gebhart/patrepeval huggingface dataset:
Discovery of potent inhibitors for SARS-CoV-2's main protease by ligand-based/structure-based virtual screening, MD simulations, and binding energy calculations (2020)

COVID-19 has caused lockdowns all over the world in early 2020, as a global pandemic. Both theoretical and experimental efforts are seeking to find an effective treatment to suppress the virus. In silico drug design can play a vital role in identifying promising drug candidates against COVID-19. Herein, we focused on the main protease of SARS-CoV-2 that has crucial biological functions in the virus. We performed a ligand-based virtual screening followed by a docking screening for testing approved drugs and bioactive compounds listed in the DrugBank and ChEMBL databases. The top 8 docking results were advanced to all-atom MD simulations to study the relative stability of the protein-ligand interactions. MD simulations support that the catalytic residue, His41, has a neutral side chain with a protonated delta position. An absolute binding energy (ΔG) of -42 kJ mol-1 for the protein-ligand (Mpro-N3) complex has been calculated using the potential-of-mean-force (geometrical) approach. Furthermore, the relative binding energies were computed for the top docking results. Our results suggest several promising approved and bioactive inhibitors of SARS-CoV-2 Mpro as follows: a bioactive compound, ChEMBL275592, which has the best MM/GBSA binding energy; the second-best compound, montelukast, is an approved drug used in the treatment of asthma and allergic rhinitis; the third-best compound, ChEMBL288347, is a bioactive compound. Bromocriptine and saquinavir are other approved drugs that also demonstrate stability in the active site of Mpro, albeit their relative binding energies are low compared to the N3 inhibitor. This study provides useful insights into de novo protein design and novel inhibitor development, which could reduce the cost and time required for the discovery of a potent drug to combat SARS-CoV-2.
ReticularSpaces (2012)

Smart spaces research focuses on technology for multiple displays and devices for collocated participants. In most approaches, however, users have to cope with heterogeneous interfaces and information organization, as well as a lack of support for collaboration with mobile and remote users outside the smart space. In this paper, we present ReticularSpaces; a multi-display smart space system built on the principles of activity-based computing. The focus of ReticularSpaces is to support: (i) unified interaction with applications and documents through ReticularUI, a novel distributed user interfaces design; (ii) management of the complexity of tasks between users and displays; (iii) mobile users in a local, remote or 'nomadic' settings; and (iv) collaboration among local and remote users. We describe the motivation, design, and architecture of ReticularSpaces, and report from a preliminary feasibility study. The study shows that participants found ReticularSpaces useful and effective, but at the same time reveals new areas for research on smart environments.
Domain Decomposition Methods Applied to Coupled Flow-Geomechanics Reservoir Simulation (2011)

Abstract In this work, well established Domain Decomposition techniques have been studied in order to carry out efficient simulations of coupled flow/geomechanics problems by taking full advantage of current parallel computer architectures. Different solution schemes can be defined depending upon transmission conditions among sub-domain interfaces. Three different schemes, i.e. Dirichlet-Neumann, Neumann-Neumann and Mortar-FEM, are tested and the advantages and disadvantages of each of them identified. This work will focus in the coupling of different meshes and/or physics on different domains by means of the Mortar-FEM plus the above DD-Schemes. Several examples of coupling of elasticity and poroelasticity in the context of reservoir compaction and subsidence are presented. In order to facilitate the implementation of complex workflows, we have implemented an advanced Python wrapper interface that allows programming capabilities. We have applied this platform to a variety of problems ranging from near-wellbore applications to field level subsidence calculations.
Anaphylatoxin C3a receptors in asthma (2005)

The complement system forms the central core of innate immunity but also mediates a variety of inflammatory responses. Anaphylatoxin C3a, which is generated as a byproduct of complement activation, has long been known to activate mast cells, basophils and eosinophils and to cause smooth muscle contraction. However, the role of C3a in the pathogenesis of allergic asthma remains unclear. In this review, we examine the role of C3a in promoting asthma. Following allergen challenge, C3a is generated in the lung of subjects with asthma but not healthy subjects. Furthermore, deficiency in C3a generation or in G protein coupled receptor for C3a abrogates allergen-induced responses in murine models of pulmonary inflammation and airway hyperresponsiveness. In addition, inhibition of complement activation or administration of small molecule inhibitors of C3a receptor after sensitization but before allergen challenge inhibits airway responses. At a cellular level, C3a stimulates robust mast cell degranulation that is greatly enhanced following cell-cell contact with airway smooth muscle (ASM) cells. Therefore, C3a likely plays an important role in asthma primarily by regulating mast cell-ASM cell interaction.
Improvement in aligned GaN nanowire growth using submonolayer Ni catalyst films (2008)

We report a route to ultrahigh-density and highly aligned single-crystalline GaN nanowires on sapphire by employing ultrathin Ni catalyst films with submonolayer thickness. The nanowire density and the degree of alignment were found to be highly sensitive to changes in the Ni catalyst film thickness below 1nm, a regime rarely explored in catalyzed nanowire growth before. For submonolayer Ni films on sapphire, high activation energy for Ni diffusion on sapphire surface is attributed to the formation of high-density and ultrasmall Ni islands with a narrow size distribution, which in turn leads to high-density and highly aligned GaN nanowires.
Whole genome and phylogenetic analysis of two SARS-CoV-2 strains isolated in Italy in January and February 2020: additional clues on multiple introductions and further circulation in Europe (2020)

Whole genome sequences of SARS-CoV-2 obtained from two patients, a Chinese tourist visiting Rome and an Italian, were compared with sequences from Europe and elsewhere. In a phylogenetic tree, the Italian patient's sequence clustered with sequences from Germany while the tourist's sequence clustered with other European sequences. Some additional European sequences in the tree segregated outside the two clusters containing the patients' sequences. This suggests multiple SARS-CoV-2 introductions in Europe or virus evolution during circulation.
R&D-based growth literature (2003)

The aim of this paper is to illustrate in major details the innovation-driven endogenous growth theory and the related literature about R&D spillovers. We do not aspire to survey all existing papers, but the most representative of the main issues about this subject.
Dynamic Host Configuration Protocol (DHCPv4) Option for the Intra-Site Automatic Tunnel Addressing Protocol (ISATAP) (2009)

This document specifies a Dynamic Host Configuration Protocol (DHCPv4)
option for nodes that implement the Intra-Site Automatic Tunnel
Addressing Protocol (ISATAP).
Calibration of Water Distribution Hydraulic Models Using a Bayesian-Type Procedure (2007)

Estimating model parameters is a difficult, yet critical step in the use of water distribution system models. Most of the optimization-based approaches developed so far concentrate primarily on efficient and effective ways of obtaining optimal calibration parameter values. At the same time, very little effort has been made to determine the uncertainties (i.e., errors) associated with those values (and related model predictions). So far, this has typically been done using the first-order second moment (FOSM) method. Even though reasonably computationally efficient, the FOSM approach relies on several restrictive assumptions and requires computationally demanding calculation of derivatives. To overcome these limitations, the recently developed shuffled complex evolution metropolis (SCEM-UA) global optimization algorithm is linked to the Epanet2 hydraulic model and used to solve a least-squares-type calibration problem. The methodology is tested and verified on the Anytown literature case study. The main advantage of the SCEM-UA algorithm over existing approaches is that both calibration parameter values and associated uncertainties can be determined in a single optimization model run. In addition, no model linearity or parameter normality assumptions have to be made nor any derivatives calculated. The main drawback of the SCEM-UA methodology is that it could, potentially, be computationally demanding, although this is not envisaged as a major problem with current computers.
A Machine Learning Based Web Spam Filtering Approach (2016)

Web spam has the effect of polluting search engine results and decreasing the usefulness of search engines.Web spam can be classified according to the methods used to raise the web page's ranking by subverting web search engine's algorithms used to rank search results. The main types are: content spam, link spam and cloaking spam. There has been little or no work on automatically classifying web spam by type. This paper has two contributions, (i) we propose a Dual-Margin Multi-Class Hypersphere Support Vector Machine (DMMH- SVM) classifier approach to automatically classifying web spam by type, (ii) we introduce novel cloaking-based spam features which help our classifier model to achieve high precision and recall rate, thereby reducing the false positive rates. The effectiveness of the proposed model is justified analytically. Our experimental results demonstrated that DMMH-SVM outperforms existing algorithms with novel cloaking features.
Progranulin, a Glycoprotein Deficient in Frontotemporal Dementia, Is a Novel Substrate of Several Protein Disulfide Isomerase Family Proteins (2011)

The reduced production or activity of the cysteine-rich glycoprotein progranulin is responsible for about 20% of cases of familial frontotemporal dementia. However, little is known about the molecular mechanisms that govern the level and secretion of progranulin. Here we show that progranulin is expressed in mouse cortical neurons and more prominently in mouse microglia in culture and is abundant in the endoplasmic reticulum (ER) and Golgi. Using chemical crosslinking, immunoprecipitation, and mass spectrometry, we found that progranulin is bound to a network of ER Ca(2+)-binding chaperones including BiP, calreticulin, GRP94, and four members of the protein disulfide isomerase (PDI) family. Loss of ERp57 inhibits progranulin secretion. Thus, progranulin is a novel substrate of several PDI family proteins and modulation of the ER chaperone network may be a therapeutic target for controlling progranulin secretion.
Use of Predicted Risk of Mortality to evaluate the efficacy of anticytokine therapy in sepsis (1996)

Using an appropriate analytic model, a statistically significant increase in survival time from rhIL-1ra was measured. A direct relationship was found between a patient's Predicted Risk of Mortality at study entry to efficacy of rhIL-1ra. Individual risk or severity assessment may be a useful tool for evaluating the clinical benefit of new therapeutic approaches to sepsis and for monitoring outcomes at the bedside.
Area-Selective Atomic Layer Deposition of Lead Sulfide: Nanoscale Patterning and DFT Simulations (2010)

Area-selective atomic layer deposition (ALD) of lead sulfide (PbS) was achieved on octadecyltrichlorosilane (ODTS)-patterned silicon substrates. We investigated the capability of ODTS self-assembled monolayers (SAMs) to deactivate the ALD PbS surface reactions as a function of dipping time in ODTS solution. The reaction mechanism was investigated using density functional theory (DFT), which showed that the initial ALD half-reaction is energetically unfavorable on a methyl-terminated SAM surface. Conventional photolithography was used to create oxide patterns on which ODTS SAMs were selectively grown. Consequently, PbS thin films were grown selectively only where ODTS was not present, whereas deposition was blocked in regions where ODTS was grown. The resulting fabricated patterns were characterized by scanning electron microscopy and Auger electron spectroscopy, which demonstrated that ALD PbS was well confined to defined patterns with high selectivity by ODTS SAMs. In addition, AFM lithography was employed to create nanoscale PbS patterns. Our results show that this method can be applied to various device-fabrication processes, presenting new opportunities for various nanofabrication schemes and manifesting the benefits of self-assembly.
Initiation of Hepatitis C Virus Infection Requires the Dynamic Microtubule Network (2009)

Early events leading to the establishment of hepatitis C virus (HCV) infection are not completely understood. We show that intact and dynamic microtubules play a key role in the initiation of productive HCV infection. Microtubules were required for virus entry into cells, as evidenced using virus pseudotypes presenting HCV envelope proteins on their surface. Studies carried out using the recent infectious HCV model revealed that microtubules also play an essential role in early, postfusion steps of the virus cycle. Moreover, low concentrations of vinblastin and nocodazol, microtubule-affecting drugs, and paclitaxel, which stabilizes microtubules, inhibited infection, suggesting that microtubule dynamic instability and/or treadmilling mechanisms are involved in HCV internalization and early transport. By protein chip and direct core-dependent pull-down assays, followed by mass spectrometry, we identified beta- and alpha-tubulin as cellular partners of the HCV core protein. Surface plasmon resonance analyses confirmed that core directly binds to tubulin with high affinity via amino acids 2-117. The interaction of core with tubulin in vitro promoted its polymerization and enhanced the formation of microtubules. Immune electron microscopy showed that HCV core associates, at least temporarily, with microtubules polymerized in its presence. Studies by confocal microscopy showed a juxtaposition of core with microtubules in HCV-infected cells. In summary, we report that intact and dynamic microtubules are required for virus entry into cells and for early postfusion steps of infection. HCV may exploit a direct interaction of core with tubulin, enhancing microtubule polymerization, to establish efficient infection and promote virus transport and/or assembly in infected cells.
Photo-ribonucleotide reductase β2 by selective cysteine labeling with a radical phototrigger (2011)

Photochemical radical initiation is a powerful tool for studying radical initiation and transport in biology. Ribonucleotide reductases (RNRs), which catalyze the conversion of nucleotides to deoxynucleotides in all organisms, are an exemplar of radical mediated transformations in biology. Class Ia RNRs are composed of two subunits: α2 and β2. As a method to initiate radical formation photochemically within β2, a single surface-exposed cysteine of the β2 subunit of Escherichia coli Class Ia RNR has been labeled (98%) with a photooxidant ([Re ] = tricarbonyl(1,10-phenanthroline)(methylpyridyl)rhenium(I)). The labeling was achieved by incubation of S355C-β2 with the 4-(bromomethyl)pyridyl derivative of [Re] to yield the labeled species, [Re]-S355C-β2. Steady-state and time-resolved emission experiments reveal that the metal-to-ligand charge transfer (MLCT) excited-state (3)[Re ](∗) is not significantly perturbed after bioconjugation and is available as a phototrigger of tyrosine radical at position 356 in the β2 subunit; transient absorption spectroscopy reveals that the radical lives for microseconds. The work described herein provides a platform for photochemical radical initiation and study of proton-coupled electron transfer (PCET) in the β2 subunit of RNR, from which radical initiation and transport for this enzyme originates.
An Intronic Polymorphism of the <i>hMLH1</i> Gene Contributes Toward Incomplete Genetic Testing for HNPCC (2002)

Hereditary non-polyposis colorectal cancer (HNPCC) is a common hereditary cancer. Genetic testing is complicated by the multiple DNA mismatch repair genes that underlie the disorder. Many suspected HNPCC families have no germ-line mutation identified. We reassessed an unusual family that appeared to have 2 individuals homozygous for a germline mutation within exon 1 of the hMLH1 gene. A few rare individuals with two inherited mutations in one of the mismatch repair genes have been reported and appear to have a distinct clinical appearance. However, there were no clinical features in the family discussed here that were consistent with constitutive lack of hMLH1. Redesigning the intronic primers for exon 1 identified a common polymorphism located within the original intronic primer site. The polymorphism prevented amplification of the wild-type allele, giving the erroneous appearance of homozygous inheritance of the mutated allele. Likewise, common intronic polymorphisms, if located within primer sequences on the chromosome harboring the HNPCC germ-line mutation could restrict amplification to only the wild-type allele, which may contribute significantly to the low success rate of identifying mutations in HNPCC families.
PEDF induces p53-mediated apoptosis through PPAR gamma signaling in human umbilical vein endothelial cells (2007)

Our observations indicate that PEDF induces HUVECs apoptosis through the sequential induction of PPARgamma and p53 overexpression. With the growing interest in anti-angiogenesis as a novel approach to cancer therapy, defining the mechanism of PEDF-mediated HUVEC apoptosis may facilitate the development of new therapeutics.
Enlarged Waist Combined With Elevated Triglycerides Is a Strong Predictor of Accelerated Atherogenesis and Related Cardiovascular Mortality in Postmenopausal Women (2005)

The combined presence of EWET may be the best indicator of cardiovascular risk in postmenopausal women. Other components of the MS-NCEP add little medical value to screening in general practices.
Immunity and Tolerance Induced by Intestinal Mucosal Dendritic Cells (2016)

Dendritic cells present in the digestive tract are constantly exposed to environmental antigens, commensal flora, and invading pathogens. Under steady-state conditions, these cells have high tolerogenic potential, triggering differentiation of regulatory T cells to protect the host from unwanted proinflammatory immune responses to innocuous antigens or commensals. On the other hand, these cells must discriminate between commensal flora and invading pathogens and mount powerful immune response against pathogens. A potential result of unbalanced tolerogenic versus proinflammatory responses mediated by dendritic cells is associated with chronic inflammatory conditions, such as Crohn's disease, ulcerative colitis, food allergies, and celiac disease. Herein, we review the dendritic cell population involved in mediating tolerance and immunity in mucosal surfaces, the progress in unveiling their development in vivo, and factors that can influence their functions.
ICCAD-2013 CAD contest in technology mapping for macro blocks and benchmark suite (2013)

As technology advances, there is an increasing need in the industrial domain for an algorithm that can map macro blocks. This type of algorithm would solve several front-end problems. For example, existing structural or functional algorithms cannot solve the challenge of mapping large-scale functions without boundary information. Fortunately, in practical problems, we only consider the target mapping functions that are the constructs of the datapath, and these macro blocks are easily recognized through their special arithmetic signatures. In this problem, the contestants need to design a mapping algorithm that recognizes macro blocks and replaces the mapped region with the macro blocks. Therefore, we can fairly evaluate the quality of the mapping algorithm as the size reduction of the revised netlist. Under our well-designed benchmarks, we will clearly differentiate the capability of proposed algorithms with several indexes. We look forward to triggering the academic area to investigate on this problem.
Assessment of renal graft function by perioperative monitoring of cortical microcirculation in kidney transplantation.1 (2003)

Thermodiffusion could be clinically applicable for the perioperative monitoring of renal graft perfusion. Intraoperative reduction of cortical microcirculation has a high predictive value with respect to detection of delayed renal function. Postoperatively, impaired renal microperfusion is associated with acute tubular necrosis. Living-related donor grafts show less microcirculatory alteration than cadaveric kidneys.
Leveraging pre-silicon data to diagnose out-of-specification failures in mixed-signal circuits (2014)

Diagnosing out-of-specification failures in mixed-signal circuits has become increasingly challenging due to: (1) failures caused by interactions between input-signal conditions and design uncertainties, and (2) the need to identify critical input and uncertainty conditions that cause these regions. We propose a simulation-driven approach that first uses ensemble learning to extract if -- then rules that naturally solve both problems. By ranking, pruning and clustering these rules, we then construct non-linear failure regions which can be directly employed for pre-silicon debug, as demonstrated on a phase-locked loop circuit. Furthermore, these regions can be used to guide test pattern generation and/or assist with post-silicon debug.
Growth factors and feeder cells promote differentiation of human embryonic stem cell into dopaminergic neurons: a novel role of fibroblast growth factor-20 (2008)

Human embryonic stem cells (hESCs) are a potential source of dopaminergic neurons for treatment of patients with Parkinson's disease (PD). Dopaminergic neurons can be derived from hESCs and display a characteristic midbrain phenotype. Once transplanted, they can induce partial behavioral recovery in animal models of PD. However, the potential research field faces several challenges that need to be overcome before clinical application of hESCs in a transplantation therapy in PD can be considered. These include low survival of the hESC-derived, grafted dopaminergic neurons after transplantation; unclear functional integration of the grafted neurons in the host brain; and, the risk of teratoma/tumor formation from the transplanted cells. This review is focused on our recent efforts to improve the survival of hESC-dervied dopaminergic neurons. In a recent study, we examined the effect of fibroblast growth factor (FGF)-20 in the differentiation of hESCs into dopaminergic neurons. We supplemented cultures of hESCs with FGF-20 during differentiation on PA6 mouse stromal cells for 3 weeks. When we added FGF-20 the yield of neurons expressing tyrosine hydroxylase increased. We demonstrated that at least part of the effect is contributed by enhanced cell differentiation towards the dopaminergic phenotype as well as reduced cell death. We compare our results with those obtained in other published protocols using different sets of growth factors. Taken together, our data indicate that FGF-20 has potent effects to generate large number of dopaminergic neurons derived from hESCs, which may be useful for hESC-based therapy in PD.