gebhart/patrepeval huggingface dataset:
Formulation for stable and efficient implementation of the rigorous coupled-wave analysis of binary gratings (1995)

The rigorous coupled-wave analysis technique for describing the diffraction of electromagnetic waves by periodic grating structures is reviewed. Formulations for a stable and efficient numerical implementation of the analysis technique are presented for one-dimensional binary gratings for both TE and TM polarization and for the general case of conical diffraction. It is shown that by exploitation of the symmetry of the diffraction problem a very efficient formulation, with up to an order-of-magnitude improvement in the numerical efficiency, is produced. The rigorous coupled-wave analysis is shown to be inherently stable. The sources of potential numerical problems associated with underflow and overflow, inherent in digital calculations, are presented. A formulation that anticipates and preempts these instability problems is presented. The calculated diffraction efficiencies for dielectric gratings are shown to converge to the correct value with an increasing number of space harmonics over a wide range of parameters, including very deep gratings. The effect of the number of harmonics on the convergence of the diffraction efficiencies is investigated. More field harmonics are shown to be required for the convergence of gratings with larger grating periods, deeper gratings, TM polarization, and conical diffraction.
Preclinical characterization of CG53135 (FGF-20) in radiation and concomitant chemotherapy/radiation-induced oral mucositis. (2003)

CG53135 demonstrates potent, regimen-dependent activity in hamster models of OM. The activity was regimen dependent. BrdUrd incorporation studies confirmed that CG53135 had proliferative activity in vivo with a favorable pharmacokinetic profile. Based in part on work described herein, CG53135 has received approval from the United States Food and Drug Administration to be evaluated in a Phase I clinical trial of cancer patients at risk for developing OM.
In Vitro Resistance Studies of Hepatitis C Virus Serine Protease Inhibitors, VX-950 and BILN 2061 (2004)

We have used a structure-based drug design approach to identify small molecule inhibitors of the hepatitis C virus (HCV) NS3.4A protease as potential candidates for new anti-HCV therapies. VX-950 is a potent NS3.4A protease inhibitor that was recently selected as a clinical development candidate for hepatitis C treatment. In this report, we describe in vitro resistance studies using a subgenomic replicon system to compare VX-950 with another HCV NS3.4A protease inhibitor, BILN 2061, for which the Phase I clinical trial results were reported recently. Distinct drug-resistant substitutions of a single amino acid were identified in the HCV NS3 serine protease domain for both inhibitors. The resistance conferred by these mutations was confirmed by characterization of the mutant enzymes and replicon cells that contain the single amino acid substitutions. The major BILN 2061-resistant mutations at Asp(168) are fully susceptible to VX-950, and the dominant resistant mutation against VX-950 at Ala(156) remains sensitive to BILN 2061. Modeling analysis suggests that there are different mechanisms of resistance to VX-950 and BILN 2061.
Structure of the Bone Morphogenetic Protein Receptor ALK2 and Implications for Fibrodysplasia Ossificans Progressiva (2012)

Bone morphogenetic protein (BMP) receptor kinases are tightly regulated to control development and tissue homeostasis. Mutant receptor kinase domains escape regulation leading to severely degenerative diseases and represent an important therapeutic target. Fibrodysplasia ossificans progressiva (FOP) is a rare but devastating disorder of extraskeletal bone formation. FOP-associated mutations in the BMP receptor ALK2 reduce binding of the inhibitor FKBP12 and promote leaky signaling in the absence of ligand. To establish structural mechanisms of receptor regulation and to address the effects of FOP mutation, we determined the crystal structure of the cytoplasmic domain of ALK2 in complex with the inhibitors FKBP12 and dorsomorphin. FOP mutations break critical interactions that stabilize the inactive state of the kinase, thereby facilitating structural rearrangements that diminish FKBP12 binding and promote the correct positioning of the glycine-serine-rich loop and αC helix for kinase activation. The balance of these effects accounts for the comparable activity of R206H and L196P. Kinase activation in the clinically benign mutant L196P is far weaker than R206H but yields equivalent signals due to the stronger interaction of FKBP12 with R206H. The presented ALK2 structure offers a valuable template for the further design of specific inhibitors of BMP signaling.
Minireview: cryptic translocations and telomere integrity. (1992)

There are now several case reports of subtle or translocation events involving telomeric ends of chromosomes, events which were not detected by conventional cytogenetic methods but were detected by molecular cytogenetic methods. For present purposes, a cryptic translocation will be defined as one that is sufficiently subtle that it would not be reliably detected, in the majority of diagnostic laboratories, by G-band analysis at the 400-500 band stage of resolution. Questions raised by the discovery of cryptic translocations include the following: (1) When should a cryptic translocation or deletion event be suspected and molecular techniques be employed? (2) What technology is best for investigation of cryptic translocations? (3) Are cryptic translocation and deletion events involving telomeres any more common than submicroscopic deletions elsewhere in the genome? In this short review, I would like to describe these recent case reports, as well as relevant new research on the structure and polymorphism of human telomeres. Several investigators have raised the intriguing possibility that polymorphism in human telomeres could play a role in cryptic translocation events (Brown et al. 1990; Wilkie et al. 1991). If this proves to be true, it could represent a major source of human pathology that has not previously been appreciated.
The Antifungal Activity of RsAFP2, a Plant Defensin from <i>Raphanus sativus</i>, Involves the Induction of Reactive Oxygen Species in <i>Candida albicans</i> (2007)

RsAFP2 (Raphanus sativus antifungal peptide 2), an antifungal plant defensin isolated from seed of R. sativus, interacts with glucosylceramides (GlcCer) in membranes of susceptible yeast and fungi and induces membrane permeabilization and fungal cell death. However, using carboxyfluorescein-containing small unilamellar vesicles containing purified GlcCer, we could not observe permeabilization as a consequence of insertion of RsAFP2 in such vesicles. Therefore, we focused on a putative RsAFP2-induced signaling cascade downstream of RsAFP2-binding to GlcCer in fungal membranes. We show that RsAFP2 induces reactive oxygen species (ROS) in Candida albicans wild type in a dose-dependent manner, but not at all in an RsAFP2-resistant DeltagcsC. albicans mutant that lacks the RsAFP2-binding site in its membranes. These findings indicate that upstream binding of RsAFP2 to GlcCer is needed for ROS production leading to yeast cell death. Moreover, the antioxidant ascorbic acid blocks RsAFP2-induced ROS generation, as well as RsAFP2 antifungal activity. These data point to the presence of an intracellular plant defensin-induced signaling cascade, which involves ROS generation and leads to fungal cell growth arrest.
Generative Portrait Sketching (2005)

We consider the problem of generating art with a computer system, as it relates to the understanding of a drawing style. Our system in its present development is able to sketch faces automatically, starting from a picture, typically a photographic snapshot of a scene with humans. Once a digital image is considered, the system automatically finds where some of the faces (or face-like patterns) are and isolate these. Each face image pattern is then used to produce a stylised portrait. The style which the system aims at using is derived from the one the first author has developed over the years in his artistic practice. The goal is for the final system to mimic the process developed by the artist, rather than aiming at results exactly reproducing his way of drawing a portrait. Nevertheless, the produced sketches are in the style of the artist. Various steps in the process of producing a sketch by the artist were isolated, including: image segmentation, filtering, shape selection and depiction, filling and shading. The implementation of these steps relies on an understanding of human visual perception, of the artist’s work process, and of advances made in computer vision. 1.
Epidermal growth factor-receptor mutations and the clinical outcome in male smokers with squamous cell carcinoma of lung (2008)

22136 Background: Epidermal growth factor receptor (EGFR) mutations in non-small cell lung cancer (NSCLC) have been reported to be related to certain clinical characteristics (i.e., female, non-smokers with adenocarcinoma) and gefitinib responsiveness. This exploratory analysis was performed within a prospective phase II study to determine the clinical outcome and the incidence of EGFR mutations in male smokers with squamous cell carcinoma, who were treated with EGFR tyrosine kinase inhibitor gefitinib. Methods: We analyzed the incidence of EGFR mutations in NSCLC specimens from 69 Korean patients who were treated with gefitinib in a prospective study. For a subset of 20 male patients with squamous cell carcinoma and a history of smoking, pretreatment tumor tissue samples were obtained and analyzed for EGFR mutations (exons 18 to 21). Results: EGFR mutations were found in 3 (15%) out of 20 patients, including in-frame deletions within exon 19 (n=2) and L858R missence mutation in exon 21 (n=1). The 3 patients with EGFR mutations responded to EGFR tki therapy, whereas only one of remaining 17 patients with wild-type EGFR achieved clinical response. Trends toward longer progression-free survival (5.8 vs. 2.4 months; P=0.07) and overall survival (9.6 vs. 7.2 months; P=0.76) were noted in patients with EGFR mutations compared to those with wild-type EGFR, respectively. Conclusions: Although male smokers with squamous cell carcinoma have not been considered ideal candidates for treatment with gefitinib, significant incidence of EGFR mutations was observed. No significant financial relationships to disclose.
Perspectives of arterial gene therapy for the prevention of restenosis (1996)

Restenosis remains the main limitation of interventional cardiology. Restenosis is an important target for gene therapy since it is frequent (30% of patients), costly (estimated $2 billion annually), refractory to all pharmacological therapies, and related, at least in part, to smooth muscle cell proliferation which is an inviting target for antiproliferative molecular strategies. Because cell division is ultimately controlled by intranuclear events, the protein product of genes selected for their antiproliferative effects usually remains inside the cells. Consequently, the transfer of growth-inhibitory genes needs to be efficient-i.e., involve a large proportion of smooth muscle cells populating the angioplasty site. To date, adenoviral vectors are, by far, the most efficient vectors to perform in vivo arterial gene delivery. These vectors, as well as others, have been recently used to demonstrate that therapeutic genes encoding cytolytic (thymidine kinase) or cytostatic (hypophosphorylatable retinoblastoma protein, endothelial nitric oxide synthase, gax, etc.) products successfully inhibit smooth muscle cell proliferation and related intimal hyperplasia. Despite substantial progress, major technical issues remain to be addressed before gene therapy is applied to clinical restenosis. First-generation recombinant adenoviruses evoke both cellular and humoral immune responses leading to local toxicity and transient gene expression. Moreover, the low efficiency of gene transfer to atherosclerotic arteries may further impair the biological effect of antiproliferative genes. Finally, restenosis is a multifactorial phenomenon in which intimal hyperplasia plays an important but not exclusive role. Prevention of constrictive remodeling should also be taken into account in an integrated genetic strategy to prevent restenosis.
New concepts in pathogenesis and treatment of diabetic retinopathy (2001)

Retinal neovascularization is a major feature of proliferative diabetic retinopathy, which represents a major public health problem, being responsible for more irreversible blindness in persons of middle and older age than any other pathology. The societal burden of ocular neovascularization has prompted extensive research into its mechanisms. The aim of this review will be to briefly summarize the current knowledge regarding the clinical and laboratory findings of diabetic retinopathy. From an investigational view, studies of ocular neovascularization provide important informations, often permitting real-time, serial observations of neovascularization in vivo. This allows investigators to analyse the relevance of specific pathogenic concepts regarding the mechanisms of angiogenesis in vivo. This review will additionally describe current concepts regarding the pathogenesis and treatment of diabetic retinopathy.
Trends and Correlates of Class 3 Obesity in the United States From 1990 Through 2000 (2002)

The prevalence of class 3 obesity is increasing rapidly among adults. Because these extreme BMI levels are associated with the most severe health complications, the incidence of various diseases will increase substantially in the future.
LCoS nematic SLM characterization and modeling for diffraction efficiency optimization, zero and ghost orders suppression (2012)

Pixilated spatial light modulators are efficient devices to shape the wavefront of a laser beam or to perform Fourier optical filtering. When conjugated with the back focal plane of a microscope objective, they allow an efficient redistribution of laser light energy. These intensity patterns are usually polluted by undesired spots so-called ghosts and zero-orders whose intensities depend on displayed patterns. In this work, we propose a model to account for these discrepancies and demonstrate the possibility to efficiently reduce the intensity of the zero-order up to 95%, the intensity of the ghost up to 96% and increase diffraction efficiency up to 44%. Our model suggests physical cross-talk between pixels and thus, filtering of addressed high spatial frequencies. The method implementation relies on simple preliminary characterization of the SLM and can be computed a priori with any phase profile. The performance of this method is demonstrated employing a Hamamatsu LCoS SLM X10468-02 with two-photon excitation of fluorescent Rhodamine layers.
Acute downregulation of connexin43 at wound sites leads to a reduced inflammatory response, enhanced keratinocyte proliferation and wound fibroblast migration (2006)

Experimental downregulation of connexin43 (Cx43) expression at skin wound sites appears to markedly improve the rate and quality of healing, but the underlying mechanisms are currently unknown. Here, we have compared physiological and cell biological aspects of the repair process with and without Cx43 antisense oligodeoxynucleotide treatment. Treated wounds exhibited accelerated skin healing with significantly increased keratinocyte and fibroblast proliferation and migration. In vitro knockdown of Cx43 in a fibroblast wound-healing model also resulted in significantly faster healing, associated with increased mRNA for TGF-β1, and collagen α1 and general collagen content at the wound site. Treated wounds showed enhanced formation of granulation tissue and maturation with more rapid angiogenesis, myofibroblast differentiation and wound contraction appeared to be advanced by 2-3 days. Recruitment of both neutrophils and macrophages was markedly reduced within treated wounds, concomitant with reduced leukocyte infiltration. In turn, mRNA levels of CC chemokine ligand 2 and TNF-α were reduced in the treated wound. These data suggest that, by reducing Cx43 protein with Cx43-specific antisense oligodeoxynucleotides at wound sites early in the skin healing process repair is enhanced, at least in part, by accelerating cell migration and proliferation, and by attenuating inflammation and the additional damage it can cause.
Amiloride-Insensitive Currents of the Acid-Sensing Ion Channel-2a (ASIC2a)/ASIC2b Heteromeric Sour-Taste Receptor Channel (2003)

Acid-sensing ion channel-2a (ASIC2a) is an amiloride-blockable proton-gated cation channel, probably contributing to sour-taste detection in rat taste cells. To isolate another subtype of the sour-taste receptor, we screened a rat circumvallate papilla cDNA library and identified ASIC2b, an N-terminal splice variant of ASIC2a. Reverse transcription-PCR analyses confirmed the expression of ASIC2b transcripts in the circumvallate papilla and, moreover, demonstrated its expression in the foliate and fungiform papillae. Immunohistochemical analyses revealed that ASIC2b, as well as ASIC2a, was expressed in a subpopulation of taste cells in the circumvallate, foliate, and fungiform papillae, and some of the cells displayed both ASIC2a and ASIC2b immunoreactivities. Subsequent coimmunoprecipitation studies with circumvallate papillae extracts indicated that ASIC2b associated with ASIC2a to form assemblies and, together with our immunohistochemical findings, strongly suggested that both ASIC2 subunits formed heteromeric channels in taste cells in the circumvallate, foliate, and fungiform papillae. Oocyte electrophysiology demonstrated that the ASIC2a/ASIC2b channel generated maximal inward currents at a pH of < or =2.0, which is in agreement with the in vivo pH sensitivity of rat taste cells, and that the amiloride sensitivity of the heteromer decreased with decreasing pH and was almost completely abolished at a pH of 2.0. These findings provide persuasive explanations for the amiloride insensitivity of acid-induced responses of rat taste cells.
Hydrophilic and cationic latex particles for the specific extraction of nucleic acids (1999)

The adsorption of BSA and RNA onto hydrophilic and thermosensitive poly(N-isopropyl-acrylamide) (NIPAM) latex particles was described as a function of pH, ionic strength and temperature. The hydrogel poly(NIPAM) latex was synthesized by precipitation polymerization in the presence of a cationic amino-containing monomer. The latex obtained was characterized in terms of particle size, and electrophoretic mobility as a function of pertinent variables: pH, temperature and ionic strength. The adsorption of BSA onto the latex was investigated to identify the conditions at which the adsorbed amount of BSA was negligible. The adsorption of RNA was studied to establish the conditions which give rise to maximal adsorption of RNA. In order to favor the desorption of RNA, desorption was investigated by changing the pH, ionic strength, and temperature. The adsorption of BSA was found to be lower at 20 than at 40 degrees C. However, the adsorption of RNA is drastically affected by the pH and the ionic strength of the medium. Maximal adsorbed amounts were obtained at acidic pH, 20 degrees C, and low ionic strength. The adsorption is shown to decrease when the pH, temperature and ionic strength increase, implying that the adsorption was mainly governed by electrostatic interactions. Maximal release of RNA molecules was obtained at high ionic strength and basic pH.
Exploiting clustering and phrases for context-based information retrieval (1997)

This paper explores exploiting the synergy between document clustering and phrasal analysis for the purpose of automatically constructing a corrrex~-busedretrieval system.A contex~consists of two components -a cluster of logically related articles (its exrension) and a small set of salient concepts, represented by words and phrases and organized by the cluster's key terms (its irr~ertsion).At inn-time, the system presents contexts that best match the result list of a user's natural language query.The user can then choose a context and manipulate the intensionsd component to both browse the context's extension and launch new searches over the entire database.We argue that the focused relevance feedback provided by contexts, at a level of abstraction higher than individual documents and lower than the database as a whole, provides a natural way for users to refine vague information needs and helps to blur the distinction between searching and browsing.The I%zraphrase interface, running over a database of business-related news articles, is used to illustrate the advantages of such a context-based retrieval paradigm.
Homeobox C9 suppresses Beclin1-mediated autophagy in glioblastoma by directly inhibiting the transcription of death-associated protein kinase 1 (2015)

Collectively, our data indicate that HOXC9 is an oncogene in glioblastoma. We have revealed its role in the control of autophagy, and we suggest that HOXC9 is a novel and promising therapeutic target.
The IBM System/370 vector architecture (1986)

Discussed is the instruction-set architecture of the IBM System/370 vector facility, a compatible extension of the System/370 architecture. Both the base system, which is a general-purpose System/370 processor, and the optional vector facility employ a register type of organization. Data formats are the same, arithmetic operations produce exactly the same results, arithmetic exceptions are handled in the same way, and instructions are precisely interruptible for page faults and other causes in the same manner as those of the base system. This approach permits substantially increased performance on vectorizable programs with only a modest increase in hardware and software, while retaining the ability to run existing nonvector programs unchanged.
Characterization of Aspergillus niger Pectate Lyase A, (2000)

The Aspergillus niger plyA gene encoding pectate lyase A (EC 4.2.99. 3) was cloned from a chromosomal lambda(EMBL4) library using the Aspergillus nidulans pectate lyase encoding gene [Dean, R. A., and Timberlake, W. E. (1989) Plant Cell 1, 275-284] as a probe. The plyA gene was overexpressed using a promoter fusion with the A. niger pyruvate kinase promoter. Purification of the recombinant pectate lyase A resulted in the identification of two enzyme forms of which one appeared to be N-glycosylated and the other appeared to be free of N-glycosylation. The two enzyme forms showed identical specific activities. The N-glycosylation free pectate lyase A was further characterized with respect to product formation on polygalacturonic acid (alpha-1,4 linked D-galacturonic acid) and mode of action on oligogalacturonides of degree of polymerization 2-8. The bond cleavage frequencies for tetra-, penta-, and hexagalacturonides were studied as a function of [CaCl(2)]. The bond cleavage frequencies changed in a [CaCl(2)]-dependent way for penta- and hexagalacturonide. Kinetic studies using tetra- and hexagalacturonide revealed a strong sigmoidal [CaCl(2)]-dependent relation. The role of Ca(2+) ions in substrate binding is discussed.