gebhart/patrepeval huggingface dataset:
A micro-channel heat sink with integrated temperature sensors for phase transition study (1999)

A unique technique of maskless and self-aligned Si etch between bonded wafers was developed and applied to fabricate a micro-channel heat sink integrated with a heater and an array of temperature sensors. The technique allowed the formation of self-aligned and self-stopped etching of grooves between the bonded wafers. The device, consisting of distributed sensors, allowed direct temperature measurements to evaluate local heat transfer rates under forced convection boiling conditions. Temperature distributions along the heat sink were measured for different levels of power dissipation. The onset of critical heat flux condition was investigated as a function of channel size and liquid flow rate. The results suggest that the bubble dynamic mechanism in micro-channels maybe different from that with conventional channels.
BRAF Kinase Activation via Chromosomal Rearrangement in Radiation-Induced and Sporadic Thyroid Cancer (2005)

Activating point mutations of the BRAF gene have been recently described in a variety of human tumors. In a study published in the Journal of Clinical Investigation, we reported a novel mechanism of activation of this gene via paracentric inversion of chromosome 7q. The fusion protein, AKAP9-BRAF, contains the intact kinase domain and lacks the autoinhibitory N-terminal portion of BRAF. It exhibited constitutive activation of BRAF kinase and was transforming for NIH3T3 cells. This finding represents the first demonstration of RAF activation by chromosomal rearrangement in human tumors. AKAP9-BRAF was more common in radiation-induced thyroid tumors, whereas point mutations of BRAF predominated in sporadic tumors of the same type, demonstrating the association between environmental factors and specific mechanisms of BRAF activation.
Different mucins are produced by the surface epithelium and the submucosa in human trachea: identification of MUC5AC as a major mucin from the goblet cells (1996)

Mucins were extracted from the epithelial surface and the submucosal tissue of human trachea in order to enrich glycoproteins from the goblet cells and the submucosal glands respectively. The macromolecules were purified using density-gradient centrifugation, and the presence of the MUC5AC mucin was investigated using an antiserum raised against a synthetic peptide based on the sequence of the MUC5AC apoprotein. Mucins from the surface epithelium showed a higher reactivity with the antiserum relative to carbohydrate than those from the submucosa, and ion-exchange HPLC of reduced subunits revealed the presence of two distinct mucin populations in the samples. The predominant species from the surface epithelium was more acidic than the major population from the submucosa and showed a strong reactivity with the anti-MUC5AC anti-serum. In contrast, the major portion of the submucosal mucins were less acidic and showed no MUC5AC reactivity, although a more acidic population did react with the antibody. Rate-zonal centrifugation showed that the MUC5AC mucin from the surface epithelium is smaller than the major submucosal mucin, and that both are composed of subunits. Immunolocalization confirmed that the MUC5AC mucin from human trachea originates from the goblet cells and that this glycoprotein is not a major product of the submucosal glands.
Evaluation of perianal fistulas in patients with Crohn's disease. (2005)

Crohn's disease is a chronic inflammatory disorder that can affect any part of the gastrointestinal tract from the mouth to the anus. The disease is characterized by transmural inflammation that can be complicated by the development of fibrotic strictures, perforation, abscess formation, and fistulization. Perianal fistulas may arise from inflamed or infected anal glands (fistula-in-ano) and/or penetration of fissures or ulcers of the rectum or anal canal.[1] Classification of fistulas in Crohn's disease is based on the origin and terminus of the fistulous tract. Fistulas may develop between 2 segments of bowel (enteroenteric fistula), a segment of bowel and an adjacent organ (eg, enterovesicular), or between a segment of bowel and the skin (enterocutaneous).[2,3] Fistulas that communicate with the skin are known as external fistulas; those that communicate with adjacent structures within the abdomen and pelvis are known as internal fistulas.[2] Population-based estimates of the lifetime risk of fistula development in Crohn's disease range from 14% to 38%.[4–6] The development of fistulas may precede or coincide with the diagnosis of Crohn's disease. One cohort study estimated the rate of fistula formation preceding the diagnosis of Crohn's disease to be 45%.[4,5,7] Rates of spontaneous fistula closure are low, with estimates ranging from as low as 6% to 13% in placebo-treated patients in randomized controlled trials of 6-mercaptopurine (6-MP) and infliximab.[8,9] Spontaneous remission rates of simple fistulas-in-ano have been reported to be as high as 50%.[7,10]
Synthesis of Potential Antineoplastic Agents. XV. Some 1,4-Bisamides of 1,2,3,4-Tetrahydroquinoxaline1,2 (1966)

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTSynthesis of Potential Antineoplastic Agents. XV. Some 1,4-Bisamides of 1,2,3,4-Tetrahydroquinoxaline1,2Peter Schuyler, Frank D. Popp, Adria Catala Noble, Dru W. Alwani, and Barry R. MastersCite this: J. Med. Chem. 1966, 9, 5, 704–707Publication Date (Print):September 1, 1966Publication History Published online1 May 2002Published inissue 1 September 1966https://pubs.acs.org/doi/10.1021/jm00323a015https://doi.org/10.1021/jm00323a015research-articleACS PublicationsRequest reuse permissionsArticle Views106Altmetric-Citations4LEARN ABOUT THESE METRICSArticle Views are the COUNTER-compliant sum of full text article downloads since November 2008 (both PDF and HTML) across all institutions and individuals. These metrics are regularly updated to reflect usage leading up to the last few days.Citations are the number of other articles citing this article, calculated by Crossref and updated daily. Find more information about Crossref citation counts.The Altmetric Attention Score is a quantitative measure of the attention that a research article has received online. Clicking on the donut icon will load a page at altmetric.com with additional details about the score and the social media presence for the given article. Find more information on the Altmetric Attention Score and how the score is calculated. Share Add toView InAdd Full Text with ReferenceAdd Description ExportRISCitationCitation and abstractCitation and referencesMore Options Share onFacebookTwitterWechatLinked InRedditEmail Other access optionsGet e-Alertsclose Get e-Alerts
All‐trans retinoic acid displays multiple effects on the growth, lipogenesis and adipokine gene expression of AML‐I preadipocyte cell line (2012)

Adipose tissue is a potential site of retinoic acid (RA) action, but its physiological significance remains to be clarified. We have examined the effect of all-trans retinoic acid (ATRA) on growth and differentiation of preadipocytes, and on adipokine gene expression in mature adipocytes using human preadipocyte cell model, AML-I. Both ATRA and 9-cis RA induced growth arrest in AML-I preadipocyte at between 50 and 100 µM, which was accompanied by apoptosis. Western blotting showed a loss of NF-κB, Bcl-2 and p-Akt, and the accumulation of Bad and Akt in cytoplasm of ATRA-treated AML-I preadipocytes. Exposure of AML-I to ATRA or 9-cis RA increased intracellular lipid accumulation in a time-dependent manner compared to vehicle-treated cells. Expression of fatty acid synthase (FAS) and peroxisome proliferator-activated receptor-γ (PPAR-γ) proteins was increased in ATRA-treated cells. Thus, both ATRA and 9-cis RA promoted differentiation, inhibited proliferation and induced apoptosis in AML-I preadipocytes. ATRA also modulated adipokine expression by increasing the mRNA level of adipocytokines (adiponectin, leptin and LPL), and by inhibiting PAI-1 mRNA expression in mature AML-I adipocytes. The data suggest that ATRA exerts a wide range of effects--growth arrest, apoptosis, lipogenesis and modulation of adipokine gene expression--during the maturation of preadipocytes into adipocytes.
Modulation of p53 C-Terminal Acetylation by mdm2, p14ARF, and Cytoplasmic SirT2 (2013)

Acetylation of C-terminal lysine residues in the p53 tumor suppressor is associated with increased stability and transcription factor activity. The function, protein level, and acetylation of p53 are downregulated by mdm2, which in its turn is inhibited by the p14(ARF) tumor suppressor. Here, we show that p14(ARF) increases the level of p53 acetylated at lysine 382 in a nuclear chromatin-rich fraction. Unexpectedly, this accumulation of p53AcK382 is dramatically enhanced in the presence of ectopic mdm2. In light of these observations, we propose that p14(ARF) increases the binding of p53-mdm2 complexes to chromatin, thereby limiting the access of protein deacetylases to p53. Supporting this notion, we show that p53AcK382 can be deacetylated in the cytoplasm and that sirtuin SirT2 catalyzes this reaction. These results help understand why inhibition of both SirT1 and SirT2 is needed to achieve effective activation of p53 by small-molecule sirtuin inhibitors.
Plasma and Cerebrospinal Fluid Interleukin-6 Concentrations in Posttraumatic Stress Disorder (2001)

PTSD patients have increased CSF concentrations of IL-6. Their plasma IL-6 is not elevated but is more tightly associated with noradrenergic output in these patients than in normals. Both findings might be explained by the low cortisol secretion previously reported in PTSD as a result of lowered glucocorticoid suppression of IL-6 secretion. High levels of CSF IL-6 may reflect neurodegeneration or compensatory neuroprotection.
Phase I trial of an interleukin-2 (IL-2) fusion toxin (DAB486IL-2) in hematologic malignancies expressing the IL-2 receptor (1992)

DAB486IL-2 is a recombinant fusion toxin in which the native receptor binding domain of diphtheria toxin has been replaced with human interleukin-2 (IL-2). It selectively binds and intoxicates only cells that bear the high-affinity receptor for IL-2. In the first clinical trial of a genetically engineered ligand fusion-toxin, we have treated 18 patients with chemotherapy-resistant IL-2 receptor expressing hematologic malignancies with escalating doses of DAB486IL-2. The maximal tolerated dose of a daily intravenous bolus of DAB486IL-2 was 0.1 mg/kg per day for 10 doses, established by asymptomatic, reversible elevations of hepatic transaminases without changes in other tests of liver function. Other mild reversible side effects noted were rash, nausea, elevated creatinine, chest tightness, and fever. Pharmacokinetic analysis showed a monophasic clearance of 5.8 +/- 0.7 minutes with peak levels of 3,549 +/- 1,041 mg/mL at the 0.1 mg/kg dose. Approximately 50% of patients developed an antibody response to diphtheria toxin or DAB486IL-2. The presence of such antibodies did not preclude patients from experiencing an antitumor response as four of the six patients with antitumor effect had detectable antibody titers. Although this was a phase I trial designed to define the safety of DAB486IL-2, remissions were observed in three patients lasting from 5 to over 18 months. The ability to achieve significant tumor reductions in this group of heavily treated patients is encouraging and suggests additional trials are warranted in hematologic malignancies.
The Genome of M. acetivorans Reveals Extensive Metabolic and Physiological Diversity (2002)

Methanogenesis, the biological production of methane, plays a pivotal role in the global carbon cycle and contributes significantly to global warming. The majority of methane in nature is derived from acetate. Here we report the complete genome sequence of an acetate-utilizing methanogen, Methanosarcina acetivorans C2A. Methanosarcineae are the most metabolically diverse methanogens, thrive in a broad range of environments, and are unique among the Archaea in forming complex multicellular structures. This diversity is reflected in the genome of M. acetivorans. At 5,751,492 base pairs it is by far the largest known archaeal genome. The 4524 open reading frames code for a strikingly wide and unanticipated variety of metabolic and cellular capabilities. The presence of novel methyltransferases indicates the likelihood of undiscovered natural energy sources for methanogenesis, whereas the presence of single-subunit carbon monoxide dehydrogenases raises the possibility of nonmethanogenic growth. Although motility has not been observed in any Methanosarcineae, a flagellin gene cluster and two complete chemotaxis gene clusters were identified. The availability of genetic methods, coupled with its physiological and metabolic diversity, makes M. acetivorans a powerful model organism for the study of archaeal biology. [Sequence, data, annotations and analyses are available at http://www-genome.wi.mit.edu/.]
Nitric Oxide and Angiogenesis in Cardiovascular Disease (2002)

Ischemic heart disease and peripheral artery disease mainly develop as a consequence of atherosclerotic lesion formation. Angiogenesis, the formation of new blood vessels from the preexisting vascular bed, is of paramount importance in the maintenance of vascular integrity both in the repair process of damaged tissue (wound healing) and in the formation of collateral vessels in response to tissue ischemia. Angiogenesis is a complex process that is orchestrated by a multitude of cytokines/chemokines and growth factors. In its broadest sense, angiogenesis cannot be viewed as a single process. It is likely that different mediators are involved in different phases of angiogenesis. Vascular endothelial cells produce nitric oxide (NO), an endothelium-derived labile molecule, which maintains vascular homeostasis and thereby prevents vascular atherosclerotic changes. In patients with ischemic heart disease and peripheral artery disease, the release of endothelium-derived NO is decreased, which plays an important role in the atherosclerotic disease progression. In recent years, endothelium-derived NO has been shown to modulate angiogenesis in vitro and in vivo. In this review, we summarize recent progress in the field of the NO-mediated regulation of postnatal angiogenesis.
Herpes simplex virus NV1020 as a novel and promising therapy for hepatic malignancy (2008)

We have found that NV1020 is a safe, novel therapeutic agent for treatment of refractory hepatic malignancy.
Parsing Natural Scenes and Natural Language with Recursive Neural Networks (2011)

Recursive structure is commonly found in the inputs of different modalities such as natural scene images or natural language sentences. Discovering this recursive structure helps us to not only identify the units that an image or sentence contains but also how they interact to form a whole. We introduce a max-margin structure prediction architecture based on recursive neural networks that can successfully recover such structure both in complex scene images as well as sentences. The same algorithm can be used both to provide a competitive syntactic parser for natural language sentences from the Penn Treebank and to outperform alternative approaches for semantic scene segmentation, annotation and classification. For segmentation and annotation our algorithm obtains a new level of state-of-theart performance on the Stanford background dataset (78.1%). The features from the image parse tree outperform Gist descriptors for scene classification by 4%. 1.
Structure and flexibility of the endosomal Vps34 complex reveals the basis of its function on membranes (2015)

Phosphatidylinositol 3-kinase Vps34 complexes regulate intracellular membrane trafficking in endocytic sorting, cytokinesis, and autophagy. We present the 4.4 angstrom crystal structure of the 385-kilodalton endosomal complex II (PIK3C3-CII), consisting of Vps34, Vps15 (p150), Vps30/Atg6 (Beclin 1), and Vps38 (UVRAG). The subunits form a Y-shaped complex, centered on the Vps34 C2 domain. Vps34 and Vps15 intertwine in one arm, where the Vps15 kinase domain engages the Vps34 activation loop to regulate its activity. Vps30 and Vps38 form the other arm that brackets the Vps15/Vps34 heterodimer, suggesting a path for complex assembly. We used hydrogen-deuterium exchange mass spectrometry (HDX-MS) to reveal conformational changes accompanying membrane binding and identify a Vps30 loop that is critical for the ability of complex II to phosphorylate giant liposomes on which complex I is inactive.
Ubiquitin carboxyl-terminal hydrolase acts on ubiquitin carboxyl-terminal amides. (1985)

Ubiquitin carboxyl-terminal hydrolase (formerly known as ubiquitin carboxyl-terminal esterase), from rabbit reticulocytes, has been shown to hydrolyze thiol esters formed between the ubiquitin carboxyl terminus and small thiols (e.g. glutathione), as well as free ubiquitin adenylate (Rose, I. A., and Warms, J. V. B. (1983) Biochemistry 22, 4234-4237). We now show that this enzyme hydrolyzes amide derivatives of the ubiquitin carboxyl terminus, including those of lysine (epsilon-amino), glycine methyl ester, and spermidine. It also hydrolyzes ubiquitin COOH-terminal hydroxamic acid, but is inactivated under the conditions for assaying ubiquitin-hydroxylamine adduct hydrolysis. Amide adducts formed between ubiquitin and epsilon-amino groups of protein lysine residues are much poorer substrates than is the ubiquitin amide of the epsilon-amino group of free lysine. The enzyme is thus a general hydrolase that recognizes the ubiquitin moiety, but is highly selective for small ubiquitin derivatives. It probably functions to regenerate ubiquitin from adventitiously formed ubiquitin amides and thiol esters. It also has the correct specificity to function in regenerating ubiquitin from small ubiquitin peptides that are probable end products of ubiquitin-dependent proteolysis. A simple, large-scale preparation of the enzyme from human erythrocytes is described.
Elimination of anti-Gal B cells by ??-Gal ricin1 (2002)

Administration of alpha-gal ricin results in specific elimination of anti-Gal B cells in alpha 1,3GT KO mice. The elimination of these B cells may prove to be helpful in attempts to achieve immune tolerance to alpha-gal epitopes in primates.
Characterization of the Prediabetic State (1997)

First degree relatives of patients with non-insulin-dependent diabetes mellitus (NIDDM) have a 40% risk of developing NIDDM during their lifetime and the risk seems to be greater if the disease is inherited from the mother than from the father. It has also become clear that metabolic abnormalities are demonstrable long before the disease becomes manifest. The prediabetic state is associated with a predisposition to abdominal obesity, insulin resistance, lipid disorders, high blood pressure, and microalbuminuria, ie, the metabolic or insulin resistance syndrome. It is, however, not yet known whether treatment of these abnormalities is able to prevent progression to manifest NIDDM.
Effect of colesevelam on liver fat quantified by magnetic resonance in nonalcoholic steatohepatitis: A randomized controlled trial (2012)

Colesevelam increases liver fat in patients with NASH as assessed by MRI as well as MRS without significant changes seen on histology. Thus, MRI and MRS may be better than histology to detect longitudinal changes in hepatic fat in NASH. Underlying mechanisms and whether the small MR-detected increase in liver fat has clinical consequences is not known.
EFFECT OF MITOMYCIN C ON THE GROWTH OF SOME ANIMAL VIRUSES (1961)

We introduce an intuitive particle-based model of time-symmetric quantum physics that gives a concrete description of what goes on in the time between projective measurements of a quantum system. The time-symmetry in this model means that we ...Physical interpretations of the time-symmetric formulation of quantum mechanics, due to Aharonov, Bergmann, and Lebowitz are discussed in terms of weak values. The most direct, yet somewhat naive, interpretation uses the time-symmetric formulation to ...
Monitoring the Safety of a Smallpox Vaccination Program in the United States: Report of the Joint Smallpox Vaccine Safety Working Group of the Advisory Committee on Immunization Practices and the Armed Forces Epidemiological Board (2008)

In December 2002, the Centers for Disease Control and Prevention's Advisory Committee on Immunization Practices and the Department of Defense Armed Forces Epidemiological Board formed a joint Smallpox Vaccine Safety Working Group (SVS WG) to provide independent safety oversight for smallpox vaccination safety-monitoring systems. From January 2003 through June 2004, the SVS WG reviewed individual and aggregate safety data on postvaccination adverse events. Serious adverse events were rare because of careful education, prevaccination screening, and strict attention to vaccination-site management. Recent vaccinees safely cared for high-risk patients, adhering to recommended site care. Human immunodeficiency virus-infected individuals without severe immunosuppression had uncomplicated vaccination reactions. Epidemiological studies supported a causal relationship between myocarditis and/or pericarditis and smallpox vaccination. Data supported neutrality regarding hypothesized causal associations between vaccination and dilated cardiomyopathy or ischemic cardiac disease. The SVS WG concurs with recommendations to defer from vaccination any person with >/=3 ischemic cardiac disease risk factors.
RING Domain E3 Ubiquitin Ligases (2009)

E3 ligases confer specificity to ubiquitination by recognizing target substrates and mediating transfer of ubiquitin from an E2 ubiquitin-conjugating enzyme to substrate. The activity of most E3s is specified by a RING domain, which binds to an E2 approximately ubiquitin thioester and activates discharge of its ubiquitin cargo. E2-E3 complexes can either monoubiquitinate a substrate lysine or synthesize polyubiquitin chains assembled via different lysine residues of ubiquitin. These modifications can have diverse effects on the substrate, ranging from proteasome-dependent proteolysis to modulation of protein function, structure, assembly, and/or localization. Not surprisingly, RING E3-mediated ubiquitination can be regulated in a number of ways. RING-based E3s are specified by over 600 human genes, surpassing the 518 protein kinase genes. Accordingly, RING E3s have been linked to the control of many cellular processes and to multiple human diseases. Despite their critical importance, our knowledge of the physiological partners, biological functions, substrates, and mechanism of action for most RING E3s remains at a rudimentary stage.