gebhart/patrepeval huggingface dataset:
Nelfinavir/ritonavir reduces acinar injury but not inflammation during mouse caerulein pancreatitis (2009)

There is no clinical treatment that reduces acinar injury during pancreatitis. Human immunodeficiency virus (HIV) protease inhibitors (PI), including nelfinavir (NFV) and ritonavir (RTV), may reduce the rate of pancreatitis in HIV-infected patients. Since permeability transition pore (PTPC)-mediated mitochondrial dysfunction occurs during pancreatitis, and we have shown that PI prevents PTPC opening, we studied its effects in a model of pancreatitis. The effect of NFV plus RTV (NFV/RTV) or vehicle on caerulein-induced pancreatitis in mice was compared by measuring changes in mitochondrial membrane potential in vitro and cytochrome c leakage in vivo. Histological and inflammatory makers were also compared. NFV/RTV improved DiOC6 retention in acini exposed to caerulein in vitro. In vivo NFV prevented cytosolic leakage of cytochrome c and reduced pancreatic acinar injury, active caspase-3 staining, TUNEL-positive acinar cells, and serum amylase (P < 0.05). Conversely, trypsin activity, serum cytokine levels, and pancreatic and lung inflammation were unaffected. NFV/RTV reduces pancreatic injury and acinar cell death in experimental mouse caerulein-induced pancreatitis but does not impact inflammation.
Degranulation, membrane addition, and shape change during chemotactic factor-induced aggregation of human neutrophils. (1982)

Neutrophils stimulated by the chemotactic factor formyl-methionyl-leucyl-phenyl-alanine (FMLP) undergo a transient change in surface properties that permits the cells to adhere more readily to surfaces and to each other. This transient change can be monitored by light scattering as stimulated neutrophils form aggregates while stirred in a platelet aggregometer. Maximum change in light scattering occurs within 1 min and correlates with an increase in the percentage of cells that are in aggregates of four or more cells and a decrease in the percentage of single cells. With time (3-5 min), small aggregates disappear and single cells reappear. The transient change in adhesiveness is accompanied by a persistent change in cell shape; the cells become polarized and protrude ruffles from one sector of the cell surface. During aggregation the cells adhere to one another with smooth sides together and ruffles pointed outward. During disaggregation the cells dissociate laterally with the simultaneous internalization of membrane in the region opposite the ruffles. Particle bound to the surface by charge (thorotrast, cationized ferritin) are concentrated and internalized in this region. The change in cell shape from round to ruffled occurs within seconds, suggesting that membrane is added to the cell surface from an intracellular store. We therefore quantified surface membrane by electron microscopy morphometry and measured a 25% increase within 10 s of adding FMLP. The source of new membrane appeared to be the specific granule membrane since the kinetics of granule discharge (between 30% and 50% of all release occurs in the first 10 s) correlate with the appearance of new membrane. Furthermore, the amount of membrane that appears at the cell surface at 10 s correlates with that lost from intracellular granules in that time. Chemotaxin-induced aggregation thus begins with granule discharge and membrane addition followed by protrusion of ruffles. Adherence is maximal at 60 s and the gradual loss of adhesiveness that follows is associated with uropod formation and enhanced endocytic activity.
The Analgetic Action of Dimethyl Sulfoxide (DMSO) Ointment in Arthrosis: A Double Blind Study (1971)

SummaryThe analgetic action of 50 % DMSO ointment and placebo ointment was studied in patients with arthrosis by the double blind method. A total of 100 treatment experiments of one month each were carried out. Favourable results were obtained in 76 % of the cases with both ointments. Since even placebo gives good subjective results in musculoskeletal diseases like arthrosis, the necessity of double blind tests in studies of this type is emphasized because of the psychic components of these chronic diseases.
Group-Lasso on Splines for Spectrum Cartography (2011)

The unceasing demand for continuous situational awareness calls for innovative and large-scale signal processing algorithms, complemented by collaborative and adaptive sensing platforms to accomplish the objectives of layered sensing and control. Towards this goal, the present paper develops a spline-based approach to field estimation, which relies on a basis expansion model of the field of interest. The model entails known bases, weighted by generic functions estimated from the field's noisy samples. A novel field estimator is developed based on a regularized variational least-squares (LS) criterion that yields finite-dimensional (function) estimates spanned by thin-plate splines. Robustness considerations motivate well the adoption of an overcomplete set of (possibly overlapping) basis functions, while a sparsifying regularizer augmenting the LS cost endows the estimator with the ability to select a few of these bases that “better” explain the data. This parsimonious field representation becomes possible, because the sparsity-aware spline-based method of this paper induces a group-Lasso estimator for the coefficients of the thin-plate spline expansions per basis. A distributed algorithm is also developed to obtain the group-Lasso estimator using a network of wireless sensors, or, using multiple processors to balance the load of a single computational unit. The novel spline-based approach is motivated by a spectrum cartography application, in which a set of sensing cognitive radios collaborate to estimate the distribution of RF power in space and frequency. Computer simulations and tests on real data corroborate that the estimated power spectrum density atlas yields the desired RF state awareness, since the maps reveal spatial locations where idle frequency bands can be reused for transmission, even when fading and shadowing effects are pronounced.
Protein‐protein recognition analyzed by docking simulation (1991)

Antibody-lysozyme and protease-inhibitor complexes are reconstituted by docking lysozyme as a rigid body onto the combining site of the antibodies and the inhibitors onto the active site of the proteases. Simplified protein models with one sphere per residue are subjected to simulated annealing using a crude energy function where the attractive component is proportional to the interface area. The procedure finds clusters of orientations in which a steric fit between the two protein components is achieved over a large contact surface. With five out of six complexes, the native structure of the complexes determined by X-ray crystallography is among those retained. Docked complexes are then subjected to conformational energy refinement with full atomic detail. With Fab HyHEL 5 and lysozyme, a native-like complex has the lowest refined energy. It can also be retrieved when starting with the X-ray structure of free lysozyme. However, some non-native complexes cannot be rejected: they form large interfaces, have a large number of H-bonds, and few unpaired polar groups. While these are necessary features of protein-protein recognition, they are not sufficient in determining specificity.
Site-specific mutagenesis of the catalytic subunit of cholera toxin: substituting lysine for arginine 7 causes loss of activity (1991)

Cholera and pertussis toxins each contain a subunit with ADP-ribosyltransferase activity, sharing a region of nearly identical amino acid sequence near the NH2 terminus. Previous investigations have shown that substitution of a lysine residue for Arg-9 in the catalytic A subunit of pertussis toxin substantially eliminates its enzyme activity. We now report that substitution of lysine for the position-equivalent Arg-7 of cholera toxin subunit A leads to a similar loss of catalytic activity. This result suggests a correlation of function with structure between the sequence-related cholera and pertussis toxin A subunits and may contribute to the design of a vaccine containing an enzymatically inert analog of cholera toxin.
Vascular Endothelial Growth Factor Trap in Non–Small Cell Lung Cancer (2007)

Several drugs currently in development target the vascular endothelial growth factor (VEGF) pathway, a validated target in the treatment of non-small cell lung cancer (NSCLC). Most clinical trial data generated to date have been with either bevacizumab, a monoclonal antibody to VEGF, or small-molecule inhibitors of VEGF receptor (VEGFR) tyrosine kinase activity (sunitinib, sorafenib, and ZD6474). VEGF Trap, an engineered soluble receptor made from extracellular domains of VEGFR1 and VEGFR2, binds to all isoforms of VEGF and to placental growth factor. VEGF Trap binds to VEGF-A and VEGF-B with markedly higher affinity than bevacizumab. The toxicities seen in phase I trials of s.c. and i.v. administration of VEGF Trap, hypertension and proteinuria, are similar to those seen with other molecules that target the VEGF pathway. In the s.c. VEGF Trap phase I trial, significant radiographic improvement was observed in a patient with heavily pretreated NSCLC. Ongoing phase I trials are evaluating combinations of VEGF Trap with platinum-based doublets and single-agent docetaxel. The activity of single-agent VEGF Trap in NSCLC is being assessed in a multicenter phase II trial.
The Rationale of the Angle Principles of Treatment for Cases of Malocclusion in Class II, Division I. (2009)

Abstract No Abstract Available. *Read before the Third Annual Meeting of The Edward H. Angle Society of Orthodontia at Pasadena, California.
Applications of machine learning and rule induction (1995)

M achine learning is the study of computational methods for improving performance by mechanizing the acquisition of knowledge from experience. Expert performance requires much domain-specific knowledge, and knowledge engineering has produced hundreds of AI expert systems that are now used regularly in industry. Machine learning aims to provide increasing levels of automation in the knowledge engineering process, replacing much time-consuming human activity with automatic techniques that improve accuracy or efficiency by discovering and exploiting regularities in training data. The ultimate test of machine learning is its ability to produce systems that are used regularly in industry, education, and elsewhere.
DFB laser with nonuniform coupling coefficient realized by double-layer buried grating (1993)

A technique for the realization of a nonuniform grating coupling coefficient kappa , and its implementation in distributed-feedback (DFB) lasers is presented. This technique, which is an extension of the buried-grating concept, offers precise control of the coupling coefficient and enables a kappa -ratio greater than 10. DFB lasers with an asymmetric kappa -variation have been fabricated using this method. A front-to-rear facet output power ratio close to five was obtained, qualitatively in agreement with simulations.< <ETX xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">&gt;</ETX>
Free-Running Activity Rhythms in the Rat: Entrainment by Melatonin (1983)

The pineal gland hormone melatonin may play a role in synchronization of rat circadian rhythms. Free-running activity rhythms of the rat were entrained by a daily melatonin injection, with entrainment occurring when the onset of activity coincided with the time of daily injections. When injections were stopped, activity rhythms became free-running again. Thus in pharmacological experiments, the time of day of melatonin administration is crucial.
Phase II study of lapatinib in combination with vinorelbine, as first- or second-line therapy in women with HER2-overexpressing metastatic breast cancer. (2013)

621 Background: Lapatinib (L), an inhibitor of epidermal growth factor receptor and human epidermal growth factor receptor 2 (HER2) is approved in combination with capecitabine for second-line treatment of HER2+ metastatic breast cancer (MBC). Vinorelbine (V)is a semi-synthetic vinca alkaloid approved for use in patients (pts) with MBC. A previous phase I trial provided a maximum tolerated dose of L plus V. Methods: This was a multicenter, phase II study (LPT111110; NCT00709618) to evaluate the efficacy and safety of L plus V in women with histologically confirmed stage IV HER2+ MBC, ≤1 prior chemotherapeutic regimen (no prior L or V was allowed; prior trastuzumab was permitted) and a Zubrod performance status of 0-2. Pts received L (1500 mg daily) plus V (20 mg/m 2 IV on Days 1, 8, 15) in a 4-week treatment cycle until disease progression or study withdrawal. Primary endpoint: overall response rate (ORR). Secondary endpoints: progression-free survival (PFS), overall survival, time to response (TTR), duration of response (DOR), time to progression, and safety assessments. Results: The study was terminated after three years due to slow enrollment; 60 pts were planned and 44 enrolled and were treated. The ORR was 41% (95% CI: 26.4%-55.4%; 4 complete responses, 14 partial responses). Investigator-assessed median (95% CI) PFS, TTR, and DOR were 24.1 (16.9-36.7), 7.5 (7.1–8.1), and 32.0 (18.0-42.3) weeks, respectively. Survival data are not available since data collection was terminated after discontinuation of study treatment. All pts experienced at least 1 adverse event (AE). Conclusions: The combination of L plus V resulted in a 41% ORR and was generally well tolerated. However, definitive conclusions could not be drawn as the study was terminated early and not powered for inference testing. Further exploration of L plus V is warranted to clearly define the role of this novel combination in the treatment of HER2+ MBC. Clinical trial information: NCT00709618. [Table: see text]
A Machine-Oriented Vulnerability Database for Automated Vulnerability Detection and Processing (2004)

The number of security vulnerabilities discovered in computer systems has increased explosively. Currently, in order to keep track of security alerts, system administrators rely on vulnerability databases such as: CERT Coordination Centre, Securityfocus BugTraq and Sans Vulnerabilities Notes Database. Such databases are designed primarily to be read and understood by humans. Given the speed at which an exploit becomes available once a vulnerability is known, and the frequency of occurrence of such vulnerabilities, manual human intervention is too slow, time-consuming and may not be effective. We propose the design of a new vulnerability database which is oriented to be machine readable and processable rather than human oriented. This allows automated response to a vulnerability alert rather than relying on manual intervention of system administrators. With this approach, many kinds of automatic processing of alerts become feasible. We show the value of such a database by constructing a prototype sample scanner for Unix systems tailored for Linux RedHat and FreeBSD. We envisage that our work can help spur a development of far more effective vulnerability databases to benefit a wide-ranging user community.
HUGO: Hierarchical mUlti-reference Genome cOmpression for aligned reads (2013)

Background and objective Short-read sequencing is becoming the standard of practice for the study of structural variants associated with disease. However, with the growth of sequence data largely surpassing reasonable storage capability, the biomedical community is challenged with the management, transfer, archiving, and storage of sequence data. Methods We developed Hierarchical mUlti-reference Genome cOmpression (HUGO), a novel compression algorithm for aligned reads in the sorted Sequence Alignment/Map (SAM) format. We first aligned short reads against a reference genome and stored exactly mapped reads for compression. For the inexact mapped or unmapped reads, we realigned them against different reference genomes using an adaptive scheme by gradually shortening the read length. Regarding the base quality value, we offer lossy and lossless compression mechanisms. The lossy compression mechanism for the base quality values uses k-means clustering, where a user can adjust the balance between decompression quality and compression rate. The lossless compression can be produced by setting k (the number of clusters) to the number of different quality values.
Potato glycoalkaloids (1980)

This review shall attempt to summarize the significance of glycoalkaloids in potato products. Specific areas that are discussed include the types and distribution of glycoalkaloids identified in potatoes, facts affecting their rates of formation and biosynthesis, control measures to minimize their formation, methods of analysis, and the health implications of such compounds along with their flavor properties.
Aura in some patients with familial hemiplegic migraine can be stopped by intranasal ketamine (2000)

Migraine aura is probably caused by cortical-spreading depression. No treatment for acute and severe migraine aura has been described previously. The effect of ketamine (25 mg intranasally) was studied in 11 patients with severe, disabling auras resulting from familial hemiplegic migraine. In five patients ketamine reproducibly reduced the severity and duration of the neurologic deficits, whereas in the remaining six patients no beneficial effect was seen. Ketamine offers, for the first time, a possible treatment option for severe and prolonged aura.
Mechanism for Room-Temperature Single-Atom Lateral Manipulations on Semiconductors using Dynamic Force Microscopy (2007)

Vacancy-mediated lateral manipulations of intrinsic adatoms of the Si(111)-(7x7) surface at room temperature are reported. The topographic signal during the manipulation combined with force spectroscopy measurements reveals that these manipulations can be ascribed to the so-called pulling mode, and that the Si adatoms were manipulated in the attractive tip-surface interaction regime at the relatively low short-range force value associated to the manipulation set point. First-principles calculations reveal that the presence of the tip induces structural relaxations that weaken the adatom surface bonds and manifests in a considerable local reduction of the natural diffusion barriers to adjacent adsorption positions. Close to the short-range forces measured in the experiments, these barriers are lowered near the limit that enables a thermally activated hopping at room temperature.
An internal targeting signal directing proteins into the mitochondrial intermembrane space (1999)

Import of most nucleus-encoded preproteins into mitochondria is mediated by N-terminal presequences and requires a membrane potential and ATP hydrolysis. Little is known about the chemical nature and localization of other mitochondrial targeting signals or of the mechanisms by which they facilitate membrane passage. Mitochondrial heme lyases lack N-terminal targeting information. These proteins are localized in the intermembrane space and are essential for the covalent attachment of heme to c type cytochromes. For import of heme lyases, the translocase of the mitochondrial outer membrane complex is both necessary and sufficient. Here, we report the identification of the targeting signal of mitochondrial heme lyases in the third quarter of these proteins. The targeting sequence is highly conserved among all known heme lyases. Its chemical character is hydrophilic because of a large fraction of both positively and negatively charged amino acid residues. These features clearly distinguish this signal from classical presequences. When inserted into a cytosolic protein, the targeting sequence directs the fusion protein into the intermembrane space, even in the absence of a membrane potential or ATP hydrolysis. The heme lyase targeting sequence represents the first topogenic signal for energy-independent transport into the intermembrane space and harbors two types of information. It assures accurate recognition and translocation by the translocase of the mitochondrial outer membrane complex, and it is responsible for driving the import reaction by undergoing high-affinity interactions with components of the intermembrane space.
Quinoxaline chemistry. Part 4. 2(R)-anilinoquinoxalines as nonclassical antifolate agents. Synthesis, structure elucidation and evaluation of in vitro anticancer activity. (1995)

Thirty-five quinoxalines bearing a substituted aniline group on position 2 and various substituents on positions 3,6,7 and 8 were prepared in order to evaluate in vitro anticancer activity. Structural elucidation of some isomeric quinoxalinones formed by ring closure of 4-substituted-1,2-diaminobenzenes with dicarbonyl compounds was achieved by comparison with one isomer coming from an unambiguous independent route. Preliminary in vitro screening at NCI showed that many compounds exhibited a moderate to strong growth inhibition activity on various cell lines between 10(-5) and 10(-4) molar concentrations.
XENORHABDUS AND PHOTORHABDUS SPP.: Bugs That Kill Bugs (1997)

Xenorhabdus and Photorhabdus spp. are gram negative gamma proteobacteria that form entomopathogenic symbioses with soil nematodes. They undergo a complex life cycle that involves a symbiotic stage, in which the bacteria are carried in the gut of the nematodes, and a pathogenic stage, in which susceptible insect prey are killed by the combined action of the nematode and the bacteria. Both bacteria produce antibiotics, intracellular protein crystals, and numerous other products. These traits change in phase variants, which arise when the bacteria are maintained under stationary phase conditions in the laboratory. Molecular biological studies suggest that Xenorhabdus and Photorhabdus spp. may serve as valuable model systems for studying signal transduction and transcriptional and posttranscriptional regulation of gene expression. Such studies also indicate that these bacterial groups, which had been previously considered to be very similar, may actually be quite different at the molecular level.
Azathioprine pharmacokinetics after intravenous, oral, delayed release oral and rectal foam administration. (1996)

Azathioprine delivered to the colon by delayed release oral and rectal foam formulations considerably reduced systemic 6-mercaptopurine bioavailability. The therapeutic potential of these colonic delivery methods, which can potentially limit toxicity by local delivery of high doses of azathioprine, should be investigated in patients with inflammatory bowel disease.
Down-Regulation of Basophil Function by Human CD200 and Human Herpesvirus-8 CD200 (2005)

Human and rodent CD200 are recognized by the inhibitory CD200R, and these molecules play an important role in the regulation of the immune system. Several viruses, such as human herpesvirus-6 (HHV-6), HHV-7, and HHV-8, possess a CD200 homologue, suggesting that these viruses regulate the immune response via CD200R. In this study, we analyzed the effect of human CD200 and the viral CD200 homologues on human CD200R-expressing cells. We found that human CD200R is predominantly expressed on basophils in amounts higher than on other human peripheral blood leukocytes. Furthermore, the viral CD200 homologues as well as human CD200 were recognized by human CD200R, and the activation of basophils was down-regulated by these CD200 proteins. These results suggested that CD200R is an important regulatory molecule of basophil activation. In addition, the presence of CD200 homologues on several viruses suggests a potentially unique relationship between basophil function and viral infection.