gebhart/patrepeval huggingface dataset:
A Novel Susceptibility Locus for Type 1 Diabetes on Chr12q13 Identified by a Genome-Wide Association Study (2008)

We have discovered a type 1 diabetes locus at 12q13 that is replicated in an independent cohort of type 1 diabetic patients and confers a type 1 diabetes risk comparable with that of the 16p13 locus we recently reported. These two loci are identical to two loci identified by the whole-genome association study of the Wellcome Trust Case-Control Consortium, a parallel independent discovery that adds further support to the validity of the GWA approach.
Toward Synthetic Viruses: Endosomal pH-Triggered Deshielding of Targeted Polyplexes Greatly Enhances Gene Transfer in vitro and in vivo (2004)

Nonviral vectors should undergo "virus-like" changes compatible with the steps of gene delivery. Poly(ethylene) glycol (PEG) shielding of DNA/polycation polyplexes protects from nonspecific interactions with the extracellular environment. pH-triggered removal of the shield within the endosome may be advantageous. Polycation and PEG were linked via acylhydrazides or pyridylhydrazines. The pyridylhydrazone prepared from polylysine and propionaldehyde-PEG showed the greatest acid-dependent hydrolysis; at pH 5, 37 degrees C for 10 min, 90% hydrolyzed, while at pH 7.4 the half-life was 1.5 h. Particle size and zeta potential measurements of the polyplexes showed complete deshielding within 1 h at pH 5, while at pH 7.4 the shield remained at 4 h, 37 degrees C. For gene transfection a targeting conjugate was also included in the polyplex, transferrin as ligand for K562 and Neuro2A cells and epidermal growth factor for HUH-7 and Renca-EGFR cells. Marker gene expression showed that the reversibly shielded polyplexes exhibited up to 2 log orders of magnitude higher gene expression in vitro and 1 log magnitude higher gene expression in an in vivo mouse model, compared to the stably shielded control polyplexes. Engineering of polyplexes with more dynamic domains is an encouraging new direction in nonviral vector design.
Maximizing calcium uptake by plants (1979)

Abstract This review paper examines the relative importance of the major factors which influence the uptake of Ca by crop plants. Sources of soil Ca and the significance of mass flow and diffusion in Ca uptake are discussed. The cation composition of the soil solution, the form and level of N‐nutrition, root extension, morphology and distribution in the soil, and the specific plant species and cultivar are all important in regulating Ca uptake at the soil/plant root level. The close relationship between Ca uptake and water uptake by plant roots is of further importance. The specific effects of Ca on membrane structure and function are also discussed in relation to the uptake process.
Increased sympathetic venoconstriction and reactivity to norepinephrine in mesenteric veins in anesthetized DOCA-salt hypertensive rats (2007)

Increased sympathetic nervous activity (SNA) elevates venomotor tone in deoxycorticosterone acetate (DOCA)-salt hypertension. We studied the mechanisms by which the SNA increases venomotor tone in DOCA-salt hypertension by making in situ intracellular recordings of venous smooth muscle cell (VSMC) membrane potential (E(m)) and measurement of outside diameter (OD) in mesenteric veins (MV) and mesenteric arteries (MA) of anesthetized rats. We also studied norepinephrine (NE)- and endothelin-1 (ET-1)-induced increases in MA or MV perfusion pressure (PP) in vitro. E(m) in DOCA-salt MV was depolarized compared with sham MV. Prazosin hyperpolarized VSMC E(m) in DOCA-salt but not in sham MV. NE concentration-response curves (CRCs) for OD decreases in MV from DOCA-salt rats were left-shifted with an increased maximum response (E(max)) compared with sham MV. NE CRCs for OD decreases in MA were right-shifted with reduced E(max) in DOCA-salt compared with sham rats. ET-1 CRCs were similar in DOCA-salt and sham MV but were right-shifted with reduced E(max) in DOCA-salt MA. NE CRCs for MAPP increases were left-shifted without a change in E(max) in DOCA-salt rats. NE did not change MVPP. MAPP and MVPP for ET-1 CRCs were similar in sham and DOCA-salt rats, but E(max) for MAPP was reduced in DOCA-salt rats. Hematoxylin staining revealed hypertrophy in DOCA-salt MA but not in MV. We conclude that there is increased reactivity to NE released from the sympathetic nervous system in DOCA-salt MV that causes VSMC depolarization and increased venomotor tone. In DOCA-salt rats, in vivo ET-1 reactivity is maintained in MV, but reduced in MA.
Transgenic Small Interfering RNA Halts Amyotrophic Lateral Sclerosis in a Mouse Model (2005)

Many autosomal dominant diseases such as familial amyotrophic lateral sclerosis (ALS) with copper/zinc superoxide dismutase (SOD1) mutation may be induced by missense point mutations that result in the production of proteins with toxic properties. Reduction in the encoding of proteins from such mutated genes can therefore be expected to improve the disease phenotype. The duplex of 21-nucleotide RNA, known as small interfering RNA (siRNA), has recently emerged as a powerful gene silencing tool. We made transgenic (Tg) mice with modified siRNA, which had multiple mismatch alternations within the sense strand, to prevent the "shutdown phenomenon" of transgenic siRNA. Consequently, the in vivo knockdown effect of siRNA on SOD1 expression did not diminish over four generations. When we crossed these anti-SOD1 siRNA Tg mice with SOD1G93A Tg mice, a model for ALS, siRNA prevented the development of disease by inhibiting mutant G93A SOD1 production in the central nervous system. Our findings clearly proved the principle that siRNA-mediated gene silencing can stop the development of familial ALS with SOD1 mutation.
Regulation of Pancreatic Beta-Cell Mass (2005)

Beta-cell mass regulation represents a critical issue for understanding diabetes, a disease characterized by a near-absolute (type 1) or relative (type 2) deficiency in the number of pancreatic beta cells. The number of islet beta cells present at birth is mainly generated by the proliferation and differentiation of pancreatic progenitor cells, a process called neogenesis. Shortly after birth, beta-cell neogenesis stops and a small proportion of cycling beta cells can still expand the cell number to compensate for increased insulin demands, albeit at a slow rate. The low capacity for self-replication in the adult is too limited to result in a significant regeneration following extensive tissue injury. Likewise, chronically increased metabolic demands can lead to beta-cell failure to compensate. Neogenesis from progenitor cells inside or outside islets represents a more potent mechanism leading to robust expansion of the beta-cell mass, but it may require external stimuli. For therapeutic purposes, advantage could be taken from the surprising differentiation plasticity of adult pancreatic cells and possibly also from stem cells. Recent studies have demonstrated that it is feasible to regenerate and expand the beta-cell mass by the application of hormones and growth factors like glucagon-like peptide-1, gastrin, epidermal growth factor, and others. Treatment with these external stimuli can restore a functional beta-cell mass in diabetic animals, but further studies are required before it can be applied to humans.
Antimicrobial prophylaxis for primary immunodeficiencies (2009)

Currently, antibiotic prophylaxis is guided by the common microbial pathogens seen in specific immunodeficiencies, and experience with other chronic illnesses such as cystic fibrosis, HIV, and immunosuppression from transplantation. Controlled studies are necessary to address the preferred antimicrobial and immunomodulator regimens for most of the primary immunodeficiencies.
Microgeometry capture and RGB albedo estimation by photometric stereo without demosaicing (2017)

We present a photometric stereo-based system for retrieving the RGB albedo and the fine-scale details of an opaque surface. In order to limit specularities, the system uses a controllable diffuse illumination, which is calibrated using a dedicated procedure. In addition, we rather handle RAW, non-demosaiced RGB images, which both avoids uncontrolled operations on the sensor data and simplifies the estimation of the albedo in each color channel and of the normals. We finally show on real-world examples the potential of photometric stereo for the 3D-reconstruction of very thin structures from a wide variety of surfaces.
Application of turbo codes for discrete multi-tone modulation schemes (2003)

A multi-tone QAM modulation technique suitable for discrete multi-tone (DMT) systems based on the combination of the so called turbo codes and trellis code modulation (TCM) is presented. The advantage of this system is its high coding gain together with the bandwidth efficiency which is suitable for asymmetric digital subscriber line (ADSL) modems for twisted pair wires. Some suggestion is given to combat burst noise, frequency selective noise, or interference in the design of the turbo code. The results are compared to the recommended 16 state 4-dimensional Wei code in the ANSI standard. Simulation results demonstrate substantial coding gain for all QAM modulation levels from 4 QAM to 256 QAM.
SETD2 and PBRM1 inactivation in the development of clear cell renal cell carcinoma (2016)

Kidney cancer of the clear cell type is often lethal and causes more than 100,000 deaths worldwide every year. Understanding the biology of this cancer type may help to develop better ways to diagnose and treat it. Damage in DNA (genes) is present in all cancer cells and clear cell kidney cancer is no exception. Exactly how these DNA changes contribute to the development of kidney cancer is still mostly unclear. The PhD study undertaken by Jun Li (Genetics department, UMCG) looked at the effects of damage in 2 genes that appear to be important in kidney cancer: SETD2 and PBRM1. Normal kidney cells cannot be grown in culture for many days, but after silencing the SETD2 gene the growth potential of these cells in became abnormally large. This suggests that damage to SETD2 can contribute to the change from normal kidney cells into cancer cells. In contrast, silencing the PBRM1 gene did not show this effect. However, it did cause changes in the activity of other genes, especially of some involved in immune response. These changes were, more strongly, also observed in kidney cancer cells. Together, these findings contribute to our further understanding of the biology of kidney cancer and may help in improving diagnostics and treatment of this aggressive cancer type.
The accelerated ripening of cholesterol-reduced Cheddar cheese by crosslinked β-cyclodextrin (2008)

This study was carried out to investigate the influence of salt content on cholesterol-reduced Cheddar cheese obtained by a treatment with crosslinked beta-cyclodextrin (beta-CD) and to find if the ripening process was accelerated in cholesterol-reduced cheese. The crosslinked beta-CD used was made by adipic acid. A primary study indicated that the chemical and rheological properties were not changed by the salt addition and the composition of Cheddar cheese treated with crosslinked beta-CD was similar to untreated Cheddar cheese. Approximately 91 to 92% cholesterol reduction was observed in the cheeses that were treated using beta-CD. In a subsequent study, we found accelerated ripening by the crosslinked beta-CD based on the productions of short-chain free fatty acids and free amino acids. In rheological properties, elasticity, cohesiveness, and gumminess scores in the cholesterol-reduced Cheddar cheese were significantly greater at 5 wk ripening than those in the control at 4 mo ripening. At the early stage of ripening, most flavor properties such as rancidity, bitterness, and off-flavor in the cholesterol-reduced cheese were greater. With ripening, however, those scores changed to similar or lower scores than those in the control. The present study indicated that the crosslinked beta-CD treatment for cholesterol removal showed accelerated ripening effect on the properties of Cheddar cheese.
Chronic peripheral administration of corticotropin-releasing factor causes colonic barrier dysfunction similar to psychological stress (2008)

Chronic psychological stress causes intestinal barrier dysfunction and impairs host defense mechanisms mediated by corticotrophin-releasing factor (CRF) and mast cells; however, the exact pathways involved are unclear. Here we investigated the effect of chronic CRF administration on colonic permeability and ion transport functions in rats and the role of mast cells in maintaining the abnormalities. CRF was delivered over 12 days via osmotic minipumps implanted subcutaneously in wild-type (+/+) and mast cell-deficient (Ws/Ws) rats. Colonic segments were excised for ex vivo functional studies in Ussing chambers [short-circuit current (Isc), conductance (G), and macromolecular permeability (horseradish peroxidase flux)], and analysis of morphological changes (mast cell numbers and bacterial host-interactions) was determined by light and electron microscopy. Chronic CRF treatment resulted in colonic mucosal dysfunction with increased Isc, G, and horseradish peroxidase flux in+/+but not in Ws/Ws rats. Furthermore, CRF administration caused mast cell hyperplasia and abnormal bacterial attachment and/or penetration into the mucosa only in+/+rats. Finally, selective CRF agonist/antagonist studies revealed that stimulation of CRF-R1 and CRF-R2 receptors induced the elevated secretory state and permeability dysfunction, respectively. Chronic CRF causes colonic barrier dysfunction in rats, which is mediated, at least in part, via mast cells. This information may be useful in designing novel treatment strategies for stress-related gastrointestinal disorders.
Ablation of renal tumors with absolute ethanol: a new technique. (1981)

Transcatheter injection of absolute ethanol into the renal artery is an effective method of producing renal ablation. There has been no evidence of inadvertent damage to vessels or tissues remote from the target organ. The "postembolization syndrome" of pain, nausea, vomiting, and fever is minimal when compared with other methods of renal artery occlusion. Multiple mechanisms of action of intraarterial ethanol are proposed, including perivascular tissue toxicity, sludging of erythrocytes in small arteries, small artery spasm, and endothelial damage. Experience with this technique in six patients has resulted in specific recommendations regarding the amount and method of injection of ethanol. Angiographic criteria indicating adequate renal ablation are described.
A New Family of Biisoquinoline Chelates (2006)

Abstract Four 8,8′‐diaryl‐substituted 3,3′‐biisoquinoline ligands have been synthesized and characterized. The key feature of this new family of chelates is their endotopic but sterically nonhindering nature. All four ligands were made from a common 8‐bromoisoquinolin‐3‐ol precursor; between three and twelve synthetic steps were necessary to obtain the products. The reported synthetic procedures allow for gram‐scale production of these biisoquinolines. (© Wiley‐VCH Verlag GmbH &amp; Co. KGaA, 69451 Weinheim, Germany, 2007)
Effect of Sodium Cromoglycate on Mast Cell Mediators during Hyperpnea in Athletes (2010)

The results support mast cell activation with release of bronchoconstrictive mediators after hyperpnea in athletes with and without EIB and inhibition by SCG. The degree of airway responsiveness to the specific mediator released is likely to determine whether or not bronchoconstriction will occur after EVH.
Fast and Slow Cyclic Nucleotide-dissociation Sites in cAMP-dependent Protein Kinase Are Transposed in Type Iβ cGMP-dependent Protein Kinase (1996)

Both cyclic GMP-dependent protein kinase (cGK) and cyclic AMP-dependent protein kinase (cAK) contain two distinct cyclic nucleotide-binding sites referred to as fast and slow sites based on cyclic nucleotide dissociation behavior. In cAK, the fast site lies amino-terminal to the slow site, and sequence homologies between cAK and cGK have suggested similar positioning for the sites in cGK. Recombinant human type Ibeta cGK (wild type (WT) cGK) was overexpressed, and the properties of purified WT cGK and native type Ibeta cGK were similar. cGK was mutated singly at Thr-193 (T193A, T193V, and T193S) and Thr-317 (T317A, T317V, and T317S), which have been predicted to provide cGMP specificity in the cGMP-binding sites of cGK; a double mutant (T193A/T317A) was produced also. Compared with WT cGK, half-maximal activation (Ka) of mutant cGKs by cGMP was increased 2- (T317A), 27- (T193A), or 63-fold (T193A/T317A), but the Ka for cAMP of these mutants was essentially unchanged. The T193A and T193V mutants had a large increase in the rate of the slow component of [3H]cGMP dissociation, but in the T317A and T317V mutants, there was no change in the slow component. The T193S and T317S mutants had only minor effects on [3H]cGMP dissociation, thus establishing the importance of the hydroxyl group of Thr-193 and -317 for cGMP binding to cGK. Thus, in type Ibeta cGK, the slow cGMP-binding site is identified as the amino-terminal site in contrast to the order assigned to the fast and slow cAMP-binding sites of cAK.
Comparison between bone-conducted ultrasound and audible sound in speech recognition (2009)

With BCU, the maximum percentage correct totaled about 75%. Our comparison of the hearing confusion with ACAS and BCU according to the individual syllabic nuclear group showed a clear difference in the incorrect rates. In addition, the stimulus nuclear groups were often perceived in other nuclear groups in BCU.
Pharmacological Studies on the Anti-Inflammatory Effect of a Semi-Synthetic Polysaccharide (Pentosan Polysulfate) (1973)

Certain biochemical characteristics of pentosan polysulfate (SP 54) indicated possible antiphlogistic properties of this substance. Our extensive investigations with different models of acute inflammatory reactions (rat paw edema induced by hyaluronidase, trypsin, carrageenin or kaolin) have shown that pentosan polysulfate has a pronounced anti-inflammatory and antiphlogistic effect, although it has no analgetic properties. In contrast to other well-known antiphlogistic drugs, such as salicylate, pyrazolone or anthranilic acid derivatives, pentosan polysulfate exerts its strong anti-inflammatory effect on <i>all </i>types of experimental edema. This outstanding antiphlogistic and anti-inflammatory potency of pentosan polysulfate can be explained by a suppression of hyaluronidase, histamine and certain complement factors as well as by its specifically vasotropic and stabilizing effects.
Analysis of clustering techniques to detect hand signs (2002)

The term multimedia has a different meaning to different communities. The computer industry uses this term to refer to a system that can display audio and video clips. Generally speaking, a multimedia system supports multiple presentation modes to convey information. Humans have five senses: sight, hearing, touch, smell and taste. In theory, a system based on this generalized definition must be able to convey information in support of all senses. This would be a step towards virtual environments that facilitate total recall of an experience. This study builds on our previous work with audio and video servers and explores haptic data in support of touch and motor skills. It investigates the use of clustering techniques to recognize hand signs using haptic data. An application of these results is communication devices for the hearing impaired.
Directed elimination of senescent cells by inhibition of BCL-W and BCL-XL (2016)

Senescent cells, formed in response to physiological and oncogenic stresses, facilitate protection from tumourigenesis and aid in tissue repair. However, accumulation of such cells in tissues contributes to age-related pathologies. Resistance of senescent cells to apoptotic stimuli may contribute to their accumulation, yet the molecular mechanisms allowing their prolonged viability are poorly characterized. Here we show that senescent cells upregulate the anti-apoptotic proteins BCL-W and BCL-XL. Joint inhibition of BCL-W and BCL-XL by siRNAs or the small-molecule ABT-737 specifically induces apoptosis in senescent cells. Notably, treatment of mice with ABT-737 efficiently eliminates senescent cells induced by DNA damage in the lungs as well as senescent cells formed in the epidermis by activation of p53 through transgenic p14(ARF). Elimination of senescent cells from the epidermis leads to an increase in hair-follicle stem cell proliferation. The finding that senescent cells can be eliminated pharmacologically paves the way to new strategies for the treatment of age-related pathologies.
Systemic Lupus Erythematosus (1991)

Although the cause of systemic lupus erythematosus remains unknown, pathogenic mechanisms are becoming clearer. Both genetic and environmental factors have been implicated in the induction and in the perpetuation of lupus. Implicated environmental triggers include ultraviolet light, chemicals (hydrazines, hair dyes, drugs), some foods, and possibly infectious agents. Lupus is mediated by the immune system. Patients have excess numbers of antibody-forming cells, including those that produce antibodies reactive with self-antigens. Patients also have an increased number of activated T cells, some of which help B cells to produce autoantibodies. A loss of tolerance is a critical immune abnormality in lupus; many of the activated helper T cells may result from a failure in normal tolerance mechanisms. A hematopoietic stem-cell defect could give rise to both B- and T-cell abnormalities. Such a stem-cell abnormality might lead to both a loss of self-tolerance and polyclonal B-cell activation. Antigen-driven, T-cell-dependent expansion of B-cell clones would then give rise to pathogenic autoantibodies, including anti-DNA. We believe that lupus is a syndrome: Patients differ regarding specific inciting factors and immune defects. Some patients have genetically conditioned abnormalities, similar to those found in mice with lupus; others have a combination of genetic and acquired defects. We hope that insights into pathogenesis lead to improved and more individualized therapy.
Fever therapy revisited (2005)

The phenomenon of spontaneous regression and remission from cancer has been observed by many physicians and was described in hundreds of publications. However, suggestive clues on cause or trigger are sparse and not substantiated by much experimental evidence. In this review, literature is surveyed and summarised and possible causes are discussed. At least in a larger fraction of cases a hefty feverish infection is linked with spontaneous regression in time and is investigated as putative trigger. Epidemiological and immunological evidence is put into perspective. An online forum to discuss the possible application of fever therapy in the future can be accessed at http://bioinfo.tg.fh-giessen.de/fever-and-cancer.