gebhart/patrepeval huggingface dataset:
A phase I dose-escalation study of the Hsp90 inhibitor STA-9090 administered twice weekly in patients with solid tumors. (2010)

3083 Background: STA-9090 is a potent, next-generation Hsp90 inhibitor that is structurally unrelated to the first-generation ansamycin class of Hsp90 inhibitors, such as 17-AAG and IPI-504, and has shown superior activity and an improved safety profile relative to these agents in preclinical studies. Methods: Patients with solid tumor malignancies who have exhausted standard of care treatment options are eligible. Patients receive STA-9090 as a 1-hr infusion twice weekly for 3 weeks of a 28-day cycle. Serial PK samples are obtained on days 1 and 15 of cycle 1. Safety assessments included the number and grade of AEs, changes from baseline in laboratory parameters, and ECG changes. Results: Data are presented for the first 29 patients (13 M, 16 F; median age 55 yrs, range 32-81; ECOG status range 0-2) treated at dose levels ranging from 2 mg/m2 to 25 mg/m2. The AEs reported in >20% of patients were fatigue, nausea, anemia, diarrhea, vomiting, anorexia, and headache; the majority of these AEs were mild to moderate in severity. A DLT of elevated LFTs was reported in the 10 mg/m2 cohort. STA-9090 shows linear pharmacokinetics, exhibits rapid distribution, has a mean terminal phase half life of 10-14 hours and no accumulation in plasma. The MTD has not been reached, and dose escalation continues with a total of 32 patients enrolled at doses up to 50 mg/m2. Preliminary signs of clinical activity have been observed and include a durable PR in a patient with melanoma and tumor shrinkage with prolonged SD in several patients with different tumor types, including melanoma and NSCLC. Conclusions: STA-9090 has been well tolerated at dose levels up to 25 mg/m2 administered twice weekly. Preliminary safety profile and activity signals warrant continued evaluation of STA-9090 using a twice weekly dosing regimen. Author Disclosure Employment or Leadership Position Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Synta Synta Synta
Enantioselective Synthesis of 3H-Pyrrolo[1,2-a]indole-2-carbaldehydes via an Organocatalytic Domino Aza-Michael/Aldol Condensation Reaction (2009)

A simple organocatalytic aza-Michael/aldol condensation domino reaction protocol opens an efficient and enantioselective entry to the tricyclic pyrrolo indole core, a characteristic structural unit of many bioactive natural products.
Local Anesthetics as Antimicrobial Agents: A Review (2008)

Local anesthetics not only serve as agents for pain control, but possess antimicrobial activity as well. In such a capacity, local anesthetics can be considered as an adjunct to traditional antimicrobial use in the clinical or laboratory setting. Additionally, caution should be exercised when administering local anesthetics prior to diagnostic procedures in which culture specimens are to be obtained, as the antimicrobial activity of the local anesthetic could lead to false-negative results or suboptimal culture yields.
Prospective Study of Corneal Collagen Cross-linking Efficacy and Tolerance in the Treatment of Keratoconus and Corneal Ectasia (2012)

This study shows that corneal collagen cross-linking can stabilize progressive corneal ectasia, both primary and secondary, with no induced iatrogenic effects.
Control of Lytic Function by Mitogen-activated Protein Kinase/Extracellular Regulatory Kinase 2 (ERK2) in a Human Natural Killer Cell Line: Identification of Perforin and Granzyme B Mobilization by Functional ERK2 (1998)

The signal pathways that control effector function in human natural killer (NK) cells are little known. In this study, we have identified the critical role of the mitogen-activated protein kinase (MAPK) pathway in NK lysis of tumor cells, and this pathway may involve the mobilization of granule components in NK cells upon interaction with sensitive tumor target cells. Evidence was provided by biological, biochemical, and gene transfection methods. NK cell binding to tumor cells for 5 min was sufficient to maximally activate MAPK/extracellular signal-regulatory kinase 2 (ERK2), demonstrated by its tyrosine phosphorylation and by its ability to function as an efficient kinase for myelin basic protein. MAPK activation was achieved in NK cells only after contact with NK-sensitive but not NK-resistant target cells. In immunocytochemical studies, cytoplasmic perforin and granzyme B were both maximally redirected towards the tumor contact zone within 5 min of NK cell contact with tumor cells. A specific MAPK pathway inhibitor, PD098059, could block not only MAPK activation but also redistribution of perforin/granzyme B in NK cells, which occur upon target ligation. PD098059 also interfered with NK lysis of tumor cells in a 5-h 51Cr-release assay, but had no ability to block NK cell proliferation. Transient transfection studies with wild-type and dominant-negative MAPK/ERK2 genes confirmed the importance of MAPK in NK cell lysis. These results document a pivotal role of MAPK in NK effector function, possibly by its control of movement of lytic granules, and clearly define MAPK involvement in a functional pathway unlinked to cell growth or differentiation.
Genetic Mapping of Agronomic Traits Using Recombinant Inbred Lines of Soybean (1996)

Many agronomic traits of interest to plant breeders are quantitative. Recombinant inbred (RI) lines are particularly useful in genetic mapping studies of quantitative traits. A recombinant inbred population was derived from the Glycine max (L.) Merr. parents ‘Minsoy’ and ‘Noir 1’. This soybean population was used to investigate the genetic basis of several agronomic traits: days to flower (Rl), days to maturity (R8), reproductive period (RS‐R1), plant height, lodging score, height divided by lodging (the ability of tall plants to stand upright), seed protein content, seed oil content, seed size, yield, seed number, yield divided by height (the yield from short plants), leaf width, leaf length, and leaf area. In this RI population, transgressive segregation was observed for all of these traits. As expected, height and lodging were correlated, as were height and maturity; height and maturity with yield; and leaf length and width with leaf area. Height divided by lodging and yield divided by height showed little correlation with other traits, indicating that these traits measured new plant phenotypes. A genetic map was constructed for this population, with restriction fragment length polymorphism markers, simple sequence repeat markers and classical markers. Approximately 2000 cM of linkage was defined. The data were used to identify quantitative trait loci (QTLs) by linking quantitative phenotypes to qualitative genetic markers. for many traits, a few QTLs accounted for a large proportion of the variation observed. QTLs for most of the traits were associated with three linkage groups, often with the same genetic locus within the linkage group. At the level of resolution of the genetic map for this population, it was not possible to determine whether these QTLs have pleiotrophic effects or are clusters of separate, tightly linked genes. The data suggest that separation of QTLs for different traits (such as maturity or lodging and yield) may be difficult, but that this RI population will be useful in resolving questions concerning marker assisted selection of quantitative traits.
Adhesion of Activated Platelets to Endothelial Cells: Evidence for a GPIIbIIIa-dependent Bridging Mechanism and Novel Roles for Endothelial Intercellular Adhesion Molecule 1 (ICAM-1), αvβ3 Integrin, and GPIbα (1998)

Although it has been reported that activated platelets can adhere to intact endothelium, the receptors involved have not been fully characterized. Also, it is not clear whether activated platelets bind primarily to matrix proteins at sites of endothelial cell denudation or directly to endothelial cells. Thus, this study was designed to further clarify the mechanisms of activated platelet adhesion to endothelium. Unstimulated human umbilical vein endothelial cell (HUVEC) monolayers were incubated with washed, stained, and thrombin-activated human platelets. To exclude matrix involvement, HUVEC were harvested mechanically and platelet binding was measured by flow cytometry. Before the adhesion assay, platelets or HUVEC were treated with different receptor antagonists. Whereas blockade of platelet beta1 integrins, GPIbalpha, GPIV, P-selectin, and platelet-endothelial cell adhesion molecule (PECAM)-1 did not reduce platelet adhesion to HUVEC, blockade of platelet GPIIbIIIa by antibodies or Arg-Gly-Asp (RGD) peptides markedly decreased adhesion. Moreover, when platelets were treated with blocking antibodies to GPIIbIIIa-binding adhesive proteins, including fibrinogen and fibronectin, and von Willebrand factor (vWF), platelet binding was also reduced markedly. Addition of fibrinogen, fibronectin, or vWF further increased platelet adhesion, indicating that both endogenous platelet-exposed and exogenous adhesive proteins can participate in the binding process. Evaluation of the HUVEC receptors revealed predominant involvement of intercellular adhesion molecule (ICAM)-1 and alphavbeta3 integrin. Blockade of these two receptors by antibodies decreased platelet binding significantly. Also, there was evidence that a component of platelet adhesion was mediated by endothelial GPIbalpha. Blockade of beta1 integrins, E-selectin, P-selectin, PECAM-1, vascular cell adhesion molecule (VCAM)-1 and different matrix proteins on HUVEC did not affect platelet adhesion. In conclusion, we show that activated platelet binding to HUVEC monolayers is mediated by a GPIIbIIIa-dependent bridging mechanism involving platelet-bound adhesive proteins and the endothelial cell receptors ICAM-1, alphavbeta3 integrin, and, to a lesser extent, GPIbalpha.
Statistical Thermodynamics of Chain Molecule Liquids. I. An Equation of State for Normal Paraffin Hydrocarbons (1964)

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTStatistical Thermodynamics of Chain Molecule Liquids. I. An Equation of State for Normal Paraffin HydrocarbonsP. J. Flory, R. A. Orwoll, and A. VrijCite this: J. Am. Chem. Soc. 1964, 86, 17, 3507–3514Publication Date (Print):September 1, 1964Publication History Published online1 May 2002Published inissue 1 September 1964https://pubs.acs.org/doi/10.1021/ja01071a023https://doi.org/10.1021/ja01071a023research-articleACS PublicationsRequest reuse permissionsArticle Views1390Altmetric-Citations815LEARN ABOUT THESE METRICSArticle Views are the COUNTER-compliant sum of full text article downloads since November 2008 (both PDF and HTML) across all institutions and individuals. These metrics are regularly updated to reflect usage leading up to the last few days.Citations are the number of other articles citing this article, calculated by Crossref and updated daily. Find more information about Crossref citation counts.The Altmetric Attention Score is a quantitative measure of the attention that a research article has received online. Clicking on the donut icon will load a page at altmetric.com with additional details about the score and the social media presence for the given article. Find more information on the Altmetric Attention Score and how the score is calculated. Share Add toView InAdd Full Text with ReferenceAdd Description ExportRISCitationCitation and abstractCitation and referencesMore Options Share onFacebookTwitterWechatLinked InRedditEmail Other access optionsGet e-Alertsclose Get e-Alerts
VMRPC: A high efficiency and light weight RPC system for virtual machines (2010)

Despite advances in high performance inter-domain communication for virtual machines (VM), data intensive applications developed for VMs based on traditional remote procedure call (RPC) mechanism still suffer from performance degradation due to the inherent inefficiency of data serialization/deserilization operation. This paper presents VMRPC, a light-weight RPC framework specifically designed for VMs that leverages heap and stack sharing to circumvent unnecessary data copying and serialization/deserilization, and achieve high performance. Our evaluation shows that the performance of VMRPC is an order of magnitude better than traditional RPC systems and existing alternative inter-domain communication mechanisms. We adopt VMRPC in a real system, and the experiment results exhibit that the performance of VMRPC is even competitive to native environment.
Mast cells and myofibroblasts in keloid: a light microscopic, immunohistochemical and ultrastructural study. (1995)

A light microscopic, immunohistochemical and ultrastructural study was done on 2 patients with active pruritic keloids. The primary cell was the myofibroblast with prominent rough endoplasmic reticulum and bundles of myofilaments with focal densities in the cytoplasm. Enhanced secretory activity was reflected in the prominence of the Golgi apparatus and the frequent presence of intracellular collagen within the tubular membranes. The number of mast cells was increased and they were closely associated with myofibroblasts with frequent direct cell contacts. The filopodia of the mast cells were seen intimately applied along the cell membrane of the myofibroblasts. Degranulated mast cells contained few and electron-lucent granules. Discharge of the contents of granules into the interstitial matrix was encountered. Mast cell granules were also seen lying free in the interstitium. In the vicinity of the degranulated mast cells the interstitial matrix was oedematous containing granular material and the myofibroblasts showed considerable dilation of the rough endoplasmic reticulum and vacuole formation. The intimate relationship and interaction between mast cells and myofibroblasts support the important role of mast cells and their mediators in the pathogenesis of keloid.
Quantum interference between transverse spatial waveguide modes (2017)

Integrated quantum optics has the potential to markedly reduce the footprint and resource requirements of quantum information processing systems, but its practical implementation demands broader utilization of the available degrees of freedom within the optical field. To date, integrated photonic quantum systems have primarily relied on path encoding. However, in the classical regime, the transverse spatial modes of a multi-mode waveguide have been easily manipulated using the waveguide geometry to densely encode information. Here, we demonstrate quantum interference between the transverse spatial modes within a single multi-mode waveguide using quantum circuit-building blocks. This work shows that spatial modes can be controlled to an unprecedented level and have the potential to enable practical and robust quantum information processing.
Proving program termination (2011)

In contrast to popular belief, proving termination is not always impossible.
Prevention of autoimmune disease due to lymphocyte modulation by the B-subunit ofEscherichia coli heat-labile enterotoxin (1997)

We demonstrate that the receptor binding moiety of Escherichia coli heat-labile enterotoxin (EtxB) can completely prevent autoimmune disease in a murine model of arthritis. Injection of male DBA/1 mice at the base of the tail with type II collagen in the presence of complete Freund's adjuvant normally leads to arthritis, as evidenced by inflammatory infiltration and swelling of the joints. A separate injection of EtxB at the same time as collagen challenge prevented leukocyte infiltration, synovial hyperplasia, and degeneration of the articular cartilage and reduced clinical symptoms of disease by 82%. The principle biological property of EtxB is its ability to bind to the ubiquitous cell surface receptor GM1 ganglioside, and to other galactose-containing glycolipids and galactoproteins. The importance of receptor interaction in mediating protection from arthritis was demonstrated by the failure of a non-receptor-binding mutant of EtxB to elicit any protective effect. Analysis of T cell responses to collagen, in cultures of draining lymph node cells, revealed that protection was associated with a marked increase in interleukin 4 production concomitant with a reduction in interferon gamma levels. Furthermore, in protected mice there was a significant reduction in anti-collagen antibody levels as well as an increase in the IgG1/IgG2a ratio. These observations show that protection is associated with a shift in the Th1/Th2 balance as well as a general reduction in the extent of the anti-type II collagen immune response. This suggests that EtxB-receptor-mediated modulation of lymphocyte responses provides a means of preventing autoimmune disease.
Aerobically Derived Lactate Stimulates Revascularization and Tissue Repair via Redox Mechanisms (2007)

Hypoxia serves as a physiologic cue to drive an angiogenic response via HIF-dependent mechanisms. Interestingly, minor elevation of lactate levels in the tissue produces the same effect under aerobic conditions. Aerobic glycolysis contributes to lactate accumulation in the presence of oxygen, especially under inflammatory conditions. We previously postulated that aerobic lactate accumulation, already known to stimulate collagen deposition, will also stimulate angiogenesis. If substantiated, this concept would advance understanding of wound healing and aerobic angiogenesis because lactate accumulation has many aerobic sources. In this study, Matrigel plugs containing a powdered, hydrolyzable lactate polymer were implanted into the subcutaneous space of mice. Lactate monomer concentrations in the implant were consistent with wound levels for more than 11 days. They induced little inflammation but considerable VEGF production and were highly angiogenic, as opposed to controls. Arterial hypoxia abrogated angiogenesis. Furthermore, inhibition of lactate dehydrogenase by using oxamate also prevented the angiogenic effects of lactate. Lactate monomer, at concentrations found in cutaneous wounds, stabilized HIF-1alpha and increased VEGF levels in aerobically cultured human endothelial cells. Accumulated lactate, therefore, appears to convey the impression of "metabolic need" for vascularization, even in well-oxygenated and pH-neutral conditions. Lactate and oxygen together stimulate angiogenesis and matrix deposition.
Dietary eicosapentaenoic acid and docosahexaenoic acid from fish oil. Their incorporation into advanced human atherosclerotic plaques. (1991)

The incorporation of fatty acids from dietary fish oil was measured in obstructive atherosclerotic plaques removed from 11 patients fed fish oil, rich in omega-3 fatty acids, for 6-120 days before a planned arterial endarterectomy. The fatty acids of plasma and atheroma were analyzed with special reference to docosahexaenoic acid (DHA, 22:6) and eicosapentaenoic acid (EPA, 20:5), the principal omega-3 fatty acids of fish oil. The omega-3 fatty acid content increased greatly in plasma from 0.9% of fatty acids to 14.8% in cholesteryl esters, from 3.8% to 22.1% in phospholipids, and from 1.3% to 21.9% in triglycerides. The omega-3 fatty acid content of the atherosclerotic plaques was also greater when compared with that of plaques removed from 18 non-fish oil-fed controls. The omega-3 fatty acid in cholesteryl esters of the plaques was 4.9% in the experimental group versus 1.4% in control plaque, in phospholipids it was 8.8% versus 1.8%, and in triglycerides it was 4.7% versus 0.7% (p less than 0.001 for each lipid class). The two major omega-3 fatty acids (DHA and EPA) behaved differently. Compared with their respective plasma levels, relatively more DHA than EPA was deposited into the plaques. Whereas the increase of omega-3 fatty acids in plasma reached a plateau 3 weeks after initiation of fish oil feeding, a linear increase in plaque omega-3 fatty acids continued with time. As a result of the changes in fatty acid composition, the lipid classes of both plasma and plaque had a higher unsaturation index in the fish oil-fed group.(ABSTRACT TRUNCATED AT 250 WORDS)
Lung Protection by Cathepsin C Inhibition: A New Hope for COVID-19 and ARDS? (2020)

Cathepsin C (CatC) is a cysteine dipeptidyl aminopeptidase that activates most of tissue-degrading elastase-related serine proteases. Thus, CatC appears as a potential therapeutic target to impair protease-driven tissue degradation in chronic inflammatory and autoimmune diseases. A depletion of proinflammatory elastase-related proteases in neutrophils is observed in patients with CatC deficiency (Papillon-Lefèvre syndrome). To address and counterbalance unwanted effects of elastase-related proteases, chemical inhibitors of CatC are being evaluated in preclinical and clinical trials. Neutrophils may contribute to the diffuse alveolar inflammation seen in acute respiratory distress syndrome (ARDS) which is currently a growing challenge for intensive care units due to the outbreak of the COVID-19 pandemic. Elimination of elastase-related neutrophil proteases may reduce the progression of lung injury in these patients. Pharmacological CatC inhibition could be a potential therapeutic strategy to prevent the irreversible pulmonary failure threatening the life of COVID-19 patients.
PDDL2.1: An Extension to PDDL for Expressing Temporal Planning Domains (2003)

In recent years research in the planning community has moved increasingly toward s application of planners to realistic problems involving both time and many typ es of resources. For example, interest in planning demonstrated by the space res earch community has inspired work in observation scheduling, planetary rover ex ploration and spacecraft control domains. Other temporal and resource-intensive domains including logistics planning, plant control and manufacturing have also helped to focus the community on the modelling and reasoning issues that must be confronted to make planning technology meet the challenges of application. The International Planning Competitions have acted as an important motivating fo rce behind the progress that has been made in planning since 1998. The third com petition (held in 2002) set the planning community the challenge of handling tim e and numeric resources. This necessitated the development of a modelling langua ge capable of expressing temporal and numeric properties of planning domains. In this paper we describe the language, PDDL2.1, that was used in the competition. We describe the syntax of the language, its formal semantics and the validation of concurrent plans. We observe that PDDL2.1 has considerable modelling power --- exceeding the capabilities of current planning technology --- and presents a number of important challenges to the research community.
Identification of In Vivo-Interacting Domains of the Murine Coronavirus Nucleocapsid Protein (2009)

The coronavirus nucleocapsid protein (N), together with the large, positive-strand RNA viral genome, forms a helically symmetric nucleocapsid. This ribonucleoprotein structure becomes packaged into virions through association with the carboxy-terminal endodomain of the membrane protein (M), which is the principal constituent of the virion envelope. Previous work with the prototype coronavirus mouse hepatitis virus (MHV) has shown that a major determinant of the N-M interaction maps to the carboxy-terminal domain 3 of the N protein. To explore other domain interactions of the MHV N protein, we expressed a series of segments of the MHV N protein as fusions with green fluorescent protein (GFP) during the course of viral infection. We found that two of these GFP-N-domain fusion proteins were selectively packaged into virions as the result of tight binding to the N protein in the viral nucleocapsid, in a manner that did not involve association with either M protein or RNA. The nature of each type of binding was further explored through genetic analysis. Our results defined two strongly interacting regions of the N protein. One is the same domain 3 that is critical for M protein recognition during assembly. The other is domain N1b, which corresponds to the N-terminal domain that has been structurally characterized in detail for two other coronaviruses, infectious bronchitis virus and the severe acute respiratory syndrome coronavirus.