gebhart/patrepeval huggingface dataset:
Subcellular segregation of distinct heteromeric NMDA glutamate receptors in the striatum (2003)

Functional N-methyl-d-aspartate (NMDA) glutamate receptors are composed of heteromeric complexes of NR1, the obligatory subunit for channel activity, and NR2 or NR3 family members, which confer variability in the properties of the receptors. Recent studies have provided evidence for the existence of both binary (containing NR1 and either NR2A or NR2B) and ternary (containing NR1, NR2A, and NR2B) receptor complexes in the adult mammalian brain. However, the mechanisms regulating subunit assembly and receptor localization are not well understood. In the CNS, NMDA subunits are present both at intracellular sites and the post-synaptic membrane of neurons. Using biochemical protein fractionation and co-immunoprecipitation approaches we have found that in rat striatum binary NMDA receptors are widely distributed, and can be identified in the light membrane, synaptosomal membrane, and synaptic vesicle-enriched subcellular compartments. In contrast, ternary receptors are found exclusively in the synaptosomal membranes. When striatal proteins are chemically cross-linked prior to subcellular fractionation, ternary NMDA receptors can be precipitated from the light membrane and synaptic vesicle-enriched fractions where this type of receptor complex is not detectable under normal conditions. These findings suggest differential targeting of distinct types of NMDA receptor assemblies between intracellular and post-synaptic sites based on subunit composition. This targeting may underlie important differences in the regulation of the transport pathways involved in both normal as well as pathological receptor functions.
PRINTS and its automatic supplement, prePRINTS (2003)

The PRINTS database houses a collection of protein fingerprints. These may be used to assign uncharacterised sequences to known families and hence to infer tentative functions. The September 2002 release (version 36.0) includes 1800 fingerprints, encoding approximately 11 000 motifs, covering a range of globular and membrane proteins, modular polypeptides and so on. In addition to its continued steady growth, we report here the development of an automatic supplement, prePRINTS, designed to increase the coverage of the resource and reduce some of the manual burdens inherent in its maintenance. The databases are accessible for interrogation and searching at http://www.bioinf.man.ac.uk/dbbrowser/PRINTS/.
In vivo toxicity of cationic micelles and liposomes (2014)

This study investigates the toxicity of cationic micelles and liposomes utilized as nanocarriers in gene and drug delivery, demonstrating its effects on the lungs, spleen and liver.
Microfluidic flow focusing: Drop size and scaling in pressure versus flow‐rate‐driven pumping (2005)

We experimentally study the production of micrometer-sized droplets using microfluidic technology and a flow-focusing geometry. Two distinct methods of flow control are compared: (i) control of the flow rates of the two phases and (ii) control of the inlet pressures of the two phases. In each type of experiment, the drop size l, velocity U and production frequency f are measured and compared as either functions of the flow-rate ratio or the inlet pressure ratio. The minimum drop size in each experiment is on the order of the flow focusing contraction width a. The variation in drop size as the flow control parameters are varied is significantly different between the flow-rate and inlet pressure controlled experiments.
The detection of specific antibody formation to recall antigens after human bone marrow transplantation (1986)

The results of this study show that donor-derived immunity can be detected and persists in long-term survivors with and without chronic graft-v-host disease (GVHD) after human marrow grafting. Seventy-one marrow recipients (60 long-term and 11 short-term survivors) were studied for the presence of specific serum IgG antibodies to tetanus toxoid (TT), and 46 marrow recipients (35 long-term and 11 short-term) were tested for antibodies to diphtheria toxoid (DT) and measles virus after marrow grafting using an enzyme-linked immunosorbent assay. Of the 60 long-term survivors, 31 were healthy and 29 had chronic GVHD. None of the recipients were immunized to the test antigens postgrafting. Most long-term healthy recipients exhibited antibody titers to the recall test antigens, whereas only a minority of those with chronic GVHD had antibody titers to recall antigens. In healthy long-term recipients (greater than or equal to one year postgrafting) whose donors were immune to the test antigens, 25 of 31 had titers to TT, 11 of 17 had titers to DT, and 12 of 20 had titers to measles. In recipients with C-GVHD, 13 of 29 had titers to TT, six of 15 had titers to DT, and six of 15 had titers to measles virus. Within 100 days postgrafting, 11 of 11 had anti-TT titers, ten of ten had anti-DT titers, and seven of eight had antimeasles virus titers.
MEK and the inhibitors: from bench to bedside (2013)

Four distinct MAP kinase signaling pathways involving 7 MEK enzymes have been identified. MEK1 and MEK2 are the prototype members of MEK family proteins. Several MEK inhibitors are in clinical trials. Trametinib is being evaluated by FDA for the treatment of metastatic melanoma with BRAF V600 mutation. Selumetinib has been studied in combination with docetaxel in phase II randomized trial in previously treated patients with advanced lung cancer. Selumetinib group had better response rate and progression-free survival. This review also summarized new MEK inhibitors in clinical development, including pimasertib, refametinib, PD-0325901, TAK733, MEK162 (ARRY 438162), RO5126766, WX-554, RO4987655 (CH4987655), GDC-0973 (XL518), and AZD8330.
Arithmetic coding revisited (2002)

During its long gestation in the 1970s and early 1980s, arithmetic coding was widely regarded more as an academic curiosity than a practical coding technique. One factor that helped it gain the popularity it enjoys today was the publication in 1987 of source code for a multi symbol arithmetic coder in Communications of the ACM. Now (1995), our understanding of arithmetic coding has further matured, and it is timely to review the components of that implementation and summarise the improvements that we and other authors have developed since then. We also describe a novel method for performing the underlying calculation needed for arithmetic coding. Accompanying the paper is a "Mark II" implementation that incorporates the improvements we suggest. The areas examined include: changes to the coding procedure that reduce the number of multiplications and divisions and permit them to be done to low precision; the increased range of probability approximations and alphabet sizes that can be supported using limited precision calculation; data structures for support of arithmetic coding on large alphabets; the interface between the modelling and coding subsystems; the use of enhanced models to allow high performance compression. For each of these areas, we consider how the new implementation differs from the CACM package.
PARTICLE FORMATION BY RAPID EXPANSION OF SUPERCRITICAL SOLUTIONS (2002)

This body of work is intended to serve as a proof of concept for the application of supramolecular chemistry in drug development. More specifically, this work is designed to evaluate crystal doping by recrystallization from supercritical media. The rapid nucleation and growth implicit to supercritical fluid based crystallizations were tested in doping drug crystals with structurally related impurities. The ultimate motive was to tailor the physicochemical properties of active pharmaceutical ingredients (APT) through crystal doping. This, in tum provides the ability to tie functionality to APl's at early stages of drug discovery and synthesis. Methods. The rapid expansion of supercritical solution (RESS) process was evaluated for these purposes. Pure and co-solvent modified supercritical fluid C02 was used as the recrystallizing solvent. The supercritical region investigated for these studies included pressures from I 07 l-9000psi and temperatures ranging from 31-100°C. The pharmaceutical solids studied included a-naphthalene acetic acid, aspirin, benzoic acid, caffeine, chlorpropamide, indomethacin, naproxen, phenytoin, piroxicam, salicylic acid, theobromine, theophylline, tolbutamide and urea. For comparison purposes, model chlorpropamide+urea system was also recrystallized from three liquid organic solvents using evaporative crystallization. The composition, morphology and the energetics of the crystals thus produced are characterized utilizing techniques such as microscopy (polarizing optical, SEM), thennal analysis (DSC, mDSC, TGA and thennomicroscopy) and HPLC. Results. Selective extraction and a reduction in crystallinity were consistently seen in all of the drug-impurity mixtures cocrystallized by RESS process. ln addition, a number of interesting phenomena were revealed. These include habit modification, solubility enhancement, particle size reduction, eutectic formation, amorphous conversion, hydrate formation and polymorph conversion. In viewing each of these phenomena from an application standpoint, this work serves as proof of concept for enhancing the physicochemical and mechanical attributes of APl's using supercritical fluid crystal doping. Comparative evaluation studies indicated RESS to be superior to organic so lventbased recrystallizations in crystal doping. In summary, RESS offers great promise as a hybrid technique to control both the crystalline and the particle morphologies of API's in a single stage. Conclusions. The presence of an impurity in the crystallization medium exhibits varied effects depending on the phase in which it is present prior to nucleation and its affinity to the host relative to the crystallizing solvent. This in turns dictates the rate at which it nucleates and grows in relation to that of the host. The domain of effects that these kinetics dictate on one extreme includes the fomrntion ofa
Oocyte-Specific Genes Affect Folliculogenesis, Fertilization, and Early Development (2007)

Although cell-autonomous genetic programs pursued by germ and somatic cells are of critical import, intimate interplays between the two cell types are also essential for normal development of the female gonad. Recent studies demonstrate that oocytes play active roles in coordinating the growth and differentiation of somatic cells during folliculogenesis and affect successful outcomes at fertilization and early development. Mouse transgenesis has been particularly useful in defining germ-cell specific genes and their roles in folliculogenesis (e.g., DAZLA, FIGLA, NOBOX, SOHLH1, YBX2, CPEB1, GDF9), fertilization (e.g., ZP1, ZP2, ZP3), and preimplantation embryonic development (e.g., NPM2, ZAR1, NALP5, DPPA3). Continued identification of novel oocyte-specific genes and the annotation of their functions will provide additional insight into the genetic pathways regulating ovarian development. The knowledge gained from mouse models will no doubt benefit the understanding of human biology and treatment of reproductive failure.
Characterization of porin and ompR mutants of a virulent strain of Salmonella typhimurium: ompR mutants are attenuated in vivo (1989)

The ompC, ompD, and ompF genes encode the three major porins of Salmonella typhimurium. ompR encodes a positive regulator required for the expression of ompC and ompF. Transposon-generated mutations in ompC, ompD, ompF, and ompR were introduced into the S. typhimurium mouse virulent strain SL1344 by P22-mediated transduction. Following preliminary characterization in vitro, the strains were used to challenge BALB/c mice by using the oral or intravenous route. Strains harboring ompC or ompF mutations were as virulent as SL1344 after oral challenge. Strains harboring ompD mutations had a slight reduction in virulence. In contrast, ompR mutants failed to kill BALB/c mice after oral challenge and the intravenous 50% lethal dose was reduced by approximately 10(5). The ompR mutants persisted in murine tissues for several weeks following oral or intravenous challenge. Furthermore, mice orally immunized with these ompR mutant strains were well protected against challenge with virulent SL1344.
Vascular Endothelial Growth Factor and the Eye: Biochemical Mechanisms of Action and Implications for Novel Therapies (1997)

Ophthalmic complications arising from pathologic intraocular neovascularization are responsible for the majority of visual loss in most developed countries. Among the many disorders associated with intraocular neovascularization are retinopathy of prematurity, diabetic retinopathy and age-related macular degeneration. These conditions are the leading causes of blindness among infants, those of working age and the elderly, respectively. For nearly half a century the clinical findings associated with these conditions have suggested that the action of growth factors may play a pivotal role in the pathogenesis of these diseases. However, the exact molecules involved and their mechanisms of action have remained incompletely understood. Recently, studies have begun to elucidate the major molecules and intracellular pathways involved in regulating neovascular eye disorders. Vascular endothelial growth factor has been implicated as a major mediator of intraocular neovascularization and permeability. The recent insights into the mechanisms of intraocular angiogenesis have provided new targets for novel nondestructive therapeutic agents directed toward preventing the visual loss associated with ophthalmic neovascular disorders.
Contrast‐enhanced in vivo magnetic resonance microscopy of the mouse brain enabled by noninvasive opening of the blood‐brain barrier with ultrasound (2010)

The use of contrast agents for neuroimaging is limited by the blood-brain barrier (BBB), which restricts entry into the brain. To administer imaging agents to the brain of rats, intracarotid infusions of hypertonic mannitol have been used to open the BBB. However, this technically challenging approach is invasive, opens only a limited region of the BBB, and is difficult to extend to mice. In this work, the BBB was opened in mice, using unfocused ultrasound combined with an injection of microbubbles. This technique has several notable features: it (a) can be performed transcranially in mice; (b) takes only 3 min and uses only commercially available components; (c) opens the BBB throughout the brain; (d) causes no observed histologic damage or changes in behavior (with peak-negative acoustic pressures of 0.36 MPa); and (e) allows recovery of the BBB within 4 h. Using this technique, Gadopentetate Dimeglumine (Gd-DTPA) was administered to the mouse brain parenchyma, thereby shortening T(1) and enabling the acquisition of high-resolution (52 × 52 × 100 micrometers(3)) images in 51 min in vivo. By enabling the administration of both existing anatomic contrast agents and the newer molecular/sensing contrast agents, this technique may be useful for the study of mouse models of neurologic function and pathology with MRI.
Cell‐free production of active E. coli thioredoxin reductase and glutathione reductase (2004)

Escherichia coli thioredoxin reductase (TR) and glutathione reductase (GR) are dimeric proteins that require a flavin adenine dinucleotide (FAD) cofactor for activity. A cell-free protein synthesis (CFPS) reaction supplemented with FAD was used to produce TR at 760 microg/ml with 89% of the protein being soluble. GR accumulated to 521 microg/ml in a cell-free reaction with 71% solubility. The TR produced was fully active with a specific activity of 1390 min(-1). The GR had a specific activity of 139 U/mg, which is significantly more active than reported for GR purified from cells. The specific activity for both TR and GR decreased without FAD supplementation. This research demonstrates that CFPS can be used to produce enzymes that are multimeric and require a cofactor.
Entrapped Collagen Type 1 Promotes Differentiation of Embryonic Pancreatic Precursor Cells into Glucose-Responsive β-Cells When Cultured in Three-Dimensional PEG Hydrogels (2009)

Development of an alternative source of functional, transplantable beta-cells to replace or supplement cadaveric tissue is critical to the future success of islet cell transplantation therapy. Embryonic pancreatic precursor cells are desirable as a renewable source of beta-cells as they are both proliferative and inherently capable of pancreatic cell differentiation. We have previously shown that precursor cells undergo selective beta-cell differentiation when dissociated and photoencapsulated in a polyethylene glycol (PEG) hydrogel network; however, these cells remained immature and were not glucose responsive. Collagen type 1 supports mature cell viability and function in many cell types and we hypothesized that incorporating it within our gels may support differentiating beta-cells and facilitate beta-cell maturation. For these studies, collagen-1 was entrapped with dissociated pancreatic precursor cells in a PEG hydrogel matrix (PEGCol) with the following key findings: (1) mature, glucose-responsive, islet-like structures differentiated from spontaneously forming precursor cell clusters in PEGCol, but not unmodified PEG, hydrogels; (2) a balance existed between providing sufficient collagen-1 signaling to support precursor cell development and providing an overabundance of adhesive sites allowing contaminating mesenchymal cells to thrive' and (3) mechanical stability provided by the PEG hydrogel platform is important for successful precursor cell culture, as PEGCol hydrogels encourage glucose responsiveness and high-insulin gene expression, while pure collagen gel cultures, with the same collagen concentration, have negligible insulin gene expression. These results indicate that PEGCol hydrogels are a useful culture platform to promote differentiation of a glucose-responsive beta-cell population from dissociated precursor cells.
TRAM, a predicted RNA-binding domain, common to tRNA uracil methylation and adenine thiolation enzymes (2001)

A previously undetected conserved domain is identified in two distinct classes of tRNA-modifying enzymes, namely uridine methylases of the TRM2 family and enzymes of the MiaB family that are involved in 2-methylthioadenine formation. This domain, for which the acronym TRAM is proposed after TRM2 and MiaB, is predicted to bind tRNA and deliver the RNA-modifying enzymatic domains to their targets. In addition to the two families of RNA-modifying enzymes, the TRAM domain is present in several other proteins associated with the translation machinery and in a family of small, uncharacterized archaeal proteins that are predicted to have a role in the regulation of tRNA modification or translation. Secondary structure prediction indicates that the TRAM domain adopts a simple beta-barrel fold. In addition, sequence analysis of the MiaB family enzymes showed that they share the predicted catalytic site with biotin and lipoate synthases and probably employ the same mechanism for sulfur insertion into their respective substrate.
Development of the EQ-5D-Y: a child-friendly version of the EQ-5D (2010)

The newly developed EQ-5D-Y is a useful tool to measure HRQOL in young people in an age-appropriate manner.
Diffusion, Joule heating, and band broadening in capillary gel electrophoresis of DNA (1995)

We calculated the longitudinal and transverse diffusion coefficients for a DNA molecule undergoing gel electrophoresis in the limit where it is reptating through a dense polymer matrix. Our results indicate that both diffusion coefficients increase with the electric field intensity. The transverse and longitudinal diffusion coefficients are roughly equal for regular field intensities, but the former dominates for the high field intensities normally used for capillary gel electrophoresis (CE). This has important implications for the optimization of CE. Our results clearly show that the naive use of the zero-field diffusion constant, the Einstein relation or the longitudinal diffusion constant when calculating the contribution of the parabolic temperature profile to band broadening may lead to large overestimates under typical CE conditions. Finally, we show that the field-dependent diffusion coefficients may be responsible for the existence of an optimal field intensity for CE, even if Joule heating is neglected.
Registration in the MIL Domain (1996)

This RFC describes the policy for the registration of second level
domains under the .MIL domain. This memo provides information for
the Internet community. This memo does not specify an Internet
standard of any kind.
2-benzoxazolyl and 2-benzimidazolyl hydrazones derived from 2-acetylpyridine: A novel class of antitumor agents (2001)

Here we describe the effects of novel benzoxazol-2-yl and benzimidazol-2-yl hydrazones derived from 2-pyridinecarbaldehyde and 2-acetylpyridine. The IC(50) values for inhibition of cell proliferation in KB-3-1, CCRF-CEM, Burkitt's lymphoma, HT-29, HeLa, ZR-75 and MEXF276L by most of the novel compounds are in the nanomolar range. In colony-forming assays with human tumor xenografts the compounds 2-actylpyridine benzoxazol-2-ylhydrazone (EPH52), 2-acetylpyridine benzoimidazol-2-ylhydrazone (EPH61) and 2-acetylpyridine 1-methylbenzoimidazol-2-ylhydrazone (EPH116) exhibited above-average inhibition of colon carcinoma (IC(50) = 1.3-4.56 nM); EPH52 and EPH116 also exhibited above-average inhibition of melanoma cells. As shown with human liver microsomes, EPH116 is only moderately metabolized. The compound inhibited the growth of human colon cancer xenografts in nude mice in a dose-dependent manner. Thiosemicarbazones derived from 2-formylpyridines have been shown to be inhibitors of ribonucleotide reductase (RR). The following results show that RR is not the target of the novel compounds: cells overexpressing the M2 subunit of RR and resistant to the RR inhibitor hydroxyurea are not cross-resistant to the novel compounds; inhibition of RR occurs at 6- to 73-fold higher drug concentrations than that of inhibition of cell proliferation; the pattern of cell cycle arrest in S phase induced by the RR inhibitor hydroxyurea is not observed after treatment with the novel compounds; and a COMPARE analysis with the related compounds 2-acetylpyrazine benzothiazol-2-ylhydrazone (EPH95) and 3-acetylisoquinoline benzoxazol-2-ylhydrazone (EPH136) showed that the pattern of these compounds is not related to any of the standard antitumor drugs. Therefore, these novel compounds show inhibition of colon cancers and exhibit a novel mechanism of action.