gebhart/patrepeval huggingface dataset:
Natural-Products-Inspired Use of the gem -Dimethyl Group in Medicinal Chemistry (2017)

The gem-dimethyl moiety is a structural feature frequently found in many natural products of clinical interest, including, but not limited to, taxanes, epothilones, statins, retinoids, di-/triterpenes, noviose deoxysugar, and antibiotics derived from β-lactams, macrolides, and aminocoumarins. Inspired by this time-tested moiety, medicinal chemists have widely explored its use in developing bioactive molecules because of the possibility to (1) increase target engagement, potency, and selectivity through van der Waals interactions and entropically favorable restriction to a bioactive conformation, (2) mitigate toxicity, (3) obtain superior DMPK profile, (4) modulate the p K<sub>a</sub> of nearby functionality, (5) induce symmetry into a monomethyl substituted chiral center, and (6) apply the Thorpe-Ingold conformational effect in an o-hydroxydihydrocinnamic acid based prodrug design. The aim of this Perspective is to illustrate how medicinal chemists have elegantly employed the gem-dimethyl group to obtain clinically useful drugs and to provide synthetic methods to install a gem-dimethyl group.
Isolation and initial characterization of the 5' flanking region of the human and murine cyclic guanosine monophosphate-phosphodiesterase beta-subunit genes. (1996)

The beta-PDE 5' region features match those of a highly tissue-specific gene in which factors restricted to the retina might play a role in gene activation. Elements conserved through evolution in the human and mouse sequences were found and analyzed as potential cis-acting elements. The availability of the human beta-PDE 5' upstream sequence will allow patients with retinal degeneration to be screened for possible mutations in these control sequences.
The novel picornavirus Equine rhinitis B virus contains a strong type II internal ribosomal entry site which functions similarly to that of Encephalomyocarditis virus (2001)

Equine rhinitis B virus (ERBV) has recently been classified as an Erbovirus, a new genus in the Picornaviridae family. ERBV is distantly related to members of the Cardiovirus and Aphthovirus genera which utilize a type II internal ribosome entry sequence (IRES) to initiate translation. We show that ERBV also possesses the core stem-loop structures (H-L) of a type II IRES. The function of the ERBV IRES was characterized using bicistronic plasmids that were analysed both by transfection into BHK-21 cells and by in vitro transcription and translation in rabbit reticulocyte lysates. In both systems, a region encompassed by nucleotides (nt) 189-920 downstream of the poly(C) tract was required for maximal translation. This sequence includes stem-loops H-L as well as four additional upstream stem-loops. Nt 904 corresponds to the second of three in-frame AUG codons located immediately downstream of the polypyrimidine tract (nucleotides 869-880). Site-directed mutagenesis demonstrated that AUG2 is the major initiation codon despite the appropriate positioning of AUG1 16 nt downstream of the polypyrimidine tract. In direct IRES competition experiments, the ERBV IRES was able to compete strongly for translation factors with the IRES of Encephalomyocarditis virus (EMCV). This was true when the assays were performed in vitro (with the IRESs competing either in cis or trans) and in vivo (with the IRESs competing in cis). A comparative analysis of the strength of several IRESs revealed that the ERBV IRES, like that of the EMCV, is a powerful inducer of translation and may have similar potential for use in mammalian expression systems.
Transplantation of neuronal cells induced from human mesenchymal stem cells improves neurological functions after stroke without cell fusion (2010)

The options for treating stroke are limited, but stem cells hold promise as a therapy because of their multipotency. Neuronal cells derived from mesenchymal stem cells (MSC) were reported to have more therapeutic effect than MSCs. For elucidating the therapeutic mechanism of neuronal cells, here we generated a model of focal cerebral infarction by performing left common carotid artery occlusion in adult gerbils. We transfected human trabecular bone-derived MSCs (hMSCs) with the Notch intracellular domain to induce their differentiation into neuronal cells (hN-MSCs). These cells were stereotaxically transplanted into the local ischemic hemisphere 4 days after the occlusion. Behavioral analyses were conducted 28 days after transplantation, and then fluorescence in situ hybridization (FISH) and a histological evaluation were performed. Histologically, transplanted cells were distributed around the periinfarct region, and approximately 8.5% and 4.2% of hN-MSCs and hMSCs survived, respectively; 53.2% ± 9.6% of hN-MSCs were microtubule-associated protein 2(+) (MAP-2(+) ) and extended neurites, whereas only 0.9% ± 0.3% of hMSCs were MAP-2(+) . In FISH, human nucleus-specific signals were detected in both hN-MSCs and hMSCs grafted brains, but no transplanted cell had a merged gerbil-specific nuclear signals. hN-MSC-transplanted animals showed significantly better recovery than animals given control vehicle in the T-maze, bilateral asymmetry, and open field tests. These findings suggested that hN-MSCs have greater therapeutic potential than hMSCs for stroke and that cell fusion does not primarily contribute to the therapeutic mechanism of MSC transplantation.
Detection of logical coupling based on product release history (2002)

Code-based metrics such as coupling and cohesion are used to measure a system's structural complexity. But dealing with large systems-those consisting of several millions of lines-at the code level faces many problems. An alternative approach is to concentrate on the system's building blocks such as programs or modules as the unit of examination. We present an approach that uses information in a release history of a system to uncover logical dependencies and change patterns among modules. We have developed the approach by working with 20 releases of a large Telecommunications Switching System. We use release information such as version numbers of programs, modules, and subsystems together with change reports to discover common change behavior (i.e. change patterns) of modules. Our approach identifies logical coupling among modules in such a way that potential structural shortcomings can be identified and further examined, pointing to restructuring or reengineering opportunities.
Optical amplification of 1.06-µ InAs&lt;inf&gt;1-x&lt;/inf&gt;P&lt;inf&gt;x&lt;/inf&gt;injection-laser emission (1970)

A system gain of 40 dB was realized with a semiconductor injection-laser oscillator operating into a neodymium-glass-fiber laser amplifier. InAsP ingots were grown by a modified Czochralski technique. The injection laser was fabricated from a mixed crystal of InAs <inf xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">0.17</inf> P <inf xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">0.83</inf> . This composition was chosen because laser emission occurs at 1.063 μ at liquid nitrogen temperatures. The p-n junction was obtained by zinc diffusion under phosphorus pressure. The method of fabricating contacts and the Fabry-Perot cavity is described, and optical and electrical characteristics of the devices are given. Coarse tuning of the lasing wavelength is based on <tex xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">x</tex> . Fine tuning can be accomplished by temperature variation of the laser junction in accordance with <tex xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">d\lambda/dT = 1.6</tex> Å/°K between 80- 140°K. The injection laser was optically mated to the samarium-clad neodymium-glass-fiber amplifier by microscope optics and a gimbal-mounted reflector. Design details of the optical amplifier are given in context with optimum low-noise-level operation. The peak optical amplifier wavelength can be varied over a 100- Å interval by appropriate choice of the host-glass composition. The injection-laser pulse was delayed until the spontaneous emission had reached its peak for a maximum observed gain of approximately <tex xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">5 \times 10^{4}</tex> .
<title>Binary Vector Dissimilarity Measures for Handwriting Identification</title> (2003)

Several dissimilarity measures for binary vectors are formulated and examined for their recognition capability in handwriting identification for which the binary micro-features are used to characterize handwritten character shapes. Pertaining to eight dissimilarity measures, i.e., Jaccard-Needham, Dice, Correlation, Yule, Russell-Rao, Sokal-Michener, Rogers-Tanmoto and Kulzinsky, the discriminary power of ten individual characters and their combination is exhaustively studied. Conclusions are made on how to choose a dissimilarity measure and how to combine hybrid features.
MICROEMULSION SYSTEMS WITH A NONIONIC COSURFACTANT (1980)

ABSTRACT The conditions to obtain W/0 microemulsions using ionic surfactants and a nonionic cosurfactant, a polyoxyethylene alkyl ether, were investigated. The length of the polyoxyethylene chain was critical to obtain the typical water solubilization maximum The variation of the W/0 microemulsion region with hydrocarbon content was different from that of the usual type of microemulsions having a medium chain length alcohol as cosurfactant. In the present systems the W/0 microemulsion region was not a direct continuation of the inverse micellar area at zero content of hydrocarbon. Addition of hydrocarbon was necessary for the formation of inverse micelles The microemulsion regions were sensitive to the kind of hydrocarbon used; a sign of the importance of the nonionic surfactant for the stability of this kind of microemulsions.
Dependence of Fluorescence Intensity on the Spectral Overlap between Fluorophores and Plasmon Resonant Single Silver Nanoparticles (2007)

We investigate the fluorescence from dyes coupled to individual DNA-functionalized metal nanoparticles. We use single-particle darkfield scattering and fluorescence microscopy to correlate the fluorescence intensity of the dyes with the localized surface plasmon resonance (LSPR) spectra of the individual metal nanoparticles to which they are attached. For each of three different dyes, we observe a strong correlation between the fluorescence intensity of the dye and the degree of spectral overlap with the plasmon resonance of the nanoparticle. On average, we observe the brightest fluorescence from dyes attached to metal nanoparticles that have a LSPR scattering peak approximately 40-120 meV higher in energy than the emission peak of the fluorophore. These results should prove useful for understanding and optimizing metal-enhanced fluorescence.
Molecular characterization of the GCN4-DNA complex. (1990)

We report studies of the DNA complex formed by GCN4, a transcriptional activator of eukaryotic amino acid biosynthetic operons. The DNA thermodynamic binding domain, defined by primer extension analysis, spans at least 18 base pairs, a site much larger than the 9-base-pair consensus defined by homology with naturally occurring binding sites. Chemical modification experiments reveal multiple sites of protein-DNA contact: methylation of any guanine N-7 or adenine N-3, ethylation of any phosphate oxygen, or elimination of any nucleoside within a region spanning nearly one and a half turns of the double helix reduces the binding affinity of the complex measurably. Nevertheless, the protein yields no detectable hydroxyl radical footprint, implying that the minor groove is reagent-accessible in the protein-DNA complex. These chemical modification patterns indicate that GCN4 does not utilize any of the DNA-recognition motifs of paradigm DNA-binding proteins. Assays to detect DNA bending induced by truncated or intact GCN4 indicate that protein conformation and not a protein-induced bend is responsible for the anomalous electrophoretic behavior of GCN4-DNA complexes.
Integrated Satellite Navigation and Strapdown Attitude and Heading References for Civil Air Carriers (1981)

The air carrier avionics arena is witnessing some interesting evolutionary developments in flight guidance. Among these are the strapdown attitude and heading reference system, the ring laser gyro inertial navigator and the Omega/VLF navigator. Passive navigation systems are now available which emulate VOR/DME. However, there is another development on the horizon which could be revolutionary. It is the Global Positioning System, which has the potential to overtake many of the developments now becoming available. This paper addresses the design and capability of an integrated GPS/strapdown AHRS as a replacement for the pure inertial navigator and other sensors now widely used by the air carriers. This integrated system simultaneously exhibits the excellent verticality of a dynamically erected AHRS and the outstanding position and velocity accuracy of the satellite navigator. The splendid velocity accuracy of GPS, even with the C/A code and controlled position accuracy, provides the key link to the potential of the integrated system. The system does not require external air speed or heading but can use encoded barometric altitude. As an output the system can provide a comprehensive slate of vehicle data for the flight management, flight control and flight instrument systems. This single system will outperform the pure inertial navigator at substantially less acquisition and maintenance cost. The potential for global and continuous position is not available at any price. The system can also be fitted with the same kind of VOR/DME emulation now appearing in other passive navigators. Unprecedented capability and economy in air carrier operations are in the offing in this new generation of flight guidance avionics.
A Randomized, Cross-Over Trial of Once-Daily Versus Twice-Daily Parathyroid Hormone 1–34 in Treatment of Hypoparathyroidism (1998)

Once-daily sc injection of PTH 1-34 can normalize mean serum and urine calcium levels in patients with hypoparathyroidism; however, once-daily PTH has diminishing effects on serum calcium after 12 h, such that serum calcium levels fall below the normal range in some patients. Once-daily PTH also causes a marked increase in bone turnover, with persistent increases in markers of bone formation and resorption. To test the hypothesis that a twice-daily PTH regimen can produce more physiological control than a once-daily regimen, we performed a randomized cross-over trial, lasting 28 weeks, in 17 adult subjects with hypoparathyroidism. Each 14-week study arm was divided into a 2-week inpatient dose-adjustment phase and a 12-week outpatient phase. The PTH dose (given sc once daily at 0900 h or twice daily with one dose at 0900 h and the other at 2100 h) was adjusted to maintain both serum and urine calcium within, or close to, the normal range. During the second half of the day (12-24 h), twice-daily PTH increased serum calcium and magnesium levels more effectively than once-daily PTH. In patients with calcium receptor mutations (CaR), once-daily PTH normalized urine calcium, provided that serum calcium was maintained at levels below normal range. However, twice-daily PTH treatment produced higher mean serum calcium in patients with CaR with no significant rise in urine calcium excretion, and with no significant differences in either serum or urine calcium levels between CaR and patients with acquired or idiopathic hypoparathyroidism. Thus, treatment with twice-daily PTH is the better regimen for patients with CaR to overcome their tendency to hypercalciuria while producing near-normal levels of serum calcium. The total daily PTH dose was markedly reduced with the twice-daily regimen (twice daily 46+/-52 vs. once daily 97+/-60 microg/day, P < 0.001). We conclude that a twice-daily PTH regimen provides effective treatment of hypoparathyroidism and reduces the variation in serum calcium levels at a lower total daily PTH dose.
Effects of testosterone enanthate in normal men: experience from a multicenter contraceptive efficacy study. World Health Organization Task Force on Methods for the Regulation of Male Fertility. (1996)

Testosterone enanthate administration in a contraceptive trial produced significant but reversible effects on skin, muscle, liver, lipid metabolism, and hemopoietic functions that varied between population groups. These effects reflect the relatively high peak levels and fluctuations of plasma T produced by the weekly T enanthate regimen rather than an inherent feature of hormonal male contraception. The results highlight the need for long-acting preparations of T with more stable delivery kinetics.
Shell-Restricted Swelling and Core Compression in Poly(N-isopropylacrylamide) Core−Shell Microgels (2003)

We report on an investigation of the structural relationship between the core and shell components in stimuli-sensitive core/shell microgels. Photon correlation spectroscopy measurements indicate that the presence of the shell alters the extent of core swelling. Core particles composed of poly(N-isopropylacrylamide-co-acrylic acid) (pNIPAm-co-AAc) undergo volume changes as a function of temperature and pH, where deprotonation of the acidic sites results in a volume increase (particle swelling). The addition of a poly(N-isopropylacrylamide) (pNIPAm) shell restricts the core from swelling to its native volume both above and below the pKa of acrylic acid. Furthermore, the pH responsive core undergoes only small temperature-induced volume changes above the characteristic lower critical solution temperature (LCST) of pNIPAm (31 °C) at pH values where the acid groups are fully deprotonated. The addition of a pNIPAm shell results in compression of the core and induces a large volume change at the pNIPAm LCST. These effects are dependent on the degree of cross-linking in the core and shell. Particles synthesized with lower concentrations of N,N‘-methylenebis(acrylamide) display greater degrees of shell-restricted swelling and compression upon the addition of a pNIPAm shell with an identical cross-linker concentration. These results are interpreted in terms of a previously proposed radial cross-linker density gradient, which places topological restraints upon the core following shell addition.
Los niños de la inmortalidad. El duelo y su desmentida (2013)

La inscripción de la muerte en la estructura es la condición de surgimiento del sujeto del deseo. Desde la antigüedad hasta nuestros días, las variaciones de lo que rodea a la muerte y el duelo impacta de manera diferente en las subjetividades. En la modernidad se le dispensa al niño un lugar de privilegio para hacer usufructo de él como respuesta a lo real de la muerte. El trabajo enuncia algunas reflexiones sobre el duelo no elaborado en la madre y las consecuencias sobre la constitución subjetiva del niño, estableciendo una relación cercana entre la función materna, como perversión normal y el duelo patológico ligado al fetichismo como alternativa a la castración. La clínica con niños pequeños que presentan dificultades en su constitución subjetiva nos ha mostrado que en su historia genealógica vienen a ofrecerse como sustituto para sostener la subjetividad materna frente a un duelo no satisfecho.
The natural killer T cell ligand α‐galactosylceramide prevents or promotes pristane‐induced lupus in mice (2005)

Systemic lupus erythematosus is a systemic autoimmune disease characterized by inflammation in organs such as kidneys and presence of autoantibodies against nuclear antigens. We have previously shown that CD1d deficiency in BALB/c mice exacerbates lupus nephritis and autoantibody production induced by the hydrocarbon oil pristane. Here, we have tested the impact of activating CD1d-restricted natural killer T (NKT) cells on pristane-induced lupus-like autoimmunity in BALB/c and SJL mice. Repeated in vivo treatment of pristane-injected BALB/c mice with the NKT cell ligand alpha-galactosylceramide (alpha-GalCer) prior to the onset of florid disease suppressed proteinuria, in a manner that was dependent on CD1d and IL-4 expression. In sharp contrast, however, similar treatment of pristane-injected SJL mice with alpha-GalCer resulted in increased proteinuria. Consistent with these dichotomous effects of NKT cell activation on the development of lupus-like autoimmunity, NKT cells in BALB/c and SJL/J mice exhibited a mixed Th1/Th2 and a Th1-biased cytokine production profile, respectively. These findings demonstrate that NKT cell activation with alpha-GalCer suppresses or promotes pristane-induced lupus-like autoimmunity in mice, in a strain-dependent manner.
Topic Hierarchy Generation for Text Segments: A Practical Web-based Approach (2008)

documents and queries from users, into a well-formed topic hierarchy. In this paper, we address the problem of generating topic hierarchies for diverse text segments with a general and practical approach that uses the Web as an additional knowledge source. Unlike long documents, short text segments typically do not contain enough information to extract reliable features. This work investigates the possibilities of using highly ranked search-result snippets to enrich the representation of text segments. A hierarchical clustering algorithm is then designed for creating the hierarchical topic structure of text segments. Text segments with close concepts can be grouped together in a cluster, and relevant clusters linked at the same or near levels. Different from traditional clustering algorithms, which tend to produce cluster hierarchies with a very unnatural shape, the algorithm tries to produce a more natural and comprehensive tree hierarchy. Extensive experiments were conducted on different domains of text segments, including subject terms, people names, paper titles, and natural language questions. The obtained experimental results have shown the potential of the proposed approach, which provides a basis for the in-depth analysis of text segments on a larger scale and is believed able to benefit many information systems.
Crystallization and preliminary X-ray analysis of recombinant glutamate mutase and of the isolated component S from Clostridium cochlearium (1998)

Glutamate mutase [varepsilon2sigma2(B12)1] was reconstituted by incubating purified components E (varepsilon2) and S (sigma2) from Clostridium cochlearium, both produced in Escherichia coli, with either aquo- or cyanocobalamin. The inactive glutamate mutase obtained was crystallized with polyethyleneglycol 4000 as precipitant. Crystals are monoclinic with space group P21 and have cell dimensions a = 64.6, b = 113.2, c = 108.4 A and beta = 96.0 degrees for the glutamate mutase reconstituted with aquocobalamin. They diffract to a resolution of at least 2.7 A. Isolated component S was crystallized in the presence of an excess of cyanocobalamin, yielding red crystals of space group I422 with unit-cell dimensions of a = b = 69.9 and c = 107.1 A. The crystals diffract to about 3.2 A resolution. Native data sets were collected for both crystal forms.