gebhart/patrepeval huggingface dataset:
Regulation of Transcriptional Activation Domain Function by Ubiquitin (2001)

The ability of transcriptional activation domains (TADs) to signal ubiquitin-mediated proteolysis suggests an involvement of the ubiquitin-proteasome pathway in transcription. To probe this involvement, we asked how ubiquitylation regulates the activity of a transcription factor containing the VP16 TAD. We show that the VP16 TAD signals ubiquitylation through the Met30 ubiquitin-ligase and that Met30 is also required for the VP16 TAD to activate transcription. The requirement for Met30 in transcription is circumvented by fusion of ubiquitin to the VP16 activator, demonstrating that activator ubiquitylation is essential for transcriptional activation. We propose that ubiquitylation regulates TAD function by serving as a dual signal for activation and activator destruction.
A distinct type of sialyl Lewis X antigen defined by a novel monoclonal antibody is selectively expressed on helper memory T cells (1993)

A subset of human helper memory T cells is known to adhere to E- selectin expressed on cytokine-activated endothelial cells. However, sialyl Lex antigen, the carbohydrate ligand for E-selectin, has been hardly detectable on these cells, at least when typical anti-sialyl Lex antibodies were used for detection. One of the MoAbs (2F3, IgM), which we raised against a chemically synthesized sialyl Lex glycolipid preparation, is found to react selectively to CD4+ CD45RObright+ CD45RA- helper memory T cells among peripheral lymphocytes in healthy individuals. The specificity of the antibody is in clear contrast to that of the hitherto reported typical anti-sialyl Lex antibodies FH-6 and SNH-3. These classical anti-sialyl Lex antibodies were known to react to a subset of natural killer (NK) cells, but were not reactive with any particular subset of resting peripheral T or B cells of healthy individuals if the cells were not activated. On the other hand, the newly generated 2F3 antibody specifically reacted to helper memory T cells, and did not react to NK cells, B cells, or any T cells other than helper memory T cells. When tested against the sialyl Lex-active glycolipid antigen, the reactivity of 2F3 was not significantly different from that of the classical anti-sialyl Lex antibodies. But when tested against oligosaccharides prepared from cellular glycoproteins, 2F3 detected a distinct set of O-linked oligosaccharides, which were not reactive to the classical anti-sialyl Lex antibodies. Our results suggest that various molecular species of sialyl Lex antigens are present on carbohydrate side chains of cellular glycoproteins, and that helper memory T cells express a distinct type of sialyl Lex antigen that is defined by 2F3 but is not efficiently detected by other typical anti-sialyl Lex antibodies. Among cultured lymphocytic leukemia cells, the adult T-cell leukemia (ATL) cells preferentially expressed the 2F3-defined antigen, and acute lymphocytic leukemia cells rarely expressed the antigen. The cultured ATL cells expressing the 2F3-defined antigen showed a clear E-selectin-dependent adhesion to cytokin-activated endothelial cells, and the 2F3-defined sialyl Lex antigen served as a ligand for E-selectin as ascertained by the clear inhibition of adhesion with the 2F3 antibody.(ABSTRACT TRUNCATED AT 400 WORDS)
Interleukin-7 (IL-7) Knockout Mice. Implications for Lymphopoiesis and Organ-Specific Immunity (1998)

Interleukin-7 (IL-7) is produced by both immune and non-immune cells including stromal cell lines, B-cells, monocytes/macrophages, follicular dendritic cells, keratinocytes, and gut epithelial cells. The development of IL-7 knockout mice aided to elucidate the role of this multifaceted cytokine in lymphopoiesis. Additionally, IL-7 gene-deleted mice may represent an excellent model in order to define the functional role of locally secreted IL-7 in organ-specific immunity and in anti-microbial responses as well. For instance, analysis of IL-7 gene-deleted mice revealed reduced numbers of total T-lymphocytes with preservation of the CD4/CD8 ratio and increased ratio of alpha beta + T-cells compared to gamma delta + T-cells. Transition of pro-T-cells to pre-T-cells was impaired. Cell marker analysis of thymocytes in IL-7 -/- mice suggested that IL-7 may induce expression of as yet unidentified cytokine receptors, and that IL-7 may also be critically involved in T-cell differentiation. However, there are clear differences in the requirements of alpha beta or gamma delta T-cells for IL-7. In general, IL-7 appears to serve as the major growth and differentiation factor for gamma delta T-cells. IL-7 -/- mice are characterized by a block of maturation of V gamma 3low, CD24+ T-cells to V gamma 3high, CD24low T-cells. Thus, IL-7 does not only represent a 'maintenance factor', but rather a cytokine required for successful thymic and extrathymic development and maturation of gamma delta T-cells. gamma delta + intestinal intraepithelial lymphocytes (iIEL) are absent in IL-7 -/- animals. In contrast, alpha beta + iIEL can be detected in IL-7 gene-deleted animals, but not in gamma c, or in JAK-3 deficient mice suggesting that alternative cytokines may be involved in development of iIEL alpha beta + T-cells, but not necessarily for gamma delta T-cells. To this end, IL-7 has predominantly been studied in the context of B- and T-cell development. With the availability of IL-7 gene-deleted mice, the paracrine effects of IL-7, which may be secreted in vivo by non-immune cells including keratinocytes or gut epithelial cells, can now be critically examined.
Enantioselective Organocatalytic Conjugate Addition of N Heterocycles to α,β‐Unsaturated Aldehydes (2007)

Stickstoff hilft Stickstoff: Chirale Amine katalysieren die enantioselektive Addition von N-heterocyclischen Spezies an α,β-ungesättigte Verbindungen in hohen Ausbeuten und mit Enantioselektivitäten bis 94 % ee (siehe Schema; TMS=Trimethylsilyl). Die Zwischenstufen und Übergangszustände des Katalysezyklus wurden mithilfe von DFT-Rechnungen identifiziert. Supporting information for this article is available on the WWW under http://www.wiley-vch.de/contents/jc_2001/2007/z604854_s.pdf or from the author. Please note: The publisher is not responsible for the content or functionality of any supporting information supplied by the authors. Any queries (other than missing content) should be directed to the corresponding author for the article.
Bioenergetic cost of making an adenosine triphosphate molecule in animal mitochondria (2010)

The catalytic domain of the F-ATPase in mitochondria protrudes into the matrix of the organelle, and is attached to the membrane domain by central and peripheral stalks. Energy for the synthesis of ATP from ADP and phosphate is provided by the transmembrane proton-motive-force across the inner membrane, generated by respiration. The proton-motive force is coupled mechanically to ATP synthesis by the rotation at about 100 times per second of the central stalk and an attached ring of c-subunits in the membrane domain. Each c-subunit carries a glutamate exposed around the midpoint of the membrane on the external surface of the ring. The rotation is generated by protonation and deprotonation successively of each glutamate. Each 360° rotation produces three ATP molecules, and requires the translocation of one proton per glutamate by each c-subunit in the ring. In fungi, eubacteria, and plant chloroplasts, ring sizes of c(10)-c(15) subunits have been observed, implying that these enzymes need 3.3-5 protons to make each ATP, but until now no higher eukaryote has been examined. As shown here in the structure of the bovine F(1)-c-ring complex, the c-ring has eight c-subunits. As the sequences of c-subunits are identical throughout almost all vertebrates and are highly conserved in invertebrates, their F-ATPases probably contain c(8)-rings also. Therefore, in about 50,000 vertebrate species, and probably in many or all of the two million invertebrate species, 2.7 protons are required by the F-ATPase to make each ATP molecule.
Results of Screening Colonoscopy among Persons 40 to 49 Years of Age (2002)

Colonoscopic detection of colorectal cancer is uncommon in asymptomatic persons 40 to 49 years of age. The noncancerous lesions are equally distributed proximally and distally. The low yield of screening colonoscopy in this age group is consistent with current recommendations about the age at which to begin screening in persons at average risk.
Citizen Sensing, Social Signals, and Enriching Human Experience (2009)

In this article, I introduce the exciting paradigm of citizen sensing enabled by mobile sensors and human computing - that is, humans as citizens on the ubiquitous Web, acting as sensors and sharing their observations and views using mobile devices and Web 2.0 services.
Breast health. Challenges and promises. (1996)

There has been significant improvement in breast health care in the United States over the past few decades primarily due to advances in health research by diverse teams of basic scientists, physicians, pharmacists, industries, nurses, and social workers. This research has involved inquiries about fundamental biological alterations in breast cancer, differences in diagnostic modalities, and treatment options and various outcome studies. Increase in public awareness of breast cancer, an interest in women's health issues, advances in radiologic imaging, development of new chemotherapeutic agents and the availability of molecular genetic testings have brought remarkable opportunities to a new insight in breast cancer. These efforts have resulted in earlier detection and prolonged disease-free intervals, however, the overall survival time has remained the same. This is mainly attributable to the wide range of individual therapy for breast cancer, which responds to a range of disease curable by surgery alone to one refractory to treatment and marked by rapid metastatic progression. Challenges remain in fostering adequate funding for biomedical, as well as behavioral and social research. Attempts should also be made to promote clinical and population-based studies and to emphasize the value of effective delivery of health-care services to all women with benign, high risk, premalignant and malignant breast disease.
Thymidine phosphorylase induces carcinoma cell oxidative stress and promotes secretion of angiogenic factors. (2000)

Thymidine phosphorylase (TP) (E.C. 2.4.2.4), also known as platelet-derived endothelial cell growth factor, is a potent angiogenic factor. The expression of TP correlates with poor prognosis in a range of tumor types. 2-Deoxy-D-ribose-1-phosphate, a product of thymidine catabolism by TP, is a strongly reducing sugar that generates oxygen radical species during the early stages of protein glycation. We show that thymidine induces oxidative stress in TP-overexpressing carcinoma cells, promoting secretion of the stress-induced angiogenic factors vascular endothelial growth factor and interleukin-8, and inducing matrix metalloproteinase-1. Our findings outline a putative mechanism for TP-induced angiogenesis and identify novel targets for intervention.
Enzyme Applications in Detergency and in Manufacturing Industries (2003)

Applications of enzymes in industrial and food processes have undergone remarkable developments in several areas in the last 10-20 years: detergent, textile, grain wet milling, food, monogastric animal feed, pulp & paper, leather, natural polymer modifications, organic chemical synthesis, diagnostics, etc. Recombinant DNA technology and protein engineering are currently the main technologies in the design and production of new industrial enzymes, because they allow to reach high production yields of purified products at competitive costs and to design new enzymes with novel properties well adapted to industrial conditions. Of the major classes of enzymes, about 80% of current industrial enzymes are hydrolases (e.g., carbohydrolases, esterases) and are extracellularly produced for ease of downstream recovery after fermentation. In recent years, a few oxidoreductases have been commercially introduced (e.g., catalase, peroxidase, laccase) and even one lyase (pectate lyase for raw cotton bioscouring). In this review, we give an overview of enzyme applications in: detergency, textile and leather, which are the three areas that represent the majority of industrial enzyme uses. In detergency, enzymes contribute to the highly efficient removal of stains made of proteins, starch and grease from garments and fabrics, thereby enhancing the action of surfactants and improving the performance of the washing process. In the textile industry, cellulases, amylases, proteases, catalases, pectin lyase, peroxidase and laccase, have all become enzymes commonly used in textile mills, dyehouses and industrial laundries. In tanneries, application of proteases at the bating step to soften the hides and prepare them for tanning has been a key step in leather making ever since ancient times. A vast range of proteases is now available for soaking, bating and for unhairing raw hides, and of lipases for degreasing. Keywords: monogastric, amylases, cellulases, tanneries
Distinguishing Different DNA Heterozygotes by High-Resolution Melting (2005)

High-resolution melting was recently introduced as a technique to genotype single-nucleotide polymorphisms (SNPs) within small amplicons (1). This closed-tube method (including rapid-cycle PCR) can be completed in <15 min and does not require real-time PCR instruments (2), allele-specific PCR (3), or fluorescently labeled oligonucleotides (4)(5)(6). The process is made possible by heteroduplex-detecting DNA dyes that can be used at saturating concentrations without inhibiting PCR (7). Wild-type and homozygous mutant samples are distinguished by melting temperature ( T m) shifts. Heterozygous samples are best distinguished from homozygotes, not by T m, but by altered curve shape. Heterozygous samples produce heteroduplexes that melt at lower temperatures than homoduplexes. Melting curves of amplified heterozygotes include 2 homoduplexes and 2 heteroduplexes, giving a skewed composite melting curve easily distinguished from the curves for homozygotes by curve shape (1).

However, it was not clear whether different heterozygotes within the same amplicon could be distinguished from each other based on curve shape differences. Four different classes of SNPs have been defined based on the homo- and heteroduplexes that are produced after amplification (1). Because the heteroduplex mismatches of SNPs in different classes are different, their melting curves should be distinguishable if the resolution of the instrumentation is sufficient. It is also possible that different heterozygotes in the same class may be distinguishable. Although the mismatches are the same, nearest-neighbor stability parameters depend on the bases adjacent to the mismatches; therefore, the predicted stabilities are often different.

We selected DNA samples retrospectively from those submitted to ARUP Laboratories for standard clinical genotyping of HFE , factor V Leiden, and factor II polymorphisms. DNA was extracted from blood samples by use of the MagNa Pure instrument (Roche) and genotyped by use of adjacent hybridization probe (HybProbe™) methods (4)(5) on a LightCycler®. …
Topical Undecylenic Acid for Herpes Simplex Labialis: A Multicenter, Placebo‐Controlled Trial (1997)

A multicenter, patient-initiated, double-blind, placebo-controlled trial of 15% undecylenic acid cream was conducted with 573 patients with recurrent herpes labialis. Treatment was applied 5 or 6 times daily until crusting and then thrice daily until healing. Patients were assessed daily until 48 h after crusting and then every other day until healing. Undecylenic acid significantly reduced the incidence and duration of viral shedding and the duration and severity of itching but did not increase abortive episodes or reduce times to healing, crusting, or progression of lesion size. When treatment was initiated during the prodrome, the time to crusting was reduced (P = .02) and the area under the symptom-time curve for pain and tenderness was reduced, approaching statistical significance (P = .06). Active treatment was well tolerated but caused dysgeusia and local irritation. Undecylenic acid 15% cream reduces viral shedding in recurrent herpes labialis, but clinical benefits are minimal and largely restricted to patients initiating therapy during the prodrome.
Scavenging Byproducts in the Sulfoxide Glycosylation Reaction:  Application to the Synthesis of Ciclamycin 0 (1999)

We have developed a direct and efficient route for the synthesis of ciclamycin 0 using the sulfoxide glycosylation reaction to form the glycosidic linkages. In the course of completing the synthesis of ciclamycin 0, we developed new glycosylation conditions that improve the outcome of the sulfoxide reaction. The conditions involve the addition of agents that scavenge phenylsulfenyl triflate, a highly reactive byproduct that forms following activation of anomeric sulfoxides with triflic anhydride.
Mutation in CEP290 Discovered for Cat Model of Human Retinal Degeneration (2007)

A mutation in the CEP290 gene is reported in a cat pedigree segregating for autosomal recessive (AR) late-onset photoreceptor degeneration (rdAc). An initial screen of 39 candidate genes and genomic locations failed to detect linkage to cat rdAc. Linkage was ultimately established on cat B4 with 15 simple tandem repeat markers (logarithm of odds [LOD] range 4.83-15.53, Theta = 0.0), in a region demonstrating conserved synteny to human chromosome 12, 84.9-90.63 Mb. The sequence of 10 genes with feline retinal expression was examined in affected and unaffected individuals. A single-nucleotide polymorphism was characterized in intron 50 of CEP290 (IVS50 + 9T>G) that creates a strong canonical splice donor site, resulting in a 4-bp insertion and frameshift in the mRNA transcript, with subsequent introduction of a stop codon and premature truncation of the protein. A population genetic survey of 136 cats demonstrated that the rdAc mutation is in low frequency in Abyssinian populations (0.13, Sweden; 0.07, United States) and absent in breeds of non-Abyssinian heritage. Mutations in CEP290 have recently been shown to cause two human diseases, Joubert syndrome, a syndromic retinal degeneration, and Leber's congenital amaurosis, an AR early-onset retinal dystrophy. Human AR retinitis pigmentosa is among the most common causes of retinal degeneration and blindness, with no therapeutic intervention available. This identification of a large animal model for human retinal blindness offers considerable promise in developing gene-based therapies.
Differential effects of c-myb and c-fes antisense oligodeoxynucleotides on granulocytic differentiation of human myeloid leukemia HL60 cells. (1990)

To gain some insight into the role of c-myb and c-fes in myeloid differentiation, the authors have analyzed the ability of HL60 cells to differentiate in response to several different inducers after inhibition of c-myb and c-fes function. This function has been inhibited almost completely by using deoxynucleotides complementary to two 18-nucleotide sequences of c-myb and c-fes encoding mRNA. After 5 days in culture, in several separate experiments with different oligomer preparations, more than 90% growth inhibition was observed in c-myb antisense-treated HL60 cells. At this time, independent of the differentiation inducer used, c-myb antisense-treated HL60 cells differentiate only along the monocytic pathway, whereas in sense oligomer-treated cultures, retinoic acid and dimethyl sulfoxide induced granulocytic differentiation. No perturbation of the HL60 cell growth was observed after 5 days of treatment with antisense c-fes oligomer. However, induction to granulocytic differentiation by retinoic acid and dimethyl sulfoxide resulted in progressive cell death, whereas monocytic differentiation by other differentiation inducers was only marginally affected. These results suggest that granulocytic, unlike monocytic, differentiation requires c-myb-conditioned proliferation and the activity of the protein encoded by c-fes.
Significant differences in type IV pilin allele distribution among Pseudomonas aeruginosa isolates from cystic fibrosis (CF) versus non-CF patients (2004)

Type IV pili (TFP) are important colonization factors of the opportunistic pathogen Pseudomonas aeruginosa, involved in biofilm formation and attachment to host cells. This study undertook a comprehensive analysis of TFP alleles in more than 290 environmental, clinical, rectal and cystic fibrosis (CF) isolates of P. aeruginosa. Based on the results, a new system of nomenclature is proposed, in which P. aeruginosa TFP are divided into five distinct phylogenetic groups. Each pilin allele is stringently associated with characteristic, distinct accessory genes that allow the identification of the allele by specific PCR. The invariant association of the pilin and accessory genes implies horizontal transfer of the entire locus. Analysis of pilin allele distribution among isolates from various sources revealed a striking bias in the prevalence of isolates with group I pilin genes from CF compared with non-CF human sources (P<0.0001), suggesting this particular pilin type, which can be post-translationally modified by glycosylation via the action of TfpO (PilO), may confer a colonization or persistence advantage in the CF host. This allele was also predominant in paediatric CF isolates (29 of 43; 67.4 %), showing that this bias is apparent early in colonization. Group I pilins were also the most common type found in environmental isolates tested. To the authors' knowledge, this is the first example of a P. aeruginosa virulence factor allele that is strongly associated with CF isolates.
Aminopeptidases and Angiogenesis (2003)

A number of proteases, including matrix metalloproteinases and plasminogen activators, have been shown to be involved in angiogenesis. In addition, recent reports suggest that aminopeptidases also play roles in angiogenesis. These peptidases regulate the N-terminal modification of proteins and peptides required in processes such as maturation, activation, or degradation, and thereby they are related to a variety of physiological and pathological processes. At least three aminopeptidases are reported to be involved in angiogenesis, namely, type 2 methionine aminopeptidase, aminopeptidase N, and adipocyte-derived leucine aminopeptidase/puromycin-insensitive leucyl-specific aminopeptidase. This review will focus on the possible role of these aminopeptidases in angiogenesis.
Human Papillomavirus Vaccine: History, Immunology, Current Status, and Future Prospects (2005)

Southwest Gynecologic Oncology Associates, Inc., Albuquerque, New Mexico Correspondence: Luis Alfonso Padilla-Paz, MD, Southwest Gynecologic Oncology Associates, Inc., 500 Walter Street, NE, Suite 508, Albuquerque, NM 87102. E-mail: [email protected]
Express Specifications Warranties for Manufacturing Purchases: The Essential Contract Right in the Age of Quality (1986)

Previously, he was Senior Attorney at