gebhart/patrepeval huggingface dataset:
Results of a phase II study of picoplatin with docetaxel and prednisone in first-line treatment of castration-resistant prostate cancer (CRPC) (2009)

5140 Background: Picoplatin (Pico) was designed to overcome platinum resistance and has the potential for improved safety compared to other platinum agents. Previously, a PSA response rate of 25% was observed when Pico monotherapy was infused at 120 mg/m 2 Q3W (N = 20). Recently, a 34-patient Phase I study was performed to investigate the safety and efficacy of Pico in combination with docetaxel (D) + prednisone (pred) as first-line therapy for metastatic CRPC. Picoplatin therapy was well-tolerated at a dose of 120 mg/m 2 and 19 of 32 evaluable pts (59%) achieved a confirmed PSA response. Methods: 32 patients with chemotherapy-naïve CRPC and disease progression received Pico (120 mg/m 2 ) and D (75 mg/m 2 ) Q3W with pred 5 mg po bid for up to 10 cycles. PSA responses were defined as a reduction from baseline of at least 50% maintained for at least 4 weeks. CT and bone scans were also evaluated. Tumor response was measured using RECIST. Results: Patients received a median of 10 cycles (range = 1–10). Median baseline PSA was 340.8 ng/mL (range 5.6–3019). One pt had no baseline PSA data. Of the 24 patients with evaluable post-treatment PSA, 83% (95% CI 64–93%) had PSA decreases &lt;50% of baseline, and in 8 of these (33% of the evaluable population), PSA reached normal levels (&lt; 4 ng/mL). In the intent-to-treat population, the PSA response rate was 63% (95% CI 45–77%). 13 patients evaluated by CT scan had measurable disease; 6 pts had SD by RECIST, 4 had PD, and 3 were not evaluable. The most common adverse events were alopecia (36%), asthenia (32%), neutropenia (29%), increased creatinine (23%), and thrombocytopenia (19%). No neurotoxicity ≥ grade 2 was observed. Conclusions: Picoplatin was safely administered to patients with CRPC as 1 st -line therapy at 120 mg/m 2 Q3W with full doses of docetaxel and prednisone, resulting in a PSA response rate of 83% of evaluable patients. These results support further development of picoplatin as a novel combination with docetaxel for the treatment of CRPC. [Table: see text]
Treatment of Diarrhea Caused byGiardia intestinalisandEntamoeba histolyticaorE. dispar:A Randomized, Double‐Blind, Placebo‐Controlled Study of Nitazoxanide (2001)

A prospective randomized, double-blind, placebo-controlled study was conducted to assess the efficacy and safety of nitazoxanide in the treatment of diarrhea caused by Giardia intestinalis or Entamoeba histolytica and/or E. dispar in 89 adults and adolescents, 22 of whom were diagnosed with G. intestinalis, 53 with E. histolytica and/or E. dispar, and 14 with both G. intestinalis and E. histolytica and/or E. dispar. The study medication was administered as 1 nitazoxanide 500-mg tablet or a matching placebo twice daily for 3 days. Thirty-eight (81%) of 47 patients in the nitazoxanide treatment group resolved diarrhea within 7 days (median, 3 days) after initiation of treatment, versus 17 (40%) of 42 in the placebo group (P=.0002). With its efficacy in treating a broad spectrum of enteric protozoan pathogens, nitazoxanide could play an important role in the management of diarrhea caused by enteric protozoa, reducing morbidity and costs associated with these diarrheal illnesses.
IUPAC-NIST Solubility Data Series 68. Halogenated Aliphatic Hydrocarbon Compounds C3–C14 With Water (1999)

This volume covers the solubilities of halogenated aliphatic C3–C14 compounds with water, heavy water, and electrolyte solutions. All data were critically examined for their reliability and best value estimates were selected on the basis of such evaluations. Referenced works are presented in the standard IUPAC-NIST Solubility Data Series format. Reported and best value data are presented in tabular form and, where justified, data correlation equations and graphical illustrations are provided. Throughout the volume, SI conventions have been employed as the customary units. The importance of these data arises from the fact that halogenated aliphatics have considerable commercial uses in a variety of applications such as industrial chemicals, process raw materials, solvents, and the like. In such applications they are often in contact with water and are routinely exposed to the atmosphere. Sometimes such contact and exposure results from spillage, leakage, or mishandling. Reliable data are essential for concentration estimates for the halogenated aliphatics in drinking and ground water, foodstuffs, human tissue, marine organisms, and the atmosphere. The halogenated aliphatics are of particular interest to health scientists, engineers, environmentalists, and atmospheric chemists in that they represent a class of chemical materials which has many significant industrial applications. However, at the same time, some of this class of substances have been shown to be carcinogenic and also to be especially harmful for the earth’s atmospheric and natural water composition. Indeed, the chemical reactivity of some halogenated aliphatics has resulted in atmospheric ozone depletion. The high ozone depletion potentials of such chemical substances emphasizes the importance of having available complete, accurate, and reliable data for mutual solubilities with water. The availability of such data is essential for estimates of halogenated aliphatic hydrocarbon levels in both natural water and aqueous industrial liquids which result from industrial fabrication, industrial liquids which result from industrial fabrication, industrial waste removal processes, and the like. The data also provide significant solubility values for studies concerning the health of humans and other biological systems.
Mouse connexin37: cloning and functional expression of a gap junction gene highly expressed in lung. (1991)

The coding sequence (333 amino acids) of a new connexin protein, designated mouse connexin37 (Cx37 or Cx37.6) due to the deduced theoretical molecular mass of 37.600 kD, has been determined from cDNA and genomic clones. As seen in other connexins, its gene has no introns within the coding region and the deduced amino acid sequence is predicted to have similar topology to other connexins that form intercellular channels. The amino acid sequence of mouse Cx37 is most similar to rat connexin43 (59% identity) and Xenopus connexin38 (66% identity) when compared from the NH2 terminus to the end of the fourth putative transmembrane region. When expressed in Xenopus oocytes Cx37 forms functional intercellular channels that exhibit more sensitive and rapid gating in response to voltage than any previously characterized vertebrate gap junction. Under stringent conditions the Cx37 cDNA hybridizes to an mRNA of 1.7 kb that is found highly abundant in lung and to progressively lesser extents in brain, kidney, skin, spleen, liver, intestine, and heart. Embryonic brain, kidney, and skin express two to fivefold higher levels of the Cx37 transcript than the corresponding adult tissues. Cx37 transcripts were also found to increase two to threefold in response to retinoic acid treatment of cultured embryonic carcinoma F9 cells.
Prediction of the Brain−Blood Distribution of a Large Set of Drugs from Structurally Derived Descriptors Using Partial Least-Squares (PLS) Modeling (1999)

In this study, the multivariate partial least-squares projections to latent structures (PLS) technique was used for modeling the brain-blood concentration ratio (BB) of 61 structurally diverse compounds. The PLS model was based on molecular descriptors that can be calculated for any compound simply from a knowledge of its molecular structure, and the model included several topological and constitutional descriptors. The PLS analysis resulted in a significant three-component model with the following statistics: r = 0.922, Q = 0.867, s = 0.318, n = 58, and F = 102. The predictive ability of the model was assessed by means of crossvalidation and also by using BB partitioning data, BBB permeability data, and 1 set of qualitative brain penetration data, resulting in BB distribution data for 97 compounds. The results indicate that the PLS model developed is statistically sound and is sufficiently robust for predictive use. Taking into account the great ease of computation and interpretation of the derived model, it may be of general utility in predicting BB ratios for a very wide range of new drugs.
The binding of human plasminogen to fibrin and fibrinogen. (1983)

The binding of human plasminogen to fibrin was studied using 125Lplasminogen and uniform suspensions of noncross-linked or cross-linked human fibrin.Of the two types of plasminogen, the proteolytically modified form (NJ&-terminal lysine; Lys-plasminogen) showed a high binding affinity for both forms of fibrin, having a dissociation constant of 0.32 p~ and two binding sites per fibrin monomeric unit.Binding could be inhibited by w-aminocarboxylic acids such as lysine or e-aminocaproic acid (EACA).Nonlinear least squares computer analysis of the competition curve with EACA indicated that dissociation of Lys-plasminogen from fibrin occurred through the binding of one EACA molecule per plasminogen with a K d Of 18 pM.Native plasminogen (NHz-terminal glutamic acid; Glu-plasminogen) and its isolated elastase digestion fragments, K123, K4, and Vah-plasminogen, also bound to cross-linked fibrin with about 2 binding sites per monomeric unit but with much lower affinities.Dissociation constants were 38 p~ for Glu-plasminogen, 61 p~ for K123, 160 pM for K4, and 170 pM for v a hplasminogen.Computer analysis of the inhibition of this binding by EACA indicated that only one lysinebinding site was involved in the interaction between any of the plasminogen fragments and fibrin but that two sites were involved in the Glu-plasminogen-fibrin interaction, with K d values of 10 pM and 440 p.With only the high affinity lysine-binding site on Glu-plasminogen blocked by EACA, fibrinogen still enhanced the rate of Glu-plasminogen activation over &fold.Hence, while two lysine-binding sites may be involved in binding to fibrin, it is the lower affinity binding site that interacts with fibrin(ogen) to accelerate activation.By sucrose density ultracentrifugation Glu-plasminogen did not bind to fibrinogen, while Lys-plasminogen and fibrinogen did form a complex which had a dissociation constant of about 1 m ~.Of the fibrinogen plasmic degradation fragments, only Fragment E bound Lys-plasminogen, having a dissociation constant of about 8.3 q.The elastase digestion fragment of plasminogen, K123, also formed a complex with fibrinogen as well as with Fragment E. Unlike Lys-plasminogen, a difference was noted in the binding of the two carbohydrate forms of K123 to fibrinogen.Only the K123 which lacked the asparagine-linked carbohydrate chain bound to fibrinogen, but both K123 forms bound F'ragment E. Just as in the plasminogen-fibrin binding studies, all of these complexes could be inhibited by aaminocarboxylic acids.
Serological studies and isolations of serotype hardjo and Leptospira biflexa strains from horses of Argentina (1976)

Three pathogenic leptosipras and 12 saprophytic Leptospira biflexa strains were isolated from 72 apparently normal horse kidneys collected at an abattoir in Argentina. Cross-agglutination reaction patterns of the pathogens showed that they were antigenically homologous with members of the Hebdomadis group. When one of the strains was compared to Hebdomadis serotypes in reciprocal agglutination-absorption tests, it was found to be serologically homologous to serotype hardjo. This is the first known report of an isolation of this serotype from horses. Serological tests were also carried out on randomly collected abattoir sera from 245 horses to determine the prevalence of equine leptospirosis. Significant antibody titers (1:100 or greater) were found in 74.6% of the sera. Predominant reactions occurred with the antigens pomona, hebdomadis group, pyrogenes, tarassovi, and canicola. Agglutination tests performed with antigen prepared with one of the saprophytic biflexa isolates showed seropositive reactions in 99.1% of the equine sera, with agglutination titers ranging from 1:100 to 1:3,200. Absorption of selected horse sera with the saprophytic strain removed the agglutinins to Leptospira interrogans serotypes. This suggests the possibility that L. biflexa strains may act as an antigenic stimulus and account for some of the persistent multiple cross-reaction patterns of equine sera with pathogenic serotypes.
Dissecting the signaling and mechanical functions of the dystrophin-glycoprotein complex (2006)

Duchenne muscular dystrophy is a severe disorder caused by mutations in the dystrophin gene. Dystrophin is required for assembly of the dystrophin-glycoprotein complex and provides a mechanically strong link between the cytoskeleton and the extracellular matrix. Several proteins in the complex also participate in signaling cascades, but the relationship between these signaling and mechanical functions in the development of muscular dystrophy is unclear. To explore the mechanisms of myofiber necrosis in dystrophin-deficient muscle, we tested the hypothesis that restoration of this complex without a link to the cytoskeleton ameliorates dystrophic pathology. Transgenic mice were generated that express Dp116, a non-muscle isoform of dystrophin that assembles the dystrophin-glycoprotein complex, in muscles of dystrophin-deficient mdx(4cv) mice. However, the phenotype of these mice was more severe than in controls. Displacement of utrophin by Dp116 correlated with the severity of dystrophy in different muscle groups. Comparison with other transgenic lines demonstrated that parts of the dystrophin central rod domain were required to localize neuronal nitric oxide synthase to the sarcolemma, but this was not correlated with presence or extent of dystrophy. Our results suggest that mechanical destabilization, rather than signaling dysfunction, is the primary cause of myofiber necrosis in dystrophin-deficient muscle.
A Method for the Fabrication of Low-Noise Carbon Fiber Nanoelectrodes (2001)

A new and facile method has been developed for the fabrication of low-noise carbon fiber microelectrodes (CFMEs) and carbon fiber nanoelectrodes (CFNEs). The carbon fiber was flame-fuse sealed in the tip of the glass capillary. The CFMEs were made by cutting the protruding carbon fiber to the desired length, and the CFNEs were achieved by etching the protruding carbon on the flame to form a nanometer-scale tip. The tip of CFNEs can be controlled within the range from 100 to 300 nm. Thus, no epoxy wax was involved in the CFMEs and CFNEs. The experimental results of inspecting CFMEs and CFNEs by scanning electron microscopy demonstrated that the surface of the electrodes and the glass/fiber interface are very smooth. Therefore, the noise caused by the glass/fiber of these electrodes is much lower than that of the electrodes fabricated conventionlly. The electrodes were characterized by ferricyanide, catecholamine (dopamine,DA), norepinephrine (NE), and epinephrine (E)) and 5-hydroxytryptamine (5-HT) neurotransmitters using CV, LSV, DPV, and FSCV. The results showed that the CFMEs and CFNEs have very excellent electrochemical behavior and high sensitivity. The CV and DPV detection limits of DA, NE, and E are 7.6 x 10(-8), 7.0 x 10(-8), and 5.0 x 10(-8) mol/L, and the DPV detection limits of DA, NE, and E are 4.0 x 10(-8), 1.0 x 10(-7), and 2.2 x 10(-7) mol/L, respectively. This experiment offers a new and facile method for the fabrication of CFMEs and CFNEs of very high sensitivity and low noise.
CAL-101, a p110δ selective phosphatidylinositol-3-kinase inhibitor for the treatment of B-cell malignancies, inhibits PI3K signaling and cellular viability (2010)

Phosphatidylinositol-3-kinase p110δ serves as a central integration point for signaling from cell surface receptors known to promote malignant B-cell proliferation and survival. This provides a rationale for the development of small molecule inhibitors that selectively target p110δ as a treatment approach for patients with B-cell malignancies. We thus identified 5-fluoro-3-phenyl-2-[(S)-1-(9H-purin-6-ylamino)-propyl]-3H-quinazolin-4-one (CAL-101), a highly selective and potent p110δ small molecule inhibitor (half-maximal effective concentration [EC(50)] = 8nM). Using tumor cell lines and primary patient samples representing multiple B-cell malignancies, we have demonstrated that constitutive phosphatidylinositol-3-kinase pathway activation is p110δ-dependent. CAL-101 blocked constitutive phosphatidylinositol-3-kinase signaling, resulting in decreased phosphorylation of Akt and other downstream effectors, an increase in poly(ADP-ribose) polymerase and caspase cleavage and an induction of apoptosis. These effects have been observed across a broad range of immature and mature B-cell malignancies, thereby providing a rationale for the ongoing clinical evaluation of CAL-101.
The CGRP receptor antagonist BIBN4096BS peripherally alleviates inflammatory pain in rats (2013)

Calcitonin gene-related peptide (CGRP) is known to play a major role in the pathogenesis of pain syndromes, in particular migraine pain. Here we focus on its implication in a rat pain model of inflammation, induced by injection of complete Freund adjuvant (CFA). The nonpeptide CGRP receptor antagonist BIBN4096BS reduces migraine pain and trigeminal neuronal activity. Here we demonstrate that the compound reduces inflammatory pain and spinal neuronal activity. Behavioural experiments reveal a reversal of the CFA-induced mechanical hypersensitivity and monoiodoacetate (MIA)-induced weight-bearing deficit in rats after systemic drug administration. To further investigate the mechanism of action of the CGRP antagonist in inflammatory pain, in vivo electrophysiological studies were performed in CFA-injected rats. Recordings from wide dynamic range neurons in deep dorsal horn layers of the lumbar spinal cord confirmed a reduction of neuronal activity after systemic drug application. The same amount of reduction occurred after topical administration onto the paw, with resulting systemic plasma concentrations in the low nanomolar range. However, spinal administration of BIBN4096BS did not modify the neuronal activity in the CFA model. Peripheral blockade of CGRP receptors by BIBN4096BS significantly alleviates inflammatory pain.
Interleukin-1 Receptor Antagonist Gene Polymorphism and Coronary Artery Disease (1999)

IL-1RN*2 was significantly associated with SVD. A difference in genetic association between SVD and MVD was also apparent.
The Role of CXCR7/RDC1 as a Chemokine Receptor for CXCL12/SDF-1 in Prostate Cancer (2007)

Several reports have recently documented that CXCR7/RDC1 functions as a chemokine receptor for SDF-1/CXCL12, which regulates a spectrum of normal and pathological processes. In this study, the role of CXCR7/RDC1 in prostate cancer (PCa) was explored. Staining of high density tissue microarrays demonstrates that the levels of CXCR7/RDC1 expression increase as the tumors become more aggressive. In vitro and in vivo studies with PCa cell lines suggest that alterations in CXCR7/RDC1 expression are associated with enhanced adhesive and invasive activities in addition to a survival advantage. In addition, it was observed that CXCR7/RDC1 levels are regulated by CXCR4. Among the potential downstream targets of CXCR7/RDC1 are CD44 and cadherin-11, which are likely to contribute to the invasiveness of PCa cells. CXCR7/RDC1 also regulates the expression of the proangiogenic factors interleukin-8 or vascular endothelial growth factor, which are likely to participate in the regulation of tumor angiogenesis. Finally, we found that signaling by CXCR7/RDC1 activates AKT pathways. Together, these data demonstrate a role for CXCR7/RDC1 in PCa metastasis and progression and suggest potential targets for therapeutic intervention.
Commercialization of low temperature copper thermocompression bonding for 3D integrated circuits (2008)

Thesis (M. Eng.)--Massachusetts Institute of Technology, Dept. of Materials Science and Engineering, 2008.
Influence of Brown Midrib, Leafy, and Transgenic Hybrids on Corn Forage Production (2001)

Hybrid selection strongly influences corn ( Zea mays L.) forage production. Limited forage production and quality information exists for leafy and transgenic hybrids [ Bacillus thuringiensis (Bt) and herbicide resistant]. We compared dry matter (DM) yield, forage quality, and estimated milk yields of these and brown midrib hybrids with dual‐purpose hybrids for 3 yr at harvest densities of 66000 and 84000 plants ha −1 . Transgenic hybrids had no effect on DM and milk yields, so we do not recommend Bt hybrids under conditions of low infestation of European corn borer ( Ostrinia nubilalis Hubner). Leafy hybrids had similar DM and milk yields as hybrids of similar maturity. Brown midrib hybrids, which had DM yields that were about 20% less than those of hybrids of similar maturity, had 40 to 80 g kg −1 greater in vitro true digestibility (IVTD) and 70 to 200 g kg −1 greater neutral detergent fiber (NDF) digestibility. Brown midrib hybrids had the greatest or least milk yields among hybrids, depending on hybrid and year. Leafy and brown midrib hybrids mostly had low harvest index (HI) values, which had strong negative correlations with NDF in all years (−0.71, −0.44, and −0.90). Brown midrib hybrids had high NDF digestibility, which had strong positive correlations with IVTD (0.80, 0.88, and 0.86). Currently, we do not recommend brown midrib hybrids because of inconsistent milk yields and high seed costs. Development of brown midrib and leafy hybrids with greater HI values should result in excellent forage hybrids.
Two- to 9-Year Outcome After Autologous Chondrocyte Transplantation of the Knee (2000)

Autologous cultured chondrocyte transplantation was introduced in Sweden in 1987 for the treatment of large (1.5-12.0 cm2) full thickness chondral defects of the knee. The clinical, arthroscopic, and histologic results from the first 101 patients treated using this technique are reported in this study. Patients were assessed retrospectively using three types of endpoints: patient and physician derived clinical rating scales (five validated and two new); arthroscopic assessment of cartilage fill, integration, and surface hardness; and standard histochemical techniques. Ninety-four patients with 2- to 9-years followup were evaluable. Good to excellent clinical results were seen in individual groups as follows: isolated femoral condyle (92%), multiple lesions (67%), osteochondritis dissecans (89%), patella (65%), and femoral condyle with anterior cruciate ligament repair (75%). Arthroscopic findings in 53 evaluated patients showed good repair tissue fill, good adherence to underlying bone, seamless integration with adjacent cartilage, and hardness close to that of the adjacent tissue. Hypertrophic response of the periosteum or graft or both was identified in 26 arthroscopies; seven were symptomatic and resolved after arthroscopic trimming. Graft failure occurred in seven (four of the first 23 and three of the next 78) patients. Histologic analysis of 37 biopsy specimens showed a correlation between hyalinelike tissue (hyaline matrix staining positive for Type II collagen and lacking a fibrous component) and good to excellent clinical results. The good clinical outcomes of autologous chondrocyte transplantation in this study are encouraging, and clinical trials are being done to assess the outcomes versus traditional fibrocartilage repair techniques.
A Phase I Pharmacologic Study of Necitumumab (IMC-11F8), a Fully Human IgG1 Monoclonal Antibody Directed Against EGFR in Patients with Advanced Solid Malignancies (2010)

Well tolerated, necitumumab is associated with preliminary evidence of antitumor activity, and achieves biologically relevant concentrations throughout the dosing period. The recommended dose of necitumumab for further clinical development is 800 mg (flat dose) weekly or every 2 weeks based on the clinical setting.