gebhart/patrepeval huggingface dataset:
Inhibition of retinal and choroidal neovascularization by a novel KDR kinase inhibitor. (2005)

Oral dosing of the described KDR kinase inhibitor effectively inhibits neovascularization in two well-established animal models of ocular neovascularization. These data suggest that compounds of this class may prove to be useful for the treatment of a variety of ocular neovascular diseases using a convenient oral dosing regimen.
Self-enabling T cells (2011)

In this issue of Blood , Pospori and colleagues demonstrate that T cells genetically modified to express a receptor specific for a self-peptide derived from the tumor antigen Wilms Tumor 1 are not deleted in the thymus and undergo activation in the periphery, thus acquiring functionality without
Microwave Assisted Reaction of Condensed Thiophenes With Electron Poor Olefins (2003)

아미노싸이에노피리다진(1a, b)과 아미노싸이에노쿠마린(2)은 DMFDMA와 축합반응을 하여 아미딘(3a, b)을 형성한다. 이 화합물들을 N-페닐말레이마이드와 반응시키면 화합물 9와 10이 얻어진다. 반면에 3a, b, 4, 18, 19, 20을 말레산 무수물과 반응시키면 포밀 유도체인 5a, b, 6, 21, 22, 23 들이 얻어진다. 아미딘 화합물 3a, b 를 다이에틸 퓨마레이트와 반응시키면 가수분해산물인 아미딘 14를 거쳐 11이 얻어진다. N-페닐말레이마이드를 마이크로웨이브 오븐에서 반응시키면 [2+2]와 [2+2+2] 고리첨가반응 산물이 얻어진다. Aminothienopyridazines 1a, b and aminothienocoumarin 2 condensed with DMFDMA to yield amidines 3a, b and 4. These compounds reacted with N-phenylmaleimide to yield 9 and 10. On the other hand reacting 3a, b, 4, 18, 19 and 20 with maleic anhydride afforded only the formylated derivatives 5a, b, 6, 21, 22 and 23 respectively. The reaction of 3a, b with diethyl fumarate afforded 11, formed most likely via hydrolysis of the amidine 14 during working up the reaction mixture. Irradiation of N-phenylmaleimide in microwave oven afforded [2+2] and [2+2+2] cycloaddition product.
Intracellular Water Exchange for Measuring the Dry Mass, Water Mass and Changes in Chemical Composition of Living Cells (2013)

We present a method for direct non-optical quantification of dry mass, dry density and water mass of single living cells in suspension. Dry mass and dry density are obtained simultaneously by measuring a cell's buoyant mass sequentially in an H2O-based fluid and a D2O-based fluid. Rapid exchange of intracellular H2O for D2O renders the cell's water content neutrally buoyant in both measurements, and thus the paired measurements yield the mass and density of the cell's dry material alone. Utilizing this same property of rapid water exchange, we also demonstrate the quantification of intracellular water mass. In a population of E. coli, we paired these measurements to estimate the percent dry weight by mass and volume. We then focused on cellular dry density - the average density of all cellular biomolecules, weighted by their relative abundances. Given that densities vary across biomolecule types (RNA, DNA, protein), we investigated whether we could detect changes in biomolecular composition in bacteria, fungi, and mammalian cells. In E. coli, and S. cerevisiae, dry density increases from stationary to exponential phase, consistent with previously known increases in the RNA/protein ratio from up-regulated ribosome production. For mammalian cells, changes in growth conditions cause substantial shifts in dry density, suggesting concurrent changes in the protein, nucleic acid and lipid content of the cell.
Apoptosis in the Retina: The Silent Death of Vision (2000)

Pathogenetic mechanisms of retinal degeneration include cell loss by apoptosis. This gene-regulated mode of single-cell death occurs in a number of widespread human diseases such as neurodegeneration. The knowledge of genes and signaling in retinal apoptosis is expanding and opens up therapeutic strategies to ameliorate blinding retinal diseases.
Refractory nonmotor symptoms in male patients with Parkinson disease due to testosterone deficiency: a common unrecognized comorbidity. (2002)

The findings from this study reveal the heretofore unrecognized high prevalence of testosterone deficiency in elderly male patients with PD similar to that found in the general population. These symptoms, which may be refractory to antidepressants, anxiolytics, and antiparkinsonian medications, may respond to treatment with testosterone. More rigorous controlled studies will need to be undertaken to examine the treatment of this common comorbidity in male patients with PD.
GenBank (2002)

The GenBank sequence database incorporates publicly available DNA sequences of more than 105 000 different organisms, primarily through direct submission of sequence data from individual laboratories and large-scale sequencing projects. Most submissions are made using the BankIt (web) or Sequin programs and accession numbers are assigned by GenBank staff upon receipt. Data exchange with the EMBL Data Library and the DNA Data Bank of Japan helps ensure comprehensive worldwide coverage. GenBank data is accessible through NCBI's integrated retrieval system, Entrez, which integrates data from the major DNA and protein sequence databases along with taxonomy, genome, mapping, protein structure and domain information, and the biomedical literature via PubMed. Sequence similarity searching is provided by the BLAST family of programs. Complete bimonthly releases and daily updates of the GenBank database are available by FTP. NCBI also offers a wide range of World Wide Web retrieval and analysis services based on GenBank data. The GenBank database and related resources are freely accessible via the NCBI home page at http://www.ncbi.nlm.nih.gov.
Virus-specific cytotoxic T cell-mediated lysis of lymphocytes in vitro and in vivo (1993)

Virus-specific CTL play a major role in early antiviral protection against lymphocytic choriomeningitis virus (LCMV). When mice are infected with high doses of certain LCMV isolates, the initiated CTL response may vanish before the virus is eliminated completely. To evaluate the possibility that this may be because of CTL lysing CTL, we studied the susceptibility to lysis of LCMV-specific CTL clones and of primary immune spleen cells in vitro and in vivo. Confirming earlier reports, CTL were lysed in vitro when incubated with their specific Ag peptide; lysis was MHC restricted because T cell clones derived from allogeneic bone marrow chimeras that do not express the correct restriction element were not susceptible to mutual CTL lysis. The density of CTL cultures correlated with the degree of inactivation of CTL, indicating that CTL lysed each other mutually rather than committed suicide. To assess CTL-mediated lysis of CTL in vivo, mice were infected s.c. into the footpad with LCMV, and shortly before the CTL-dependent footpad swelling developed by day 6 to 7, specific peptide was injected locally. The regional lymph node (LN) was reduced in size, contained about 10 times fewer cells, and only 2% to 3% of the lytic activity when compared with several control LN. This drastic local effect was observed within a few hours and was accompanied by DNA fragmentation. Thus, in this model system, peptide loading of lymph node cells may lead to CTL-mediated cytotoxicity and death of T cells (including CD8+ effector cells and other LN cells) in vivo. These results may suggest that, during overwhelming virus infections, lysis of CTL passively loaded with relevant released peptides possibly may contribute to the impairment of immune responses.
Bacillus subtilis as a tool for vaccine development: from antigen factories to delivery vectors (2005)

Bacillus subtilis and some of its close relatives have a long history of industrial and biotechnological applications. Search for antigen expression systems based on recombinant B. subtilis strains sounds attractive both by the extensive genetic knowledge and the lack of an outer membrane, which simplify the secretion and purification of heterologous proteins. More recently, genetically modified B. subtilis spores have been described as indestructible delivery vehicles for vaccine antigens. Nonetheless both production and delivery of antigens by B. subtilis strains face some inherent obstacles, as unstable gene expression and reduced immunogenicity that, otherwise, can be overcome by already available gene technology approaches. In the present review we present the status of B. subtilis-based vaccine research, either as protein factories or delivery vectors, and discuss some alternatives for a better use of genetically modified strains.
Activation of ATF6 and an ATF6 DNA binding site by the endoplasmic reticulum stress response. (2000)

ATF6 is a member of the basic-leucine zipper family of transcription factors. It contains a transmembrane domain and is located in membranes of the endoplasmic reticulum. ATF6 has been implicated in the endoplasmic reticulum (ER) stress response pathway since it can activate expression of GRP78 and other genes induced by the ER stress response. ER stress appears to activate ATF6 by cleavage from the ER membrane and translocation to the nucleus. However, direct DNA binding by ATF6 had not been demonstrated. In this report, we have identified a consensus DNA binding sequence for ATF6. This site is related to but distinct from ATF1/CREB binding sites. The site was placed in a reporter gene and was specifically activated by ATF6 overexpression and was strongly induced by the ER stress response. A dominant negative form of ATF6 blocked ER stress induction of both ATF6 site and GRP78 reporter genes. We further found that GAL4-ATF6 could be activated by ER stress. These results demonstrate that ATF6 is a direct target of the ER stress response. A proximal sensor of the ER stress response, human IRE1 (hIRE1), was sufficient to activate the ATF6 reporter gene, while a dominant negative form of hIRE1 blocked ER stress activation, suggesting that hIRE1 is upstream of ATF6 in the ER stress signaling pathway.
Ascorbic Acid Enhances Differentiation of Embryonic Stem Cells Into Cardiac Myocytes (2003)

Ascorbic acid induces cardiac differentiation in ES cells. This study demonstrates the potential for chemically modifying the cardiac differentiation program of ES cells.
Simultaneous localization of cosmids and chromosome R-banding by fluorescence microscopy: application to regional mapping of human chromosome 11. (1990)

A technique for nonradioactive in situ hybridization on human metaphase chromosomes has been developed to localize human cosmid clones. The simple procedure using two fluorescent dyes (fluorescein and propidium iodide) allows the simultaneous identification of chromosomal R-bands and hybridization signal in a single screening of the slides. This technique has been used for rapid correlation of the genetic and physical map of chromosome 11q13-qter in the region of genes responsible for ataxia-telangiectasia and tuberous sclerosis.
Divergent Evolution in Metabotropic Glutamate Receptors (2004)

The metabotropic glutamate receptors (mGluRs) are G-protein-coupled receptors involved in the regulation of glutamatergic synapses. Surprisingly, the evolution-arily distant Drosophila mGluR shares a very similar pharmacological profile with its mammalian orthologues (mGlu2R and mGlu3R). Such a conservation in ligand recognition indicates a strong selective pressure during evolution to maintain the ligand recognition selectivity of mGluRs and suggests that structural constraints within the ligand binding pocket (LBP) would hinder divergent evolution. Here we report the identification of a new receptor homologous to mGluRs found in Anopheles gambiae, Apis mellifera, and Drosophila melanogaster genomes and called AmXR, HBmXR, and DmXR, respectively (the mXRs group). Sequence comparison associated with three-dimensional modeling of the LBP revealed that the residues contacting the amino acid moiety of glutamate (the alpha-COO(-) and NH(3)(+) groups) were conserved in mXRs, whereas the residues interacting with the gamma-carboxylic group were not. This suggested that the mXRs evolved to recognize an amino acid different from glutamate. The Drosophila cDNA encoding DmXR was isolated and found to be insensitive to glutamate or any other standard amino acid. However, a chimeric receptor with the heptahelical and intracellular domains of DmXR coupled to G-protein. We found that the DmX receptor was activated by a ligand containing an amino group, which was extracted from Drosophila head and from other insects (Anopheles and Schistocerca). No orthologue of mXR could be detected in Caenorhabditis elegans or human genomes. These data indicate that the LBP of the mGluRs has diverged in insects to recognize a new ligand.
Study of photopolymers. XXXIV. Etherification and esterification reactions of polymers with (o, m, or p)‐bromomethylnitrobenzene using the DBU method and the photochemical properties of the resulting polymers (1990)

Abstract Poly[4‐(4‐nitrobenzyloxy)styrene] was synthesized with a high degree of etherification by the reaction of poly(4‐hydroxystyrene) (PHST) with p ‐bromomethylnitrobenzene ( p ‐BMNB) using 1,8‐diazabicyclo‐[5,4,0]‐7‐undecene (DBU) in hexamethylphosphoramide (HMPA). Poly[4‐(3‐nitrobenzyloxy)styrene] and poly[4‐(2‐nitrobenzyloxy)styrene] were also prepared with a high degree of etherification by the corresponding reaction with m ‐ or o ‐BMNBs. However, the degrees of etherification of PHST with these BMNBs were relatively low when the reactions were carried out in other aprotic polar solvents such as DMF, DMSO, and N ‐methyl‐2‐pyrrolidone. On the other hand, poly(4‐introbenzyl methacrylate) (PPNBMA), poly(3‐nitrobenzyl methacrylate) (PMNBMA), and poly(2‐nitrobenzyl methacrylate) (PONBMA) were synthesized with a high degree of esterification by the reaction of poly(methacrylic acid) with the corresponding BMNBs using DBU in DMSO at 30°C. The photochemical properties of the resulting poly(nitrobenzyl methacrylate)s were examined, and it was found that the rates of photodecomposition of PPNBMA and PMNBMA were promoted by the addition of tributylamine and trifluoromethanesulfonic acid, respectively. However, the rate of photodecomposition of PONBMA was not affected by addition of the base or the acid.
The -104G nucleotide of the human CYP21 gene is important for CYP21 transcription activity and protein interaction (1998)

CYP21 gene encodes the steroid 21-hydroxylase (P450c21) that is involved in steroidogenesis in the adrenal cortex. Mutations occurring on CYP21 which convert it to the neighboring pseudogene, CYP21P, are found in patients with congenital adrenal hyperplasia (CAH), an autosomal recessive disease. We previously reported that the CYP21P pseudogene had lower transcription activity when compared with the active CYP21 gene. The sequences determining the basal transcription activity of the human CYP21 gene are located within the 166 bp region upstream from the transcriptional start site. Within this region, only 4 nucleotides are different between the active CYP21 and the CYP21P pseudogene; they are located at the -117, -104, -101 and -94 positions from the start site of the gene. Here, we report that the CYP21 gene-specific G nucleotide sequence at the -104 position is required for its basal transcription activity driven by the native TATA box of the human CYP21 gene. When this single nucleotide is changed to the CYP21P sequence, the basal transcription activity decreases by approximately 80% in transient transfection assay. In addition, our data from gel retardation assay show that this sequence is also critical for interaction with nuclear proteins from adrenal cells. These results therefore suggest that the single G sequence of the human CYP21 gene is crucial for the expression of its basal transcription activity, and this may be influenced by the interaction with specific nuclear proteins from the adrenal gland.
Exercise as a mediator of psychological and nutritional effects of testosterone therapy in HIV+ men (1998)

Exercise as a mediator of psychological and nutritional effects of testosterone therapy in HIV+ men. Med. Sci. Sports Exerc., Vol. 30, No. 6, pp. 811-817, 1998. Purpose: The purpose of this study was to determine whether exercise mediates the psychological and nutritional effects of testosterone therapy in men with symptomatic HIV illness, low serum testosterone, and clinical symptoms of hypogonadism. Methods: A 12-wk open trial of biweekly intramuscular testosterone injections was conducted, with 54 men completing the trial and exercise assessments. Most (71%) men were diagnosed with AIDS; 41% had a CD4 < 50. One-third of the men were diagnosed with major depression, and nearly half had some evidence of wasting. Twenty-nine men (54%) engaged in exercise (predominantly resistance training) during the trial. Exercisers did not differ from nonexercisers on any measure of psychological well being or nutritional status at baseline. Results: After 12 wk of testosterone treatment, those who exercised showed significant improvement in mood (Hamilton Rating Scale for Depression; HAM-D) and overall distress (Brief Symptom Inventory; BSI) (P < 0.000 for both), as well as a significant increase in body cell mass (P < 0.01) and lean body mass (mean increase of 2.6 kg; P < 0.000) as measured by bioelectric impedance analysis. In contrast, nonexercisers showed improvement on the HAM-D (P < 0.000), but not the BSI or measures of nutritional status. Conclusion: These findings indicate that exercise may be an important adjunct to testosterone therapy in the treatment of psychological distress and wasting symptoms in men with symptomatic HIV illness.
Analysis of Borderline‐Resistant Strains of Methicillin‐Resistant Staphylococcus aureus Using Polymerase Chain Reaction (1992)

Identification of methicillin-resistant Staphylococcus aureus by drug-susceptibility tests alone poses a serious problem, because a considerable number of clinical S. aureus isolates are borderline resistant to methicillin. To circumvent this problem, we have developed a quick and sensitive method of PCR amplification for the detection of mecA gene, which, coding for PBP2', is the specific genetic element of methicillin-resistant Staphylococcus aureus. This method made it possible to identify MRSA strains in a short time using as few as 30 cells as a starting material for template DNA. Using this method, we found that the strains of borderline methicillin-resistance could be accurately identified. We also found one S. aureus clinical strain, T3, which lacked mecA gene in spite of its resistance to methicillin.
Effect of Sustained Gene Delivery of Platelet‐Derived Growth Factor or Its Antagonist (PDGF‐1308) on Tissue‐Engineered Cementum (2004)

The results showed that continuous exposure to PDGF-A had an inhibitory effect on cementogenesis, possibly via the upregulation of OPN and subsequent enhancement of MNGCs at 3 weeks. On the other hand, Ad/PDGF-1308 inhibited mineralization of tissue-engineered cementum possibly due to the observed downregulation of BSP and OC and a persistence of stimulation of MNGCs. These findings suggest that continuous exogenous delivery of PDGF-A may delay mineral formation induced by cementoblasts, while PDGF is clearly required for mineral neogenesis.
VITAMIN D STATUS AND EARLY AGE-RELATED MACULAR DEGENERATION IN POSTMENOPAUSAL WOMEN (2011)

High serum 25(OH)D concentrations may protect against early AMD in women younger than 75 years.
Identification of HLA-A*0201-restricted CTL epitopes encoded by the tumor-specificMAGE-2 gene product (1997)

MAGE-2 is expressed in many tumors, including melanoma, laryngeal tumors, lung tumors and sarcomas, but not in healthy tissue, with the exception of testis. Thus, MAGE-2-derived peptides that bind to HLA class I molecules and elicit cytotoxic T lymphocyte (CTL) responses could be of significant therapeutic importance. In this study, we show that several MAGE-2-derived peptides bind with high affinity to HLA-A*0201. Three of them form complexes with HLA-A*0201 that are stable at 37 degrees C and are immunogenic in HLA-A*0201Kb transgenic mice. Moreover, CTLs against 2 of them (M2 112-120, and M2 157-166) specifically recognize cells that express both the MAGE-2 protein and HLA-A*0201Kb. These 2 peptides are processed and presented in the context of HLA-A*0201. Therefore, these peptides are candidate components in peptide-based vaccines for the treatment and prevention of several types of MAGE-2-expressing cancers.
Description of an Ectothermic TCR Coreceptor, CD8α, in Rainbow Trout (2000)

We have cloned the first CD8 alpha gene from an ectothermic source using a degenerate primer for Ig superfamily V domains. Similar to homologues in higher vertebrates, the rainbow trout CD8 alpha gene encodes a 204-aa mature protein composed of two extracellular domains including an Ig superfamily V domain and hinge region. Differing from mammalian CD8 alpha V domains, lower vertebrate (trout and chicken) sequences do not contain the extra cysteine residue (C strand) involved in the abnormal intrachain disulfide bridging within the CD8 alpha V domain of mice and rats. The trout membrane proximal hinge region contains the two essential cysteine residues involved in CD8 dimerization (alpha alpha or alpha beta) and threonine, serine, and proline residues which may be involved in multiple O-linked glycosylation events. Although the transmembrane region is well conserved in all CD8 alpha sequences analyzed to date, the putative trout cytoplasmic region differs and, in fact, lacks the consensus p56lck motif common to other CD8 alpha sequences. We then determined that the trout CD8 alpha genomic structure is similar to that of humans (six exons) but differs from that of mice (five exons). Additionally, Northern blotting and RT-PCR demonstrate that trout CD8 alpha is expressed at high levels within the thymus and at weaker levels in the spleen, kidney, intestine, and peripheral blood leukocytes. Finally, we show that trout CD8 alpha can be expressed on the surface of cells via transfection. Together, our results demonstrate that the basic structure and expression of CD8 alpha has been maintained for more than 400 million years of evolution.
The Diagnosis of Acute Intermittent Porphyria: Usefulness and Limitations of the Erythrocyte Uroporphyrinogen I Synthase Assay (1981)

In acute intermittent porphyria (AIP) the inherited metabolic defect residues in a partial enzyme deficiency at the uroporphyrinogen I synthase (URO-S) step of heme biosynthesis. Assay of this enzyme in erythrocytes is increasingly used for diagnosis of the genetic defect. Erythrocyte URO-S activity was measured by three laboratories in members of 14 AIP kindreds and found helpful for diagnosing the asymptomatic carrier state, since activity of the enzyme was usually distributed bimodally. However, a definite diagnosis of the carrier state was not always possible with this assay: approximately 7% of a total of 340 determinations were inconclusive. Repeat enzyme assays, enzyme assays by more than one laboratory, quantitative urine porphobilinogen determinations, and studies of other family members all aided in arriving at a firm diagnosis for most of those in whom a single erythrocyte URO-S measurement was inconclusive. Because the enzyme is unstable, blood specimens should be stored frozen if immediate assay is not possible.