gebhart/patrepeval huggingface dataset:
Pegylated Carboxyhemoglobin Bovine (SANGUINATE®) Restores RBCs Roundness and Reduces Pain during a Sickle Cell Vaso-Occlusive Crisis (2017)

Abstract Background: Pain during Vaso-Occlusive Crisis (VOC) is a hallmark of sickle cell disease (SCD) as deoxygenated (sickled) red blood cells (RBC) aggregate in the microvasculature due to Hemoglobin S (HbS) polymerization. PEGylated carboxyhemoglobin bovine (PEG-COHb; SANGUINATE®) was designed as a gas transfer agent to depolymerize HbS resulting from hypoxia. Prior in vitro studies have shown PEG-COHb capability to transfer carbon monoxide (CO) and oxygen (O2) to SCD hypoxic RBCs, reversing sickling. A prospective, randomized, single-dose Phase II clinical study is in progress (NCT02411708) evaluating the safety and efficacy of PEG-COHb in the treatment of severe VOC including pain reduction in the ambulatory setting. This study is also evaluating the levels of RBC sickling following treatment and association with pain scoring. Methods: Participants were randomized to a PEG-COHb (320 mg/kg) or saline (placebo) arm, in addition to standard treatment and IV opioid per institutional practice. Pain was assessed using a 10-point pain scale at screening, pre-infusion, hourly until discharge, 24-hours, 72-hours, and Day 7 post-infusion. Blood was collected at pre-infusion, time for readiness to discharge and 72 hours post-infusion to assess RBC shape morphology changes using image-based flow cytometry. Results: Interim results showed PEG-COHb treated subjects experienced significant reduction at discharge in pain score of 4.3 (±0.3) compared to 2.4 (±0.6) reduction in the placebo arm (p&amp;lt;0.01) (Fig 1). All PEG-COHb participants exhibited RBC morphology changes consistent with unsickling shortly after administration (Fig 2). There were no drug-related severe adverse events. Conclusions: PEG-COHb appeared to be safe, well tolerated, and associated with significantly reduced pain scores. The flow cytometry analysis of blood samples revealed PEG-COHb treatment reverted RBC to a more normal round morphology when compared to the placebo group. Individual patient data showed a trend between RBC unsickling (roundness) and pain score reductions. These results are consistent with depolymerization of HbS resulting from transfer of CO and/or O2 to sickled RBCs and O2 delivery to hypoxic tissue. This study supports advanced clinical trials of PEG-COHb as a potential therapy to reduce the pain associated with VOC. Disclosures Buontempo: Prolong Pharmaceuticals: Employment. Jubin: Prolong Pharmaceuticals: Employment. Buontempo: Prolong Pharmaceuticals: Employment. Real: Prolong Pharmaceuticals: Employment. Kazo: Prolong Pharmaceuticals: Employment. O'Brien: Prolong Pharmaceuticals: Employment. Adeel: Prolong Pharmaceuticals: Employment. Abuchowski: Prolong Pharmaceuticals: Employment, Membership on an entity's Board of Directors or advisory committees.
A necessidade de previsão em lei das transgressões militares que implicam em cerceamento da liberdade (2012)

This paper approaches the need for prediction in law of freedom restriction disciplinary sanctions to make it applicable as administrative military disciplinary penalties. The military institutions, organized with basis on hierarchy and discipline, have, in its large majority, its disciplinary regulations imposed by the decrees of executive power. The 1988’ Federal Constitution establishes at its article 5, LXI, that the prison for disciplinary transgression will be allowed for the hypotheses provided by law. The doubt remains installed because this constitutional structure, in view of the understanding that it could not be imposed on freedom restriction supported by a decree. However, according to most authors, the new constitutional order has approved the disciplinary regulations imposed by decrees as if were ordinary laws, making it valid and applicable, except specific rules that conflict with the constitution. Of course, part of the doctrine opposes to this argument, claiming that the new constitutional order did not accept those regulations, which must be established through specific legislative process. To respond to questions, it was used bibliographic research in books of doctrine, scientific articles and legal doctrine sites. Regarding the universe of methods that provide the logic bases of scientific research, it was used inductive method.
Development of a SNP validation toolset for wheat (2015)

Recent advances in high-throughput technologies and the corresponding growth of the bioinformatics databases, a lot of bioinformatics tools have been constantly developed and published in journals for data-intensive genetic analysis. However, repoducibility has been one of the biggest challenges in delivering bioinformatics. Virtualisation is one of the most commonly used solutions by creating virtualised and isolated environments for running different bioinformatics tools. Containerisation, however, is a more recent, promising, scalable and reproducible approach for delivering bioinformatics. It allows running bioinformatics tools on preconfigured containerised environments, which is lightweight and can be easily updated and shared between researchers. This dissertation has evaluated a bioinformatics toolkit previously developed for genetic marker design in preconfigured containers. The objectives for this dissertation were (1) to improve marker design software to correctly handle melt prediction of amplicons with multiple SNPs, (2) using containerised environments to design and screen PCR assay to (a) validate candidate SNPs detected by GBS of barley H. bulbosum introgression line, (b) validate QTL markers of wheat identified by GWAS on chromosome 1A, and (c) convert SNPs from 90K SNP chip for the bread wheat A genome to HRM markers.
&lt;title&gt;MapSnapper: engineering an efficient algorithm for matching images of maps from mobile phones&lt;/title&gt; (2007)

The MapSnapper project aimed to develop a system for robust matching of low-quality images of a paper map taken from a mobile phone against a high quality digital raster representation of the same map. The paper presents a novel methodology for performing content-based image retrieval and object recognition from query images that have been degraded by noise and subjected to transformations through the imaging system. In addition the paper also provides an insight into the evaluation-driven development process that was used to incrementally improve the matching performance until the design specifications were met.
Evidence for a dilator function of 8‐iso prostaglandin F<sub>2α</sub> in rat pulmonary artery (1997)

1. 8-Iso prostaglandin F2 alpha (8-iso PGF2 alpha) is one of a series of prostanoids formed independently of the cyclo-oxygenase pathway. It has been shown to be upregulated in many conditions of oxidant stress where its formation is induced by free radical-catalysed actions on arachidonic acid. As 8-iso PGF2 alpha is formed in vivo in diseases in which oxidant stress is high such as septic shock, we have assessed the relative potency and efficacy of this compound in pulmonary arteries from control and lipopolysaccharide (LPS)-treated rats. 2. Several studies have characterized the contractile actions of 8-iso PGF2 alpha on various smooth muscle preparations, but its potential dilator actions have not been addressed. Thus these studies examined both the contractile and dilator actions of 8-iso PGF2 alpha in rat pulmonary artery rings. The thromboxane mimetic U46619, PGE2 sodium nitroprusside (SNP) and acetyl choline (ACh) were used for comparison. Each prostanoid had to be dissolved in ethanol to a maximum concentration of 1 x 10-2 M. At high concentrations, ethanol directly contracted pulmonary vessels. We were therefore limited by the actions of the vehicle such that we were unable to add prostanoids at concentrations higher than 1 x 10-4 M. In some cases this meant that maximum responses were not achieved and in these cases the Emax and pD2 values are apparent estimates. 3. The following rank order of potency was obtained from contractile studies; U46619 > 8-iso PGF2 alpha > PGE2, each prostanoid producing concentration-dependent contractions (10(-10)-3 x 10(-4) M, 10(-9)-10(-4) M, 10(-8)-10(-4) M, respectively). As has been shown previously for other smooth muscle preparations, the thromboxane receptor (TP) antagonist ICI 192605, (1 x 10(-6), 1 x 10(-5) and 1 x 10(-4) M), inhibited the contractions of 8-iso PGF2 alpha in a concentration-dependent fashion. 4. The nitric oxide synthase inhibitor, NG-nitro-L-arginine methyl ester (L-NAME; 1 x 10(-4) M), enhanced the contractile function of both 8-iso PGF2 alpha and PGE2, but had no effect on that caused by U46619. Similarly, L-NAME inhibited the dilator function of all agents tested except the exogenous nitric oxide (NO) donor SNP indicating that PGE2 and 8-iso PGF2 alpha like ACh, act through the release of NO. The specificity of the effects of L-NAME were confirmed in studies with the inactive enantiomer D-NAME (1 x 10(-4) M), which did not affect the contractile or the dilator actions of 8-iso PGF2 alpha. Furthermore, ICI 192605 enhanced the dilator actions of 8-iso PGF2 alpha, suggesting that the dilator component of 8-iso PGF2 alpha was achieved via activation of a non-TP receptor. 5. Isoprostanes may modulate vascular tone by a direct action on TP receptors to cause contraction and via a distinct receptor leading to the release of NO to cause dilation.
Glaucoma ocular Alzheimer s disease (2003)

Glaucoma is a chronic neurodegeneration of the optic nerve and one of the leading causes of vision loss in the world among the aging. Retinal ganglion cells (RGCs) have been shown to die by apoptosis, or programmed cell death. Central to apoptosis is the activation of specific proteases, termed caspases. Caspases are activated in chronic neurodegenerations such as Alzheimer's disease (AD) as well as in RGCs after optic nerve transection. In rat glaucoma models we have shown that caspase-3, a major effector of the apoptotic cascade, is activated in RGCs and cleaves amyloid precursor protein (APP) to produce neurotoxic fragments that include amyloid-beta. Caspase-8, which initiates apoptosis after activation of receptors of the tumor necrosis factor (TNF) superfamily, is also activated in RGCs. This suggests a new hypothesis for RGC death in glaucoma involving chronic amyloid-beta neurotoxicity, mimicking AD at the molecular level. With loss of the protective effect of APP and upregulation of toxic APP fragments, RGCs die from chronic caspase activation, loss of synaptic homeostasis, amyloid-beta cytotoxicity and excitotoxicity. The benefits are that treatments for AD could be used to treat glaucoma, and strategies developed to treat glaucoma could treat other neurodegenerations.
Febrile temperature but not proinflammatory cytokines promotes phosphatidylserine expression on <i>Plasmodium falciparum</i> malaria‐infected red blood cells during parasite maturation (2010)

Intraerythrocytic maturation of the malaria parasite Plasmodium falciparum is associated with profound changes in the asymmetry of phospholipids in the lipid bilayer of the parasitized red blood cells (pRBCs). These changes may contribute to adherence of pRBCs to endothelial cells. This study investigates the effect of febrile temperature and proinflammatory cytokines on phosphatidylserine (PS) expression on the exofacial surface of pRBCs during parasite maturation. The expression of PS on the pRBCs was determined by flow cytometry using fluorescein-labeled annexin V, which specifically binds to PS and a vital nucleic acid fluorochrome for parasite staining. The results showed that PS expression on the surface of pRBCs increased in association with parasite maturation, especially at the late parasite stage. Furthermore, the growth of P. falciparum also accelerated senescence of the uninfected RBCs in parasite cultures. Exposure to febrile temperature led to significant increases in the expression of PS on the surface of pRBCs, particularly at the late parasite stage associated with the virulence strain of the parasite. In contrast, proinflammatory cytokines had no detectable effect on PS expression on pRBCs. These data suggest that PS molecule expression is more dependent on fever, parasitemia, parasite strain, and virulence than on cytokine exposure. These findings contribute to our understanding of the factors that are involved in malaria pathogenesis.
Comment on “Optical-fiber-based Mueller optical coherence tomography” (2004)

We comment on the recent Letter by Jiao et al. [Opt. Lett. 28, 1206 (2003)] in which a polarization-sensitive optical coherence tomography system was presented. Interrogating a sample with two orthogonal incident polarization states cannot always recover birefringence correctly. A previously presented fiber-based polarization-sensitive system was inaccurately characterized, and its method of eliminating the polarization distortion caused by single-mode optical fiber was presented earlier by Saxer et al. [Opt. Lett. 25, 1355 (2000)].
Targeted mRNA demethylation using an engineered dCas13b-ALKBH5 fusion protein (2020)

Studies on biological functions of N6-methyladenosine (m6A) modification in mRNA have drawn significant attention in recent years. Here we describe the construction and characterization of a CRISPR-Cas13b-based tool for targeted demethylation of specific mRNA. A fusion protein, named dm6ACRISPR, was created by linking a catalytically inactive Type VI-B Cas13 enzyme from Prevotella sp. P5-125 (dPspCas13b) to m6A demethylase AlkB homolog 5 (ALKBH5). dm6ACRISPR specifically demethylates m6A of targeted mRNA such as cytochrome b5 form A (CYB5A) to increase its mRNA stability. It can also demethylate β-catenin-encoding CTNNB1 mRNA that contains multiple m6A sites to trigger its translation. In addition, the dm6ACRISPR system incurs efficient demethylation of targeted epitranscriptome transcripts with limited off-target effects. Targeted demethylation of transcripts coding for oncoproteins such as epidermal growth factor receptor (EGFR) and MYC can suppress proliferation of cancer cells. Together, we provide a programmable and in vivo manipulation tool to study mRNA modification of specific genes and their related biological functions.
The structures of <i>c</i> <i>i</i> <i>s</i>-polyacetylene and highly conducting derivatives (1978)

The structures of cis-polyacetylene and polyacetylene–iodine derivatives have been investigated by x-ray diffraction and crystal packing analysis. Results obtained for cis-polyacetylene are consistent with the space group Pnma with one CH per asymmetric unit and a chain symmetry (m1̄)t. Hence, the structure is analogous to that of orthorhombic polyethylene. For a structure with such a concentration of π electrons there is minimal overlap between parallel π orbitals. The π orbitals are almost orthogonal for four of the six closest neighbors of a given chain. Based on x-ray diffraction and spectroscopic results, a model is proposed for the structure of the highly conducting polyacetylene–iodine complexes. According to this model, linear arrays of polyhalide ions (principally in the form of I−3) substitute in positions of displaced polyacetylene chains. At high dopant concentrations, alternate close-packed layers of polyacetylene are separated by a layer consisting of such polyhalide arrays. This model predicts a limiting charge transfer of 0.11 electron on the average per carbon atom in the polyacetylene chain.
Identification of pediatric septic shock subclasses based on genome-wide expression profiling (2009)

Genome-wide expression profiling can identify pediatric septic shock subclasses having clinically relevant phenotypes.
Corticotropin-releasing factor 1 receptor antagonists: a patent review (2013)

Antagonists of the CRF₁ receptor have failed to demonstrate clinical utility. All of the compounds evaluated are similar structures and are allosteric inhibitors of the CRF₁ receptor. Further clinical evaluation of new compounds appears unlikely unless novel structures are identified that interact with the receptor distinct to the first-generation antagonists.
Method for retrieving effective properties of locally resonant acoustic metamaterials (2007)

Acoustic metamaterials can be described by effective material properties such as mass density and modulus. We have developed a method to extract these effective properties from reflection and transmission coefficients, which can be measured experimentally. The dependency of effective properties on the positions of the boundaries of the acoustic metamaterial is discussed, and a proper procedure to determine the boundaries is presented. This retrieval method is used to analyze various acoustic metamaterials, and metamaterials with negative effective properties are reported.
Real-time parallel optical analog-to-digital conversion (1980)

A technique for optically performing parallel analog-to-digital conversion on incoherent two-dimensional inputs at real-time rates is described. The system uses a birefringent optical real-time input transducer combined with a detector array and optical thresholding. Quantization and bit plane outputs are produced in parallel without scanning. An experimental system with three-bit accuracy is described.
Cell growth and detachment from protein‐coated PNIPAAm‐based copolymers (2007)

The cultivation of cells requires the use of unfavorable proteolytic enzymes, which cause cell-surface modification and also need considerable optimization. Recently, with the development of smart polymers, research has looked to using thermoresponsive polymers as cell culture substrates. These novel surfaces allow the cultivation of cells without using enzymes by utilizing the thermoresponsive phase transition property of poly(N-isopropylacrylamide) (PNIPAAm). Copolymers of PNIPAAm and N-tert-butyl-acrylamide (NtBAm) with varying ratios were synthesized and solvent cast. The copolymer films are coated with cell adhesion promoters such as collagen, poly-L-lysine, and laminin to increase their cell adhesion and growth properties. Cell activity measured by the alamarBlue and PicoGreen assays is similar for coated copolymer films and standard tissue culture plastic controls. Deposition of cell adhesion promoters onto the copolymer films was characterized by scanning electron microscopy (SEM) and atomic force microscopy (AFM). Cell detachment from the copolymer films is dependent on copolymer composition and is not affected by the surface coatings of extracellular matrix (ECM) proteins. The results demonstrate a versatile method for the cultivation of cells while eliminating the need for the use of digestive enzymes such as trypsin.
A new application for liposomes in cancer therapy (1993)

We have tested a new type of immunoliposomes which may effectively mediate the targeting of enzymes to be used for site-specific prodrug activation (immuno-enzymosomes). The enzyme beta-glucuronidase, capable of activating the prodrug epirubicin-glucuronide (epi-glu), was coupled to the external surface of immunoliposomes directed towards ovarian cancer cells. A significant increase in cytotoxicity of the prodrug epi-glu was shown when the in vitro cultured cancer cells were pretreated with these immuno-enzymosomes.
Trade and Environmental Quality: A Review of the Evidence (1996)

At the heart of the current debate between environmentalists and the trade community lie differences of opinion about the impact that trade liberalization has on environmental quality. This article reviews economists'evidence on the physical trade-environment link. Contrary to interpretations from the trade community, the evidence lends no support to claims that positive income effects from economic expansion dominate negative scale effects. On the other hand, the evidence does not support environmentalists' arguments that trade is a significant source of environmental degradation, nor that trade liberalization has induced significant international migration of dirty industries.
Novel fractional-N PLL frequency synthesizer with reduced phase error (2002)

Conventionally, the division ratio of the programmable divider in the Phase Locked Loop (PLL) frequency synthesizer is an only integer. Therefore, it has been hoped to realize the fractional-N programmable divider which can divide not only an integer step but also a fractional step. In this paper, a new fractional-N programmable divider for the PLL frequency synthesizer is proposed. In this divider, the width of phase error pulse which phase detector produces in every period of reference frequency is decreased by introducing the new division ratio (N+1/2) besides N and (N+1).
An Innovative Approach to Understanding Shale Gas Well Behavior Based on a Performance Catalogue Fingerprint (2012)

Abstract Shale gas wells performance is governed by the interaction between reservoir rock and the completion. However, external factors such as liquid loading, inefficient completion, and in some cases offset wells, can also influence performance. The large volume of shale gas wells necessitates the development of quick diagnostic tools. The linear transient flow behavior is well documented in shale gas wells; however, the post-linear transient flow behavior and the impact of non-reservoir phenomena are not. The objective of this paper is to provide a signature catalogue based on well performance fingerprints to quickly diagnose well history for dominant production mechanisms. To build the catalogue, both synthetic models and actual well history were used. All the data generated were analyzed using a consistent in-house shale gas workflow. This paper documents well performance signatures for various reservoir and non-reservoir phenomena. The synthetic models provided a controlled basis to study for aspects of reservoir and completion phenomena difficult to measure in the field such as the sequence of flow regimes, the impact of different completion configurations, pressure dependent permeability and conductivity, as well as fracture complexity. Actual field histories from various shale gas plays were used to study the impact of processes that are normally observed in field data but are difficult to predict by a model such as liquid loading, fracture cleanup, data quality and impact of artificial lift. The signature catalogue shows impact of different completion configuration and reservoir phenomena during the periods of constant linear transient productivity index and on the decline in productivity index once the fracture interference starts. The impact of inadequate completion cleanup is captured on the linear flow plot as a completion resistance factor. The impact of shut-in, diagnostics for liquid loading, and inconsistent or questionable data has also been analyzed. The behavior of the wells with complex fracture geometries, pressure dependent permeability and pressure dependent completion properties is also catalogued. This fingerprint catalogue is a valuable resource for the engineer as it allows for prompt identification of abnormal well behaviors and provides a diagnostic method for identifying various production mechanisms.
Pyrimidines. 65. Synthesis of 6‐substituted thieno[2,3‐<i>d</i>]pyrimidine‐2,4(1<i>H</i>,3<i>H</i>)‐diones (1990)

Abstract Several 6‐substituted thieno[2,3‐ d ]pyrimidine‐2,4(1 H ,3 H )‐dione derivatives were synthesized. 6‐Ethoxycarbonyl derivatives 3 and 7 were prepared by treatment of 6‐chloro‐5‐formyluracil 1 and 6‐chloro‐5‐cyanouracil 6 with ethyl 2‐mercaptoacetate in the presence of a base. Electrophilic substitution reactions (Vilsmeier‐Haack reaction, bromination, and nitration) of 5,6‐unsubstituted thieno[2,3‐ d ]pyrimidine 9 , prepared by condensation of 6‐mercaptouracil 8 with chloroacetaldehyde, afforded the corresponding 6‐formyl‐, 6‐bromo‐, and 6‐nitrothieno[2,3‐ d ]pyrimidines 10, 15 and 16 , respectively.