gebhart/patrepeval huggingface dataset:
Diabetes reduces the cholesterol exporter ABCA1 in mouse macrophages and kidneys (2009)

Accumulation of cholesterol in arterial macrophages may contribute to diabetes-accelerated atherosclerotic cardiovascular disease. The ATP-binding cassette transporter ABCA1 is a cardioprotective membrane protein that mediates cholesterol export from macrophages. Factors elevated in diabetes, such as reactive carbonyls and free fatty acids, destabilize ABCA1 protein in cultured macrophages, raising the possibility that impaired ABCA1 plays an atherogenic role in diabetes. We therefore examined the modulation of ABCA1 in two mouse models of diabetes. We isolated peritoneal macrophages, livers, kidneys, and brains from type 1 non-obese diabetic (NOD) mice and mice made diabetic by viral-induced autoimmune destruction of pancreatic beta-cells, and we measured ABCA1 protein and mRNA levels and cholesterol contents. ABCA1 protein levels and cholesterol export activity were reduced by 40-44% (P<0.01) in peritoneal macrophages and protein levels by 48% (P<0.001) in kidneys in diabetic NOD mice compared with nondiabetic animals, even though ABCA1 mRNA levels were not significantly different. A similar selective reduction in ABCA1 protein was found in peritoneal macrophages (33%, P<0.05) and kidneys (35%, P<0.05) from the viral-induced diabetic mice. In liver and brain, however, diabetes had no effect or slightly increased ABCA1 protein and mRNA levels. The reduced ABCA1 in macrophages and kidneys was associated with increased cholesterol content. Impaired ABCA1-mediated cholesterol export could therefore contribute to the increased atherosclerosis and nephropathy associated with diabetes.
Novel Drug Delivery System to Bone Using Acidic Oligopeptide: Pharmacokinetic Characteristics and Pharmacological Potential (2001)

We synthesized fifteen oligopeptides consisting of Asp or Glu conjugated with a fluorescent probe, 9- fluorenylmethylchloroformate (Fmoc). In the in vitro binding assay to putative hydroxyapatite (HA), the affinities of these conjugates depended only on the number of amino acid residues, not on their optical characters (L or D) or their species (Asp or Glu). In an in vivo experiment involving a single i.v. injection of Fmoc-D-Asp oligopeptides into mice, peptides consisting of over six Asp residues were selectively distributed to the bone. Then, we synthesized estradiol-17 beta-succinate-(L-Asp)6 [E2-(L-Asp)6] and studied its pharmacokinetic characteristics and its antiosteoporotic effects on ovariectomized (OVX) mice. Although the distribution volume of E2-(L-Asp)6 was significantly smaller than that of E2, E2-(L-Asp)6 was selectively distributed in the bone after i.v. injection and gradually decreased during 7 days. E2-(L-Asp)6 effectively prevented OVX-induced bone loss, without altering the uterine weight, in the dosage range of 0.11 to 1.1 mumol/kg once a week, while E2 increased both the bone mineral density and uterine weight at 0.37 mumol/kg every third day. The results suggest that acidic oligopeptide may be useful for drug delivery to bone and E2-(L-Asp)6 is a good candidate as an anti-osteoporosis drug without the adverse side effects of E2.
Halcyon: an accurate basecaller exploiting an encoder–decoder model with monotonic attention (2020)

The source code (halcyon) can be found at https://github.com/relastle/halcyon.
Touch-typing with a stylus (1993)

One of the attractive features of keyboards is that they support novice as well as expert users. Novice users enter text using "hunt-and-peck," experts use touch-typing. Although it takes time to learn touch-typing, there is a large payoff in faster operation.
Masked Presentations of Emotional Facial Expressions Modulate Amygdala Activity without Explicit Knowledge (1998)

Functional magnetic resonance imaging (fMRI) of the human brain was used to study whether the amygdala is activated in response to emotional stimuli, even in the absence of explicit knowledge that such stimuli were presented. Pictures of human faces bearing fearful or happy expressions were presented to 10 normal, healthy subjects by using a backward masking procedure that resulted in 8 of 10 subjects reporting that they had not seen these facial expressions. The backward masking procedure consisted of 33 msec presentations of fearful or happy facial expressions, their offset coincident with the onset of 167 msec presentations of neutral facial expressions. Although subjects reported seeing only neutral faces, blood oxygen level-dependent (BOLD) fMRI signal in the amygdala was significantly higher during viewing of masked fearful faces than during the viewing of masked happy faces. This difference was composed of significant signal increases in the amygdala to masked fearful faces as well as significant signal decreases to masked happy faces, consistent with the notion that the level of amygdala activation is affected differentially by the emotional valence of external stimuli. In addition, these facial expressions activated the sublenticular substantia innominata (SI), where signal increases were observed to both fearful and happy faces--suggesting a spatial dissociation of territories that respond to emotional valence versus salience or arousal value. This study, using fMRI in conjunction with masked stimulus presentations, represents an initial step toward determining the role of the amygdala in nonconscious processing.
Adaptive self-tuning memory in DB2 (2006)

DB2 for Linux, UNIX, and Windows Version 9.1 introduces the Self-Tuning Memory Manager (STMM), which provides adaptive self tuning of both database memory heaps and cumulative database memory allocation. This technology provides state-of-the-art memory tuning combining control theory, runtime simulation modeling, cost-benefit analysis, and operating system resource analysis. In particular, the nove use of cost-benefit analysis and control theory techniques makes STMM a breakthrough technology in database memory management. The cost-benefit analysis allows STMM to tune memory between radically different memory consumers such as compiled statement cache, sort, and buffer pools. These methods allow for the fast convergence of memory settings while also providing stability in the presence of system noise. The tuning mode has been found in numerous experiments to tune memory allocation as well as expert human administrators, including OLTP, DSS, and mixed environments. We believe this is the first known use of cost-benefit analysis and control theory in database memory tuning across heterogeneous memory consumers.
A radioimmunoassay for erythropoietin (1979)

A radioimmunoassay for erythropoietin has been developed using 125I labeled pure human erythropoietin and an anti-erythropoietin antiserum produced in a rabbit immunized with human erythropoietin. Two techniques are presented for labeling erythropoietin, both resulting in an immunologically reactive labeled reactant. One method involves the use of lactoperoxidase and the other a reagent known as IODO-GEN. The second International Reference Preparation of human erythropoietin is used as a standard and a double antibody scheme is used for the separation of the free and antibody bound labeled hormone. The radioimmunoassay is sensitive to an absolute amount of erythropoietin equivalent to 0.4 milliunits. Bioassays for erythropoietin require approximately 100 times this amount. The use of pure erythropoietin as the labeled reactant has removed certain discrepancies seen in previous attempts to develop radioimmunoassays for this hormone, e.g., sera from patients without kidneys do not give the high values previously seen. Sera from anemic individuals not only give rise to high radioimmunoassay values but also show a parallel relationship with the erythropoietin standard when halving dilutions are analyzed. Desialated erythropoietin is also reactive with the same parallelism. Bleeding of a normal individual increases the serum erythropoietin level and transfusion decreases it. Erythropoietin from a variety of laboratory animals is also reactive in the radioimmunoassay, with very high values being observed in hypoxic animals.
Nuclear translocation of the photoreceptor phytochrome B is necessary for its biological function in seedling photomorphogenesis (2003)

The phytochrome (phy) family of sensory photoreceptors (phyA to phyE in Arabidopsis) enables plants to optimize their growth and development under natural light environments. Subcellular localization studies have shown that the photoreceptor molecule is induced to translocate from cytosol to nucleus by light, but direct evidence of the functional relevance of this translocation has been lacking. Here, using a glucocorticoid receptor-based fusion protein system, we demonstrate that both photoactivation and nuclear translocation combined are necessary and sufficient for the biological function of phyB. Conversely, neither artificial nuclear translocation of non-photoactivated phyB nor artificial retention of photoactivated phyB in the cytosol provides detectable biological activity. Together these data indicate that signal transfer from photoactivated phyB to its primary signaling partner(s) is localized in the nucleus, and conversely suggest the absence of a cytosolic pathway from photoactivated phyB to light-responsive genes.
Neuromyelitis optica: Evaluation of 871 attacks and 1,153 treatment courses (2015)

Particularly myelitis and bilateral optic neuritis have poor remission rates. Escalation of attack therapy improves outcome. PE/IA may increase recovery in isolated myelitis.
Rapid and sensitive detection of CpG-methylation using methyl-binding (MB)-PCR (2006)

Methylation of CpG islands is associated with transcriptional repression and, in cancer, leads to the abnormal silencing of tumor suppressor genes. We have developed a novel technique for detecting CpG-methylated DNA termed methyl-binding (MB)-PCR. This technique utilizes a recombinant protein with high affinity for CpG-methylated DNA that is coated onto the walls of a PCR vessel and selectively captures methylated DNA fragments from a mixture of genomic DNA. The retention and, hence, the degree of methylation of a specific DNA fragment (e.g. a CpG island promoter of a specific gene) is detected in the same tube by gene-specific PCR. MB-PCR does not require bisulfite treatment or methylation-sensitive restriction and provides a quick, simple and extremely sensitive technique allowing the detection of methylated DNA, in particular in tumor tissue or tumor cells from limited samples. Using this novel approach, we determined the methylation status of several established and candidate tumor suppressor genes and identified the ICSBP gene, encoding the myeloid and B-cell-specific transcription factor interferon consensus sequence-binding protein, as a target for aberrant hypermethylation in acute myeloid leukemia.
Complete correction of hyperbilirubinemia in the Gunn rat model of Crigler-Najjar syndrome type I following transient in vivo adenovirus-mediated expression of human bilirubin UDP-glucuronosyltransferase. (1996)

Recombinant adenoviral vectors are useful for the in vivo expression of genes in hepatocytes. Adenoviral vectors deleted in E1a, E1b, and E3b were constructed and used to study in vivo expression of the major human bilirubin UDP-glucuronosyltransferase isoform (HUG Br1) under the transcriptional control of the cytomegalovirus (CMV) immediate-early promoter-enhancer (H5.010CMV hugBr1). As a control, a recombinant adenoviral vector containing the beta-galactosidase reporter gene driven by the CMV promoter-enhancer was employed (H5. 010CMVlacZ). Recombinant virus was expanded following exposure to E1 transcomplementing (293) cells and concentrated to t titer of approximately 10(13) particles per milliliter. A rat model for Crigler-Najjar syndrome type I deficient in HUG Br1 (ie the Gunn rat) was injected with 5 X 10(9) plaque-forming units (p.f.u.) via the portal vein of either H5.010CMVhugBr1 or H5. 010CMVlacZ. Rats from each set were killed at 3 days, 11 days and 22 days after infusion. Liver total cellular DNA, RNA and protein were analyzed for the transgene and the transgene product at the specified times. Analysis of livers by Southern blot hybridization demonstrates sequence-specific hybridization to adenoviral vector DNA, and Northern blot hybridization demonstrates sequence-specific hybridization to transgene-derived RNA. DNA levels peak at approximately one copy number at 3 days and decline over 22 days. RNA and Western blot analyses demonstrate overexpression of message and protein at 3 days, declining over 22 days. In virto functional assay for bilirubin glucuronosyl-transferase activity demonstrates overexpression of bilirubin UDP-glucurosyltransferase function. In situ hybridization of frozen sections to detect expressed mRNA using beta-galactosidasederived 35S-labeled riboprobes demonstrates adenovirus-derived transgene expression in hepatocytes. Significant drops in serum bilirubin levels were noted following expression of HUG Br1 but not beta-galactosidase. The drop in serum bilirubin correlates with the appearance of bilirubin glucuronides in bile. In summary, recombinant adenoviral vectors were used to demonstrate in vivo complementation of the genetic defect in Gunn rat livers with the HUG Br1 cDNA leading to a resolution of hyperbilirubinemia lasting approximately 7 weeks. These studies suggest that delivery of the HUG Br1 cDNA might provide a reasonable therapeutic benefit for Crigler-Najjar syndrome type I patients, as safe and efficacious gene delivery systems are developed.
Characterization of the Yucatan miniature pig skin and small intestine for pharmaceutical applications. (1986)

Yucatan miniature pig skin and gastrointestinal tract have been characterized as potential models for human organ systems in in vitro and in vivo pharmaceutical experiments. Histology of pig skin and the flux of one classical drug, caffeine, are described. The Yucatan small intestine was examined morphologically. Both Yucatan skin and GI tract were found to have similarities to man.
Strain Compensation in Silicon by Diffused Impurities (1969)

A method to avoid dislocation generation in boron or phosphorus‐diffused layers is presented. This method, called strain compensation, considerably reduces dislocation generation in the diffused layers. This strain compensation is brought about because impurities such as tin and boron, or tin and phosphorus, have been diffused simultaneously into the silicon, with tin counteracting the stresses produced by the solute lattice contraction of the boron or the phosphorus. Transmission electron micrographs are provided as evidence of this phenomenon.
CRB1 has a cytoplasmic domain that is functionally conserved between human and Drosophila (2001)

Mutations in the human Crumbs homologue 1 (CRB1) gene cause severe retinal dystrophies, ranging from retinitis pigmentosa to Leber congenital amaurosis. The CRB1 gene is expressed specifically in human retina and brain and encodes a protein homologous to the Drosophila Crumbs protein. In crumbs mutant embryos apico-basal polarity of epithelial cells is lost, leading to widespread epidermal cell death. The small cytoplasmic domain of Crumbs organizes an intracellular protein scaffold that defines the assembly of a continuous zonula adherens. The crumbs mutant phenotype can be partially rescued by expression of just the membrane-bound cytoplasmic domain, and overexpression of this domain in a wild-type background results in a multilayered epidermis. A striking difference between CRB1 and Crumbs was that the latter contains a transmembrane region and a 37 amino acid cytoplasmic domain. Here we describe an alternative splice variant of human CRB1 that encodes a cytoplasmic domain 72% similar to that of Drosophila Crumbs. Two intracellular subdomains that are necessary for function in Drosophila are absolutely conserved. Rescuing and overexpression studies in Drosophila show that the cytoplasmic domains are functionally related between these distant species. This suggests that CRB1 organizes an intracellular protein scaffold in the human retina. Human homologues of proteins binding to Crumbs may be part of this complex and represent candidate genes for retinal dystrophies.
Reprogramming of Human Somatic Cells Using Human and Animal Oocytes (2009)

There is renewed interest in using animal oocytes to reprogram human somatic cells. Here we compare the reprogramming of human somatic nuclei using oocytes obtained from animal and human sources. Comparative analysis of gene expression in morula-stage embryos was carried out using single-embryo transcriptome amplification and global gene expression analyses. Genomic DNA fingerprinting and PCR analysis confirmed that the nuclear genome of the cloned embryos originated from the donor somatic cell. Although the human-human, human-bovine, and human-rabbit clones appeared morphologically similar and continued development to the morula stage at approximately the same rate (39, 36, and 36%, respectively), the pattern of reprogramming of the donor genome was dramatically different. In contrast to the interspecies clones, gene expression profiles of the human-human embryos showed that there was extensive reprogramming of the donor nuclei through extensive upregulation, and that the expression pattern was similar in key upregulation in normal control embryos. To account for maternal gene expression, enucleated oocyte transcriptome profiles were subtracted from the corresponding morula-stage embryo profiles. t-Test comparisons (median-normalized data @ fc>4; p<0.005) between human in vitro fertilization (IVF) embryos and human-bovine or human-rabbit interspecies somatic cell transfer (iSCNT) embryos found between 2400 and 2950 genes that were differentially expressed, the majority (60-70%) of which were downregulated, whereas the same comparison between the bovine and rabbit oocyte profiles found no differences at all. In contrast to the iSCNT embryos, expression profiles of human-human clones compared to the age-matched IVF embryos showed that nearly all of the differentially expressed genes were upregulated in the clones. Importantly, the human oocytes significantly upregulated Oct-4, Sox-2, and nanog (22-fold, 6-fold, and 12-fold, respectively), whereas the bovine and rabbit oocytes either showed no difference or a downregulation of these critical pluripotency-associated genes, effectively silencing them. Without appropriate reprogramming, these data call into question the potential use of these discordant animal oocyte sources to generate patient-specific stem cells.
Induction of cytokines in mice with parainfluenza pneumonia (1995)

The possible involvement of cytokines in the acute viral pneumonia induced by the murine parainfluenza type 1 virus, Sendai virus, was studied. Cytokine profiles for both the respiratory tract and the draining mediastinal lymph node (MLN) of virus-infected C57BL/6J mice were quantified by using the single-cell cytokine (ELISPOT) assay with freshly isolated cell populations and enzyme-linked immunosorbent assay for lung lavage fluids and culture supernatants. Maximal levels of interleukin 2 (IL-2), gamma interferon (IFN-gamma), tumor necrosis factor, IL-6, and IL-10 were detected at the inflammatory site 7 to 10 days after infection, about the time that virus is cleared from the lung. The frequencies of cells producing IL-2, IL-4, IL-6, IL-10, IFN-gamma, and tumor necrosis factor were much higher for the bronchoalveolar lavage (BAL) cell population than for the MLN cell population. Cytokine production after in vitro restimulation of MLN cells was dominated by IL-2 and IFN-gamma, with low levels of IL-10 and IL-6 also being present. Most of the cytokine was produced by the CD4+ cells, although the CD8+ subset was also involved. No IL-4 was found in the BAL fluid or in culture supernatants from restimulated BAL or MLN cells, although a high frequency of IL-4-producing cells was demonstrated in the BAL population by ELISPOT analysis.
Photoisomerization in different classes of azobenzene (2011)

Azobenzene undergoes trans→cis isomerization when irradiated with light tuned to an appropriate wavelength. The reverse cis→trans isomerization can be driven by light or occurs thermally in the dark. Azobenzene's photochromatic properties make it an ideal component of numerous molecular devices and functional materials. Despite the abundance of application-driven research, azobenzene photochemistry and the isomerization mechanism remain topics of investigation. Additional substituents on the azobenzene ring system change the spectroscopic properties and isomerization mechanism. This critical review details the studies completed to date on the 3 main classes of azobenzene derivatives. Understanding the differences in photochemistry, which originate from substitution, is imperative in exploiting azobenzene in the desired applications.
An Efficient Synthesis of 1,3-Thiazole (1985)

The cyclocondensation of methyl dithiocarbamate with chloroacetaldehyde in aqueous ethanol affords 2-methylthio-1,3-thiazole (82-88%) which is demethylsulfenylated to 1,3-thiazole (78-81%) by reaction with lithium in liquid ammonia followed by hydrolysis with aqueous ammonium chloride.
Ultrasensitive and High-Throughput Fluorescence Analysis of Droplet Contents with Orthogonal Line Confocal Excitation (2010)

This paper describes a simple modification to traditional confocal fluorescence detection that greatly improves signal-to-noise (s/n) for the high-speed analysis of droplet streams. Rather than using the conventional epi geometry, illumination of the droplet was in the form of a line that is orthogonal to both the direction of flow and the light-collection objective. In contrast to the epi geometry where we observed high levels of scattering background from the droplets, we detected more than 10-fold less background (depending on the laser power used) when orthogonal-line-confocal illumination was used. We characterized this improvement using a standard microfluidic platform over a range of analyte concentrations and observed an improvement in limits of detection of greater than 10. Using this method, we were able to analyze picomolar concentrations of analytes contained within picoliter-volume droplets at a rate of greater than 350 droplets per second.
Pancreatic pre-proglucagons are encoded by two separate mRNAs. (1981)

Poly(A) RNA prepared from anglerfish islets programs the synthesis in a wheat germ cell-free system of two proteins of Mr = 14,500 and Mr = 12,500 that are both immunoprecipitated by an antiserum prepared to pancreatic glucagon of Mr = 3,500 (29 amino acids). We provide evidence by cDNA hybridizations and nucleotide sequence analyses that these two proteins are precursors of glucagon and that they are encoded by separate genes. Two cloned recombinant cDNAs prepared from the islet mRNAs individually hybrid-selected mRNAs that directed the cell-free synthesis of each of the two glucagon-related proteins. Nucleotide sequence analysis of the cDNA corresponding to the Mr = 14,500 protein revealed a coding sequence for a peptide of 29 amino acids flanked by Lys-Arg sequences typical of those found at the sites of post-translational cleavages of hormone precursors. Twenty of the 29 amino acids in the sequence are identical with those found in the sequence of mammalian pancreatic glucagon. The second of the two cDNAs completely hybrid-arrested the translation of the mRNA encoding the smaller glucagon precursor of Mr = 12,500 but had no effect on the translation of the mRNA encoding the Mr = 14,500 precursor. The cDNA corresponding to this Mr = 14,500 precursor hybridized to the DNA of bacterial colonies containing the cDNA for the Mr = 12,500 precursor. Thus, two separate but partially homologous mRNAs encode the two pre-proglucagons.