gebhart/patrepeval huggingface dataset:
Melanocortin-4 Receptor Antagonists as Potential Therapeutics in the Treatment of Cachexia (2007)

The melanocortin-4 (MC4) receptor subtype plays a pivotal role in body weight regulation. Knock-out or mutation of MC4 receptors in animals or humans leads to severe obesity and acute or sub-acute antagonism of central MC4 receptors produces an increase in food intake and a decrease in metabolism. Knock-out or antagonism of MC4 receptors in animal models of cachexia leads to a protection from anorexia and the loss of both lean and fat body mass, suggesting that an MC4 antagonist may be beneficial in wasting diseases, which are poorly treated by available therapies. Considerable progress has been made in the discovery of non-peptide antagonists with high affinity and selectivity for MC4 receptors. Optimization of these compounds has produced molecules that are active upon systemic administration and are effective in protecting against cachectic symptoms in animal models of tumor-induced wasting. Further development of such compounds is greatly anticipated as a potential means to combat the cachexia that results from chronic diseases such as cancer, AIDS, renal failure, liver failure, congestive heart failure and lung disease.
Age-related changes in the structur ea nd function of skeletal muscles (2007)

Summary 1. Fo ra nimals of all ages, during acti vation of skeletal muscles and the subsequent contraction, the balance between the force developed by the muscle and the external load determines whether the muscle shortens, remains at fixed length (isometric), or is lengthened. With maximum activation, the force developed is least during shortening, intermediate when muscle length is f ixed, and greatest during lengthening contractions. During lengthening contractions, when force is high, muscles may be injured by the contractions. 2. ‘Frailty’ and ‘failure to thri ve ’a re most frequently observed in elderly ,p hysically inactive p eople. A ‘frail’ person is defined as one of small stature, with muscles that are atrophied, weak, and easily f atigued. The condition of ‘failure to thrive ’i st ypified by a lack of response to welldesigned programs of nutrition and physical activity. 3. With aging, skeletal muscle atroph yi nh umans appears to be inevitable. A gradual loss of muscle fibres begins at approximately age 50 years and continues such that by age 80, ~50% of the fibres are lost from the limb muscles that have been studied. Fo rb oth humans and rats, the observation that the timing and magnitude of the loss of motor units is similar to that for muscle fibres, suggests that the mechanism responsible for the loss of fibres and the loss of whole motor units is the same. The degree of atroph yo f the fibres that remain is lar gely dependent on the habitual leve lo fp hysical activity of the individual. 4. ‘Master athletes’ maintain a high le ve lo ffi tness throughout their life span. Even among master athletes, performance of marathon runners and weight lifters declines after about 40 years of age, with peak le vels of performance decreased by ~50% by age 80. The success of the master athletes and of previously sedentary elderly who undertak ew ell-designed, carefully administered training programs provide dramatic evidence that age-associated atrophy, w eakness, and fatigability can be slowed but not halted.
The Prevalence of Non-Alcoholic Fatty Liver Disease in Patients With Inflammatory Bowel Disease (2017)

Introduction: It is well-established that central obesity, insulin resistance, and dysplipidemia are common risk factors for the development of non-alcoholic fatty liver disease (NAFLD). Patients with inflammatory bowel disease (IBD), including Crohn's disease (CD) and ulcerative colitis (UC), often do not have features of the metabolic syndrome. The chronic inflammatory state of IBD may predispose to development of fatty liver, as inflammation is a part of the pathogenesis of fatty liver. The aim of this study is to determine the prevalence of fatty liver in those with diagnosed IBD. Methods: A retrospective chart review was performed on 300 consecutive outpatients with diagnosis codes consistent with IBD (UC, CD, and indeterminate colitis) from 2009-2015 at a single urban academic medical center. IBD diagnosis was biopsy proven or as confirmed by outpatient gastroenterologist documentation. Patients were excluded if they had co-existing liver disease, history of liver transplantation, or paucity of clinical/laboratory data. Demographic information, in addition to liver function tests, BMI, medications, results of imaging studies, and comorbidities, including hypertension and diabetes were recorded. ALT values were deemed abnormal if value > 29. Results: Of the 300 patients with IBD reviewed, 201 patients met criteria and were included in the study. There were 74 patients (36.8%) with an ALT >29. Of those with elevated ALT, 34.1% had UC, and 38.6% had CD. Of those with an ALT >29, 38.0% of patients did not have any follow-up imaging performed. Of those who had imaging, 29.0% (8 patients) had evidence of either steatosis or fatty infiltration. Those who were noted to have hepatic steatosis or fatty liver had mean BMI 32.4, (range 19-46). This compares to an average BMI of 27.1 (range 15-47) for the 199 patients in the IBD cohort that had BMI available. Of the 8 patients who had radiographic evidence of steatosis or fatty infiltration, 50% of them had evidence of HTN and DM. Four of the 8 patients were also actively getting anti-TNF medications. Conclusion: Almost a third of patients with IBD had ALT elevation, and a third of these patients were found to have radiographic evidence of steatosis. Our study confirms the high prevalence of ALT elevation in IBD patients of which a large percentage could be attributable to NAFLD. NAFLD is a potentially serious cause of liver injury and IBD patients, specifically those with metabolic syndrome, may be at increased risk.
Potent and Long-Acting Corticotropin Releasing Factor (CRF) Receptor 2 Selective Peptide Competitive Antagonists (2002)

We present evidence that members of the corticotropin releasing factor (CRF) family assume distinct structures when interacting with the CRF(1) and CRF(2) receptors. Predictive methods, physicochemical measurements, and structure-activity relationship studies have suggested that CRF, its family members, and competitive antagonists such as astressin [cyclo(30-33)[DPhe(12),Nle(21),Glu(30),Lys(33),Nle(38)]hCRF((12-41))] assume an alpha-helical conformation when interacting with their receptors. We had shown that alpha-helical CRF((9-41)) and sauvagine showed some selectivity for CRF receptors other than that responsible for ACTH secretion(1) and later for CRF2.(2) More recently, we suggested the possibility of a helix-turn-helix motif around a turn encompassing residues 30-33(3) that would confer high affinity for both CRF(1) and CRF(2)(2,4) in agonists and antagonists of all members of the CRF family.(3) On the other hand, the substitutions that conferred ca. 100-fold CRF(2) selectivity to the antagonist antisauvagine-30 [[DPhe(11),His(12)]sauvagine((11-40))] did not confer such property to the corresponding N-terminally extended agonists. We find here that a Glu(32)-Lys(35) side chain to side chain covalent lactam constraint in hCRF and the corresponding Glu(31)-Lys(34) side chain to side chain covalent lactam constraint in sauvagine yield potent ligands that are selective for CRF(2). Additionally, we introduced deletions and substitutions known to increase duration of action to yield antagonists such as cyclo(31-34)[DPhe(11),His(12),C(alpha)MeLeu(13,39),Nle(17),Glu(31),Lys(34)]Ac-sauvagine((8-40)) (astressin(2)-B) with CRF(2) selectivities greater than 100-fold. CRF receptor autoradiography was performed in rat tissue known to express CRF(2) and CRF(1) in order to confirm that astressin(2)-B could indeed bind to established CRF(2) but not CRF(1) receptor-expressing tissues. Extended duration of action of astressin(2)-B vs that of antisauvagine-30 is demonstrated in the CRF(2)-mediated animal model whereby the inhibition of gastric emptying of a solid meal in mice by urocortin administered intraperitoneally at time zero is antagonized by the administration of astressin(2)-B but not by antisauvagine-30 at times -3 and -6 h while both peptides are effective when given 10 min before urocortin.
SAW and BAW technologies for RF filter applications: A review of the relative strengths and weaknesses (2008)

Acoustic filter technologies based on piezoelectric materials play a key role in wireless communication as they guarantee spectral integrity of RF signals. SAW filters have been used for this purpose since the early days of mobile phones. BAW filters are a relatively recent addition to the technology portfolio. Each technology claims to have unique advantages over the other. This paper gives a detailed review of the strength and weaknesses for both technologies. The aspects covered include process complexity, unique features, performance parameters and limitations. The application space for RF filters will be mapped out to identify areas where either SAW or BAW dominates or where they compete. Both technologies follow a steep path of improvements which involves introducing new materials, processes and design methods. Rivalry put aside there are many areas where advanced SAW and BAW can benefit from each other.
Use of Nanomaterials in Cementing Applications (2012)

Abstract The two principal functions of oilwell cementing are to restrict fluid movement between zones within the formation and to bond and support the casing. Apart from these, the cement sheath also protects casing from corroding, protects the casing from shock loads when drilling deeper, and plugs lost circulation or thief zones. Once cement is placed in the wellbore, initial setting occurs wherein development of compressive strength becomes more important for further drilling operations. Early strength development is important to help ensure structural support to the casing and hydraulic and mechanical isolation of downhole intervals. Delays in strength development cause significant amounts of lost time because of the need to wait on cement (WOC). Typically, an accelerator is often used to enable early strength development in cement. It is desired that an accelerator should improve overall compressive strength without causing excessive gelation. Nanomaterials (being smaller in size and higher in surface area) are used in several fields, including catalysis, polymers, electronics, and biomedicals. Because of a higher surface area, these materials can also be used in oilwell cementing to accelerate the cement hydration process. Moreover, they are often required in small quantities. This paper documents a case in which nanosilica was used in cement formulations to develop high early strength. Nanosilica also helps enhance final compressive strength and helps control fluid loss. Using the correct quantity of nanosilica, it is possible to design cement slurry with low rheology and good mechanical properties while controlling fluid loss.
Structure and expression of TIS21, a primary response gene induced by growth factors and tumor promoters (1991)

The TIS21 gene is a primary response gene that is induced rapidly and transiently in 3T3 cells by the tumor promoter and mitogen tetradecanoyl phorbol acetate. The predicted open reading frame of the TIS21 cDNA encodes a protein of 158 amino acids with no obvious similarity to any known protein. Antiserum prepared to TIS21 recombinant protein produced in Escherichia coli precipitates a 17-kDa protein from Swiss 3T3 cells. The 2040-nucleotide 3'-untranslated region of the cDNA includes an unusual T18 sequence. The TIS21 gene has a single 1.4-kilobase intron which interrupts the open reading frame and is otherwise identical to the cDNA sequence. The 5'-flanking sequence of the TIS21 gene contains TATA and CAAT box-type sequences, three potential Sp1 sites, two putative cyclic AMP response elements, two potential AP1 binding elements, and an AP2 element. A possible Z-DNA structure of 29 AC repeats is present 660 nucleotides from the start of transcription. Expression from a luciferase reporter construct containing a 460-nucleotide fragment of the TIS21 promoter is induced by tetradecanoyl phorbol acetate, forskolin, epidermal growth factor, and serum, despite the absence of a consensus serum response element.
Factor VIII Lacking the C2 Domain Retains Cofactor Activity in Vitro (2010)

Factor (F) VIII consists of a heavy chain (A1A2B domains) and light chain (A3C1C2 domains). The activated form of FVIII, FVIIIa, functions as a cofactor for FIXa in catalyzing the membrane-dependent activation of FX. Whereas the FVIII C2 domain is believed to anchor FVIIIa to the phospholipid surface, recent x-ray crystal structures of FVIII suggest that the C1 domain may also contribute to this function. We constructed a FVIII variant lacking the C2 domain (designated DeltaC2) to characterize the contributions of the C1 domain to function. Binding affinity of the DeltaC2 variant to phospholipid vesicles as measured by energy transfer was reduced approximately 14-fold. However, the activity of DeltaC2 as measured by FXa generation and one-stage clotting assays retained 76 and 36%, respectively, of the WT FVIII value. Modest reductions ( approximately 4-fold) were observed in the functional affinity of DeltaC2 FVIII for FIXa and rates of thrombin activation. On the other hand, deletion of C2 resulted in significant reductions in FVIIIa stability ( approximately 3.6-fold). Thrombin generation assays showed peak thrombin and endogenous thrombin potential were reduced as much as approximately 60-fold. These effects likely result from a combination of the intermolecular functional defects plus reduced protein stability. Together, these results indicate that FVIII domains other than C2, likely C1, make significant contributions to membrane-binding and membrane-dependent function.
Treatment of Chronic Wounds With Bone Marrow–Derived Cells (2003)

Directly applied bone marrow-derived cells can lead to dermal rebuilding and closure of nonhealing chronic wounds.
Autonomous authoring tools for hypertext (2007)

Autonomous authoring tools are routinely used to expedite the translation of large document collections into functioning hypertexts. They are also used to add hyperlinks to pre-existing hypertext structures. In this survey we describe a taxonomy of autonomous hypertext authoring tools. The classification of any given system is determined by the type and nature of the document analysis it performs.
The recognition specificity of a murine helper T cell for hemagglutinin of influenza virus A/PR/8/34. (1983)

A T cell line was established in long-term tissue culture from spleen cells of BALB/c mice immunized with influenza virus PR8 (A/PR/8/34(H1N1)) by continuous restimulation with PR8 virus and syngeneic x-irradiated spleen cells. This T cell line and clones derived from it have now been propagated for over 1 yr "in vitro". The T cell line and the clones, upon stimulation with Con A in the absence of antigen and irradiated spleen cells, as upon stimulation in the presence of antigen and adherent cells, produce T cell growth factors, B cell replication and maturation factors, and colony-stimulating factors, as tested by restimulation of proliferation of a clone of cytolytic murine T cells, of lipopolysaccharide-activated B cell blasts, and by macrophage/granulocyte colony formation of murine bone marrow cells, respectively. The T cell line and the clones help syngeneic B cells in the presence of syngeneic irradiated spleen cells and PR8 virus to proliferate and mature into clones of cells secreting virus-specific antibodies. In the presence of PR8 virus and of a bystander antigen, such as sheep red cells, B cells specific for this bystander antigen are also induced. Adoptive transfer of the T cells i.v. into syngeneic nu/nu BALB/c mice enable the recipient mice to produce, upon challenge with PR8, virus-specific antibodies and to clear virus infection of the lung. The virus-specific T cell line and the clones are restricted by H-2 antigens of the d-haplotype, probably by Iad, and recognize a determinant on the hemagglutinin (HA) molecule of PR8 virus. Fifty to 100 fmol of virus-associated or free HA suffice for stimulation as measured by proliferation assays. The stimulating determinant is present on the HA of all natural virus isolates of the H1 subtype, is absent from virus isolates of the H2 and H3 subtypes, and is abolished if glutamic acid at position 115 of the HA1 polypeptide of PR8 is replaced by lysine.
Case Studies in Pathological Science (1992)

Scientists are often viewed as com? mitted to tru h, unbiased by e o? tion, open to new ideas, and profes? sionally and personally unselfish, according to Michael J. Mahoney, an American author and psychologist. Similar sentiments have given rise to a widespread image of the archetypal scientist?someone painstakingly ob? taining objective data, testing every side of a question and disregarding personal interests. Like other arche? types, however, this flawlessly compe? tent and dispassionate scientist does not exist. Even scientists may lose objectiv? ity in the pursuit of truth. John Locke, the 17th-century English empiricist, recognized this possibility when he wrote: Error is not a fault of our knowledge, but a mistake of our judg? ment giving assent to that which is not true.... It is in man's power to content himself with the proofs he has, if they favor the opinion that suits with his in? clinations or interest, and so stop from further research. Errors in science created by a loss of objectivity consistently exhibit a simi? lar set of characteristics. Irving Lang muir, the late Nobel prize-winning chemist from General Electric, generat? ed a formal model of this syndrome and called it pathological science. He de? scribed six of this dis? ease. I have condensed Langmuir's six symptoms into two characteristics and added a third, which I believe is the most important.
Effect of cimetidine suspension on appetite and weight in overweight subjects. (1993)

Intake of cimetidine suspension 30 minutes before meals in overweight subjects may lead to reduced hunger, less food intake, and subsequent weight loss. This effect may be due to the suppression of gastric acid secretion. Cimetidine suspension may be a valuable adjunct in treating obesity.
Isoprostanes: markers and mediators of oxidative stress (2004)

Some years ago it was discovered that prostaglandin F2-like compounds are formed in vivo by nonenzymatic free radical-catalyzed peroxidation of arachidonic acid. Because these compounds are a series of isomers that contain the prostane ring of prostaglandins, they were termed F2-isoprostanes. Intermediates in the isoprostane pathway are prostaglandin H2-like compounds that become reduced to form F2-isoprostanes but also undergo rearrangement in vivo to form E2-, D2-, A2-, J2-isoprostanes, isothromboxanes, and highly reactive gamma-ketoaldehydes, termed isoketals. Analogous compounds have also been shown to be formed from free radical mediated oxidation of docosoahexaenoic acid. Because docosahexaenoic acid is highly enriched in neurons, these compounds have been termed neuroprostanes and neuroketals. An important aspect of the discovery of isoprostanes is that measurement of F2-isoprostanes has emerged as one of the most reliable approaches to assess oxidative stress status in vivo, providing an important tool to explore the role of oxidative stress in the pathogenesis of human disease. Measurement of F4-neuroprostanes has also proved of value in exploring the role of oxidative stress in neurodegenerative diseases. Products of the isoprostane pathway have been found to exert potent biological actions and therefore may participate as physiological mediators of disease.
Bifunctional protein required for asymmetric cell division and cell-specific transcription in Bacillus subtilis. (1996)

During sporulation in Bacillus subtilis an asymmetric cell division gives rise to unequal progeny called the prepore and the mother cell. Gene expression in the prespore is initiated by cell-specific activation of the transcription factor sigma(F). Three proteins participate in the regulation of sigma(F) activity. The first, SpoIIAB, is an inhibitor of sigma(F), that is, an anti-sigma factor. SpoIIAB is also a protein kinase that catalyzes phosphorylation of the second regulatory protein SpoIIAA (the anti-anti-sigma factor), and thus inactivates it. A third protein, SpoIIE, was shown recently to be able to dephosphorylate SpoIIAA-P in vitro. Here we show that SpoIIE is a bifunctional protein with two critical roles in the establishment of cell fate. First, we confirm by the use of in vivo experiments that it regulates the release of sigma(F) activity by dephosphorylating SpoIIAA-P. Second, we show that SpoIIE is needed for normal formation of the asymmetric septum that separates the prespore from the mother cell. Combination of these two functions in a single polypeptide may serve to couple the release of the cell-specific transcription factors with the formation of the differentiating cells.
Demonstration of a Relaxin Receptor and Relaxin-Stimulated Tyrosine Phosphorylation in Human Lower Uterine Segment Fibroblasts (1998)

To elucidate the mechanism of relaxin action, we studied the binding characteristics of human relaxin and its effects on intracellular concentrations of cAMP and tyrosine phosphorylation of cellular proteins in a model system of human cervix, human lower uterine segment fibroblasts. Human relaxin labeled with 125I bound specifically to a single class of high-affinity relaxin binding sites, distinct from insulin receptors, with a mean (±sem) dissociation constant (Kd) of 4.36 ± 1.7 × 10−9m and a mean of 3220 ± 557 binding sites per cell in human lower uterine segment fibroblasts. Relaxin, in quantities that were shown previously to stimulate intracellular levels of cAMP in other cell types, had no effect on intracellular levels of cAMP in human lower uterine segment fibroblasts even in the presence of the phosphodiesterase inhibitor 3-isobutyl-1-methyl-xanthine (IBMX). Incubation of the cells with relaxin caused a significant increase in tyrosine phosphorylation of a protein with an apparent Mr of approximately 220 kDa in these cells. In concert with results of recent studies that demonstrated that the Mr of the relaxin receptor is approximately 220 kDa, our data suggest that the phosphorylated protein is likely to be the relaxin receptor.
Distinct Responses of Interleukin-6 and Other Laboratory Parameters to Treatment in a Patient with Polyarteritis Nodosa—A Case Report (1992)

The authors describe a patient in whom the serum levels of interleukin-6 (IL-6) and other laboratory parameters were monitored. The IL-6 and C-reactive protein (CRP) levels, which were extremely high before treatment, declined rapidly with administration of prednisolone. Rheumatoid factor, IgG, and platelets count declined more gradually. Thus, determination of the serum IL-6 level might be useful in diagnosing and monitoring polyarteritis nodosa.