gebhart/patrepeval huggingface dataset:
Synthesis of Potent Non-imidazole Histamine H3-Receptor Antagonists (1998)

Histamine has been converted into a non-imidazole H3-receptor histamine antagonist by addition of a 4-phenylbutyl group at the N alpha-position followed by removal of the imidazole ring. The resulting compound, N-ethyl-N-(4-phenylbutyl)amine, remarkably has a Ki = 1.3 microM as an H3 antagonist. Using this as a lead compound, a novel series of homologous O and S isosteric tertiary amines was synthesised and structure-activity studies furnished N-(5-phenoxypentyl)pyrrolidine (Ki = 0.18 +/- 0.10 microM, for [3H]histamine release from rat cerebral cortex synaptosomes) which, more importantly, was active in vivo. Substitution of NO2 into the para position of the phenoxy group gave N-(5-p-nitrophenoxypentyl)pyrrolidine, UCL 1972 (Ki = 39 +/- 11 nM), ED50 = 1.1 +/- 0.6 mg/kg per os in mice on brain tele-methylhistamine levels.
Formation of Stable DNA Loops by Incorporation of Nonpolar, Non‐Hydrogen‐Bonding Nucleoside Isosteres (1996)

The stability of hairpin structures formed from oligonucleotides depends on the units in the loop region. When the nonpolar nucleoside isosteres 1–3 replace the natural nucleosides thymidine and deoxyadenosine in the loop linking two octanucleotides, the corresponding duplex DNAs are considerably more stable than the natural analogues.
Saponins with an Unusual Secoursene Skeleton from Sesamum alatum THONN. (1992)

Abstract Three new saponins, alatoside A–C ( 4a, 5 , and 6a , resp.), with a 18,19‐secours‐12‐ene skeleton were isolated from the aerial parts of Sesamum alatum T HONN . (Pedaliaceae) by preparative liquid chromatography. Their structures were elucidated by spectroscopic methods, including X‐ray diffraction analysis, and by chemical degradation (acidic and enzymatic hydrolyses). In addition, verbascoside ( 1 ) and two cyclohexylethanol derivatives, rengyol ( 2a ) and isorengyol ( 3a ), were isolated and identified.
l-Isoleucine Production with Corynebacterium glutamicum: Further Flux Increase and Limitation of Export (1996)

The synthesis of l-isoleucine with Corynebacterium glutamicum involves 11 reaction steps, in at least five of which activity or expression is regulated. We used four genes and alleles encoding feedback-resistant enzymes (Fbr) in various combinations to assay flux increase through the sequence. During strain construction, the order of genes overexpressed was important. Only when ilvA(Fbr) was first overexpressed could hom(Fbr) be introduced. This succession apparently prevents the toxic accumulation of biosynthesis intermediates. The best strain constructed (SM13) was characterized by high-level expression of hom(Fbr), thrB, and ilvA(Fbr). With this strain a yield of 0.22 g of l-isoleucine per g of glucose was obtained, with a maximal specific productivity of 0.10 g of l-isoleucine per g (dry weight) per h. In strain SM13, with the high metabolite flux through the reaction sequence, effects on (i) other enzyme levels, (ii) time-dependent variations with process time, and (iii) concentrations of cytosolic intermediates were quantified. Most importantly, the intracellular l-isoleucine concentration is always higher at all process times than the extracellular concentration. The intracellular concentration rises to 110 mM, whereas extracellularly only 60 mM is accumulated. Also the immediate l-isoleucine precursor 2-ketomethyl valerate accumulates in the cell. Therefore, in the high-level l-isoleucine producer SM13, the export of this amino acid is the major limiting reaction step and therefore is a new target of strain design for biotechnological purposes.
Mycobacterial Codon Optimization Enhances Antigen Expression and Virus-Specific Immune Responses in RecombinantMycobacterium bovisBacille Calmette-Guerin Expressing Human Immunodeficiency Virus Type 1 Gag (2005)

Although its potential for vaccine development is already known, the introduction of recombinant human immunodeficiency virus (HIV) genes to Mycobacterium bovis bacille Calmette-Guérin (BCG) has thus far elicited only limited responses. In order to improve the expression levels, we optimized the codon usage of the HIV type 1 (HIV-1) p24 antigen gene of gag (p24 gag) and established a codon-optimized recombinant BCG (rBCG)-p24 Gag which expressed a 40-fold-higher level of p24 Gag than did that of nonoptimized rBCG-p24 Gag. Inoculation of mice with the codon-optimized rBCG-p24 Gag elicited effective immunity, as evidenced by virus-specific lymphocyte proliferation, gamma interferon ELISPOT cell induction, and antibody production. In contrast, inoculation of animals with the nonoptimized rBCG-p24 Gag induced only low levels of immune responses. Furthermore, a dose as small as 0.01 mg of the codon-optimized rBCG per animal proved capable of eliciting immune responses, suggesting that even low doses of a codon-optimized rBCG-based vaccine could effectively elicit HIV-1-specific immune responses.
Genome-wide association study of antisocial personality disorder (2016)

The pathophysiology of antisocial personality disorder (ASPD) remains unclear. Although the most consistent biological finding is reduced grey matter volume in the frontal cortex, about 50% of the total liability to developing ASPD has been attributed to genetic factors. The contributing genes remain largely unknown. Therefore, we sought to study the genetic background of ASPD. We conducted a genome-wide association study (GWAS) and a replication analysis of Finnish criminal offenders fulfilling DSM-IV criteria for ASPD (N=370, N=5850 for controls, GWAS; N=173, N=3766 for controls and replication sample). The GWAS resulted in suggestive associations of two clusters of single-nucleotide polymorphisms at 6p21.2 and at 6p21.32 at the human leukocyte antigen (HLA) region. Imputation of HLA alleles revealed an independent association with DRB1*01:01 (odds ratio (OR)=2.19 (1.53-3.14), P=1.9 × 10(-5)). Two polymorphisms at 6p21.2 LINC00951-LRFN2 gene region were replicated in a separate data set, and rs4714329 reached genome-wide significance (OR=1.59 (1.37-1.85), P=1.6 × 10(-9)) in the meta-analysis. The risk allele also associated with antisocial features in the general population conditioned for severe problems in childhood family (β=0.68, P=0.012). Functional analysis in brain tissue in open access GTEx and Braineac databases revealed eQTL associations of rs4714329 with LINC00951 and LRFN2 in cerebellum. In humans, LINC00951 and LRFN2 are both expressed in the brain, especially in the frontal cortex, which is intriguing considering the role of the frontal cortex in behavior and the neuroanatomical findings of reduced gray matter volume in ASPD. To our knowledge, this is the first study showing genome-wide significant and replicable findings on genetic variants associated with any personality disorder.
A phenotypic and molecular characterization of the fmr1‐tm1Cgr Fragile X mouse (2004)

Fragile X Syndrome is the most common form of inherited mental retardation. It is also known for having a substantial behavioral morbidity, including autistic features. In humans, Fragile X Syndrome is almost always caused by inactivation of the X-linked FMR1 gene. A single knockout mouse model, fmr1-tm1Cgr, exists. In this report we further characterize the cognitive and behavioral phenotype of the fmr1-tm1Cgr Fragile X mouse through the use of F1 hybrid mice derived from two inbred strains (FVB/NJ and C57BL/6J). Use of F1 hybrids allows focus on the effects of the fmr1-tm1Cgr allele with reduced influence from recessive alleles present in the parental inbred strains. We find that the cognitive phenotype of fmr1-tm1Cgr mice, including measures of working memory and learning set formation that are known to be seriously impacted in humans with Fragile X Syndrome, are essentially normal. Further testing of inbred strains supports this conclusion. Thus, any fmr1-tm1Cgr cognitive deficit is surprisingly mild or absent. There is, however, clear support presented for a robust audiogenic seizure phenotype in all strains tested, as well as increased entries into the center of an open field. Finally, a molecular examination of the fmr1-tm1Cgr mouse shows that, contrary to common belief, it is not a molecular null. Implications of this finding for interpretation of the phenotype are discussed.
Copper Indium Selenides and Related Materials for Photovoltaic Devices (2002)

Abstract Solar cells based on copper ternary chalcogenide compounds and alloys have emerged over the last 20 years as a promising solution to the problem of high-cost solar cells. Solar power conversion efficiencies exceed 21% in laboratory devices using thin films of these materials, and their characteristic thinness results in negligible direct materials costs per unit area compared with wafers. Photovoltaic devices made from these materials have also been shown to be intrinsically stable, circumventing the historical disadvantage of degradation typical of earlier thin film solar cell technologies. However, these copper chalcogenide devices and materials are relatively complex. This article provides an overview of the current state of our scientific understanding and technological development of them.
Low temperature germanium to silicon direct wafer bonding using free radical exposure (2010)

A low temperature germanium (Ge) to silicon (Si) wafer bonding method was demonstrated by in situ radical activation bonding in vacuum. In order to gain further insight into the bonding mechanism, the Ge surface chemistry after either oxygen or nitrogen radical activation was analyzed by means of angle-resolved x-ray photoelectron spectroscopy. After low temperature direct bonding of Ge to Si followed by annealing at 200 and 300 °C, advanced imaging techniques were used to characterize the bonded interface.
“Link-Functionalized” Polymers:  An Unusual Macromolecular Architecture through Bifunctional Initiation (1997)

Bimetallic complexes of the type (C5Me5)2Sm−R−Sm(C5Me5)2 were used for the living bis-initiated polymerization of methyl methacrylate and ε-caprolactone, giving polymers with discrete functionalities at the center of the backbone (“link-functionalized”). Poly(methyl methacrylate) containing olefin units was prepared from [(C5Me5)2Sm]2(μ-η3-CH2CHCH−)2 and related allyl compounds, although slow and/or inefficient initiation of polymerization is observed for complexes in which R is a bulky, heteroatom, or coordinating group. In contrast, the polymerization of ε-caprolactone may be carried out with good control in the presence of both sterically hindering and electron-rich moieties. Polylactones incorporating aromatic, cumulene, and amine/imine groups were synthesized through one-step bimetallic initiation in this manner. Differences between lanthanide(III) methacrylate and lactone polymerizations, differences between lanthanide(III) and aluminum(III) lactone polymerizations, and the presence of transesterification in the lactone system are discussed.
Selection and immunochemical analysis of lipooligosaccharide mutants of Neisseria gonorrhoeae (1988)

The identification of enterobacterial mutants that contain alterations in the lipopolysaccharide (LPS) oligosaccharide core structure facilitated the development of the model of the physicochemical and immunochemical structures of enteric LPS. Results of recent immunochemical studies have suggested that the structural model of the lipooligosaccharides (LOSs) of Neisseria gonorrhoeae may differ from the enteric LPS model. The difficulties in the analysis of the wild-type gonococcal LOS have precluded understanding of the precise nature of the LOS structure. This study was undertaken to isolate a series of mutants of N. gonorrhoeae 1291 that had sequential saccharide deletions in the LOS. Results of preliminary studies suggested that the pyocin, designated pyocin C, allowed selection of gonococci with such mutant LOS structures. Results also indicated that the receptor for pyocin C binding was an LOS component. Pyocin C selection led to the isolation of five strains with LOS patterns on sodium dodecyl sulfate-polyacrylamide gels which differed from the LOS of parent strain 1291. In this system, the Mr of the parent LOS was 4,715, while the LOSs from the mutant strains demonstrated progressive saccharide deletions, with Mrs of 4,230, 4,089, 3,627, 3,262, and 3,197. Protein patterns of these mutants on sodium dodecyl sulfate-polyacrylamide gels were qualitatively similar to those of the parent strains. Results of studies with five monoclonal antibodies specific for neisserial LOS indicated that shared as well as unique epitopes were present on the mutant LOSs. Results of ketodeoxyoctonate analysis of the mutant LOSs indicated that the majority of the ketodeoxyoctonate residues may be substituted on C-4 or C-5. Chemical and immunological analysis of such LOS mutants should expedite the development of the model for the structure of gonococcal LOS.
Isometric and Eccentric Force Generation Assessment of Skeletal Muscles Isolated from Murine Models of Muscular Dystrophies (2013)

Critical to the evaluation of potential therapeutics for muscular disease are sensitive and reproducible physiological assessments of muscle function. Because many pre-clinical trials rely on mouse models for these diseases, isolated muscle function has become one of the standards for Go/NoGo decisions in moving drug candidates forward into patients. We will demonstrate the preparation of the extensor digitorum longus (EDL) and diaphragm muscles for functional testing, which are the predominant muscles utilized for these studies. The EDL muscle geometry is ideal for isolated muscle preparations, with two easily accessible tendons, and a small size that can be supported by superfusion in a bath. The diaphragm exhibits profound progressive pathology in dystrophic animals, and can serve as a platform for evaluating many potential therapies countering fibrosis, and promoting myofiber stability. Protocols for routine testing, including isometric and eccentric contractions, will be shown. Isometric force provides assessment of strength, and eccentric contractions help to evaluate sarcolemma stability, which is disrupted in many types of muscular dystrophies. Comparisons of the expected results between muscles from wildtype and dystrophic muscles will also be provided. These measures can complement morphological and biochemical measurements of tissue homeostasis, as well as whole animal assessments of muscle function.
The Power of One Move: Hashing Schemes for Hardware (2010)

In a standard multiple-choice hashing scheme, each item is stored in one of hash table buckets. The availability of choice in where items are stored improves space utilization. These schemes are often very amenable to a hardware implementation, such as in a router. Recently, researchers have discovered powerful variants where items already in the hash table may be moved during the insertion of a new item. Unfortunately, these schemes occasionally require a large number of items to be moved to perform an insertion, making them inappropriate for a hardware implementation. We show that it is possible to significantly increase the space utilization of multiple-choice hashing schemes by allowing at most one item to be moved during an insertion. Furthermore, our schemes can be effectively analyzed, optimized, and compared using numerical methods based on fluid limit arguments, without resorting to much slower simulations.
Direction of unusual mixed-ligand metal–organic frameworks: a new type of 3-D polythreading involving 1-D and 2-D structural motifs and a 2-fold interpenetrating porous network (2005)

The reaction of Cu(II) or Cd(II) acetate with mixed ligands terephthalic (tp) and 3,5-bis(4-pyridyl)-4-amino-1,2,4-triazole (bpt) under the same conditions affords two unusual metal-organic frameworks, in which represents a new type of polythreaded supramolecular architecture consisting of distinct 1-D and 2-D coordination polymers within one crystal, however, has an interpenetrating porous network with two similar laterally interlocking 2-D (4,4) layers.
Synergistic activity of components of mycobacteria and mutant Salmonella in causing regression of line-10 tumors in guinea pigs. (1979)

Intratumor injections of oil-in-water emulsions containing mycobacterial whole-cell extraction residues, cell walls, or cell wall skeletons combined with a phenol:water extract of heptoseless (Re) mutant Salmonella typhimurium produced high percentages of regression of line 10 hepatocellular carcinomas in strain 2 guinea pigs. Injection of one of the mycobacterial components plus Salmonella extract cured higher percentages of tumor-bearing animals than did treatment with either microbial substance alone.

Mycobacterial whole-cell extraction residues and cell wall skeletons exposed to hydrochloric acid, potassium hydroxide, or organic solvents produced residues with varying antitumor activity. Interaction of these microbial substances with oil droplets was measured by determining the nitrogen content of the oil and aqueous phases of oil-in-water emulsions containing the test substances. A linear, positive correlation was found between tumor regressive activity and capability of the mycobacterial substances to interact with oil droplets of oil-in-water emulsions.

However, interaction of radiolabeled Salmonella extract and radiolabeled cell wall skeleton with oil droplets revealed that neither of these materials affected the binding of the other with oil droplets. Thus, the synergistic antitumor activity obtained by combined treatment with cell wall skeleton and Salmonella extract was not a consequence of the enhanced interaction of the microbial materials with the oil phase of the therapeutic oil-in-water emulsions. Presumably, the synergistic antitumor effect of combined therapy was due to individual, host-mediated responses to the two microbial substances. These as yet unknown biological responses culminated in expression of potent tumor regressive activity.
Electro-optic characteristics of de Vries tilted smectic liquid crystals: Analog behavior in the smectic A* and smectic C* phases (2002)

Chiral smectic A liquid crystal materials of the de Vries type (with molecules tilted relative to the layer normal) exhibit analog field-induced (electroclinic) optic axis rotation accompanied by an increase in birefringence. We identify two such de Vries smectic A* materials and use them to develop and test models for these characteristic electro-optic effects. These materials also exhibit colossal analog field-induced optic axis rotation in the lower temperature smectic C* phase, a consequence of polarization charge stabilization, and of polarization screening of the applied field in the liquid crystal.
Untersuchungen an 1,3‐Dicarbonylverbindungen, 11. Mitt. Anellierte Chinolone II, N‐ und O‐Alkylierungsprodukte (1979)

Abstract Die 1,3‐Dicarbonylverbindungen 2 und 6 cyclisieren beim Erhitzen mit Polyphosphorsäure zu den Chinolonen 3 und 7 . Die Chinolone 3a, 7a und 10 geben mit Ethyljodid/NaH/DMF ausschließlich die O‐alkylierten Chinoline 11 .
Should we use cells, biomaterials, or tissue engineering for cartilage regeneration? (2016)

For a long time, cartilage has been a major focus of the whole field of tissue engineering, both because of the constantly growing need for more effective options for joint repair and the expectation that this apparently simple tissue will be easy to engineer. After several decades, cartilage regeneration has proven to be anything but easy. With gratifying progress in our understanding of the factors governing cartilage development and function, and cell therapy being successfully used for several decades, there is still a lot to do. We lack reliable methods to generate durable articular cartilage that would resemble the original tissue lost to injury or disease. The question posed here is whether the answer would come from the methods using cells, biomaterials, or tissue engineering. We present a concise review of some of the most meritorious efforts in each area, and propose that the solution will most likely emerge from the ongoing attempts to recapitulate certain aspects of native cartilage development. While an ideal recipe for cartilage regeneration is yet to be formulated, we believe that it will contain cell, biomaterial, and tissue engineering approaches, blended into an effective method for seamless repair of articular cartilage.
Regulation of 4E-BP1 phosphorylation: a novel two-step mechanism (1999)

The multisubunit eukaryotic translation initiation factor (eIF) 4F recruits 40S ribosomal subunits to the 5' end of mRNA. The eIF4F subunit eIF4E interacts directly with the mRNA 5' cap structure. Assembly of the eIF4F complex is inhibited by a family of repressor polypeptides, the eIF4E-binding proteins (4E-BPs). Binding of the 4E-BPs to eIF4E is regulated by phosphorylation: Hypophosphorylated 4E-BP isoforms interact strongly with eIF4E, whereas hyperphosphorylated isoforms do not. 4E-BP1 is hypophosphorylated in quiescent cells, but is hyperphosphorylated on multiple sites following exposure to a variety of extracellular stimuli. The PI3-kinase/Akt pathway and the kinase FRAP/mTOR signal to 4E-BP1. FRAP/mTOR has been reported to phosphorylate 4E-BP1 directly in vitro. However, it is not known if FRAP/mTOR is responsible for the phosphorylation of all 4E-BP1 sites, nor which sites must be phosphorylated to release 4E-BP1 from eIF4E. To address these questions, a recombinant FRAP/mTOR protein and a FRAP/mTOR immunoprecipitate were utilized in in vitro kinase assays to phosphorylate 4E-BP1. Phosphopeptide mapping of the in vitro-labeled protein yielded two 4E-BP1 phosphopeptides that comigrated with phosphopeptides produced in vivo. Mass spectrometry analysis indicated that these peptides contain phosphorylated Thr-37 and Thr-46. Thr-37 and Thr-46 are efficiently phosphorylated in vitro by FRAP/mTOR when 4E-BP1 is bound to eIF4E. However, phosphorylation at these sites was not associated with a loss of eIF4E binding. Phosphorylated Thr-37 and Thr-46 are detected in all phosphorylated in vivo 4E-BP1 isoforms, including those that interact with eIF4E. Finally, mutational analysis demonstrated that phosphorylation of Thr-37/Thr-46 is required for subsequent phosphorylation of several carboxy-terminal serum-sensitive sites. Taken together, our results suggest that 4E-BP1 phosphorylation by FRAP/mTOR on Thr-37 and Thr-46 is a priming event for subsequent phosphorylation of the carboxy-terminal serum-sensitive sites.
Coffee “Breaks” Alzheimer's Disease (2009)

The major pathologic event of Alzheimer’s disease (AD) is the accumulation in the brain of amyloid-β (Aβ), a heterogeneous set of peptides that results from the sequential proteolysis operated by the βand the γsecretase on the amyloid-β protein precursor (AβPP). Accumulation of Aβ derives from the unbalance between its production and clearance, determined by various genetic and epigenetic factors [1]. The formation of small, soluble, Aβ aggregates in the cerebral extracellular space and inside neurons is the early effect of the increased Aβ levels, as well as the fundamental step of Aβ neurotoxicity. Indeed, Aβ oligomers impair synaptic activity [2] and induce molecular changes that favor the formation of neurofibrillary pathology and Lewy bodies [3]. According to this view of the pathologic process, the current strategies of “disease modifying therapies” in AD aim to lower Aβ brain levels, decreasing the production, promoting the clearance, and hampering the aggregation. But, so far, the trials conducted in AD patients have been disappointing, because of either the negative results [4], or the serious clinical side effects/complications [5]. In this issue, Arendash et al. [6] provide evidence that caffeine is a potential pathogenetic therapy of AD. Caffeine, at the corresponding dose of five coffee cupsa-day in humans, improved cognitive impairment of