gebhart/patrepeval huggingface dataset:
Tyrosine-phosphorylated Vav1 as a Point of Integration for T-cell Receptor- and CD28-mediated Activation of JNK, p38, and Interleukin-2 Transcription (2000)

In this study we identified tyrosine-phosphorylated Vav1 as an early point of integration between the signaling routes triggered by the T-cell receptor and CD28 in human T-cell leukemia cells. Costimulation resulted in a prolonged and sustained phosphorylation and membrane localization of Vav1 in comparison to T-cell receptor activation alone. T-cell stimulation induced the recruitment of Vav1 to an inducible multiprotein T-cell activation signaling complex at the plasma membrane. Vav1 activated the mitogen-activated protein kinases JNK and p38. The Vav1-mediated activation of JNK employed a pathway involving Rac, HPK1, MLK3, and MKK7. The costimulation-induced activation of p38 was inhibited by dominant negative forms of Vav1, Rac, and MKK6. Here we show that Vav1 also induces transcription factors that bind to the CD28RE/AP element contained in the interleukin-2 promoter. A detailed mutational analysis of Vav1 revealed a series of constitutively active and nonfunctional forms of Vav1. Almost all inactive versions were mutated in their Dbl homology domain and behaved as dominant negative mutants that impaired costimulation-induced activation of JNK, p38, and CD28RE/AP-dependent transcription. In contrast to NF-AT-dependent transcription, Vav1-mediated transcriptional induction of the CD28RE/AP element in the interleukin-2 promoter could only partially be inhibited by cyclosporin A, suggesting a dual role of Vav1 for controlling Ca(2+)-dependent and -independent events.
Allelic association of human dopamine D2 receptor gene in alcoholism (1990)

In a blinded experiment, we report the first allelic association of the dopamine D<sub>2</sub>receptor gene in alcoholism. From 70 brain samples of alcoholics and nonalcoholics, DNA was digested with restriction endonucleases and probed with a clone that contained the entire 3' coding exon, the polyadenylation signal, and approximately 16.4 kilobases of noncoding 3' sequence of the human dopamine D<sub>2</sub>receptor gene (λhD2G1). In the present samples, the presence of A1 allele of the dopamine D<sub>2</sub>receptor gene correctly classified 77% of alcoholics, and its absence classified 72% of nonalcoholics. The polymorphic pattern of this receptor gene suggests that a gene that confers susceptibility to at least one form of alcoholism is located on the q22-q23 region of chromosome 11. (<i>JAMA</i>. 1990;263:2055-2060)
Sequencing in nanofabricated arrays: A feasibility study (1997)

The feasibility of using nanofabricated arrays as electrophoretic chambers for DNA sequencing is investigated. A specific array design, consisting of rows of closely spaced posts, separated by longer open spaces, is proposed. Molecules driven through the array by an electric field get hooked over obstacles at successive rows and their progress through the device is delayed as a consequences. The dependence of the delay time on molecular size is derived. Numerical evaluation indicates that a device of modest dimensions, operating at high fields, can rapidly resolve oligonucleotides containing several hundred bases.
Iron Oxide Enhanced MR Imaging of the Liver and Spleen: Review of the First Five Years. (1991)

Superparamagnetic iron oxide (SPIO) particles are a potent new class of MR contrast agents affording improved detection of hepatic and splenic neoplasms. In this report we review the development of this agent through preclinical studies and early clinical results at Massachusetts General Hospital during a 5 year investigation. SPIO particles are sequestered by normal reticuloendothelial system (RES) phagocytic Kupffer cells but are not retained in tumor tissue. Consequently, there is a five fold increase in T2 relaxation between normal RES tissue and tumor with a comparable advantage in quantitative signal to noise ratio, contrast to noise ratio and lesion detectibility in the liver and spleen at MR imaging. Increased lesion conspicuity can be exploited to decrease threshold size for lesion detection to less than 3 mm. Clinically beneficial effects occur with a variety of mildly T2-weighted spin-echo pulse sequences; gradient-echo techniques show even greater benefit after administration of SPIO. Metabolically, pharmaceutical grade preparations are biodegradable and bioavailable, being rapidly turned over into body iron stores and incorporated into erythrocyte hemoglobin. Early dose escalation clinical trials have identified a probable clinical dose range of 10-20 mumol Fe/kg body weight. SPIO compounds evaluated to date are still investigational in the United States. Newer commercial formulations currently being evaluated may extend clinical safety margins.
Metalloproteinase Inhibition Reduces Constrictive Arterial Remodeling After Balloon Angioplasty (2000)

Metalloproteinase inhibition by Batimastat significantly reduced late lumen loss after balloon angioplasty by inhibition of constrictive arterial remodeling, whereas neointima formation was not inhibited by MMP inhibition.
Repairing Multiple Failures with Coordinated and Adaptive Regenerating Codes (2011)

Erasure correcting codes are widely used to ensure data persistence in distributed storage systems. This paper addresses the simultaneous repair of multiple failure in such codes. We go beyond existing work (i.e., regenerating codes by Dimakis et al.) and propose coordinated regenerating codes allowing devices to coordinate during simultaneous repairs thus further reducing the costs. We define optimal coordinated regenerating codes outperforming existing codes for simultaneous repairs with respect to both storage and repair costs. We prove that deliberately delaying repairs does not bring additional gains (i.e., regenerating codes are optimal as long as each failure can be repaired before a second one occurs). Finally, we propose adaptive regenerating codes that self-adapt to the system state and prove they are optimal.
Furopyridines. I. Synthesis of furo[2,3‐c]pyridine (1982)

Abstract The parent framework of furo[2,3‐c]pyridine has been synthesized. 3‐Furoic acid chloride ( 2 ) was reduced with bis(triphenylphosphine) copper(1) tetrahydroborate to afford 3‐furaldehyde ( 3 ) which was condensed with malonic acid to give β‐(3‐furyl)acrylic acid ( 4 ). The acrylic acid 4 was converted to the acid azide ( 5 ), which in turn was cyclized to give furo[2,3‐c]pyridin‐7(6 H )‐one ( 6 ) by heating at 180° in diphenylmethane. The pyridone 6 was chlorinated with phosphorus oxychloride, followed by reduction with zinc and acetic acid to give furo[2,3‐ c ]pyridine ( 8 ).
A Pilot Study on Brain‐to‐Plasma Partition of 10,11‐Dyhydro‐10‐hydroxy‐5H‐dibenzo(b,f)azepine‐5‐carboxamide and MDR1 Brain Expression in Epilepsy Patients Not Responding to Oxcarbazepine (2005)

Pharmacologic failure of OXC in pharmacoresistant epilepsy is unlikely to be due to alterations in drug metabolism. 10-OHCBZ does not appear to cross the blood-brain barrier by simple diffusion, and it acts as a substrate of P-gp. The level of expression of MDR1 is inversely correlated with 10-OHCBZ concentration in the epileptic tissue. P-gp may play a role in the pharmacoresistance to OXC by determining the attainment of insufficient concentrations of its active metabolite at neuronal targets.
AZD9150, a next-generation antisense oligonucleotide inhibitor of STAT3 with early evidence of clinical activity in lymphoma and lung cancer (2015)

Next-generation sequencing technologies have greatly expanded our understanding of cancer genetics. Antisense technology is an attractive platform with the potential to translate these advances into improved cancer therapeutics, because antisense oligonucleotide (ASO) inhibitors can be designed on the basis of gene sequence information alone. Recent human clinical data have demonstrated the potent activity of systemically administered ASOs targeted to genes expressed in the liver. We describe the preclinical activity and initial clinical evaluation of a class of ASOs containing constrained ethyl modifications for targeting the gene encoding the transcription factor STAT3, a notoriously difficult protein to inhibit therapeutically. Systemic delivery of the unformulated ASO, AZD9150, decreased STAT3 expression in a broad range of preclinical cancer models and showed antitumor activity in lymphoma and lung cancer models. AZD9150 preclinical activity translated into single-agent antitumor activity in patients with highly treatment-refractory lymphoma and non-small cell lung cancer in a phase 1 dose-escalation study.
Novel cisplatin-incorporated polymeric micelles can eradicate solid tumors in mice. (2003)

Polymeric micelles incorporating cisplatin (CDDP) were prepared through the polymer-metal complex formation between CDDP and poly(ethylene glycol)-poly(glutamic acid) block copolymers, and their utility as a tumor-targeted drug delivery system was investigated. CDDP-incorporated micelles (CDDP/m) had a size of 28 nm with remarkably narrow distribution. CDDP/m were very stable in distilled water even in long-time storage, but exhibited a sustained drug release accompanied with the decay of the carrier itself in physiological saline. These micelles showed remarkably prolonged blood circulation and effectively accumulated in solid tumors (Lewis lung carcinoma cells) according to the passive targeting manner (20-fold higher than free CDDP). Reduced accumulation of the micelles in normal organs provided high selectivity to the tumor. In vivo antitumor activity assay demonstrated that both free CDDP and the CDDP/m had significant antitumor activity in C 26-bearing mice compared with nontreatment (P < 0.05 for free CDDP; P < 0.01 for CDDP/m), but complete tumor regression was observed only for the treatment with CDDP/m. Four of 10 mice treated with CDDP/m (4 mg/kg; five times administration at 2-day intervals) showed complete tumor regression with no significant body weight loss, whereas free CDDP treatment at the same drug dose and regime resulted in tumor survivals and approximately 20% of body weight loss. These data suggest that CDDP/m could be a promising formulation of CDDP for the targeted therapy of solid tumors.
Aggregated proteoglycan synthesis in organ cultures of human nucleus pulposus. (1979)

Proteoglycans isolated under associative conditions in the presence of protease inhibitors from human nucleus pulposus contained 17% aggregate and 83% non-aggregating monomer (Kav = 0.5 on Sepharose CL-2B). Isolated aggregate after reduction and alkylation was resolved into two components (Kav = 0.15 and 0.43) on Sepharose CL-2B. Labeled proteoglycans isolated from parallel samples pulsed with [35S]sulfate and chased for up to 18 h were present largely as aggregated material (up to 78%). Reduction and alkylation of the labeled samples gave a labeled proteoglycan monomer with Kav = 0.15. Both the labeled and unlabeled chondroitin sulfate chains had the same distribution on Sepharose CL-6B and equivalent molecular weights (Mr = 2.0 x 10(3)). After chondroitinase ABC digestion, the unlabeled keratan sulfate-protein core was polydisperse with a Kav = 0.38 on Sepharose CL-4B while the labeled keratan sulfate-protein core had a Kav = 0.05. This indicates that the newly synthesized proteoglycan had a large core protein and suggests that the proteoglycans present in nucleus pulposus are originally synthesized as large molecular weight, aggregating proteoglycans.
Blockade of Osteopontin Inhibits Glomerular Fibrosis in a Model of Anti-Glomerular Basement Membrane Glomerulonephritis (2010)

Neutralization of OPN inhibited progression of fibrosis in vivo when given at early fibrotic stage. Thus, OPN may be a therapeutic target for glomerular fibrosis.
Exploring the efficacy of cyclic vs static aspiration in a cerebral thrombectomy model: an initial proof of concept study (2013)

Cyclic aspiration significantly outperformed static aspiration in speed and overall clearance of synthetic clots in our experimental model. Within cyclic aspiration, efficacy is improved by increasing cycle frequency, utilizing specific pressure cycle waveforms and using water rather than air as the aspiration medium. These findings provide a starting point for altering existing thrombectomy technology or perhaps the development of new technologies with higher recanalization rates.
Adeno-associated virus: a vector system for efficient introduction and integration of DNA into a variety of mammalian cell types. (1988)

Adeno-associated virus (AAV) is a single-stranded DNA parvovirus that is dependent on adenovirus or herpesvirus for reproductive functions. We describe the construction of recombinant AAV vectors containing the chloramphenicol acetyltransferase gene or the neomycin phosphotransferase gene. These vectors carried their respective genes into a wide variety of cell types, including primary skin fibroblasts and hematopoietic cells. Infection efficiencies varied with cell type and ranged up to 3.0%. Coinfection of two different recombinant viruses was also used to introduce two different sequences simultaneously into a given cell. Finally, methods for obtaining recombinant AAV vectors with minimal contamination of wild-type virus are described. These various attributes of AAV vectors make them a viable DNA transduction system.
Graft repair of a peripheral nerve without the sacrifice of a healthy donor nerve by the use of acutely dissociated autologous Schwann cells (2005)

We hypothesised that pieces of nerve that are normally trimmed away during graft repair could be a source of Schwann cells and used to create an autologous cell-containing nerve graft. To test the idea a transsection injury was made on the rat sciatic nerve. Seven days later, pieces from the proximal and distal stumps were used for immediate isolation of its non-neuronal cells. These cells, of which 80% were Schwann cells, were injected into a silicone tube bridging a 10 mm gap on the same nerve. Tubes containing cells showed superior regeneration of nerve fibres across the gap compared with tubes with no cells. This new repair technique is rapid, does not require the sacrifice of a healthy donor nerve, or the time-consuming culturing and expansion of Schwann cells. The method has the potential to replace current methods for repair of extended nerve injuries.
Introduction by molecular cloning of artifactual inverted sequences at the 5' terminus of the sense strand of bovine parathyroid hormone cDNA. (1981)

To study the structure and function of the gene for parathyroid hormone, we obtained recombinant plasmids containing bovine parathyroid hormone cDNA. The nucleotide sequence at the 5' terminus (relative to the sense strand) of the cDNA insert in a recombinant plasmid, pPTHi4, was different from that previously reported for the bovine parathyroid hormone cDNA insert of another recombinant plasmid, pPTHm1 [Kronenberg, H. M., McDevitt, B. F., Majzoub, J. A., Nathans, J., Sharp, P. A., Potts, J. T., Jr. & Rich, A. (1979) Proc. Natl. Acad. Sci. USA 76, 4981-4985]. The first 50 nucleotides of the pPTHm1 insert were an inverted complement of nucleotides 2-51 of the pPTHi4 insert. the cDNA insert of another plasmid, pPTHi8, contained a sequence identical to nucleotides 2-51 of the pPTHi4 insert but also contained an additional 42 bases at the 5' terminus. The first 41 bases of the pPTHi8 insert were an inverted repeat of an internal sequence of the pPTHi4 insert corresponding to nucleotides 184-224. Restriction endonuclease analysis of pPTHi8 indicated that the internal sequence corresponding to this region was retained. The nucleotide sequence of a restriction fragment hybridized to parathyroid hormone mRNA and extended toward the 5' terminus of the mRNA with reverse transcriptase confirmed that the sequence at the 5' terminus of the pPTHi4 insert was an accurate copy of the parathyroid hormone mRNA sequence. These data suggest that two types of sequence rearrangements may occur at the 5' terminus, as occurred in pPTHm1, and (ii) an inverted repeat of an internal sequence, as occurred in pPTHi8.
The Regulation and Expression of c-myc in Normal and Malignant Cells (1986)

Exhausted CD8 T (Tex) cells are a distinct cell lineage that arise during chronic infections and cancers in animal models and humans. Tex cells are characterized by progressive loss of effector functions, high and sustained inhibitory receptor expression, ...Read More
Preparation, morphologies, and properties of positively charged quaternized poly(phthalazinone ether sulfone ketone) nanofiltration membranes (2009)

Abstract Positively charged quaternized poly(phthalazinone ether sulfone ketone) (QAPPESK) nanofiltration (NF) membranes were prepared from chloromethylated poly(phthalazinone ether sulfone ketone) by the dye/wet phase inversion method with N ‐methyl‐2‐pyrrolidone (NMP) and N,N ‐dimethylacetamide (DMAc) as solvents. The effects of the ratio of NMP to DMAc, the evaporation time, the evaporation temperature, and the coagulation temperature on membrane performance were evaluated by the orthogonal design method. The results showed that the optimal preparation conditions were an NMP/DMAc ratio of 2/8, an evaporation time of 5 min at 70°C, and a coagulation temperature lower than 5°C. The effects of the additive type and concentration on the QAPPESK NF membrane cross‐section morphology and performance were investigated in detail. Furthermore, QAPPESK NF membranes exhibited good thermal stability with stable membrane performance for 120 h at 60°C. © 2009 Wiley Periodicals, Inc. J Appl Polym Sci, 2009
Near-Optimal Hashing Algorithms for Approximate Nearest Neighbor in High Dimensions (2006)

We present an algorithm for the c-approximate nearest neighbor problem in a d-dimensional Euclidean space, achieving query time of O(dn <sup xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">1</sup> c2/+o(1)) and space O(dn + n <sup xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">1+1</sup> c2/+o(1)). This almost matches the lower bound for hashing-based algorithm recently obtained in (R. Motwani et al., 2006). We also obtain a space-efficient version of the algorithm, which uses dn+n log <sup xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">O(1)</sup> n space, with a query time of dn <sup xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">O(1/c2)</sup> . Finally, we discuss practical variants of the algorithms that utilize fast bounded-distance decoders for the Leech lattice
Herpes Simplex Virus Type 2 ICP47 Inhibits Human TAP but Not Mouse TAP (1998)

Herpes simplex virus serotype 1 (HSV-1) expresses an immediate-early protein, ICP47, that effectively blocks the major histocompatibility complex class I antigen presentation pathway. HSV-1 ICP47 (ICP47-1) binds with high affinity to the human transporter associated with antigen presentation (TAP) and blocks the binding of antigenic peptides. HSV type 2 (HSV-2) ICP47 (ICP47-2) has only 42% amino acid sequence identity with ICP47-1. Here, we compared the levels of inhibition of human and murine TAP, expressed in insect cell microsomes, by ICP47-1 and ICP47-2. Both proteins inhibited human TAP at similar concentrations, and the K(D) for ICP47-2 binding to human TAP was 4.8 x 10(-8) M, virtually identical to that measured for ICP47-1 (5.2 x 10(-8) M). There was some inhibition of murine TAP by both ICP47-2 and ICP47-1, but this inhibition was incomplete and only at ICP47 concentrations 50 to 100 times that required to inhibit human TAP. Lack of inhibition of murine TAP by ICP47-1 and ICP47-2 could be explained by an inability of both proteins to bind to murine TAP.
Oxygen Partial Pressure in Outer Layers of Skin: Simulation Using Three‐Dimensional Multilayered Models (2005)

Papillary loops in dermal papillae facilitate oxygen delivery to the germinal layer from the circulation. The flow rate in papillary loops affects pO2 distribution in dermal papillae. In the epidermis, however, pO2 is strongly affected by skin surface conditions.
Laryngotracheal Topicalization with Lidocaine Before Intubation Decreases the Incidence of Coughing on Emergence from General Anesthesia (2004)

Coughing on emergence can result in a number of undesirable side effects, including hypertension, tachycardia, tachyarrhythmias, increased intracranial pressure, and increased intraocular pressure. The efficacy of endotracheal spraying with lidocaine at the time of intubation in preventing coughing on emergence is unknown. In a double-blind placebo-controlled study, we randomized 50 ASA physical status I and II patients presenting for elective gynecological surgery <2 h duration to receive either endotracheal lidocaine 160 mg or placebo before intubation. Both groups were comparable in terms of demographics and intraoperative conditions. The incidence of coughing before tracheal extubation was less frequent in the lidocaine group (26%) than in the placebo group (66%, P < 0.01), as was the incidence after tracheal extubation (4% versus 30%, P = 0.022). This study supports the use of endotracheal lidocaine before intubation in patients undergoing general anesthesia for surgery <2 h duration where coughing on emergence is undesirable.
Immunotherapy of Hormone-Refractory Prostate Cancer With Antigen-Loaded Dendritic Cells (2000)

Provenge is a novel immunotherapy agent that is safe and breaks tolerance to the tissue antigen PAP. Preliminary evidence for clinical efficacy warrants further exploration.
VideoMule (2009)

With the growing proliferation of conversational media and devices for generating multimedia content, the Internet has seen an expansion in websites catering to user-generated media. Most of the user-generated content is multimodal in nature as it has videos, audio, text (in the form of tags), comments and so on. Content analysis is a challenging problem on this type of media since it is noisy, unstructured and unreliable. In this paper we propose VideoMule, a consensus learning approach for multi-label video classification from noisy user-generated videos. In our scheme, we train classification and clustering algorithms on individual modes of information such as user comments, tags, video features and so on. We then combine the results of trained classifiers and clustering algorithms using a novel heuristic consensus learning algorithm which as a whole performs better than each individual learning model.
Transducin-α C-terminal Peptide Binding Site Consists of C-D and E-F Loops of Rhodopsin (1997)

The binding of heterotrimeric GTP-binding proteins (G-proteins) to serpentine receptors involves several independent contacts. We have deduced the points of interaction between mutant bovine rhodopsins and alphat-(340-350), a peptide corresponding to the C terminus of the alpha subunit (alphat) of bovine retinal G-protein, transducin. Direct binding of alphat-(340-350) to rhodopsin stabilizes the activated metarhodopsin II state (M II), consequently uncoupling the rhodopsin-transducin interaction. This peptide action requires two segments on the cytoplasmic domain of rhodopsin: the Tyr136-Val137-Val138-Val139 sequence on the C-D loop and the Glu247-Lys248-Glu249-Val250-Thr251 sequence on the E-F loop. We propose that a tertiary interaction of these two loop regions forms a pocket for binding the alphat C terminus of the transducin during light transduction in vivo. In most G-proteins, the C termini of alpha subunits are important for interaction with receptors, and, in several serpentine receptors, regions similar to those in rhodopsin are essential for G-protein activation, indicating that the interaction described here may be a generally applicable mode of G-protein binding in signal transduction.