gebhart/patrepeval huggingface dataset:
Genes and arthritis (1995)

Familial clustering is a common feature of many different arthritic conditions which can be explained by shared genetic or environmental influences or a combination of these. The aetiology of some of these diseases (e.g. multiple epiphyseal dysplasia, Lesch-Nyan syndrome) is clearly monogenic but the majority of common rheumatic conditions, such as osteoarthritis (OA) and rheumatoid arthritis (RA) are complex and multi-factorial with a polygenic component. In the last 10 years there has been spectacular progress in unravelling the underlying genetic mechanisms of many monogenic disorders including many that affect the musculoskeletal system. Among these osteogenesis imperfecta (OI) and the Marfan syndrome are striking examples in which molecular defects of matrix protein components of the mesodermal tissues have been revealed. In particular, the power of modern molecular genetics both to test candidate genes (e.g. collagen in OI) and to identify genes where no prior knowledge of the protein defects exists (e.g. fibrillin in the Marfan syndrome) has proved quite remarkable. In the near future many of the techniques that have been applied successfully to these monogenic diseases can be expected to provide insights into the genetic component of common diseases, such as rheumatoid arthritis. However, it is important to realize before embarking on these studies that even monogenic diseases may provide significant problems of analysis and interpretation. Some of these problems are exemplified below (e.g. phenocopies, mosaicism, imprinting).
Photovoltaic microinverter using single-stage isolated high-frequency link series resonant topology (2011)

In this paper, PhotoVoltaic (PV) microinverter using a single-stage high-frequency ac link series resonant topology is proposed. The inverter has two active bridges, one at the front-end of PV module and the other at the output or utility side. The active bridges are interfaced through a series resonant tank and a high frequency transformer. A novel phase-shift modulation technique to regulate the current into utility is proposed. Steady-state analysis using sinusoidal approximation is presented to determine the magnitude of output current into utility. Soft-switching operation is ensured in all switches in the converter due to resonant nature of the circuit. The inverter has advantages of minimal power conversion stages, high-switching frequency operation and low switching losses and hence ideally suited for low power module integrated applications.
Time-Reversal UWB Wireless Communication-Based Train Control in Tunnel (2009)

This paper reports an evaluation of UWB radio technology and Time-Reversal (TR) technique in tunnel environments for train-to-wayside communication. UWB technology has the potential to offer simultaneous ground-totrain communication, train location and obstacle detection in front of the trains. Time-Reversal channel pre-filtering facilitates signal detection and helps reduce interference. Thus, UWB-TR combination provides a challenging, economically sensible, as well as technically effective alternative solution to existing signaling technologies used in urban transport systems. This paper deals with deterministic channel modeling and its characterization in tunnel environment. It reports simulation performance evaluation of UWB-TR combinations in the developed channel model.
Activation of the small GTP-binding proteins rho and rac by growth factor receptors (1995)

The small GTP-binding proteins, rho and rac, control signal transduction pathways that link growth factor receptors to the activation of actin polymerization. In Swiss 3T3 cells, rho proteins mediate the lysophosphatidic acid and bombesin-induced formation of focal adhesions and actin stress fibres, whilst rac proteins are required for the platelet-derived growth factor-, insulin-, bombesin- and phorbol ester (phorbol 12-myristate 13-acetate)-stimulated actin polymerization at the plasma membrane that results in membrane ruffling. To investigate the role of p85/p110 phosphatidylinositol 3-kinase in the rho and rac signalling pathways, we have used a potent inhibitor of this activity, wortmannin. Wortmannin has no effect on focal adhesion or actin stress fibre formation induced by lysophosphatidic acid, bombesin or microinjected recombinant rho protein. In contrast, it totally inhibits plasma membrane edge-ruffling induced by platelet-derived growth factor and insulin though not by bombesin, phorbol ester or microinjected recombinant rac protein. We conclude that phosphatidylinositol 3,4,5 trisphosphate mediates activation of rac by the platelet-derived growth factor and insulin receptors. The effects of lysophosphatidic acid on the Swiss 3T3 actin cytoskeleton can be blocked by the tyrosine kinase inhibitor, tyrphostin. Since tyrphostin does not inhibit the effects of microinjected rho protein, we conclude that lysophosphatidic acid activation of rho is mediated by a tyrosine kinase.
Gastroesophageal reflux disease-should we adopt a new conceptual framework? (2002)

Gastroesophageal reflux disease (GERD) has traditionally been approached as a spectrum of diseases. Over the years, this important concept affected our current understanding of the pathophysiologic mechanisms resulting in GERD. Additionally, it had a profound impact on our therapeutic approach and treatment algorithms. However, literature review reveals that there is scant data to support the spectrum paradigm. Consequently, we propose categorizing GERD into three unique groups of patients: nonerosive reflux disease, erosive esophagitis, and Barrett's esophagus. Thus far, studies have demonstrated very little movement between these groups. Although the spectrum concept focused our attention on esophageal mucosal injury, the new proposed conceptual model shifts our attention to esophageal symptoms. Furthermore, dividing GERD into three unique groups of patients will allow us to concentrate on the different mechanisms that lead to the development of each of these GERD-related disorders and thus help us to focus on the specific therapeutic modalities that will benefit each individual group of patients.
Challenges in Scaling Up Biofuels Infrastructure (2010)

Rapid growth in demand for lignocellulosic bioenergy will require major changes in supply chain infrastructure. Even with densification and preprocessing, transport volumes by mid-century are likely to exceed the combined capacity of current agricultural and energy supply chains, including grain, petroleum, and coal. Efficient supply chains can be achieved through decentralized conversion processes that facilitate local sourcing, satellite preprocessing and densification for long-distance transport, and business models that reward biomass growers both nearby and afar. Integrated systems that are cost-effective and energy-efficient will require new ways of thinking about agriculture, energy infrastructure, and rural economic development. Implementing these integrated systems will require innovation and investment in novel technologies, efficient value chains, and socioeconomic and policy frameworks; all are needed to support an expanded biofuels infrastructure that can meet the challenges of scale.
Point cloud matching based on 3D self-similarity (2012)

Point cloud is one of the primitive representations of 3D data nowadays. Despite that much work has been done in 2D image matching, matching 3D points achieved from different perspective or at different time remains to be a challenging problem. This paper proposes a 3D local descriptor based on 3D self-similarities. We not only extend the concept of 2D self-similarity [1] to the 3D space, but also establish the similarity measurement based on the combination of geometric and photometric information. The matching process is fully automatic i.e. needs no manually selected land marks. The results on the LiDAR and model data sets show that our method has robust performance on 3D data under various transformations and noises.
Bioencapsulation Technology in Meat Preservation (2005)

The fermentation process has long been used as a method of meat preservation. In order to eliminate batch to batch variation the fermentation process must be standardised. This, combined with problems associated with emerging pathogens such as enterohaemorrhagic Escherichia coli has led to a re-examination of the process of fermented meat production in order to ensure the production of a consistently high quality and safe product. Encapsulation technology can be applied to meat fermentations with the objectives of enhancing the existing methods of preservation and in developing novel methods to combat the problem of emerging and re-emerging pathogens. Encapsulation technology has been shown to be beneficial in the production of fermented meats by both direct and indirect acidification. Indirect acidification occurs after the addition of a starter culture to the meat and encapsulation technology has been observed to enhance its activity upon its addition to meat. The success of encapsulation would appear to be based on some form of spatial organisation involving a) protection and b) controlled release. The creation of a microenvironment, which provides the desired conditions or populations and the physical regulatory systems, minimises the effect of fluctuations in the macroenvironment and protects the cells from competition, predation and lysis. Controlled delivery from the microenvironment assist the cells to adapt to the new macroenvironmental conditions and then release the adapted cells under regulated conditions. Encapsulated acidulants are already in use in the United States and their use is on the increase in Europe. Problems such as discoloration and lack of binding associated with direct acidification can be overcome by encapsulation, which allows the time and rate of acid release to be controlled. Emerging pathogens are now challenging the antimicrobial hurdles present in a fermented meat product. This has led to investigations into enhancing the safety of existing manufacturing processes for fermented meats. Bacteriocins are antimicrobial agents, which are naturally produced by lactic acid bacteria. However, their ineffectiveness towards Gram-negative bacteria and their reduced activity in meat products has excluded their use until now. Combining bacteriocins, for example nisin, with other stresses enhances their activity towards Gram-negative pathogens. Encapsulation in polymer gels facilitates the optimisation of conditions for in situ nisin production and permits the controlled release of bacteriocins into the macroenvironment. Therefore, this technology has the potential to facilitate the use of bacteriocins produced by lactic acid bacteria in meat products as a means of overcoming potential problems associated with emerging pathogens.
Nuclear localization and cell cycle regulation of a murine protein tyrosine phosphatase. (1994)

MPTP is a murine homolog of the human T-cell protein tyrosine phosphatase (PTPase) and the rat PTP-S enzyme. Enzymatic activity of this ubiquitously expressed protein was demonstrated in immunoprecipitates from NIH 3T3 cells and in recombinant protein overexpressed in bacteria. Expression of beta-galactosidase-MPTP MPTP chimeric proteins in COS1 cells identified a nuclear localization signal at the carboxyl terminus of the MPTP that was sufficient to direct beta-galactosidase as well as a tagged version of the MPTP to the nucleus. Deletion analysis of amino acids within the nuclear targeting signal showed that this sequence does not conform to the bipartite type of nuclear localization signals. Furthermore, it was shown that the steady-state levels of MPTP RNA fluctuate in a cell cycle-specific manner. On the basis of these experiments, we discuss the possible function of MPTP in the cell cycle and other nuclear processes.
p16INK4a Expression and Clinicopathologic Parameters in Renal Cell Carcinoma (2006)

The absence of p16INK4a expression in most tumour cells indicates that p16INK4a could be involved in the tumourigenesis of RCC. Immunohistochemically detected positivity for p16INK4a is a positive prognosticator for specific survival in both uni- and multivariate analyses.
An antibody-based biomarker discovery method by mass spectrometry sequencing of complementarity determining regions (2010)

Autoantibodies are increasingly used as biomarkers in the detection of autoimmune disorders and cancer. Disease specific antibodies are generally detected by their binding to specific antigens. As an alternative approach, we propose to identify specific complementarity determining regions (CDR) of IgG that relate to an autoimmune disorder or cancer instead of the specific antigen(s). In this manuscript, we tested the technical feasibility to detect and identify CDRs of specific antibodies by mass spectrometry. We used a commercial pooled IgG preparation as well as purified serum IgG fractions that were spiked with different amounts of a fully human monoclonal antibody (adalimumab). These samples were enzymatically digested and analyzed by nanoLC Orbitrap mass spectrometry. In these samples, we were able to identify peptides derived from the CDRs of adalimumab. These peptides could be detected at an amount of 110 attomole, 5 orders of magnitude lower than the total IgG concentration in these samples. Using higher energy collision induced dissociation (HCD) fragmentation and subsequent de novo sequencing, we could successfully identify 50% of the detectable CDR peptides of adalimumab. In addition, we demonstrated that an affinity purification with anti-dinitrophenol (DNP) monoclonal antibody enhanced anti-DNP derived CDR detection in a serum IgG background. In conclusion, specific CDR peptides could be detected and sequenced at relatively low levels (attomole-femtomole range) which should allow the detection of clinically relevant CDR peptides in patient samples.
Experimental and Computational Investigation of C−N Bond Activation in Ruthenium N-Heterocyclic Carbene Complexes (2010)

A combination of experimental studies and density functional theory calculations is used to study C-N bond activation in a series of ruthenium N-alkyl-substituted heterocyclic carbene (NHC) complexes. These show that prior C-H activation of the NHC ligand renders the system susceptible to irreversible C-N activation. In the presence of a source of HCl, C-H activated Ru(I(i)Pr(2)Me(2))'(PPh(3))(2)(CO)H (1, I(i)Pr(2)Me(2) = 1,3-diisopropyl-4,5-dimethylimidazol-2-ylidene) reacts to give Ru(I(i)PrHMe(2))(PPh(3))(2)(CO)HCl (2, I(i)PrHMe(2) = 1-isopropyl-4,5-dimethylimidazol-2-ylidene) and propene. The mechanism involves (i) isomerization to a trans-phosphine isomer, 1c, in which hydride is trans to the metalated alkyl arm, (ii) C-N cleavage to give an intermediate propene complex with a C2-metalated imidazole ligand, and (iii) N-protonation and propene/Cl(-) substitution to give 2. The overall computed activation barrier (ΔE(++)(calcd)) corresponds to the isomerization/C-N cleavage process and has a value of +24.4 kcal/mol. C-N activation in 1c is promoted by the relief of electronic strain arising from the trans disposition of the high-trans-influence hydride and alkyl ligands. Experimental studies on analogues of 1 with different C4/C5 carbene backbone substituents (Ru(I(i)Pr(2)Ph(2))'(PPh(3))(2)(CO)H, Ru(I(i)Pr(2))'(PPh(3))(2)(CO)H) or different N-substituents (Ru(IEt(2)Me(2))'(PPh(3))(2)(CO)H) reveal that Ph substituents promote C-N activation. Calculations confirm that Ru(I(i)Pr(2)Ph(2))'(PPh(3))(2)(CO)H undergoes isomerization/C-N bond cleavage with a low barrier of only +21.4 kcal/mol. Larger N-alkyl groups also facilitate C-N bond activation (Ru(I(t)Bu(2)Me(2))'(PPh(3))(2)(CO)H, ΔE(++)(calcd) = +21.3 kcal/mol), and in this case the reaction is promoted by the formation of the more highly substituted 2-methylpropene.
A facile and efficient synthesis of d6‐labeled PU‐H71, a purine‐scaffold Hsp90 inhibitor (2009)

Abstract PU‐H71 is a purine‐scaffold Hsp90 inhibitor currently undergoing late stage preclinical evaluation for the treatment of cancer. In this investigation, we present a simple method for the synthesis of d 6 ‐labeled PU‐H71 for use as an internal standard to accurately quantitate the drug in biological matrices based on an LC‐MS‐MS method. PU‐H71‐d 6 was synthesized in five steps using readily available 1,3‐dibromopropane‐d 6 and is an important compound for the advancement of our clinical program. Copyright © 2009 John Wiley &amp; Sons, Ltd.
Epidemiology and treatment of gastric Campylobacter pylori infection: more questions than answers. (1990)

Two-hundred and ten consecutive patients undergoing routine gastroscopy were additionally investigated for evidence of Campylobacter pylori (C.p.). 106 patients were positive in one or more tests: 99.1% using a rapid urease detecting test (CLO-test), 80.2% histology, 78.3% cytology and 60% culture. We found no difference between the CLO-test results from biopsies taken from different parts of the stomach in individual patients. C.p. was found in 100% of patients with significant chronic antral gastritis, 67.7% with gastric ulcers, 65% with duodenal ulcers and in 12.1% of normal individuals. The C.p. infection was apparently eliminated in 50% of cases treated with bismuth subsalicylate (BSS) for four weeks. The combination of BSS with amoxicillin, tinidazole or an H2-receptor antagonist offered no advantage over BSS alone. Treatment with BSS led to improvement in symptoms and histological findings including healing of ulcers in patients with or without persistent C.p. infection. The recurrence of C.p. infection after apparently successful treatment was, however, 75% in 4 weeks. In conclusion, C.p. infection correlates strongly with the presence of chronic gastritis, and significantly with gastric and duodenal ulceration. The best diagnostic approach is the combination of a rapid urease detecting test and histology. C.p. infection is of long duration and difficult to eliminate. The most effective treatment for C.p. infection remains BSS as single agent.
Pseudomonas aeruginosa biofilms in the respiratory tract of cystic fibrosis patients (2009)

The present study was undertaken to investigate the appearance and location of Pseudomonas aeruginosa in the cystic fibrosis (CF) lung and in sputum. Samples include preserved tissues of CF patients who died due to chronic P. aeruginosa lung infection prior to the advent of intensive antibiotic therapy, explanted lungs from 3 intensively treated chronically P. aeruginosa infected CF patients and routine sputum from 77 chronically P. aeruginosa infected CF patients. All samples were investigated microscopically using hematoxylin-eosin (HE), Gram and alcian-blue stain, PNA FISH and immunofluorescence for alginate.Investigation of the preserved tissues revealed that prior to aggressive antibiotic therapy, P. aeruginosa infection and destruction of the CF lung correlated with the occurrence of mucoid (alginate) bacteria present in aggregating structures surrounded by pronounced polymorphonuclear-leukocyte (PMN) inflammation in the respiratory zone (9/9). Non-mucoid bacteria were not observed here, and rarely in the conductive zone (1/9). However, in the explanted lungs, the P. aeruginosa aggregates were also mucoid but in contrast to the autopsies, they were very rare in the respiratory zone but abundant in the sputum of the conductive zone (3/3), which also contained abundances of PMNs (3/3). Non-mucoid and planktonic P. aeruginosa were also observed here (3/3).In conclusion, the present intensive antibiotic therapy of chronic P. aeruginosa infections, at the Copenhagen CF Centre, seems to restrain but not eradicate the bacteria from the conductive zone, whereas the remaining healthy respiratory zone appears to be protected, for a long period, from massive biofilm infection. This strongly suggests that the conductive zone serves as a bacterial reservoir where the bacteria are organized in mucoid biofilms within the mucus, protected against antibiotics and host defenses.
Optimizing levodopa therapy for Parkinson&rsquo;s disease with levodopa/carbidopa/entacapone: implications from a clinical and patient perspective (2008)

After 40 years of clinical experience, levodopa remains the gold standard treatment for Parkinson's disease (PD) despite the recent emergence of a host of new therapies. Some physicians are cautious when prescribing levodopa because of its association with motor complications. Evidence now suggests that levodopa-associated complications are a result of deep troughs in delivery of levodopa to the brain caused by the short plasma half-life of conventional levodopa formulations (levodopa and a dopa decarboxylase inhibitor [DDCI]). Dosing strategies, such as dose increases and dose fractionation, may be effective in the short term. For the longer-term, levodopa/carbidopa/entacapone provides pharmacokinetically optimized levodopa therapy that significantly increases the plasma half-life and bioavailability of levodopa, providing more consistent plasma levodopa levels without deep troughs. Evidence from clinical trials in PD patients experiencing re-emergence of symptoms due to wearing-off has consistently shown that levodopa/DDCI and entacapone significantly increases ON-time and affords greater functionality, as measured by the Unified Parkinson's Disease Rating Scale (UPDRS) with conventional levodopa. These trials have also shown that levodopa/DDCI and entacapone is generally well tolerated, with notable adverse events including worsening dyskinesia, nausea and diarrhea. Patients experiencing re-emergence of symptoms due to wearing-off may benefit from optimized levodopa therapy with levodopa/carbidopa/entacapone.
Differential Methylation Hybridization Array of Endometrial Cancers Reveals Two Novel Cancer-Specific Methylation Markers (2007)

The 5' CpG islands for SESN3 and TITF1 are novel cancer-specific methylation markers. Methylation at these loci is strongly associated with aberrant MLH1 methylation in endometrial cancers. SESN3, TITF1 and MLH1 methylation did not predict overall survival or disease-free survival in this large cohort of patients with endometrioid endometrial cancer.
Neem — An Omnipotent Plant: A Retrospection (2004)

Abstract For Abstract see ChemInform Abstract in Full Text.
Tyrphostin induced growth inhibition: correlation with effect on p210bcr-abl autokinase activity in K562 chronic myelogenous leukemia. (1994)

We have examined a series of tyrosine kinase inhibitors structurally related to erbstatin (tyrphostins) for inhibition of p210bcr-abl autokinase activity in vitro and for growth inhibition of chronic myelogenous leukemia (CML)K562 cells. Of the tyrphostins with IC50 for growth < 50 microM, AG814, AG946, AG952, AG896, AG953, AG956 and AG957 (structurally related to lavendustin A and piceatannol) completely inhibited p210bcr-abl kinase activity in an immune complex kinase assay. Another group of tyrphostins (AG807, AG568, AG763, AG1076, AG490, AG1318, AG556, AG1319, AG555 and AG1111) inhibits growth of K562 cells but not p210bcr-abl tyrosine kinase activity. Of the compounds which inhibit growth and p210bcr-abl tyrosine kinase activity, AG957 inhibits DNA synthesis as early as 2 h (60% inhibition at 20 microM of AG957), a time and concentration of drug where RNA and protein synthesis were not affected. AG957 inhibits p210bcr-abl tyrosine phosphorylation in living cells by 1 h without an inhibition of total protein phosphorylation. Growth inhibition by AG957 was reversible after 4 h of exposure, but irreversible after 24 h. AG957 can be considered as an important lead structure for the development of anti-bcr-abl tyrosine kinase antagonists. These data also raise the possibility that bcr-abl kinase activity is directly linked to maintenance of DNA synthesis in Philadelphia chromosome positive (Ph+) CML cells.
A H3PO4 preswelling strategy to enhance the proton conductivity of a H2SO4-doped polybenzimidazole membrane for vanadium flow batteries (2016)

A H<sub>3</sub>PO<sub>4</sub> preswelling strategy is proposed to prepare H<sub>2</sub>SO<sub>4</sub>-doped polybenzimidazole (PBI) membranes with improved ADL and proton conductivity for vanadium flow battery.