gebhart/patrepeval huggingface dataset:
Modulators of the Nuclear Receptor Retinoic Acid Receptor-Related Orphan Receptor-γ (RORγ or RORc) (2014)

As the biology surrounding the nuclear receptor retinoic acid receptor-related orphan receptor-gamma (RORγ or RORc) continues to evolve, significant effort has been invested in discovering modulators of this potentially important target for the treatment of metabolic and immunological diseases. Several major pharmaceutical and biotechnology companies have disclosed RORc inhibitors or partnered with other players in the field. In this perspective, we discuss both the biology and the underlying structural biology of RORc, and summarize the RORc modulators disclosed in the scientific and patent literature.
Antithrombin-III treatment limits disseminated intravascular coagulation in endotoxemia. (1989)

Gram-negative septicemia/endotoxemia remains a serious clinical disorder that is often complicated by disseminated intravascular coagulation (DIC). Plasma antithrombin-III (AT-III) levels usually decrease during gram-negative septicemia/endotoxemia, and even moderate decreases in this major inhibitor of the coagulation system are associated with serious DIC. We demonstrated in an earlier study that prophylactic treatment of rats with 250 U/kg of AT-III followed by endotoxin challenge markedly attenuates DIC, indices of organ damage, and metabolic dysfunction. The present study was to determine whether treatment with 250 U/kg AT-III 1 hr after endotoxin challenge would be similarly efficacious. Rats treated with 250 U/kg of AT-III inactivated by human sputum elastase (ATX) served as protein controls. Blood samples for analysis were obtained 4 hr after AT-III or ATX treatment (5 hr after endotoxin challenge). Rats in the ATX treatment group exhibited abnormalities characteristic of endotoxemia, i.e., decreased fibrinogen levels and platelet counts, increases in prothrombin time and activated partial thromboplastin time, elevated serum glutamic oxaloacetic transaminase (SGOT) and alkaline phosphatase (AKP), and hypoglycemia. Treatment with AT-III markedly and significantly (P less than .05) attenuated all of these abnormalities, although survival was not increased. This study strongly suggests that supplementation of plasma AT-III is efficacious after the development of sepsis, although not as efficacious as prophylactic treatment.
SR protein-specific kinase 1 is highly expressed in testis and phosphorylates protamine 1 (1999)

Arginine/serine protein kinases constitute a novel class of enzymes that can modify arginine/serine (RS) dipeptide motifs. SR splicing factors that are essential for pre-mRNA splicing are among the best characterized proteins that contain RS domains. TwoSRprotein-specifickinases, SRPK1 and SRPK2, have been considered as highly specific for the phosphorylation of these proteins, thereby contributing to splicing regulation. However, despite the fact that SR proteins are more or less conserved among metazoa and have a rather ubiquitous tissue distribution we now demonstrate that SRPK1 is predominantly expressed in testis. In situ expression analysis on transverse sections of adult mouse testis shows that SRPK1 mRNA is abundant in all germinal cells but not in mature spermatozoa. RS kinase activity was found primarily in the cytosol and only minimal activity was detected in the nucleus. In a search for testis-specific substrates of SRPK1 we found that the enzyme phosphorylates human protamine 1 as well as a cytoplasmic pool of SR proteins present in the testis. Protamine 1 belongs to a family of small basic arginine-rich proteins that replace histones during the development of mature spermatozoa. The result of this progressive replacement is the formation of a highly compact chromatin structure devoid of any transcriptional activity. These findings indicate that SRPK1 may have a role not only in pre-mRNA splicing, but also in the condensation of sperm chromatin.
Protein Adsorption From Biofluids on Silica Nanoparticles: Corona Analysis as a Function of Particle Diameter and Porosity (2015)

A study on the adsorption of proteins from fetal bovine serum (FBS) on spherical dense and mesoporous silica nanoparticles with a wide range of diameters, from 70 to 900 nm, is presented. Monodisperse populations of particles with a range of diameters were obtained through modifications of the Stöber method. Extensive characterization of the particles was then performed using N2 physisorption, TEM, DLS, and ζ-potential. Following serum exposure, proteomic evaluation in concert with thermogravimetric analysis revealed the associated concentrations of each protein identified in the hard corona. Small particles adsorbed the largest amount of protein, due to their larger external surface area. Proteins with low molecular weights (<50 kDa) constituted the majority of the protein corona, totaling between 60 and 80% of the total mass of adsorbed protein. Here, the higher surface curvature of small particles favors the enrichment of smaller proteins. Porosity does not promote protein adsorption but improves deposition of the low molecular weight protein fraction due to the size-exclusion effect related to pore diameter. These results have important implications for the use of dense and porous silica nanoparticles in biomedical applications.
Avoiding the Ends: Internal Epitope Tagging of Proteins Using Transposon Tn7 (2015)

Peptide tags fused to proteins are used in a variety of applications, including as affinity tags for purification, epitope tags for immunodetection, or fluorescent protein tags for visualization. However, the peptide tags can disrupt the target protein function. When function is disrupted by fusing a peptide to either the N or C terminus of the protein of interest, identifying alternative ways to create functional tagged fusion proteins can be difficult. Here, we describe a method to introduce protein tags internal to the coding sequence of a target protein. The method employs in vitro Tn7-transposon mutagenesis of plasmids for random introduction of the tag, followed by subsequent Gateway cloning steps to isolate alleles with mutations in the coding sequence of the target gene. The Tn7-epitope cassette is designed such that essentially all of the transposon is removed through restriction enzyme digestion, leaving only the protein tag at diverse sites internal to the ORF. We describe the use of this system to generate a panel of internally epitope-tagged versions of the Saccharomyces cerevisiae GPI-linked membrane protein Dcw1 and the Candida glabrata transcriptional regulator Sir3. This internal protein tagging system is, in principle, adaptable to tag proteins in any organism for which Gateway-adapted expression vectors exist.
CONTEXT-SENSITIVE LANGUAGE MODELING FOR LARGE SETS OF PROPER NOUNS IN MULTIMODAL DIALOGUE SYSTEMS (2006)

We explore several language modeling strategies for increasing the recognition accuracy among large sets of proper nouns in a map- based multimodal dialogue system which provides restaurant information. In particular, we evaluate several mechanisms for exploiting dialogue context, the two most promising of which involve a semi- static metropolitan-region based large set of proper nouns competing with a smaller, in-focus subset. We show that these techniques decrease word, concept, and proper noun error rates under several training conditions. We also present a technique to generalize sparse training data through derived templates to improve language model robustness.
Nuclear Factor-κB Contributes to Hedgehog Signaling Pathway Activation through Sonic Hedgehog Induction in Pancreatic Cancer (2006)

The hedgehog (Hh) signaling pathway, which functions as an organizer in embryonic development, is implicated in the development of various tumors. In pancreatic cancer, pathway activation is reported to result from aberrant expression of the ligand, sonic Hh (Shh). However, the details of the mechanisms regulating Shh expression are not yet known. We hypothesized that nuclear factor-kappaB (NF-kappaB), a hallmark transcription factor in inflammatory responses, contributes to the overexpression of Shh in pancreatic cancer. In the present study, we found a close positive correlation between NF-kappaB p65 and Shh expression in surgically resected pancreas specimens, including specimens of chronic pancreatitis and pancreatic adenocarcinoma. We showed that blockade of NF-kappaB suppressed constitutive expression of Shh mRNA in pancreatic cancer cells. Further activation of NF-kappaB by inflammatory stimuli, including interleukin-1beta, tumor necrosis factor-alpha, and lipopolysaccharide, induced overexpression of Shh, resulting in activation of the Hh pathway. Overexpression of Shh induced by these stimuli was also suppressed by blockade of NF-kappaB. NF-kappaB-induced Shh expression actually activated the Hh pathway in a ligand-dependent manner and enhanced cell proliferation in pancreatic cancer cells. In addition, inhibition of the Hh pathway as well as NF-kappaB suppressed the enhanced cell proliferation. Our data suggest that NF-kappaB activation is one of the mechanisms underlying Shh overexpression in pancreatic cancer and that proliferation of pancreatic cancer cells is accelerated by NF-kappaB activation in part through Shh overexpression.
Radiofrequency Catheter Ablation of Atrial Tachycardia with Unusual Left Atrial Sites of Origin: Report of Two Cases (1996)

Two cases of successful radiofrequency catheter ablation of adult-onset atrial tachycardia originating from the left atrium adjacent to the mitral annulus are presented. Endocardial catheter activation mapping performed by retrograde or atrial transseptal approach revealed presystolic activation at the successful ablation site in both patients, and fractionation during sinus rhythm and tachycardia in one. The 12-lead electrocardiographic P wave appearance was suggestive of a left atrial tachycardia origin in both cases.
Cloning and characterisation of a group II allergen from the dust mite Tyrophagus putrescentiae (1998)

The complete cDNA encoding a major allergen from the dust mite Tyrophagus putrescentiae, Tyr p 2, has been sequenced and expressed. A degenerate primer was designed to the N-terminal amino acid sequence of the 16-kDa protein. The complete cDNA sequence was achieved by using reverse transcriptase PCR, PCR+1, standard cloning and sequencing techniques. The cDNA of Tyr p 2 is 552 nucleotides in length from the start codon including 126 nucleotides after the stop codon up to the beginning of the poly(A) tail. The leader sequence consists of 15 amino acids. Regarding the predicted amino acid sequence, there are no potential N-glycosylation sites (N-X-S/T). The sequence showed similarity to group II allergens from other mite species, and some regions are completely conserved. To show that the cloned cDNA sequence was coding for an allergen, Tyr p 2 was expressed in Escherichia coli and shown to react with a T. putrescentiae-positive serum pool.
Methyl-directed DNA Mismatch Correction (1989)

In 1964 Robin Holliday (1) proposed the correction of DNA base pair mismatches within recombination intermediates as the basis for gene conversion. The existence of the mismatch repair systems implied by this proposal is now well established. Activities that recognize and process base pairing errors within the DNA helix have been identified in bacteria, fungi, and mammalian cells. However, the functions and mechanisms of such systems are best understood in Escherichia coli, an organism that possesses at least three distinct mismatch correction pathways. These three systems are involved not only in the processing of recombination intermediates but also contribute in a major way to the genetic stability of the organism, a function anticipated for mismatch repair by Tiraby and Fox and by Wagner and Meselson. The significance of mismatch correction in the maintenance of low spontaneous mutability becomes apparent when one considers that seven E. coli mutator genes (dam, mutD, mutH, mutL, mutS, mutU, and mutY) have been implicated in mismatch repair. This minireview will summarize information on the most extensively studied E. coli system for mismatch correction, the methyl-directed pathway for processing of DNA biosynthetic errors and intermediates in genetic recombination. A discussion of other E. coli mismatch correction systems may be found in the recent literature and in several recent reviews. Mismatch repair pathways in other organisms and descriptions of the structural properties of mispaired bases may also be found in several of these reviews.
A TLR5 Agonist Inhibits Acute Renal Ischemic Failure (2011)

Reperfusion of ischemic organs induces a potent inflammatory response initiated by the generation of reactive oxygen species that directly damage tissue and promote leukocyte infiltration and activation that also mediate tissue injury. We recently found that radiation-induced tissue injury, which is caused by radiation-induced reactive oxygen species, is attenuated by administration of CBLB502, a pharmacologically optimized derivative of the TLR5 agonist flagellin. Therefore, we tested the ability of CBLB502 to attenuate injury in a murine model of acute ischemic renal failure. CBLB502 given 30 min before imposition of bilateral renal pedicle occlusion provided marked protection against the renal dysfunction and inflammation that follows reperfusion of ischemic kidneys, including marked decreases in leukocyte infiltration, proinflammatory cytokine production, and tubular injury. Importantly, CBLB502 given within 30 min after ischemic kidney reperfusion reproduced the protective effects of pretreatment with the TLR5 agonist, indicating a window following reperfusion in which CBLB502 administration abrogates acute renal ischemic failure. Bone marrow-reconstituted chimeras were used to show that the protective effects of CBLB502 could be delivered by intact MyD88 signaling on renal parenchymal cells. Consistent with this, Ab staining of kidney sections indicated that cells lining the renal vasculature expressed TLR5. Overall, these results indicate the use of TLR5 agonists as mitigators and protectants of acute renal ischemic failure.
Magnetically Activated Stereoscopic Vision System for Laparoendoscopic Single-Site Surgery (2012)

In this paper, the authors present an innovative vision platform for laparoendoscopic single-site (LESS) surgery based on a wired and magnetically activated 5-degrees-of-freedom robot with stereovision. The stereoscopic vision module, developed using two off-the-shelf cameras and a light emitting diodes lighting system, is mounted on the robot tip. An autostereoscopic screen is adopted to display the surgical scenario as an alternative to 3-D helmets or polarizing glasses. A rough position of the stereocamera can be determined along the abdominal wall by dragging the robot with a set of external permanent magnets (EPMs). Once the camera is set in the desired position, the EPMs provide fixation, while the internal mechanism allows fine tilt adjustment. Considering the deformable round shape of the insufflated abdomen wall and in order to replicate the precise roll motion usually provided by the endoscopist's hands, this prototype embeds an actuated mechanism that adjusts the stereocamera horizon and thus prevents any visual discomfort. Finally, the platform was preliminarily tested in vivo in a LESS scenario, demonstrating its advantages for eliminating potential conflicts with the operative tools and enabling the introduction of an additional instrument through the same access port used for stereoscopic vision.
Studies on the constituents of Veratrum plants. II. Constituents of Veratrum nigrum L. var. ussuriense. (1). Structure and 1H- and 13C-nuclear magnetic resonance spectra of a new alkaloid, verussurinine, and related alkaloids. (1991)

Alkaloidal constituents of the roots and rhizoma of Veratrum nigrum L. var. ussuriense (Liliaceae), which are used as a source of the Chinese crude drug "Li-lu, " were examined and a new alkaloid named verussurinine and six known alkaloids have been isolated. The structure of verussurinine was determined to be 16-O-(2-methylbutyroyl)germine (1) by means of spectroscopic methods, and six other alkaloids were identified as germidine (2), germerine (3), 15-O-(2-methylbutyroyl)germine (4), verazine (5), jervine (6), and neogermbudine (7), Complete assignments of the proton and carbon-13 nuclear magnetic resonance (1H- and 13C-NMR) signals of these alkaloids are also presented.
STAT3‐Mediated astrogliosis protects myelin development in neonatal brain injury (2012)

These results suggest that myelin development is regulated by a mechanism involving crosstalk between microglia and oligodendrocyte progenitors. Reactive astrocytes may modify this signaling in a STAT3-dependent manner, preventing the pathological expression of TGFβ-1 in microglia and the impairment of oligodendrocyte maturation.
Simultaneous source separation using dithered sources (2008)

We describe a new algorithm that uses known firing times to separate data from two or more impulsive, simultaneous seismic sources. Synthetic and field data tests show that the algorithm works well, especially when the data are not spatially aliased. Aliasing effects can be reduced if assumptions, such as that the data are in some sense sparse, are made.
Expression and Activity of the POU Transcription Factor SCIP (1990)

POU proteins have been shown to transcriptionally active cell-specific genes and to participate in the determination of cell fate. It is therefore thought that these proteins function in development through the stable activation of genes that define specific developmental pathways. Evidence is provided here for an alternative mode of action. The primary structure of SCIP, a POU protein expressed by developing Schwann cells of the peripheral nervous system, was deduced and SCIP activity was studied. Both in normal development and in response to nerve transection, SCIP expression was transiently activated only during the period of rapid cell division that separates the premyelinating and myelinating phases of Schwann cell differentiation. In cotransfection assays, SCIP acted as a transcriptional repressor of myelin-specific genes.
The Molecular Origin of Like-Charge Arginine−Arginine Pairing in Water (2009)

Molecular dynamics simulations show significant like-charge pairing of guanidinium side chains in aqueous poly-arginine, while this effect is absent in aqueous poly-lysine containing ammonium-terminated side chains. This behavior of the guanidinium group is revealed also by protein database searches, having important biochemical implications. Combination of molecular dynamics simulations with explicit solvent and ab initio calculations employing a polarizable continuum model of water allows one to rationalize the formation of contact ion pairs between guanidinium cations in terms of individual interactions at the molecular level.
Queueing in high-performance packet switching (1988)

The authors study the performance of four different approaches for providing the queuing necessary to smooth fluctuations in packet arrivals to a high-performance packet switch. They are (1) input queuing, where a separate buffer is provided at each input to the switch; (2) input smoothing, where a frame of b packets is stored at each of the input line to the switch and simultaneously launched into a switch fabric of size Nb*Nb; (3) output queuing, where packets are queued in a separate first-in first-out (FIFO) buffer located at each output of the switch; and (4) completely shared buffering, where all queuing is done at the outputs and all buffers are completely shared among all the output lines. Input queues saturate at an offered load that depends on the service policy and the number of inputs N, but is approximately 0.586 with FIFO buffers when N is large. Output queuing and completely shared buffering both achieve the optimal throughput-delay performance for any packet switch. However, compared to output queuing, completely shared buffering requires less buffer memory at the expense of an increase in switch fabric size.< <ETX xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">&gt;</ETX>
The Management of Thrombosis in the Antiphospholipid-Antibody Syndrome (1995)

The risk of recurrent thrombosis in patients with the antiphospholipid-antibody syndrome is high. Long-term anticoagulation therapy in which the international normalized ratio is maintained at or above 3 is advisable in these patients.
Enhanced Production of Surfactin from Bacillus subtilis by Continuous Product Removal and Metal Cation Additions (1981)

The lipopeptide, surfactin, is produced by Bacillus subtilis. A study has been made on large-scale production of this surfactant. A good yield was obtained from a glucose substrate fermentation by continuously removing the product by foam fractionation. The surfactin could be easily recovered from the collapsed foam by acid precipitation. The yield was also improved by the addition of either iron or manganese salts. Hydrocarbon addition to the medium, which normally increases biosurfactant production, completely inhibited surfactin production by B. subtilis.
Fluorogenic assay for rapid detection of Escherichia coli in food (1985)

An assay procedure to screen for Escherichia coli in foods by using 4-methylumbelliferyl-beta-D-glucuronide (MUG) incorporated into lauryl tryptose (LST) broth was evaluated. The beta-glucuronidase produced by E. coli cleaves the MUG substrate to yield a fluorescent end product. E. coli-negative samples can be identified by lack of fluorescence in LST-MUG within 24 h. MUG was not inhibitory to coliforms and E. coli. Over 1,400 food and dairy samples were tested to compare the standard three-tube most-probable-number procedure with the MUG-containing or non-MUG-containing LST procedure. LST-MUG testing detected a greater number of E. coli, with a lower false-positive rate (1.4%) and in a shorter time, than did the standard procedure. All false-positive results in the LST-MUG testing were attributable to beta-glucuronidase-producing staphylococci. No false-negative result was encountered. Use of MUG in LST broth obviates the EC broth step, allowing a 2.5-day procedure to a completed E. coli test versus the present 4- to 6-day standard most-probable-number method.
Mass spectrometric and capillary electrophoretic investigation of heparin, heparinases, and related compounds (1998)

Thesis (Ph. D.)--Massachusetts Institute of Technology, Dept. of Chemistry, 1998.
β-Elimination and Peptide Bond Hydrolysis:  Two Distinct Mechanisms of Human IgG1 Hinge Fragmentation upon Storage (2007)

We expand the understanding of hinge-region degradation of human IgG1 monoclonal antibodies. First, our data more accurately confirm previously proposed hydrolysis of the CO−NH peptide bonds within the IgG1 heavy chain C(220)DKTHTC hinge sequence. Second, we provide evidence that the adjacent heavy chain S219−C220 bond is cleaved by a different mechanism. The cleavage of S219−C220 becomes more pronounced with elevated pH (pH > 7) as does the formation of light-chain−heavy-chain thioether linkage, another IgG1 degradation product whose mechanism has remained unknown. Careful application of bioanalytical methods and mass spectrometry provide strong evidence for a central role of a β-elimination mechanism to account for the S219−C220 cleavage as well as the formation of the thioether linkage product.