gebhart/patrepeval huggingface dataset:
Claudin 4 Protein Expression in Primary and Metastatic Pancreatic Cancer (2004)

We performed a comprehensive immunohistochemical evaluation of claudin 4 protein expression in paraffin-embedded tissue samples from 72 patients with primary infiltrating pancreatic cancer, 38 patients with metastatic pancreatic cancer, and a panel of normal control tissue samples from various organs. In 11 samples of primary infiltrating pancreatic cancer, foci of pancreatic intraepithelial neoplasia (PanIN) were present and also were analyzed for claudin 4 protein expression. Intense positive claudin 4 immunolabeling was noted within virtually all primary (71/72 [99%]) and metastatic (49/49 [100%]) pancreatic cancer tissue samples analyzed and in 10 of 11 samples of PanIN. In all cases, immunolabeling was noted in a membranous distribution. Claudin 4 protein also was detectable in normal breast, prostate, bladder, and gastrointestinal mucosa, although expression was substantially less intense than that seen in pancreatic cancer tissue samples. Our findings support the use of claudin 4 as a target for novel therapeutics or radioimaging of infiltrating pancreatic cancer. Furthermore, the finding of claudin 4 overexpression within pancreatic intraepithelial neoplasia, the precursor lesion of pancreatic cancer, suggests a potential benefit of imaging claudin 4 before the development of an invasive carcinoma.
Tolerance to allopregnanolone with focus on the GABA‐A receptor (2010)

Many studies have suggested a relationship between stress, sex steroids, and negative mental and mood changes in humans. The progesterone metabolite allopregnanolone is a potent endogenous ligand of the γ-amino butyric acid -A (GABA-A) receptor, and the most discussed neuroactive steroid. Variations in the levels of neuroactive steroids that influence the activity of the GABA-A receptor cause a vulnerability to mental and emotional pathology. There are physiological conditions in which allopregnanolone production increases acutely (e.g. stress) or chronically (e.g. menstrual cycle, pregnancy), thus exposing the GABA-A receptor to high and continuous allopregnanolone concentrations. In such conditions, tolerance to allopregnanolone may develop. We have shown that both acute and chronic tolerances can develop to the effects of allopregnanolone. Following the development of acute allopregnanolone tolerance, there is a decrease in the abundance of the GABA-A receptor α4 subunit and the expression of the α4 subunit mRNA in the ventral-posteriomedial nucleus of the thalamus. Little is known about the mechanism behind allopregnanolone tolerance and its effects on assembly of the GABA-A receptor composition. The exact mechanism of the allopregnanolone tolerance phenomena remains unclear. The purpose of this review is to summarize certain aspects of current knowledge concerning allopregnanolone tolerance and changes in the GABA-A receptors.
Analysis of the Role of Heat Shock Protein (Hsp) Molecular Chaperones in Polyglutamine Disease (1999)

Polyglutamine (polygln) diseases are a group of inherited neurodegenerative disorders characterized by protein misfolding and aggregation. Here, we investigate the role in polygln disease of heat shock proteins (Hsps), the major class of molecular chaperones responsible for modulating protein folding in the cell. In transfected COS7 and PC12 neural cells, we show that Hsp40 and Hsp70 chaperones localize to intranuclear aggregates formed by either mutant ataxin-3, the disease protein in spinocerebellar ataxia type 3/Machado-Joseph disease (SCA3/MJD), or an unrelated green fluorescent protein fusion protein containing expanded polygln. We further demonstrate that expression of expanded polygln protein elicits a stress response in cells as manifested by marked induction of Hsp70. Studies of SCA3/MJD disease brain confirm these findings, showing localization of Hsp40 and, less commonly, Hsp70 chaperones to intranuclear ataxin-3 aggregates. In transfected cells, overexpression of either of two Hsp40 chaperones, the DNAJ protein homologs HDJ-1 and HDJ-2, suppresses aggregation of truncated or full-length mutant ataxin-3. Finally, we extend these studies to a PC12 neural model of polygln toxicity in which we demonstrate that overexpression of HDJ-1 suppresses polygln aggregation with a parallel decrease in toxicity. These results suggest that expanded polygln protein induces a stress response and that specific molecular chaperones may aid the handling of misfolded or aggregated polygln protein in neurons. This study has therapeutic implications because it suggests that efforts to increase chaperone activity may prove beneficial in this class of diseases.
Ciliary Neurotrophic Factor for Acceleration of Peripheral Nerve Regeneration: An Experimental Study (2004)

The objective of this study was to investigate the effect of topically administrated ciliary neurotrophic factor (CNTF) on peripheral nerve regeneration. Sixty-eight Sprague Dawley rats underwent a unilateral sciatic nerve transection and silicon tubulization, with a 10-mm gap between the proximal and distal nerve stumps. Recombinant human CNTF (1 mg/kg) was injected into the rats of the experimental group, while normal saline was injected into the control group animals. Electrophysiologic and histologic studies, including nerve morphometry and electron microscopic observation, were performed at 1, 3, and 4 months postoperatively. HRP tracing was carried out at 3 months postoperatively to label spinal-cord, ventral-horn, and dorsal-root ganglia. The results revealed that CNTF-treated animals showed a higher motor nerve conduction velocity of the sciatic nerve and a higher muscle action potential amplitude of the anterior tibial muscle, compared to the controls ( p < 0.01). Nerves repaired with CNTF had larger axon diameter, greater number of axons, and more advanced myelination ( p < 0.05). More HRP-labeled motor neurons were also found in the ventral horns of CNTF-treated animals. These results indicate that topical application of CNTF to the injury site potentiates motor nerve axonal regrowth and axon maturation during peripheral nerve regeneration.
Multiphase Organic Synthesis in Microchannel Reactors (2006)

"Miniaturization" is one of the most important aspects in today's technology. Organic chemistry is no exception. The search for highly effective, controllable, environmentally friendly methods for preparing products is of prime importance. The development of multiphase organic reactions in microchannel reactors has gained significant importance in recent years to allow novel reactivity, and has led to many fruitful results that are not attainable in conventional reactors. This Focus Review aims to shed light on how effectively multiphase organic reactions can be conducted with microchannel reactors by providing examples of recent remarkable studies, which have been grouped on the basis of the phases involved.
Population, Evolutionary and Genomic Consequences of Interference Selection (2002)

Weakly selected mutations are most likely to be physically clustered across genomes and, when sufficiently linked, they alter each others' fixation probability, a process we call interference selection (IS). Here we study population genetics and evolutionary consequences of IS on the selected mutations themselves and on adjacent selectively neutral variation. We show that IS reduces levels of polymorphism and increases low-frequency variants and linkage disequilibrium, in both selected and adjacent neutral mutations. IS can account for several well-documented patterns of variation and composition in genomic regions with low rates of crossing over in Drosophila. IS cannot be described simply as a reduction in the efficacy of selection and effective population size in standard models of selection and drift. Rather, IS can be better understood with models that incorporate a constant "traffic" of competing alleles. Our simulations also allow us to make genome-wide predictions that are specific to IS. We show that IS will be more severe at sites in the center of a region containing weakly selected mutations than at sites located close to the edge of the region. Drosophila melanogaster genomic data strongly support this prediction, with genes without introns showing significantly reduced codon bias in the center of coding regions. As expected, if introns relieve IS, genes with centrally located introns do not show reduced codon bias in the center of the coding region. We also show that reasonably small differences in the length of intermediate "neutral" sequences embedded in a region under selection increase the effectiveness of selection on the adjacent selected sequences. Hence, the presence and length of sequences such as introns or intergenic regions can be a trait subject to selection in recombining genomes. In support of this prediction, intron presence is positively correlated with a gene's codon bias in D. melanogaster. Finally, the study of temporal dynamics of IS after a change of recombination rate shows that nonequilibrium codon usage may be the norm rather than the exception.
Nonsurgical Breast Enlargement Using an External Soft-Tissue Expansion System by Roger K. Khouri, M.D., Ingrid Schlenz, M.D., Brian J. Murphy, M.D., and Thomas J. Baker, M.D. (2000)

Received for publication March 1, 2000. Sumner A. Slavin, M.D. 1101 Beacon Street Brookline, Mass. 02446
High-volume optical vortex multiplexing and de-multiplexing for free-space optical communication (2011)

We report an approach to the increase of signal channels in free-space optical communication based on composed optical vortices (OVs). In the encoding process, conventional algorithm employed for the generation of collinearly superimposed OVs is combined with a genetic algorithm to achieve high-volume OV multiplexing. At the receiver end, a novel Dammann vortex grating is used to analyze the multihelix beams with a large number of OVs. We experimentally demonstrate a digitized system which is capable of transmitting and receiving 16 OV channels simultaneously. This system is expected to be compatible with a high-speed OV multiplexing technique, with potentials to extremely high-volume information density in OV communication.
Next-Generation Sequencing: From Basic Research to Diagnostics (2009)

In the relatively short time frame since 2005, NGS has fundamentally altered genomics research and allowed investigators to conduct experiments that were previously not technically feasible or affordable. The various technologies that constitute this new paradigm continue to evolve, and further improvements in technology robustness and process streamlining will pave the path for translation into clinical diagnostics.
Cl 2 reactive ion etching for gate recessing of AlGaN/GaN field-effect transistors (1999)

An effective gate recess etch process has been applied to AlGaN/GaN modulation-doped field-effect transistors (MODFETs), utilizing low power Cl2 reactive ion etching. In comparison to GaAs-based materials, GaN shows a greater robustness to ion damage under ion bombardment at very low ion energies (&amp;lt;70 V). It suggests that a viable gate recess etch process is possible. Recessed gate AlGaN/GaN MODFETs with gate to drain breakdown higher than −80 V have been demonstrated with an optimized lower power Cl2 reactive ion etching.
A Controlled Trial of the Effect of Folate Supplements on Homocysteine, Lipids and Hemorheology in End-Stage Renal Disease (2000)

Elevated plasma homocysteine (Hcy), dyslipidemia and hemorheological abnormalities all occur commonly in end-stage renal disease (ESRD) and are recognized risk factors for arteriosclerosis. To study the effect of folate supplementation on these factors we conducted a randomized controlled trial. Thirteen hemodialysis (HD) and 8 continuous ambulatory peritoneal dialysis (CAPD) patients received either 5 mg folic acid daily or placebo for 3 months. After 1 and 3 months, fasting blood samples were taken for Hcy, lipid profile, blood and plasma viscosity, red blood cell (RBC) osmotic fragility, plasma fibrinogen concentration and in vivo platelet aggregability. At baseline, the CAPD patients had a higher mean plasma fibrinogen concentration than the HD patients and they also tended to have higher mean plasma viscosity. Folate-treated patients showed marked increases in RBC folate and an average decrease in plasma Hcy concentration of 33%. Mean total cholesterol, LDL cholesterol and triglyceride concentrations decreased significantly in the CAPD patients who took folate. Folate had no significant effect on hemorheology. In conclusion, folate supplements in ESRD reduce plasma Hcy concentrations and may improve lipid profiles. In our patients, hemorheological abnormalities were more marked in patients on CAPD than in those on HD and were not improved by folate supplementation.
On Bayesian Analysis of Mixtures with an Unknown Number of Components (with discussion) (1997)

Summary New methodology for fully Bayesian mixture analysis is developed, making use of reversible jump Markov chain Monte Carlo methods that are capable of jumping between the parameter subspaces corresponding to different numbers of components in the mixture. A sample from the full joint distribution of all unknown variables is thereby generated, and this can be used as a basis for a thorough presentation of many aspects of the posterior distribution. The methodology is applied here to the analysis of univariate normal mixtures, using a hierarchical prior model that offers an approach to dealing with weak prior information while avoiding the mathematical pitfalls of using improper priors in the mixture context.
A Microfabricated Deuterium Ion Source for Compact Neutron Generators (2013)

Active neutron interrogation is generally accepted as a reliable means of detecting the illicit transportation of special nuclear materials, in particular highly enriched uranium. The development of portable active neutron interrogation systems for field detection applications could be facilitated by the use of a new deuterium ion source which has the potential to advance many of the performance limiting aspects of exiting compact, accelerator-driven neutron generators. The ion source being investigated is a gated array of sharp metal tips that uses high electric fields to generate deuterium ion currents through the physical processes of field ionization and field desorption. The deuterium ions produced by the source are extracted and used to drive a D-D (or D-T) fusion reaction to create neutrons. The basic microstructure for the ion source array is derived from modern semiconductor microfabrication technology for field emitter arrays, though many structural modifications have been made in an attempt to reach the required operating fields of the ion generation processes. Pulsed (field desorption) and d.c. (field ionization) tests conducted with each array design type developed thus far indicate a steady improvement in array tip operating fields. Field ionization studies were conducted with arrays at source temperatures of 77 K and 293 K. Newly developed arrays have demonstrated field ionization currents upwards of ~50 nA, which is roughly 50% of the maximum ion production possible, as presently fabricated. Neutron production by field ionization was demonstrated for the first time from the microfabricated arrays. A maximum neutron yield of 95 n/s (6300 n/s/sqcm of array active area) was observed from a 1.5 sqmm array using a D-D fusion reaction at -90 kV. Field desorption studies at 77 K and 293 K were conducted in parallel with field ionization testing. To date, the arrays have consistently demonstrated the field desorption of deuterium ions from array tip surfaces. The number of deuterium ions desorbed was quantified and found to be significantly less than predicted. The low deuterium ion yields have been attributed to the presence of surface contaminants that inhibit the adsorption of deuterium. As such, thermal and hydrogen plasma cleaning methods are being investigated to condition the array tip surfaces. For both field ionization and field desorption, improved array designs that can achieve higher tip operating fields are required before predicted neutron yields (>10^9 n/s/sqcm) can be demonstrated.
Functional Orientation of the Acyltransferase Domain in a Module of the Erythromycin Polyketide Synthase (1998)

Modular polyketide synthases (PKSs), such as the 6-deoxyerythronolide B synthase (DEBS), catalyze the biosynthesis of structurally complex and medicinally important natural products. These large multienzymes are organized into a series of functional units known as modules. Each dimeric module contains two catalytically independent clusters of active sites homologous to those of vertebrate fatty acid synthases. Earlier studies have shown that modules consist of head-to-tail homodimers in which ketosynthase (KS) and acyl carrier protein (ACP) domains are contributed by opposite subunits to form a catalytic center. Here, we probe the functional topology of the acyltransferase (AT) domain which transfers the methylmalonyl moiety of methylmalonyl-CoA onto the phosphopantetheine arm of the ACP domain. Using a bimodular derivative of DEBS, the AT domain of module 2 (AT2) was inactivated by site-directed mutagenesis. Heterodimeric protein pairs were generated in vitro between the inactivated AT2 (AT2 degrees) polypeptide and an inactive KS1 (KS1 degrees) or KS2 (KS2 degrees) protein. Both of these hybrid proteins supported polyketide synthesis, suggesting that AT2 can perform its function from either subunit. The apparent catalytic rate constants for each of the two hybrid protein pairs, KS1 degrees/AT2 degrees and KS2 degrees/AT2 degrees, were identical, indicating that no significant kinetic preference exists for a particular AT2-ACP2 combination. These results suggest that the AT domain can be shared between the two clusters of active sites within the same dimeric module. Such a novel structural organization might provide a functional advantage for the efficient biosynthesis of polyketides.
Expression cloning and characterization of human 17 beta-hydroxysteroid dehydrogenase type 2, a microsomal enzyme possessing 20 alpha-hydroxysteroid dehydrogenase activity (1993)

17 beta-Hydroxysteroid dehydrogenase (17 beta-HSD) is an enzyme crucial to the regulation of intracellular levels of biologically active steroid hormones in a variety of tissues. Here, we report the isolation, structure, and characterization of a cDNA encoding the human 17 beta-HSD type 2. A 1.4-kilobase cDNA was identified, and DNA sequence analysis indicated that 17 beta-HSD type 2 was a protein of 387 amino acids with a predicted molecular weight of 42,782. The protein contained an amino-terminal type II signal-anchor motif and a carboxyl-terminal endoplasmic reticulum retention motif, which suggested that 17 beta-HSD type 2 was associated with the membranes of the endoplasmic reticulum. 17 beta-HSD type 2 was capable of catalyzing the interconversion of testosterone and androstenedione as well as estradiol and estrone. The enzyme also demonstrated 20 alpha-HSD activity toward 20 alpha-dihydroprogesterone. The amount of 17 beta-HSD type 2 mRNA in placenta was found to be high. The data suggest that the 17 beta-HSD type 2 cDNA encodes the microsomal 17 beta-HSD of human placenta, described by several laboratories.
Über Oxalsäure‐imidchloride. II (1909)

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Directed evolution of mammalian paraoxonases PON1 and PON3 for bacterial expression and catalytic specialization (2003)

Serum paraoxonases (PONs) are a group of enzymes that play a key role in organophosphate (OP) detoxification and in prevention of atherosclerosis. However, their structure and mechanism of action are poorly understood. PONs seem like jacks-of-all-trades, acting on a very wide range of substrates, most of which are of no physiological relevance. Family shuffling and screening lead to the first PON variants that express in a soluble and active form in Escherichia coli. We describe variants with kinetic parameters similar to those reported for PONs purified from sera and others that show dramatically increased activities. In particular, we have evolved PON1 variants with OP-hydrolyzing activities 40-fold higher than wild type and a specificity switch of >2,000-fold, producing PONs specialized for OP rather than ester hydrolysis. Analysis of the newly evolved variants provides insights into the evolutionary relationships between different family members.
Improved Assays for Determining the Cytosolic Access of Peptides, Proteins, and Their Mimetics (2013)

Proteins and other macromolecules that cross biological membranes have great potential as tools for research and next-generation therapeutics. Here, we describe two assays that effectively quantify the cytosolic localization of a number of previously reported peptides and protein domains. One assay, which we call GIGI (glucocorticoid-induced eGFP induction), is an amplified assay that informs on relative cytosolic access without the need for sophisticated imaging equipment or adherent cells. The second, GIGT (glucocorticoid-induced eGFP translocation), is a nonamplified assay that informs on relative cytosolic access and exploits sophisticated imaging equipment to facilitate high-content screens in live cells. Each assay was employed to quantify the cytosolic delivery of several canonical "cell permeable peptides," as well as more recently reported minimally cationic miniature proteins and zinc finger nuclease domains. Our results show definitively that both overall charge as well as charge distribution influence cytosolic access and that small protein domains containing a discrete, helical, penta-Arg motif can dramatically improve the cytosolic delivery of small folded proteins such as zinc finger domains. We anticipate that the assays described herein will prove useful to explore and discover the fundamental physicochemical and genetic properties that influence both the uptake and endosomal release of peptidic molecules and their mimetics.
Frequency Control in Isolated/Islanded Microgrids Through Voltage Regulation (2015)

This paper presents a frequency control mechanism for an isolated/islanded microgrid through voltage regulation. The proposed scheme makes use of the load voltage sensitivity to operating voltages and can be easily adopted for various types of isolated microgrids. The proposed controller offers various advantages, such as allowing the integration of significant levels of intermittent renewable resources in isolated/islanded microgrids without the need for large energy storage systems, providing fast and smooth frequency regulation with no steady-state error, regardless of the generator control mechanism. The controller requires no extra communication infrastructure, and only local voltage and frequency is used as feedback. The performance of the controller is evaluated and validated through various simulation studies in the PSCAD/EMTDC software environment based on a realistic microgrid test system, using small-perturbation stability analysis to demonstrate the positive effect of the proposed controller in system damping.