gebhart/patrepeval huggingface dataset:
Requirement for DARPP-32 in Progesterone-Facilitated Sexual Receptivity in Female Rats and Mice (2000)

DARPP-32, a dopamine- and adenosine 3',5'-monophosphate (cAMP)-regulated phosphoprotein (32 kilodaltons in size), is an obligate intermediate in progesterone (P)-facilitated sexual receptivity in female rats and mice. The facilitative effect of P on sexual receptivity in female rats was blocked by antisense oligonucleotides to DARPP-32. Homozygous mice carrying a null mutation for the DARPP-32 gene exhibited minimal levels of P-facilitated sexual receptivity when compared to their wild-type littermates. P significantly increased hypothalamic cAMP levels and cAMP-dependent protein kinase activity. These increases were not inhibited by a D1 subclass dopamine receptor antagonist. P also enhanced phosphorylation of DARPP-32 on threonine 34 in the hypothalamus of mice. DARPP-32 activation is thus an obligatory step in progestin receptor regulation of sexual receptivity in rats and mice.
CRYSTAL: Inducing a Conceptual Dictionary (1995)

One of the central knowledge sources of an information extraction system is a dictionary of linguistic patterns that can be used to identify the conceptual content of a text. This paper describes CRYSTAL, a system which automatically induces a dictionary of "concept-node definitions" sufficient to identify relevant information from a training corpus. Each of these concept-node definitions is generalized as far as possible without producing errors, so that a minimum number of dictionary entries cover the positive training instances. Because it tests the accuracy of each proposed definition, CRYSTAL can often surpass human intuitions in creating reliable extraction rules.
Secondary malignant giant‐cell tumour of bone: molecular abnormalities of p53 and H‐ras gene correlated with malignant transformation (2001)

Our results suggest that multiple oncogene or tumour suppressor gene mutations may play an important role during malignant transformation in conventional giant-cell tumours.
High serum levels of YKL‐40 in patients with squamous cell carcinoma of the head and neck are associated with short survival (2007)

YKL-40 is a glycoprotein secreted by macrophages, neutrophils and malignant tumor cells. Elevated serum levels of YKL-40 are associated with poor prognosis in several malignancies. In this study, we examined the prognostic value of serum YKL-40 before treatment and during follow-up in patients with squamous cell carcinoma of the head and neck (HNSCC). YKL-40 was determined by ELISA retrospectively in serum from 173 patients with primary HNSCC before treatment and up to 2 years after treatment. Median follow-up time was 7.9 years. YKL-40 protein expression in tumor biopsies was assessed by immunohistochemistry in 50 patients. Pretreatment serum YKL-40 was elevated in 53%. Patients with high serum YKL-40 had shorter survival than patients with normal serum YKL-40 (33 vs. 84 months; p = 0.008). Multivariate Cox analysis including pretreatment serum YKL-40, age, sex, primary tumor site, TNM classification and treatment demonstrated that TNM classification (HR = 2.61, p = 0.02) and serum YKL-40 (log-transformed continuous variable: HR = 1.55, p < 0.0001) were independent prognostic variables of overall survival (OS). Multivariate Cox analysis demonstrated that TNM classification (HR = 5.77, p = 0.001) and serum YKL-40 (dichotomous variable: HR = 2.75, p = 0.01) were independent predictors of recurrence-free survival. During follow-up after radiotherapy, a high serum YKL-40 (log-transformed continuous variable) in patients with TNM Stage III and IV disease predicted poorer OS within 6 months (HR = 1.95, p < 0.0001). Immunohistochemical analysis showed YKL-40 expression in the malignant tumor cells. In conclusion, serum YKL-40 was demonstrated to be an independent prognostic biomarker of recurrence-free and overall survival in patients with HNSCC.
Differential roles of sleep spindles and sleep slow oscillations in memory consolidation (2017)

Abstract Sleep plays an important role in consolidation of recent memories. However, the mechanisms of consolidation remain poorly understood. In this study, using a realistic computational model of the thalamocortical network, we demonstrated that sleep spindles (the hallmark of N2 stage sleep) and slow oscillations (the hallmark of N3 stage sleep) both facilitate spike sequence replay as necessary for consolidation. When multiple memories were trained, the local nature of spike sequence replay during spindles allowed replay of the memories independently, while during slow oscillations replay of the weak memory was competing to the strong memory replay. This led to the weak memory extinction unless when sleep spindles (N2 sleep) preceded slow oscillations (N3 sleep), as observed during natural sleep. Our study presents a mechanistic explanation for the role of sleep rhythms in memory consolidation and proposes a testable hypothesis how the natural structure of sleep stages provides an optimal environment to consolidate memories. Significant Statement Numerous studies suggest importance of NREM sleep rhythms – spindles and slow oscillations - in sleep related memory consolidation. However, synaptic mechanisms behind the role of these rhythms in memory and learning are still unknown. Our new study predicts that sleep replay - the neuronal substrate of memory consolidation - is organized within the sleep spindles and coordinated by the Down to Up state transitions of the slow oscillation. For multiple competing memories, slow oscillations facilitated only strongest memory replay, while sleep spindles allowed a consolidation of the multiple competing memories independently. Our study predicts how the basic structure of the natural sleep stages provides an optimal environment for consolidation of multiple memories.
Abstract 2477: Engineered toxin bodies: A next-generation immunotoxin scaffold with novel immuno-oncology functionality (2015)

Abstract The potential of immunotoxins in oncology has been largely limited due to problems with immunogenicity as well as a limited number of appropriate targets. Advances in genetic engineering and molecular biology have been applied to overcome these limitations. Molecular Templates has developed engineered toxin bodies (ETBs), a next-generation recombinant immunotoxin scaffold based on the Shiga-like toxin A subunit specifically directed to cancer cells via antibody fragment binding domains. ETBs have been de-immunogenized through the systematic and comprehensive removal of B- and T-cell epitopes. Data from the repeat administration of ETBs in animal models demonstrates the dramatically reduced immunogenicity of these ETBs and supports the potential for their use in solid tumor settings. The ETB scaffold was also engineered to force the internalization of receptors that typically do not internalize. This property of forced internalization expands the universe of possible targets; the company's lead compound, MT-3724, is the first immunotoxin to CD20 to enter the clinic and is currently in a phase I study for refractory NHL. MT-3724 rapidly internalizes and potently kills CD20+ lymphoma cells. Additionally, we have taken advantage of the immunotoxin's localization to the cytosol to engineer in a novel immuno-oncology mechanism of action: MHC class I antigens derived from human cytomegalovirus (HCMV) have been genetically fused to the immunotoxin scaffold in order to mark these cells as targets for cytotoxic T lymphocyte (CTL) mediated cell lysis. We have detected these foreign protein derived antigens displayed on the surface of ETB-intoxicated cancer cells in context with MHC class I molecules. Because antigen presentation does not require de novo protein synthesis, this mechanism of action is complementary to the inactivation of ribosomal function by ETBs. Since a large portion of the populace has a robust population of high-affinity effector T-cells targeting HCMV, the presentation of these antigens on ETB-intoxicated cancer cells may recruit a CTL response to tumor cells that is not dependent on genetically engineering host T-cells or blocking checkpoint inhibitors. The recruitment of a CTL response has the potential to act additively or synergistically to the direct cell kill activity of the ETB and may expand the potential efficacy of these immunotoxins. Citation Format: Erin K. Willert, Garrett L. Robinson, Sangeetha Rajagopalan, Brigitte Brieschke, Jennifer Erdman, Jane Neill, Rodney Flores, Julia Foree, William Null, Jensing Liu, Jack P. Higgins. Engineered toxin bodies: A next-generation immunotoxin scaffold with novel immuno-oncology functionality. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 2477. doi:10.1158/1538-7445.AM2015-2477
Photopheresis for the Prevention of Rejection in Cardiac Transplantation (1998)

In this pilot study, the addition of photopheresis to triple-drug immunosuppressive therapy significantly decreased the risk of cardiac rejection without increasing the incidence of infection.
Anti‐Biofouling Properties of Polymers with a Carboxybetaine Moiety (2008)

The resistance of random copolymers of BMA and CMB against biofouling was evaluated. The amount of proteins adsorbed onto the CMB copolymers was smaller than that onto other polymers (non-ionic polymers and copolymers of ordinary ionic monomers and BMA) and decreased with an increase in the content of CMB residues. Furthermore, there was a dramatic decrease in the number of cells (platelets and fibroblasts) that adhered to the CMB copolymers compared with that to other polymers. In contrast with this, CMB copolymers were slightly perturbative to both complement and coagulation systems. However, the overall results suggest that zwitterionic moieties are effective for making polymer materials biocompatible due to their excellent anti-biofouling property.
C-peptide immunochemiluminometric assay developed from two seemingly identical polyclonal antisera. (1992)

Two goats were immunized with synthetic C-peptide. Their antisera were immunopurified separately on a C-peptide affinity column. The purified antibodies from one goat were labeled with acridinium ester; the other goat's antibodies were immobilized on plastic beads. Standards were synthetic C-peptide. The new immunochemiluminometric assay (ICMA) for C-peptide was compared with our routine radioimmunoassay (RIA) by using Novo's 125I-labeled C-peptide and Cambridge Medical's antiserum. Good correlations were found between the new ICMA and the RIA (r = 0.951; ICMA = 1.07 RIA + 147; n = 112). The new ICMA showed good recoveries (91 percent to 108 percent) of added C-peptide and parallelism of diluted specimens. The incubation time was shortened from 48 hours for RIA to five hours for ICMA. In addition, it was shown that polyclonal antisera from two animals immunized by the same antigen and purified by the same affinity column can be used to prepare immunometric assays.
Data-driven functional clustering reveals dominance of face, place, and body selectivity in the ventral visual pathway (2012)

Regions selective for faces, places, and bodies feature prominently in the literature on the human ventral visual pathway. Are selectivities for these categories in fact the most robust response profiles in this pathway, or is their prominence an artifact of biased sampling of the hypothesis space in prior work? Here we use a data-driven structure discovery method that avoids the assumptions built into most prior work by 1) giving equal consideration to all possible response profiles over the conditions tested, 2) relaxing implicit anatomical constraints (that important functional profiles should manifest themselves in spatially contiguous voxels arising in similar locations across subjects), and 3) testing for dominant response profiles over images, rather than categories, thus enabling us to discover, rather than presume, the categories respected by the brain. Even with these assumptions relaxed, face, place, and body selectivity emerge as dominant in the ventral stream.
Comparison of Inflammation, Organ Damage, and Oxidant Stress Induced by Salmonella enterica Serovar Muenchen Flagellin and Serovar Enteritidis Lipopolysaccharide (2002)

Gram-negative sepsis is related to the activation of interconnected inflammatory cascades in response to bacteria and their products. Recent work showed that flagellin, the monomeric subunit of bacterial flagella, triggers innate immune responses mediated by Toll-like receptor 5. Here, we compared the effects of Salmonella enterica serovar Enteritidis lipopolysaccharide (LPS) and recombinant Salmonella enterica serovar Muenchen flagellin administered intravenously (100 microg) to mice. Flagellin and LPS both elicited a prototypical systemic inflammatory response, with increased levels of tumor necrosis factor alpha, gamma interferon, interleukin 6 and 10, and nitrate in plasma. Flagellin induced a widespread oxidative stress, evidenced by an increase in malondialdehyde and a decrease in reduced glutathione in most organs, as well as liver (increased plasma aminotransferases), but not renal, injury. Alternatively, LPS resulted in a less severe oxidative stress and triggered renal, but not liver, damage. Sequestration of polymorphonuclear neutrophils (increased myeloperoxidase activity) in the lungs was observed with both toxins, while only LPS recruited neutrophils in the gut. In additional experiments, the simultaneous administration of small doses of LPS and flagellin (10 microg) induced a synergistic enhancement of the production of proinflammatory cytokines. Our data support a novel concept implicating flagellin as a mediator of systemic inflammation, oxidant stress, and organ damage induced by gram-negative bacteria.
Differential Modulation of Stimulatory and Inhibitory Fcγ Receptors on Human Monocytes by Th1 and Th2 Cytokines (2001)

Immune complex-mediated inflammatory responses are initiated by Fc gamma R on phagocytes. We report in this study that an inhibitory receptor, Fc gamma RIIb2, is expressed on circulating human monocytes, and when co-cross-linked with stimulatory Fc gamma R it down-regulates effector function. Fc gamma RIIb2 expression is increased by IL-4 and decreased by IFN-gamma, in contrast to the activating receptor, Fc gamma RIIa, which is increased by IFN-gamma and decreased by IL-4. Thus, Th1 and Th2 cytokines differentially regulate the opposing Fc gamma R systems, altering the balance of activating and inhibiting Fc gamma R. The detection and cytokine modulation of Fc gamma RIIb2 in human myeloid cells provide evidence of a negative regulator of immune complex-mediated responses in human phagocytes and offer a new approach to limit Ab-triggered inflammation in autoimmune disease.
On the limits of electronic ATM switching (1996)

This article discusses the principal advantages and limitations of electronic switching in asynchronous transfer mode (ATM) networks. Key design parameters of ATM switch implementations are defined, and their relationships with respect to performance, complexity, and cost are modeled and discussed. Design and implementation experience is reported on a very high-performance four-input, four-output ATM switch that has been designed as part of the DARPA-sponsored "Thunder and Lightning" project at the University of California, Santa Barbara. This research project is focused on the design and prototype demonstration of ATM links and electronic switches operating at 40 Gb/s per link (TDM), with potential scalability to 100 Gb/s. Such aggressive link rates are near the implementation limits for electronic ATM switches; they place severe requirements on switch architecture, particularly the buffering scheme.
'Dramatic Consequences': James Mcpherson Analyzes Antietam (2002)

What motivated you to choose this moment from among all others of the Civil War? James M. McPherson (jm):The finding and verification of a copy of Lee's Orders no.191 was potentially one of the great windfalls of military history.If McClellan had acted immediately instead of waiting six hours after he was certain of the genuineness of the orders, and if he had ordered the Union VI and IX Corps to march through the night to be in a position to attack the South Mountain passes at first light on September 14, he might have destroyed a considerable part of Lee's army in detail and would also have saved the Union garrison at Harpers Ferry.This might have enabled McClellan to carry out Lincoln's injunction to Destroy the rebel army, if possible.It might have brought the end of the war closer.It would have rescued McClellan's reputation.But it just was not in McClellan to move decisively, quickly, and aggressively, and thus the opportunity for a truly decisive victory on September 14 or 15 slipped through his hands.But the finding of the orders did set in train a series of events that led to the battle of Antietam, which, despite its equivocal tactical outcome, was nevertheless a strategic Union victory that changed the course of the war by causing Britain and France to back off from diplomatic recognition of the Confederacy, preventing probable Democratic takeover of the House of Representatives in the 1862 northern elections, arresting a disastrous decline in northern morale, and giving Lincoln the opportunity he had been awaiting to issue the Emancipation Proclamation.
Quantitative analysis of cytokine gene expression in rheumatoid arthritis. (1990)

Previous studies of the cytokine profile of rheumatoid arthritis (RA) have been primarily limited to the assessment of the levels of these mediators in synovial fluid (SF) or synovial tissues (ST) by biologic or immunologic assays. We have studied cytokine gene expression in RA by in situ hybridization of SF cells, enzymatically dispersed ST cells, and frozen sections of ST. RA ST cells (n = 7) were studied and a high percentage of cells hybridized to the following anti-sense probes: IL-6 = 19 +/- 3.3%; IL-1 beta = 9.9 +/- 1.7%; TNF-alpha = 5.8 +/- 1.4%; granulocyte-macrophage-CSF = 2.2 +/- 0.8%; transforming growth factor-beta 1 = 1.3 +/- 0.2% (p less than 0.05 for each compared to sense probes). Similar results were found using osteoarthritis ST cells, although the percentage of cells expressing the IL-6 gene (7.1 +/- 2.5%) was significantly less in osteoarthritis compared to RA. RA ST cells did not significantly bind the IFN-gamma probe (0.2 +/- 0.1% positive), although they were capable of expressing the IFN-gamma gene if stimulated with PHA. The OKM1+ population of ST cells (i.e., macrophage lineage cells) was greatly enriched for IL-1 beta and TNF-alpha, whereas the OKM1- population (lymphocytes, fibroblasts, and type B synoviocytes) was enriched for IL-6. The vast majority of cells expressing the IL-6 gene were non-T cells. Furthermore, hybridization to RA ST frozen sections localized IL-6 mRNA to the synovial lining layer, which is comprised of type A and type B synoviocytes. In contrast to the high level of cytokine gene expression observed in ST, SF cells did not hybridize significantly to any of the cytokine probes. If stimulated with LPS or PHA, SF cells expressed IL-1 beta or IFN-gamma genes, respectively.
Self-Terminating Growth of Platinum Films by Electrochemical Deposition (2012)

A self-terminating rapid electrodeposition process for controlled growth of platinum (Pt) monolayer films from a K(2)PtCl(4)-NaCl electrolyte has been developed that is tantamount to wet atomic layer deposition. Despite the deposition overpotential being in excess of 1 volt, Pt deposition was quenched at potentials just negative of proton reduction by an alteration of the double-layer structure induced by a saturated surface coverage of underpotential deposited H (H(upd)). The surface was reactivated for further Pt deposition by stepping the potential to more positive values, where H(upd) is oxidized and fresh sites for the adsorption of PtCl(4)(2-) become available. Periodic pulsing of the potential enables sequential deposition of two-dimensional Pt layers to fabricate films of desired thickness, relevant to a range of advanced technologies.
Distribution and consenus of branch point signals in eukaryotic genes: a computerized statistical analysis (1990)

An intermediate stage in the process of eukaryotic RNA splicing is the formation of a lariat structure. It is anchored at an adenosine residue in intron between 10 and 50 nucleotides upstream of the 3' splice site. A short conserved sequence (the branch point sequence) functions as the recognition signal for the site of lariat formation. It has been generally assumed that the branch point is recognized mainly by the presence of its unique sequence where the lariat is formed. However, the known branch point consensus sequence is found to be distributed nearly randomly throughout the gene sequence with only a slightly higher frequency in the expected lariat region. Further, the known consensus sequence is found to be clearly inadequate to specify branch points. These observations have implications for understanding the mechanism of branch point recognition in the process of splicing, and the possible evolution of the branch point signal.
Target Cell-specific DNA Transfer Mediated by a Chimeric Multidomain Protein (1996)

Based on the multidomain structure of the bacterial Pseudomonas exotoxin A, a recombinant fusion protein was constructed which serves as a target cell-specific carrier for the transfer of DNA via receptor-mediated endocytosis. The protein consists of three functional domains: 1) an ErbB-2 -specific single chain antibody confers target cell specificity, 2) the exotoxin A translocation domain facilitates endosome escape, and 3) a DNA binding domain derived from the yeast GAL4 protein enable sequence-specific high affinity binding to DNA. Carrier protein purified from bacterial lysates displayed both ErbB-2-specific and DNA sequence-specific binding in vitro. Complexes which formed spontaneously by the interaction of the fusion protein with a luciferase reporter gene construct carrying a GAL4-specific recognition sequence, after condensation of the DNA and compensation of excess negative charge with poly-L-lysine were able to transfect ErbB-2-expressing cells in vitro in a cell-specific manner. Transient expression of the luciferase gene driven by the SV40 early promoter was observed and correlates with the amount of carrier protein in the complex. Truncated forms of the carrier protein lacking either the cell recognition domain or the translocation domain failed to facilitate efficient DNA transfer.
NEXT-GENERATION MICROFILTER: LARGE SCALE, CONTI- NUOUS MAMMALIAN CELL RETENTION FOR PERFUSION BIO- REACTORS (2014)

In this study, we report on the development of the first membrane-less, clog-free microfiltration platform for ultra-high throughput (up to 1000 mL/min) cell separation, using a massively-multiplexed array of inertial microfluidic cell sorting channels. Our developed system consists of multiple layer (10~20) of PDMS sheets with embossed microchannels (i.e., ~ 200 individual spirals) bonded together for continuous size-based cell sorting from a large volume of biological fluid. Subsequent perfusion culture experiments using the cell retention system show the potential to significantly enhance overall efficiency of perfusion cell culture.