gebhart/patrepeval huggingface dataset:
Proteases as therapeutics (2011)

Proteases are an expanding class of drugs that hold great promise. The U.S. FDA (Food and Drug Administration) has approved 12 protease therapies, and a number of next generation or completely new proteases are in clinical development. Although they are a well-recognized class of targets for inhibitors, proteases themselves have not typically been considered as a drug class despite their application in the clinic over the last several decades; initially as plasma fractions and later as purified products. Although the predominant use of proteases has been in treating cardiovascular disease, they are also emerging as useful agents in the treatment of sepsis, digestive disorders, inflammation, cystic fibrosis, retinal disorders, psoriasis and other diseases. In the present review, we outline the history of proteases as therapeutics, provide an overview of their current clinical application, and describe several approaches to improve and expand their clinical application. Undoubtedly, our ability to harness proteolysis for disease treatment will increase with our understanding of protease biology and the molecular mechanisms responsible. New technologies for rationally engineering proteases, as well as improved delivery options, will expand greatly the potential applications of these enzymes. The recognition that proteases are, in fact, an established class of safe and efficacious drugs will stimulate investigation of additional therapeutic applications for these enzymes. Proteases therefore have a bright future as a distinct therapeutic class with diverse clinical applications.
On the amination of azaheterocycles. A new procedure for the introduction of an amino group (1982)

Abstract A new method of amination of diazines and triazines, using potassium amide, liquid ammonia and potassium permanganate, has been described.
Stress and Stress Management Strategies Among Botswana Women Lecturers. (1996)

A stress inventory was constructed to explore the origin and the effects of stress including stress management strategies experienced by women lecturing in higher education. The highest ranking severe stressor identified by the respondents is students' class boycotts, followed by uncertainties about the future of their institution and dual roles. The researchers also revealed that there is a relationship between relaxation strategies for fatigue, academic qualification, and number of students per class. A membership was also found between day-planning and the number of children the respondents have.
A cyclic peptide analogue of the loop III region of platelet‐derived growth factor‐BB is a synthetic antigen for the native protein (1999)

We report the synthesis and characterization of a cyclic peptide analogue of the loop III region of platelet-derived growth factor (PDGF) B-chain sequence, cyclo(73Arg-Lys-Ile-Glu-Ile-Val-Arg-Lys-Lys81-Cys), incorporating a C-terminus cysteine residue for the conjugation to a carrier protein. The synthesis involved solid-phase chemistry, utilizing Fmoc-tBu chemistry and acid labile side-chain protecting groups, followed by 'head-to-tail' cyclization using the allyl-protected glutamic acid anchored on its side chain to the solid support with HATU/HOAt as the coupling agent. Conformational differences between the cyclic and its linear counterpart PDGF peptides were determined by circular dichroism measurements in aqueous media. High titre antisera were raised to both cyclic and linear peptide immunogens. Antisera raised to the cyclic peptide cross-reacted with PDGF-BB in both Western blot and ELISA, whereas antisera raised to the linear peptide had no reactivity with PDGF-BB. The cyclic peptide (conformational design analogue) produces an immunogen which is able to antigenically mimic the secondary structure of loop III of PDGF-BB and forms a basis from which further small molecular mimetics of PDGF may be designed for use as both immunogens and also potential agonists/antagonists of PDGF. Similarly constructed immunogens may also be useful in the design of vaccines which direct responses to loop regions in other target proteins.
The advanced glycation end‐product Nϵ‐carboxymethyllysine promotes progression of pancreatic cancer: implications for diabetes‐associated risk and its prevention (2018)

Diabetes is an established risk factor for pancreatic cancer (PaC), together with obesity, a Western diet, and tobacco smoking. The common mechanistic link might be the accumulation of advanced glycation end-products (AGEs), which characterizes all of the above disease conditions and unhealthy habits. Surprisingly, however, the role of AGEs in PaC has not been examined yet, despite the evidence of a tumour-promoting role of receptor for advanced glycation end-products (RAGE), the receptor for AGEs. Here, we tested the hypothesis that AGEs promote PaC through RAGE activation. To this end, we investigated the effects of the AGE N<sup>ϵ</sup> -carboxymethyllysine (CML) in human pancreatic ductal adenocarcinoma (PDA) cell lines and in a mouse model of Kras-driven PaC interbred with a bioluminescent model of proliferation. Tumour growth was monitored in vivo by bioluminescence imaging and confirmed by histology. CML promoted PDA cell growth and RAGE expression, in a concentration-dependent and time-dependent manner, and activated downstream tumourigenic signalling pathways. These effects were counteracted by RAGE antagonist peptide (RAP). Exogenous AGE administration to PaC-prone mice induced RAGE upregulation in pancreatic intraepithelial neoplasias (PanINs) and markedly accelerated progression to invasive PaC. At 11 weeks of age (6 weeks of CML treatment), PaC was observed in eight of 11 (72.7%) CML-treated versus one of 11 (9.1%) vehicle-treated [control (Ctr)] mice. RAP delayed PanIN development in Ctr mice but failed to prevent PaC promotion in CML-treated mice, probably because of competition with soluble RAGE for binding to AGEs and/or compensatory upregulation of the RAGE homologue CD166/ activated leukocyte cell adhesion molecule, which also favoured tumour spread. These findings indicate that AGEs modulate the development and progression of PaC through receptor-mediated mechanisms, and might be responsible for the additional risk conferred by diabetes and other conditions characterized by increased AGE accumulation. Finally, our data suggest that an AGE reduction strategy, instead of RAGE inhibition, might be suitable for the risk management and prevention of PaC. Copyright © 2018 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.
Cell replacement therapy in neurological disease (2006)

Diseases of the brain and spinal cord represent especially daunting challenges for cell-based strategies of repair, given the multiplicity of cell types within the adult central nervous system, and the precision with which they must interact in both space and time. Nonetheless, a number of diseases are especially appropriate for cell-based therapy, in particular those in which single phenotypes are lost, and in which the re-establishment of vectorially specific connections is not entirely requisite for therapeutic benefit. We review here a set of potential therapeutic indications that meet these criteria as potentially benefiting from the transplantation of neural stem and progenitor cells. These include: (i) transplantation of phenotypically restricted neuronal progenitor cells into diseases of a single neuronal phenotype, such as Parkinson's disease; (ii) implantation of mixed progenitor pools into diseases characterized by the loss of a limited number of discrete phenotypes, such as spinal cord injury and the motor neuronopathies; (iii) transplantation of glial and nominally oligodendrocytic progenitor cells as a means of treating disorders of myelin; and (iv) transplantation of neural stem cells as a means of treating lysosomal storage disorders and other diseases of enzymatic deficiency. Among the diseases potentially approachable by these strategies, the myelin disorders, including the paediatric leucodystrophies as well as adult traumatic and inflammatory demyelinations, may present the most compelling targets for cell-based neurological therapy.
Modified Sommerfeld's Integral and Its Applications (1936)

The purpose of this paper is to obtain a certain integral expressing the fundamental wave function and with the aid of this integral to calculate the radiation resistances of small doublets and small loops placed inside an infinite hollow cylinder. Some applications of this integral to calculation of radiation from parallel wires in free space are also discussed.
Characteristic instability of fibre loop soliton lasers (1992)

It is experimentally demonstrated that the inherent instability in short pulse, fibre loop, soliton lasers is associated with a resonant exchange of energy which takes place when the overall fibre loop size is comparable to that of the associated soliton period. The instability is characterised by the apperance of spectral sidebands, which can extend to several orders. In the time domain the instability can lead to multipulse outputs and chaotic or quasiperiodic behaviour.
Trans-Translation:  The tmRNA-Mediated Surveillance Mechanism for Ribosome Rescue, Directed Protein Degradation, and Nonstop mRNA Decay (2007)

The accurate flow of genetic information from DNA to RNA to protein is essential for all living organisms. An astonishing array of quality-assurance mechanisms have evolved to ensure that high degree of fidelity is maintained at every stage of this process. One of the most fascinating quality-control mechanisms involves tmRNA, also known as SsrA or 10Sa RNA. tmRNA is a versatile and highly conserved bacterial molecule endowed with the combined structural and functional properties of both a tRNA and a mRNA. The tmRNA system orchestrates three key biological functions: (1) recognition and rescue of ribosomes stalled on aberrant mRNAs, (2) disposal of the causative defective mRNAs, and (3) addition of a degradation tag to ribosome-associated protein fragments for directed proteolysis. Although not essential in Escherichia coli, tmRNA activity is essential for bacterial survival under adverse conditions and for virulence in some, and perhaps all, pathogenic bacteria. Recent evidence suggests that in addition to its quality-control function the tmRNA system might also play a key regulatory role in certain physiological pathways. This review will focus on recent advances in our understanding of the structural properties, mechanistic details, and physiological significance of this unique RNA and its principal protein partners.
Resistive-Pulse Measurements with Nanopipettes: Detection of Vascular Endothelial Growth Factor C (VEGF-C) Using Antibody-Decorated Nanoparticles (2015)

Quartz nanopipettes have recently been employed for resistive-pulse sensing of Au nanoparticles (AuNP) and nanoparticles with bound antibodies. The analytical signal in such experiments is the change in ionic current caused by the nanoparticle translocation through the pipette orifice. This paper describes resistive-pulse detection of cancer biomarker (Vascular Endothelial Growth Factor-C, VEGF-C) through the use of antibody-modified AuNPs and nanopipettes. The main challenge was to differentiate between AuNPs with attached antibodies for VEGF-C and antigen-conjugated particles. The zeta-potentials of these types of particles are not very different, and, therefore, carefully chosen pipettes with well-characterized geometry were necessary for selective detection of VEGF-C.
Safety and Immunogenicity of a Purified F Protein Respiratory Syncytial Virus (PFP‐2) Vaccine in Seropositive Children with Bronchopulmonary Dysplasia (1998)

Respiratory syncytial virus (RSV) causes serious respiratory illness in preterm children with bronchopulmonary dysplasia. In a prospective randomized placebo-controlled trial, 21 children received one dose of PFP-2 (purified fusion [F] protein) vaccine or influenza vaccine (placebo). Children were followed for adverse reactions and RSV illness over two respiratory seasons. Sera were obtained for determination of IgG titers to RSV F protein and neutralizing antibody titers before and 1, 6, and 12 months after vaccination. Adverse reactions were few. Four-fold F protein rises occurred in 9 of 10 PFP-2 and 0 of 11 placebo recipients. Six PFP-2 recipients had low prevaccination neutralizing antibody titers (< 1:450); all had 4-fold rises. By 12 months, F protein and neutralizing antibody titers in all 21 children were similar. RSV illness occurred in 6 of 11 placebo versus 1 of 10 PFP-2 recipients (P = .06); 1 placebo child required hospitalization. PFP-2 vaccine appears safe and immunogenic and may protect children with bronchopulmonary dysplasia against serious RSV disease on reinfection.
Pyrolysis of Waste Paper: Characterization and Composition of Pyrolysis Oil (2005)

This article presents the results of an experimental study of waste paper pyrolysis in tubular furnace pyrolysis equipment. Pyrolysis of waste paper has been conducted in different pyrolysis temperatures and heating rates to investigate the product distribution and yields of pyrolysis products. The pyrolysis oil was characterized by elemental analysis and various chromatographic and spectroscopic techniques, which are HPLC, 1H NMR, FTIR, and UV. The results of spectroscopic and chromatographic analysis show that there are four main different compounds in bio-oil: anhydrosugars, carboxyl compounds, carbonyl compounds and aromatic compounds.
Rapid updates of GIS databases from digital images (2002)

Our goal is to improve the way in which Geographic Information System (GIS) databases are created, updated and utilized. We are building software systems that will enable users to rapidly and inexpensively acquire, update, analyze and visualize high-resolution digital elevation maps (DEM), ortho-images, and other GIS products from digital images collected by a wide range of aerial and satellite platforms. The low cost and short turnaround time for these products will enable education and research institutes, government agencies and commercial organizations to expand the scope of their GIS applications, especially in the areas of environmental monitoring, change detection, and urban planning.
Abstract PR02: A personalized neoantigen vaccine in patients with high risk melanoma (2016)

Abstract Neoantigens arise from somatic tumor mutations and can encode amino acid changes, generating peptides with the potential to bind to HLA molecules. Since these neoepitopes provide exquisite tumor specificity and are expected to be highly immunogenic as they are not subject to central tolerance, they were long-envisioned as highly valuable tumor antigens. Growing evidence has supported tumor neoepitopes as key antigens triggering immune-mediated tumor killing in vivo across settings of effective cancer immunotherapy, including checkpoint blockade and adoptive transfer with tumor-infiltrating lymphocytes. Vaccination is a potentially effective approach for inducing tumor-specific immune responses, but has been limited by the lack of a sufficiently potent vaccine immunogen. By leveraging next-generation sequencing technologies and new analytical pipelines to systematically identify personal tumor neoantigens, in a phase 1 trial we tested the feasibility, safety, and immunogenicity of a multi-epitope cancer vaccine targeting personal tumor neoantigens in patients with high-risk melanoma. Mutations were identified by DNA and RNA sequencing; epitopes were selected based on class I HLA binding prediction algorithms. The vaccines, comprised of up to 20 long peptides spanning mutated tumor epitopes and admixed with the Toll-Like Receptor 3 agonist poly-ICLC, were administered using a prime-boost approach. Of 12 patients enrolled, the initial 6 patients who received the full set of priming and booster vaccinations experienced only minimal adverse events, consisting of mild and transient injection site reaction, flu-like symptoms, and rash. We identified strong, polyfunctional CD4+ and CD8+ T cell responses against multiple neoepitopes in all dosed patients. Processing and presentation of neoantigens on autologous tumors was confirmed by mass spectrometry and recognition of autologous tumor by vaccine-induced neoantigen-specific T cells was verified. These studies show that a personalized neoantigen vaccine is safe, feasible, and strongly immunogenic in cancer patients. The data should reinvigorate the field of cancer vaccines, providing a rational path for the building of combinatorial approaches to extend their efficacy. Citation Format: Patrick A. Ott, Zhuting Hu, Derin B. Keskin, Sachet A. Shukla, Jing Sun, Ed Fritsch, Nir Hacohen, Catherine J. Wu. A personalized neoantigen vaccine in patients with high risk melanoma [abstract]. In: Proceedings of the Second CRI-CIMT-EATI-AACR International Cancer Immunotherapy Conference: Translating Science into Survival; 2016 Sept 25-28; New York, NY. Philadelphia (PA): AACR; Cancer Immunol Res 2016;4(11 Suppl):Abstract nr PR02.
58.3: A Solid‐state Multi‐planar Volumetric Display (2003)

Abstract The DepthCube™ 3D display is a solid‐state multi‐planar volumetric display system in which a DLP based high speed projector projects slices of the 3D scene onto a stack of LC scattering shutters acting as an electronically controlled projection volume. The scattering shutters are based on Polymer Stabilized Cholesteric Texture material. Highly continuous appearing 3D images are obtained through multi‐planar anti‐aliasing.
Negative autoregulation of the Arabidopsis homeobox gene ATHB‐2 (2001)

The Arabidopsis homeobox gene ATHB-2 is tightly regulated by light signals, and is thought to direct morphological changes during shade avoidance responses. To understand how ATHB-2 mediates light signals in plant morphogenesis, we investigated its transcriptional network. We constructed a gene encoding a chimeric transcription factor (HD-Zip-2-V-G) that is expected to activate target genes of ATHB-2 in a glucocorticoid-dependent manner. In transgenic Arabidopsis plants expressing HD-Zip-2-V-G, glucocorticoid treatment activates the ATHB-2 gene itself, independent of de novo protein synthesis. An in vitro DNase I-footprinting experiment showed that recombinant ATHB-2 protein specifically bound to an ATHB-2 promoter region. These complementary results indicate that ATHB-2 recognizes its own promoter. Consistent with the fact that ATHB-2 itself has been shown to act as a repressor, expression of the endogenous ATHB-2 gene was repressed in transgenic plants overexpressing an ATHB-2 transgene. Moreover, target-gene analysis using the HD-Zip-2-V-G suggested that ATHB-2 recognizes other HD-Zip II subfamily genes. We conclude that ATHB-2 has a negative autoregulatory loop and may be involved in a complicated transcriptional network involving paralogous genes, as is the case with animal homeobox genes.
The Dorsomedial Hypothalamic Nucleus Revisited: 1998 Update (1998)

This article reviews data that have accumulated since the early 1970s on the role of the dorsomedial hypothalamic nucleus (DMN) in neuroendocrine and autonomic homeostasis. Both the ventromedial hypothalamic nucleus (VMN) and the lateral hypothalamic area (LHA) project to the DMN, which in turn projects to the paraventricular nucleus of the hypothalamus (PVN), thus placing the DMN at an important nodal point of neuroendocrine/autonomic circuitries. The DMN is composed of cells and fibers containing neuropeptide Y (NPY), and the nutritional status (starvation-refeeding) is reflected in NPY levels of both VMN and DMN in Sprague-Dawley, Zucker (fa/fa), and corpulent rats (cp/cp JCR:LA). The DMN is involved in the final common pathway of corticotrophin-releasing hormone (CRH) secretion by the PVN, sympathetic nervous system outflow to the adrenal gland, and brown adipose tissue (BAT) thermogenesis. The DMN is also part of a "fear circuitry" regulating cardiovascular responses to stress such as myocardial blood flow and the tachycardia associated with the defense reaction. This appears to be mediated by a gamma amino butyric acid (GABA) mechanism. Although exhibiting reduced ponderal and linear growth and hypophagia and hypodipsia, the rat with DMN lesions (DMNL rat) has normal body composition, anabolic hormone levels, and intermediary metabolism, and it responds normally to numerous endocrine, nutritional, intra- and extracellular thirst and body weight-regulatory challenges. The DMNL rat shows normal efficiency of food utilization, but shows an attenuated response to the feeding-stimulatory effect of insulin. The only other lesion-induced abnormalities are hyperprolactinemia and a disrupted circadian corticosterone rhythm. The hyperprolactinemia in DMNL rats appears to be related to an attenuation of dopamine (DA). Rats with DMNL are capable of mating and can bear offspring, but there is a dramatic effect on litter size and other litter parameters that only improves when one parent is a DMNL rat. Antiaging effects produced by DMNL are evident in the prevention of age-associated microalbuminuria and kidney lesions, as well as, in prevention of the age-related decline in circulating insulin-like growth factor I (IGF-I). Recent evidence suggests that DMN, together with the VMN and the arcuate nucleus (ARC) of the hypothalamus, may be part of the circuitry that is responsive to the feedback signal from adipose tissue by the hormone leptin. The above findings and others suggest that the DMN plays a diverse role in physiological regulatory processes.
Determination of agarose gel pore size: Absorbance measurements vis a vis other techniques (2006)

The absorbance measurements in the wavelength range 700 nm to 800 nm were used to probe the agarose gel topology evolution and extract the pore size of the trapped solvent. By following the changes in absorbance and pore size, the gelation process could be clearly divided into three stages - induction stage, gelation stage and pseudo-equilibrium stage. The gelation mechanism is explained as a nucleation and growth process. Following the kinetics of gelation using dynamic light scattering is complicated by multiple scattering (for high concentrations) and large fluctuations in intensity and relaxation time. Comparatively, scanning the absorption spectrum is fast and the method is suitable for a wide range of concentrations and setting temperatures. Pore size determination using absorbance is a fast and non-invasive method when compared to the DNA electrophoresis measurements, which extend over several hours and use probe diffusion.
Reduction of dietary phosphorus absorption by phosphorus binders. A theoretical, in vitro, and in vivo study. (1989)

Antacids used to decrease phosphorus absorption in patients with renal failure may be toxic. To find more efficient or less toxic binders, a three-part study was conducted. First, theoretical calculations showed that phosphorus binding occurs in the following order of avidity: Al3+ greater than H+ greater than Ca2+ greater than Mg2+. In the presence of acid (as in the stomach), aluminum can therefore bind phosphorus better than calcium or magnesium. Second, in vitro studies showed that the time required to reach equilibrium varied from 10 min to 3 wk among different compounds, depending upon solubility in acid and neutral solutions. Third, the relative order of effectiveness of binders in vivo was accurately predicted from theoretical and in vitro results; specifically, calcium acetate and aluminum carbonate gel were superior to calcium carbonate or calcium citrate in inhibiting dietary phosphorus absorption in normal subjects. We concluded that: (a) inhibition of phosphorus absorption by binders involves a complex interplay between chemical reactions and ion transport processes in the stomach and small intestine; (b) theoretical and in vitro studies can identify potentially better in vivo phosphorus binders; and (c) calcium acetate, not previously used for medical purposes, is approximately as efficient as aluminum carbonate gel and more efficient as a phosphorus binder than other currently used calcium salts.