gebhart/patrepeval huggingface dataset:
The interleukin 2 receptor (IL-2R): the IL-2R alpha subunit alters the function of the IL-2R beta subunit to enhance IL-2 binding and signaling by mechanisms that do not require binding of IL-2 to IL-2R alpha subunit. (1992)

Interleukin 2 (IL-2)-mediated signaling through its high-affinity receptor involves a complex interrelationship between IL-2 and two IL-2-binding chains, IL-2R alpha and beta chains. Previously with the reagents available it was difficult to define functional interactions between these two IL-2R subunits involved in IL-2 binding and signal transduction. To extend our understanding of the interplay between the two binding subunits we have done studies with the monoclonal antibody HIEI, which interferes with interaction of IL-2R alpha and beta chains (IL-2R alpha and IL-2R beta, respectively). Furthermore, we used two forms of IL-2, recombinant native IL-2 and F42A, an IL-2 analog (Phe-42----Ala substitution) that binds only to IL-2R beta. Analog F42A manifested 75-100% of the bioactivity of wild-type IL-2. This observation is inconsistent with the strict hierarchical IL-2-binding affinity conversion model previously proposed by Saito and coworkers [Saito Y., Sabe, H., Suzuki, N., Kondo, S., Ogura, T., Shimizu, A. & Honjo, T. (1988) J. Exp. Med. 168, 1563-1572] that predicted an ordered sequence of events in which IL-2 must first bind to IL-2R alpha before its interaction with IL-2R beta. Previous investigations using IL-2 variants were interpreted to show that IL-2R alpha merely acts to concentrate IL-2 to the cell surface and that no other meaningful interaction occurred between IL-2R alpha and IL-2R beta. However, our data are inconsistent with this view. We draw this conclusion on the basis of our observation that antibody HIEI, which reacts with an epitope of IL-2R alpha and interferes with interaction of this chain and IL-2R beta, inhibits the IL-2-dependent proliferative effects mediated by analog F42A. Furthermore, by blocking interaction of IL-2R alpha and IL-2R beta with the antibody HIEI, a decrease in the affinity of radiolabeled analog F42A for IL-2R beta was seen. In our proposed model IL-2R alpha contributes several functions to IL-2-mediated signaling through the high-affinity IL-2R. These functions include concentration of IL-2 within the two-dimensional surface of the plasma membrane as well as alteration of the functional capacity of IL-2R beta, an effect that does not require prior binding of IL-2R to IL-2R alpha. The IL-2R alpha-mediated augmentation of IL-2R beta functions involves affinity conversion of IL-2R beta, increasing its affinity for IL-2, and may involve facilitation of Il-2-mediated signaling after binding of IL-2 to this IL-2R beta.
Ligand-induced sequestering of branchpoint sequence allows conditional control of splicing (2008)

These findings provide the ability to control splicing pattern at will and should have important implications for basic, biotechnological, and biomedical research.
Animal Models of C-Reactive Protein (2014)

As the main theme of this special issue, CRP not only is an inflammatory marker but also has diverse biological functions associated with different diseases. To investigate CRP's physiologies and their relationship with human pathological significance, it is essential to use appropriate animal models for translational research. The most popular models for the study of CRP are transgenic mice. However, researchers should be careful when extrapolating the findings derived from these animal models. This review will discuss the current concerns on CRP transgenic mice and rabbits.
Predictors of Hypotension After Induction of General Anesthesia (2005)

Hypotension after induction of general anesthesia is a common event. In the current investigation, we sought to identify the predictors of clinically significant hypotension after the induction of general anesthesia. Computerized anesthesia records of 4096 patients undergoing general anesthesia were queried for arterial blood pressure (BP), demographic information, preoperative drug history, and anesthetic induction regimen. The median BP was determined preinduction and for 0-5 and 5-10 min postinduction of anesthesia. Hypotension was defined as either: mean arterial blood pressure (MAP) decrease of >40% and MAP <70 mm Hg or MAP <60 mm Hg. Overall, 9% of patients experienced severe hypotension 0-10 min postinduction of general anesthesia. Hypotension was more prevalent in the second half of the 0-10 min interval after anesthetic induction (P < 0.001). In 2406 patients with retrievable outcome data, prolonged postoperative stay and/or death was more common in patients with versus those without postinduction hypotension (13.3% and 8.6%, respectively, multivariate P < 0.02). Statistically significant multivariate predictors of hypotension 0-10 min after anesthetic induction included: ASA III-V, baseline MAP <70 mm Hg, age > or =50 yr, the use of propofol for induction of anesthesia, and increasing induction dosage of fentanyl. Smaller doses of propofol, etomidate, and thiopental were not associated with less hypotension. To avoid severe hypotension, alternatives to propofol anesthetic induction (e.g., etomidate) should be considered in patients older than 50 yr of age with ASA physical status > or =3. We conclude that it is advisable to avoid propofol induction in patients who present with baseline MAP <70 mm Hg.
Molecular cloning and expression of T11 cDNAs reveal a receptor-like structure on human T lymphocytes. (1987)

The T11 (CD2) sheep-erythrocyte-binding protein is a T-cell surface molecule involved in activation of T lymphocytes and thymocytes, including those lacking the T3-Ti antigen-receptor complex. The primary structure of T11 was deduced from protein microsequencing and cDNA cloning. The mature human protein appears to be divided into three domains: a hydrophilic 185 amino acid external domain bearing only limited homology to the T-cell surface protein T4 and the immunoglobulin kappa light chain variable region, a 25 amino acid hydrophobic transmembrane segment, and a 126 amino acid cytoplasmic domain rich in prolines and basic residues. Transfection of cDNAs encoding either the 1.7- or the 1.3-kilobase T11 mRNA into COS-1 cells resulted in expression of surface T11 epitopes as well as sheep-erythrocyte-binding capacity. The predicted structure is consistent with the possibility that T11 functions in signal transduction.
Structural Differences between the Lignin−Carbohydrate Complexes Present in Wood and in Chemical Pulps (2005)

Lignin-carbohydrate complexes (LCCs) were prepared in quantitative yield from spruce wood and from the corresponding kraft and oxygen-delignified pulps and were separated into different fractions on the basis of their carbohydrate composition. To obtain an understanding of the differences in lignin structure and reactivity within the various LCC fractions, thioacidolysis in combination with gas chromatography was used to quantify the content of beta-O-4 structures in the lignin. Periodate oxidation followed by determination of methanol was used to quantify the phenolic hydroxyl groups. Furthermore, size exclusion chromatography (SEC) of the thioacidolysis fractions was used to monitor any differences between the original molecular size distribution and that after the delignification processes. Characteristic differences between the various LCC fractions were observed, clearly indicating that two different forms of lignin are present in the wood fiber wall. These forms are linked to glucomannan and xylan, respectively. On pulping, the different LCCs have different reactivities. The xylan-linked lignin is to a large extent degraded, whereas the glucomannan-linked lignin undergoes a partial condensation to form more high molecular mass material. The latter seems to be rather unchanged during a subsequent oxygen-delignification stage. On the basis of these findings, a modified arrangement of the fiber wall polymers is suggested.
Trusting trusted hardware: towards a formal model for programmable secure coprocessors (1998)

Secure coprocessors provide a foundation for many exciting electronic commerce applications, as previous work [20, 21] has demonstrated. As our recent work [6, 13, 14] has explored, building a high-end secure coprocessor that can be easily programmed and deployed by a wide range of third parties can be an important step toward realizing this promise. But this step requires trusting trusted hardware -- and achieving this trust can be di#cult in the face of a problem and solution space that can be surprisingly complex and subtle. Formal methods provide one means to express, verify, and analyze such solutions (and would be required for such a solution to be certified at FIPS 140-1 Level 4). This paper discusses our current efforts to apply these principles to the architecture of our secure coprocessor. We present formal statements of the security goals our architecture needs to provide; we argue for correctness by enumerating the architectural properties from which these goals can be proven; we argue for conciseness by showing how eliminating properties causes the goals to fail; but we discuss how simpler versions of the architecture can satisfy weaker security goals. We view this work as the beginning of developing formal models to address the trust challenges arising from using trusted hardware for electronic commerce.
Reboxetine in clinical practice: a review. (2012)

Reboxetine is a selective noradrenaline reuptake inhibitor (NaRI), the first drug of a new antidepressant class. Reboxetine has been approved for the treatment of Major Depression in many European countries, but the application for approval was rejected in the United States. It has been found useful in Narcolepsy, ADHD, Panic Attack Disorder, treatment of depression in patients with Parkinson' s Disease. Moreover reboxetine has been proposed as an effective and safe therapeutic option for Cocaine Dependence Disorder. Despite a large number of studies have documented that reboxetine was equally effective in treating major depressive illness compared to other antidepressants, recent reports argue reboxetine to be ineffective and potentially harmful for the treatment of acute depression. Aim of the present review is to summarize and discuss the last literature findings, comparing risks and benefits of reboxetine usage in everyday clinical practice.
Identity of the cholesterol-raising factor from boiled coffee and its effects on liver function enzymes. (1994)

Boiled coffee contains an unidentified lipid that raises serum cholesterol. We studied the effects of the ingestion of coffee oil fractions of increasing purity in volunteers in order to identify the cholesterol-raising factor. In 15 volunteers who ingested 0.75 g/d of a non-triglyceride-fraction from coffee oil for 4 weeks, mean cholesterol increased by 48 mg/dl (1.2 mmol/l) relative to placebo. In contrast, a coffee oil stripped of the non-triglyceride lipids cafestol and kahweol had no effect. In three volunteers, purified cafestol (73 mg/d) plus kahweol (58 mg/d) increased cholesterol by 66 mg/dl (1.7 mmol/l) after 6 weeks. Oil from Robusta beans, which contains cafestol but negligible kahweol, also raised serum cholesterol. These findings show that cafestol is at least partly responsible for the cholesterol-raising effect of boiled coffee. Coffee oils and brews containing cafestol consistently increased serum triglycerides and alanine amino-transferase, and depressed serum creatinine and gamma-glutamyl-transferase (GGT). After withdrawal GGT activity rose above baseline. Norwegians who habitually consumed 5-9 cups of boiled coffee per day had higher serum cholesterol levels and lower GGT but no higher alanine aminotransferase activity than controls. Thus, serum cholesterol is raised by cafestol and possibly also kahweol, both natural components of coffee beans. The mechanism of action is unknown but is accompanied by alterations in liver function enzymes.
Recherches sur la nature du menthonitrile de Wallach (1949)

Abstract Le menthonitrile de Wallach s'est révélé être un mélange de deux corps présentant une isomérie de position de la double liaison. Le premier, —‐ désigné sous le nom de mentho‐citronellylnitrile — est le diméthyl‐3,7‐ène‐6‐caprylonitrile. Le second est le diméthyl‐3,7‐ène‐7‐caprylonitrile: il est identique au citronellylnitrile.
Scalable, behavior-based malware clustering (2009)

Anti-malware companies receive thousands of malware samples every day. To process this large quantity, a number of automated analysis tools were developed. These tools execute a malicious program in a controlled environment and produce reports that summarize the program’s actions. Of course, the problem of analyzing the reports still remains. Recently, researchers have started to explore automated clustering techniques that help to identify samples that exhibit similar behavior. This allows an analyst to discard reports of samples that have been seen before, while focusing on novel, interesting threats. Unfortunately, previous techniques do not scale well and frequently fail to generalize the observed activity well enough to recognize related malware. In this paper, we propose a scalable clustering approach to identify and group malware samples that exhibit similar behavior. For this, we first perform dynamic analysis to obtain the execution traces of malware programs. These execution traces are then generalized into behavioral profiles, which characterize the activity of a program in more abstract terms. The profiles serve as input to an efficient clustering algorithm that allows us to handle sample sets that are an order of magnitude larger than previous approaches. We have applied our system to real-world malware collections. The results demonstrate that our technique is able to recognize and group malware programs that behave similarly, achieving a better precision than previous approaches. To underline the scalability of the system, we clustered a set of more than 75 thousand samples in less than three hours. 1
Enantioselective Total Synthesis of Cylindramide (2004)

Key steps in the convergent enantioselective synthesis of the cytotoxic natural product (see structural formula) are tandem Michael addition/electrophilic trapping reactions, Sonogashira coupling, Julia–Kocienski olefination, and macrocyclization. Formation of the tetramic acid completed the synthesis.
Expression of human adenosine deaminase in mice transplanted with hemopoietic stem cells infected with amphotropic retroviruses. (1990)

Amphotropic recombinant retroviruses were generated carrying sequences encoding human adenosine deaminase (ADA). Transcription of the human ADA gene was under control of a hybrid long terminal repeat in which the enhancer from the Moloney murine leukemia virus was replaced by an enhancer from the F101 host-range mutant of polyoma virus. Hemopoietic stem cells in murine bone marrow were infected with this virus under defined culture conditions. As a result, 59% of day-12 colony forming unit spleen (CFU-S) stem cells became infected without any in vitro selection. Infected CFU-S were shown to express human ADA before transplantation and this expression sustained upon in vivo maturation. Mice transplanted with infected bone marrow exhibited human ADA expression in lymphoid, myeloid, and erythroid cell types. Moreover, human ADA expression persisted in secondary and tertiary transplanted recipients showing that human ADA-expressing cells were derived from pluripotent stem cells. These characteristics of our amphotropic viruses make them promising tools in gene therapy protocols for the treatment of severe combined immunodeficiency caused by ADA deficiency. In this respect it is also relevant that the viral vector that served as backbone for the ADA vector was previously shown to be nonleukemogenic.
Affinity, Kinetic, and Structural Study of the Interaction of 3-O-Sulfotransferase Isoform 1 with Heparan Sulfate (2006)

The 3-O-sulfonation of glucosamine residues in heparan sulfate (HS) by 3-O-sulfotransferase (3-OST) is a key substitution that is present in HS sequences of biological importance, in particular HS anticoagulant activity. Six different isoforms of 3-OST have been identified that exhibit different substrate specificity. In this paper the affinity and kinetics of the interaction between 3-O-sulfotransferase isoform 1 (3-OST-1) and HS have been examined using surface plasmon resonance (SPR). 3-OST-1 binds with micomolar affinity to HS (K(D) = 2.79 microM), and this interaction is apparently independent of the presence of the coenzyme, 3'-phosphoadenosine 5'-phosphosulfate (PAPS). A conformational change in the complex has also been detected, supporting data from previous studies. Selected 3-OST-1 mutants have provided valuable information of amino acid residues that participate in 3-OST-1 interaction with HS substrate and its catalytic activity. The results from this study contribute to understanding the substrate specificity among the 3-OST isoforms and in the mechanism of 3-OST-1-catalyzed biosynthesis of anticoagulant HS.
Requirement for MD-1 in cell surface expression of RP105/CD180 and B-cell responsiveness to lipopolysaccharide (2002)

RP105 is a B-cell surface molecule that has been recently assigned as CD180. RP105 ligation with an antibody induces B-cell activation in humans and mice, leading to proliferation and up-regulation of a costimulatory molecule, B7.2/CD86. RP105 is associated with an extracellular molecule, MD-1. RP105/MD-1 has structural similarity to Toll-like receptor 4 (TLR4)/MD-2. TLR4 signals a membrane constituent of Gram-negative bacteria, lipopolysaccharide (LPS). MD-2 is indispensable for TLR4-dependent LPS responses because cells expressing TLR4/MD-2, but not TLR4 alone, respond to LPS. RP105 also has a role in LPS responses because B cells lacking RP105 show hyporesponsiveness to LPS. Little is known, however, regarding whether MD-1 is important for RP105-dependent LPS responses, as MD-2 is for TLR4. To address the issue, we developed mice lacking MD-1 and generated monoclonal antibodies (mAbs) to the protein. MD-1-null mice showed impairment in LPS-induced B-cell proliferation, antibody production, and B7.2/CD86 up-regulation. These phenotypes are similar to those of RP105-null mice. The similarity was attributed to the absence of cell surface RP105 on MD-1-null B cells. MD-1 is indispensable for cell surface expression of RP105. A role for MD-1 in LPS responses was further studied with anti-mouse MD-1 mAbs. In contrast to highly mitogenic anti-RP105 mAbs, the mAbs to MD-1 were not mitogenic but antagonistic on LPS-induced B-cell proliferation and on B7.2 up-regulation. Collectively, MD-1 is important for RP105 with respect to B-cell surface expression and LPS recognition and signaling.
Revised Surveillance Case Definitions for HIV Infection Among Adults, Adolescents, and Children Aged (2008)

For adults and adolescents (i.e., persons aged >/=13 years), the human immunodeficiency virus (HIV) infection classification system and the surveillance case definitions for HIV infection and acquired immunodeficiency syndrome (AIDS) have been revised and combined into a single case definition for HIV infection. In addition, the HIV infection case definition for children aged <13 years and the AIDS case definition for children aged 18 months to <13 years have been revised. No changes have been made to the HIV infection classification system, the 24 AIDS-defining conditions for children aged <13 years, or the AIDS case definition for children aged <18 months. These case definitions are intended for public health surveillance only and not as a guide for clinical diagnosis. Public health surveillance data are used primarily for monitoring the HIV epidemic and for planning on a population level, not for making clinical decisions for individual patients. CDC and the Council of State and Territorial Epidemiologists recommend that all states and territories conduct case surveillance of HIV infection and AIDS using the 2008 surveillance case definitions, effective immediately.
Definition of a lipopolysaccharide-responsive element in the 5'-flanking regions of MuRantes and crg-2. (1994)

Macrophages are stimulated by lipopolysaccharide (LPS) of gram-negative organisms. The changes in LPS-stimulated macrophages include transcriptional activation of multiple immediate-early genes, which may contribute to the natural immunity to microorganisms. We have defined by deletion and mutational analysis LPS-responsive elements (LREs) in two chemokine genes, MuRantes and crg-2, which are activated in an immediate-early manner. LRE consists of two motifs, TCAYR, which is an AP-1 half site with two flanking bases, and (A/T) (G/C)NTTYC(A/T)NTTY, which resembles in part the interferon-stimulated responsive element (ISRE). The orientation of these two motifs relative to each other in MuRantes differed from that in crg-2. These two motifs are separated by 10 and 6 nonconsensus nucleotides in the MuRantes and crg-2 LREs, respectively. Stimulation of macrophage-like RAW 264.7 cells with alpha/beta interferon did not activate MuRantes, indicating that the ISRE-like motif in MuRantes does not have ISRE activity. Upon stimulation of RAW 264.7 cells with LPS, proteins capable of binding to LRE accumulate in the nuclei as measured by electrophoretic mobility shift assay. These LRE-binding proteins include c-Jun and CREB.
Immunogenicity Study of Globo H Analogues with Modification at the Reducing or Nonreducing End of the Tumor Antigen (2014)

Globo H-based therapeutic cancer vaccines have been tested in clinical trials for the treatment of late stage breast, ovarian, and prostate cancers. In this study, we explored Globo H analogue antigens with an attempt to enhance the antigenic properties in vaccine design. The Globo H analogues with modification at the reducing or nonreducing end were synthesized using chemoenzymatic methods, and these modified Globo H antigens were then conjugated with the carrier protein diphtheria toxoid cross-reactive material (CRM) 197 (DT), and combined with a glycolipid C34 as an adjuvant designed to induce a class switch to form the vaccine candidates. After Balb/c mice injection, the immune response was studied by a glycan array and the results showed that modification at the C-6 position of reducing end glucose of Globo H with the fluoro, azido, or phenyl group elicited IgG antibody response to specifically recognize Globo H (GH) and the GH-related epitopes, stage-specific embryonic antigen 3 (SSEA3) (also called Gb5) and stage-specific embryonic antigen 4 (SSEA4). However, only the modification of Globo H with the azido group at the C-6 position of the nonreducing end fucose could elicit a strong IgG immune response. Moreover, the antibodies induced by these vaccines were shown to recognize GH expressing tumor cells (MCF-7) and mediate the complement-dependent cell cytotoxicity against tumor cells. Our data suggest a new potential approach to cancer vaccine development.