gebhart/patrepeval huggingface dataset:
Pleiotropic insulin signals are engaged by multisite phosphorylation of IRS-1. (1993)

IRS-1 (insulin receptor substrate 1) is a principal insulin receptor substrate that undergoes tyrosine phosphorylation during insulin stimulation. It contains over 20 potential tyrosine phosphorylation sites, and we suspect that multiple insulin signals are enabled when the activated insulin receptor kinase phosphorylates several of them. Tyrosine-phosphorylated IRS-1 binds specifically to various cellular proteins containing Src homology 2 (SH2) domains (SH2 proteins). We identified some of the tyrosine residues of IRS-1 that undergo insulin-stimulated phosphorylation by the purified insulin receptor and in intact cells during insulin stimulation. Automated sequencing and manual radiosequencing revealed the phosphorylation of tyrosine residues 460, 608, 628, 895, 939, 987, 1172, and 1222; additional sites remain to be identified. Immobilized SH2 domains from the 85-kDa regulatory subunit (p85 alpha) of the phosphatidylinositol 3'-kinase bind preferentially to tryptic phosphopeptides containing Tyr(P)-608 and Tyr(P)-939. By contrast, the SH2 domain in GRB2 and the amino-terminal SH2 domain in SHPTP2 (Syp) specifically bind to Tyr(P)-895 and Tyr(P)-1172, respectively. These results confirm the p85 alpha recognizes YMXM motifs and suggest that GRB2 prefers a phosphorylated YVNI motif, whereas SHPTP2 (Syp) binds to a phosphorylated YIDL motif. These results extend the notion that IRS-1 is a multisite docking protein that engages various downstream regulatory elements during insulin signal transmission.
Synthesis of Optically Active Monoacid Side‐Chains of Cephalotaxus Alkaloids (2008)

Abstract The general preparation of enantiopure monoacid side‐chains of several esters of cephalotaxine is described. The strategy, similar to Weinreb's approach to the synthesis of deoxyharringtonine, used as key intermediate the chiral nonracemic epoxide 11a prepared from the commercially available monomethyl itaconate ( 8 ). The key step of the strategy was the ring‐opening of the epoxide 11a by using different organocuprate nucleophiles. Hydrogenolysis as the final step gave the monacid side‐chains of the corresponding esters of cephalotaxine in moderate to good overall yields from epoxide 11a .(© Wiley‐VCH Verlag GmbH &amp; Co. KGaA, 69451 Weinheim, Germany, 2009)
Answer keys to review questions (2009)

Extract Here we provide brief answers to the review questions presented at the end of each chapter. Chapter 1: Introduction and overview ... Chapter 2: Special relativity: the basics ... Chapter 3: Special relativity: the geometric formulation ... Chapter 4: The principle of equivalence ... Chapter 5: Metric description of a curved space ... Chapter 6: GR as a geometric theory of gravity – I ... Chapter 7: Spherically symmetric spacetime – GR tests ... Chapter 8: Black holes ... Chapter 9: The homogeneous and isotropic universe ... Chapter 10: The expanding universe and thermal relics ... Chapter 11: Inflation and the accelerating universe ... Chapter 12: Tensors in special relativity ... Chapter 13: Tensors in general relativity ... Chapter 14: GR as a geometric theory of gravity – II ... Chapter 15: Linearized theory and gravitational waves
The generation of human natural killer cells from CD34+/DR- primitive progenitors in long-term bone marrow culture (1992)

We have adapted the stroma-dependent long-term bone marrow culture (LTBMC) system to study the development of human natural killer cells (NK) from the CD34+/HLA-DR- (CD34+/DR-) BM mononuclear cell (BMMNC) population. The CD34+/DR- population does not express any known antigens associated with myeloid or lymphoid lineage and has been shown by us and others to contain primitive hematopoietic progenitors capable of both self-renewal and differentiation to myeloid lineage. CD34+/DR- cells obtained from normal human BM by fluorescence-activated cell sorting were plated on allogeneic, irradiated BM stromal layers. After 5 weeks of culture in the presence of media containing recombinant interleukin-2 and human serum, 147- +/- 21-fold expansion of cells with the morphologic appearance of large granular lymphocytes was observed. Cultured cells (84.8% +/- 1.5%) expressed the characteristic CD56+/CD3- phenotype of NK. A proportion of CD56+/CD3- cells expressed other markers of lymphoid lineage that have been associated with mature NK, including CD2 (7.8% +/- 1.2%), CD7 (19.5% +/- 2.8), CD8 (3.1% +/- 1.0%), and CD16 (4.5% +/- 1.3%). The cultured cells did not express other antigens associated with T-lymphocyte (CD3, CD5, T-cell receptor [TCR] alpha/beta and TCR gamma/delta), B-lymphocyte (CD19), myeloid (MY8, CD33, and CD71), or monocytoid (CD14 and CD15) lineage and did not express the CD34 antigen associated with hematopoietic progenitors present on the starting population. This NK population was cytotoxic against both K562 (E:T 20:1; 79% +/- 1.9%) and Raji (E:T 20:1; 38% +/- 5.7%) target cell lines. The NK progenitor frequency in the CD34+/DR- cell population determined by limiting dilution of CD34+DR- on stromal layers followed by a functional chromium release assay against K562 targets was 1:169 +/- 50 CD34+/DR- cells. The data suggest that human LTBMC developed to study myeloid differentiation can be modified to study the origin and development of the NK and possibly other lymphoid lineages. Modified cultures show that cells with morphologic, phenotypic, and functional characteristics of NK can be derived from a population of BMMNC with the phenotype of primitive hematopoietic progenitors and without phenotypic evidence of lymphoid- or myeloid- lineage commitment. Further studies will address the cell of origin and the ontogeny of human NK and other lymphoid lineages.
High level expression in Chinese hamster ovary cells of soluble forms of CD4 T lymphocyte glycoprotein including glycosylation variants. (1990)

The CD4 cell surface antigen is of interest as a marker of T lymphocytes that recognize foreign antigens in the context of MHC Class II antigen, as a receptor for the human immunodeficiency virus (HIV) and as a member of the immunoglobulin superfamily (IgSF) with four Ig-like domains present in the extracellular domain. In order to produce large amounts of soluble CD4 for x-ray crystallography and other molecular studies, a recently developed expression system based on selection via glutamine synthetase was used. Expression was attempted for rat CD4 corresponding to the full extracellular sequence (sCD4; domains 1-4), the NH2-terminal half (domains 1 and 2) and the first domain alone. Stable transfected Chinese hamster ovary cell lines were obtained that expressed sCD4 and sCD4 (half) at typical maximal levels in spent tissue culture supernatant of greater than 80 and 25 mg/liter, respectively. Domain 1 alone was not expressed and introduction of a N-linked glycosylation site did not facilitate expression. The role of glycosylation in the expression of sCD4 was investigated by mutagenesis of the constructs to remove each of the two N-linked glycosylation sites in turn and both together. All three forms were expressed at 60-120 mg/liter. The sCD4 (half) was not expressed after deletion of its N-linked site. The disulfide bonds of sCD4 were determined to be within domains 1, 2, and 4 and isolation of glycopeptides showed that both N-linked sites were glycosylated. Analysis of the hydrodynamic properties of sCD4 suggested that the molecule adopted an extended conformation in solution rather than folding to form a compact structure like an Fab. The possibility of dimerisation of CD4 was investigated but sCD4 dimers were not seen at an affinity cut-off of about 4 x 10(5) M-1.
Distributed and Secure Bootstrapping of Mobile Ad Hoc Networks (2008)

Secure bootstrapping of mobile ad hoc networks (MANETs) is a challenging problem in scenarios in which network users (or nodes) do not share trust relationships prior to the network deployment. In recent years, a number of schemes have been proposed to solve this problem, assuming either no or limited trust between the nodes prior to their deployment. Despite numerous proposals, there is no common understanding of the proposed schemes and of the trade-offs that they provide. This has consequences for both researchers and practitioners, who do not have a clear idea how to compare the schemes and how to select a scheme for a given application. In this article, we present a framework that helps in understanding and comparing schemes for secure bootstrapping of MANETs. The framework is general because it is policy-neutral and can accommodate many existing bootstrapping schemes. The proposed framework can equally serve as a good basis for the development of new MANET bootstrapping schemes; we show how the development of the framework leads to two new (classes of) distributed bootstrapping schemes. Within the framework, we not only investigate and characterize the properties of the relevant bootstrapping schemes, but also give methods for practitioners to select the relevant system parameters in the Random Walk and the (Restricted) Random Waypoint mobility models.
Sensitivity of the ground-based downwelling irradiance recorded by the FODIS sensor in respect of different angular positions (2009)

Some airborne hyperspectral sensors (e.g. AISA) can measure spectral downwelling irradiance using an additional cosine sensor mounted on a roof of an aircraft. The downwelling irradiance data, however, are rarely used for any atmospheric correction or compensation of different sun-sensor geometry, partly because they are sensitive towards continuous motion of the airborne platform. The airborne hyperspectral system AISA Eagle (Specim, Ltd., Finland), combined with the Fiber Optic Downwelling Irradiance Sensor (FODIS), were used for ground-based outdoor static measurements. The FODIS sensor was tilted into various zenith and azimuth angles. The data analysis revealed high sensitivity of the raw recorded FODIS signal towards different angular position. Simple cosine corrections reduced variation in the recorded FODIS signal. The variability (standard deviation of all measurements) decreased by 88% after the cosine correction was applied.
Local and Systemic Therapy of Human Prostate Adenocarcinoma with the Conditionally Replicating Herpes Simplex Virus Vector G207 (1999)

Prostate adenocarcinoma is the most common nonskin malignancy in males and the second most common cause of cancer death in the United States (Landis et al., 1998). Initial treatments of surgery or radiotherapy may cause impotence and/or incontinence from neural damage (Eastham and Scardino, 1998; Porter et al., 1998). When extraprostatic or metastatic disease develops, castration or pharmaceutical androgen ablation is utilized (Catalona, 1994). Androgen-resistant recurrence indicates a poor prognosis and justifies experimental chemotherapy (Oh and Kantoff, 1998). G207 (Mineta et al., 1995; Yazaki et al., 1995) is a multimutated herpes simplex virus 1 (HSV) vector that replicates within cancer cells, causing cellular death; however, replication is limited in normal cells, including those of the nervous system. In vitro, G207 at a low multiplicity of infection (MOI of 0.01) is oncolytic for multiple human prostate cancer cells. In athymic mice, a single intraneoplastic inoculation of G207 completely eradicates >22% of established subcutaneous human prostate cancer tumors irrespective of hormonal responsiveness. Two intraneoplastic inoculations of G207 completely eradicated two of three recurrent previously irradiated tumors and two intravenous administration of G207 induced tumor regression in distant subcutaneous tumors and completely eradicated one-fourth of the tumors.
Optimal antisense target reducingINSintron 1 retention is adjacent to a parallel G quadruplex (2014)

Splice-switching oligonucleotides (SSOs) have been widely used to inhibit exon usage but antisense strategies that promote removal of entire introns to increase splicing-mediated gene expression have not been developed. Here we show reduction of INS intron 1 retention by SSOs that bind transcripts derived from a human haplotype expressing low levels of proinsulin. This haplotype is tagged by a polypyrimidine tract variant rs689 that decreases the efficiency of intron 1 splicing and increases the relative abundance of mRNAs with extended 5' untranslated region (5' UTR), which curtails translation. Co-expression of haplotype-specific reporter constructs with SSOs bound to splicing regulatory motifs and decoy splice sites in primary transcripts revealed a motif that significantly reduced intron 1-containing mRNAs. Using an antisense microwalk at a single nucleotide resolution, the optimal target was mapped to a splicing silencer containing two pseudoacceptor sites sandwiched between predicted RNA guanine (G) quadruplex structures. Circular dichroism spectroscopy and nuclear magnetic resonance of synthetic G-rich oligoribonucleotide tracts derived from this region showed formation of a stable parallel 2-quartet G-quadruplex on the 3' side of the antisense retention target and an equilibrium between quadruplexes and stable hairpin-loop structures bound by optimal SSOs. This region interacts with heterogeneous nuclear ribonucleoproteins F and H that may interfere with conformational transitions involving the antisense target. The SSO-assisted promotion of weak intron removal from the 5' UTR through competing noncanonical and canonical RNA structures may facilitate development of novel strategies to enhance gene expression.
Non-invasive alternating current stimulation induces recovery from stroke (2010)

Non-invasive rtACS applied to post-stroke patients can modulate brain plasticity and induce recovery from neurological deficits long after the early post lesion recovery is over.
Bioenergetic and Functional Consequences of Bone Marrow–Derived Multipotent Progenitor Cell Transplantation in Hearts With Postinfarction Left Ventricular Remodeling (2007)

Thus, allogeneic pMultistem improved BZ energetics, regional contractile performance, and global left ventricular ejection fraction. These improvements may have resulted from paracrine effects that include increased vascular density in the BZ and spared myocytes in the infarct zone.
Targeting the c-Met Pathway Potentiates Glioblastoma Responses to γ-Radiation (2005)

Targeting the SF/HGF/c-Met pathway markedly potentiates the anti-glioma response to gamma-radiation. Clinical trials using novel SF/HGF/c-Met pathway inhibitors in glioma and other malignancies associated with c-Met activation should ultimate include concurrent radiation and potentially other cytotoxic therapeutics.
Augmentation of Antiproliferative Activity of Interferon Alfa Against Human Bladder Tumor Cell Lines by Encapsulation of Interferon Alfa Within Liposomes (1989)

Present therapy for human bladder cancer includes the intravesical administration of antiproliferative agents, such as recombinant human interferon alfa (IFN-alpha). The administration of cytotoxic molecules encapsulated in liposomes could provide a more efficient method for such therapy. Therefore, we determined whether encapsulation of the recombinant human IFN-alpha hybrid BBDD within liposomes will produce antitumor effects against the human bladder cancer cell line 253J superior to those observed with free IFN-alpha. Adherent cells were cultured in medium alone, in medium containing different concentrations of IFN-alpha, or in medium containing multilamellar liposomes (phosphatidylcholine-phosphatidylserine at a molar ratio of 7:3) that encapsulated saline or IFN-alpha. Cell growth was determined 96-120 hours later. Additional control groups consisted of target cells cultured with free IFN-alpha or with IFN-alpha plus liposomes containing saline. Cytostasis mediated by free IFN-alpha alone or IFN-alpha in the presence of liposome-saline was identical and ranged from 0%-30% (10 IU/mL) to 45%-70% (1,000 IU/mL). Liposomes containing saline produced no effects. Liposome-encapsulated IFN-alpha produced significantly greater growth inhibition than free IFN-alpha: 40%-70% (10 IU/mL) and 80%-90% (1,000 IU/mL), respectively. Moreover, a 253J variant subline selected for resistance to free IFN-alpha was sensitive to IFN-alpha presented in liposomes. These data suggest that the encapsulation of antiproliferative agents such as IFN-alpha in liposomes can improve therapeutic results.
A super cut-off CMOS (SCCMOS) scheme for 0.5-V supply voltage with picoampere stand-by current (2000)

A super cut-off CMOS (SCCMOS) scheme is proposed and demonstrated by measurement to achieve high-speed and low stand-by current CMOS VLSIs in sub-1-V supply voltage regime. By overdriving the gate of a cut-off MOSFET, the SCCMOS suppresses leakage current below 1 pA per logic gate in a stand-by mode while high-speed operation in an active mode is possible with low-threshold voltage of 0.1-0.2 V. The SCCMOS pushes the low-voltage operation limit 0.2 V further down compared with conventional schemes while maintaining the same stand-by current level.
Tachyplesin, a class of antimicrobial peptide from the hemocytes of the horseshoe crab (Tachypleus tridentatus). Isolation and chemical structure. (1988)

A cationic peptide, designated tachyplesin, was isolated from acid extracts of horseshoe crab (Tachypleus tridentatus) hemocyte debris. It consists of 17 residues and the structure determined by Edman degradation is: (formula; see text) The carboxyl-terminal end of this peptide was identified as arginine alpha-amide, and the whole sequence including the alpha-amide was also confirmed by fast atom bombardment mass spectrometry, indicating a mass value of 2263. Tachyplesin inhibits growth of both Gram-negative and -positive bacteria at low concentrations and formed a complex with bacterial lipopolysaccharide. Tachyplesin seems likely to act as antimicrobial peptide for self-defense in the horseshoe crab against invading microorganisms.
Inactivation of Ras by Clostridium sordellii Lethal Toxin-catalyzed Glucosylation (1996)

The lethal toxin (LT) from Clostridium sordellii belongs to the family of large clostridial cytotoxins causing morphological alterations in cultured cell lines accompanied by destruction of the actin cytoskeleton. C. sordellii LT exhibits 90% homology to Clostridium difficile toxin B, which has been recently identified as a monoglucosyltransferase (Just, I., Selzer, J., Wilm, M., von Eichel-Streiber, C., Mann, M., and Aktories, K. (1995) Nature 375, 500-503). We report here that LT too is a glucosyltransferase, which uses UDP-glucose as cosubstrate to modify low molecular mass GTPases. LT selectively modifies Rac and Ras, whereas the substrate specificity of toxin B is confined to the Rho subfamily proteins Rho, Rac, and Cdc42, which participate in the regulation of the actin cytoskeleton. In Rac, both toxin B and LT share the same acceptor amino acid, threonine 35. Glucosylation of Ras by LT results in inhibition of the epidermal growth factor-stimulated p42/p44 MAP-kinase signal pathway. LT is the first bacterial toxin to inactivate Ras in intact cells.
Combinatorial Peptide Library Protocols (1997)

Shmuel Cabilly presents in Combinatorial Peptide Library Protocols a collection of new and unique techniques for the construction and use of peptide libraries. These powerful methods-often detailed here by their pioneers-include protocols for the chemical synthesis of peptide libraries, for constructing peptide libraries that are displayed on the surface of filamentous phage or bacteria, and for the rapid screening of these libraries for molecules with biospecific properties. Additional methods permit identifying specific enzyme substrates, investigating the recognition spectra of various binding proteins, epitope mapping, and identifying mimotopes. Combinatorial Peptide Library Protocols offers novice and experienced investigators alike the ability to select molecules from a randomized pool having specific biological activities. Its state-of-the-art techniques, combined with clear step-by-step instructions, make this book an essential tool in the selection of peptides suitable for drug development
Similarity and Homology (1991)

Properly approached, molecular sequence data is a rich source of knowledge capable of teaching us much about the structure, function, and evolution of biological macromolecules. To effectively realize this potential, however, some understanding of the process of and theoretical basis for sequence comparison is needed as well as a variety of practical tools to access and manipulate the data. The volume of molecular sequence data has long since surpassed human information processing capacity for even simple tasks such as searching for related sequences, and with the ever increasing rate at which new sequences are being produced, the need for computer-assisted analysis becomes more and more acute. Automated tools can extend human capabilities by orders of magnitude in both speed and accuracy. The educated application of these automated tools is an essential part of modern molecular biology research.
Micro air bubble manipulation by electrowetting on dielectric (EWOD): transporting, splitting, merging and eliminating of bubbles (2006)

This paper describes various manipulations of micro air bubbles using electrowetting on dielectric (EWOD): transporting, splitting, merging and eliminating. First, in order to understand the response of bubbles to EWOD, the contact angle modulation is measured in a capped air bubble and confirmed to be in good agreement with the Lippmann–Young equation until saturation. Based on the contact angle measurement, testing devices for the bubble manipulations are designed and fabricated. Sequential activations of patterned electrodes generate continuous bubble transportations. Bubble splitting is successfully realized by activating a single electrode positioned in the middle of bubble base. However, it is found that there are criteria that make splitting possible only in certain conditions. For successful splitting, smaller channel gap, larger bubble size, wider splitting electrode and/or larger contact angle changes by EWOD are preferred. These criteria are verified by a series of experiments as well as a static analysis. Bubble merging is achieved by moving bubbles towards each other in two different channel configurations: (1) channel I, where bubbles are in contact with the bottom channel plate only, and (2) channel II, where bubbles in contact with the top as well as bottom channel plates. Furthermore, eliminating a bubble to the ambient air is accomplished. All the bubble manipulation techniques may provide a versatile integrated platform not only to manipulate micro objects by utilizing micro bubbles as micro carriers, but also to enable a discrete bubble-based gas analysis system.