gebhart/patrepeval huggingface dataset:
How to Make a DNA Chip (2002)

Microarrays are one of the hottest areas in biological research today. Microarrays have been mostly applied to nucleic acid analysis, specifically to the assessment of which genes are being expressed and at what level. Early microarrays were prepared by using photolithographic methods, which were more commonly used for integrated circuit ("computer chip") production. Hence the colloquial term "DNA chip" came into being. The completion of the sequencing of the human genome and that of many other organisms makes the determination of gene function an important next step in understanding the role of DNA in the processes of life. DNA microarrays are an excellent tool to address this question because their numerous probe sites enable the analysis of many genes simultaneously. With good experience in this initial use, many further applications of microarrays are being developed, including genotyping in research and genetic diagnosis in medicine. DNA microarrays have made abundantly clear the power of vast parallelism in biological analysis, which is raising interest in other types of microarrays (small-molecule, protein). Many applications for DNA microarrays have been developed and clearly many more will emerge through the creativity of the scientists who use them. In early studies, users produced their own microarrays. The apparent power of microarrays has demanded improvements in production methods, and technologies from physical sciences and engineering are now being applied to DNA chips. Many branches of chemistry can contribute to improved methods: from synthetic chemistry (to attach or prepare DNA), to the physical chemistry of surfaces, to analytical chemistry (to assess surface reactions).
The EMBL data library (1988)

The EMBL Data Library was the first internationally supported central resource for nucleic acid sequence data. Working in close collaboration with its American counterpart, GenBank (1), the library prepares and makes available to the scientific community a comprehensive collection of the published nucleic acid sequences. This paper describes briefly the contents of the database, how it is available, and possible future enhancements of Data Library services.
Electronic analog of the electro-optic modulator (1990)

We propose an electron wave analog of the electro-optic light modulator. The current modulation in the proposed structure arises from spin precession due to the spin-orbit coupling in narrow-gap semiconductors, while magnetized contacts are used to preferentially inject and detect specific spin orientations. This structure may exhibit significant current modulation despite multiple modes, elevated temperatures, or a large applied bias.
Accurate estimation of glomerular filtration in the intensive care unit (1993)

Address requests for reprints to: Robert N. Sladen, MB, Department of Anesthesiology, Box 3094, Duke University Medical Center, Durham, NC 27710.
Beyond single-agent bortezomib: combination regimens in relapsed multiple myeloma (2006)

Bortezomib-based combinations show promising activity in relapsed or refractory multiple myeloma, including reversal of chemoresistance to previously used agents. As high complete and overall response rates translate into longer survival, bortezomib-based combinations appear likely to have a significant impact on the multiple myeloma treatment algorithm and on the course of the disease itself.
Formal methods for generating protocol conformance test sequences (1990)

The four major methods of conformance test generation reported in the literature are reviewed: transition tours; distinguishing sequences; characterizing sequences; and unique input/output sequences. These methods are used to test the control portion of a protocol specification. The conformance testing concepts developed in the standards world are summarized. Their relationship with the four formal methods is discussed.< <ETX xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">&gt;</ETX>
Pharmacokinetic, Biodistribution, and Biophysical Profiles of TNF Nanobodies Conjugated to Linear or Branched Poly(ethylene glycol) (2012)

Covalent attachment of poly(ethylene glycol) (PEG) to therapeutic proteins has been used to prolong in vivo exposure of therapeutic proteins. We have examined pharmacokinetic, biodistribution, and biophysical profiles of three different tumor necrosis factor alpha (TNF) Nanobody-40 kDa PEG conjugates: linear 1 × 40 KDa, branched 2 × 20 kDa, and 4 × 10 kDa conjugates. In accord with earlier reports, the superior PK profile was observed for the branched versus linear PEG conjugates, while all three conjugates had similar potency in a cell-based assay. Our results also indicate that (i) a superior PK profile of branched versus linear PEGs is likely to hold across species, (ii) for a given PEG size, the extent of PEG branching affects the PK profile, and (iii) tissue penetration may differ between linear and branched PEG conjugates in a tissue-specific manner. Biophysical analysis (R(g)/R(h) ratio) demonstrated that among the three protein-PEG conjugates the linear PEG conjugate had the most extended time-average conformation and the most exposed surface charges. We hypothesized that these biophysical characteristics of the linear PEG conjugate accounts for relatively less optimal masking of sites involved in elimination of the PEGylated Nanobodies (e.g., intracellular uptake and proteolysis), leading to lower in vivo exposure compared to the branched PEG conjugates. However, additional studies are needed to test this hypothesis.
Inhibition of nitric-oxide synthase 2 by aminoguanidine provides neuroprotection of retinal ganglion cells in a rat model of chronic glaucoma (1999)

Glaucoma is an optic neuropathy with cupping of the optic disk, degeneration of retinal ganglion cells, and characteristic visual field loss. Because elevated intraocular pressure (IOP) is a major risk factor for progression of glaucoma, treatment has been based on lowering IOP. We previously demonstrated inducible nitric-oxide synthase (NOS-2) in the optic nerve heads from human glaucomatous eyes and from rat eyes with chronic, moderately elevated IOP. Using this rat model of unilateral glaucoma, we treated a group of animals for 6 months with aminoguanidine, a relatively specific inhibitor of NOS-2, and compared them with an untreated group. At 6 months, untreated animals had pallor and cupping of the optic disks in the eyes with elevated IOP. Eyes of aminoguanidine-treated animals with similar elevations of IOP appeared normal. We quantitated retinal ganglion cell loss by retrograde labeling with Fluoro-Gold. When compared with their contralateral control eyes with normal IOP, eyes with elevated IOP in the untreated group lost 36% of their retinal ganglion cells; the eyes with similarly elevated IOP in the aminoguanidine-treated group lost less than 10% of their retinal ganglion cells. Pharmacological neuroprotection by inhibition of NOS-2 may prove useful for the treatment of patients with glaucoma.
Scale and performance in a distributed file system (1988)

The Andrew File System is a location-transparent distributed tile system that will eventually span more than 5000 workstations at Carnegie Mellon University. Large scale affects performance and complicates system operation. In this paper we present observations of a prototype implementation, motivate changes in the areas of cache validation, server process structure, name translation, and low-level storage representation, and quantitatively demonstrate Andrews ability to scale gracefully. We establish the importance of whole-file transfer and caching in Andrew by comparing its performance with that of Sun Microsystems NFS tile system. We also show how the aggregation of files into volumes improves the operability of the system.
Control by Signaling Modulators of the Sorting of Canalicular Transporters in Rat Hepatocyte Couplets: Role of the Cytoskeleton (2000)

Hormonal control of the restoration of hepatocanalicular polarity in short-term cultured hepatocyte couplets was analyzed. One hour following isolation, couplets were unable to accumulate the fluorescent bile acid analogue, cholyl-lysyl-fluorescein (CLF), and showed a nonpolarized distribution of F-actin and mrp2 over the cell body. A progressive, time-dependent restoration of couplet-polarized function and morphology was reached after 4 hours of culture. Both dibutyryl cyclic adenosine monophosphate (DBcAMP) and the Ca(2+)-elevating compound, thapsigargin, accelerated restoration of normal couplet morphology and function. The DBcAMP-mediated stimulus was inhibited by the Ca(2+) chelator, 1, 2-bis-(o-aminophenoxy)-ethene-N,N,N',N'-tetra-acetate tetra-(acetomethyl)ester (BAPTA/AM), but not by the protein kinase A (PKA) inhibitors, KT5720 or H89, suggesting that Ca(2+) elevation rather than PKA activation is involved. N-(6-aminohexyl-5-chloro-1-napththalenesulfonamide (W-7), a calmodulin inhibitor, and the protein kinase C (PKC) activator, phorbol dibutyrate, inhibited both the basal and the DBcAMP-stimulated recovery of functional polarity, whereas staurosporine and Gö 6976, 2 PKC inhibitors, accelerated the basal recovery of polarized function. Disruption of the microtubule cytoskeleton by colchicine induced only minor changes under basal, but not under DBcAMP-stimulated, conditions. The Golgi complex disruptor, brefeldin A, significantly delayed, and the microfilament-disrupting agent, cytochalasin D, fully blocked, both processes. However, DBcAMP stimulated trafficking of vesicles containing CLF to the pericanalicular region under the last condition. Our results indicate that restoration of couplet polarity following isolation occurs via a Ca(2+)-calmodulin-mediated mechanism, which depends on microfilament, but not on microtubule integrity. A second pathway is activated by DBcAMP activation via Ca(2+)-calmodulin formation, whose requirements with respect to cytoskeletal components are opposite. PKC has a negative regulatory role in both pathways.
Virus-specific CD8+ T-cell responses in mice transgenic for a T-cell receptor beta chain selected at random (1994)

The consequences of severely limiting the T-cell receptor (TCR) repertoire available for the response to intranasal infection with an influenza A virus or with Sendai virus have been analyzed by using H-2k mice (TG8.1) transgenic for a TCR beta-chain gene (V beta 8.1D beta 2J beta 2.3C beta 2). Analyzing the prevalence of V beta 8.1+ CD8+ T cells in lymph node cultures from nontransgenic (non-TG) H-2k controls primed with either virus and then stimulated in vitro with the homologous virus or with anti-CD3 epsilon showed that this TCR is not normally selected from the CD8+ T-cell repertoire during these infections. However, the TG8.1 mice cleared both viruses and generated virus-specific effector cytotoxic T lymphocytes (CTL) and memory CTL precursors, though the responses were delayed compared with the non-TG controls. Depletion of the CD4+ T-cell subset had little effect on the course of influenza virus infection but substantially slowed the development of the Sendai virus-specific CTL response and virus elimination in both the TG8.1 and non-TG mice, indicating that CD4+ helpers are promoting the CD8+ T-cell response in the Sendai virus model. Even so, restricting the available T-cell repertoire to lymphocytes expressing a single TCR beta chain still allows sufficient TCR diversity for CD8+ T cells (acting in the presence or absence of the CD4+ subset) to limit infection with an influenza A virus and a parainfluenza type 1 virus.
Pathology of the TSH receptor. (1999)

Gain of function and loss of function mutations of the TSH receptor have been implicated in the pathogenesis of various thyroid diseases. Gain of function mutations, when somatic, are the first cause of autonomous nodules; when germline, they are responsible for hereditary non-autoimmune toxic thyroid hyperplasia and for some cases of sporadic congenital hyperthyroidism. A subset of mutations modifying the receptor selectivity have recently been found to be involved in the pathogenesis of familial gestational hyperthyroidism. These mutations are of great interest for understanding the mechanism of receptor activation. Loss of function mutations of the TSH receptor are responsible for different phenotypes ranging from asymptomatic resistance to TSH to overt congenital hypothyroidism.
Glutamate neurotoxicity, oxidative stress and mitochondria (2001)

The excitatory neurotransmitter glutamate plays a major role in determining certain neurological disorders. This situation, referred to as 'glutamate neurotoxicity' (GNT), is characterized by an increasing damage of cell components, including mitochondria, leading to cell death. In the death process, reactive oxygen species (ROS) are generated. The present study describes the state of art in the field of GNT with a special emphasis on the oxidative stress and mitochondria. In particular, we report how ROS are generated and how they affect mitochondrial function in GNT. The relationship between ROS generation and cytochrome c release is described in detail, with the released cytochrome c playing a role in the cell defense mechanism against neurotoxicity.
Differential TdT expression in acute leukemia by flow cytometry: a quantitative study. (1995)

Terminal deoxynucleotidyl transferase (TdT) has long been considered a diagnostic marker for acute lymphoblastic leukemia. Reports of TdT-positive cells in acute myeloid leukemia have lately questioned its diagnostic value. TDT has been detected mainly by microscopy methods: immunofluorescence and immunocytochemistry. The aim of this study was to reevaluate the diagnostic importance of TdT in acute leukemia by using flow cytometry with a method that allows quantitative analysis. Fifty-eight cases of acute leukemia were studied and TdT expression was quantified using calibrated fluorescent beads. The highest TdT values were found in B lineage acute lymphoblastic leukemia (ALL) while acute myeloid leukemia (AML) had the lowest values, even in cases with a high percentage of TdT-positive cells. Biphenotypic leukemia had intermediate values between B-lineage and T-lineage acute leukemia. The difference between these groups was statistically significant (P < 0.0001). The TdT assay by flow cytometry was more precise than immunocytochemistry because it recognizes quantitative differences between ALL and AML. It is also valuable in better defining the maturation stages in pre-B ALL and T-ALL. We conclude that quantitative flow cytometry of TdT re-establishes the diagnostic value of this enzyme and has potential applications for the study of minimal residual disease.
Prophylactic Administration of Respiratory Syncytial Virus Immune Globulin to High-Risk Infants and Young Children (1993)

Administration of high doses of respiratory syncytial virus immune globulin is a safe and effective means of preventing lower respiratory tract infection in infants and young children at high risk for this disease.
Electrical modeling of extremely large packages (2002)

Highly complex packages are analyzed by breaking them into large regions or blocks that are joined at their boundaries and solving for the currents using a moment method approach. Blocks are isolated from each other, except along the boundaries between blocks, and this serves to connect the blocks together. Full coupling is maintained within each block. The procedure is applied to structures where the coupling is expected to fall off rapidly, for instance in structures that have one or more contiguous reference planes and thus have nearby return currents. The examples involve a two-mesh-plane structure that contains one or more signal lines. The results are verified through a number of experiments and through comparison with known results for canonical transmission line structures.
Heterotransplantation of human prostatic tissue (1987)

Pieces of human prostatic tissue (approximately 1 mm3) were encapsulated in XM-50 Amicon hollow fibers and either implanted into the testis of an adult male rat or placed in culture. The protein synthetic capacity of such tissue pieces removed 1-42 days later was monitored by TCA precipitation, SDS-PAGE, and autoradiography. The results showed that tissue pieces retained their functional protein synthetic elements after this procedure. A newly developed solid-phase enzyme immunoassay for human prostatic antigen (PA), described in this report, was used to monitor PA levels in the serum of the recipient host or culture media. In some instances PA was detected 1-2 weeks postimplantation, a result that implies maintenance of functional secretory elements in vivo. Finally, morphology of tissue pieces 1-2 weeks postimplantation sometimes showed the presence of ductal epithelia and stromal elements in distribution patterns typical of those seen in fresh biopsy samples. We conclude that the function and structure of prostatic tissue implanted intrastesticularly compares favorably with that maintained in conventional explant culture. As such, the hollow fiber method offers promise for a new way of monitoring hormonal and/or chemotherapy testing of human prostatic tissue.
Identification and Functional Analysis of Novel Nonstructural Proteins of Human Bocavirus 1 (2015)

Human bocavirus 1 infection causes respiratory diseases, including acute wheezing in infants, of which life-threatening cases have been reported. In vitro, human bocavirus 1 infects polarized human bronchial airway epithelium cultured at an air-liquid interface that mimics the environment of human lower respiratory airways. Viral nonstructural proteins are often important for virus replication and pathogenesis in infected tissues or cells. In this report, we identified three new nonstructural proteins of human bocavirus 1 that are expressed during infection of polarized human bronchial airway epithelium. Among them, we proved that one nonstructural protein is critical to the replication of the virus in polarized human bronchial airway epithelium. The creation of nonreplicating infectious HBoV1 mutants may have particular utility in vaccine development for this virus.
Trajectory sampling for direct traffic observation (2000)

Traffic measurement is a critical component for the control and engineering of communication networks. We argue that traffic measurement should make it possible to obtain the spatial flow of traffic through the domain, i.e., the paths followed by packets between any ingress and egress point of the domain. Most resource allocation and capacity planning tasks can benefit from such information. Also, traffic measurements should be obtained without a routing model and without knowledge of network state. This allows the traffic measurement process to be resilient to network failures and state uncertainty. We propose a method that allows the direct inference of traffic flows through a domain by observing the trajectories of a subset of all packets traversing the network. The key advantages of the method are that (i) it does not rely on routing state, (ii) its implementation cost is small, and (iii) the measurement reporting traffic is modest and can be controlled precisely. The key idea of the method is to sample packets based on a hash function computed over the packet content. Using the same hash function will yield the same sample set of packets in the entire domain, and enables us to reconstruct packet trajectories.
The Price of Correlation Risk: Evidence from Equity Options (2009)

ABSTRACT We study whether exposure to marketwide correlation shocks affects expected option returns, using data on S&amp;P100 index options, options on all components, and stock returns. We find evidence of priced correlation risk based on prices of index and individual variance risk. A trading strategy exploiting priced correlation risk generates a high alpha and is attractive for CRRA investors without frictions. Correlation risk exposure explains the cross‐section of index and individual option returns well. The correlation risk premium cannot be exploited with realistic trading frictions, providing a limits‐to‐arbitrage interpretation of our finding of a high price of correlation risk.
Circularly permuted dihydrofolate reductase of E.coli has functional activity and a destabilized tertiary structure (1994)

Three circularly permuted variants of Escherichia coli dihydrofolate reductase genes were constructed. Linkers coding tri- and pentapeptides were used to connect the natural 5'- and 3'-terminal ends. Only one variant of circularly permuted protein with tripeptide linker and the cleavage of the peptide bond between 107 and 108 amino acid residues was produced in a good yield. The expressed protein was insoluble in the cells, but at pH 8.0 and higher the isolated protein was soluble. Enzymatic assay and physical studies have shown that permuted dihydrofolate reductase has a destabilized tertiary structure. Only the addition of the natural substrates or inhibitors lead to the protein with the native-like structure and functional activity.
Illinois-LH: A Denotational and Distributional Approach to Semantics (2014)

This paper describes and analyzes our SemEval 2014 Task 1 system. Its features are based on distributional and denotational similarities; word alignment; negation; and hypernym/hyponym, synonym, and antonym relations.
Bispecific antibodies for dual-modality cancer therapy: killing two signaling cascades with one stone. (2006)

The additive and synergistic therapeutic effects derived from combinations of chemotherapeutic drugs and radiation have established an indispensable paradigm: cancer must be attacked on multiple fronts. However, the increased antitumor efficacy of such combinational regimens is also associated with severe systemic toxicity, as these drugs cannot selectively target tumor cells. Monoclonal antibodies (mAbs), which have exquisite specificity for their antigens, are becoming an increasingly important class of antitumor agents, as they enhance the efficacy of various therapeutic regimens without significantly increasing systemic toxicity. Furthermore, preclinical and early clinical evidence indicate that combinations of antibody-based drugs provide even greater efficacy with minimal side effects. Unfortunately, the research, manufacturing and regulatory costs of mAb development pose a significant barrier to the use of antibody-based combination therapies. An emerging alternative is the use of dual-targeting bispecific antibodies (BsAbs). BsAbs are derived from the recombination of variable domains of two antibodies with different specificities; BsAbs are thus capable of binding both antigens of their parental antibodies. With the recent progress that has been made in antibody engineering technology, BsAbs that simultaneously target two tumor-associated molecules (eg, growth factor receptors) are being heralded for their potential to deliver two therapeutic moieties in a single molecule.
Delayed Postischemic Hyperthermia in Awake Rats Worsens the Histopathological Outcome of Transient Focal Cerebral Ischemia (1996)

The present findings provide evidence that, after a transient focal ischemic insult, the postischemic brain becomes abnormally sensitive to the effects of delayed temperature elevation, even of moderate degree. The threshold for aggravation of ischemic injury by delayed hyperthermia appears to be approximately 40 degrees C. Body-temperature measurements, in both awake and anesthetized animals, may not accurately reflect brain temperature under these conditions. The present study stresses that fever of even moderate degree in the days following brain ischemia may markedly exacerbate brain injury.