gebhart/patrepeval huggingface dataset:
Bacterial Carriers and Virus-Like-Particles as Antigen Delivery Devices: Role of Dendritic Cells in Antigen Presentation (2001)

Replicating attenuated strains of intracellular bacteria like Salmonella typhimurium, Listeria monocytogenes or Mycobacterium bovis Bacille Calmette Guérin (BCG), and non-replicating virus-like-particles (VLP) consisting, for instance, of the VP1-surface component of polyoma virus offer great potential as heterologous carriers delivering foreign protein antigens for immune recognition. Moreover, attenuated S. typhimurium and L. monocytogenes strains hold also great promise as delivery vehicles for DNA vaccines. Polyoma virus-specific VLP consisting of VP1-pentamers are also of interest as carrier devices for eukaryotic expression plasmids. At first sight these different replicating and non-replicating types of vehicles have little in common, but from an immunological point of view viable bacteria and non-viable VLP are both well suited for evoking protective immune responses via several routes of vaccine administration. As these antigen carriers generate humoral and cell-mediated immunity, the heterologous antigens are not only targeted to appropriate pathways of major histocompatibility (MHC) class I and class II antigen processing and presentation, but also generate an adequate cytokine milieu for promoting antigen-specific responses. The most prominent advantage of these carrier devices is presented by their capacity to directly target antigenic proteins or DNA vaccines to immature dendritic cells (DC) along their maturation pathway. Mature DC are the key antigen presenting cell population which efficiently mediates antigen transport to organised lymphoid tissues for the initiation of T cell responses. In general, uptake of these diverse antigen delivery systems by antigen presenting cells (APC) finally lead to efficacious immune responses in the control of pathogenic microorganisms and tumours.
Mevinolin: a highly potent competitive inhibitor of hydroxymethylglutaryl-coenzyme A reductase and a cholesterol-lowering agent. (1980)

Mevinolin, a fungal metabolite, was isolated from cultures of Aspergillus terreus. The structure and absolute configuration of mevinolini and its open acid form, mevinolinic acid, were determined by a combination of physical techniques. Mevinolin was shown to be 1,2,6,7,8,8a-hexahydro-beta, delta-dihydroxy-2,6-dimethyl-8-(2-methyl-1-oxobutoxy)-1-naphthalene-hepatanoic acid delta-lactone. Mevinolin in the hydroxy-acid form, mevinolinic acid, is a potent competitive inhibitor of 3-hydroxy-3-methylglutaryl-coenzyme A reductase [mevalonate: NADP+ oxidoreductase (CoA-acylating), EC 1.1.1.34]; its Ki of 0.6 nM can be compared to 1.4 nM for the hydroxy acid form of the previously described related inhibitor, ML-236B (compactin, 6-demethylmevinolin). In the rat, orally administered sodium mevinolinate was an active inhibitor of cholesterol synthesis in an acute assay (50% inhibitory dose = 46 microgram/kg). Furthermore, it was shown that mevinolin was an orally active cholesterol-lowering agent in the dog. Treatment of dogs for 3 weeks with mevinolin at 8 mg/kg per day resulted in a 29.3 +/- 2.5% lowering of plasma cholesterol.
Fluorescent Indicator Methods to Assay Functional CFTR Expression in Cells (2003)

Halide-sensitive fluorescent indicators have been useful in cystic fibrosis (CF) research in assaying functional cystic fibrosis transmembrane conductance regulator (CFTR) expression in cells. Some applications (for review, see refs. 1 and 2) have included measurements in native airway cells (), demonstration that CFTR is a chloride channel (,), functional analysis of mutant CFTRs (-), and analysis of the efficacy of CFTR gene replacement in human gene therapy trials (-). A promising new application of halide indicators is in high-throughput screening to discover drugs that may correct defective cellular processing and/or function of disease-causing CFTR mutants. Another new application is the use of cell-impermeable chloride indicators to measure chloride concentration in the airway surface liquid in cell culture models and in the in vivo trachea (). The first biological application of a chloride indicator, SPQ, was reported in 1987 (). As described below, numerous advances in indicator technology have been made since the first report, including the development of cell-permeable (), cell-impermeable (,), long-wavelength (,), and dual-wavelength () indicators, as well as the development of a targetable green fluorescent protein-based halide indicator (). The major advantages of a fluorescence-based assay of CFTR function are sensitivity, technical simplicity, and the ability to assay function in single cells and heterogeneous cell mixtures. Fluorescence assays are rapid, quantitative, and technically simple, and can be performed using fluorescence microscopy, automated fluorescence plate readers, or cell cytometry. In contrast, assays using radioactive 36Cl require relatively large amounts of materials, are technically difficult, and cannot be used to study single cells or heterogeneous cell mixtures. Single-channel electrophysiological measurements of CFTR function are also technically challenging and generally not suitable for screening applications; however, it should be noted that data on single-channel properties (open probability, gating kinetics, current-voltage relationships) cannot be obtained by fluorescence methods. This chapter describes the available fluorescence-based assays of CFTR function. Technical details and useful practical hints are provided, and potential pitfalls are mentioned.
Dexamethasone inhibits Glioma-induced Formation of Capillary like Structures in vitro and Angiogenesis in vivo (1997)

Dexamethasone is used frequently in brain tumor therapy of patients. In animal models it is known to inhibit the angiogenesis of solid tumors. We addressed the question, if this is also true in brain tumors. C6 malignant glioma and 9L gliosarcoma cells were implanted into rat-brains. Dexamethasone 3 mg/kg/d intraperitoneal increased the survival compared to saline treated controls. The tumors size and the vascular density were smaller in the dexamethasone groups in both models. In vitro dexamethasone inhibited the growth of the C6 cells but not of 9L cells. Thus the growth inhibition of brain tumors in vivo appeared to be mediated partly by direct growth inhibition of tumor cells in C6 cells but additionally by antiangiogenesis in both tumor models. Several in vitro models were used to address the mechanisms of antiangiogenesis. There was no effect of dexamethasone on the proliferation of central nervous endothelial cells and no effect on the formation of capillary like structures on matrigel. Dexamethasone inhibited, however, the formation of capillary like structures in a coculture model with glioma cells in vitro. Surprisingly, progesterone had the same effect in this model. The in vitro effect was mediated via glucocorticoid receptors since receptor antagonists could inhibit it. The primary target appeared to be the tumor cell because only this cell had the complete set of receptors. These data show, that antiangiogenic therapeutic effects are possible by influencing primarily the tumor cell. This way of targeting might be of value for future developments of new strategies.
Carbonylative Suzuki‐Miyaura Cross‐Coupling Over Pd NPs/Rice‐Husk Carbon‐Silica Solid Catalyst: Effect Of 1,4‐Dioxane Solvent (2018)

Abstract With the aim of investigating the role of solvent in directing the product selectivity in carbonylative Suzuki‐Miyaura cross‐coupling (CSMC), Rice‐Husk (RH) derived carbon‐silica supported palladium nanoparticle (PdNPs/C‐SiO 2 ) catalysts were prepared and characterized by various techniques. The structural and textural properties of these catalysts have been determined by XRD, BET, SEM, TEM, FT‐IR and XPS. In CSMC over Pd NPs/C‐SiO 2 catalysts solvents are playing a critical role in directing the product selectivity particularly with 1, 4‐dioxane solvent biaryl ketone alone formed from iodobenzene, carbon monoxide and phenylboronic acid, addressing the in‐situ formation of phenylboronate ester from 1, 4‐dioxane solvent and phenyl boronic acid and subsequent biaryl ketone formation with 100% selectivity and appealing catalytic activity ( Extreamly high TON= 3,61,650).
Very low complexity interpolative speech coding at 1.2 to 2.4 kbps (2002)

The recently-introduced waveform interpolation (WI) coders provide good-quality speech at low rates but may be too complex for commercial use. This paper proposes new approaches to low-complexity WI speech coding at rates of 1.2 and 2.4 kbps. The proposed coders are 4 to 5 times faster than the previously reported ones. At 2.4 kbps, the complexity is about 7.5 and 2.5 MFLOPS for the encoder and decoder, respectively. At 1.2 kbps, the complexity is about 6 and 2.3 MFLOPS for the encoder and decoder, respectively. Informal subjective evaluation shows that, at 2.4 kbps, the quality is close to that of the high-complexity coders. The quality does not significantly degrade at 1.2 kbps and it is considered sufficient for messaging applications.
OVX1 and CEA in Patients with Colon Carcinoma, Colon Polyps and Benign Colon Disorders (1998)

The OVX1 tumor marker promises to complement CA125 for detection of early stage ovarian carcinoma. OVX1 has also been shown to be elevated in colon cancer patients. This study is designed to assess serum OVX1 levels in patients with specific stages of colon cancer, colon polyps or other GI disorders. Serum OVX1 and CEA were measured by radioimmunoassay or enzyme immunoassay for 206 patients at the time of colonoscopy or staging for colon carcinoma. In patients with stage I, II, III, or IV colon carcinoma, serum OVX1 was positive in 37%, 48%, 74% and 63%, respectively. Fifty-three percent of patients with colon polyps had elevated OVX1 levels, while OVX1 levels were positive in only 7% of healthy controls. If both OVX1 and CEA were considered, at least one of these markers was elevated in 36%, 60%, 79% or 89% of patients with stage I, II, III or IV colon carcinoma, respectively. The majority of patients with inflammatory bowel disease or diverticulosis also had elevated OVX1 levels. Both markers were positive in 27% of patients with colon carcinoma, and not in any patients with a normal colonoscopy or with a diagnosis of diverticulosis or hemorrhoids. In conclusion, serum OVX1 improves the sensitivity of CEA for detecting colon polyps and colon cancer; however, the use of OVX1 in this setting is hindered by its elevation in non-malignant colonic processes.
New DNS RR Definitions (1990)

This memo defines five new DNS types for experimental purposes. This
RFC describes an Experimental Protocol for the Internet community, and
requests discussion and suggestions for improvements.
Studies on spin labeled ribonucleic acids encapsulated by viral proteins (1978)

Spin labeled poly rA (sl-poly rA) was encapsulated by the coat proteins of two plant viruses having different morphologies: TMV, a rigid rod and CCMV, an icosahedral sphere. Electron microscopy showed that the resultant particles were morphologically similar to the parent virus from which the coat protein was obtained. Encapsulation produced progressive immobilization of the spin label. The motion of the spin label attached to TMV-sl-poly rA appears anisotropic with a correlation time about the long axis of approximately 5 x 10(-6) sec. Exogenous nuclease had no effect on the epr spectrum of this nucleo-protein complex. The epr spectrum of CCMV-sl-poly rA was isotropic with a correlation time less than 5 x 10(-7). CCMV-sl-poly rA was partially degraded by T2 ribonuclease. Theoretical calculations of correlation times for the motion of the nucleo-protein particles were similar to the experimentally derived values suggesting that the nucleo-protein particles are tightly packed with little potential for internal motion.
Phosphoramidate Pronucleotides:  A Comparison of the Phosphoramidase Substrate Specificity of Human and Escherichia coli Histidine Triad Nucleotide Binding Proteins (2007)

To facilitate the delivery of nucleotide-based therapeutics to cells and tissues, a variety of pronucleotide approaches have been developed. Our laboratory and others have demonstrated that nucleoside phosphoramidates can be activated intracellularly to the corresponding 5'-monophosphate nucleotide and that histidine triad nucleotide binding proteins (Hints) are potentially responsible for their bioactivation. Hints are conserved and ubiquitous enzymes that hydrolyze phosphoramidate bonds between nucleoside 5'-monophosphate and an amine leaving group. On the basis of the ability of nucleosides to quench the fluorescence of covalently linked amines containing indole, a sensitive, continuous fluorescence-based assay was developed. A series of substrates linking the naturally fluorogenic indole derivatives to nucleoside 5'-monophosphates were synthesized, and their steady state kinetic parameters of hydrolysis by human Hint1 and Escherichia coli hinT were evaluated. To characterize the elemental and stereochemical effect on the reaction, two P-diastereoisomers of adenosine or guanosine phosphoramidothioates were synthesized and studied to reveal a 15-200-fold decrease in the specificity constant (kcat/Km) when the phosphoryl oxygen is replaced with sulfur. While a stereochemical preference was not observed for E. coli hinT, hHint1 exhibited a 300-fold preference for d-tryptophan phosphoramidates over l-isomers. The most efficient substrates evaluated to date are those that contain the less sterically hindering amine leaving group, tryptamine, with kcat and Km values comparable to those found for adenosine kinase. The apparent second-order rate constants (kcat/Km) for adenosine tryptamine phosphoramidate monoester were found to be 107 M-1 s-1 for hHint1 and 106 M-1 s-1 for E. coli hinT. Both the human and E. coli enzymes preferred purine over pyrimidine analogues. Consistent with observed hydrogen bonding between the 2'-OH group of adenosine monophosphate and the active site residue, Asp43, the second-order rate constant (kcat/Km) for thymidine tryptamine phosphoramidate was found to be 3-4 orders of magnitude smaller than that for uridine tryptamine phosphoramidate for hHint1 and 2 orders of magnitude smaller than that for E. coli hinT. Ara-A tryptamine phosphoramidate was, however, shown to be a good substrate with a specificity constant (kcat/Km) only 10-fold lower than the value for adenosine tryptamine phosphoramidate. Consequently, nucleoside phosphoramidates containing unhindered primary amines and either an alpha or beta 2'-OH group should be easily bioactivated by Hints with efficiencies rivaling those for the 5'-monophosphorylation of nucleosides by nucleoside kinases. The differential substrate specificity observed for human and E. coli enzymes represents a potential therapeutic rationale for the development of selective antibiotic phosphoramidate pronucleotides.
Molecular Mediators of Asthma: Current Insights (1996)

With advances in molecular biology, the complex inflammatory events that underlie asthma are being unraveled. The players are diverse, involving two populations each of mast cells and helper T cells, eosinophils, bronchial endothelial and epithelial cells, and an array of vasoactive and bronchoactive mediators. The clinical message is already clear: Treat the inflammation early.
Multispectral imaging using compact compound optics (2004)

A very thin image capturing system called TOMBO (thin observation module by bound optics) is developed with compound-eye imaging and digital post-processing. As an application of TOMBO, a multispectral imaging system is proposed. With a specific arrangement of the optical system, spatial points can be observed by multiple photodetectors simultaneously. A filter array inserted in front of the image sensor enables observation of the spectrum of the target. The captured image is reconstructed by a modified pixel rearranging method extended to treat multi-channel spectral data, in which pixels in the captured image are geometrically rearranged onto a multi-channel virtual image plane. Experimental results of the image reconstruction show the effectiveness of the proposed system.
DARPin-targeting of Measles Virus: Unique Bispecificity, Effective Oncolysis, and Enhanced Safety (2013)

Oncolytic virotherapy is an emerging treatment modality that uses replication-competent viruses to destroy cancers. Many naturally occurring viruses have a preferential, although nonexclusive, tropism for tumors and tumor cells. In addition, specific targeting of cancer cells can be achieved at the virus entry level. We optimized retargeting of cell entry by elongating the measles virus attachment protein with designed ankyrin repeat proteins (DARPins), while simultaneously ablating entry through the natural receptors. DARPin-targeted viruses were strongly attenuated in off-target tissue, thereby enhancing safety, but completely eliminated tumor xenografts. Taking advantage of the unique properties of DARPins of being fused without generating folding problems, we generated a virus simultaneous targeting two different tumor markers. The bispecific virus retained the original oncolytic efficacy, while providing proof of concept for a strategy to counteract issues of resistance development. Thus, DARPin-targeting opens new prospects for the development of personalized, targeted therapeutics.
DNAX Accessory Molecule-1 Mediated Recognition of Freshly Isolated Ovarian Carcinoma by Resting Natural Killer Cells (2007)

Although natural killer (NK) cells are well known for their ability to kill tumors, few studies have addressed the interactions between resting (nonactivated) NK cells and freshly isolated human tumors. Here, we show that human leukocyte antigen class I(low) tumor cells isolated directly from patients with advanced ovarian carcinoma trigger degranulation by resting allogeneic NK cells. This was paralleled by induction of granzyme B and caspase-6 activities in the tumor cells and significant tumor cell lysis. Ovarian carcinoma cells displayed ubiquitous expression of the DNAX accessory molecule-1 (DNAM-1) ligand PVR and sparse/heterogeneous expression of the NKG2D ligands MICA/MICB and ULBP1, ULBP2, and ULBP3. In line with the NK receptor ligand expression profiles, antibody-mediated blockade of activating receptor pathways revealed a dominant role for DNAM-1 and a complementary contribution of NKG2D signaling in tumor cell recognition. These results show that resting NK cells are capable of directly recognizing freshly isolated human tumor cells and identify ovarian carcinoma as a potential target for adoptive NK cell-based immunotherapy.
Multi-Objective Optimization Using Evolutionary Algorithms (2001)

From the Publisher:
Evolutionary algorithms are relatively new, but very powerful techniques used to find solutions to many real-world search and optimization problems. Many of these problems have multiple objectives, which leads to the need to obtain a set of optimal solutions, known as effective solutions. It has been found that using evolutionary algorithms is a highly effective way of finding multiple effective solutions in a single simulation run. · Comprehensive coverage of this growing area of research · Carefully introduces each algorithm with examples and in-depth discussion · Includes many applications to real-world problems, including engineering design and scheduling · Includes discussion of advanced topics and future research · Features exercises and solutions, enabling use as a course text or for self-study · Accessible to those with limited knowledge of classical multi-objective optimization and evolutionary algorithms The integrated presentation of theory, algorithms and examples will benefit those working and researching in the areas of optimization, optimal design and evolutionary computing. This text provides an excellent introduction to the use of evolutionary algorithms in multi-objective optimization, allowing use as a graduate course text or for self-study.
Identifying a High Fraction of the Human Genome to be under Selective Constraint Using GERP++ (2010)

Computational efforts to identify functional elements within genomes leverage comparative sequence information by looking for regions that exhibit evidence of selective constraint. One way of detecting constrained elements is to follow a bottom-up approach by computing constraint scores for individual positions of a multiple alignment and then defining constrained elements as segments of contiguous, highly scoring nucleotide positions. Here we present GERP++, a new tool that uses maximum likelihood evolutionary rate estimation for position-specific scoring and, in contrast to previous bottom-up methods, a novel dynamic programming approach to subsequently define constrained elements. GERP++ evaluates a richer set of candidate element breakpoints and ranks them based on statistical significance, eliminating the need for biased heuristic extension techniques. Using GERP++ we identify over 1.3 million constrained elements spanning over 7% of the human genome. We predict a higher fraction than earlier estimates largely due to the annotation of longer constrained elements, which improves one to one correspondence between predicted elements with known functional sequences. GERP++ is an efficient and effective tool to provide both nucleotide- and element-level constraint scores within deep multiple sequence alignments.
Clinical significance of RBC alloantibodies and autoantibodies in sickle cell patients who received transfusions (2002)

The alloimmunization rate is 29 percent in pediatric and 47 percent in adult sickle cell patients when partial or extended RBC antigen match is not performed. However, the delayed serologic and/or hemolytic transfusion reactions did not result in severe clinical outcome in most instances. The most important adverse event was hyperhemolysis, which may be triggered by a transfusion, but was not prevented by matching for RBC antigens. In most instances, the cause of hyperhemolysis was multifactorial.
Single-molecule detection of DNA hybridization (2003)

We demonstrate the detection of nanometer-scale conformational changes of single DNA oligomers through a micromechanical technique. The quantity monitored is the displacement of a micrometer-size bead tethered to a surface by the probe molecule undergoing the conformational change. This technique allows probing of conformational changes within distances beyond the range of fluorescence resonance energy transfer. We apply the method to detect single hybridization events of label-free target oligomers. Hybridization of the target is detected through the conformational change of the probe.
Interior point methods for placement (1994)

In VLSI layout optimization, the placement problem is usually solved with simulated annealing or heuristic algorithms. These procedures often begin with random initial configurations but may benefit greatly (in terms of execution time or quality of solution) when good initial relative placements are provided. Weis and Mlynski [1987] have presented a linear programming formulation for generating relative placements. In this paper, we show how efficient interior point and preconditioned conjugate gradient methods can be applied to solve large sparse linear programs based on Weis and Mlynski's approach.< <ETX xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">&gt;</ETX>