gebhart/patrepeval huggingface dataset:
Current and Novel Treatment Options for Actinic Keratosis (2004)

Actinic keratosis (AK), located on sun-exposed areas of the skin, is an increasing global health burden. Multiple ablative and topical treatment options are available to manage this disease; however, topical treatment options are receiving significant interest because AK is commonly associated with areas of substantial photodamage, and destructive modalities cannot effectively treat subclinical AK. Several topical therapies, including 0.5% and other 5-fluorouracil concentrations, photodynamic therapy, 3% diclofenac sodium gel, and imiquimod 5% cream, are indicated in the treatment of AK. This article will review key data on the efficacy and safety of several topical therapies in the treatment and management of AK. The review includes discussions of imiquimod 5% cream, approved in 2004 in the treatment of AK of the face or scalp. Whether administered as monotherapy or adjunctive therapy, topical therapies provide the opportunity to effectively manage AK and will likely emerge as an important tool for healthcare providers.
Structural-RNN: Deep Learning on Spatio-Temporal Graphs (2016)

Deep Recurrent Neural Network architectures, though remarkably capable at modeling sequences, lack an intuitive high-level spatio-temporal structure. That is while many problems in computer vision inherently have an underlying high-level structure and can benefit from it. Spatiotemporal graphs are a popular tool for imposing such high-level intuitions in the formulation of real world problems. In this paper, we propose an approach for combining the power of high-level spatio-temporal graphs and sequence learning success of Recurrent Neural Networks (RNNs). We develop a scalable method for casting an arbitrary spatio-temporal graph as a rich RNN mixture that is feedforward, fully differentiable, and jointly trainable. The proposed method is generic and principled as it can be used for transforming any spatio-temporal graph through employing a certain set of well defined steps. The evaluations of the proposed approach on a diverse set of problems, ranging from modeling human motion to object interactions, shows improvement over the state-of-the-art with a large margin. We expect this method to empower new approaches to problem formulation through high-level spatio-temporal graphs and Recurrent Neural Networks.
The Trill Incremental Analytics Engine (2014)

This technical report introduces Trill – a new query processor for analytics. Trill fulfills a combination of three requirements for a query processor to serve the diverse big data analytics space: (1) Query Model: Trill is based on a tempo-relational model that enables it to handle streaming and relational queries with early results, across the latency spectrum from real-time to offline; (2) Fabric and Language Integration: Trill is architected as a high-level language library that supports rich data-types and user libraries, and integrates well with existing distribution fabrics and applications; and (3) Performance: Trill’s throughput is high across the latency spectrum. For streaming data, Trill’s throughput is 2-4 orders of magnitude higher than today’s comparable streaming engines. For offline relational queries, Trill’s throughput is comparable to a major modern commercial columnar DBMS. Trill uses a streaming batched-columnar data representation with a new dynamic compilation-based system architecture that addresses all these requirements. In this technical report, we describe Trill’s new design and architecture, and report experimental results that demonstrate Trill’s high performance across diverse analytics scenarios. We also describe how Trill’s ability to support diverse analytics has resulted in its adoption across many usage scenarios at Microsoft.
Modes of a two-dimensional phase-locked array of vertical-cavity surface-emitting lasers (1990)

A simple formalism is reported for studying the modes of an infinite two-dimensional (2-D) phase-locked array of vertical-cavity surface-emitting diode lasers. In this approach, the Helmholtz equation is approximately separated into products of solutions of the associated one-dimensional (linear) arrays. This formalism allows the knowledge gained from years of research into the modal properties of linear diode arrays to be applied directly to 2-D arrays. As a result, it is expected that both 2-D gain-guided and index-guided arrays (except those with excess gain in the low-index channels) will lase in the high-order mode characterized by emission into four distinct off-axis far-field lobes. In contrast, it is expected that properly constructed 2-D leaky-mode arrays would lase preferentially in the fundamental mode well above threshold.
Improved amplification system for detection of hepatitis C virus genome that simultaneously differentiates viral genotypes. (1996)

An improved system for amplification of hepatitis C virus genome (HCV) was developed based on a multiplex nested polymerase chain reaction format. Two sets of oligonucleotide primers were used simultaneously. One was derived from the conserved sequences in the 5' non-coding region of the viral genome which can bind to the viral genome of all genotypes. The other set of primers was designed from a sequence in the nonstructural-5 region of HCV. HCV genotypes 1 and 3 can be differentiated by the banding patterns of amplified DNA products. All of 39 samples containing the HCV genotype 1 could be amplified with primers in the 5' non-coding region only, whereas 92% of those with genotype 3 could be amplified by both primer sets. In addition, HCV RNA can be detected in 81% of 84 anti-HCV-positive blood donors and in 0% of 34 anti-HCV-negative cases. Of the HCV RNA-positive specimens, 69% showed genotype 1-like patterns while 31% showed genotype 3-like patterns. The detection rate of HCV RNA in this study was much higher than that in our previous report due to the improvement of new primers which can detect all genotypes of the virus. In conclusion, this improved amplification system is a sensitive method for rapid identification of HCV RNA in clinical specimens that can simultaneously differentiate the two most common genotypes of HCV found in Thailand.
Anticodon shift in tRNA: a novel mechanism in missense and nonsense suppression. (1983)

In a previous publication, an unusual UGG-reading missense suppressor caused by insertion of an extra adenylate residue in the anticodon loop of an Escherichia coli glycine tRNA was described. In this study, we provide in vivo evidence that the additional nucleotide causes an "anticodon shift" by one nucleotide in the 3' direction and that the "new" anticodon can explain the unanticipated coding properties of the suppressor. We converted the UGG suppressor with ethyl methanesulfonate, a base-substitution mutagen, to suppressors that read codons related to UGG by a single base change. Sequence analysis of each mutant tRNA revealed that its mutational alteration was an anticipated base change in one of the three nucleotides of the "new" anticodon. Although the new suppressors read codons beginning with A or U, the mutant tRNAs lack the customary hypermodified nucleosides on the 3' side of the anticodon. As determined on the basis of their in vivo coding specificities, the new mutant tRNAs do not continue to utilize the original anticodon triplet for decoding. Furthermore, the failure of the UGG suppressor to correct frameshift mutations throughout each of three genes of the trp operon suggests that the addition of a nucleotide to the anticodon loop of a tRNA does not necessarily result in out-of-frame decoding by the tRNA. Therefore, a "frameshift" mutation in a tRNA has principally changed the triplet codon recognition properties of the molecule.
Removal of Flatulence Factor of some Pulses by Microbial Fermentation (1981)

The pulses are cultivated in almost all civilized parts of the world. These make some regular contribution in the diet of all people.
Carbapenem and Cephalosporin Resistance among Enterobacteriaceae in Healthcare-Associated Infections, California, USA1 (2019)

We analyzed antimicrobial susceptibility test results reported in healthcare-associated infections by California hospitals during 2014-2017. Approximately 3.2% of Enterobacteriaceae reported in healthcare-associated infections were resistant to carbapenems and 26.9% were resistant to cephalosporins. The proportion of cephalosporin-resistant Escherichia coli increased 7% (risk ratio 1.07, 95% CI 1.04-1.11) per year during 2014-2017.
Substrate specificity of bacterial glycerophospholipid:cholesterol acyltransferase (1982)

The substrate specificity of a bacterial analogue of the plasma enzyme lecithin:cholesterol acyltransferase (LCAT) has been examined with small unilamellar liposomes and Triton mixed micelles. In contrast to LCAT, the microbial enzyme is capable of using all of the naturally occurring phospholipids as acyl donors. In general reaction rate depends more on the length or degree of unsaturation of the acyl chains than on the nature of the phospholipid head group. Among a series of disaturated phosphatidylcholines in liposomes, dilauroylphosphatidylcholine is the preferred acyl donor. Like LCAT, the enzyme will catalyze acyl transfer by using other alcohols in addition to cholesterol. Of saturated straight chain primary alcohols 1-decanol is the preferred acyl acceptor. Cholesterol, however, is a far better acceptor than any non-sterol alcohol tested. Other steroids with equatorial hydroxyls at position C-3 and trans-fused A:B rings will also act as acceptors whereas those steroids with axial hydroxyls at C-3 or cis-fused rings are inhibitors of acyl transfer. The ability of steroids to act as acyl acceptors may be due to the nature of their interaction with the phospholipid acyl donor.
Platelet-derived growth factor binds specifically to receptors on vascular smooth muscle cells and the binding becomes nondissociable. (1982)

Radioiodinated platelet-derived growth factor (125I-PDGF) was used in studies of PDGF binding sites on vascular smooth muscle cells. There was an excellent correlation between the ability of 125I-PDGF to stimulate cell proliferation and to bind specifically to cultured vascular smooth muscle cells. The half-maximal concentration for both processes was 0.1 nM. There were 50,000 binding sites per cell. Reduced PDGF, prepared by treatment of PDGF with 20 mM dithiothreitol, had neither the ability to bind to smooth muscle cells nor to stimulate cellular proliferation. Epidermal growth factor, nerve growth factor, fibroblast growth factor, and histone B did not compete for the binding sites at a concentration of 10 nM. 125I-PDGF binding was slowly reversible at 4 degrees C and was rapidly and totally reversible after a 1-min incubation at 37 degrees C. After continued incubation at 37 degrees C, the binding became irreversible. The half-time for formation of the nondissociable state of 125I-PDGF binding was approximately equal to 5 min at 37 degrees C. The nondissociable state of binding was not formed at 4 degrees C even after 1 hr of incubation. These data suggest that the sites we labeled are the PDGF receptors that mediate PDGF's mitogenic action and that a nondissociable state of PDGF binding is formed at 37 degrees C. It is likely that nondissociable PDGF represents internalized ligand or binding to sites that are converted to a high-affinity state after the ligand binds.
Control of common symptoms in advanced cancer. (1994)

In common with any medical problem, careful assessment and an analytical approach are the keystones to effective symptom control in advanced cancer. When dealing with such symptoms the multi-faceted pathophysiology must be considered, and due attention paid to the affective component of pain and other symptoms. Adequate care given to history taking and a knowledge of the likely pathogenesis of symptoms in advanced cancer can prevent unnecessary investigations and fruitless trials of inappropriate symptomatic remedies. The treatment chosen should be the simplest effective regimen tailored to the individual patient. The importance of explanation to the patient cannot be overstated and is an integral part of any treatment and the sole component of many. This paper reviews the management of common symptoms in advanced cancer (dyspnoea, nausea and vomiting, constipation, anorexia-cachexia syndrome, hypercalcaemia, confusion, insomnia and depression.
Regulation of fibroblast cyclooxygenase synthesis by interleukin-1. (1988)

We have prepared polyclonal antiserum against sheep seminal vesicle prostaglandin H synthase (also termed cyclooxygenase) which cross-reacted with human cyclooxygenase, thereby enabling us to directly determine the synthetic rate of cyclooxygenase protein and its modulation by the monokine interleukin-1 (IL-1). Cultured human dermal fibroblast cells were labeled with [35S]methionine, and the membrane-bound cyclooxygenase was solubilized and immunoprecipitated 35S-labeled fibroblast cyclooxygenase migrated on sodium dodecyl sulfate-polyacrylamide gel electrophoresis with a molecular size of approximately 73,000 daltons, similar to that of native sheep cyclooxygenase and of cyclooxygenase covalently labeled by [3H]aspirin, i.e. [3H]acetylcyclooxygenase. Additional validation of the immunoprecipitated 35S-labeled cyclooxygenase band indicated that it was specifically displaced by unlabeled sheep cyclooxygenase. N-terminal amino acid radiosequence analysis of [3H]proline-labeled cyclooxygenase revealed [3H]proline residues in positions 3, 6, and 8, consistent with the previously reported N-terminal sequence of sheep cyclooxygenase. Endoglycosidase H treatment of 35S-labeled fibroblast cyclooxygenase caused a decline in apparent molecular size (due to removal of mannose residues) which was similar to that seen with the native sheep cyclooxygenase. [35S]Methionine pulse-chase experiments indicated a half-life of 1 h for fibroblast cyclooxygenase. The monokine interleukin-1 stimulated fibroblast cyclooxygenase synthesis in a time- and dose-dependent fashion; as little as 0.03 unit/ml of IL-1 produced significant stimulation of 35S-labeled cyclooxygenase synthesis. Maximum stimulation was 3-10-fold after preincubation of the cells with 0.3 unit/ml of IL-1 for 12-16 h. IL-1 treatment of cells yielded parallel dose-response curves for stimulation of prostaglandin E2 formation, increased cellular cyclooxygenase activity, and increased synthetic rate of newly formed cyclooxygenase, suggesting that the IL-1 effect is mediated mainly, if not solely, via induction of cyclooxygenase synthesis.
NF-κB Controls Expression of Inhibitor IκBα: Evidence for an Inducible Autoregulatory Pathway (1993)

The eukaryotic transcription factor nuclear factor-kappa B (NF-kappa B) participates in many parts of the genetic program mediating T lymphocyte activation and growth. Nuclear expression of NF-kappa B occurs after its induced dissociation from its cytoplasmic inhibitor I kappa B alpha. Phorbol ester and tumor necrosis factor-alpha induction of nuclear NF-kappa B is associated with both the degradation of performed I kappa B alpha and the activation of I kappa B alpha gene expression. Transfection studies indicate that the I kappa B alpha gene is specifically induced by the 65-kilodalton transactivating subunit of NF-kappa B. Association of the newly synthesized I kappa B alpha with p65 restores intracellular inhibition of NF-kappa B DNA binding activity and prolongs the survival of this labile inhibitor. Together, these results show that NF-kappa B controls the expression of I kappa B alpha by means of an inducible autoregulatory pathway.
Vibration‐Energy‐Harvesting System: Transduction Mechanisms, Frequency Tuning Techniques, and Biomechanical Applications (2019)

Vibration-based energy-harvesting technology, as an alternative power source, represents one of the most promising solutions to the problem of battery capacity limitations in wearable and implantable electronics, in particular implantable biomedical devices. Four primary energy transduction mechanisms are reviewed, namely piezoelectric, electromagnetic, electrostatic, and triboelectric mechanisms for vibration-based energy harvesters. Through generic modeling and analyses, it is shown that various approaches can be used to tune the operation bandwidth to collect appreciable power. Recent progress in biomechanical energy harvesters is also shown by utilizing various types of motion from bodies and organs of humans and animals. To conclude, perspectives on next-generation energy-harvesting systems are given, whereby the ultimate intelligent, autonomous, and tunable energy harvesters will provide a new energy platform for electronics and wearable and implantable medical devices.
Agents and strategies in development for improved management of herpes simplex virus infection and disease (2005)

The quiet pandemic of herpes simplex virus (HSV) infections has plagued humanity since ancient times, causing mucocutaneous infection such as herpes labialis and herpes genitalis. Disease symptoms often interfere with every-day activities and occasionally HSV infections are the cause of life-threatening or sight-impairing disease, especially in neonates and the immuno-compromised patient population. After infection the virus persists for life in neurons of the host in a latent form, periodically reactivating and often resulting in significant psychosocial distress for the patient. Currently no cure is available. So far, vaccines, ILs, IFNs, therapeutic proteins, antibodies, immunomodulators and small-molecule drugs with specific or non-specific modes of action lacked either efficacy or the required safety profile to replace the nucleosidic drugs acyclovir, valacyclovir, penciclovir and famciclovir as the first choice of treatment. The recently discovered inhibitors of the HSV helicase-primase are the most potent development candidates today. These antiviral agents act by a novel mechanism of action and display low resistance rates in vitro and superior efficacy in animal models. This review summarises the current therapeutic options, discusses the potential of preclinical or investigational drugs and provides an up-to-date interpretation of the challenge to establish novel treatments for herpes simplex disease.
Effect of Guggulsterone and Cembranoids ofCommiphora mukulon Pancreatic Phospholipase A2: Role in Hypocholesterolemia (2008)

Guggulsterone (7) and cembranoids (8-12) from Commiphora mukul stem bark resin guggul were shown to be specific modulators of two independent sites that are also modulated by bile salts (1-6) to control cholesterol absorption and catabolism. Guggulsterone (7) antagonized the chenodeoxycholic acid (3)-activated nuclear farnesoid X receptor (FXR), which regulates cholesterol metabolism in the liver. The cembranoids did not show a noticeable effect on FXR, but lowered the cholate (1)-activated rate of human pancreatic IB phospholipase A2 (hPLA2), which controls gastrointestinal absorption of fat and cholesterol. Analysis of the data using a kinetic model has suggested an allosteric mechanism for the rate increase of hPLA2 by cholate and also for the rate-lowering effect by certain bile salts or cembranoids on the cholate-activated hPLA2 hydrolysis of phosphatidylcholine vesicles. The allosteric inhibition of PLA2 by certain bile salts and cembranoids showed some structural specificity. Biophysical studies also showed specific interaction of the bile salts with the interface-bound cholate-activated PLA2. Since cholesterol homeostasis in mammals is regulated by FXR in the liver for metabolism and by PLA2 in the intestine for absorption, modulation of PLA2 and FXR by bile acids and selected guggul components suggests novel possibilities for hypolipidemic and hypocholesterolemic therapies.
Distinct Fibroblast Growth Factor (FGF)/FGF Receptor Signaling Pairs Initiate Diverse Cellular Responses in the Oligodendrocyte Lineage (2005)

Fibroblast growth factors (FGFs) have been implicated in numerous cellular processes, including proliferation, migration, differentiation, and survival. Whereas FGF-2, the prototypic ligand in a family of 22 members, activates all four tyrosine kinase FGF receptors (FGFR1-FGFR4), other members demonstrate a higher degree of selectivity. Oligodendrocytes (OLs), the myelin-producing cells of the CNS, are highly influenced by FGF-2 at all stages of their development. However, how other FGFs and their cognate receptors orchestrate the development of OLs is essentially undefined. Using a combination of specific FGF ligands and receptor blocking antibodies, we now show that FGF-8 and FGF-17 target OL progenitors, inhibiting their terminal differentiation via the activation of FGFR3, whereas FGF-9 specifically targets differentiated OLs, triggering increases in process growth via FGFR2 signaling; FGF-18 targets both OL progenitors and OLs via activation of both FGFR2 and FGFR3. These events are highly correlated with changes in FGF receptor expression from FGFR3 to FGFR2 as OL progenitors differentiate into mature OLs. In addition, we demonstrate that, although activation of FGFR1 by FGF-2 leads to proliferation of OL progenitors, it produces deleterious effects on differentiated OLs (i.e., aberrant reentry into cell cycle and down-regulation of myelin proteins with a loss of myelin membrane). These data suggest that ligand availability, coupled with changes in FGF receptor expression, yield a changing repertoire of ligand-receptor signaling complexes that contribute critically to the regulation of both normal OL development and potential OL/myelin pathogenesis.
Human Pot1 (Protection of Telomeres) Protein: Cytolocalization, Gene Structure, and Alternative Splicing (2002)

Fission yeast Pot1 (protection of telomeres) is a single-stranded telomeric DNA binding protein with a critical role in ensuring chromosome stability. A putative human homolog (hPot1) was previously identified, based on moderate sequence similarity with fission yeast Pot1 and telomere end-binding proteins from ciliated protozoa. Using indirect immunofluorescence, we show here that epitope-tagged hPot1 localizes to telomeres in interphase nuclei of human cells, consistent with a direct role in telomere end protection. The hPOT1 gene contains 22 exons, most of which are present in all cDNAs examined. However, four exons are subject to exon skipping in some transcripts, giving rise to five splice variants. Four of these are ubiquitously expressed, whereas the fifth appears to be specific to leukocytes. The resultant proteins vary significantly in their ability to form complexes with single-stranded telomeric DNA as judged by electrophoretic mobility shift assays. In addition to these splice variants, the Pot1 family is expanded by the identification of six more genes from diverse species. Pot1-like proteins have now been found in plants, animals, yeasts, and microsporidia.
Secondary quantization of gray-level images for minimum visual distortion (1992)

In digital imaging systems it is often necessary to reduce the bit precision of an image due to limitations in transmission or storage. The 8 bit storage of a 12 bit medical image is a good example. Generally, the input images are linearly quantized, and the goal is to find the fixed, digital mapping that preserves the highest image quality at the reduced bit precision. Since the response of the visual system to brightness differences is nonlinear, the optimal mapping is nonlinear. The traditional approach is to use one of the commonly accepted models of the visual system, e.g. a logarithm or power-law, to construct a Look-Up-Table (LUT) that performs the digital mapping. This paper will demonstrate that this approach is visually suboptimal for finite input precision, even if the visual model is perfect. A better method for constructing the digital mapping or LUT will be derived by posing the problem as a combinational optimization problem of taking N bits from M bits, where N is less than M, such that a visual distortion metric is minimized. Computer generated images will be used to demonstrate the method in a 12 bit to 8 bit application, and a 6 bit to 2 bit example will be included to illustrate its convergence characteristics.