESA hyporesponse include iron deficiency and inflammation, and to a lesser degree, secondary hyperparathyroidism, inadequate dialysis, malnutrition, and concomitant medications. Management of ESA hyporesponse is multipronged and involves treating low level infections, ensuring adequate nutrition, and optimizing iron status and dialysis modality, although some patients can remain refractory. Inflammation directly increases production and secretion of hepcidin, contributes to an impaired response to hypoxia, and suppresses proliferation of erythroid progenitors. Coordination of renal and hepatic erythropoietin (EPO) production and iron metabolism is under the control of hypoxia-inducible factors (HIF), which are in turn regulated by HIF-prolyl hydroxylases (HIF-PHs). HIF-PHs and hepcidin are therefore attractive potential drug targets particularly in patients with ESA hyporesponse. Several oral HIF-PH inhibitors have been evaluated in patients with anemia of CKD and have been shown to increase Hb and reduce hepcidin regardless of inflammation, iron status, or dialysis modality. These sustained effects are achieved through more modest increases in endogenous EPO compared with ESAs. Key Messages: Treatments that address ESA hyporesponse remain a significant unmet clinical need in patients with anemia of CKD. New therapies such as HIF-PH inhibitors have the potential to address fundamental aspects of ESA hyporesponse and provide a new therapeutic option in these patients.
Potent Neutralizing Antibodies Elicited by RBD-Fc-Based COVID-19 Vaccine Candidate Adjuvanted by the Th2-Skewing iNKT Cell Agonist

The development of a safe and effective COVID-19 vaccine is of paramount importance to terminate the current pandemic. An adjuvant is crucial for improving the efficacy of the subunit COVID19 vaccine. α-Galactosylceramide (αGC) is a classical iNKT cell agonist which causes the rapid production of Th1- and Th2-associated cytokines; we, therefore, expect that the Th1- or Th2-skewing analogues of αGC can better enhance the immunogenicity of the receptor-binding domain in the spike protein of SARS-CoV-2 fused with the Fc region of human IgG (RBD-Fc). Herein, we developed a universal synthetic route to the Th1-biasing (α-C-GC) and Th2-biasing (OCH and C20:2) analogues. Immunization of mice demonstrated that αGC-adjuvanted RBD-Fc elicited a more potent humoral response than that observed with Alum and enabled the sparing of antigens. Remarkably, at a low dose of the RBD-Fc protein (2 μg), the Th2-biasing agonist C20:2 induced a significantly higher titer of the neutralizing antibody than that of Alum.
Arcuate and Preoptic Kisspeptin Neurons Exhibit Differential Projections to Hypothalamic Nuclei and Exert Opposite Postsynaptic Effects on Hypothalamic Paraventricular and Dorsomedial Nuclei in the Female Mouse

Abstract Kisspeptin (Kiss1) neurons provide indispensable excitatory input to gonadotropin-releasing hormone (GnRH) neurons, which is important for the coordinated release of gonadotropins, estrous cyclicity and ovulation. However, Kiss1 neurons also send projections to many other brain regions within and outside the hypothalamus. Two different populations of Kiss1 neurons, one in the arcuate nucleus (Kiss1ARH) and another in the anteroventral periventricular nucleus (AVPV) and periventricular nucleus (PeN; Kiss1AVPV/PeN) of the hypothalamus are differentially regulated by ovarian steroids, and are believed to form direct contacts with GnRH neurons as well as other neurons. To investigate the projection fields from Kiss1AVPV/PeN and Kiss1ARH neurons in female mice, we used anterograde projection analysis, and channelrhodopsin-assisted circuit mapping (CRACM) to explore their functional input to select target neurons within the paraventricular (PVH) and dorsomedial (DMH) hypothalamus, key preautonomic nuclei. Cre-dependent viral (AAV1-DIO-ChR2 mCherry) vectors were injected into the brain to label the two Kiss1 neuronal populations. Immunocytochemistry (ICC) for mCherry and neuropeptides combined with confocal microscopy was used to determine the projection-fields of both Kiss1 neuronal groups. Whole-cell electrophysiology and optogenetics were used to elucidate the functional input to the PVH and DMH. Our analysis revealed many common but also several clearly separate projection fields between the two different populations of Kiss1 neurons. In addition, optogenetic stimulation of Kiss1 projections to PVH prodynorphin, Vglut2 and DMH CART-expressing neurons, revealed excitatory glutamatergic input from Kiss1ARH neurons and inhibitory GABAergic input from Kiss1AVPV/PeN neurons. Therefore, these steroid-sensitive Kiss1 neuronal groups can differentially control the excitability of target neurons to coordinate autonomic functions with reproduction.
Dual-modified PCL-PEG nanoparticles for improved targeting and therapeutic efficacy of docetaxel against colorectal cancer

Abstract Polycaprolactone-poly (ethylene glycol) block copolymer (PCL-PEG) based nanoparticles were prepared for the intravenous administration of docetaxel (DTX). PCL-PEG-Tyr and PCL-PEG-Ang were synthesized by using tyrosine (Tyr) and angiopep-2 (Ang) as coupling ligands, and dual-modified PCL-PEG-based nanoparticles (PCL-PEG-Tyr/Ang) were prepared. The physicochemical properties, in vitro drug release, in vitro cytotoxicity, in vitro cellular uptake efficiency, in vivo biodistribution and in vivo antitumor efficacy of PCL-PEG-based nanoparticles were investigated. The PCL-PEG-based nanoparticles were spherical with a mean diameter of 100 nm and high encapsulation efficiencies (> 85%). The results of in vitro drug release showed that the PCL-PEG-based nanoparticles loaded with DTX had sustained-release characteristics. For in vitro cytotoxicity tests, the dual-modified PCL-PEG-based nanoparticles (PCL-PEG-Tyr/Ang) demonstrated the minimum IC50 value (2.94 µg/mL) compared with other PCL-PEG-based nanoparticles. In addition, the cellular uptake of coumarin-6 (C6) in HT29 cells was observed and determined in the PCL-PEG-Tyr/Ang nanoparticles group, which was significantly higher than that in the other PCL-PEG-based groups and C6 solution group. The results of in vivo imaging showed that dual-modified PCL-PEG nanoparticles had better tumor targeting than the other PCL-PEG-based nanoparticles. In the HT29 tumor-xenografted nude mice model, DTX-loaded PCL-PEG-Tyr/Ang nanoparticles also had a significantly higher inhibitory efficacy on tumor growth than Taxotere®-treated group. These results indicated that the dual-modified PCL-PEG-based nanoparticles (PCL-PEG-Tyr/Ang) could be a promising anticancer drug delivery system.