gebhart/patrepeval huggingface dataset:
Open label gabapentin treatment for pain in multiple sclerosis (1997)

Pain is a frequent and distressing complaint in patients with multiple sclerosis (MS) and may present a difficult therapeutic problem. Conventional therapy is moderately effective and includes, among others, a variety of anticonvulsant medications. Gabapentin (Neurontin) is a new generation antiepileptic drug which appears to be advantageous in treatment of intractable pain of reflex sympathetic dystrophy. This study investigates the benefits of open-label treatment with gabapentin for pain control in 25 patients with MS. Excellent to moderate pain relief was obtained in a substantial number of patients. Throbbing pains and needles, and cramping pains responded best, and dull aching pains responded least to the medication. There was no significant change in distribution and type of pain as a result of this treatment. Mild to moderate side effects were observed. Cautious escalation of the dose of gabapentin is advisable in MS patients. Further clinical trials with larger patient groups are recommended.
Phosphatidylcholine for Steroid-Refractory Chronic Ulcerative Colitis (2007)

Phosphatidylcholine reduced corticosteroid dependence more than placebo in patients with chronic steroid-refractory ulcerative colitis. The next step is long-term trials to evaluate the sustainability of steroid withdrawal in these patients. ClinicalTrials.gov registration number: NCT00259545.
LRP6 transduces a canonical Wnt signal independently of Axin degradation by inhibiting GSK3's phosphorylation of β-catenin (2008)

Wnt/beta-catenin signaling controls various cell fates in metazoan development and is misregulated in several cancers and developmental disorders. Binding of a Wnt ligand to its transmembrane coreceptors inhibits phosphorylation and degradation of the transcriptional coactivator beta-catenin, which then translocates to the nucleus to regulate target gene expression. To understand how Wnt signaling prevents beta-catenin degradation, we focused on the Wnt coreceptor low-density lipoprotein receptor-related protein 6 (LRP6), which is required for signal transduction and is sufficient to activate Wnt signaling when overexpressed. LRP6 has been proposed to stabilize beta-catenin by stimulating degradation of Axin, a scaffold protein required for beta-catenin degradation. In certain systems, however, Wnt-mediated Axin turnover is not detected until after beta-catenin has been stabilized. Thus, LRP6 may also signal through a mechanism distinct from Axin degradation. To establish a biochemically tractable system to test this hypothesis, we expressed and purified the LRP6 intracellular domain from bacteria and show that it promotes beta-catenin stabilization and Axin degradation in Xenopus egg extract. Using an Axin mutant that does not degrade in response to LRP6, we demonstrate that LRP6 can stabilize beta-catenin in the absence of Axin turnover. Through experiments in egg extract and reconstitution with purified proteins, we identify a mechanism whereby LRP6 stabilizes beta-catenin independently of Axin degradation by directly inhibiting GSK3's phosphorylation of beta-catenin.
Perspectives on Fatigue from the Study of Chronic Fatigue Syndrome and Related Conditions (2010)

Fatigue is a symptom whose causes are protean and whose phenotype includes physical, mood, and behavioral components. Chronic fatigue syndrome (CFS) is an illness that has strong biological underpinnings and no definite etiology. Diagnostic criteria established by the Centers for Disease Control and Prevention have helped classify CFS as an overlap of mood, behavioral, and biological components. These include the presence of fatigue for more than 6 months associated with a diminution of functional activity and somatic symptoms, and pain not attributable to a specific diagnosis or disease. Four of the following criteria need to be present: sore throat, impaired memory or cognition, unrefreshing sleep, postexertional fatigue, tender glands, aching stiff muscles, joint pain, and headaches. Many researchers have observed that CFS shares features in common with other somatic syndromes, including irritable bowel syndrome, fibromyalgia, and temporomandibular joint dysfunction. Correlations between inflammation and infection, augmented sensory processing, abnormalities of neurotransmitters, nerve growth factors, low levels of serotonin and norepinephrine, abnormalities of homeostasis of the stress system, and autonomic dysfunction may be hallmarks of CFS. The relative contributions of each of these abnormalities to the profound fatigue associated with CFS need to be explored further to better evaluate and treat the syndrome.
Structural requirements for adhesion of soluble recombinant murine vascular cell adhesion molecule-1 to alpha 4 beta 1. (1994)

This study describes the identification of seven amino acid residues of the vascular cell adhesion molecule (VCAM-1) that influence binding to the alpha 4 beta 1 receptor. Using recombinant murine VCAM-1-IgG, which is bound by both mouse (WEHI 231) and human (Ramos) lymphoid cells, two approaches demonstrated the crucial role of the first two NH2-terminal Ig-like domains in binding: (a) blocking monoclonal anti-mouse VCAM-1 antibodies bound to only truncation variants that included the first two domains; (b) site-direct mutagenesis of the first NH2-terminal domain showed that alanine substitution of the amino acid residues R36, D40, K46, S54, N65, T72, and E81 partially or completely reduced adherence by human and/or mouse cells. Of these D40, when mutated to A, N, or K (but not E), showed complete abrogation of adherence by mouse and human cells, as well as inability to bind blocking anti-murine VCAM-1 antibody MVCAM.A429, while not inducing gross structural perturbations in VCAM-1. By molecular modeling, the D40 residue was located on a beta turn connecting two beta strands defined as C and D. The residues R36, K46, S54, N65, T72, and E81, which perturb cell adherence and caused small changes to gross structure, are conformationally near or adjacent to D40. Although these residues, identified as crucial for cell adhesion, are all located in domain 1, it is evident that there is a structural requirement for domains 1 and 2 to be intact so that cell adhesive function can occur.
ClC-3 expression enhances etoposide resistance by increasing acidification of the late endocytic compartment (2007)

Resistance to anticancer drugs and consequent failure of chemotherapy is a complex problem severely limiting therapeutic options in metastatic cancer. Many studies have shown a role for drug efflux pumps of the ATP-binding cassette transporters family in the development of drug resistance. ClC-3, a member of the CLC family of chloride channels and transporters, is expressed in intracellular compartments of neuronal cells and involved in vesicular acidification. It has previously been suggested that acidification of intracellular organelles can promote drug resistance by increasing drug sequestration. Therefore, we hypothesized a role for ClC-3 in drug resistance. Here, we show that ClC-3 is expressed in neuroendocrine tumor cell lines, such as BON, LCC-18, and QGP-1, and localized in intracellular vesicles co-labeled with the late endosomal/lysosomal marker LAMP-1. ClC-3 overexpression increased the acidity of intracellular vesicles, as assessed by acridine orange staining, and enhanced resistance to the chemotherapeutic drug etoposide by almost doubling the IC(50) in either BON or HEK293 cell lines. Prevention of organellar acidification, by inhibition of the vacuolar H(+)-ATPase, reduced etoposide resistance. No expression of common multidrug resistance transporters, such as P-glycoprotein or multidrug-related protein-1, was detected in either the BON parental cell line or the derivative clone overexpressing ClC-3. The probable mechanism of enhanced etoposide resistance can be attributed to the increase of vesicular acidification as consequence of ClC-3 overexpression. This study therefore provides first evidence for a role of intracellular CLC proteins in the modulation of cancer drug resistance.
Measurement of depression in patients with chronic obstructive pulmonary disease (COPD) (2003)

The HDSS can be recommended as a suitable depression rating scale for COPD patients.
Reducing manufacturing costs: the dynamic tolerance system (2019)

Can tolerance limits in production be extended without violating the specifications of design and development? Adherence to tolerances is crucial for the technical quality of a manufactured good. Fit functions of modules often involve highly precise tolerances, incurring high costs. To avoid or at least reduce these costs, this paper develops a new approach to tolerances, the Dynamic Tolerance System. This approach allows the manufacturer to expand the tolerance limits of single parts of an assembly group and enables the production of assembly groups that are subject to specific fit functions. Thereby, the Dynamic Tolerance System does not intervene in the design process, does not require expensive machines or error-prone control-loops, and does not use complex assembly procedures. Rather, it relies on modern measurement systems and the infrastructure already developed and deployed within the framework of Industry 4.0 to extend tolerance limits in production without violating the designer’s specifications.
A novel class of enkephalinase inhibitors containing a C-terminal sulfo group (1992)

A new series of sulfonic acids were synthesized and tested for their enkephalinase inhibitory activity. Among them, the most potent was N-(2-benzyl-3-mercaptopropionyl)metanilic acid 10i with an IC50 value of 0.27 nM. Several other analogues (10a,b,j,n,o,gg,hh) showed the inhibitory activity comparable to or greater than thiorphan (IC50 = 2.6 nM), a C-terminal carboxyl-containing inhibitor of enkephalinase. Thus compounds containing a C-terminal sulfo group, instead of the C-terminal carboxyl group, were found to show a remarkably high level of inhibition of enkephalinase. The analgesic activity of 10b, (S)-10b, and (R)-10b was also evaluated by the phenylbenzoquinone writhing test.
Efficient hybridization between Lycopersicon esculentum and L. peruvianum via ‘embryo rescue’ and in vitro propagation (1996)

Abstract For the transfer of valuable traits from wild species into the cultivated tomato, excised globular‐stage embryos 13 and 15 days after pollination (DAP) were cultured in vitro. Plants were regenerated from interspecific crosses of Lycopersicon esculentum cv. ‘Early pink’× L. peruvianum PI270435, and backcrosses of L. esculentum ‘Giban (JF) No. 1’× (‘Early pink’× PI270435). Somatic embryos and single cotyledons emerged on hypocotyl sections of the embryos. Five to nine plantlets per embryo were obtained by clonal propagation. The hybrid nature of the plants is confirmed by comparing hybrids and parents in their ability to regenerate shoots from leaf segments in vitro , by comparing plant morphology and characteristics and by chromosome number. This study describes an efficient ‘embryo rescue’ method, as well as somatic embryogenesis by clonal propagation. A novel and simple method for the characterization of the interspecific hybrids is also reported.
Methylnaltrexone Progenics. (2002)

Progenics is developing methylnaltrexone (MNTX), an opioid antagonist licensed from UR Labs and the University of Chicago, for the potential treatment of the side effects of opioid pain therapy, such as constipation and post-operative bowel dysfunction. MNTX was discovered at the University of Chicago and subsequently licensed by UR Labs. In October 2001, Progenics entered into an agreement with UR Labs to obtain exclusive worldwide rights to the drug [423791]. MNTX is in phase II trials, with phase III studies expected to begin in 2002 [423791]. In October 2001, a double-blind, randomized, phase II study evaluating sc MNTX in cancer patients for the treatment of opioid-induced constipation was initiated at the University of Chicago Medical Center [423791]. In December 2001, the company stated that it was preparing to initiate phase IIb trials of the compound in opioid-induced constipation and post-operative bowel dysfunction [423791], [432507]. These trials were initiated in February 2002 [440995].
Fields of Experts: A Framework for Learning Image Priors (2005)

We develop a framework for learning generic, expressive image priors that capture the statistics of natural scenes and can be used for a variety of machine vision tasks. The approach extends traditional Markov random field (MRF) models by learning potential functions over extended pixel neighborhoods. Field potentials are modeled using a Products-of-Experts framework that exploits nonlinear functions of many linear filter responses. In contrast to previous MRF approaches all parameters, including the linear filters themselves, are learned from training data. We demonstrate the capabilities of this Field of Experts model with two example applications, image denoising and image inpainting, which are implemented using a simple, approximate inference scheme. While the model is trained on a generic image database and is not tuned toward a specific application, we obtain results that compete with and even outperform specialized techniques.
Embedding invisible information in color images (2002)

We describe a method for embedding information in color images. A model of human color vision is used to ensure that the embedded signal is invisible. Sinusoidal signals are embedded so that they can be detected (decoded) without use of the original image. The sinusoids act as a grid, providing a coordinate frame on the image. We use the grid to automatically scale and align (deskew) images that have been printed and then scanned.
Application of In Vivo Induced Antigen Technology (IVIAT) to Bacillus anthracis (2008)

In vivo induced antigen technology (IVIAT) is an immuno-screening technique that identifies bacterial antigens expressed during infection and not during standard in vitro culturing conditions. We applied IVIAT to Bacillus anthracis and identified PagA, seven members of a N-acetylmuramoyl-L-alanine amidase autolysin family, three P60 family lipoproteins, two transporters, spore cortex lytic protein SleB, a penicillin binding protein, a putative prophage holin, respiratory nitrate reductase NarG, and three proteins of unknown function. Using quantitative real-time PCR comparing RNA isolated from in vitro cultured B. anthracis to RNA isolated from BALB/c mice infected with virulent Ames strain B. anthracis, we confirmed induced expression in vivo for a subset of B. anthracis genes identified by IVIAT, including L-alanine amidases BA3767, BA4073, and amiA (pXO2-42); the bacteriophage holin gene BA4074; and pagA (pXO1-110). The exogenous addition of two purified putative autolysins identified by IVIAT, N-acetylmuramoyl-L-alanine amidases BA0485 and BA2446, to vegetative B. anthracis cell suspensions induced a species-specific change in bacterial morphology and reduction in viable bacterial cells. Many of the proteins identified in our screen are predicted to affect peptidoglycan re-modeling, and our results support significant cell wall structural remodeling activity during B. anthracis infection. Identification of L-alanine amidases with B. anthracis specificity may suggest new potential therapeutic targets.
Short-term and long-term epoprostenol (prostacyclin) therapy in pulmonary hypertension secondary to connective tissue diseases: results of a pilot study (1999)

The aim of this study was to examine the role of p38 mitogen-activated protein (MAP) kinase in interleukin (IL)-8 expression in tumour necrosis factor (TNF)-alpha- and IL-1alpha-stimulated human pulmonary vascular endothelial cells. To this end, the phosphorylation and activation of p38 MAP kinase and the effect of SB 203580, a specific inhibitor of p38 MAP kinase activity, on p38 MAP kinase activity and IL-8 expression in TNF-alpha- and IL-1alpha-stimulated human pulmonary vascular endothelial cells were examined. TNF-alpha- and IL-1alpha- induced phosphorylation and activation of p38 MAP kinase and IL-8 expression in human pulmonary endothelial cells. Inhibition of TNF-alpha- and IL-1alpha-induced p38 MAP kinase activity by SB 203580 inhibited TNF-alpha- and IL-1alpha-induced IL-8 protein production as well as IL-8 messenger ribonucleic acid (mRNA) expression, indicating that SB 203580 was effective at the transcriptional level. These results indicate that p38 mitogen-activated protein kinase plays an important role in the tumour necrosis factor-alpha- and interleukin-1alpha-activated signalling pathway which regulates interleukin-8 expression in human pulmonary vascular endothelial cells.
Intravitreal bevacizumab (Avastin(R)) for macular oedema secondary to retinal vein occlusion: 12-month results of a prospective clinical trial (2008)

Intravitreal therapy using bevacizumab appears to be a safe and effective treatment in patients with macular oedema secondary to retinal vein occlusion. However, the main limitations of this treatment modality are its short-term effectiveness and high recurrence rate.
Mechanical tugging force regulates the size of cell–cell junctions (2010)

Actomyosin contractility affects cellular organization within tissues in part through the generation of mechanical forces at sites of cell-matrix and cell-cell contact. While increased mechanical loading at cell-matrix adhesions results in focal adhesion growth, whether forces drive changes in the size of cell-cell adhesions remains an open question. To investigate the responsiveness of adherens junctions (AJ) to force, we adapted a system of microfabricated force sensors to quantitatively report cell-cell tugging force and AJ size. We observed that AJ size was modulated by endothelial cell-cell tugging forces: AJs and tugging force grew or decayed with myosin activation or inhibition, respectively. Myosin-dependent regulation of AJs operated in concert with a Rac1, and this coordinated regulation was illustrated by showing that the effects of vascular permeability agents (S1P, thrombin) on junctional stability were reversed by changing the extent to which these agents coupled to the Rac and myosin-dependent pathways. Furthermore, direct application of mechanical tugging force, rather than myosin activity per se, was sufficient to trigger AJ growth. These findings demonstrate that the dynamic coordination of mechanical forces and cell-cell adhesive interactions likely is critical to the maintenance of multicellular integrity and highlight the need for new approaches to study tugging forces.
Identification of a gene, MLL, that spans the breakpoint in 11q23 translocations associated with human leukemias. (1991)

Recurring chromosomal translocations involving chromosome 11, band q23, have been observed in acute lymphoid leukemias and especially in acute myeloid leukemias. We recently showed that breakpoints in four 11q23 translocations, t(4;11)(q21;q23), t(6;11)(q27;q23), t(9;11)(p22;q23), and t(11;19)(q23;p13.3), were contained within a yeast artificial chromosome clone bearing the CD3D and CD3G gene loci. We have identified within the CD3 yeast artificial chromosome a transcription unit that spans the breakpoint junctions of the 4;11, 9;11, and 11;19 translocations, and we describe two other, related transcripts that are upregulated in the RS4;11 cell line. We have named this gene MLL (myeloid/lymphoid, or mixed-lineage, leukemia.
SCOFF, the development of an eating disorder screening questionnaire (2009)

The SCOFF, which has been adapted for use in diverse languages, appears highly effective as a screening instrument and has been widely adopted to raise the index of suspicion of an eating disorder.
Cyanobacterial Phytochrome-like PixJ1 Holoprotein Shows Novel Reversible Photoconversion Between Blue- and Green-absorbing Forms (2004)

The gene, pixJ1 (formerly pisJ1), is predicted to encode a phytochrome-like photoreceptor that is essential for positive phototaxis in the unicellular cyanobacterium Synechocystis sp. PCC 6803 [Yoshihara et al. (2000) Plant Cell Physiol. 41: 1299]. The PixJ1 protein was overexpressed as a fusion with a poly-histidine tag (His-PixJ1) and isolated from Synechocystis cells. A zinc-fluorescence assay suggested that a linear tetrapyrrole was covalently attached to the His-PixJ1 protein as a chromophore. His-PixJ1 showed novel photoreversible conversion between a blue light-absorbing form (Pb, lambdaAmax=425-435 nm) and a green light-absorbing form (Pg, lambdaAmax=535 nm). Dark incubation led Pg to revert to Pb, indicative of stability of the Pb form in darkness. Red or far-red light irradiation, which is effective for photochemical conversion of the known phytochromes, produced no change in the spectra of Pb and Pg forms. Site-directed mutagenesis revealed that a Cys-His motif in the second GAF domain of PixJ1 is responsible for binding of the chromophore. Possible chromophore species are discussed with regard to the novel photoconversion spectrum.
Atherosclerosis: A unifying disorder with diverse manifestations (1998)

The epidemiology, costs, and comorbidities associated with atherosclerosis and the role of newer antiplatelet agents are reviewed. Cardiovascular disease is the leading cause of death in the United States. More than 60 million Americans have one or more types of cardiovascular disease. The total annual cost of coronary heart disease has been estimated at $95 billion. Patients with an existing atherosclerotic disease in one vascular bed are at high risk of having an ischemic vascular event in the same or another vascular bed. Peripheral arterial disease is a strong marker for underlying cerebrovascular and cardiovascular disease. The common link among these diseases is atherosclerosis leading to atherothrombosis. Platelets play an integral role in atherosclerosis and the formation of arterial thrombus as well as in subsequent acute events such as ischemic stroke, myocardial infarction, and vascular death. Arterial thrombosis can be mediated by shear-stress-induced platelet aggregation. Currently, only one third to one half of all eligible patients with stroke, myocardial infarction, or peripheral arterial disease receive antiplatelet therapy. Thienopyridines such as ticlopidine and clopidogrel are effective inhibitors of shear-stress-induced and endothelial-injury-induced platelet aggregation. Advances in antiplatelet therapy provide an opportunity to use newer antiplatelet agents in the prevention of atherosclerosis-related morbidity and mortality; therapeutic approaches should be directed toward recognizing atherosclerosis as a generalized disease process and preventing ischemic events in multiple vascular beds.