gebhart/patrepeval huggingface dataset:
Familial Wiedemann-Beckwith syndrome and a second Wilms tumor locus both map to 11p15.5. (1989)

Wilms tumor of the kidney occurs with increased frequency in association with two clinically and cytogenetically distinct congenital syndromes, the Wiedemann-Beckwith syndrome (WBS) and the triad of aniridia, genitourinary anomalies, and mental retardation (WAGR). Constitutional deletions in the latter situation and similar alterations in sporadic Wilms tumors have implicated the chromosomal 11p13 region in neoplastic development. In contrast, some sporadic cases of WBS have been reported to have a constitutional duplication of chromosome 11p15. In order to resolve this seeming paradox, we have analyzed a family segregating WBS for linkage to DNA markers mapped to chromosome 11p. Consonant with the cytogenetic alterations in sporadic WBS cases, we obtained evidence for tight linkage of the mutation causing the syndrome to markers located at 11p15.5. Also consistent with this localization, we identified a subset of Wilms tumors, not associated with WBS, which have attained somatic homozygosity through mitotic recombination, with the smallest shared region of overlap being distal to the beta-globin complex at 11p15.5. These data provide evidence that familial WBS likely results from a defect at the same genetic locus as does its sporadic counterpart. Further, the data suggest there is another locus, distinct from that involved in the WAGR syndrome, which plays a role in the association of Wilms tumor with WBS.
Monoclonal antibody that defines the prostate specific antigen (1989)

A monoclonal antibody to a protein with a single band in the 30-kD region was obtained from fusion of Balb/C mouse spleen cells immunized with epithelial fractions of BPH, with the myeloma cell line P3 x 63 Ag8 6.5.3 by standard procedures. This antigen was characterized in immunobinding studies with various cellular and target antigens and in immunoperoxidase staining.
Inhibiting a Spinal Dynorphin A Component Enhances Intrathecal Morphine Antinociception in Mice (1993)

Morphine given intracerebroventricularly releases spinal dynorphin A (Dyn) in mice. The present study was undertaken to determine whether morphine given intrathecally (IT) released Dyn. We demonstrated that the antinociceptive action of morphine was enhanced by procedures that are known to attenuate Dyn action. First, coadministration of the opiate antagonists, naloxone (5 fg), norbinaltorphimine (5 fg) or beta-funaltrexamine (0.25 ng) with IT morphine (0.15 microgram, 5 min) increased antinociceptive percentage maximum possible effect (%MPE) from 30% to 65%. Second, dynorphin antiserum (5 micrograms, 1 h, IT), which neutralizes Dyn action, enhanced morphine (0.2 microgram, 5 min, IT) action; MPE of 27% was increased to 60%. Third, production of desensitization to the antagonistic action of Dyn, IT, by pretreatment with morphine [10 mg/kg, 3 h, subcutaneously (SC)], or 2 micrograms, 3 h, IT) or Dyn (1 ng, 1 h, IT) increased the 30% MPE of IT morphine to 60%. Naloxone [1 ng/kg, intraperitoneally (IP)] enhanced IT morphine at a peak time of 20 min. Nalmefene [1 to 100 ng/kg, per os (PO)] enhanced IT morphine action. In conclusion, the present study showed that IT morphine putatively released spinal Dyn.
STIM1 Mediates Hypoxia-Driven Hepatocarcinogenesis via Interaction with HIF-1 (2015)

Hypoxia and intracellular Ca2+ transients are fundamental traits of cancer, whereas the route and regulation of Ca2+ mobilization in hypoxic tumorigenesis are unknown. Here, we show that stromal-interaction molecule 1 (STIM1), an ER Ca2+ sensor, correlates with elevated hypoxia-inducible factor-1 alpha (HIF-1α) in hypoxic hepatocarcinoma cells (HCCs) and is upregulated during hepatocarcinoma growth. HIF-1 directly controls STIM1 transcription and contributes to store-operated Ca2+ entry (SOCE). STIM1-mediated SOCE is also required for HIF-1 accumulation in hypoxic HCCs via activation of Ca2+/calmodulin-dependent protein kinase II and p300. Administration of YC-1, a HIF-1 inhibitor, or knockdown of HIF1A significantly diminishes hypoxia-enhanced STIM1 and suppresses tumorigenesis. Moreover, ectopic expression of STIM1 or HIF-1α partially reverses impaired growth of tumors treated with YC-1. These results suggest a mutual dependency and regulation of STIM1 and HIF-1 in controlling Ca2+ mobilization and hypoxic tumor growth and highlight a potential target for early hypoxia-related intervention.
Bile Salt Hydrolase of Bifidobacterium longum —Biochemical and Genetic Characterization (2000)

A bile salt hydrolase (BSH) was isolated from Bifidobacterium longum SBT2928, purified, and characterized. Furthermore, we describe for the first time cloning and analysis of the gene encoding BSH (bsh) in a member of the genus Bifidobacterium. The enzyme has a native molecular weight of 125,000 to 130,000 and a subunit molecular weight of 35,024, as determined from the deduced amino acid sequence, indicating that the enzyme is a tetramer. The pH optimum of B. longum BSH is between 5 and 7, and the temperature optimum is 40 degrees C. The enzyme is strongly inhibited by thiol enzyme inhibitors, indicating that a Cys residue is likely to be involved in the catalytic reaction. The BSH of B. longum can hydrolyze all six major human bile salts and at least two animal bile salts. A slight preference for glycine-conjugated bile acids was detected based on both the specificity and the K(m) values. The nucleotide sequence of bsh was determined and used for homology studies, transcript analysis, and construction and analysis of various mutants. The levels of homology with BSH of other bacteria and with penicillin V acylase (PVA) of Bacillus sphaericus were high. On the basis of the similarity of BSH and PVA, whose crystal structure has been elucidated, BSH can be classified as an N-terminal nucleophile hydrolase with Cys as the N-terminal amino acid. This classification was confirmed by the fact that a Cys1Ala exchange by site-directed mutagenesis resulted in an inactive protein. Reverse transcription-PCR experiments revealed that bsh is part of an operon containing at least two genes, bsh and glnE (GlnE is glutamine synthetase adenylyltransferase). Two UV-induced BSH-negative mutants and one spontaneous BSH-negative mutant were isolated from B. longum SBT2928 cultures and characterized. These mutants had point mutations that inactivated bsh by premature termination, frameshift, or amino acid exchange.
Biomarkers in Alzheimer's disease drug development (2011)

Developing new therapies for Alzheimer's disease (AD) is critically important to avoid the impending public health disaster imposed by this common disorder. Means must be found to prevent, delay the onset, or slow the progression of AD. These goals will be achieved by identifying disease-modifying therapies and testing them in clinical trials. Biomarkers play an increasingly important role in AD drug development. In preclinical testing, they assist in decisions to develop an agent. Biomarkers in phase I provide insights into toxic responses and drug metabolism and in Phase II proof-of-concept trials they facilitate go/no-go decisions and dose finding. Biomarkers can play a role in identifying presymptomatic patients or specific patient subgroups. They can provide evidence of target engagement before clinical changes can be expected. Brain imaging can serve as a primary outcome in Phase II trials and as a key secondary outcome in Phase III trials. Magnetic resonance imaging is currently best positioned for use in large multicenter clinical trials. Cerebrospinal fluid (CSF) measures of amyloid beta protein (Aβ), tau protein, and hyperphosphorylated tau (p-tau) protein are sensitive and specific to the diagnosis of AD and may serve as inclusion criteria and possibly as outcomes in clinical trials targeting relevant pathways. Plasma measures of Aβ are of limited diagnostic value but may provide important information as a measure of treatment response. A wide variety of measures of detectable products of cellular processes are being developed as possible biomarkers accessible in the cerebrospinal fluid and plasma or serum. Surrogate markers that can function as outcomes in pivotal trials and reliably predict clinical outcomes are needed to facilitate primary prevention trials of asymptomatic persons where clinical measures may be of limited value. Fit-for-purpose biomarkers are increasingly available to guide AD drug development decisions.
Regulation of DAF-2 receptor signaling by human insulin and ins-1, a member of the unusually large and diverse C. elegans insulin gene family (2001)

The activity of the DAF-2 insulin-like receptor is required for Caenorhabditis elegans reproductive growth and normal adult life span. Informatic analysis identified 37 C. elegans genes predicted to encode insulin-like peptides. Many of these genes are divergent insulin superfamily members, and many are clustered, indicating recent diversification of the family. The ins genes are primarily expressed in neurons, including sensory neurons, a subset of which are required for reproductive development. Structural predictions and likely C-peptide cleavage sites typical of mammalian insulins suggest that ins-1 is most closely related to insulin. Overexpression of ins-1, or expression of human insulin under the control of ins-1 regulatory sequences, causes partially penetrant arrest at the dauer stage and enhances dauer arrest in weak daf-2 mutants, suggesting that INS-1 and human insulin antagonize DAF-2 insulin-like signaling. A deletion of the ins-1 coding region does not enhance or suppress dauer arrest, indicating a functional redundancy among the 37 ins genes. Of five other ins genes tested, the only other one bearing a predicted C peptide also antagonizes daf-2 signaling, whereas four ins genes without a C peptide do not, indicating functional diversity within the ins family.
A DECREASE IN 1 H NUCLEAR MAGNETIC RESONANCE SPECTROSCOPICALLY DETERMINED CITRATE IN HUMAN SEMINAL FLUID ACCOMPANIES THE DEVELOPMENT OF PROSTATE ADENOCARCINOMA (2005)

To our knowledge this study is the first to use high resolution NMR of semen to diagnose prostate cancer. Given the known effects of adenocarcinoma on prostate metabolism, the study indicates that high resolution H NMR can be used to measure citrate in seminal fluid, potentially providing a new, rapid, noninvasive screening method.
Subcutaneous injections of low-dose veltuzumab (humanized anti-CD20 antibody) are safe and active in patients with indolent non-Hodgkin's lymphoma (2010)

Subcutaneous injections of low-dose veltuzumab are convenient, well tolerated, and capable of achieving sustained serum levels, B-cell depletion, and durable objective responses in indolent non-Hodgkin's lymphoma. (Clinicaltrials.gov identifier: NCT00546793).
Reconstruction of the elastic cartilage by isolated chondrocytes in autogeneic transplants. (1970)

Introduction It was found (MosKALEWSKI and KAWIAK [1965], MosKALEWSKI et al. [1966]) that chondrocytes isolated from adult hyaline cartilage are able to reconstruct cartilage in auto· or allogeneic transplants. Cartilage formed at the site of injection of the chon­ drocytes was of a similar morphological character to the material used for isolation. However, the intercellular matrix of the hyaline cartilage has a relatively limited number of distinct morphological features which could be utilized in following the development of such reconstructing cartilage. Therefore, in the present study an attempt was made to isolate chondrocytes from mature elastic cartilage and to com­ pare the process of reconstruction occurring after their transplantation with that of normal cartilage development. Since adult elastic tissue exhibits very slow elastin turnover (KAO et al. [1961], SLACK [1954]) it was also expected that our experimental model could offer some in­ formation on the ability of mature cells to undertake de novo the formation of elastic fibers.
Interaction of the v-Rel oncoprotein with cellular transcription factor Sp1 (1994)

We previously showed that v-Rel, the oncoprotein of the avian retrovirus Rev-T, can increase expression from promoters containing binding sites for the cellular transcription factor Sp1 in chicken embryo fibroblasts (S. Sif, A.J. Capobianco, and T.D. Gilmore, Oncogene 8:2501-2509, 1993). In those experiments, v-Rel appeared to increase the transactivating function of Sp1; that is, v-Rel stimulated transactivation by a GAL4-Sp1 protein that lacked the Sp1 DNA-binding domain. We have now shown that in vitro-synthesized v-Rel and GAL4-Sp1 form a complex that can be immunoprecipitated with either anti-Sp1 or anti-v-Rel antiserum. We have also shown that a glutathione S-transferase (GST)-Sp1 fusion protein can specifically interact with in vitro-translated v-Rel and with in vivo-synthesized v-Rel from transformed chicken spleen cells. In addition, we have found that the abilities of wild-type and two mutant forms of v-Rel to increase transactivation by Sp1 in vivo correlate with their abilities to interact with Sp1 in vitro. The sequences important for the interaction of v-Rel with Sp1 in vitro have been mapped to the first 147 amino acids of v-Rel. Other Rel proteins, such as c-Rel, RelA, p52, and p50, were also able to form a complex with Sp1 in vitro. These results suggest that v-Rel increases expression from Sp1 site-containing promoters by functionally interacting with Sp1 and that cellular Rel proteins and Sp1 are likely to interact to influence transcription from natural promoters.
Seamless On-Wafer Integration of Si(100) MOSFETs and GaN HEMTs (2009)

The first on-wafer integration of Si(100) MOSFETs and AlGaN/GaN high electron mobility transistors (HEMTs) is demonstrated. To enable a fully Si-compatible process, we fabricated a novel Si(100)-GaN-Si(100) virtual substrate through a wafer bonding and etch-back technique. The high thermal stability of nitride semiconductors allowed the fabrication of Si MOSFETs on this substrate without degrading the performance of the GaN epilayers. After the Si devices were fabricated, the nitride epilayer is exposed, and the nitride transistors are processed. By using this technology, GaN and Si devices separated by less than 5 mum from each other have been fabricated, which is suitable for building future heterogeneous integrated circuits.
PhoP-PhoQ activates transcription of pmrAB, encoding a two-component regulatory system involved in Salmonella typhimurium antimicrobial peptide resistance (1996)

Antimicrobial cationic peptides are a host defense mechanism of many animal species including mammals, insects, and amphibians. Salmonella typhimurium is an enteric and intracellular pathogen that interacts with antimicrobial peptides within neutrophil and macrophage phagosomes and at intestinal mucosal surfaces. The Salmonella spp. virulence regulators, PhoP and PhoQ, activate the transcription of genes (pag) within macrophage phagosomes necessary for resistance to cationic antimicrobial peptides. One PhoP-activated gene, pagB, forms an operon with pmrAB (5' pagB-pmrA-pmrB 3'), a two-component regulatory system involved in resistance to the antimicrobial peptides polymyxin, azurocidin (CAP37), bactericidal/permeability-increasing protein (BPI or CAP57), protamine, and polylysine. Expression of pmrAB increased transcription of pagB-pmrAB by activation of a promoter 5' to pagB. pmrAB is also expressed from a second promoter, not regulated by PhoP-PhoQ or PmrA-PmrB, located within the pagB coding sequence. S. typhimurium strains with increased pag locus expression were demonstrated to be polymyxin resistant because of induction of pagB-pmrAB; however, PmrA-PmrB was not responsible for the increased sensitivity of PhoP-null mutants to NP-1 defensin. Therefore, PhoP regulates at least two separate networks of genes responsible for cationic antimicrobial peptide resistance. These data suggest that resistance to the polymyxin-CAP family is controlled by a cascade of regulatory protein expression that activates transcription upon environmental sensing.
Differential development of fetal and adult haemoglobin profiles in colony culture: isolation of fetal nucleated red cells by two-colour fluorescence labelling. (1998)

Fetal cells in maternal peripheral blood are a source of fetal DNA for prenatal genetic diagnosis, but their numbers are so small and variable that a reliable isolation procedure has yet to be demonstrated. The problem of scarcity may be overcome by amplification of fetal progenitor cells in cultures from maternal blood samples. One challenge is to identify post-culture fetal cells and colonies. We have found that the progeny of fetal and adult erythroid progenitors developed differential haemoglobin profiles in co-culture. Fetus-derived cells initially made only fetal haemoglobin (HbF) and began to express adult haemoglobin (HbA) only after intracellular HbF had reached maximum levels, which occurred after c 7 d in culture. By this time the large majority of adult-derived erythroid cells contained already high levels of HbA alone or combined with HbE Using the HbF+ HbA- criterion, we were able to flow-sort fetal cells with up to nearly 50% purity from some post-termination blood cultures, and with >90% purity in cultures from maternal blood spiked with 1% blood from the fetus. Fetal cell purity depended on culture time and serum supplement. After 7-10 d, purity was higher in low concentrations of human cord serum (1-3%) than in the standard 30% fetal calf serum. This was reversed at later times. Thus, if fetal clonogenic erythroid cells were present in maternal blood. their progeny could be isolated from most adult erythoid cells based on haemoglobin profiles. Cultures using CD34+ cells could be performed complementary to other methods targeting more mature fetal cells in the same maternal blood samples, thus increasing the overall chances of finding fetal cells and potentially providing clonal isolation of such cells.
Molecular Mechanism of Active Ca2+ Reabsorption in the Distal Nephron (2002)

The identification of the epithelial Ca(2+) channel (ECaC) complements the group of Ca(2+) transport proteins including calbindin-D28K, Na(+)/Ca(2+) exchanger and plasma membrane Ca(2+)-ATPase, which are co-expressed in 1,25(OH)2D3- responsive nephron segments. ECaC constitutes the rate-limiting apical entry step in the process of active transcellular Ca(2+) transport and belongs to a superfamily of Ca(2+) channels that includes the vanilloid receptor and transient receptor potential channels. This new Ca(2+) channel consists of six transmembrane-spanning domains, including a pore-forming hydrophobic stretch between domain 5 and 6. The C- and N-terminal tails contain several conserved regulatory sites, implying that the channel function is modulated by regulatory proteins. The distinctive functional properties of ECaC include a constitutively activated Ca(2+) permeability, a high selectivity for Ca(2+), hyperpolarization-stimulated and Ca(2+)-dependent feedback regulation of channel activity, and 1,25(OH)2D3-induced gene activation. This review covers the distinctive properties of this new highly Ca(2+)-selective channel and highlights the implications for active transcellular Ca(2+) reabsorption in health and disease.
FPGA design of a coordinate descent data detector for large-scale MU-MIMO (2016)

We propose a new, low-complexity data-detection algorithm and a corresponding high-throughput FPGA design for 3GPP LTE-based large-scale (or massive) multi-user (MU) multiple-input multiple-output (MIMO) wireless communication systems. Our algorithm performs approximate minimum mean-square error (MMSE) data detection using coordinate descent (CD), which enables near-MMSE performance at low computational complexity, even for systems with hundreds of antennas at the base station (BS). We design a high-throughput VLSI architecture for 3GPP LTE wideband systems with a deep and interleaved pipeline, which can be parametrized at design time to support various antenna configurations. Our CD-based data detector achieves 379Mb/s throughout, while using 24 k LUTs and 771 DSP units on a Xilinx Virtex-7 FPGA for a 128 BS antenna, 8 user large-scale MU-MIMO system.
Accumulation of hydrogen peroxide is an early and crucial step for paclitaxel‐induced cancer cell death both in vitro and in vivo (2006)

Intracellular events following paclitaxel binding to microtubules that lead to cell death remain poorly understood. Because reactive oxygen species (ROS) are involved in the cytotoxicity of anticancer agents acting through independent molecular targets, we explored the role of ROS in paclitaxel cytotoxicity. Within 15 min after in vitro exposure of A549 human lung cancer cells to paclitaxel, a concentration-dependent intracellular increase in O(o)(2)(-) and H(2)O(2) levels was detected by spectrofluorometry. Addition of N-acetylcysteine (NAC) or glutathione, two H(2)O(2) scavenger, induced a 4-fold increase in paclitaxel IC(50). Delaying NAC co-incubation by 4 hr, resulted in a 3-fold reduction in cell protection. The glutathione synthesis inhibitor, buthionine sulfoximine significantly increased paclitaxel cytotoxicity and H(2)O(2) accumulation, but did not modify O(o)(2)(-) levels. Co-incubation with diphenylene iodonium suggested that paclitaxel induced-O(o)(2)(-) production was in part associated with increased activity of cytoplasmic NADPH oxidase. Concomitant treatment with inhibitors of caspases 3 and 8 increased cell survival but did not prevent the early accumulation of H(2)O(2.) To evaluate the role of ROS in paclitaxel antitumoral activity, mice were injected with LLC1 lung cancer cells and treated with paclitaxel i.p. and/or NAC. The antitumoral activity of paclitaxel in mice was abolished by NAC. In conclusion, the accumulation of H(2)O(2) is an early and crucial step for paclitaxel-induced cancer cell death before the commitment of the cells into apoptosis. These results suggest that ROS participate in vitro and in vivo to paclitaxel cytotoxicity.
CD8+-T-Cell Response to Secreted and Nonsecreted Antigens Delivered by RecombinantListeria monocytogenesduring Secondary Infection (2002)

Understanding how existing antivector immunity impacts live vaccine delivery systems is critical when the same vector system may be used to deliver different antigens. We addressed the impact of antivector immunity, elicited by immunization with attenuated actA-deficient Listeria monocytogenes, on the CD8(+)-T-cell response to a well-characterized lymphocytic choriomeningitis virus epitope, NP118-126, delivered by infection with recombinant L. monocytogenes. Challenges of immune mice with actA-deficient and with wild-type recombinant L. monocytogenes generated similar numbers of CD8(+) T cells specific for the NP118-126 epitope. High-dose immunization with actA-deficient L. monocytogenes resulted in substantial numbers of CD8(+) T cells specific for the L. monocytogenes LLO91-99 epitope in the effector and memory stages of the T-cell response. Challenge of these immune mice with recombinant L. monocytogenes resulted in rapid control of the infection and decreased CD8(+)-T-cell responses against both the secreted and nonsecreted form of the recombinant antigen compared to the response of naïve mice. In contrast, mice immunized with a low dose of actA-deficient L. monocytogenes had approximately 10-fold fewer effector and memory T cells specific for LLO91-99 and a substantially higher CD8(+)-T-cell response against the recombinant antigen after challenge with recombinant L. monocytogenes. Although mice immunized with low-dose actA-deficient L. monocytogenes had a substantial recall response to LLO91-99, which reached the same levels by 5 to 7 days postchallenge as that in high-dose-immunized mice, they exhibited decreased ability to control L. monocytogenes replication. Thus, the level of antivector immunity impacts the control of infection and efficiency of priming responses against new antigens introduced with the same vector.