gebhart/patrepeval huggingface dataset:
Medical Therapy for Crohn’s Disease: Top-Down or Step-Up? (2007)

The emergency of effective biological therapy in the treatment of Crohn's disease (CD) has led to a clinical debate about 'step-up versus top-down strategy'. Step-up refers to the classic therapeutic approach, namely progressive intensification of treatment as disease severity increases. Top-down refers to the early introduction, in all CD patients, of intensive therapies, including biological agents and immunosuppressive drugs, with the aim of avoiding complications and improving quality of life, starting from the assumption that these drugs may interfere with the natural history of the disease. Very recently the Belgian IBD research group together with the Gut Club of North Holland designed 'the Step Up versus Top Down Trial'. Combination of infliximab with immunosuppressives at onset was better than the current standard approach in terms of both induction and maintenance of remission. However, several observations still limit the use of infliximab as first-line treatment in adult CD patients. In particular, the epidemiological observation that over 50% of CD patients have a mild disease over time and will never require aggressive therapies is against the indiscriminate use of top-down strategy. Lack of markers able to identify high-risk patients, discussions about long-term safety and the high costs of infliximab are further factors supporting a more careful approach to the management of CD.
T cell growth factor receptors. Quantitation, specificity, and biological relevance (1981)

To examine directly the hypothesis that T cell growth factor (TCGF) interacts with target cells in a fashion similar to polypeptide hormones, the binding of radiolabeled TCGF to various cell populations was investigated. The results indicate that TCGF interacts with activated T cells via a receptor through which it initiates the T cell proliferative response. Internally radiolabeled TCGF, prepared from a human T leukemia cell line and purified by gel filtration and isoelectric focusing, retained biological activity and was uniform with respect to size and charge. Binding of radiolabeled TCGF to TCGF-dependent cytolytic T cells occurred rapidly (within 15 rain at 37 degrees C) and was both saturable and largely reversible. In addition, at 37 degrees C, a receptor- and lysosome-dependent degradation of TCGF occurred. Radiolabeled TCGF binding was specific for activated, TCGF-responsive T cells. Whereas unstimulated lymphocytes of human or murine origin and lipopolysaccharide-activated B cell blasts expressed few if any detectable binding sites, lectin- or alloantigen-activated cells had easily detectable binding sites. Moreover, compared with lectin- or alloantigen-activated T cells, long-term TCGF-dependent cytolytic and helper T cell lines and TCGF-dependent neo-plastic T cell lines bound TCGF with a similar affinity (dissociation constant of 5-25 pM) and expressed a similar number of receptor sites per cell (5,000-15,000). In contrast, a number of TCGF-independent cell lines of T cell, B cell, or myeloid origin did not bind detectable quantities of radiolabeled TCGF. Binding of radiolabeled TCGF to TCGF-responsive cells was specific, in that among several growth factors and polypeptide hormones tested, only TCGF competed for binding. Finally, the relative magnitude of T cell proliferation induced by a given concentration of TCGF closely paralleled the fraction of occupied receptor sites. As the extent of T cell clonal expansion depends on TCGF and on the TCGF receptor, the dissection of the molecular events surrounding the interaction of TCGF and its receptor that these studies permit, should provide new insight into the hormonelike regulation of the immune response by this lymphokine.
Interactions between hydrophobic side chains within α‐helices (1995)

The thermodynamic basis of helix stability in peptides and proteins is a topic of considerable interest. Accordingly, we have computed the interactions between side chains of all hydrophobic residue pairs and selected triples in a model helix, using Boltzmann-weighted exhaustive modeling. Specifically, all possible pairs from the set Ala, Cys, His, Ile, Leu, Met, Phe, Trp, Tyr, and Val were modeled at spacings of (i, i + 2), (i, i + 3), and (i, i + 4) in the central turn of a model poly-alanyl alpha-helix. Significant interactions--both stabilizing and destabilizing-- were found to occur at spacings of (i, i + 3) and (i, i + 4), particularly in side chains with rings (i.e., Phe, Tyr, Trp, and His). In addition, modeling of leucine triples in a helix showed that the free energy can exceed the sum of pairwise interactions in certain cases. Our calculated interaction values both rationalize recent experimental data and provide previously unavailable estimates of the constituent energies and entropies of interaction.
Biological equivalence of natural bovine and recombinant human alpha-endothelial cell growth factors. (1987)

The cDNA encoding human alpha-endothelial cell growth factor (alpha-ECGF) has been engineered for high-level expression in Escherichia coli. Induction of bacterial cultures harboring the recombinant plasmid pMJ26 results in the appearance of a prominent 16-kDa polypeptide. This protein has been purified from bacterial lysates using a rapid, 2-step procedure employing heparin-Sepharose affinity based chromatography and reversed-phase high pressure liquid chromatography. Recombinant human alpha-ECGF was compared to bovine brain-derived alpha-ECGF in three biological assays: receptor binding on murine lung capillary endothelial cells (LE-II cells), stimulation of [3H]thymidine incorporation in LE-II cells, and stimulation of human umbilical vein endothelial cell proliferation. The results demonstrate that the recombinant human mitogen has the same biological potency as the bovine brain-derived material. Fluorescence spectroscopy was used to study the interaction between recombinant ECGF and heparin. Heparin-binding resulted in a 40% reduction in the intrinsic fluorescence of ECGF, consistent with a heparin-induced conformational change. The intrinsic fluorescence of ECGF also varied as a function of pH.
An overview of heuristic solution methods (2004)

Besides those analysts who are already familiar with a number of heuristic methods, this paper should also be of interest to those analysts and managers who, although not yet aware of specific heuristic approaches, are quite comfortable with the use of mathematical modelling as an aid to decision making. It is concerned with obtaining usable solutions to well-defined mathematical representations of real-world problem situations. Heuristic procedures are defined and reasons for their importance are listed. A wide variety of heuristic methods, including several metaheuristics, are described. In each case, references for further details, including applications, are provided. There is also considerable discussion related to performance evaluation.
Colloid–polymer mixtures in the protein limit (2006)

This review discusses the structure and phase behaviour of mixtures of colloidal particles and non-adsorbing polymers in the protein limit of large polymers and small colloids. The vast majority of work on colloid-polymer mixtures has been concerned with the colloid limit of large colloidal particles and small polymer chains. In this regime, the diameter of the colloidal particles, , is larger than the characteristic size of the polymer-taken as twice their radius of gyration, . The opposite limit, of size ratios , is called the protein limit due to the common practice of adding polymer to protein solutions in order to aid protein crystallisation. Theoretical predictions for systems in the protein limit are considered briefly and then the main focus is on recent experimental studies of mixtures in the protein limit.
<title>Multisensor system self-calibration</title> (1995)

This paper will address the topic of multisensor self-calibration in vision metrology systems employing still-video imagery. Under this approach greater fidelity is afforded in the recovery of sensor interior orientation and distortion parameters. Moreover, a combination of wide- and narrow-angle imaging sensors affords a better insight into the problems of in-plane image distortion and out-of-plane sensor surface deformation, which are often overlooked sources of error in metric applications of CCD cameras. This on-site calibration approach is demonstrated in the measurement, to better than 1 to 100,000 accuracy, of a 5m X 2.5m bond tool used in aircraft manufacturing.
Small Animal Models of Heart Failure (2009)

T he study of heart failure requires viable animal models whereby chronic changes in myocardial structure and function can evolve and the progression of heart failure and left ventricular (LV) dysfunction can be quantified. During the past 40 years, basic and translational scientists have used small animal models to explore the pathophysiology of heart failure and to develop novel therapies that might slow the progression of this prevalent and fatal disease. The purpose of this review is to describe commonly used heart failure models in rodents and to cite examples of how these models have been used to evaluate novel therapies for the treatment of heart failure.
Transgenic Mice and Analysis of B-Cell Tolerance (1992)

Understanding the mechanism of immunological tolerance to self-antigens remains a fundamental problem in immunology. Transgenic mice carrying rearranged antigen-receptor genes have provided a window into the events involved in this process, by allowing the development and fate of antigen-specific lymphocytes to be followed in vivo. In the B-cell lineage, as in T cells, self-reactive cells have been found to undergo several distinct fates in vivo: they can be physically eliminated, functionally inactivated, or they can persist unchanged or become activated. As discussed in this review, direct visualization of the fate of self-reactive cells resolves one of the key issues in tolerance. Achieving a precise understanding of the cellular and molecular events leading to lymphocyte deletion, anergy, or activation nevertheless remains a challenge for the future.
Intracranial intraarterial thrombolysis facilitated by microcatheter navigation through an occluded cervical internal carotid artery (1996)

This report covers a series of four patients with acute cervical carotid occlusion and profound neurological deficits who were treated with intracranial intraarterial thrombolysis. All of the patients presented with arm plegia with variable leg involvement and two of them had global aphasia. Angiography identified occlusion of the proximal internal carotid artery (ICA) in each case and intracranial thromboembolus of the supraclinoid ICA and/or its branches. Catheter navigation through the occluded ICA segment was straightforward in three patients and somewhat difficult in one patient with an 80% ICA stenosis. Intraarterial urokinase infusion along with mechanical clot disruption was performed at the clot site in the middle cerebral artery, supraclinoid ICA, and/or anterior cerebral artery. All patients had recanalization of the treated artery after urokinase infusion. Antegrade flow through the ICA was reestablished in two patients, and good collateral filling across the anterior communicating artery was established in the other two. All patients had major pretreatment deficits (mean National Institutes of Health (NIH) Stroke Score 24 +/-4) with significant improvement noted at 3 months posttreatment (NIH Stroke Score 7 +/-6;p=0.03). Two patients made a dramatic early recovery. Postprocedure computerized tomography revealed no abnormality in one and asymptomatic basal ganglia high density from repeated local contrast injections in two patients. On the basis of their findings in this small study group the authors suggest that catheter navigation through a presumably occluded carotid artery is feasible and possibly effective in thrombolytic therapy of intracranial thrombolysis. Further study with clinical trials is necessary to determine the safety and efficacy of this technique.
Effects of placental proteases on maternal and fetal blood pressure in normal pregnancy and preeclampsia (1996)

Although many protease exist in human placenta, their physiologic roles are still unknown. Our study showed that placenta proteases metabolize vasoactive peptides possibly derived from the fetus. Because vasopressin and angiotensin are known to play an important role in normal and aberrant (preeclampsia) fetal-placental circulation, the clearance of these peptides in the placenta is important in controlling fetal blood pressure. Vasopressin and angiotensin act as a fetal-placental vasoconstrictor; therefore, placental proteases in human placenta are likely to work as a clearance factor for these peptides. Although human and animal pregnancy is normally associated with a refractory response to the pressor effect of exogenously infused angiotensin II, patients with preeclampsia, as well as nonpregnant women, are sensitive to the pressor effect of angiotensin II. Our study suggested that the decreased pressor responsiveness to angiotensin II in pregnancy is caused by increased inactivation of angiotensin II by angiotensinase in pregnant serum and the placenta. Although vasopressinase and angiotensinase activities increase with advancing gestation in normal pregnant sera, the activities of both enzymes in severe preeclampsia sera were clearly lower than those in normal pregnancy. Therefore, it is reasonable to speculate that the increased sensitivity to angiotensin II of preeclampsia is attributable to the decreased degradation of angiotensin II by placental angiotensinase. The negative correlations between the systolic to diastolic ratio obtained from pulsed Doppler measurement techniques and the activities of both enzymes in preeclampsia sera suggested that the systolic to diastolic ration, which reflected constriction of placental vessels, is influenced by the concentration of vasoactive peptides in the fetal-placental circulation due to changes in the activities of placental proteases. Placental proteases play important roles in controlling fetal and maternal blood pressure through regulation of the concentration of vasoactive peptides in the interface (placenta) between fetus and mother.
Inhibition of apoptosis prevents West Nile virus induced cell death (2007)

We found that WNV infection induces cell death in the brain-derived tumour cell line T98G by apoptosis under involvement of constituents of the extrinsic as well as the intrinsic apoptotic pathways. Our results illuminate the molecular mechanism of WNV-induced neural cell death.
Glucagon and the a Cell (1981)

IN this review we examine the role of glucagon, a polypeptide produced by the islets of Langerhans and a biologic antagonist of insulin. The effects of glucagon balance those of insulin so that fluctuations in blood sugar levels in response to sudden changes in fluxes of fuels are prevented.By definition, relative hyperglucagonemia is present in all forms of diabetes in which glucose production exceeds glucose disposal and thus causes "endogenous hyperglycemia"; in the absence of glucagon-like biologic activity the massive hepatic overproduction of glucose and ketones observed in uncontrolled diabetes does not occur, even in the total absence of . . .
Report from the Advanced Technologies and Treatments for Diabetes meeting, London, 16-19 February 2011 : cutting edge of diabetes technology (2011)

After completion of yet another successful ATTD conference, the mind is suitably topped up with the latest advances in diabetes care. This is the fourth annual conference, which has grown from a mere 250 delegates in 2008 to over 1 200 delegates in 2011, testimony to the thirst for knowledge in the diabetes field and the calibre of the content of this meeting. The ATTD meeting provides a forum for exchange of ideas with chief opinion leaders and researchers in diabetes and what follows is a summary of some of the major themes and sessions.
19-Nor-1-alpha-25-dihydroxyvitamin D2 (Paricalcitol) safely and effectively reduces the levels of intact parathyroid hormone in patients on hemodialysis. (1998)

Paricalcitol (19-nor-1alpha-25-dihydroxyvitamin D2), a new vitamin D analog developed for the treatment of secondary hyperparathyroidism, was evaluated in three double-blind, placebo-controlled, dose-escalating, randomized multicenter trials. A total of 78 patients (40 Paricalcitol injection, 38 placebo) achieved treatment phase eligibility, which included intact parathyroid hormone (iPTH) > or = 400 pg/ml, normalized serum calcium levels between 8.0 and 10.0 mg/dl, and calcium x phosphorus product values less than 75. Study end points included a decrease in iPTH of at least 30% or a maximum of five dose escalations. After a 4-wk washout, paricalcitol or placebo was administered intravenously three times per week after dialysis for 12 wk. Study drug was started at a dose of 0.04 microg/kg and was increased by 0.04 microg/kg every 2 wk to a maximal allowable dose of 0.24 microg/kg or until at least a 30% decrease in serum iPTH was achieved. The dose of paricalcitol that decreased iPTH by at least 30% became the maintenance dose. Of 40 patients receiving paricalcitol, 27 (68%) had at least a 30% decrease in serum iPTH for 4 consecutive weeks, compared with three of 38 patients (8%) receiving placebo (P < 0.001). For patients who received 12 wk of treatment with paricalcitol, the levels of iPTH decreased significantly from 795+/-86 to 406+/-106 pg/ml (P < 0.001), whereas the values for PTH were 679+/-41 pg/ml before and 592+/-41 pg/ml after 12 wk of therapy in patients receiving placebo (P=NS). Also, there was a significant difference between treatment groups for the change from baseline PTH levels (P < 0.001). Paricalcitol treatment resulted in a significant reduction in serum alkaline phosphatase from 148+/-23 U/L to 101+/-14 U/L (P < 0.001) in patients treated for 12 wk compared with 120+/-9 U/L to 130+/-11 U/L (P=NS) in patients receiving placebo for 12 wk. Importantly, hypercalcemia did not occur before achieving target serum iPTH levels in any of the paricalcitol-treated patients. There was no significant difference for the change from baseline in serum phosphorus within or between treatment groups. There was no significant difference in adverse events between the paricalcitol and placebo-treated groups. These studies demonstrate that paricalcitol safely and effectively suppresses iPTH levels in hemodialysis patients. This second generation vitamin D analog may have a wider therapeutic window than current vitamin D preparations, and thus may allow reduction in PTH with less hypercalcemia.
Basolateral Secretion of Amyloid Precursor Protein in Madin-Darby Canine Kidney Cells Is Disturbed by Alterations of Intracellular pH and by Introducing a Mutation Associated with Familial Alzheimer's Disease (1995)

The analysis of potential sorting signals in amyloid precursor protein (APP) by site-directed mutagenesis and the disturbance of metabolic pathways by drugs is used here to define the parameters that determine polarized secretion of APP in Madin-Darby canine kidney cells. Endogenously produced APP751/770 and APP695 produced from transfected constructs are secreted almost exclusively into the basolateral compartment. The sorting mechanism is highly dependent on intracellular pH as demonstrated by its sensitivity to primary amines and inhibitors of the acidifying vacuolar protein ATPase. The role of potential basolateral sorting signals in the cytoplasmic, transmembrane, and beta A4 amyloid region of APP was investigated. Neither deletion of the endocytosis and putative basolateral sorting signal GY.NPTY nor complete deletion of the cytoplasmic domain causes apical secretion of soluble APP. Further deletion of the transmembrane domain and of the beta A4 amyloid region confirmed that the major basolateral sorting determinant resides in the extracellular domain of APP. Increased beta-secretase cleavage of APP after introduction of the "swedish" double mutation causes apical missorting of about 20% of beta-secretase-cleaved APP. The data underline the complexity of processing and sorting APP in polarized cells and suggest a possible problem of protein sorting in Alzheimer's Disease.
European evaluation of a new hyaluronic acid filler incorporating lidocaine (2008)

The new hyaluronic acid filler incorporating lidocaine provides a more comfortable injection experience and improved aesthetic result for most patients compared with other dermal fillers used previously.
A second human calcitonin/CGRP gene (1985)

The calcitonin (CT) gene is alternatively expressed in a tissue-specific fashion producing either the calcium regulatory hormone CT in the thyroid or the neuropeptide calcitonin gene related peptide (CGRP) in the brain. In medullary carcinoma of the thyroid both peptides are produced. We present here evidence for the existence in the human genome of a second CT gene, which is also expressed in human medullary thyroid carcinoma. This gene encodes a second human CGRP, differing from the known human CGRP in 3 of the 37 amino acids.
Antiparkinsonian effect of a new selective adenosine A2Areceptor antagonist in MPTP-treated monkeys (1999)

Adenosine A2A receptor antagonists have antiparkinsonian effects of their own with a reduced propensity to elicit dyskinesias. They might therefore be useful agents in the treatment of PD.
Nonideal sampling and interpolation from noisy observations in shift-invariant spaces (2006)

Digital analysis and processing of signals inherently relies on the existence of methods for reconstructing a continuous-time signal from a sequence of corrupted discrete-time samples. In this paper, a general formulation of this problem is developed that treats the interpolation problem from ideal, noisy samples, and the deconvolution problem in which the signal is filtered prior to sampling, in a unified way. The signal reconstruction is performed in a shift-invariant subspace spanned by the integer shifts of a generating function, where the expansion coefficients are obtained by processing the noisy samples with a digital correction filter. Several alternative approaches to designing the correction filter are suggested, which differ in their assumptions on the signal and noise. The classical deconvolution solutions (least-squares, Tikhonov, and Wiener) are adapted to our particular situation, and new methods that are optimal in a minimax sense are also proposed. The solutions often have a similar structure and can be computed simply and efficiently by digital filtering. Some concrete examples of reconstruction filters are presented, as well as simple guidelines for selecting the free parameters (e.g., regularization) of the various algorithms
A Critical Study of Human Resource Development Practices in Selected Indian Industries (2016)

Human Factor is the most important resource that makes the difference amongst nations as well as the organizations. According to World Bank's Assessment of 192 countries on an average physical capital which claims itself as the most important proactive wealth accounts only for 16 percent of the total wealth, natural capital accounts for 20 percent but the ‘human capital’ accounts for 64 percent. Human capital is the only resource with an apparent potential to develop better ideas and get appreciated over the time period. Human capital refers to the knowledge and skills of the individuals which acquired and developed through education, training and experience. This paper focused on HRD practices in various industries.