gebhart/patrepeval huggingface dataset:
Generalized frequency division multiplexing: Analysis of an alternative multi-carrier technique for next generation cellular systems (2012)

Generalized frequency division multiplexing (GFDM) is a new concept that can be seen as a generalization of traditional OFDM. The scheme is based on the filtered multi-carrier approach and can offer an increased flexibility, which will play a significant role in future cellular applications. In this paper we present the benefits of the pulse shaped carriers in GFDM. We show that based on the FFT/IFFT algorithm, the scheme can be implemented with reasonable computational effort. Further, to be able to relate the results to the recent LTE standard, we present a suitable set of parameters for GFDM.
Blockade of Programmed Death Ligand 1 Enhances the Therapeutic Efficacy of Combination Immunotherapy against Melanoma (2010)

Inhibition of antitumor T cell responses can be mediated by the productive interaction between the programmed death-1 (PD-1) receptor on T cells and its ligand PD-L1. PD-L1 is highly expressed on both murine bone marrow-derived dendritic cells (DCs) and B16 melanoma. In this study, in vitro blockade of PD-L1 interaction on DCs led to enhanced IFN-gamma production and cytotoxicity by Ag-specific T cells. In vivo, the systemic administration of anti-PD-L1 Ab plus melanoma peptide-pulsed DCs resulted in a higher number of melanoma peptide-specific CD8(+) T cells, but this combination was insufficient to delay the growth of established B16 melanoma. Although the addition of 600 rad of total body irradiation delayed tumor growth, further adoptive transfer of Ag-specific CD8(+) T cells was needed to achieve tumor regression and long-term survival of the treated mice. Lymphopenic mice treated with anti-PD-L1 Ab demonstrated increased activation and persistence of adoptively transferred T cells, including a higher number of CD8(+) T cells infiltrating the tumor mass. Together, these studies support the blocking of PD-L1 signaling as a means to enhance combined immunotherapy approaches against melanoma.
Application of Multivalent Displays on Metalloprotease-Dependent Cleavage of Semaphorin 4D in Synapse Development (2012)

Semaphorin 4D (Sema4D) is expressed in the brain as a transmembrane protein and has been shown to regulate the development and maturation of GABAergic synapses via an unknown mechanism. Preliminary studies in the Paradis laboratory have shown that Sema4D is cleaved extracellularly in neurons with accumulation of an intracellular, C-terminal fragment. Using Western Blotting to monitor appearance of the Sema4D C-terminal cleavage product, we have demonstrated that Sema4D cleavage is metalloprotease-dependent in HEK293T cells using the metalloprotease activator, PMA, and broad spectrum metalloprotease inhibitor, GM6001. Additionally, we have used selective inhibitors for the metalloproteases ADAM10 and ADAM17, and our data suggest that ADAM10 cleaves Sema4D in HEK293T cells. We are currently exploring multivalent presentations of small molecule inhibitors to target Sema4D cleavage in neurons. To this end, we have synthesized a polymeric scaffold derived from the ring-opening metathesis polymerization (ROMP) amenable to subsequent appendage with amine-bearing small molecule inhibitors. Conjugation of the commercially available metalloprotease inhibitor, TAPI-2, to the polymeric scaffold generates a multivalent metalloprotease inhibitor. We have shown a 100-fold enhancement of TAPI-2 inhibition potency from the multivalent display and we propose that such a display can potentially improve inhibitor selectivity. To optimize multivalent inhibitor effectiveness, we will explore variations in the valency (polymer length), inhibitor density, and inhibitor ligand structures and gauge the effects of these structural variations using our Western blotting assay. We will then apply the most effective inhibitor on rat hippocampal neurons to test the role of metalloproteases on Sema4D cleavage in the brain.
Medicinal chemistry for the 21st century : a 'Chemistry for the 21st Century' monograph (1992)

Part 1 New lead discovery - historical perspectives: past approaches to discovering new drugs reflections and perspectives strategies for the creation of new drugs - trends in lead identification - a structural approach from membrane to genomic pharmacoloy or from short-term to long-term effects future applications of oligonucleotides in antiviral and antitumoral chemotherapy. Part 2 Protein structure - function relationships - cloning and structural studies on recepors and enzymes: the impact of molecular biology upon drug reseach - multiple targets provided by the reverse pharmacology a structural basis of proteinase-protein inhibitor interation detection of new enzymes and receptors by hybridization technique - new approaches to isolation, expression, expression and molecular modelling of proteases new era of biochemistry - cytokine signal transduction molecular diversity of signal transduction systems - a puzzle for pharmacologists of today and tomorrow. Part 3 Pharmacophore studies_ pharmacophore mimickry modelling - the future of the computer-aided drug design pharmacophore identification based on molecular electrostatic potentials (MEPS) synthesis of peptido-memetics - rational design of peptidomimetics - structural and pharmacological aspects - nonpeptide legands for peptide receptors peptidomimetric researc, design and synthesis peptidomimetics as tools for the initiation and analysis of peptide and protein secondary structure the prospects for unnatural proteins by design optimization - on the future of QSAR computer assisted drug designing in the 21st century. Part 4 Bioavailability manipulations - prodrugs: trends in design of prodrugs for improved drug delivery drug targeting - antibody based drug targeting approaches - perspectives and challenges novel drug delivery systems lipid microsphere preparations and lecithinized peptides for drug delivery systems.
Simultaneous Detection of Multiple Nucleic Acid Targets in a Homogeneous Format (1996)

The acridinium ester 4-(2-succinimidyloxycarbonylethyl)phenyl-10-methylacridinium 9-carboxylate trifluoromethane sulfonate (AE), which reacts rapidly with alkaline hydrogen peroxide to produce light, has been used as a detection label in a number of assay procedures, including nucleic acid probe-based systems [Nelson et al. (1995) in Nonisotopic Probing, Blotting and Sequencing (Kricka, L. J., Ed.) pp 391-428, Academic Press, Inc., San Diego, CA]. We have synthesized a number of derivatives of this AE and characterized their chemiluminescent properties. These derivatives display significant differences in the kinetics of the chemiluminescence reaction as well as optimal pH for light production. These differences allow two or more derivatives to be simultaneously detected and quantitated in a single reaction vessel. Several of these derivatives have been covalently linked to nucleic acid probe molecules and have been further characterized in regard to chemiluminescence properties as well as hydrolysis of the ester bond in both single- and double-stranded conformations. On the basis of these properties, homogeneous assay formats utilizing DNA probes labeled with various AE derivatives were developed. Simultaneous detection and quantitation of Chlamydia trachomatis and Neisseria gonorrhoeae, the gag and pol regions of HIV, and wild-type and mutant HIV sequences was achieved with high sensitivity and discrimination.
sFlt-1 gene-transfected fibroblasts: a wound-specific gene therapy inhibits local cancer recurrence. (2001)

Local recurrence occurs frequently at the site of injury after surgical resection. On the other hand, fibroblasts have been shown to accumulate in the injured area to heal and remodel the damaged tissues. Therefore, fibroblasts are likely to be useful as wound-specific vectors for delivery of genes to sites of surgically injury. The present study was performed to investigate wound-specific migration of exogenously administered fibroblasts and efficacy of gene therapy using genetically engineered fibroblasts in an i.p. wound recurrence model in rats. We demonstrated that fibroblasts transfected with the GFP gene accumulated specifically around the site of injury immediately after i.p. injection. Then, fibroblasts transfected with an adenovirus designated as AdFex that encoded the soluble form of Flt-1 (sFlt-1), a vascular endothelial growth factor receptor, were administered i.p. to the rats to examine inhibition of tumor growth. At day 16 after implantation, a significantly smaller tumor volume and less microvessel density in wound sites were observed in the AdFex/fibroblast-treated rats than in controls. Furthermore, this treatment also resulted in an improved survival rate. In conclusion, autologous fibroblasts show promise as a wound-specific vector for gene therapy, and administration of sFlt-1 gene-engineered fibroblasts contributed to local control of the tumor around the injured tissue.
Perception, Disability and the Conservation Environment (1995)

This paper sets out to examine die means of communication on conservation sites and suggests possible concepts that might be applied to the design of systems to provide communication for all visitors, including those generally considered as having perceptual disabilities. It examines what needs to be communicated in a conservation environment and to whom. The perceptual characteristics of visitors and resulting methods of communication are discussed in relation to the simulation of environments in analogous and interactive forms. The Dorcas Project, designed by Dog Rose, is described and the tactile to sound module discussed.
General theory of doubly periodic arrays over an arbitrary finite field and its applications (1978)

A general theory of doubly periodic (DP) arrays over an arbitrary finite field GF <tex xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">(q)</tex> is presented. First the basic properties of DP arrays are examined. Next modules of linear recurring (LR) arrays are defined and their algebraic properties discussed in connection with ideals in an extension ring <tex xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">\tilde{R}</tex> of the ring <tex xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">R</tex> of bivariate polynomials with coefficients in GF <tex xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">(q)</tex> . A finite <tex xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">\tilde{R}</tex> -module of DP arrays is shown to coincide with the <tex xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">\tilde{R}</tex> -module of LR arrays dermed by a zero-dimensional ideal in <tex xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">\tilde{R}</tex> . Equivalence relations between DP arrays are explored, i.e., rearrangements of arrays by means of unimodular transformations. Decimation and interleaving of arrays are defined in a two-dimensional sense. The general theory is followed by application to irreducible LR arrays. Among irreducible arrays, <tex xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">M</tex> -arrays are a two-dimensional analog of <tex xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">M</tex> -sequences and may be constructed from <tex xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">M</tex> -sequences by means of unimodular transformations. The results of this paper are also important in studying properties of Abelian codes.
CGS 19755 (Selfotel): A Novel Neuroprotective Agent Against CNS Injury (1996)

The hypothesis that excitoxicity is a mechanism of damage following different types of cerebral injury including global and focal ischemia (34), and head and spinal cord trauma (6,7,9,25) has been supported by numerous findings. During ischemia for example, glutamate neurotoxicity is mediated in part through N-methyl-D-aspartate (NMDA) receptors, since selective antagonists to this receptor protect against hypoxic-ischemic injury (10,35,41). In the last few years, different NMDA antagonists have been developed and tested; they can be divided into competitive and noncompetitive antagonists. Noncompetitive NMDA antagonists are extremely lipophilic and reach high levels in the brain after systemic administration. Various studies have demonstrated that these agents provide neuroprotection against hypoxic-ischemic injury (for review see ref. 29). Many competitive NMDA antagonists are hydrophilic and require direct cerebral administration to obtain high brain levels. Newer competitive NMDA blockers, such as cis-4-phosphonomethyl-2-piperidine carboxylic acid (CGS 19755, selfotel), provide neuroprotection against global ischemia, focal ischemia, and trauma when given systemically (2,3,32,33). Selfotel is currently being studied in multicenter safety and efficacy trials for stroke (17) and head trauma (6).
Interprocedural compilation of irregular applications for distributed memory machines (1995)

Data parallel languages like High Performance Fortran (HPF) are emerging\nas the architecture independent mode of programming distributed memory\nparallel machines. In this paper, we present the interprocedural\noptimizations required for compiling applications having irregular data\naccess patterns, when coded in such data parallel languages. We have\ndeveloped an Interprocedural Partial Redundancy Elimination (IPRE)\nalgorithm for optimized placement of runtime preprocessing routine and\ncollective communication routines inserted for managing communication in\nsuch codes. We also present three new interprocedural optimizations:\nplacement of scatter routines, deletion of data structures and use of\ncoalescing and incremental routines. We then describe how program slicing\ncan be used for further applying IPRE in more complex scenarios. We have\ndone a preliminary implementation of the schemes presented here using the\nFortran D compilation system as the necessary infrastructure. We present\nexperimental results from two codes compiled using our system to\ndemonstrate the efficacy of the presented schemes. \n(Also cross-referenced as UMIACS-TR-95-43)
Development of Infectivity by the Plasmodium berghei Sporozoite (1975)

Studies were done on the development of infectivity during ontogeny of the sporozoite of the rodent malaria parasite, Plasmodium berghei. Populations of sporozoites were separated from the oocysts, the hemocoel, and the salivary glands, with special precautions being taken to avoid cross-contamination between the different populations. The results indicated that populations of salivary gland sporozoites were more than 10,000 times as infective as populations of oocyst sporozoites from the same mosquitoes. The development of this infectivity appears to be asynchronous, in some cases taking place in the hemocoel, while in other cases not occurring until after the sporozoites have invaded the salivary glands. Thus, the development of infectivity seems to be time-dependent rather than site-dependent. There is also a continued increase in sporozoite infectivity during their residence in the salivary gland. The development of infectivity may be associated with other aspects of sporozoite maturation, including changes in their antigenicity and motility.
Subunit M2 of mammalian ribonucleotide reductase. Characterization of a homogeneous protein isolated from M2-overproducing mouse cells. (1985)

The M2 subunit of mammalian ribonucleotide reductase was purified to homogeneity from hydroxyurearesistant, M2-overproducing mouse cells.The purification procedure involved affinity chromatography on an anti-tubulin antibody-Sepharose column and high performance gel permeation chromatography.The pure protein is a dimer of M, = 88,000, containing stoichiometric amounts of a non-heme iron center and a tyrosyl free radical.The radical is destroyed by hydroxyurea but can readily be regenerated on incubation of the radical-free protein alone with iron-dithiothreitol in the presence of air.The ability to spontaneously regenerate the tyrosyl radical distinguishes protein M2 from the corresponding subunit of Escherichia coli ribonucleotide reductase, protein B2, but apart from that the two proteins are very similar.
CD4+ suppressor cells of autoimmune encephalomyelitis respond to T cell receptor‐associated determinants on effector cells by interleukin‐4 secretion (1992)

We have previously demonstrated that CD4+ suppressor T cells (Ts) inhibit the secretion of interferon (IFN)-gamma, but not interleukin (IL)-2, by effector cells of experimental autoimmune encephalomyelitis (EAE). Moreover, CD4+ Ts appear to regulate IFN-gamma by secretion of transforming growth factor-beta. We now show that CD4+ Ts produce a lymphokine with IL-4 activity in response to a determinant associated with EAE effector cells. CD4+ Ts do not proliferate or secrete IFN-gamma, IL-2, or IL-4 in response to myelin basic protein, nor do CD4+ Ts proliferate or secrete IL-2 when co-cultured with irradiated EAE effector cells. Rather, CD4+ Ts secrete IL-4 when co-cultured with either irradiated effector spleen cells or irradiated encephalitogenic line cells. CD4+ Ts do not secrete IL-4 in response to OVA-primed spleen cells, suggesting that the suppressor cells recognize a determinant specific to encephalitogenic T cells. Furthermore, CD4+ Ts secrete IL-4 when cultured with synthetic T cell receptor (TcR) V beta 8, but not TcR V beta 14 peptide, in the presence of antigen-presenting cells. This response is major histocompatibility complex class II restricted as demonstrated by inhibition of the response with anti-class II monoclonal antibody. These results suggest that CD4+ Ts recognize a determinant associated with TcR on the surface of EAE effector cells and respond by secreting IL-4, in a manner analogous to the Th2 lymphocyte subtype.
Foreign direct investment in developing countries : patterns, policies, and prospects (1991)

This study provides a summary of patterns, policies, and prospects concerning the foreign direct investment (FDI) in developing countries. The focus of the study is on host country policies, but the policies of home governments and international institutions are also analyzed. The emphasis of the study is on the factors that affect the patterns and trends of FDI in developing countries. Implicit to the study is the theme that FDI can make significant contributions to the long-term development process and that policy reforms that contribute to greater FDI are consequently desirable. The analysis of FDI presented here is based in substantial part on the findings of 11 country studies. The author found that the public policy environment for FDI has improved in recent years. There is more appreciation of FDI's contributions (such as transfer of technology and managerial skills, export market development, stimulation of local entrepreneurship, competition and innovation) and greater appreciation of the role of the private sector and private investment in development. The study concludes with a projection of the prospects for FDI flows to developing countries.
Superconducting microwave resonator for millikelvin magnetic resonance force microscopy (2003)

We have fabricated a superconducting resonator capable of generating a strong microwave magnetic field in a small (100 μm) volume for low temperature magnetic resonance experiments. While the resonator was specifically developed for use at millikelvin temperatures in a dilution refrigerator, where the total cooling power is limited to a few hundred microwatts, it is also useful at temperatures up to 5 K. The resonator consists of a 220 μm diameter, 2-1/2 turn niobium coil resonating with a short section of niobium microstripline. At a resonance frequency of 3 GHz, the loaded Q of the resonator was 780. The field strength was characterized by performing electron spin nutations. Operating at 100 mK with 320 μW of dissipated power, the resonator generated a field of 4 G at a distance of 100 μm from the coil.
Pan-Private Streaming Algorithms (2010)

Abstract: Collectors of confidential data, such as governmental agencies, hospitals, or search engine providers, can be pressured to permit data to be used for purposes other than that for which they were collected. To support the data curators, we initiate a study of pan-private algorithms; roughly speaking, these algorithms retain their privacy properties even if their internal state becomes visible to an adversary. Our principal focus is on streaming algorithms, where each datum may be discarded immediately after processing.
Enhanced proliferative cellular responses to HIV-1 V3 peptide and gp120 following immunization with V3:Ty virus-like particles. (1992)

The induction of CD4+ T-helper (Th) cell responses is likely to be an important requirement of vaccine candidates designed to prevent or moderate human immunodeficiency virus-1 (HIV-1) infection. We have investigated the ability of hybrid Ty virus-like particles carrying the V3 loop region of the HIV-1 IIIB envelope gp120 (V3:Ty-VLP) to elicit V3-specific proliferative responses. Significant proliferation in response to stimulation in vitro with homologous IIIB V3 peptide was observed following immunization of mice with V3:Ty-VLP either as an aluminium hydroxide precipitate or without adjuvant. Responses to MN V3 peptide were also observed in certain mouse haplotypes. To assess the effect of presenting the V3 loop in this particulate form, we compared the responses induced by V3:Ty-VLP with those obtained with two non-particulate immunogens, recombinant gp120 (rgp120) and V3 peptide conjugated to albumin. V3-specific responses to V3 peptide in vitro were reproducibly higher following immunization with V3:Ty-VLP than with either rgp120 or V3-albumin coagulate (V3-alb). The data indicate that immunization with the V3 loop as a hybrid Ty-VLP results in enhanced proliferative responses to V3 peptide and recognition of rgp120 in vitro. Some cross-reactivity of Th cells for V3 sequences from different isolates was also observed.
Chemically Diverse Group I p21-Activated Kinase (PAK) Inhibitors Impart Acute Cardiovascular Toxicity with a Narrow Therapeutic Window (2016)

p21-activated kinase 1 (PAK1) has an important role in transducing signals in several oncogenic pathways. The concept of inhibiting this kinase has garnered significant interest over the past decade, particularly for targeting cancers associated with PAK1 amplification. Animal studies with the selective group I PAK (pan-PAK1, 2, 3) inhibitor G-5555 from the pyrido[2,3-d]pyrimidin-7-one class uncovered acute toxicity with a narrow therapeutic window. To attempt mitigating the toxicity, we introduced significant structural changes, culminating in the discovery of the potent pyridone side chain analogue G-9791. Mouse tolerability studies with this compound, other members of this series, and compounds from two structurally distinct classes revealed persistent toxicity and a correlation of minimum toxic concentrations and PAK1/2 mediated cellular potencies. Broad screening of selected PAK inhibitors revealed PAK1, 2, and 3 as the only overlapping targets. Our data suggest acute cardiovascular toxicity resulting from the inhibition of PAK2, which may be enhanced by PAK1 inhibition, and cautions against continued pursuit of pan-group I PAK inhibitors in drug discovery.
A Virus amongst the Penguins (2008)

Despite its perceived isolation, Antarctica has been invaded by many non-native species, including pathogens. It is not surprising that wildlife in Antarctica could acquire parasites and diseases, but recent evidence of a common poultry virus in emperor penguins has captured scientific interest. Dr Gary Miller and his colleagues have been investigating the origin, spread and nature of the virus in emperor penguins at Auster rookery.