gebhart/patrepeval huggingface dataset:
BAY 1024767 blocks androgen receptor mutants found in castration-resistant prostate cancer patients (2016)

Androgen receptor (AR) mutations arise in patients developing resistance to hormone deprivation therapies. Here we describe BAY 1024767, a thiohydantoin derivative with strong antagonistic activity against nine AR variants with mutations located in the AR ligand-binding domain (LBD), and against wild-type AR. Antagonism was maintained, though reduced, at increased androgen levels. Anti-tumor efficacy was evidenced in vivo in the KuCaP-1 prostate cancer model which bears the W741C bicalutamide resistance mutation and in the syngeneic prostate cancer rat model Dunning R3327-G. The prevalence of six selected AR mutations was determined in plasma DNA originating from 100 resistant patients and found to be at least 12%. Altogether the results show BAY 1024767 to be a strong antagonist for several AR mutants linked to therapy resistance, which opens the door for next-generation compounds that can benefit patients based on their mutation profile.
High-performance GRID Database Manager for Scientific Data (2002)

The GRID initiative provides an infrastructure for distributed computations among widely distributed high-performance computers. This will allow for exchanging and processing very large amounts of data. The LOFAR project (www.nfra.nl/lofar) is an international initiative to build a versatile, geographically distributed, multi-point radio facility for astrophysics, space physics, atmospheric physics, and radio research, utilizing very high performance GRID computing. LOIS is a proposed Swedish outrigger to LOFAR providing a software radar. As the volume of processed data by LOFAR/LOIS is very large and dynamic there will be need for very high performing data management systems. For this a high-performance stream-oriented distributed data manager and query processor is being developed that allows very efficient execution of database queries to streamed data involving numerical and other data. Very high performance is attained by utilizing many object-relational main-memory database engines running on PCs and connected through the GRID. The project leverages upon a highperformance, extensible, and object-oriented database engine, the Amos II kernel, developed in the Uppsala Database Laboratory. A very high performing stream-oriented DBMS is being developed for representing and querying non-relational data representations extracted from the data flows used in space and environmental physics applications. Of particular interest is the development of new distributed data population and query processing techniques for this kind of applications and thereby utilizing distributed and scalable data structures for high-performance stream data processing.
Short-Term Therapy With Peroxisome Proliferation-Activator Receptor-α Agonist Wy-14,643 Protects Murine Fatty Liver Against Ischemia–Reperfusion Injury (2009)

NASH and SS livers are both more susceptible to IRI. Mechanisms include possible distortion of the microvasculature by swollen fat-laden hepatocytes, and enhanced production of several cytokines. The beneficial effects of Wy-14,643 may be exerted by dampening adhesion molecule and cytokine responses, and activating NF-kappaB, IL-6 production, and p38 kinase to effect cell cycle entry.
Use of absolute lymphocyte counts to predict response to chemotherapy and survival in diffuse large B-cell lymphoma (2007)

8082 Background: Absolute lymphocyte counts (ALCs) at diagnosis has been shown to be an independent prognostic factor in patients with follicular lymphoma (FL) although the precise mechanism was not fully elucidated. The current study evaluated the impact of Absolute lymphocyte counts (ALCs) at diagnosis in patients with diffuse large B-cell lymphoma (DLBCL) on the response to chemotherapy and survival. Methods: The treatment outcomes of the patients receiving CHOP (n=101) or R-CHOP chemotherapy (n=122) were compared according to ALCs at diagnosis (&lt;1.0 vs. = 1.0×10 9 /L). Results: Forty-two patients (19%) had a lower ALC count at diagnosis (CHOP, 23 [23%]; R-CHOP, 19 [16%]). The lower ALCs showed a good correlation with IPI (p&lt;0.001), performance (p&lt;0.001), LDH (p&lt;0.001), stage (p=0.004), extranodal involvement (p=0.011), but not with age or sex. A significant difference of response rate was noted according to ALCs in favor of a higher ALCs (CR: 80% vs. 60%, p=0.005; ORR: 93% vs. 78%, p=0.003). In addition, event-free survival (EFS) was worse in a lower ALC group than higher ALC group: median duration of EFS, 1,773 days vs. 326 days (p&lt;0.001). The OS was also in favor of a higher ALC group: median duration of OS, 3,000 days vs. 695 days (p&lt;0.001). In multivariate analysis, ALC at diagnosis was an independent predictive factor for CR (HR 2.717, p=0.009) and prognostic factor for EFS (HR 2.148, p=0.004) or OS (HR 2.863, p=0.002). Conclusion: The ALCs at diagnosis appears to predict the survival of DLBCL patients. Our findings suggested that the ALCs at diagnosis may reflect host's immune status against DLBCL, implying that immune system of host will play a critical role on survival of DLBCL patients. No significant financial relationships to disclose.
Standards for epidemiologic studies and surveillance of epilepsy (2011)

Worldwide, about 65 million people are estimated to have epilepsy. Epidemiologic studies are necessary to define the full public health burden of epilepsy; to set public health and health care priorities; to provide information needed for prevention, early detection, and treatment; to identify education and service needs; and to promote effective health care and support programs for people with epilepsy. However, different definitions and epidemiologic methods complicate the tasks of these studies and their interpretations and comparisons. The purpose of this document is to promote consistency in definitions and methods in an effort to enhance future population-based epidemiologic studies, facilitate comparison between populations, and encourage the collection of data useful for the promotion of public health. We discuss: (1) conceptual and operational definitions of epilepsy, (2) data resources and recommended data elements, and (3) methods and analyses appropriate for epidemiologic studies or the surveillance of epilepsy. Variations in these are considered, taking into account differing resource availability and needs among countries and differing purposes among studies.
Recent advances in plastic packaging of flip-chip and multichip modules (MCM) of microelectronics (1999)

The success in consumer electronics in the 1990's will be focused on low-cost and high performance electronics. Recent advances in polymeric materials (plastics) and integrated circuit (IC) encapsulants have made high-reliability very-large-scale integration (VLSI) plastic packaging a reality. High-performance polymeric materials possess excellent electrical and physical properties for IC protection. With their intrinsic low modulus and soft gel-like nature, silicone gels have become very effective encapsulants for larger, high input/output (I/O) (in excess of 10 000), wire-bonded and flip-chip VLSI chips. Furthermore, the recently developed silica-filled epoxies underfills, with the well controlled thermal coefficient of expansion (TCE), have enhanced the flip-chip and chip-on-board, direct chip attach (DCA) encapsulations. Recent studies indicate that adequate IC chip surface protection with high-performance silicone gels and epoxies plastic packages could replace conventional ceramic hermetic packages. This paper will review the IC technological trends, and IC encapsulation materials and processes. Special focus will be placed on the high-performance silicone and epoxy underfills, their chemistries and use as VLSI device encapsulants for single and multichip module applications.
Controls of Nucleosome Positioning in the Human Genome (2012)

Nucleosomes are important for gene regulation because their arrangement on the genome can control which proteins bind to DNA. Currently, few human nucleosomes are thought to be consistently positioned across cells; however, this has been difficult to assess due to the limited resolution of existing data. We performed paired-end sequencing of micrococcal nuclease-digested chromatin (MNase-seq) from seven lymphoblastoid cell lines and mapped over 3.6 billion MNase-seq fragments to the human genome to create the highest-resolution map of nucleosome occupancy to date in a human cell type. In contrast to previous results, we find that most nucleosomes have more consistent positioning than expected by chance and a substantial fraction (8.7%) of nucleosomes have moderate to strong positioning. In aggregate, nucleosome sequences have 10 bp periodic patterns in dinucleotide frequency and DNase I sensitivity; and, across cells, nucleosomes frequently have translational offsets that are multiples of 10 bp. We estimate that almost half of the genome contains regularly spaced arrays of nucleosomes, which are enriched in active chromatin domains. Single nucleotide polymorphisms that reduce DNase I sensitivity can disrupt the phasing of nucleosome arrays, which indicates that they often result from positioning against a barrier formed by other proteins. However, nucleosome arrays can also be created by DNA sequence alone. The most striking example is an array of over 400 nucleosomes on chromosome 12 that is created by tandem repetition of sequences with strong positioning properties. In summary, a large fraction of nucleosomes are consistently positioned--in some regions because they adopt favored sequence positions, and in other regions because they are forced into specific arrangements by chromatin remodeling or DNA binding proteins.
Repeated intrathecal injections of plasmid DNA encoding interleukin-10 produce prolonged reversal of neuropathic pain (2006)

Neuropathic pain is a major clinical problem unresolved by available therapeutics. Spinal cord glia play a pivotal role in neuropathic pain, via the release of proinflammatory cytokines. Anti-inflammatory cytokines, like interleukin-10 (IL-10), suppress proinflammatory cytokines. Thus, IL-10 may provide a means for controlling glial amplification of pain. We recently documented that intrathecal IL-10 protein resolves neuropathic pain, albeit briefly (approximately 2-3 h), given its short half-life. Intrathecal gene therapy using viruses encoding IL-10 can also resolve neuropathic pain, but for only approximately 2 weeks. Here, we report a novel approach that dramatically increases the efficacy of intrathecal IL-10 gene therapy. Repeated intrathecal delivery of plasmid DNA vectors encoding IL-10 (pDNA-IL-10) abolished neuropathic pain for greater than 40 days. Naked pDNA-IL-10 reversed chronic constriction injury (CCI)-induced allodynia both shortly after nerve injury as well as 2 months later. This supports that spinal proinflammatory cytokines are important in both the initiation and maintenance of neuropathic pain. Importantly, pDNA-IL-10 gene therapy reversed mechanical allodynia induced by CCI, returning rats to normal pain responsiveness, without additional analgesia. Together, these data suggest that intrathecal IL-10 gene therapy may provide a novel approach for prolonged clinical pain control.
Development of a bovine stroma-free hemoglobin solution as a blood substitute. (1983)

A glutaraldehyde-polymerized or "stabilized" B-SFHS has been developed and tested in rabbits. This solution has been found to be nontoxic in terms of animal survival, nonantigenic when administered in single large volume infusions and capable of remaining in the circulation for a prolonged period of time while retaining the ability to transport and offload oxygen. Additionally, replacement of up to two-thirds of the blood volume with SB-SFHS was found to be advantageous over replacement with plasma protein fraction in terms of survival. By virtue of its unlimited supply, this bovine hemoglobin solution represents a new option for a "blood substitute."
Glucose and Gluconate Metabolism in an Escherichia coli Mutant Lacking Phosphoglucose Isomerase (1967)

A single gene mutant lacking phosphoglucose isomerase (pgi) was selected after ethyl methane sulfonate mutagenesis of Escherichia coli strain K-10. Enzyme assays revealed no pgi activity in the mutant, whereas levels of glucokinase, glucose-6-phosphate dehydrogenase, and gluconate-6-phosphate dehydrogenase were similar in parent and mutant. The amount of glucose released by acid hydrolysis of the mutant cells after growth on gluconate was less than 2% that released from parent cells; when grown in the presence of glucose, mutant and parent cells contained the same amount of glucose residues. The mutant grew on glucose one-third as fast as the parent; it also grew much slower than the parent on galactose, maltose, and lactose. On fructose, gluconate, and other carbon sources, growth was almost normal. In both parent and mutant, gluconokinase and gluconate-6-phosphate dehydrase were present during growth on gluconate but not during growth on glucose. Assay and degradation of alanine from protein hydrolysates after growth on glucose-1-(14)C and gluconate-1-(14)C showed that in the parent strain glucose was metabolized by the glycolytic path and the hexose monophosphate shunt. Gluconate was metabolized by the Entner-Doudoroff path and the hexose monophosphate shunt. The mutant used glucose chiefly by the shunt, but may also have used the Entner-Doudoroff path to a limited extent.
The interaction between the catalytic A subunit of calcineurin and its autoinhibitory domain, in the yeast two‐hybrid system, is disrupted by cyclosporin A and FK506 (1995)

The Ca(2+)-calmodulin dependent protein phosphatase, calcineurin, is thought to mediate the action of the two immunosuppressants, cyclosporin A (CsA) and FK506. Calcineurin from all species consists of a catalytic A subunit and a regulatory peptide B, which plays an essential role in catalysis. The enzymatic function is probably also regulated by an autoinhibitory domain (AID) present in the catalytic subunit. We have used the yeast two-hybrid system to show that the putative AID of the yeast catalytic subunit Cna1 binds only to truncated Cna1, devoid of AID. Although deletion of the genes encoding the yeast catalytic subunits of calcineurin (CNA1 and CNA2) maintain the interaction, absence of the regulatory subunit Cnb1 prevents binding. Interestingly, both CsA and FK506 disrupt this interaction, whereas binding of Cna1 to calmodulin remains unaffected. This indicates that a simple cellular system, developed in yeast, could provide further insight into an understanding of calcineurin inhibition.
Anti- and Prooxidant Properties of Carotenoids (1999)

Carotenoids can be effective singlet oxygen quenchers and inhibit free-radical induced lipid peroxidation. A remarkable property of β-carotene (1a) is the change from an antioxidant to a prooxidant depending on oxygen pressure and concentration. In the present study a considerable number of carotenoids (1a, 2c, 2d, 2e, 3a, 4a, 5a, 6a, 7a, 8a, 8h, 8i, 8j, 9f, 10a, 11a, 12g) was investigated using two independent approaches: 1. Comparison of their effects on inhibition of the free-radical oxidation of methyl linoleate, and 2. The direct study of the effect of oxygen partial pressure upon their rates of oxidation. It is shown that some carotenoids (7a, 8a) are even more effective than the well-known compounds β-carotene (1a) and astaxanthin (5a) and are powerful antioxidants without any prooxidative property. Different carotenoids display different behaviour depending on chain length and end groups. The influence of these functional groups on the antioxidative reactivity is discussed.
Rare germinal unequal crossing-over leading to recombinant gene formation and gene duplication in Arabidopsis thaliana (1999)

Small, multigene families organized in a tandem array can facilitate the rapid evolution of the gene cluster by a process of meiotic unequal crossing-over. To study this process in a multicellular organism, we created a synthetic RBCSB gene cluster in Arabidopsis thaliana and used this to measure directly the frequency of meiotic, intergenic unequal crossing-over between sister chromatids. The synthetic RBCSB gene cluster was composed of a silent DeltaRBCS1B::LUC chimeric gene fusion, lacking all 5' transcription and translation signals, followed by RBCS2B and RBC3B genomic DNA. Expression of luciferase activity (luc(+)) required a homologous recombination event between the DeltaRBCS1B::LUC and the RBCS3B genes, yielding a novel recombinant RBCS3B/ 1B::LUC chimeric gene whose expression was driven by RBCS3B 5' transcription and translation signals. Using sensitive, single-photon-imaging equipment, three luc(+) seedlings were identified in more than 1 million F2 seedlings derived from self-fertilized F1 plants hemizygous for the synthetic RBCSB gene cluster. The F2 luc(+) seedlings were isolated, and molecular and genetic analysis indicated that the luc(+) trait was caused by the formation of a recombinant chimeric RBCS3B/1B::LUC gene. A predicted duplication of the RBCS2B gene also was present. The recombination resolution break points mapped adjacent to a region of intron I at which a disjunction in sequence similarity between RBCS1B and RBCS3B occurs; this provided evidence supporting models of gene cluster evolution by exon-shuffling processes. In contrast to most measures of meiotic unequal crossing-over that require the deletion of a gene in a gene cluster, these results directly measured the frequency of meiotic unequal crossing-over (approximately 3 x 10(-6)), leading to the expansion of the gene cluster and the formation of a novel recombinant gene.
Arginase, Arginine Decarboxylase, Ornithine Decarboxylase, and Polyamines in Tomato Ovaries (Changes in Unpollinated Ovaries and Parthenocarpic Fruits Induced by Auxin or Gibberellin) (1996)

Arginase (EC 3.5.3.1) activity has been found in the ovaries and Young fruits of tomato (Lycopersicon esculentum Mill. cv Rutgers).Changes in arginase, arginine decarboxylase (EC 4.1.1.19), and ornithine decarboxylase activity (EC 4.1.1.17) and levels of free and conjugated putrescine, spermidine, and spermine were determined in unpollinated ovaries and in parthenocarpic fruits during the early stages of development induced by 2,4-dichlorophenoxyacetic acid (2,4-D) or gibberellic acid (GA3). Levels of arginase, free spermine, and conjugates of the three polyamines were constant in unpollinated ovaries and characteristic of a presenescent step. A marked decrease in arginase activity, free spermine, and polyamine conjugates was associated with the initiation of fruit growth due to cell division, and when cell expansion was initiated, the absence of arginase indicated a redirection of nitrogen metabolism to the synthesis of arginine. A transient increase in arginine decarboxylase and ornithine decarboxylase was also observed in 2,4-D-induced fruits. In general, 2,4-D treatments produced faster changes than GA3, and without treatment, unpollinated ovaries developed only slightly and senescence was hardly visible. Sensitivity to 2,4-D and GA3 treatment remained for at least 2 weeks postanthesis.
Intraocular route of AAV2 vector administration defines humoral immune response and therapeutic potential. (2008)

These findings have important clinical implications for the design of AAV-mediated ocular gene transfer for retinal diseases, particularly if both eyes require sequential treatment.
Chemospecific alterations in duodenal perception and motor response in functional dyspepsia (2001)

In functional dyspepsia alterations in sensor and motor responses to intraduodenal acid and nutrients are chemospecific, suggesting an abnormality at the level of visceral afferents or mucosal chemoreceptors in these patients.
Comparison of methods for detection of hepatitis B virus DNA (1994)

We compared the performance of four assays for detection of hepatitis B virus (HBV) DNA: the PCR; the branched DNA hybridization assay (Chiron); and two hybridization assays that use liquid hybridization (Abbott) or direct membrane hybridization (MH). Testing 109 random hepatitis B surface antigen-positive patient samples, the percentages found to be HBV DNA positive among 30 hepatitis B e antigen (HBeAg)-positive samples and 79 HBeAg-negative samples were as follows: PCR, 100 and 90%; Chiron, 73 and 25%; Abbott, 67 and 13%; and MH, 40 and 8%. In six hepatitis B surface antigen-positive, HBeAg-negative samples, all three hybridization assays detected HBV DNA. Testing dilutions prepared from the Eurohep HBV DNA standards, the detection limits of the assays appeared to be the following: PCR, 2.5 x 10(2) HBV genomes per ml; Chiron, 2.5 x 10(6) genomes per ml; and Abbott and MH, 2.5 x 10(7) genomes per ml. HBV DNA levels in the dilution series, as reported by the Chiron and MH assays, were, on average, 2 times higher than calculated; the Abbott results were, on average, 19 times lower than calculated. We concluded that high levels of HBV DNA and the presence of HBeAg do not necessarily coincide, that the application of hybridization assays is limited to the monitoring of relatively high levels of HBV DNA, and that further standardization of quantitative HBV DNA assays is necessary to facilitate comparison of HBV DNA levels.
Competition between unrelated peptides recognized by H-2-Kd restricted T cells. (1988)

P815 (H-2d) target cells incubated with synthetic peptides corresponding to region 170-182 of HLA or to region 141-161 of influenza nucleoprotein (NP) are lysed by DBA/2 derived cytolytic T cells (CTL) specific for HLA or by BALB/c derived CTL-specific for NP, respectively. Both peptide Ag are recognized in the context of Kd. We show herein that these unrelated, nonhomologous peptides clearly compete reciprocally for recognition by the appropriate Kd restricted CTL. In contrast, different NP peptides that are recognized by other CTL restricted by HLA-B37, H-2-Db or KK, either failed to compete or were much less efficient as competitors than NP peptides recognized in the context of Kd. The efficiency of a peptide as a competitor correlated with its potency as an Ag. The most efficient competitor was a variant peptide of NP 147-158 with R156 deleted, which had been previously shown to be 1,000 times more efficient as an Ag than its natural homolog. Our results suggest that peptides recognized by CTL in the context of the same MHC class I restriction element may bind to the same or interdependent site(s) on the restriction molecule.