gebhart/patrepeval huggingface dataset:
Discovery of GSK1070916, a Potent and Selective Inhibitor of Aurora B/C Kinase (2010)

The Aurora kinases play critical roles in the regulation of mitosis and are frequently overexpressed or amplified in human tumors. Selective inhibitors may provide a new therapy for the treatment of tumors with Aurora kinase amplification. Herein we describe our lead optimization efforts within a 7-azaindole-based series culminating in the identification of GSK1070916 (17k). Key to the advancement of the series was the introduction of a 2-aryl group containing a basic amine onto the azaindole leading to significantly improved cellular activity. Compound 17k is a potent and selective ATP-competitive inhibitor of Aurora B and C with K(i)* values of 0.38 +/- 0.29 and 1.5 +/- 0.4 nM, respectively, and is >250-fold selective over Aurora A. Biochemical characterization revealed that compound 17k has an extremely slow dissociation half-life from Aurora B (>480 min), distinguishing it from clinical compounds 1 and 2. In vitro treatment of A549 human lung cancer cells with compound 17k results in a potent antiproliferative effect (EC(50) = 7 nM). Intraperitoneal administration of 17k in mice bearing human tumor xenografts leads to inhibition of histone H3 phosphorylation at serine 10 in human colon cancer (Colo205) and tumor regression in human leukemia (HL-60). Compound 17k is being progressed to human clinical trials.
Comprehensive security framework for the communication and storage of medical images (2003)

Confidentiality, integrity verification and access control of medical imagery and associated metadata is critical for the successful deployment of integrated healthcare networks that extend beyond the department level. As medical imagery continues to become widely accessed across multiple administrative domains and geographically distributed locations, image data should be able to travel and be stored on untrusted infrastructure, including public networks and server equipment operated by external entities. Given these challenges associated with protecting large-scale distributed networks, measures must be taken to protect patient identifiable information while guarding against tampering, denial of service attacks, and providing robust audit mechanisms. The proposed framework outlines a series of security practices for the protection of medical images, incorporating Transport Layer Security (TLS), public and secret key cryptography, certificate management and a token based trusted computing base. It outlines measures that can be utilized to protect information stored within databases, online and nearline storage, and during transport over trusted and untrusted networks. In addition, it provides a framework for ensuring end-to-end integrity of image data from acquisition to viewing, and presents a potential solution to the challenges associated with access control across multiple administrative domains and institution user bases.
Factors affecting lignin solubility (2011)

The solubility of lignin in aqueous NaOH solutions was studied in relation to the lignin molecular weight, temperature, liquid to solid ratio, and ionic strength. A new procedure for determining the content of phenolic hydroxyls in lignin was developed. A formula was suggested for calculating the lignin solubility in aqueous alkali solutions.
Dynamic voting algorithms for maintaining the consistency of a replicated database (1990)

There are several replica control algorithms for managing replicated files in the face of network partitioning due to site or communication link failures. Pessimistic algorithms ensure consistency at the price of reduced availability; they permit at most one (distinguished) partition to process updates at any given time. The best known pessimistic algorithm, voting , is a “static” algorithm, meaning that all potential distinguished partitions can be listed in advance. We present a dynamic extension of voting called dynamic voting . This algorithm permits updates in a partition provided it contains more than half of the up-to-date copies of the replicated file. We also present an extension of dynamic voting called dynamic voting with linearly ordered copies (abbreviated as dynamic-linear ). These algorithms are dynamic because the order in which past distinguished partitions were created plays a role in the selection of the next distinguished partition. Our algorithms have all the virtues of ordinary voting, including its simplicity, and provide improved availability as well. We provide two stochastic models to support the latter claim. In the first (site) model, sites may fail but communication links are infallible; in the second (link) model the reverse is true. We prove that under the site model, dynamic-linear has greater availability than any static algorithm, including weighted voting, if there are four or more sites in the network. In the link model, we consider all biconnected five-site networks and a wide variety of failure and repair rates. In all cases considered, dynamic-linear had greater availability than any static algorithm.
Condensation of muscimol or thiomuscimol with aminopyridazines yields GABA-A antagonists (1992)

Ten analogs of muscimol and thiomuscimol in which the amino function was delocalized in an amidinic system were prepared by N2 alkylation of 6-aryl-3-aminopyridazines with (chloromethyl)isoxazole or (chloromethyl)isothiazole derivatives. These muscimol and thiomuscimol derivatives show potent binding properties for GABA-A receptors (they displace [3H]GABA and [3H]gabazine) and provoke convulsions after iv injections. They fit well with the model pharmacophore proposed by our group for the GABA-A antagonists and show similar structure-activity profiles to that of the pyridazinyl-GABAs.
Fresenius AS.TEC204 Blood Bell Separator (2003)

Fresenius AS.TEC204 is a third-generation blood cell separator that incorporates the continuous centrifugal separation method and automatic control of the cell separation process. Continuous centrifugation separates cell components according to their specific gravity, and different cell components are either harvested or eliminated as needed. The interface between the red blood cell and plasma is optically detected, and the Interface Control (IFC) cooperates with different pumps, monitors and detectors to harvest required components automatically. The system is composed of three major sections; the Front Panel Unit; the Pump Unit, and the Centrifuge Unit. This unit can be used for a wide variety of clinical applications including collection of platelets, peripheral blood stem cells, bone marrow stem cells, granulocytes, mononuclear cells, and exchange of plasma or red cells, and for plasma treatment.
Gradient-index eyepiece design (1983)

A study of gradient-index eyepieces was conducted. The general performance of homogeneous eyepieces having two and three elements was examined. Axial gradients were introduced into the eyepieces in an attempt to increase the half-fields of view to 25 degrees and extend the eye reliefs to 12 mm. The homogeneous eyepieces examined were of the Huygenian, Ramsden, and Kellner configurations. These eyepieces were scaled to the specifications of f/13, 21.4-mm focal length, and magnifying power of 10X. These classic systems were optimized to produce two- and three-element homogeneous eyepieces to determine how homogeneous systems could perform with the extended eye relief and larger field of view. Axial gradient eyepieces having two and three elements were designed to the same specifications. The balance of third-order aberrations, color, and distortion was maintained or improved compared to the homogeneous systems.. The additional degrees of freedom associated with the gradient made it possible to extend the eye relief and increase the field of view of these eyepieces.
Characterizing Immunoglobulin Repertoire from Whole Blood by a Personal Genome Sequencer (2013)

In human immune system, V(D)J recombination produces an enormously large repertoire of immunoglobulins (Ig) so that they can tackle different antigens from bacteria, viruses and tumor cells. Several studies have demonstrated the utility of next-generation sequencers such as Roche 454 and Illumina Genome Analyzer to characterize the repertoire of immunoglobulins. However, these techniques typically require separation of B cell population from whole blood and require a few weeks for running the sequencers, so it may not be practical to implement them in clinical settings. Recently, the Ion Torrent personal genome sequencer has emerged as a tabletop personal genome sequencer that can be operated in a time-efficient and cost-effective manner. In this study, we explored the technical feasibility to use multiplex PCR for amplifying V(D)J recombination for IgH, directly from whole blood, then sequence the amplicons by the Ion Torrent sequencer. The whole process including data generation and analysis can be completed in one day. We tested the method in a pilot study on patients with benign, atypical and malignant meningiomas. Despite the noisy data, we were able to compare the samples by their usage frequencies of the V segment, as well as their somatic hypermutation rates. In summary, our study suggested that it is technically feasible to perform clinical monitoring of V(D)J recombination within a day by personal genome sequencers.
Error statistics of closed-loop power control in multirate DS-CDMA cellular systems (2003)

We investigate the error statistics of the close-loop power control scheme with variable spreading factors for the multi-rate services in the third generation wideband CDMA (WCDMA) system. We demonstrate that the long scrambling pseudo-noise code, besides its well known feature in differentiating users and base stations, can improve power control false command over a frequency-selective fading channel as well. Our computer simulation results indicate that the SIR measurement error can be reduced by 3 dB in a typical case, and the power control false command can be reduced from 27 % to 10 % in comparison to using pure short Walsh codes. It is shown that the close-loop power control error is a composite function of the spreading factor, target E/sub b/ / N/sub o/ and Doppler frequency. The statistics of closed loop power control false command can be easily characterized by a Bernoulli distribution with a parameter provided by our results.
RABBIT: an intelligent database assistant (1982)

We have designed and implemented an intelligent database assistant to aid the user in formulating a query. The system, named RABBIT, relies upon a new paradigm for retrieval, retrieval by reformulation, based on a psychological theory of human remembering. To make a query, the user interactively constructs a description of his target item(s) by criticizing successive example (and counterexample) instances. One of the key innovations in RABBIT is that instances from the database are presented to the user from a well-defined perspective inferred from the user's query description and the structure of the knowledge base. Among other things, this constructed perspective prevents the user from creating semantically improper query descriptions. RABBIT particularily facilitates users who approach a database with only a vague idea of what it is that they want and who thus, need to be guided in the (re)formulation of their queries. RABBIT is also of substantial value to casual users who have limited knowledge of a given database or who must deal with a multitude of databases.
In vitro cultured progenitors and precursors of cardiac cell lineages from human normal and post-ischemic hearts. (2008)

The demonstration of the presence of dividing primitive cells in damaged hearts has sparked increased interest about myocardium regenerative processes. We examined the rate and the differentiation of in vitro cultured resident cardiac primitive cells obtained from pathological and normal human hearts in order to evaluate the activation of progenitors and precursors of cardiac cell lineages in post-ischemic human hearts. The precursors and progenitors of cardiomyocyte, smooth muscle and endothelial lineage were identified by immunocytochemistry and the expression of characteristic markers was studied by western blot and RT-PCR. The amount of proteins characteristic for cardiac cells (alpha-SA and MHC, VEGFR-2 and FVIII, SMA for the precursors of cardiomyocytes, endothelial and smooth muscle cells, respectively) inclines toward an increase in both alpha-SA and MHC. The increased levels of FVIII and VEGFR2 are statistically significant, suggesting an important re-activation of neoangiogenesis. At the same time, the augmented expression of mRNA for Nkx 2.5, the trascriptional factor for cardiomyocyte differentiation, confirms the persistence of differentiative processes in terminally injured hearts. Our study would appear to confirm the activation of human heart regeneration potential in pathological conditions and the ability of its primitive cells to maintain their proliferative capability in vitro. The cardiac cell isolation method we used could be useful in the future for studying modifications to the microenvironment that positively influence cardiac primitive cell differentiation or inhibit, or retard, the pathological remodeling and functional degradation of the heart.
Improving verbose queries using subset distribution (2010)

Dealing with verbose (or long) queries poses a new challenge for information retrieval. Selecting a subset of the original query (a "sub-query") has been shown to be an effective method for improving these queries. In this paper, the distribution of sub-queries ("subset distribution") is formally modeled within a well-grounded framework. Specifically, sub-query selection is considered as a sequential labeling problem, where each query word in a verbose query is assigned a label of "keep" or "don't keep". A novel Conditional Random Field model is proposed to generate the distribution of sub-queries. This model captures the local and global dependencies between query words and directly optimizes the expected retrieval performance on a training set. The experiments, based on different retrieval models and performance measures, show that the proposed model can generate high-quality sub-query distributions and can significantly outperform state-of-the-art techniques.
Rate adaptation for adaptive HTTP streaming (2011)

Recently, HTTP has been widely used for the delivery of real-time multimedia content over the Internet, such as in video streaming applications. To combat the varying network resources of the Internet, rate adaptation is used to adapt the transmission rate to the varying network capacity. A key research problem of rate adaptation is to identify network congestion early enough and to probe the spare network capacity. In adaptive HTTP streaming, this problem becomes challenging because of the difficulties in differentiating between the short-term throughput variations, incurred by the TCP congestion control, and the throughput changes due to more persistent bandwidth changes.
Direct analysis of rat bile for acetaminophen and two of its conjugated metabolites via thermospray liquid chromatography/mass spectrometry (1987)

Bile from rats treated with acetaminophen was analyzed by direct injection onto a thermospray liquid chromatography/mass spectrometry (LC/MS) system. Two conjugated metabolites of acetaminophen were separated by the high-pressure liquid chromatographic system and analyzed by mass spectrometry. The conjugates were identified as the glutathione-acetaminophen conjugate and the glucuronide-acetaminophen conjugate by comparison of the chromatographic retention times and the mass spectra to that of the synthetic standards. No evidence of acetaminophen metabolites was observed when bile samples were subjected to direct analysis by fast atom bombardment mass spectrometry.
Factors influencing the extent and regiospecificity of cross-link formation between single-stranded DNA and reactive complementary oligodeoxynucleotides (1994)

Cross-link formation, within the duplex, by oligodeoxynucleotides containing a 5-[omega-(omega-haloacylamido)alkyl]-2'-deoxyuridine to a complementary oligodeoxynucleotide was investigated under conditions approximating the physiologic environment. The site and extent of crosslinking to the target strand were determined for several electrophilic haloacylamidoalkyl structures. The regiospecificity of alkylation was primarily determined by the length of the electrophilic haloacylamidoalkyl group, while the extent of reaction was dependent upon both the structure of the acylamidoalkyl group and the reactivity of the electrophile. Cross-linking was additionally modulated by the sequence of the duplex in the vicinity of the alkylation site. The exact placement of the electrophile adjacent to the targeted nucleophile, an N-7 group on a specific guanine base in the target strand, was the most important factor in determining the rate of reaction. With the optimal haloacylamidoalkyl structure and duplex sequence, the most rapid rate obtained was t1/2 = 1.3 h at 37 degrees C.
Identification and Characterization of Broadly Neutralizing Human Monoclonal Antibodies Directed against the E2 Envelope Glycoprotein of Hepatitis C Virus (2009)

Nearly all livers transplanted into hepatitis C virus (HCV)-positive patients become infected with HCV, and 10 to 25% of reinfected livers develop cirrhosis within 5 years. Neutralizing monoclonal antibody could be an effective therapy for the prevention of infection in a transplant setting. To pursue this treatment modality, we developed human monoclonal antibodies (HuMAbs) directed against the HCV E2 envelope glycoprotein and assessed the capacity of these HuMAbs to neutralize a broad panel of HCV genotypes. HuMAb antibodies were generated by immunizing transgenic mice containing human antibody genes (HuMAb mice; Medarex Inc.) with soluble E2 envelope glycoprotein derived from a genotype 1a virus (H77). Two HuMAbs, HCV1 and 95-2, were selected for further study based on initial cross-reactivity with soluble E2 glycoproteins derived from genotypes 1a and 1b, as well as neutralization of lentivirus pseudotyped with HCV 1a and 1b envelope glycoproteins. Additionally, HuMAbs HCV1 and 95-2 potently neutralized pseudoviruses from all genotypes tested (1a, 1b, 2b, 3a, and 4a). Epitope mapping with mammalian and bacterially expressed proteins, as well as synthetic peptides, revealed that HuMAbs HCV1 and 95-2 recognize a highly conserved linear epitope spanning amino acids 412 to 423 of the E2 glycoprotein. The capacity to recognize and neutralize a broad range of genotypes, the highly conserved E2 epitope, and the fully human nature of the antibodies make HuMAbs HCV1 and 95-2 excellent candidates for treatment of HCV-positive individuals undergoing liver transplantation.
Affine theorem for two-dimensional Fourier transform (1993)

The well known shift and similarity theorems for the Fourier transform generalise to two dimensions but new theorems come into existence in two dimensions. Simple theorems for rotation and shear distortion are examples. A theorem is presented which determines what the Fourier transform becomes when the function domain is subjected to an affine co-ordinate transformation. The full theorem contains a variety of simpler theorems as special cases. It may prove useful in its general form in image processing where sequences of affine transformations are applied.
Advances in MEMS deformable mirror technology for laser beam shaping (2007)

In recent years, demanding adaptive optics applications have driven advancements in microelectromechanical systems (MEMS) deformable mirrors. The latest developments in adaptive optics for extremely large telescopes and other astronomical applications calling for thousands of control points have pushed high actuator mirror arrays. The need to compensate for large amplitude, high order wavefront aberrations in retinal imaging have pushed for high stroke, high spatial resolution deformable mirrors. Aerospace and military defense applications with long operational life times have created demands for rugged, highly reliable micromachined devices. Finally, the impending commercialization of deformable mirrors for bioimaging applications has created a requirement for a low-cost adaptive optics solution. The variety of applications with their respective requirements has resulted in versatile MEMS devices for advanced optical control and thus well-suited for many laser beam shaping applications. This paper will describe the design, manufacturing, and testing results of the latest generation of optical quality micromachined deformable mirrors. Recent testing of a 4096 actuator deformable mirror and a newly released a 140 actuator, six micron stroke mirror will be demonstrated. A high-speed electronics driver for a 1024 actuator deformable mirror designed for laser beam shaping in optical communication will also be demonstrated. This paper will show how the applications of micromachined deformable mirrors can be extended to laser beam shaping for industrial machining, laser communication, and femto-second pulse applications.
Activated protein C alters cytosolic calcium flux in human brain endothelium via binding to endothelial protein C receptor and activation of protease activated receptor-1 (2003)

Activated protein C (APC) exerts endothelial protein C receptor (EPCR)-dependent neuroprotective effects in a brain focal ischemia model and direct cellular effects on human umbilical vein endothelial cells (HUVECs) via protease-activated receptor-1 (PAR-1). Because PAR receptors are expressed in brain endothelium and mediate intracellular calcium concentration ([Ca2+]i) signaling, we hypothesized that APC may regulate intracellular [Ca2+] flux in human brain endothelial cells (BECs) via EPCR and PAR-1. Primary cortical BECs derived from human autopsies (early passage) and HUVECs were used for [Ca2+]i imaging fluorometry. Cells were exposed for 1 minute to APC, protein C zymogen, or mutant Ser360Ala-APC, and [Ca2+]i was monitored in the presence or absence of antibodies against PAR-1, PAR-2, PAR-3, or EPCR. APC, but not protein C zymogen or the active site mutant Ser360Ala-APC, induced dose-dependent [Ca2+]i release in human BECs (Delta[Ca2+]i max = 278.3 +/- 19.5 nM; EC50 for APC = 0.23 +/- 0.02 nM, n = 70 measurements). APC-induced [Ca2+]i signaling was abolished by a cleavage site blocking anti-PAR-1 antibody, whereas anti-PAR-2 and -PAR-3 antibodies were without effect. Antibody RCR252 that ablates APC binding to EPCR blocked APC-mediated [Ca2+]i signaling, whereas anti-EPCR antibody RCR92 that does not block APC binding did not abolish the APC-induced [Ca2+]i response. Experiments using HUVECs confirmed the findings for BECs. Thapsigargin inhibited the APC-induced [Ca2+]i signal, implicating the endoplasmic reticulum as a major source for the APC-induced [Ca2+]i release. These data suggest that APC regulates [Ca2+]i in human brain endothelium and in HUVECs by binding to EPCR and signaling via PAR-1.
New algorithms for the duplication-loss model (2000)

We consider the problem of constructing a species tree given a number of gene trees. In the frameworks introduced by Goodman et al. [3], Page [10], and Guigó, Muchnik, and Smith [5] this is formulated as an optimization problem; namely, that of finding the species tree requiring the minimum number of duplications and/ or losses in order to explain the gene trees.