gebhart/patrepeval huggingface dataset:
Mining software usage data (2004)

Many software systems collect or can be instrumented to collect data about how users use them, i.e., system-user interaction data. Such data can be of great value for program understanding and reengineering purposes. We demonstrate that sequential data mining methods can be applied to discover interesting patterns of user activities from system-user interaction traces. In particular, we developed a process for discovering a special type of sequential patterns, called interaction patterns. These are sequences of events with noise, in the form of spurious events that may occur anywhere in a pattern instance. In our case studies, we applied interaction pattern mining to systems with considerable different forms of interaction: Web-based systems and legacy systems. We used the discovered patterns for user interface reengineering, and personalization. The method is promising and generalizable to other systems with different forms of interaction.
Research and Development on Therapeutic Agents and Vaccines for COVID-19 and Related Human Coronavirus Diseases (2020)

Since the outbreak of the novel coronavirus disease COVID-19, caused by the SARS-CoV-2 virus, this disease has spread rapidly around the globe. Considering the potential threat of a pandemic, scientists and physicians have been racing to understand this new virus and the pathophysiology of this disease to uncover possible treatment regimens and discover effective therapeutic agents and vaccines. To support the current research and development, CAS has produced a special report to provide an overview of published scientific information with an emphasis on patents in the CAS content collection. It highlights antiviral strategies involving small molecules and biologics targeting complex molecular interactions involved in coronavirus infection and replication. The drug-repurposing effort documented herein focuses primarily on agents known to be effective against other RNA viruses including SARS-CoV and MERS-CoV. The patent analysis of coronavirus-related biologics includes therapeutic antibodies, cytokines, and nucleic acid-based therapies targeting virus gene expression as well as various types of vaccines. More than 500 patents disclose methodologies of these four biologics with the potential for treating and preventing coronavirus infections, which may be applicable to COVID-19. The information included in this report provides a strong intellectual groundwork for the ongoing development of therapeutic agents and vaccines.
Expression of recombinant bovine .BETA.-lactoglobulin in Escherichia coli. (1990)

Bovine β-lactoglobulin A was expressed in Escherichia coli in its mature form. The gene was constructed using a cDNA clone which coded for amino acid residues Leu-11 to He-162 and a synthetic oligonucleotide coding for the initial 10 amino acids preceded by a translational start. The met-β-lactoglobulin was expressed using a tac promoter vector, pTTQ18, and accounted for approximately 15% of the total cellular protein. The recombinant met-β-lactoglobulin migrated with the same molecular weight as native β-actoglobulin A on SDS-PAGE. The majority of the met-β-lactoglobulin produced was found in an insoluble form but could be solubilized using guanidine-HCI. The renatured preparation was > 80 % pure and migrated similarly to purified β-lactoglobulin A under nondenaturing conditions.
Silicon-on-Insulator Spectral Filters Fabricated With CMOS Technology (2010)

We give an overview of recent progress in passive spectral filters and demultiplexers based on silicon-on-insulator photonic wire waveguides: ring resonators, interferometers, arrayed waveguide gratings, and echelle diffraction gratings, all benefit from the high-index contrast possible with silicon photonics. We show how the current generation of devices has improved crosstalk levels, insertion loss, and uniformity due to an improved fabrication process based on 193 nm lithography.
Targeting Alpha-Fetoprotein (AFP)–MHC Complex with CAR T-Cell Therapy for Liver Cancer (2016)

This study demonstrates that CAR T-cell immunotherapy targeting intracellular/secreted solid tumor antigens can elicit a potent antitumor response. Our approach expands the spectrum of antigens available for redirected T-cell therapy against solid malignancies and offers a promising new avenue for liver cancer immunotherapy. Clin Cancer Res; 23(2); 478-88. ©2016 AACR.
roundabout4 is essential for angiogenesis in vivo (2005)

Stereotypical patterns of vascular and neuronal networks suggest that specific genetic programs tightly control path determination and, consequently, angiogenesis and axon-guidance mechanisms. Our study focuses on one member of the roundabout family of receptors, which traditionally mediate repulsion from the midline. Here, we characterize a fourth member of this family, roundabout4 (robo4), which is the predominant roundabout (robo) that is expressed in embryonic zebrafish vasculature. Gene knockdown and overexpression approaches show that robo4 is essential for coordinated symmetric and directed sprouting of intersomitic vessels and provide mechanistic insights into this process. Also, human robo4 gene functionally compensates for loss of robo4 gene function, suggesting evolutionary conservation. This article reports an endothelial-specific function for a robo gene in vertebrates in vivo.
PCR-Enzyme Immunoassay for Detection of Streptococcus pneumoniae DNA in Cerebrospinal Fluid Samples from Patients With Culture-Negative Meningitis (1998)

A PCR-based assay was developed to amplify a conserved region of the pneumococcal autolysin gene. The amplified product was labelled with digoxigenin-labelled dUTP and was detected with a biotin-labelled probe in an enzyme immunoassay (EIA). The assay was initially tested with suspensions of various serotypes of Streptococcus pneumoniae and other gram-positive and gram-negative bacteria and was then applied to cerebrospinal fluid (CSF) specimens from patients with meningitis and those with other neurological disorders. The assay detected all the serotypes of S. pneumoniae tested, whereas all the other bacterial strains tested were negative. Seven of the 8 CSF specimens positive for pneumococcus by culture or latex agglutination (LA) were positive by PCR-EIA, whereas all 10 specimens positive for other organisms were negative. Among 11 patients with clinically diagnosed meningitis but with negative culture and LA results, 5 were positive by PCR-EIA. The assay was negative for all but one patient without meningitis; it was positive with the CSF from a child with immunodeficiency and pneumococcal abscesses on the scalp. PCR-EIA is a useful tool for the diagnosis of meningitis, especially when culture and LA are negative because of prior antibiotic treatment.
Mechanism of Activation of Human Heparanase Investigated by Protein Engineering (2004)

The aim of this study was to investigate the mechanism of activation of human heparanase, a key player in heparan sulfate degradation, thought to be involved in normal and pathologic cell migration processes. Active heparanase arises as a product of a series of proteolytic processing events. Upon removal of the signal peptide, the resulting, poorly active 65 kDa species undergoes the excision of an intervening 6 kDa fragment generating an 8 kDa polypeptide and a 50 kDa polypeptide, forming the fully active heterodimer. By engineering of tobacco etch virus protease cleavage sites at the N- and C-terminal junctions of the 6 kDa fragment, we were able to reproduce the proteolytic activation of heparanase in vitro using purified components, showing that cleavage at both sites leads to activation in the absence of additional factors. On the basis of multiple-sequence alignment of the N-terminal fragment, we conclude that the first beta/alpha/beta element of the postulated TIM barrel fold is contributed by the 8 kDa subunit and that the excised 6 kDa fragment connects the second beta-strand and the second alpha-helix of the barrel. Substituting the 6 kDa fragment with the topologically equivalent loop from Hirudinaria manillensis hyaluronidase or connecting the 8 and 50 kDa fragments with a spacer of three glycine-serine pairs resulted in constitutively active, single-chain heparanases which were comparable to the processed, heterodimeric enzyme with regard to specific activity, chromatographic profile of hydrolysis products, complete inhibition at NaCl concentrations above 600 mM, a pH optimum of pH approximately 5, and inhibition by heparin with IC(50)s of 0.9-1.5 ng/microL. We conclude that (1) the heparanase heterodimer (alpha/beta)(8)-TIM barrel fold is contributed by both 8 and 50 kDa subunits with the 6 kDa connecting fragment leading to inhibition of heparanase by possibly obstructing access to the active site, (2) proteolytic excision of the 6 kDa fragment is necessary and sufficient for heparanase activation, and (3) our findings open the way to the production of recombinant, constitutively active single-chain heparanase for structural studies and for the identification of inhibitors.
The influence of body composition on therapeutic hypothermia: a prospective observational study of patients after cardiac arrest (2008)

The body composition measures from single-frequency impedance and anthropometrics appear to be very concordant. Only TBF percentage (anthropometrics) showed a significant but clinically irrelevant influence on time needed to achieve target temperature with hypothermia. We conclude that there are no indications to adjust current cooling practice toward the body composition of patients.
Cancer immunotherapy with blocking of immune checkpoints (2013)

がんワクチンによる免疫治療では，如何にCD8T細胞を感作（プライミング）しその数を増やすか（免疫増強）という点に多大の努力が払われて来た．樹状細胞への抗原デリバリーと抗原プロセシング／提示，Toll様受容体などの刺激，即ち自然免疫系の活性化の併用などはそれに該当する．しかし十分に活性化されたＴ細胞をもってしても癌の拒絶は容易ではない．それには癌組織という特殊な環境が禍している．Ｔ細胞は癌塊内に入り込み莫大な数の癌細胞と遭遇する．癌組織内での繰り返す抗原認識の過程でＴ細胞は疲弊し，次第に本来あるべき機能を喪失していく．この疲弊（exhaustion）と呼ばれる現象は，Ｔ細胞に発現する複数の免疫抑制性分子―免疫チェックポイント分子―と腫瘍に発現するそのリガンドの結合によってもたらされる．代表的なチェックポイント分子の機能を抑制し，エフェクターＴ細胞が疲弊することなくその機能を長く維持できれば，これからのがん免疫治療に飛躍的な進展がみられるかもしれない．
Microfluidics for particle manipulation: new simulation techniques for novel devices and applications (2013)

This thesis focuses on fundamental aspects of microfluidic systems and applies relevant findings to innovative designs for advanced particle manipulation applications. Computational Fluid Dynamics (CFD) is adopted for fluid modeling, based on the Finite Volume method. The accuracy of the solutions obtained is confirmed by grid sensitivity analysis and by comparisons with experimental work. Curved microchannel features and the induced Dean flow are studied through a parametric space exploration and simulations. The Lagrange-Euler coupling method – Surface Marker Point methodology – is applied to simulate large-size particles (of comparable size to the channel). Through this simulation approach, all the forces on such particles are directly derived through solving the governing equations and the influence of these particles on the flow is considered in a fully coupled manner. A new approach – the Frozen Flow &amp; Flow Correction Coefficient method – is developed, making trans-relaxation-time simulations possible and improving computational efficiency significantly, for 3D simulations of arbitrary shape and size microparticles in complicated microfluidic channels. Detailed comparisons between simulation results and experiments involving particle sedimentation and particle equilibrium position have been conducted for methodology validation. Mechanisms of hydrodynamic particle manipulation are then studied, including hydrodynamic focusing and separation. It is found that the Tubular Pinch effect, Dean flow and the Radial Pressure Gradient effect interact to yield two distinct particle separation mechanisms. For advanced applications, particle focusing, non-magnetic and magnetic separation for neutrally buoyant particles are proposed, based on newly gained insight on the above-mentioned mechanisms. Appropriate channel designs have been proposed both for particle focusing and size-based particle separation, while the vertical-magnetic-Dean separation scheme is highlighted for magnetic separation. Finally, a new integrated system is proposed, that combines the above novel designs into a device-like ensemble. It promises to offer functionality for biomaterial separation and detection, including different types of cells, antigens and biomarkers.
Immunomodulatory effects of fusarochromanones TDP‐1 and TDP‐2 (1992)

An in vitro peripheral lymphocyte blastogenesis system was used to investigate the biological activities of the fungal toxin fusarochromanone (TDP-1) and its monoacetyl derivative TDP-2. Briefly, cultures of human or bovine peripheral lymphocytes were exposed to TDP-1 or TDP-2 and a mitogen (PHA, Con A or PWM). After a standard incubation time, cell proliferation was quantified using the MTT bioassay. Human and bovine lymphocyte proliferation was inhibited by high concentrations of TDP-1; however, bovine lymphocyte proliferation was significantly increased at low concentrations of TDP-1. TDP-2 has similar but less pronounced effects on lymphocyte proliferation.
Cryptographic Message Syntax (CMS) Algorithms (2002)

The CMS is used to digitally sign, digest, authenticate, or encrypt arbitrary message contents.
Preparation of Heterocyclic Amines by an Oxidative Amination of Zinc Organometallics Mediated by CuI: A New Oxidative Cycloamination for the Preparation of Annulated Indole Derivatives (2010)

Functionalized heterocyclic zinc reagents are easily aminated by an oxidative amination reaction of zinc amidocuprates prepared from various lithium amides. For the oxidation step, PhI(OAc)(2) proved to be the best reagent. The required heterocyclic zinc organometallics can be prepared either by direct metalation, by magnesium insertion in the presence of ZnCl(2), or by transmetalation of a suitable magnesium reagent. Furthermore, we report a new ring-closing reaction involving an intramolecular oxidative amination reaction. This reaction allows the preparation of tetracyclic heterocycles containing furan, thiophene, or indole rings.
Near-Infrared Spectroscopy versus Compartment Pressure for the Diagnosis of Lower Extremity Compartmental Syndrome Using Electromyography-Determined Measurements of Neuromuscular Function (2001)

In intensive care unit patients who cannot alert physicians to symptoms, near-infrared spectroscopy may help clinicians to avoid delayed or unnecessary prophylactic fasciotomy, and provides the benefits of a continuous, noninvasive monitoring technique.
Isolation and Selection of Rhizobium Tolerant to Pesticides and Aluminum from Acid Soils in Indonesia (2013)

Application of Rhizobium as inoculum in acid soil requires specific characters, namely high tolerance to pesticide residues, soil acidity, and high concentration of Aluminum. This study was conducted to isolate Rhizobium having these characters. Inspite of acid soils from Kalimantan, Sumatra, Sulawesi and Java; root nodules of legumes planted in those regions were used as source of isolates. Rhizobial isolation was done using direct isolation andenrichment technique. A paper disc diffusion technique was used in selecting tolerance to pesticides. The selected isolates were examined the tolerance to pH, Al, and ability to form root nodule with soybean. From soil analysis, it could be seen the correlation between pH value and Al concentration. It means that the lower pH value the higher Al concentration. The number of Rhizobium isolates and its tolerance to paraquat was depended on soil type. From 173 strains of isolated Rhizobium, 24 strains were tolerance to pesticides and Aluminum. They were able to grow in wide range of pH, namely 3 – 8, or some of them in 5 - 8. Around 92% of the selected bacteria could form root nodules with soybean plant in different number and size. Hopefully, these isolates can be applied in the pesticide polluted agricultural lands, especially in acid soils with high concentration of Al, and it can also increase soybean production.Keywords: Acid soils, aluminium, Rhizobium, pesticides
Asymptotically Optimal Tests for Multinomial Distributions (1965)

Tests of simple and composite hypothesis for multinomial distributions are considered. It is assumed that the size $\alpha_N$ of a test tends to 0 as the sample size $N$ increases. The main concern of this paper is to substantiate the following proposition: If a given test of size $\alpha_N$ is "sufficiently different" from a likelihood ratio test then there is a likelihood ratio test of size $\leqq\alpha_N$ which is considerably more powerful than the given test at "most" points in the set of alternatives when $N$ is large enough, provided that $\alpha_N \rightarrow 0$ at a suitable rate. In particular, it is shown that chi-square tests of simple and of some composite hypotheses are inferior, in the sense described, to the corresponding likelihood ratio tests. Certain Bayes tests are shown to share the above-mentioned property of a likelihood ratio test.
Influence of pH on the Aggregation Morphology of a Novel Surfactant with Single Hydrocarbon Chain and Multi-Amine Headgroups (2008)

A novel single-chain surfactant with multi-amine headgroups, bis(amidoethyl-carbamoylethyl) octadecylamine (C18N3), was synthesized. Electronmicrographic study showed that in aqueous solution C18N3 formed small micelles (10−20 nm in diameter) at pH 2.0 and changed into much larger globule vesicles sized about 0.6−2.0 μm in diameter at pH 6.8. At pH 12.0 vesicles changed to a much larger continued lyotropic lamella structure. At pH = 2, the surface tension (γ)−concentration (C) curve at pH 2 was an ordinary one, having one critical micelle concentration at 2.9 × 10-3 mol L-1 at relatively high surface tension (52 mN m-1). However, two unique transition points were observed in the γ−C plot at pH = 6.8 and 10.5, showing higher surface activity that is believed to be associated with the micelle−bilayer structure transition. The protonation degree pKa's of the three amine headgroups were found to be 6.6, 10.6, and 10.9, respectively, indicating that a complete protonation state of the headgroups occurred at pH 2.0, which is consistent with the apparent surface areas of headgroup calculated according to Gibbs adsorption isotherm. Variation of sizes and morphologies of C18N3 in aqueous solution at different pH values suggest that our synthetic surfactant may have great potential applications as a template in fabricating drug delivery, biosensors, and biomolecular devices.
Extraction and Detection of DNA from Bacillus anthracis Spores and the Vegetative Cells within 1 min (2008)

The use of a combination of low-cost technologies to both extract and detect anthrax DNA from spores and vegetative cells in two steps within 1 min is described. In a cavity, microwave energy is highly focused using thin-film aluminum "bow-tie" structures, to extract DNA from whole spores within 20 s. The detection of the released DNA, from less than 1000 vegetative cells, without additional preprocessing steps is accomplished in an additional 30 s by employing the microwave-accelerated metal-enhanced fluorescence technique. The new platform technology presented here is a highly attractive alternative method for DNA extraction and the fast detection of gram-positive bacteria and potentially other pathogenic species and cells as well.
Combined effect of recombinant CD19xCD16 diabody and thalidomide in a preclinical model of human B cell lymphoma (2004)

Combining different treatment strategies offers the possibility of improving treatment results for cancer patients. The aim of our study was therefore to investigate the combination of treatment of established s.c. human B non-Hodgkin's lymphoma in severe immune deficient mice using a recombinant bispecific CD19 x CD16 diabody (targeting natural killer cells to CD19 cells) and the angiogenesis inhibitor thalidomide. Monotherapy with either thalidomide or diabody caused an approximate 50% reduction in tumor growth rate. The combined treatment showed evidence for a synergistic effect resulting in a 74% reduction in median tumor size. In the combined treatment group, two of five animals had complete remissions of their s.c. tumor. These results suggest that a combination treatment with recombinant diabodies and angiogenesis inhibition represents a useful approach in cancer therapy.
The National Institute of Mental Health Clinical Antipsychotic Trials of Intervention Effectiveness (CATIE) Project: Schizophrenia Trial Design and Protocol Development (2003)

The National Institute of Mental Health initiated the Clinical Antipsychotic Trials of Intervention Effectiveness (CATIE) program to evaluate the effectiveness of antipsychotic drugs in typical settings and populations so that the study results will be maximally useful in routine clinical situations. The CATIE schizophrenia trial blends features of efficacy studies and large, simple trials to create a pragmatic trial that will provide extensive information about antipsychotic drug effectiveness over at least 18 months. The protocol allows for subjects who receive a study drug that is not effective to receive subsequent treatments within the context of the study. Medication dosages are adjusted within a defined range according to clinical judgment. The primary outcome is all-cause treatment discontinuation because it represents an important clinical endpoint that reflects both clinician and patient judgments about efficacy and tolerability. Secondary outcomes include symptoms, side effects, neurocognitive functioning, and cost-effectiveness. Approximately 50 clinical sites across the United States are seeking to enroll a total of 1,500 persons with schizophrenia. Phase 1 is a double-blinded randomized clinical trial comparing treatment with the second generation antipsychotics olanzapine, quetiapine, risperidone, and ziprasidone to perphenazine, a midpotency first generation antipsychotic. If the initially assigned medication is not effective, subjects may choose one of the following phase 2 trials: (1) randomization to open-label clozapine or a double-blinded second generation drug that was available but not assigned in phase 1; or (2) double-blinded randomization to ziprasidone or another second generation drug that was available but not assigned in phase 1. If the phase 2 study drug is discontinued, subjects may enter phase 3, in which clinicians help subjects select an open-label treatment based on individuals' experiences in phases 1 and 2.
A Nonparametric Approach to Pricing and Hedging Derivative Securities Via Learning Networks (1994)

We propose a nonparametric method for estimating the pricing formula of a derivative asset using learning networks. Although not a substitute for the more traditional arbitrage-based pricing fomiulas, network pricing formulas may be more accurate and computationaily more efficient alternatives when the underlying asset's price dynamics are unknown, or when the pricing equation associated with no-arbiaage condition cannot be solved analytically. To assess the potential value of network pricing formulas, we simulate Black-Scholes option prices and show that learning networks can recover the Black-Scholes fonnula from a two-year training set of daily options prices, and that the resulting network fonnula can be used successfully to both price and delta-hedge options out-of-sample. For comparison, we estimate models using four popular methods: ordinary least squares, radial basis function networks, multilayer peivepfln networks, and projection pursuit To illustrate the practical relevance of our network pricing approach, we apply it to the pricing and delta-hedging of S&P 500 fuwres options from 1987 to 1991.