gebhart/patrepeval huggingface dataset:
Neurofilament‐tubulin binding site peptide NFL‐TBS.40–63 increases the differentiation of oligodendrocytes in vitro and partially prevents them from lysophosphatidyl choline toxiciy (2013)

During multiple sclerosis (MS), the main axon cystoskeleton proteins, neurofilaments (NF), are altered, and their release into the cerebrospinal fluid correlates with disease severity. The role of NF in the extraaxonal location is unknown. Therefore, we tested whether synthetic peptides corresponding to the tubulin-binding site (TBS) sequence identified on light NF chain (NFL-TBS.40-63) and keratin (KER-TBS.1-24), which could be released during MS, modulate remyelination in vitro. Biotinylated NFL-TBS.40-63, NFL-Scramble2, and KER-TBS.1-54 (1-100 μM, 24 hr) were added to rat oligodendrocyte (OL) and astrocyte (AS) cultures, grown in chemically defined medium. Proliferation and differentiation were characterized by using specific antibodies (A2B5, CNP, MBP, GFAP) and compared with untreated cultures. Lysophosphatidyl choline (LPC; 2 × 10(-5) M) was used to induce OL death and to test the effects of TBS peptides under these conditions. NFL-TBS.40-63 significantly increased OL differentiation and maturation, with more CNP(+) and MBP(+) cells characterized by numerous ramified processes, along with myelin balls. When OL were challenged with LPC, concomitant treatment with NFL-TBS.40-63 rescued more than 50% of OL compared with cultures treated with LPC only. Proliferation of OL progenitors was not affected, nor were AS proliferation and differentiation. NFL-TBS.40-63 peptide induces specific effects in vitro, increasing OL differentiation and maturation without altering AS fate. In addition, it partially protects OL from demyelinating injury. Thus release of NFL-TBS.40-63 caused by axonal damage in vivo could improve repair through increased OL differentiation, which is a prerequisite for remyelination.
Liver cytosol corticosteroid binder IB, a new binding protein. (1975)

A new binding protein named corticosteroid Binder IB elutes just after ligandin in DEAE-Sephadex chromatograms. It has been partially purified to about 2500-fold over cytosol proteins. Calculation of the number of steroid binding sites, assuming one site per molecule of Binder IB fraction after DEAE-Sephadex chromatography, suggests a concentration of the binding protein of about 0.0004% of cytosol proteins. Its pI value is judged to be 7.5 to 8 from it elution position on DEAE-Sephadex chromatograms. IB has an apparent molecular weight of 30,500 +/- 10% by gel filtration and a Stokes radius of 20 A. Binder IB binds radioactive dexamethasone, cortisol, and corticosterone in vitro with estimated KD values of 1, 13, and 25 nM, respectively. Saturation curves are abnormal, showing two phases. The saturation curves within the physiological range of concentrations of steroid are abnormal and suggestive of cooperativity. The second phase, at concentrations of glucocortidoids above saturation and physiological levels, shows extensive binding. After fractionation from other steroid binding proteins, the specificity of binding from competition studies in vitro is dexamethasone greater than or equal to cortisol = corticosterone = estradiol-17beta greater than or equal to deoxycorticosterone = dihydrotestosterone greater than aldosterone = cortexolone greater than testosterone. Other steroids tested are less efficient ligands. The binding is probably noncovalent, but strong; and the complex becomes more dissociable as purification proceeds, suggesting a conformational change in the protein. Storage and rebinding with steroid are possible throughout the purification process, although extensive ligand dissociation and denaturation of the protein occur after the final purification step. Binding in vitro is temperature-sensitive and binding is sharply pH dependent with an optimum at 7.5. The ligand is the unmetabolized steroid as judged by extraction of steroid-IB complex with methylene chloride and subsequent thin layer chromatography. The physiological function of this protein is unknown at present and purification fo the major corticosteroid hormone receptor to homogeneity may be required before the function of Binder IB is fully understood.
Mapping protein‐protein interactions with combinatorial peptides (2001)

Now that a number of genomes have been sequenced, attention has turned to understanding the complement of proteins encoded by the genome, which has been termed the ‘proteome’. One important aspect of analysis of the proteome is the identification of which proteins interact with each other; this information is invaluable in surmising the function of each protein and inferring what cellular pathway the protein may be a component of. While a variety of methodologies is widely used to map protein-protein interactions, such as affinity purification followed by mass spectrometry and yeast two-hybrid screening (both of which were covered at this meeting), an alternative approach is the use of phage-displayed combinatorial peptides. In phage-display, short oligonucleotides are inserted within a gene encoding a capsid (coat) protein of a bacteriophage, so that each viral particle displays a different peptide sequence. While it has been possible to clone and express short peptides attached to each of the five different capsid proteins of bacteriophage M13, the protein products of gene III and VIII are popular cloning sites for expression and display. Several excellent reviews of phage-display can be found elsewhere [6,22,5]. Over the past ten years, a considerable number of phage-displayed combinatorial peptide libraries have been generated [21]. With a library of recombinant phage particles in hand, it is possible to screen them by affinity selection with a variety of protein targets. Three rounds of selection (binding, elution, propagation) are typically sufficient to screen billions of different phage-displayed combinatorial peptides for those that bind to target proteins of interest. While there have been many recent publications of successful selection experiments, some of the more notable examples are the selection of peptide ligands which bind to receptors for erythropoietin [30], N-methyl D-aspartate (NMDA) [16], thrombopoietin [7], fibroblast growth factor [3], and estrogen [17]. When peptides are chemically synthesized corresponding to what is displayed by the selected phage, they generally bind with dissociation constant (Kd) values of 5 micromolar to 10 nanomolar to their cognate receptor, and typically have agonist or antagonist activities. Many different types of targets will yield phage after affinity selection, such as enzymes [12], growth factors [10,4], nucleic acids [2], and cells [20,13]. Comparative and Functional Genomics Comp Funct Genom 2001; 2: 304–306. DOI: 10.1002 / cfg.100
Laboratory diagnosis, epizootiology, and efficacy of marker vaccines in classical swine fever: A review (2000)

Detection of classical swine fever virus (CSFV) can be achieved by a range of assays of which the most commonly used are: immunohistochemical and virus culture techniques. New developments have enabled the detection of viral proteins by enzyme-linked immunosorbent assays (ELISAs) and the detection of the viral genome by RT- PCR. So far, laboratory findings show that the latter assays may supplement or replace the conventional techniques in the near future. The detection of serum antibody against structural and non-structural proteins of CSFV has been improved by developments in recombinant DNA techniques and has lead to a range of ELISAs. Although the characteristics of these ELISAs are excellent, positive results still need to be confirmed in the virus neutralization test. The available amount of sequence data enables diagnosticians to type strains of CSFV as different by comparing several parts of the genome. In some cases, this can provide conclusive evidence if a primary or secondary outbreak has been detected. Increased efforts focused on the retrieval of relevant data on the introduction of CSFV in a pig holding and the spread of CSFV in- and between pig holding(s) has generated more insight into the epizootiology of the disease. A successful control and eradication programme for classical swine fever (CSF) can consist of zoosanitary measures and/or vaccination. The latter can compromise the export of live pigs and pig products considerably unless marker vaccines have been used. Several studies were performed to determine the efficacy of an E2 subunit vaccine and live recombinant vaccine candidates. Firstly, we determined the 95% protective dose of an E2 subunit vaccine at 32 microg E2 per dosage after a single application. Further studies with a single administration of the subunit vaccine showed that: the vaccine was stable for a prolonged period after production, was able to reduce horizontal and vertical transmission of CSFV among vaccinated pigs, and provided protection for at least 6 months. An E(rns) antibody discriminatory assay was developed for use in combination with the subunit vaccine. Evaluation of the E(rns) ELISA showed that the sensitivity of the assay was lower than but that the specificity was equal to that of existing antibody assays. Two live recombinant marker vaccines were evaluated for the induction of clinical protection and reduction of transmission of CSFV shortly after vaccination. Results showed that these vaccines provided good clinical protection 1 week after a single vaccination. Research has shown that marker vaccines can be used in the future to support the control and eradication of CSFV.
AMC-Backed Dipole Array Antenna for Beamforming Less Vulnerable to Nearby Metal Planes (2018)

This paper presents a new array antenna of printed dipoles for beamforming which avoids severely negative influence of nearby metal planes. This is made to be possible by placing a thin artificial magnetic conductor(AMC) beneath each of the printed dipole elements which are excited by a Butler matrix feed-network. The multiple beams of the AMC-backed dipole array and antenna characteristics are investigated in the vicinity of a wide metallic plane. It shows that the beams do not disappear with low vulnerability to the harsh environment.
VNRX-5133 (Taniborbactam), a Broad-Spectrum Inhibitor of Serine- and Metallo-β-Lactamases, Restores Activity of Cefepime in Enterobacterales and Pseudomonas aeruginosa (2019)

As shifts in the epidemiology of β-lactamase-mediated resistance continue, carbapenem-resistant <i>Enterobacterales</i> (CRE) and carbapenem-resistant <i>Pseudomonas aeruginosa</i> (CRPA) are the most urgent threats. Although approved β-lactam (BL)-β-lactamase inhibitor (BLI) combinations address widespread serine β-lactamases (SBLs), such as CTX-M-15, none provide broad coverage against either clinically important serine-β-lactamases (KPC, OXA-48) or clinically important metallo-β-lactamases (MBLs; e.g., NDM-1). VNRX-5133 (taniborbactam) is a new cyclic boronate BLI that is in clinical development combined with cefepime for the treatment of infections caused by β-lactamase-producing CRE and CRPA. Taniborbactam is the first BLI with direct inhibitory activity against Ambler class A, B, C, and D enzymes. From biochemical and structural analyses, taniborbactam exploits substrate mimicry while employing distinct mechanisms to inhibit both SBLs and MBLs. It is a reversible covalent inhibitor of SBLs with slow dissociation and a prolonged active-site residence time (half-life, 30 to 105 min), while in MBLs, it behaves as a competitive inhibitor, with inhibitor constant (<i>K<sub>i</sub></i> ) values ranging from 0.019 to 0.081 μM. Inhibition is achieved by mimicking the transition state structure and exploiting interactions with highly conserved active-site residues. In microbiological testing, taniborbactam restored cefepime activity in 33/34 engineered <i>Escherichia coli</i> strains overproducing individual enzymes covering Ambler classes A, B, C, and D, providing up to a 1,024-fold shift in the MIC. Addition of taniborbactam restored the antibacterial activity of cefepime against all 102 <i>Enterobacterales</i> clinical isolates tested and 38/41 <i>P. aeruginosa</i> clinical isolates tested with MIC<sub>90</sub>s of 1 and 4 μg/ml, respectively, representing ≥256- and ≥32-fold improvements, respectively, in antibacterial activity over that of cefepime alone. The data demonstrate the potent, broad-spectrum rescue of cefepime activity by taniborbactam against clinical isolates of CRE and CRPA.
Distance Map Supervised Landmark Localization for MR-TRUS Registration (2022)

In this work, we propose to explicitly use the landmarks of prostate to guide the MR-TRUS image registration. We first train a deep neural network to automatically localize a set of meaningful landmarks, and then directly generate the affine registration matrix from the location of these landmarks. For landmark localization, instead of directly training a network to predict the landmark coordinates, we propose to regress a full-resolution distance map of the landmark, which is demonstrated effective in avoiding statistical bias to unsatisfactory performance and thus improving performance. We then use the predicted landmarks to generate the affine transformation matrix, which outperforms the clinicians' manual rigid registration by a significant margin in terms of TRE.
Potential Anticancer Effects of Statins: Fact or Fiction? (2003)

Deregulation of any of the steps in cell growth, proliferation and apoptosis may result in its malignant transformation. Statins, along with their lipid-lowering potential, modify several processes in the cell cycle. These agents inhibit cell proliferation and arrest cell cycle progression by interrupting growth-promoting signals. Statins selectively induce proapoptotic protential in tumor cells and synergistically enhance proapoptotic potential of several cytotoxic agents. Statins alter angiogenic potential of cells by modulating apoptosis inhibitory effects of VEGF and decrease secretion of metalloproteases. Statins also alter adhesion and migration of tumor cells, thereby inhibiting tumor invasion and metastasis. Statins suppress rate of activation of multiple coagulation factors and thus prevent coagulation-mediated angiogenesis. Statins have been shown to have anti-tumor activity in experimental models. Various anti-neoplastic properties of statins are probably a result of inhibition of posttranslational modifications of growth regulatory proteins. Molecular mechanisms of antiproliferative, proapoptotic and antiangiogenic effects of statins are reviewed in this chapter.
Facile and Scalable Methodology for the Pyrrolo[2,1-f][1,2,4]triazine of Remdesivir (2021)

&lt;div&gt; &lt;div&gt; &lt;p&gt;Pyrrolo[2,1-f][1,2,4]triazine (&lt;b&gt;1&lt;/b&gt;) is an important regulatory starting material in the production of Remdesivir (Veklury®). Compound&lt;b&gt; 1&lt;/b&gt; was produced through a newly developed synthetic methodology utilizing the simple building blocks pyrrole, chloramine and formamidine acetate by examining the mechanistic pathway for the process optimization exercise. Triazine &lt;b&gt;1&lt;/b&gt; was obtained in 55% overall yield in a two-reactor operated process. This work describes the safety of the process, impurity profiles and control, and efforts towards the scale-up of triazine for the preparation of kilogram quantity.&lt;/p&gt; &lt;/div&gt; &lt;/div&gt; &lt;br&gt;
Analgesic effects of optogenetic inhibition of basolateral amygdala inputs into the prefrontal cortex in nerve injured female mice (2019)

Peripheral nerve injury can lead to remodeling of brain circuits, and this can cause chronification of pain. We have recently reported that male mice subjected to spared injury of the sciatic nerve undergo changes in the function of the medial prefrontal cortex (mPFC) that culminate in reduced output of layer 5 pyramidal cells. More recently, we have shown that this is mediated by alterations in synaptic inputs from the basolateral amygdala (BLA) into GABAergic interneurons in the mPFC. Optogenetic inhibition of these inputs reversed mechanical allodynia and thermal hyperalgesia in male mice. It is known that the processing of pain signals can exhibit marked sex differences. We therefore tested whether the dysregulation of BLA to mPFC signaling is equally altered in female mice. Injection of AAV-Arch3.0 constructs into the BLA followed by implantation of a fiberoptic cannula into the mPFC in sham and SNI operated female mice was carried out, and pain behavioral responses were measured in response to yellow light mediated activation of this inhibitory opsin. Our data reveal that Arch3.0 activation leads to a marked increase in paw withdrawal thresholds and latencies in response to mechanical and thermal stimuli, respectively. However, we did not observe nerve injury-induced changes in mPFC layer 5 pyramidal cell output in female mice. Hence, the observed light-induced analgesic effects may be due to compensation for dysregulated neuronal circuits downstream of the mPFC.
(2-Acetoxyphenoxy)ethyl (APOE) as a Phosphate Protecting Group in Solid-Phase Synthesis of Oligonucleotides via the Phosphoramidite Approach (2006)

The (2-acetoxyphenoxy)ethyl (APOE) group could be an alternative to the conventional 2-cyanoethyl group for phosphate protection in solid-phase oligonucleotide synthesis to circumvent DNA alkylation by acrylonitrile generated under basic condition. This group is stable during oligonucleotide synthesis and can be removed under mild conditions using aqueous ammonium hydroxide. Multiple phosphorothioate oligodeoxyribonucleotides and 2‘-O-methoxyethyl-modified oligoribonucleotide chimera were synthesized and characterized extensively. The deprotection of this group follows an intramolecular attack on the α-carbon adjacent to phosphate oxygen to liberate the oligonucleotide and an innocuous cyclic ether as side product. No modification of nucleobases was observed during deprotection of this group.
Combustion Modeling and Analysis of Hybrid Rocket Motor Internal Ballistics (2012)

In the present study, a comprehensive computational fluid dynamics model is developed for the internal ballistics study of hybrid rocket motors. A hybrid rocket motor with vortex generating mixing enhancer is proposed to increase the overall mixing and combustion efficiency, which also results in the allowance of reducing the chamber port length in the motor designs. The present 3-D computational tool with finite-rate chemistry and real-fluid models is employed to numerically assess the mixing effectiveness and combustion efficiency of a hybrid rocket motor. An extended two-equation turbulence model is employed to simulate the turbulence effects. The computational results of the present model are validated with experimental hot-fire test data, including a single-port hybrid rocket motor with or without a mixing enhancement mechanism installed. The internal ballistics and flame structures in the hybrid rocket combustion chamber are analyzed.
A Practical Preparation of Methyl 4-(Trimethylsilyl)-benzoate: An Intermediate in the Synthesis of SDZ 63135 (1995)

Abstract An improved synthesis of ester 1 is described utilizing a bromine-lithium exchange and a Grignard-mediated methoxy-carbonylation reaction starting from 1, 4-dibromobenzene. Compound 1 was converted to 2 through a condensation and dehydration sequence with an overall yield of 41.5%.
Impact of a Bacillus Direct-Fed Microbial on Growth Performance, Intestinal Barrier Integrity, Necrotic Enteritis Lesions, and Ileal Microbiota in Broiler Chickens Using a Laboratory Challenge Model (2019)

Decreases in the use of antibiotics and anticoccidials in the poultry industry have risen the appearance of necrotic enteritis (NE). The purpose of this study was to evaluate the effect of a <i>Bacillus</i> direct-fed microbial (DFM) on growth performance, intestinal integrity, NE lesions and ileal microbiota using a previously established NE-challenged model. At day-of-hatch, chicks were randomly assigned to three different groups: Negative control (NC), Positive control (PC) challenged with <i>Salmonella</i> Typhimurium (day 1), <i>Eimeria maxima</i> (EM, day 13) and <i>Clostridium perfringens</i> (CP, day 18-19), and <i>Bacillus</i>-DFM group (DFM) challenged as the PC. Body weight (BW) and body weight gain (BWG) were measured weekly. Total feed intake (FI) and feed conversion ratio (FCR) were evaluated at day 21. Liver samples were collected to assess bacterial translocation and blood samples were used to measure superoxide dismutase (SOD) and fluorescein isothiocyanate-dextran (FITC-d). Intestinal contents were obtained for determination of total IgA and microbiota analysis. NE lesion scores (LS) were performed at day 21. Chickens consuming the DFM significantly improved BW and had a numerically more efficient FCR compared to PC at day 21. Additionally, there were no significant differences in FCR between the DFM group and NC. Furthermore, the DFM group showed significant reductions in LS, IgA and FITC-d levels compared to the PC. However, there were no significant differences in SOD between the groups. The microbiota analysis indicated that the phylum <i>Proteobacteria</i> was significantly reduced in the DFM group in comparison to PC. At the genus level, <i>Clostridium, Turicibacter, Enterococcus</i>, and <i>Streptococcus</i> were reduced, whereas, <i>Lactobacillus</i> and <i>Bacillus</i> were increased in the DFM group as compared to PC (<i>p</i> < 0.05). Likewise, the DFM significantly reduced CP as compared to PC. In contrary, no significant differences were observed in bacterial composition between NC vs. DFM. In addition, beta diversity showed significant differences in the microbial community structure between NC vs. PC, and PC vs. DFM. These results suggest that the dietary inclusion of a selected DFM could mitigate the complex negative impacts caused by NE possibly through mechanism(s) that might involve modulation of the gut microbiota.
A 195mW / 55mW dual-path receiver AFE for multistandard 8.5-to-11.5 Gb/s serial links in 40nm CMOS (2013)

Demand for bandwidth in metro networks and data centers has fueled the deployment of 10Gb/s traffic over legacy data links, such as backplanes (KR) and multimode fiber (MMF) [1]. Under severe channel impairments, an ADC-based receiver with a DSP backend provides robust performance, especially for MMF applications, due to the complexity of the channel pulse response and the dynamic nature of the channel impairment. The reach of the backplane channels can also be extended, providing flexibility for system design. Applications such as 10G SFP+ DAC have less channel loss; consequently, a slicer-based binary receiver is a more viable low-power solution. This work describes the AFE of a dual-path receiver that uses both an ADC path and a slicer path for 10Gb/s multi-standard applications in 40nm CMOS.