gebhart/patrepeval huggingface dataset:
Analysis of Amide Bond Formation with an α-Hydroxy-β-amino Acid Derivative, 3-Amino-2-hydroxy-4-phenylbutanoic Acid, as an Acyl Component:  Byproduction of Homobislactone (2001)

In the synthesis of peptidomimetics containing alpha-hydroxy-beta-amino acid, the coupling of this N(beta)-protected beta-amino acid with amine components was generally performed without the protection of its alpha-hydroxyl group. However, the formation of dipeptides in low yield was often observed when sterically hindered amine components were used. Boc-Apns-OH [Apns: (2S,3S)-3-amino-2-hydroxy-4-phenylbutanoic acid, allophenylnorstatine] (6), which is one of such beta-amino acid derivatives, is intensively employed as a core structure in the development of HIV-1 protease inhibitors. There have been no precise studies, to date, that have examined amide bond formation with alpha-hydroxy-beta-amino acid derivatives as an acyl component. To determine the cause of this low-yield reaction, we studied the amide bond formation focusing on the activation step of N(beta)-protected alpha-hydroxy-beta-amino acid by using a model coupling reaction between 6 and H-Dmt-OR [Dmt: (R)-5,5-dimethyl-1,3-thiazolidine-4-carboxylic acid] (7). A significant amount of homobislactone 9 was formed through the activation of the carboxyl group of 6 to the benzotriazole-type active esters such as OBt and OAt. In addition, this homobislactone formation was markedly increased in the presence of a catalytic amount of a base, which exhibited good correlation with the low yield of the amide bond formation, suggesting that homobislactone formation is one major reason for the low yield of the amide bond formation. Moreover, homobislactones were also formed in other derivatives of the N(beta)-protected alpha-hydroxy-beta-amino acid, suggesting a common feature of this type of amino acids. The use of a strong activation method like EDC--HOAt without base addition enhanced amide bond formation, although a small amount of homobislactone may be formed during the coupling reaction.
A Novel CCK-8/GLP-1 Hybrid Peptide Exhibiting Prominent Insulinotropic, Glucose-Lowering, and Satiety Actions With Significant Therapeutic Potential in High-Fat–Fed Mice (2015)

Glucagon-like peptide-1 (GLP-1) and cholecystokinin (CCK) exert important complementary beneficial metabolic effects. This study assessed the biological actions and therapeutic utility of a novel (pGlu-Gln)-CCK-8/exendin-4 hybrid peptide compared with the stable GLP-1 and CCK mimetics exendin-4 and (pGlu-Gln)-CCK-8, respectively. All peptides significantly enhanced in vitro insulin secretion. Administration of the peptides, except (pGlu-Gln)-CCK-8 alone, in combination with glucose significantly lowered plasma glucose and increased plasma insulin in mice. All treatments elicited appetite-suppressive effects. Twice-daily administration of the novel (pGlu-Gln)-CCK-8/exendin-4 hybrid, (pGlu-Gln)-CCK-8 alone, or (pGlu-Gln)-CCK-8 in combination with exendin-4 for 21 days to high-fat-fed mice significantly decreased energy intake, body weight, and circulating plasma glucose. HbA1c was reduced in the (pGlu-Gln)-CCK-8/exendin-4 hybrid and combined parent peptide treatment groups. Glucose tolerance and insulin sensitivity also were improved by all treatment modalities. Interestingly, locomotor activity was decreased in the hybrid peptide group, and these mice also exhibited reductions in circulating triglyceride and cholesterol levels. Pancreatic islet number and area, as well β-cell area and insulinotropic responsiveness, were dramatically improved by all treatments. These studies highlight the clear potential of dual activation of GLP-1 and CCK1 receptors for the treatment of type 2 diabetes.
Lithographic strategies for 0.35-μm poly gates for random logic applications (1994)

DUV lithography using wet developable resists can be used for the poly gate definition of 0.35micrometers CMOS processes. Four years ago, we demonstrated a resolution of 0.3micrometers L/S obtained with Shipley XP 89131 resist. Nevertheless, in order to make this and other resist processes suitable for real device applications, several problems had to be overcome. First, reflective notching and linewidth variations over steps turned out to be an important limitation. Some strategy to reduce this sensitivity to reflections has to be applied. Furthermore, in order to obtain a stable and reproducible lithographic process, process latitudes should be wide. Furthermore, a comparison between positive tone and negative tone resists is made with respect to their suitability for poly gate patterning. It was observed that negatively sloped resist profiles, as a result of the use of negative tone resists, create a controllability problem during in-line SEM inspections, and such profiles result in positively sloped poly profiles after etching. Positive tone resists have positively sloped resist profiles, but they require the use of a bright field mask, and hence reflections are much more of a problem. Also, positive tone resist are more sensitive to the delay effects.
Photoaffinity labeling of human serum vitamin D binding protein and chemical cleavages of the labeled protein: identification of an 11.5-KDa peptide containing the putative 25-hydroxyvitamin D3 binding site (1991)

In this paper, we describe photoaffinity labeling and related studies of human serum vitamin D binding protein (hDBP) with 25-hydroxyvitamin D3 3 beta-3'-[N-(4-azido-2-nitrophenyl)amino]propyl ether (25-ANE) and its radiolabeled counterpart, i.e., 25-hydroxyvitamin D3 3 beta-3'-[N-(4-azido-2-nitro-[3,5-3H]phenyl)amino]propyl ether (3H-25-ANE) (Ray et al., 1986, 1991). We have carried out studies to demonstrate that (1) 25-ANE competes with 25-OH-D3 for the binding site of the latter in hDBP and (2) 3H-25-ANE is capable of covalently labeling the hDBP molecule when exposed to UV light. Treatment of a sample of purified hDBP, labeled with 3H-25-ANE, with BNPS-skatole produced two Coomassie Blue stained peptide fragments, and the majority of the radioactivity was associated with the smaller of the two peptide fragments (16.5 kDa). On the other hand, cleavage of the labeled protein with cyanogen bromide produced a peptide (11.5 kDa) containing most of the covalently attached radioactivity. Considering the primary amino acid structure of hDBP, this peptide fragment (11.5 kDa) represents the N-terminus through residue 108 of the intact protein. Thus, our results tentatively identify this segment of the protein containing the binding pocket for 25-OH-D3.
Phase I Study of U3-1287, a Fully Human Anti-HER3 Monoclonal Antibody, in Patients with Advanced Solid Tumors (2013)

U3-1287 treatment was well tolerated, and some evidence of disease stabilization was observed. Pharmacokinetic data support U3-1287 dosing of 9 to 20 mg/kg every 2 to 3 weeks. Combination studies of U3-1287 are ongoing.
Upregulation of c- MYC in cis through a Large Chromatin Loop Linked to a Cancer Risk-Associated Single-Nucleotide Polymorphism in Colorectal Cancer Cells (2010)

Genome-wide association studies have mapped many single-nucleotide polymorphisms (SNPs) that are linked to cancer risk, but the mechanism by which most SNPs promote cancer remains undefined. The rs6983267 SNP at 8q24 has been associated with many cancers, yet the SNP falls 335 kb from the nearest gene, c-MYC. We show that the beta-catenin-TCF4 transcription factor complex binds preferentially to the cancer risk-associated rs6983267(G) allele in colon cancer cells. We also show that the rs6983267 SNP has enhancer-related histone marks and can form a 335-kb chromatin loop to interact with the c-MYC promoter. Finally, we show that the SNP has no effect on the efficiency of chromatin looping to the c-MYC promoter but that the cancer risk-associated SNP enhances the expression of the linked c-MYC allele. Thus, cancer risk is a direct consequence of elevated c-MYC expression from increased distal enhancer activity and not from reorganization/creation of the large chromatin loop. The findings of these studies support a mechanism for intergenic SNPs that can promote cancer through the regulation of distal genes by utilizing preexisting large chromatin loops.
Transcatheter umbrella closure of congenital heart defects. (1987)

Between October 1984 and September 1986, we attempted transcatheter umbrella closure, using the Rashkind PDA occluder, of 12 congenital or postoperative cardiovascular defects (other than patent ductus arteriosus [PDA]) in 11 patients. In each, we used the umbrella for closure because the defect was too short and/or too large to close with conventional transcatheter methods. The defects included three post-Glenn venous communications (superior vena cava-right atrium, n = 2; azygos vein to inferior vena cava), four congenital "interatrial defects" producing cyanosis ("coronary sinus" septal defect, left superior vena cava to left atrium, patent foramen ovale, left inferior vena cava to left atrium), and five non-PDA systemic-to-pulmonary arterial communications (two congenital and three postoperative). Ten of 12 defects were embolized successfully; nine had complete or subtotal closure, and one was partially closed. The first attempted closure resulted in embolization of a 12 mm device to a lower-lobe pulmonary artery, without clinical sequelae. No other complications occurred. Clinical improvement was most dramatic in those patients whose cyanosis was relieved and less obvious when pulmonary blood flow was reduced. The Rashkind umbrella device, originally designed for closure of PDA, considerably expands the list of congenital or operative defects that can be closed nonsurgically.
Deoxyribozyme-Based Half-Adder (2003)

We have constructed a solution-phase array of three deoxyribozyme-based logic gates that behaves as a half-adder. Two deoxyribozymes mimic i(1)ANDNOTi(2) and i(2)ANDNOTi(1) gates that cleave a fluorogenic substrate, reporting through an increase in fluorescence emission at 570 nm. The third deoxyribozyme mimics an i(1)ANDi(2) gate and cleaves the other fluorogenic substrate, reporting through an increase in fluorescence emission at 520 nm. Together, this system represents the first example of a decision-making enzymatic network with two inputs and two outputs. Similar systems could be applied to control autonomous therapeutic and diagnostic devices.
Antibody-Dependent Natural Killer Cell–Mediated Cytotoxicity Engendered by a Kinase-Inactive Human HER2 Adenovirus-Based Vaccination Mediates Resistance to Breast Tumors (2010)

Cancer vaccines may have applications in the therapy and prevention of mammary carcinoma. To investigate such applications, we constructed a recombinant adenoviral vaccine expressing a kinase-inactive mutant form of human HER2 and introduced this into BALB/c wild-type (WT) or HER2 transgenic mice. Here, we report contributions by antibody responses and natural killer (NK) cells in tumor protection in this model. One i.p. vaccination protected WT mice from the HER2-expressing mouse carcinoma D2F2/E2. Half of the HER2 transgenic mice were protected fully and long term after preventive vaccination. Tumor growth in mice that eventually developed neoplastic lesions was delayed. Protection in WT and HER2 transgenic mice was associated with high or low levels of IgG2a antibodies, respectively, whereas CTLs were observed in WT but not in HER2 transgenic mice. Depleting CD4(+) or CD8(+) cells in vaccinated WT mice had limited effects, suggesting that protection was largely independent of CD4(+) or CD8(+) T cells. In contrast, antibody-mediated tumor rejection seemed to contribute significantly based on a loss of protection in mice deficient for Fc-γ RI/III or B cells. Further, a role for antibody-dependent cellular cytotoxicity (ADCC) mediated by NK cells was indicated by evidence that vaccine protection could be abolished by in vivo depletion of NK cells. Lastly, NK cells and immune sera purified from WT or HER2 transgenic mice exhibited efficient ADCC of HER2-expressing tumor cells in vitro. Our findings define a critical requirement for NK cells in vaccine-induced protection against HER2-expressing tumors.
Emeheterone: Synthesis and Structural Revision (1990)

Emeheterone, a fungal metabolite, was synthesized from DL-phenylalanine.aased on the results of this synthesis.the structure of emeheterone was redetermined as 3.6-dlbenzyl-2-hydroxy-5-methoxypyrazine 4-oxide.In a prevzoui paper, the uxzdation of 2-hydroxy-3.6-dilsobutyl-5-mettioxypyraaineby permalelc acid ( P M A ) was found to occur at N-1 and the synthesis of 2-hydroxy-3.6-d~isobutyl-5-inctl10xypyrnzine4-oxlde was conducted in three steps from 2 -l ~y d r o x y -3 .6 -d ~i s o b u t y l -5 -m e t t i o x y p y r a z i .~ Based on the results.3.6-dlbenryl-2hydroxy-5-methoxypyraz~ne 1 !l! -end 4-oxldes !Z) were synthes~zed i n the present
FGF4 and Retinoic Acid Direct Differentiation of hESCs into PDX1-Expressing Foregut Endoderm in a Time- and Concentration-Dependent Manner (2009)

In conclusion, we show that RA and FGF4 jointly direct differentiation of PDX1(+) foregut endoderm in a robust and efficient manner. RA signaling mediated by the early induction of RARbeta through AA/Wnt3a is required for PDX1 expression. Part of RA's activity is mediated by FGF signaling.
DEFICIT IRRIGATION INFLUENCES YIELD AND LYCOPENE CONTENT OF DIPLOID AND TRIPLOID WATERMELON (2003)

Many vegetable production regions in the southwestern US are strictly regulated on water use.In addition, demand for high quality and nutritious vegetables has increased.This study was performed to explore the effects of deficit irrigation on yield, fruit quality and lycopene content of red-fleshed diploid and triploid watermelon (Citrullus lanatus (Thunb) Matsum & Nakai) cultivars.Irrigation treatments were 1.0, 0.75 and 0.5 evapotranspiration (ET) rates.Cultivars used were 'Summer Flavor 710', 'RWW 8036', 'Allsweet', 'Sugarlee', and 'SWD 7302' (diploids) and 'Summer Sweet 5244', 'SWT 8706', 'Sugar Time', and 'Tri-X-Sunrise' (triploids).Total water applied through a subsurface drip system was 395, 298 and 173 mm, for the 1.0, 0.75 and 0.50 ET, respectively.Total yields were highest at 1.0 ET (53.9 t ha -1 ) compared with 0.5 ET (26.8 t ha -1 ).Triploids had a 34% higher total yield and fewer culls (2%) compared with diploid cultivars (25%).Highest yields were obtained for 'Sunrise', 'SWT 8706', and 'SWD 7302'.Highest soluble solid content was measured for 'Sugar Time' (13.4%) and was significantly higher than other cultivars (range 9.7-11.0%).Triploid cultivars had more firm flesh, compared with diploids (12.0 vs. 9.9 N).Lycopene content increased slightly with maturity (55.8 to 60.2 :g g -1 fw), and was significantly higher at 0.75 ET than 1.0 ET in melons at ripe and overripe maturity stages.Lycopene content averaged over all treatments was 60-66 :g g -1 fw for triploids and 45 to 80 µg g -1 fw for diploid fruit.
Structure of the human lipoprotein-associated coagulation inhibitor gene. Intro/exon gene organization and localization of the gene to chromosome 2. (1991)

Lipoprotein-associated coagulation inhibitor (LACI) is a multivalent, Kunitz-type proteinase inhibitor which appears to play an important role in the regulation of hemostasis. LACI directly inhibits factor Xa, and, in a Xa-dependent fashion, also inhibits the factor VIIa-tissue factor catalytic complex. Hybridization of a LACI cDNA probe to DNA isolated from a panel of human-mouse somatic cell hybrids containing different human chromosomes localized the human LACI gene to chromosome 2. In situ hybridization to metaphase chromosomes further mapped the gene to the region 2q31----2q32.1. Exons of the human LACI gene were cloned from genomic or chromosome 2-specific phage libraries and sequenced, including approximately 500 base pairs of 5' upstream DNA. The 5' DNA did not contain a prototypical TATAA box or CCAAT sequence, and attempts to identify a unique site for the initiation of transcription were unsuccessful in that primer extension and S1 nuclease protection analysis indicate multiple transcription initiation sites for LACI messages. Comparing the gene sequence with LACI cDNA sequences indicates that the gene contains nine exons and that alternative splicing can occur, resulting in the absence of exon 2 in the 5' untranslated region of some messages. The three Kunitz domains in LACI are encoded on separate exons. Introns which interrupt coding sequences all occur in the same codon phase interrupting the first and second bases of the codon triplets. The data are consistent with LACI evolving by a combination of gene segment duplications and exon shuffling.
КІЛЬКІСНА ОЦІНКА КОЛИВАНЬ ФІНАНСОВИХ ПОТОКІВ (2014)

The article is devoted to development of method of analysis and prognostication of risk of individual financial streams on an enterprise. It is lighted basic principles of construction of method, a mathematical vehicle and example of application of method of analysis of risk of individual financial stream is pointed.
The Synthesis and Conformation of Dihydroxypiperidinyl Derivates of Nucleobases as Novel Iminosugar Nucleoside Analogs (2011)

Abstract An optimized method for the synthesis of an important chiral scaffold, (3 S ,4 R ,5 R )‐1‐ N ‐Boc‐3,4‐isopropylidene‐3,4,5‐trihydroxypiperidine, was developed. Using this intermediate, the preparation of various chiral aminodihydroxypiperidines and their transformation into a series of non‐glycosidic, six‐membered azanucleosides was accomplished. NMR conformation analysis of the prepared piperidine azanucleosides revealed a preference for the chair conformation, with the nucleobase fixed in the equatorial position in all cases.
How super is superoxide? (1981)

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTHow super is superoxide?Donald T. Sawyer and Joan S. ValentineCite this: Acc. Chem. Res. 1981, 14, 12, 393–400Publication Date (Print):December 1, 1981Publication History Published online1 May 2002Published inissue 1 December 1981https://pubs.acs.org/doi/10.1021/ar00072a005https://doi.org/10.1021/ar00072a005research-articleACS PublicationsRequest reuse permissionsArticle Views5692Altmetric-Citations1156LEARN ABOUT THESE METRICSArticle Views are the COUNTER-compliant sum of full text article downloads since November 2008 (both PDF and HTML) across all institutions and individuals. These metrics are regularly updated to reflect usage leading up to the last few days.Citations are the number of other articles citing this article, calculated by Crossref and updated daily. Find more information about Crossref citation counts.The Altmetric Attention Score is a quantitative measure of the attention that a research article has received online. Clicking on the donut icon will load a page at altmetric.com with additional details about the score and the social media presence for the given article. Find more information on the Altmetric Attention Score and how the score is calculated. Share Add toView InAdd Full Text with ReferenceAdd Description ExportRISCitationCitation and abstractCitation and referencesMore Options Share onFacebookTwitterWechatLinked InRedditEmail Other access optionsGet e-Alertsclose Get e-Alerts
CUSHAW: a CUDA compatible short read aligner to large genomes based on the Burrows–Wheeler transform (2012)

http://cushaw.sourceforge.net
Specific Mutations Induced by Triplex-Forming Oligonucleotides in Mice (2000)

Triplex-forming oligonucleotides (TFOs) recognize and bind to specific duplex DNA sequences and have been used extensively to modify gene function in cells. Although germ line mutations can be incorporated by means of embryonic stem cell technology, little progress has been made toward introducing mutations in somatic cells of living organisms. Here we demonstrate that TFOs can induce mutations at specific genomic sites in somatic cells of adult mice. Mutation detection was facilitated by the use of transgenic mice bearing chromosomal copies of the supF and cII reporter genes. Mice treated with a supF-targeted TFO displayed about fivefold greater mutation frequencies in the supF gene compared with mice treated with a scrambled sequence control oligomer. No mutagenesis was detected in the control gene (cII) with either oligonucleotide. These results demonstrate that site-specific, TFO-directed genome modification can be accomplished in intact animals.
Permeability of Antidiuretic Hormone and Other Hormones Through the Dialysis Membrane in Patients Undergoing Chronic Hemodialysis (1977)

In eight patients undergoing chronic hemodialysis, ultrafiltration was performed for 1 h in each patient. The concentration of urea nitrogen, creatinine, ADH, cortisol, GH, prolactin and TSH was measured in plasma and the filtering solution, and the permeability of each substance was determined. The plasma concentration of ADH coincided with that of the filtering solution, and no significant difference was noted between the permeability of creating and ADH. In contrast, cortisol, GH, prolactin and TSH were not detected in the filtering solution. Chromatographic study showed that ADH in the filtering solution coincided with synthetic ADH. From a comparison of the permeability with the molecular weight, it was suggested that ADH in the blood exists in free form without binding with plasma proteins or neurophysin.
Fish Consumption and Risk of Sudden Cardiac Death (1998)

These prospective data suggest that consumption of fish at least once per week may reduce the risk of sudden cardiac death in men.
Initial recruitment of neutrophils to alveolar structures in acute lung injury (1991)

The adult respiratory distress syndrome and bacterial pneumonia are both characterized by an influx of neutrophils into the lung. The neutrophil has been implicated as having a "pathological" role in adult respiratory distress syndrome, in contrast to its role in bacterial pneumonia. We hypothesized that processes resulting in neutrophil recruitment to the lung are distinct, depending on whether the inflammatory stimulus arises in the intravascular or the alveolar compartment of the lung. Anesthetized sheep with lung lymph fistulas were utilized to access the three compartments of the lung relevant to studies of transpulmonary neutrophil migration. Serum, lung lymph, and bronchoalveolar lavage fluid were studied for neutrophil influx and chemotactic activity before and after administration of endotoxin by either an intravascular or inhaled alveolar route. Both groups developed significant neutrophil influx into the lymph and bronchoalveolar lavage fluid by 3 h postendotoxin. Those animals receiving intravascular endotoxin developed chemotactic gradients opposing neutrophil migration into the lung in contrast to animals receiving alveolar endotoxin, suggesting that neutrophil influx into the lung occurs by random migration.