gebhart/patrepeval huggingface dataset:
The Neural Cell Adhesion Molecule Is a Receptor for Rabies Virus (1998)

Previous reports strongly suggest that, in addition to the nicotinic acetylcholine receptor, rabies virus can use other, as-yet-unidentified receptors. We found that laboratory cell lines susceptible to rabies virus infection express the neural cell adhesion molecule (NCAM) (CD56) on their surface, whereas resistant cells do not, supporting the idea that NCAM could be a rabies virus receptor. We observed that (i) incubation with rabies virus decreases the surface expression of NCAM; (ii) treatment of susceptible cells with heparan sulfate, a ligand for NCAM, or with NCAM antibodies significantly reduces the rabies virus infection; and (iii) preincubation of rabies virus inoculum with soluble NCAM protein as a receptor decoy drastically neutralizes the capacity of rabies virus to infect susceptible cells. Moreover, we demonstrated that transfection of resistant L fibroblasts with the NCAM-encoding gene induces rabies virus susceptibility whereas absence of NCAM in the primary cortical cell cultures prepared from NCAM-deficient mice reduces the rabies virus infection and virus production. This provides evidence that NCAM is an in vitro receptor for the rabies virus. Moreover, the in vivo relevance for the use of NCAM as a receptor was demonstrated by the infection of NCAM-deficient mice, in which rabies mortality was delayed and brain invasion by rabies virus was drastically restricted. Our results showed that NCAM, which is expressed mainly in the adult nervous system, plays an important role in rabies infection. However, it cannot be excluded that receptors other than NCAM are utilized. Thus, the description of NCAM as a new rabies virus receptor would be another example of the use by viruses of more than one receptor to gain entry into the host.
Consensus-derived structural determinants of the ankyrin repeat motif (2002)

The ankyrin repeat is one of the most common, modular, protein-protein interaction motifs in nature. To understand the structural determinants of this family of proteins and extract the consensus information that defines the architecture of this motif, we have designed a series of idealized ankyrin repeat proteins containing one, two, three, or four repeats by using statistical analysis of approximately 4,000 ankyrin repeat sequences from the PFAM database. Biophysical and x-ray crystallographic studies of the three and four repeat constructs (3ANK and 4ANK) to 1.26 and 1.5 A resolution, respectively, demonstrate that these proteins are well-folded, monomeric, display high thermostability, and adopt a very regular, tightly packed ankyrin repeat fold. Mapping the degree of amino acid conservation at each position on the 4ANK structure shows that most nonconserved residues are clustered on the surface of the molecule that has been designated as the binding site in naturally occurring ankyrin repeat proteins. Thus, the consensus amino acid sequence contains all information required to define the ankyrin repeat fold. Our results suggest that statistical analysis and the consensus sequence approach can be used as an effective method to design proteins with complex topologies. These generic ankyrin repeat proteins can serve as prototypes for dissecting the rules of molecular recognition mediated by ankyrin repeats and for engineering proteins with novel biological functions.
Therapy of human colonic and lung cancer xenografts with SN-38 conjugates of anti-CEACAM5 and anti-EGP-1 humanized monoclonal antibodies (2007)

C287 CPT-11 (Camptosar®), a water-soluble prodrug of the camptothecin analog, SN-38, is clinically used in the systemic chemotherapy of colorectal, lung, and other cancers. To increase the bioavailability of SN-38 and minimize toxicity, antibody (mAb) conjugates of SN-38 were designed and evaluated in preclinical models of human colonic cancer and human non-small-cell lung cancer (NSCLC). A bifunctional SN-38, MC-Phe-Lys-PABO-CO-20-O-SN-38 (wherein MC is maleimidocaproyl and PAB is p-amidobenzyl), containing a known lysosomally-cleavable dipeptide, was synthesized and conjugated to the thiol groups of mildly reduced versions of anti-CEACAM5 humanized mAb, hMN-14; anti-EGP-1 humanized mAb, hRS7; an isotype-matched, non-targeting, anti-CD22 humanized mAb control, hLL2; and murine Ag8 (MOPC-21) control mAb. SN-38 molar substitutions in the conjugates ranged 7.1-9.9. Therapy experiments were carried out in female athymic nude mice bearing established human tumor xenografts, and consisted of non-treatment, or treatments with specific mAb-SN38 or non-targeting mAb-SN38 conjugates or an equidose mixture of specific mAb and SN-38 as follows: 0.52 mg conjugated SN-38/kg bodyweight (BW) at a schedule of either q4d × 8 (protocol-1) or q4d × 4 (protocol-2); or 0.26 mg conjugated SN-38/kg BW at a schedule of q4d × 4 (protocol-3). Animals were sacrificed when tumor volume reached 2 cm3, cachexic (20% BW loss), or in distress. In a pilot therapy study with s.c. LS174T colonic tumors (protocol-1), 4/5 animals treated with specific hMN14-SN-38 conjugate were alive at the conclusion of study on day 127 with 2 animals having unmeasurable tumors, while untreated animals (n = 5) were sacrificed by day 21 (P = 0.0027). Specificity and dose-response were established in a repeat experiment (protocol-2; n = 5) using additional controls. In a lung metastatic model of human colonic carcinoma, therapy was initiated 14 days after i.v. injection of GW-39 colonic tumor suspension (protocol-3; n = 9 or 10); median survival in the group treated with specific hMN14-SN-38 conjugate was about 2-fold greater (73.5 days versus 35-40 days) than that in the untreated group or in the groups treated with equidoses of hMN14 and SN-38 mixture or equidoses of control conjugate, hLL2-SN38 (P
The amino acid sequence of human insulin-like growth factor I and its structural homology with proinsulin. (1978)

The complete amino acid sequence of human insulin-like growth factor I (IGF-I), a polypeptide isolated from serum, has been determined. IGF-I is a single chain polypeptide of 70 amino acid residues cross-linked by three disulfide bridges. The calculated molecular weight is 7649. IGF-I displays obvious homology to proinsulin: positions 1 to 29 are homologous to insulin B chain and positions 42 to 62 to insulin A chain. A shortened "connecting" peptide with 12 residues (positions 30 to 41) compared to 30 to 35 in proinsulins shows no homology to proinsulin C peptide. An octapeptide sequence at the COOH-terminal end is also a feature not found in proinsulins. The number of differences in amino acid positions between IGF-I and insulins suggests that duplication of the gene of the common ancestor of proinsulin and IGF occurred before the time of appearance of the vertebrates. Of the 19 residues known to be invariant in all insulins so far sequenced, only glutamine A5 and asparagine A21 are replaced in IGF-I by glutamic acid and alanine, respectively. The fact that all half-cystine and glycine residues and most nonpolar core residues of the insulin monomer are conserved is compatible with a three-dimensional structure of IGF-I similar to that of insulin.
Beyond sepsis pathophysiology with cytokines: what is their value as biomarkers for disease severity? (2005)

Sepsis is a major challenge in medicine. It is a common and frequently fatal infectious condition. The incidence continues to increase, with unacceptably high mortality rates, despite the use of specific antibiotics, aggressive operative intervention, nutritional support, and anti-inflammatory therapies. Typically, septic patients exhibit a high degree of heterogeneity due to variables such as age, weight, gender, the presence of secondary disease, the state of the immune system, and the severity of the infection. We are at urgent need for biomarkers and reliable measurements that can be applied to risk stratification of septic patients and that would easily identify those patients at the highest risk of a poor outcome. Such markers would be of fundamental importance to decision making for early intervention therapy or for the design of septic clinical trials. In the present work, we will review current biomarkers for sepsis severity and especially the use of cytokines as biomarkers with important pathophysiological role.
MRI and contrast-enhanced ultrasound imaging for evaluation of focal irreversible electroporation treatment: results from a phase I-II study in patients undergoing IRE followed by radical prostatectomy (2015)

• mpMRI and contrast-enhanced ultrasound are appropriate imaging modalities for assessing IRE effects • mpMRI and CEUS are the most feasible imaging modalities to visualize IRE ablation zone • The imaging is concordant with results of histopathological examination after IRE • Grey-scale US is insufficient for assessing IRE ablations.
Protection against endotoxic shock by a tumor necrosis factor receptor immunoadhesin. (1991)

Tumor necrosis factors (TNF) alpha and beta are structurally related cytokines that mediate a wide range of immunological, inflammatory, and cytotoxic effects. During bacterial infection of the bloodstream (sepsis), TNF-alpha induction by bacterial endotoxin is thought to be a major factor contributing to the cardiovascular collapse and critical organ failure that can develop. Despite antibiotic therapy, these consequences of sepsis continue to have a high mortality rate in humans. Here we describe a potent TNF antagonist, a TNF receptor (TNFR) immunoadhesin, constructed by gene fusion of the extracellular portion of human type 1 TNFR with the constant domains of human IgG heavy chain (TNFR-IgG). When expressed in transfected human cells, TNFR-IgG is secreted as a disulfide-bonded homodimer. Purified TNFR-IgG binds to both TNF-alpha and TNF-beta and exhibits 6- to 8-fold higher affinity for TNF-alpha than cell surface or soluble TNF receptors. In vitro, TNFR-IgG blocks completely the cytolytic effect of TNF-alpha or TNF-beta on actinomycin D-treated cells and is markedly more efficient than soluble TNFR (24-fold) or monoclonal anti-TNF-alpha antibodies (4-fold) in inhibiting TNF-alpha. In vitro, TNFR-IgG prevents endotoxin-induced lethality in mice when given 0.5 hr prior to endotoxin and provides significant protection when given up to 1 hr after endotoxin challenge. These results confirm the importance of TNF-alpha in the pathogenesis of septic shock and suggest a clinical potential for TNFR-IgG as a preventive and therapeutic treatment in sepsis.
Isolation and Analysis of the Expression of Two Genes for the 81-Kilodalton Heat-Shock Proteins from Arabidopsis (1992)

We have cloned and characterized two members of the family of genes for the 81-kilodalton heat-shock proteins from Arabidopsis thaliana, HSP81-1 and HSP81-2. Comparison of the entire genomic sequence of the HSP81-1 gene with the corresponding full-length cDNA previously reported as AtHS83 (TW Conner, PR LaFayette, RT Nagao, JL Key [1990] Plant Physiol 94: 1689-1695) reveals the presence of three introns of 315, 83, and 88 base pairs. By contrast, analysis of the HSP81-2 genomic and partial cDNA sequences suggests that the HSP81-2 gene is interrupted by only two introns of 304 and 106 base pairs. The 5'-initiation sites of the two corresponding mRNAs were mapped from results of experiments with S1 nuclease. The deduced amino acid sequences of the proteins encoded by these two genes show 88% identity, and they also show striking similarities to the hsp90 family of proteins in yeast and animal cells. From the results of northern blot analysis of transcripts, it appears that the expression of the HSP81-1 gene occurs at only very low levels in the absence of heat shock and is strongly induced by heat (35 degrees C). The HSP81-2 gene is constitutively expressed at much higher levels, and its expression is moderately enhanced by elevated temperatures. Severe heat shock appears to block the splicing of the pre-mRNA transcribed from HSP81-1. We also examined the effects of arsenite and cadmium on the expression of the HSP81 genes, as well as on other groups of hsp genes in Arabidopsis. Treatment with cadmium was marginally effective in inducing hsp genes, whereas arsenite stress strongly stimulated the accumulation of each mRNA in a coordinated fashion.
Plasma Protein Acute-Phase Response in Unstable Angina Is Not Induced by Ischemic Injury (1996)

The normal levels of CRP in variant angina, despite a significantly larger number of ischemic episodes and greater total ischemic burden, and the failure of CRP values to increase in unstable angina indicate that transient myocardial ischemia, within the range of duration observed, does not itself stimulate an appreciable acute-phase response.
Planar Chips Technology for Miniaturization of Separation Systems: A Developing Perspective in Chemical Monitoring (2021)

Planar chips technology, or the micromachining of silicon or other planar materials, has its roots in the microelectronics industry and therefore includes a number of well-established and accepted techniques. Silicon can be micro-machined to produce structures having dimensions on the order of a few micrometers, making it very amenable to miniaturization. This chapter explores some aspects of miniaturization rather than providing a complete treatment of the matter. One example of how dimensionless variables can be applied to capillary separation systems has been provided by Knox and Gilbert, who derived sets of optimal conditions for capillary LC using reduced parameters. The main advantage of the diffusion-controlled system is that a considerably higher rate of separation can be obtained upon miniaturization while maintaining comparable separation efficiency. Electroosmotic propulsion can therefore meet the demands of separation systems better than a pressure-driven flow, under the condition that aqueous electrolyte solutions are the subject of analysis.
Portable Real-Time Microwave Camera at 24 GHz (2011)

This paper presents a microwave camera built upon a two-dimensional array of switchable slot antennas. The camera borrows from modulated scattering techniques to improve isolation among the array elements. The camera was designed to measure vector electric field distribution, be compact, portable, battery operated, possess high dynamic range, and be capable of producing real-time images at video frame-rate. This imaging system utilizes PIN diode-loaded resonant elliptical slot antennas as its array elements integrated in a simple and relatively low-loss waveguide network thus reducing the complexity, cost and size of the array. The sensitivity and dynamic range of this system is improved by utilizing a custom-designed heterodyne receiver and matched filter for demodulation. The performance of the multiplexing scheme, noise-floor and dynamic range of the receivers are presented as well. Sources of errors such as mutual-coupling and array response dispersion are also investigated. Finally, utilizing this imaging system for various applications such as 2-D electric field mapping, and nondestructive testing is demonstrated.
Demonstration of a pronounced effect of noncovalent binding selectivity on the (+)-CC-1065 DNA alkylation and identification of the pharmacophore of the alkylation subunit. (1991)

Studies on the structural origin of the DNA alkylation selectivity of the antitumor antibiotic (+)-CC-1065 are detailed. The sites of alkylation of double-stranded DNA were examined for simple derivatives of 7-methyl-1,2,8,8a-tetrahydrocycloprop[1,2-c]pyrrolo[3,2-e]indol- 4(5H)-one (CPI), (+)-CC-1065, and agents incorporating the parent 1,2,7,7a-tetrahydrocycloprop[1,2-c]indol-4-one (CI) left-hand subunit. The CI subunit of the agents is a much more reactive alkylating agent than the natural CPI alkylation subunit of CC-1065. Consequently, simple derivatives of CI were found to alkylate double-stranded DNA under milder conditions than were simple derivatives of CPI, and the marked similarities in the CI and CPI DNA alkylation profiles illustrate that CI represents the minimum pharmacophore of CPI. Comparisons of the DNA alkylation profiles of (+)-N-butyloxycarbonyl-CPI, (+)-N-acetyl-CPI, and (+)-CC-1065 revealed distinctions in the CPI and (+)-CC-1065 sites of alkylation, whereas the incorporation of the reactive CI electrophile into an analog of CC-1065 (CI-CDPI2) (CDPI, N3-carbamoyl-1,2-dihydro-3H-pyrrolo[3,2-e]indole-7-carboxylic acid) provided an agent that possesses the characteristic CC-1065 DNA alkylation profile (site selectivity and relative site intensity). These observations suggest that the noncovalent binding selectivity of the agents may restrict the number of available DNA alkylation sites and play a productive role in controlling the sequence-selective alkylation by effectively delivering the electrophile to A + T-rich minor groove regions of DNA possessing accessible adenine N-3 alkylation sites. In turn, the noncovalent binding selectivity may be derived from preferential binding within the narrower, sterically more accessible A + T-rich minor groove of double-stranded DNA.
How to play ANY mental game (1987)

We present a polynomial-time algorithm that, given as a input the description of a game with incomplete information and any number of players, produces a protocol for playing the game that leaks no partial information, provided the majority of the players is honest.
Radiosity for dynamic scenes in flatland with the visibility complex (1996)

Abstract The radiosity method is particularly suitable for global illumination calculations in static environments. Nonetheless, recent applications of image synthesis such as architectural simulation or lighting design require the ability to modify environments. Previous methods have attempted to deal with dynamic environments (environments where the geometry, the material properties, etc., can change)but still suffer some limitations in the case of moving objects. One of the main problems remaining is the efficient and accurate detection of which form factors must really be recomputed, since their calculation is the most time‐consuming part of the radiosity method. To correctly understand and solve this problem, we start with a method in 2D for polygonal scenes using the visibility complex. It is a powerful data structure representing the visibility relationships between objects in the plane. We have developed and implemented an algorithm which uses this structure to efficiently compute the discontinuity mesh and the form factors for static scenes. We also propose an extension to our algorithm to efficiently update only the modified form factors when an object is moving. This approach enhances our understanding and will hopefully lead to efficient solutions in 3D.
The role of regulatory T cells in the control of natural killer cells: relevance during tumor progression (2006)

Tumor immunosurveillance relies on cognate immune effectors [lymphocytes and interferon-gamma (IFN-gamma)] and innate immunity [natural killer (NK) cells, natural killer group 2, member D (NKG2D) ligands, perforin/granzyme, and tumor necrosis factor-related apoptosis-inducing ligand]. In parallel, tumor cells promote the expansion of CD4(+)CD25(+) regulatory T cells (Tregs) that counteract T-cell-based anti-tumor immunity. Moreover, accumulating evidence points to a critical role for Tregs in dampening NK cell immune responses. This review summarizes the findings showing that Tregs suppress NK cell effector functions in vitro and in vivo, i.e. homeostatic proliferation, cytotoxicity, and interleukin-12-mediated IFN-gamma production. The molecular mechanism involve selective expression of membrane-bound transforming growth factor-beta on Tregs, which downregulate NKG2D expression on NK cells in vitro and in vivo. The regulatory events dictating NK cell suppression by Tregs have been studied and are discussed. The pathological relevance of the Treg-NK cell interaction has been brought up in tumor models and in patients with cancer. Consequently, inhibition of Tregs through pharmacological interventions should be considered during NK-cell-based immunotherapy of cancer.
On creating animated presentations (2003)

Computers are used to display visuals for millions of live presentations each day, and yet only the tiniest fraction of these make any real use of the powerful graphics hardware available on virtually all of today's machines. In this paper, we describe our efforts toward harnessing this power to create better types of presentations: presentations that include meaningful animation as well as at least a limited degree of interactivity. Our approach has been iterative, alternating between creating animated talks using available tools, then improving the tools to better support the kinds of talk we wanted to make. Through this cyclic design process, we have identified a set of common authoring paradigms that we believe a system for building animated presentations should support. We describe these paradigms and present the latest version of our script-based system for creating animated presentations, called SLITHY. We show several examples of actual animated talks that were created and given with versions of SLITHY, including one talk presented at SIGGRAPH 2000 and four talks presented at SIGGRAPH 2002. Finally, we describe a set of design principles that we have found useful for making good use of animation in presentation.
Controlled nanocutting of graphene (2008)

Rapid progress in graphene-based applications is calling for new processing techniques for creating graphene components with different shapes, sizes, and edge structures. Here we report a controlled cutting process for graphene sheets, using nickel nanoparticles as a knife that cuts with nanoscale precision. The cutting proceeds via catalytic hydrogenation of the graphene lattice, and can generate graphene pieces with specific zigzag or armchair edges. The size of the nanoparticle dictates the edge structure that is produced during the cutting. The cutting occurs along straight lines and along symmetry lines, defined by angles of 60° or 120°, and is deflected at free edges or defects, allowing practical control of graphene nano-engineering.
Alkaline phosphatase fusions: sensors of subcellular location (1990)

Alkaline phosphatase fusions allow genes to be identified solely on the basis of their protein products being exported from the cytoplasm. Thus, the use of such fusions helps render biological processes which involve cell envelope and secreted proteins accessible to a sophisticated genetic analysis. Furthermore, alkaline phosphatase fusions can be used to locate export signals. Specifying such signals is an important component of studies on the structure of individual cell envelope proteins. The basis of the alkaline phosphatase fusion approach is the finding that the activity of the enzyme responds differently to different environments. Thus, the activity of the fusion protein gives evidence as to its location. This general approach of using sensor proteins which vary in their function, depending on their environment, could be extended to the study of other sorts of problems. It may be that certain enzymes will provide an assay for localization to a particular subcellular compartment, if the environment of the compartment differs from that of others. For instance, the lysosome is more acidic than other intracellular organelles. A gene fusion system employing a reporter enzyme that could show activity only at the pH of the lysosome could allow the detection of signals determining lysosomal localization. Analogous types of enzymes may be used as probes for other subcellular compartments.
Androgens in the Aging Male (1991)

Journal Article Androgens in the Aging Male Get access A. VERMEULEN A. VERMEULEN 1Department of Endocrinology, University Hospital Ghent B 9000 Ghent, Belgium Search for other works by this author on: Oxford Academic Google Scholar The Journal of Clinical Endocrinology & Metabolism, Volume 73, Issue 2, 1 August 1991, Pages 221–224, https://doi.org/10.1210/jcem-73-2-221 Published: 01 August 1991 Article history Received: 24 December 1990 Published: 01 August 1991