gebhart/patrepeval huggingface dataset:
Emerging novel therapies for advanced prostate cancer (2011)

This review examines the development and efficacy of novel treatment options for advanced prostate cancer and discusses novel therapies that are on the horizon. Since the introduction of docetaxel as the standard treatment for patients with metastatic castration-resistant prostate cancer (CRPC), a number of different agents have been tested but failed to demonstrate improvement in overall survival (OS). Recently, three novel compounds have demonstrated OS benefit and one other showed reduction in skeletal-related events (SREs). Sipuleucel-T, a novel vaccine, was approved by the US regulatory authorities in April 2010 for patients with early advanced prostate cancer. A new taxane, cabazitaxel, and abiraterone acetate, an androgen biosynthesis inhibitor, have shown an OS benefit in advanced CRPC after docetaxel, leading to drug approval. A new bone-targeting agent, denosumab, a receptor activator of nuclear factor κB ligand (RANKL) antagonist, showed a modest reduction in SREs in comparison to zoledronic acid in patients with bone metastases. Other promising novel agents are currently being tested in the clinical setting of advanced CRPC. These include, androgen receptor inhibitors (MDV3100), androgen biosynthesis inhibitors, angiogenesis inhibitors (thalidomide, lenalidomine, aflibercept, tasquinimod), a novel form of radiotherapy (radium-223), and immune-modulating compounds (PROSTVAC-VF). Improvements in progression-free survival and OS rates, observed with novel agents, in metastatic prostate cancer have led to a shift in treatment paradigm. The challenge will be to position the current established and expected novel treatments in the new landscape of metastatic prostate cancer and to determine at what point and time in the disease course they can best be administered.
Improving the Performance of Lithium–Sulfur Batteries by Conductive Polymer Coating (2011)

Rechargeable lithium–sulfur (Li–S) batteries hold great potential for next-generation high-performance energy storage systems because of their high theoretical specific energy, low materials cost, and environmental safety. One of the major obstacles for its commercialization is the rapid capacity fading due to polysulfide dissolution and uncontrolled redeposition. Various porous carbon structures have been used to improve the performance of Li–S batteries, as polysulfides could be trapped inside the carbon matrix. However, polysulfides still diffuse out for a prolonged time if there is no effective capping layer surrounding the carbon/sulfur particles. Here we explore the application of conducting polymer to minimize the diffusion of polysulfides out of the mesoporous carbon matrix by coating poly(3,4-ethylenedioxythiophene)-poly(styrene sulfonate) (PEDOT:PSS) onto mesoporous carbon/sulfur particles. After surface coating, coulomb efficiency of the sulfur electrode was improved from 93% to 97%, and capacity decay was reduced from 40%/100 cycles to 15%/100 cycles. Moreover, the discharge capacity with the polymer coating was ∼10% higher than the bare counterpart, with an initial discharge capacity of 1140 mAh/g and a stable discharge capacity of >600 mAh/g after 150 cycles at C/5 rate. We believe that this conductive polymer coating method represents an exciting direction for enhancing the device performance of Li–S batteries and can be applicable to other electrode materials in lithium ion batteries.
Colitis induced in mice with dextran sulfate sodium (DSS) is mediated by the NLRP3 inflammasome (2010)

Background The proinflammatory cytokines interleukin 1β (IL-1β) and IL-18 are central players in the pathogenesis of inflammatory bowel disease (IBD). In response to a variety of microbial components and crystalline substances, both cytokines are processed via the caspase-1-activating multiprotein complex, the NLRP3 inflammasome. Here, the role of the NLRP3 inflammasome in experimental colitis induced by dextran sodium sulfate (DSS) was examined. Methods IL-1β production in response to DSS was studied in macrophages of wild-type, caspase-1 −/− , NLRP3 −/− , ASC −/− , cathepsin B −/− or cathepsin L −/− mice. Colitis was induced in C57BL/6 and NLRP3 −/− mice by oral DSS administration. A clinical disease activity score was evaluated daily. Histological colitis severity and expression of cytokines were determined in colonic tissue. Results Macrophages incubated with DSS in vitro secreted high levels of IL-1β in a caspase-1-dependent manner. IL-1β secretion was abrogated in macrophages lacking NLRP3, ASC or caspase-1, indicating that DSS activates caspase-1 via the NLRP3 inflammasome. Moreover, IL-1β secretion was dependent on phagocytosis, lysosomal maturation, cathepsin B and L, and reactive oxygen species (ROS). After oral administration of DSS, NLRP3 −/− mice developed a less severe colitis than wild-type mice and produced lower levels of proinflammatory cytokines in colonic tissue. Pharmacological inhibition of caspase-1 with pralnacasan achieved a level of mucosal protection comparable with NLRP3 deficiency. Conclusions The NLRP3 inflammasome was identified as a critical mechanism of intestinal inflammation in the DSS colitis model. The NLRP3 inflammasome may serve as a potential target for the development of novel therapeutics for patients with IBD.
Isolation and Characterization of jararaca GPIb-BP, a Snake Venom Antagonist Specific to Platelet Glycoprotein lb (1995)

Summary A platelet glycoprotein lb-binding protein (GPIb-BP) was isolated from the snake venom of Bothrops jararaca. Jararaca GPIb-BP showed a single band with Mr of 30,000, and two distinct bands with Mr. of 17,000/13,000 under non-reducing and reducing conditions, respectively, on SDS-polyacrylamide gel electrophoresis. Jararaca GPIb-BP itself induced neither platelet aggregation nor serotonin release from platelets, but specifically bound to GPIb (40,629 ± 2,521 molecules per normal platelet, with Kd 39.1 ± 2.4 nM at saturation). The purified venom protein completely inhibited ristocetin- or botrocetin-induccd von Willebrand factor (vWF) binding, and blocked the bovine vWF binding to GPIb, with IC50 values ranging from 28 to 42 nM, without affecting the platelet aggregation induced by ADP or α-thrombin. 1251-jararaca GPIb-BP binding to GPIb was not altered by the presence of human α-thrombin. Jararaca GPIb-BP at a final concentration of 104 nM totally abolished vWF-dependent shear- induced platelet aggregation (SIPA) at a high shear stress, but had no effect on SIPA at a low shear stress. Reduced and S-carboxyamidomethylated jararaca GPIb-BP lost its inhibitory activity on SIPA. The NH2-terminal amino acid sequences of the subunits revealed a high degree of homology with those of several Ca2+-dependent lectins, especially to those of two functionally opposite venom proteins, botrocetin (a vWF-modulator) and alboaggregin-B (a GPIb- modulator).
A new ETV6/TEL partner gene, ARG (ABL-related gene or ABL2), identified in an AML-M3 cell line with a t(1;12)(q25;p13) translocation. (2000)

The ETV6/TEL gene has been reported to fuse to PDGFRbetab MDS1/EVI1, BTL, ACS2, STL, JAK2, ABL, CDX2, TRKC, AML1, and MN1. Among them, PDGFRbeta, ABL, JAK2, and TRKC are tyrosine kinases (TK). We identified a novel ETV6 partner gene, ARG (ABL-related gene or ABL2), another TK gene in a cell line established from a patient with acute myelogenous leukemia (AML-M3) with a t(15;17)(q22;q11.2) and a t(1;12)(q25;p13), which has the remarkable feature to differentiate to mature eosinophils in culture with all-trans retinoic acid and cytokines. The ETV6/ARG transcripts consisted of exon 1 to 5 of ETV6 and the 3' portion of ARG starting from exon 1B or exon 2, resulting in an open reading frame for a fusion protein consisting of the entire PNT oligomerization domain of ETV6 and all of the functional domains of ARG including the TK domain. This is the same protein structure as identified in the other ETV6 TK fusion proteins. The reciprocal ARG/ETV6 transcript was not expressed, and the normal ETV6 allele was not deleted or rearranged. Although the ABL is known to be involved in various human malignancies, ARG has not been involved in human malignancies despite its high homology to ABL. Thus, this is the first report showing involvement of ARG in human leukemia. The ETV6/ARG protein may be involved in the unique differentiation capacity of this cell line. (Blood. 2000;95:2126-2131)
Out-of-Band Radiation Comparison of GFDM, WCP-COQAM and OFDM at Equal\n Spectral Efficiency (2015)

GFDM and WCP-COQAM are amongst the candidate physical layer modulation\nformats to be used in 5G, whose claimed lower out-of-band (OOB) emissions are\nimportant with respect to cognitive radio based dynamic spectrum access\nsolutions. In this study, we compare OFDM, GFDM and WCP-COQAM in terms of OOB\nemissions in a fair manner such that their spectral efficiencies are the same\nand OOB emission reduction techniques are applied to all of the modulation\ntypes. Analytical PSD expressions are also correlated with the simulation based\nOOB emission results. Maintaining the same spectral efficiency, carrier\nfrequency offset immunities will also be compared.\n
Epicoccum nigrum P16, a Sugarcane Endophyte, Produces Antifungal Compounds and Induces Root Growth (2012)

Our work demonstrates that E. nigrum has great potential for sugarcane crop application because it is capable of increasing the root system biomass and controlling pathogens. The study of the basic aspects of the interaction of E. nigrum with sugarcane demonstrated the facultative endophytism of E. nigrum and its preference for the phylloplane environment, which should be considered in future studies of biocontrol using this species. In addition, this work contributes to the knowledge of the interaction of this ubiquitous endophyte with the host plant, and also to a better use of microbial endophytes in agriculture.
Non-Photorealistic Rendering (2001)

The ubiquity of computer-generated imagery around us, in movies, advertising or on the Internet is already being taken for granted and what impresses most people is the photorealistic quality of the images. Pictures, as we have often been told, are worth a thousand words and the information transported by an image can take many different forms. Man
Proteomics: A New Diagnostic Frontier (2006)

Advances in proteomics offer great promise for the discovery of markers that might serve as the basis for new clinical laboratory tests. There are many challenges, however, in the translation of newly discovered markers into clinical laboratory tests.
Pathology of Infertility (1993)

Focusing on the aetiology, morphology and epidemiology of lesions that interfere with the normal human reproductive process, this book covers the pathologic basis of infertility - malformations, diseases of the embryo, abnormalities of implantation and the support system of the developing embryo.
Fully decentralized AC optimal power flow algorithms (2013)

Motivated by the increasing complexity in the control of distribution level electric power systems especially in a smart grid environment, we propose fully decentralized algorithms to solve alternating current (AC) optimal power flow (OPF) problems. The key feature of the proposed algorithms is a complete decentralization of computation down to nodal level. In this way, no central or sub-area controller is needed, and the OPF problem is solved by individual nodes, which only have local knowledge of the system. Preliminary results show promising performance of the fully decentralized algorithms.
Measurement of a rugulosin-producing endophyte in white spruce seedlings (2005)

Previous studies conducted in growth chambers had demonstrated the successful experimental inoculation of white spruce seedlings with anti-insectan toxin producing needle endophytes. Needles colonized with the rugulosin-producing endophyte 5WS22E1 (DAOM 229536) contained rugulosin in concentrations that impaired spruce bud-worm growth. Here we report experimental inoculations conducted under nursery conditions. To improve the reliability of detecting successful colonization, a polyclonal assay was developed for the target endophyte 5WS22E1. It was able to reliably detect the fungus in 500 ng subsamples of colonized needles. Seventeen months post-inoculation, 330 seedlings from 1235 inoculated were colonized. A random selection of 113 colonized seedlings was analyzed for rugulosin. Needles of most (90%) contained detectable concentrations of rugulosin. The range and distribution of the rugulosin concentrations was similar to that found in earlier tests done in growth chambers.
EAE: An immunologist's magic eye (2009)

EAE comes in many shapes and colors. Individual variants of EAE present a baffling complexity of different aspects and traits, clinical, immunological, and structural. But, embedded in this seemingly chaotic image, the educated eye will discern patterns that retrace fundamental features of immune response, in particular, autoimmunity and self-tolerance. EAE and its variants thus can be likened to an autostereogram, i.e. they are an immunologist's magic eye.
Performance evaluation of amino acid substitution matrices (1993)

Several choices of amino acid substitution matrices are currently available for searching and alignment applications. These choices were evaluated using the BLAST searching program, which is extremely sensitive to differences among matrices, and the Prosite catalog, which lists members of hundreds of protein families. Matrices derived directly from either sequence-based or structure-based alignments of distantly related proteins performed much better overall than extrapolated matrices based on the Dayhoff evolutionary model. Similar results were obtained with the FASTA searching program. Improved performance appears to be general rather than family-specific, reflecting improved accuracy in scoring alignments. An implementation of a multiple matrix strategy was also tested. While no combination of three matrices performed as well as the single best matrix, BLOSUM 62, good results were obtained using a combination of sequence-based and structure-based matrices. This hybrid set of matrices is likely to be useful in certain situations. Our results illustrate the importance of matrix selection and the value of a comprehensive approach to evaluation of protein comparison tools.
High-affinity binding of an influenza hemagglutinin-derived peptide to purified HLA-DR. (1990)

Immunogenic peptides have been shown to bind detergent-solubilized class II (Ia) molecules from mice. In this investigation, we report that highly purified HLA-DR (DR) molecules in detergent solution are capable of binding a synthetic peptide (HAp) derived from the influenza hemagglutinin sequence. Although the presentation of this peptide has been demonstrated only to DR1-restricted Th cells, the association rate constants for the formation of HAp-DR1, -DR5, and -DR8 complexes were essentially identical (ka = 1.1 x 10(2) to 1.6 x 10(2) M-1 s-1). By contrast, the value of the rate constants for the dissociation of preformed HAp-DR1, -DR5, and -DR8 complexes varied nearly threefold (kd = 1.6 x 10(6) to 4.4 x 10(-6) s-1). The value of the equilibrium dissociation constants (KD) derived from these rate constants were 13 nM, 24 nM, and 28 nM, for HAp-DR1, -DR5, and -DR8 complexes, respectively. Scatchard analysis demonstrated that the KD obtained from the rate constants for the HAp-DR1 reaction was in excellent agreement with that obtained under equilibrium conditions. SDS-PAGE confirmed that the HAp-DR complexes were remarkably stable, as HAp remained associated with the DR alpha beta heterodimer after treatment of the complexes with SDS and beta-mercaptoethanol. Steady-state binding studies demonstrated that 18% of all DR1 molecules had bound HAp at equilibrium, whereas only 3.8% of all DR8 molecules had bound HAp under identical conditions. The slight differences in the KD for HAp-DR complexes suggest that differences in the affinity of a peptide for DR alleles alone may not always explain the process of MHC restriction.
Preliminary evaluation of porous metal surfaced titanium for orthopedic implants (1970)

Abstract Recent results indicate varying degrees of bone ingrowth into porous metal and ceramic bodies. Such homogeneously porous ceramic and metal implants generally possess inadequate mechanical properties, limiting their application to low stress or nonstructural applications. An experiment was performed wherein titanium porous coatings were applied to a wrought titanium bone implant. These surfaces were achieved by plasma spraying of titanium hydride powder, depositing a mixture of wellbonded titanium‐titanium oxide with pore diameters varying from .002 to .005 in. Implant specimens were placed in sheep femora for periods of 14 and 26 weeks. No adverse affects were noted. Interface shear strengths were determined by torque tests which indicated approximately a twenty‐fold increase over similar tests performed on uncoated control specimens.
Purification and characterization of thermostable beta-mannanase and alpha-galactosidase from Bacillus stearothermophilus (1990)

Bacillus stearothermophilus secretes beta-mannanase and alpha-galactosidase enzymatic activities capable of hydrolyzing galactomannan substrates. Expression of the hemicellulase activities in the presence of locust bean gum was sequential, with mannanase activity preceding expression of alpha-galactosidase activity. The hemicellulase activities were purified to homogeneity by a combination of ammonium sulfate fractionation, gel filtration, hydrophobic interaction chromatography, and ion-exchange and chromatofocusing techniques. The purified beta-D-mannanase is a dimeric enzyme (162 kilodaltons) composed of subunits having identical molecular weight (73,000). Maximal activity did not vary between pH 5.5 and 7.5. The beta-D-mannanase activity exhibited thermostability, retaining nearly full activity after incubation for 24 h at 70 degrees C and pH 6.5. The enzyme displayed high specificity for galactomannan substrates, with no-secondary xylanase or cellulase activity detected. Hydrolysis of locust bean gum yielded short oligosaccharides compatible with an endo mode of substrate depolymerization. Initial rate velocities of the mannanase activity displayed substrate inhibition and yielded estimates for Vmax and Km of 455 +/- 60 U/mg and 1.5 +/- 0.3 mg/ml, respectively, at 70 degrees C and pH 6.5. The alpha-galactosidase activity corresponded to a trimeric enzyme (247 kilodaltons) having subunits of identical molecular weight (82,000). The alpha-galactosidase had maximal activity at pH 7 to 7.5 and retained full activity after 24 h of incubation at 60 degrees C. The enzyme had only limited activity on galactomannan substrates as compared with hydrolysis of p-nitrophenyl alpha-D-galactose. Kinetics of p-nitrophenyl alpha-D-galactose hydrolysis yielded linear reciprocal plots corresponding to Vmax and Km of 195 +/- 10 U/mg and 0.25 +/- 0.02 mM, respectively, at 60 degrees C and pH 7. The characterization of the mannanase activity is consistent with its potential use in enzymatic bleaching of softwood pulps.
Selection of the simplest RNA that binds isoleucine (2003)

We have identified the simplest RNA binding site for isoleucine using selection-amplification (SELEX), by shrinking the size of the randomized region until affinity selection is extinguished. Such a protocol can be useful because selection does not necessarily make the simplest active motif most prominent, as is often assumed. We find an isoleucine binding site that behaves exactly as predicted for the site that requires fewest nucleotides. This UAUU motif (16 highly conserved positions; 27 total), is also the most abundant site in successful selections on short random tracts. The UAUU site, now isolated independently at least 63 times, is a small asymmetric internal loop. Conserved loop sequences include isoleucine codon and anticodon triplets, whose nucleotides are required for amino acid binding. This reproducible association between isoleucine and its coding sequences supports the idea that the genetic code is, at least in part, a stereochemical residue of the most easily isolated RNA-amino acid binding structures.
The PML/RAR alpha oncoprotein is a direct molecular target of retinoic acid in acute promyelocytic leukemia cells (1996)

Acute promyelocytic leukemia (APL) is characterized by the translocation, t(15;17) and the expression of a PML/RAR alpha fusion protein that is diagnostic of the disease. There is evidence that PML/RAR alpha protein acts as a dominant negative inhibitor of normal retinoid receptor function and myeloid differentiation. We now show that the PML/RAR alpha fusion product is directly downregulated in response to retinoic acid (tRA) treatment in the human APL cell line, NB4. tRA treatment induces loss of PML/RAR alpha at the protein level but not at the level of mRNA, as determined by Northern blots, by Western blots, and by ligand binding assays and in binding to RA-responsive DNA elements. We present evidence that this regulation is posttranslational. This evidence suggests that tRA induces synthesis of a protein that selectively degrades PML/RAR alpha. We further show that this loss of PML/ RAR-alpha is not limited to the unique APL cell line. NB4, because PML/RAR alpha protein is selectively downregulated by tRA when expressed in the transfected myeloid cell line U937. The loss of PML/RAR alpha may be directly linked to tRA-induced differentiation, because in a retinoid-resistant subclone of NB4, tRA does not decrease PML/RAR alpha protein expression. In NB4 cells, the specific downregulation of the fusion protein decreases the ratio of PML/RAR alpha to wild-type RAR alpha. Because the ratio of expression of PML/RAR alpha to wild-type RAR alpha and PML may be important in maintaining the dominant negative block of myelocytic differentiation, these data suggest a molecular mechanism for restoration by tRA normal myeloid differentiation in APL cells.
-Sarcoglycan compensates for lack of -sarcoglycan in a mouse model of limb-girdle muscular dystrophy (2005)

Dystrophin and the dystrophin-associated protein (DAP) complex protect the sarcolemma against contraction-induced injury and serve as a mechanical link between the extracellular matrix and the actin cytoskeleton. Some of the functional properties of the DAP complex are mediated by its sarcoglycan (SG) subcomplex, which is composed of alpha-, beta-, gamma- and delta-SGs. Autosomal recessive limb-girdle muscular dystrophy type-2D (LGMD 2D) results from reduction in SG subcomplex levels caused by specific mutations in the muscle-specific alpha-SG gene. epsilon-SG is a widely expressed homolog of the muscle-specific alpha-SG, and expression of epsilon-SG may compensate for the pathologic changes in alpha-SG function. Thus, the goal of the present study was to investigate whether overexpression of epsilon-SG can compensate for dysfunction of alpha-SG. Several transgenic mouse lines that overexpress epsilon-SG in skeletal muscle were established. Overexpression of epsilon-SG in normal mice resulted in substitution of epsilon-SG for alpha-SG in the SG complex of skeletal muscle without any obvious abnormalities. To determine whether an increase in epsilon-SG expression may prevent muscular dystrophy in the context of alpha-SG-deficiency, these epsilon-SG transgenic mice were crossed with alpha-SG deficient mice. alpha-SG-deficient mice overexpressing epsilon-SG exhibited no skeletal muscle cell membrane damage or abnormal contraction. These data suggest that the overexpression of epsilon-SG may represent a therapeutic strategy for treatment of LGMD 2D.