gebhart/patrepeval huggingface dataset:
Polarisation de la lumière de fluorescence. Vie moyenne des molécules dans l'etat excité (1926)

Sommaire - La lumière réémise parles solutions fluorescentes est, en général, partiellement polarisée. En admettant que la fluorescence est liée au passage des molécules par un état excité dans lequel elles subsistent en moyenne un temps τ (probabilité de retour en [FORMULE]), on peut calculer exactement, en utilisant les lois du mouvement brownien de rotation, quelle doit être l'influence de la viscosité η du solvant sur le taux de polarisation p de la fluorescence. On trouve : [FORMULE], V étant le volume total de N molécules du corps fluorescent, et p0, la valeur qu'aurait la polarisation si les molécules ne tournaient pas. Cette formule permet de déduire, des mesures de polarisation, la valeur de la vie moyenne τ dans l'étal excité. Elle est bien vérifiée par les solutions de fluorescéine dans des mélanges d'eau et de glycérine (p0 = 0,44; τ = 0,43 10^(-8) s). On montre que la vie moyenne réelle ainsi déterm née doit être reliée au rendement lumineux ρ de la fluorescence par la formule τ = ρτ0, τ0 étant la valeur qu'aurait la vie moyenne si les causes de retour sans émission n'existaient pas, valeur que l'on peut déterminer indirectement en mesurant l'intensité de la bande d'absorption correspondant à la fluorescence (τ0 = 0,65.10^(-8) s pour la fluorescéine dans l'eau).
Illumination of the Melanopsin Signaling Pathway (2005)

In mammals, a small population of intrinsically photosensitive retinal ganglion cells (ipRGCs) plays a key role in the regulation of nonvisual photic responses, such as behavioral responses to light, pineal melatonin synthesis, pupillary light reflex, and sleep latency. These ipRGCs also express melanopsin (Opn4), a putative opsin-family photopigment that has been shown to play a role in mediating these nonvisual photic responses. Melanopsin is required for the function of this inner retinal pathway, but its precise role in generating photic responses has not yet been determined. We found that expression of melanopsin in Xenopus oocytes results in light-dependent activation of membrane currents through the Galpha(q)/Galpha(11) G protein pathway, with an action spectrum closely matching that of melanopsin-expressing ipRGCs and of behavioral responses to light in mice lacking rods and cones. When coexpressed with arrestins, melanopsin could use all-trans-retinaldehyde as a chromophore, which suggests that it may function as a bireactive opsin. We also found that melanopsin could activate the cation channel TRPC3, a mammalian homolog of the Drosophila phototransduction channels TRP and TRPL. Melanopsin therefore signals more like an invertebrate opsin than like a classical vertebrate rod-and-cone opsin.
Functional and Biochemical Analysis of Chlamydia trachomatis MurC, an Enzyme Displaying UDP- N -Acetylmuramate:Amino Acid Ligase Activity (2003)

Chlamydiae are unusual obligate intracellular bacteria that cause serious infections in humans. Chlamydiae contain genes that appear to encode products with peptidoglycan biosynthetic activity. The organisms are also susceptible to antibiotics that inhibit peptidoglycan synthesis. However, chlamydiae do not synthesize detectable peptidoglycan. The paradox created by these observations is known as the chlamydial anomaly. The MurC enzyme of chlamydiae, which is synthesized as a bifunctional MurC-Ddl product, is expected to possess UDP-N-acetylmuramate (UDP-MurNAc):L-alanine ligase activity. In this paper we demonstrate that the MurC domain of the Chlamydia trachomatis bifunctional protein is functionally expressed in Escherichia coli, since it complements a conditional lethal E. coli mutant possessing a temperature-sensitive lesion in MurC. The recombinant MurC domain was overexpressed in and purified from E. coli. It displayed in vitro ATP-dependent UDP-MurNAc:L-alanine ligase activity, with a pH optimum of 8.0 and dependence upon magnesium ions (optimum concentration, 20 mM). Its substrate specificity was studied with three amino acids (L-alanine, L-serine, and glycine); comparable Vmax/Km values were obtained. Our results are consistent with the synthesis of a muramic acid-containing polymer in chlamydiae with UDP-MurNAc-pentapeptide as a precursor molecule. However, due to the lack of specificity of MurC activity in vitro, it is not obvious which amino acid is present in the first position of the pentapeptide.
Decreased Testosterone in Regularly Menstruating Women with Decreased Libido: A Clinical Observation (2001)

Much more information is available concerning decreased libido in postmenopausal than in premenopausal women. Even less is known about androgen deficiency in younger women. We measured total and free testosterone levels in 12 consecutive premenopausal women complaining of decreased libido. Of the 12 women, 8 had low or immeasurable levels of testosterone despite having regular menstrual periods. Androgen precursor hormones, DHEA-S and Androstenedione, were low-normal to high-normal. Treatment with oral DHEA, 50 to 100 mg per day, restored sexual desire in 6 of the 8 women, gave partial improvement in one, and failed in another. Possible significance and etiological mechanism are discussed.
ChemInform Abstract: NEW METHOD FOR THE SYNTHESIS OF 2,4‐DISUBSTITUTED MORPHOLINES (1982)

Abstract Die Acetoxyacetophenone (I) werden mit den Aminoethanolen (II) in Gegenwart von HCOOH unter den Bedingungen der Leuckart‐Wal1ach‐Reaktion zu den 2‐Aryl‐4‐alkylmorpholinen (III) umgesetzt.
Dual role of a single multienzyme complex in the oxidative decarboxylation of pyruvate and branched-chain 2-oxo acids in Bacillus subtilis (1983)

The pyruvate dehydrogenase and branched-chain 2-oxo acid dehydrogenase activities of Bacillus subtilis were found to co-purify as a single multienzyme complex. Mutants of B. subtilis with defects in the pyruvate decarboxylase (E1) and dihydrolipoamide dehydrogenase (E3) components of the pyruvate dehydrogenase complex were correspondingly affected in branched-chain 2-oxo acid dehydrogenase complex activity. Selective inhibition of the E1 or lipoate acetyltransferase (E2) components in vitro led to parallel losses in pyruvate dehydrogenase and branched-chain 2-oxo acid dehydrogenase complex activity. The pyruvate dehydrogenase and branched-chain 2-oxo acid dehydrogenase complexes of B. subtilis at the very least share many structural components, and are probably one and the same. The E3 component appeared to be identical for the pyruvate dehydrogenase, 2-oxoglutarate dehydrogenase and branched-chain 2-oxo acid dehydrogenase complexes in this organism and to be the product of a single structural gene. Long-chain branched fatty acids are thought to be essential for maintaining membrane fluidity in B. subtilis, and it was observed that the ace (pyruvate dehydrogenase complex) mutant 61142 was unable rapidly to take up acetoacetate, unlike the wild-type, indicative of a defect in membrane permeability. A single pyruvate dehydrogenase and branched-chain 2-oxo acid dehydrogenase complex can be seen as an economical means of supplying two different sets of essential metabolites.
Enrichment of human embryonic stem cell-derived NKX6.1-expressing pancreatic progenitor cells accelerates the maturation of insulin-secreting cells in vivo (2013)

Human embryonic stem cells (hESCs) are considered a potential alternative to cadaveric islets as a source of transplantable cells for treating patients with diabetes. We previously described a differentiation protocol to generate pancreatic progenitor cells from hESCs, composed of mainly pancreatic endoderm (PDX1/NKX6.1-positive), endocrine precursors (NKX2.2/synaptophysin-positive, hormone/NKX6.1-negative), and polyhormonal cells (insulin/glucagon-positive, NKX6.1-negative). However, the relative contributions of NKX6.1-negative versus NKX6.1-positive cell fractions to the maturation of functional β-cells remained unclear. To address this question, we generated two distinct pancreatic progenitor cell populations using modified differentiation protocols. Prior to transplant, both populations contained a high proportion of PDX1-expressing cells (~85%-90%) but were distinguished by their relatively high (~80%) or low (~25%) expression of NKX6.1. NKX6.1-high and NKX6.1-low progenitor populations were transplanted subcutaneously within macroencapsulation devices into diabetic mice. Mice transplanted with NKX6.1-low cells remained hyperglycemic throughout the 5-month post-transplant period whereas diabetes was reversed in NKX6.1-high recipients within 3 months. Fasting human C-peptide levels were similar between groups throughout the study, but only NKX6.1-high grafts displayed robust meal-, glucose- and arginine-responsive insulin secretion as early as 3 months post-transplant. NKX6.1-low recipients displayed elevated fasting glucagon levels. Theracyte devices from both groups contained almost exclusively pancreatic endocrine tissue, but NKX6.1-high grafts contained a greater proportion of insulin-positive and somatostatin-positive cells, whereas NKX6.1-low grafts contained mainly glucagon-expressing cells. Insulin-positive cells in NKX6.1-high, but not NKX6.1-low grafts expressed nuclear MAFA. Collectively, this study demonstrates that a pancreatic endoderm-enriched population can mature into highly functional β-cells with only a minor contribution from the endocrine subpopulation.
Type I Diabetes Mellitus (1986)

DURING the past decade a wealth of information concerning the pathogenesis of Type I diabetes has become available. Two spontaneous animal models of the disease have been discovered and characterized (the Biobreeding rat and the non-obese diabetic mouse); the importance of a gene or genes in the major histocompatibility complex in Type I diabetes of human beings, of mice, and of rats has been appreciated; and the prognostic importance of selected assays for islet-cell antibodies has been defined. T-cell abnormalities that precede diabetes have been discovered. Evidence has suggested that progressive loss of first-phase insulin secretion precedes diabetes, and immunologic . . .
Tumor Cell Targeting of Transferrin−PEG−TNF-α Conjugate via a Receptor-Mediated Delivery System:  Design, Synthesis, and Biological Evaluation (2006)

PEGylation is a procedure of growing interest for enhancing the therapeutic and biotechnological potential of peptides and proteins. Transferrin (Tf) has been proposed to be useful for targeting cancer cells. The aim of this study was to modify PEGylated recombinant human tumor necrosis factor alpha (PEG-TNF-alpha) with Tf to form Tf-PEG-TNF-alpha conjugates, which would maintain the advantages of PEGylation and also achieve the function of active targeting to tumor cells. In PEGylation reactions with 5-, 20-, 40-, and 60-fold molar excess of 3.4 kDa N-hydroxysuccinimide-PEG-maleimide (PT1, PT2, PT3, and PT4, respectively), PEG-TNF-alpha conjugates with different PEG chains were synthesized. A perfusion chromatography technique using a cation-exchange column was introduced to purify PEG-TNF-alpha conjugates. PT4 with about five PEG chains was selected as a lead candidate due to highest extent of PEGylation and maximum reaction yield. Thiolated Tf was conjugated to the maleimide group at the distal end of the PEG chains on the PEG-TNF-alpha conjugates, with the resulting Tf-PEG-TNF-alpha conjugates after purification containing approximately one Tf ligand on one TNF-alpha molecule. The conjugate of Tf and PT4 (TPT4) was selected to assess the specificity and affinity to transferrin receptor (TfR) on two kinds of tumor cells, K562 and KB. Both the receptor binding assays and the competition experiments were performed using radioligand binding analysis. The results demonstrated that TPT4 as well as Tf bound specifically to the TfR on the tumor cell surface and the affinity of the conjugate to TfR was similar to that of native Tf. In contrast, PEG-TNF-alpha demonstrated no specificity. The biodistribution and antitumor effects were investigated in S-180 tumor-bearing mice. It was found that TPT4 could markedly alter in vivo behavioral characteristics of TNF-alpha. Compared with TNF-alpha and PT4, extravasated TPT4 in tumor tissues exhibited a significantly delayed blood clearance and the highest intratumoral TNF-alpha levels. Furthermore, the inhibitory rate of tumor of TPT4 enhanced 5.3- and 1.8-fold over that of TNF-alpha and PT4, indicating that TPT4 exhibited the highest antitumor activity. These results suggested that Tf-PEG-TNF-alpha was a useful long circulating conjugate with the capabilities of specific receptor binding resulting in enhanced antitumor activity of TNF-alpha.
Determination of the Nucleotide Sequences of Heat Shock Operon groESL and the Citrate Synthase Gene ( gltA ) of Anaplasma ( Ehrlichia ) platys for Phylogenetic and Diagnostic Studies (2002)

The 1,670-bp nucleotide sequence of the heat shock operon groESL and the 1,236-bp sequence of the citrate synthase gene (gltA) of Anaplasma (Ehrlichia) platys were determined. The topology of the groEL- and gltA-based phylogenetic tree was similar to that derived from 16S rRNA gene analyses with distances. Both groESL- and gltA-based PCRs specific to A. platys were also developed based upon the alignment data.
Abatacept binds to the Fc receptor CD64 but does not mediate complement-dependent cytotoxicity or antibody-dependent cellular cytotoxicity. (2007)

Abatacept does not mediate CDC or ADCC of target B cells in vitro and has limited Fc receptor binding. These data support the concept that abatacept therapeutic activity is primarily due to the binding to CD80/86 through the CTLA4 extracellular domain and not through activities mediated by the modified Fc domain.
The Human DIMINUTO/DWARF1 Homolog Seladin-1 Confers Resistance to Alzheimer's Disease-Associated Neurodegeneration and Oxidative Stress (2000)

In Alzheimer's disease (AD) brains, selected populations of neurons degenerate heavily, whereas others are frequently spared from degeneration. To address the cellular basis for this selective vulnerability of neurons in distinct brain regions, we compared gene expression between the severely affected inferior temporal lobes and the mostly unaffected fronto-parietal cortices by using an mRNA differential display. We identified seladin-1, a novel gene, which was downregulated in large pyramidal neurons in vulnerable regions in AD but not control brains. Seladin-1 is a human homolog of the DIMINUTO/DWARF1 gene described in plants and Caenorhabditis elegans. Its sequence shares similarities with flavin-adenin-dinucleotide (FAD)-dependent oxidoreductases. In human control brain, seladin-1 was highly expressed in almost all neurons. In PC12 cell clones that were selected for resistance against AD-associated amyloid-beta peptide (Abeta)-induced toxicity, both mRNA and protein levels of seladin-1 were approximately threefold higher as compared with the non-resistant wild-type cells. Functional expression of seladin-1 in human neuroglioma H4 cells resulted in the inhibition of caspase 3 activation after either Abeta-mediated toxicity or oxidative stress and protected the cells from apoptotic cell death. In apoptotic cells, however, endogenous seladin-1 was cleaved to a 40 kDa derivative in a caspase-dependent manner. These results establish that seladin-1 is an important factor for the protection of cells against Abeta toxicity and oxidative stress, and they suggest that seladin-1 may be involved in the regulation of cell survival and death. Decreased expression of seladin-1 in specific neurons may be a cause for selective vulnerability in AD.
Novel role for αvβ5-integrin in retinal adhesion and its diurnal peak (2005)

alpha(v)beta(5)-Integrin is the sole integrin receptor at the retinal pigment epithelium (RPE)-photoreceptor interface and promotes RPE phagocytic signaling to the tyrosine kinase Mer tyrosine kinase (MerTK) once a day in response to circadian photoreceptor shedding. Herein we identify a novel role for alpha(v)beta(5)-integrin in permanent RPE-photoreceptor adhesion that is independent of alpha(v)beta(5)'s function in retinal phagocytosis. To compare retinal adhesion of wild-type and beta(5)-integrin(-/-) mice, we mechanically separated RPE and neural retina and quantified RPE protein and pigment retention with the neural retina. Lack of alpha(v)beta(5)-integrin with normal expression of other RPE integrins greatly weakened retinal adhesion in young mice and accelerated its age-dependent decline. Unexpectedly, the strength of wild-type retinal adhesion varied with a diurnal rhythm that peaked 3.5 h after light onset, after the completion of phagocytosis, when integrin signaling to MerTK is minimal. Permanent alpha(v)beta(5) receptor deficiency attenuated the diurnal peak of retinal adhesion in beta(5)-integrin(-/-) mice. These results identify alpha(v)beta(5)-integrin as the first RPE receptor that contributes to retinal adhesion, a vital mechanism for long-term photoreceptor function and viability. Furthermore, they indicate that alpha(v)beta(5) receptors at the same apical plasma membrane domain of RPE cells fulfill two separate functions that are synchronized by different diurnal rhythms.
Omega 3 fatty acids and cardiovascular disease—fishing for a natural treatment (2004)

Omega 3 fatty acids from fish and fish oils can protect against coronary heart disease. This article reviews the evidence regarding fish oils and coronary disease and outlines the mechanisms through which fish oils might confer cardiac benefits
Population pharmacokinetics/pharmacodynamics of docetaxel in phase II studies in patients with cancer. (1998)

First-course docetaxel PK is a predictor of first-course hematologic toxicity, but also of fluid retention, which is cumulative in nature. Patients with elevated hepatic enzymes have a 27% reduction in docetaxel CL and are at a higher risk of toxicity. A starting dose of 75 mg/m2 is currently being evaluated in this population. Prospective implementation of large-scale population PK/PD evaluation is feasible in early drug development and this approach generates clinically relevant findings.
Picture generation with a standard line printer (1964)

A method is described for producing gray-toned pictures on a line printer by utilizing the different degrees of blackness of standard print characters. Gray scales with 17, 32 and 64 levels have been devised. Scanned images of blood cells are used to display the technique.
Vehicle-to-Infrastructure Traffic Information System for the Work Zone Based on Dedicated Short-Range Communication (2011)

This paper describes the architecture, functionality, and field demonstration of a newly developed dedicated short-range communication (DSRC)–based vehicle-to-infrastructure communication system for improving traffic efficiency and safety in work-zone-related congestion buildup on U.S. roadways. The goal was to develop a portable system that could be easily deployed at a work-zone site to acquire and communicate important travel information, such as the start of congestion (SoC) and travel time (TT) of the driver. With this information, drivers could make informed decisions about route choice and be prepared for upcoming congestion. The system is composed of a portable roadside unit, which can engage the onboard units (OBUs) of traveling vehicles with DSRC technology to acquire necessary traffic data (speed, time, and location). With the acquired data, the roadside unit periodically estimates the SoC and the TT, which are broadcast to all vehicles in the coverage range. An OBU receiving the broadcast message calculates the distance to the SoC. The distance to the SoC and the TT are then relayed to the driver, who can make smart decisions about whether to seek an alternate route and when to expect a sudden speed reduction. Results from the field demonstration have shown that the developed system can adapt to a changing work-zone environment smoothly under various congestion patterns on the road.
Total Synthesis of (±)-Pentacycloanammoxic Acid (2004)

The first total synthesis of (+/-)-pentacycloanammoxic acid/methyl ester (1), an unusual naturally occurring fatty acid from Candidatus Brocadia anammoxidans, has been accomplished by the sequence of reactions shown in Scheme 1. The C20-structure of 1 was assembled with stereocontrol from three building blocks: cyclooctatetraene, 2-cyclopentenone, and 7-bromoheptanoic acid. The synthesis of 1 confirms the proposed structure of 1. The mode of biosynthesis and absolute configuration have yet to be clarified.
Recent Advances in Understanding the Molecular Mechanisms of the Long QT Syndrome (1995)

Competing theories to explain the congenital long QT syndrome have included an imbalance in sympathetic innervation of the heart or a defect in repolarizing ion currents. Recent studies have identified at least four chromosomal loci at which mutations cause the congenital long QT syndrome in different families. The specific genes mutated in affected individuals have been identified at two of these loci, and both encode cardiac ion channels. The affected genes are SCN5A, the cardiac sodium channel gene, and HERG, whose protein product likely underlies IKr, the rapidly activating delayed rectifier. Thus, currently available evidence indicates that the congenital long QT syndrome is a primary disease of cardiac ion channels. Abnormalities in either inward or outward currents can cause the disease. Ongoing studies are evaluating the function of the mutant ion channels and the relationship between individual mutations and the clinical manifestations of the syndrome.
Plant Virus-Derived Small Interfering RNAs Originate Predominantly from Highly Structured Single-Stranded Viral RNAs (2005)

RNA silencing is conserved in a broad range of eukaryotes and includes the phenomena of RNA interference in animals and posttranscriptional gene silencing (PTGS) in plants. In plants, PTGS acts as an antiviral system; a successful virus infection requires suppression or evasion of the induced silencing response. Small interfering RNAs (siRNAs) accumulate in plants infected with positive-strand RNA viruses and provide specificity to this RNA-mediated defense. We present here the results of a survey of virus-specific siRNAs characterized by a sequence analysis of siRNAs from plants infected with Cymbidium ringspot tombusvirus (CymRSV). CymRSV siRNA sequences have a nonrandom distribution along the length of the viral genome, suggesting that there are hot spots for virus-derived siRNA generation. CymRSV siRNAs bound to the CymRSV p19 suppressor protein have the same asymmetry in strand polarity as the sequenced siRNAs and are imperfect double-stranded RNA duplexes. Moreover, an analysis of siRNAs derived from two other nonrelated positive-strand RNA viruses showed that they displayed the same asymmetry as CymRSV siRNAs. Finally, we show that Tobacco mosaic virus (TMV) carrying a short inverted repeat of the phytoene desaturase (PDS) gene triggered more accumulation of PDS siRNAs than the corresponding antisense PDS sequence. Taken together, these results suggest that virus-derived siRNAs originate predominantly by direct DICER cleavage of imperfect duplexes in the most folded regions of the positive strand of the viral RNA.