gebhart/patrepeval huggingface dataset:
High concentrations of recombinant soluble CD4 are required to neutralize primary human immunodeficiency virus type 1 isolates. (1990)

There is substantial evidence supporting the CD4 molecule as the principal cellular receptor for the human immunodeficiency virus type 1 (HIV-1). A number of truncated recombinant soluble CD4 (sCD4) molecules have been produced and shown to easily neutralize infection of laboratory strains of HIV-1 in vitro, and clinical trials using these sCD4 preparations have begun in patients with AIDS. Infectious HIV-1 titers in the plasma and peripheral blood mononuclear cells of five patients receiving sCD4 at 30 mg/day were sequentially monitored. No significant decrease in viral titers was found during therapy. Furthermore, plasma samples from eight patients with AIDS were titrated for HIV-1 with and without the addition of sCD4 ex vivo. Despite the addition of sCD4 at up to 1 mg/ml, there was little change in plasma viral titers. Subsequently, 10 primary HIV-1 isolates were tested for their susceptibility to neutralization in vitro by one preparation of sCD4. Neutralization of these clinical isolates required 200-2700 times more sCD4 than was needed to inhibit laboratory strains of HIV-1. Similar results were observed using one other monomeric sCD4 preparation and two multimeric CD4-immunoglobulin hybrid molecules. We conclude that unlike laboratory strains, primary HIV-1 isolates require high concentrations of sCD4 for neutralization. This phenomenon may pose a formidable problem for sCD4-based therapeutics in the treatment of HIV-1 infection.
Exploring Mixed Reality in Specialized Surgical Environments (2017)

Recent technology advances in both Virtual Reality and Augmented Reality are creating an opportunity for a paradigm shift in the design of human-computer interaction systems. Delving into the Reality-Virtuality Continuum, we find Mixed Reality - systems designed to augment the physical world with virtual entities that embody characteristics of real world objects. In the medical field, Mixed Reality systems can overlay real-time and spatially accurate results onto a patient's body without the need for external screens. The complexity of these systems previously required specialized prototypes, but newly available commercial products like the Microsoft HoloLens make the technology more available. Through a combination of literature review, expert analysis, and prototyping we explore the use of Mixed Reality in healthcare. From the experience of prototyping Patiently and HoloSim, two applications for augmenting medical training, we outline considerations for the future design and development of virtual interfaces grounded in reality.
Near-Field Optical Transducer for Heat-Assisted Magnetic Recording for Beyond-10-Tbit/in2 Densities (2008)

Continuous device downscaling, growing integration densities of the nanoscale electronics and development of alternative information processing paradigms, such as spintronics and quantum computing, call for drastic increase in the data storage capacity. In this paper we review our recent results for the design, fabrication and characterization of the near-field optical transducer for heat-assisted magnetic recording for beyond the 10-Tbit/in 2 densities. In order to record information, the heat-assisted magnetic recording system uses not only magnetic but also thermal energy. For this reason the recording media with the substantially higher anisotropy could be utilized to achieve the ultra-high recording densities. In this review, we provide details of the design of the near-field transducer capable of delivering over 50 μW power into a spot with the diameter of 30 nm. Heat-assisted magnetic recording and spin-based information processing require accurate thermal management of magnetic thin films. Here we report the results of our preliminary investigation of thermal transport in Pd/CoPd/Pd magnetic multilayers with the thickness of individual layers in the nanometer range.
Towards Small‐Molecule CXCR3 Ligands with Clinical Potential (2008)

The CXCR3 chemokine receptor was first discovered in 1996 and has been shown to play an important role in several diseases, most of which are related to inflammation. This review describes in detail the development of small CXCR3 ligands and their therapeutic potential. Classes of CXCR3 antagonists with strikingly variable core structures have emerged. Some of these compounds have confirmed the beneficial role of CXCR3 antagonism in animal models of disease. One of the compounds, AMG487, progressed to Phase II clinical trials but has been withdrawn because of lack of efficacy. New antagonist classes are being developed to reveal the full therapeutic potential of CXCR3.
Double-Blind Study of Doxycycline in Acne Vulgaris (1970)

To evaluate the effectiveness of doxycycline (Vibramycin) in acne vulgaris, 62 patients with predominantly inflammatory acne were treated in a double-blind crossover study. The drug was given orally, 100 mg/day, as a single dose every morning for four weeks. No concomitant internal or external therapy was permitted. Noninflamed open and closed comedones were not affected by active or placebo treatment. A good or excellent response in the reduction of inflammatory lesions was obtained in 21 (33%) of the subjects receiving doxycycline, compared to 14 (22%) while receiving placebo. Statistically, the improvement produced by doxycycline was significant, while there was no significant improvement from the placebo.
Interferons induce normal and aberrant retinoic-acid receptors type α in acute promyelocytic leukemia cells: Potentiation of the induction of retinoid-dependent differentiation markers (1996)

Treatment of the acute promyelocytic (APL) cell line NB4 with interferon alpha (IFN(alpha)), as well as IFN(beta) and gamma, results in an increased expression of the transcripts coding for retinoic-acid receptor type alpha (RAR(alpha)) and the leukemia-specific retinoic acid receptor PML-RAR. Transcriptional induction of the RAR(alpha) and PML-RAR mRNAs is rapid and it is parallelled by an increase in the corresponding proteins. Up-regulation of RAR(alpha) and PML-RAR gene expression by IFN(alpha) is accompanied by a strong potentiation in the induction of 2 retinoid-dependent granulocytic markers, i.e., granulocyte-colony-stimulating factor receptor mRNA and leukocyte alkaline phosphatase. However, IFN(alpha) does not have any effects on the retinoid-dependent regulation of the myeloid surface markers CD11b and CD33. The IFN-dependent increase in RAR(alpha) levels and the enhancing effect of the cytokine on retinoid-dependent granulocytic markers expression may be a characteristic of PML-RAR positive cells, since the phenomena are not observed in HL-60 promyelocytes. Interferons as well as retinoids inhibit the growth of NB4 cells, although the 2 classes of compounds do not significantly interact in terms of anti-proliferative activity. These results suggest the possible use of combinations between IFNs and retinoic acid in the cyto-differentiating treatment of APL patients.
CCG supertags in factored statistical machine translation (2007)

Combinatorial Categorial Grammar (CCG) supertags present phrase-based machine translation with an opportunity to access rich syntactic information at a word level. The challenge is incorporating this information into the translation process. Factored translation models allow the inclusion of supertags as a factor in the source or target language. We show that this results in an improvement in the quality of translation and that the value of syntactic supertags in flat structured phrase-based models is largely due to better local reorderings.
Abstract 4754: Type-1 dendritic cell vaccines in combination with poly-ICLC-association between positive tetramer response and 6-month progression-free survival in patients with recurrent malignant glioma (2010)

Abstract Our previous preclinical studies have demonstrated that intramuscular (i.m.) administration of a Toll-like receptor 3 ligand poly-ICLC remarkably enhances induction of type-1 cytotoxic T-lymphocytes (CTLs) and improves therapeutic efficacy of vaccinations against glioma-associated antigen (GAA)-derived CD8+ T cell epitopes. The primary objectives of this phase I/II study were to evaluate the safety and immunogenicity of vaccinations with Type-1 α dendrititc cells (αDC1) loaded with glioma associated antigen (GAA) epitopes and administration of poly-ICLC in patients with recurrent malignant gliomas. Human leukocyte Antigen (HLA)-A2+ participants with recurrent malignant glioma received intra-lymph-node injections of type-1 dendritic cells (DCs) loaded with HLA-A2 binding GAA-peptides EphA2 (883-891), IL-13Ralpha2 (345-353:1A9V), YKL-40 (202-211) and GP100 (209-217: 2M) at two-week intervals. Participants also received twice weekly i.m. injections of 20 µg/kg poly-ICLC. Participants who demonstrated positive radiological response or stable disease without major adverse events were allowed to receive booster vaccines. Primary endpoints were assessments of safety and immunological responses by ELISPOT and tetramer assays. Clinical and radiological responses were also evaluated. To date, 19 participants (12 with glioblastoma multiforme [GBM], 4 with anaplastic astrocytoma [AA] and 3 anaplastic oligodendroglioma [AO]) have received at least 4 vaccinations with no major adverse events. Increased CD8+ cells reactive to EphA2- or IL-13Rα2-tetramers were detected in post-vaccine peripheral blood mononuclear cells (PBMC) in 9 of 11 participants evaluated. Some of these patients also demonstrated up-regulation of a chemokine receptor CXCR3 on CD8+ PBMC following vaccines, indicating that the vaccine regimen induced type-1 CTL responses. Six patients achieved progression free at 6 months (3 GBM, 2AA and 1 AO). Among these, 3 patients are currently progression free at 23 (AA), 20 (AA) or 9 (GBM) months after the first vaccine, and receiving booster vaccines every 3 months. Although the trial enrolled mixed tumor types, Fisher's exact test indicated an association between positive tetramer response and 6-month progression-free survival, suggesting a possible correlation between antigen-specific responses and clinical response. These interim data demonstrate preliminary safety, immunological and clinical activity of poly-ICLC-assisted type-1 DC-based vaccines. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 4754.
CD10 (CALLA)/neutral endopeptidase 24.11 modulates inflammatory peptide- induced changes in neutrophil morphology, migration, and adhesion proteins and is itself regulated by neutrophil activation (1991)

The common acute lymphoblastic leukemia antigen (CALLA, CD10), which is expressed on early lymphoid progenitors and neutrophils, is the zinc metalloprotease, neutral endopeptidase 24.11 (NEP, "enkephalinase"). The CD10 cell surface enzyme is known to hydrolyze a variety of biologically active peptides including met-enkephalin, formyl-met-leu-phe (f-MLP), and substance P. These three CD10/NEP substrates induce the migration and aggregation of neutrophils, suggesting that each of the peptides can function as a mediator of neutrophil inflammatory responses. Recently, inhibition of CD10/NEP was found to reduce the concentration of metenkephalin needed to activate human and invertebrate granulocytes by several orders of magnitude. Herein we show that f-MLP and substance P induce rapid changes in neutrophil morphology, migration, and adhesion molecule expression, including upregulation of Mo1 (CD11b/CD18) and shedding of LAM-1 (also known as LECAM-1, Leu8, or TQ-1, the human homologue of murine gp100MEL14). Importantly, these coordinated changes are potentiated by inhibition of cell surface CD10/NEP enzymatic activity. Neutrophil cell surface CD10/NEP enzymatic activity is also shown to be regulated by the activation state of the cell during the time period in which the enzyme has its most pronounced effects. These results suggest that in neutrophils, CD10/NEP functions to control responsiveness to multiple inflammatory peptides.
Affine precoders for reliable communications (2002)

It is known that precoding a signal prior to its transmission through an unknown finite impulse response channel facilitates the equalisation of the channel. Moreover, since linear precoders spread the spectrum, the equalisation process mitigates the effects of channel spectral nulls caused by frequency selective fading. This paper argues that certain affine precoders are more efficient than linear precoders. Here, the efficiency of a precoder is a measure of its ability to enable the receiver to recover the source signal relative to the amount of redundancy introduced by the precoder. An efficient affine precoder is heuristically derived and simulations used to demonstrate that it is superior to both the traditional training sequence method and the filter bank precoding scheme. This precoding and equalisation scheme naturally extends to time varying channels.
Expression of Anthocyanins and Proanthocyanidins after Transformation of Alfalfa with Maize Lc (2003)

Three anthocyanin regulatory genes of maize (Zea mays; Lc, B-Peru, and C1) were introduced into alfalfa (Medicago sativa) in a strategy designed to stimulate the flavonoid pathway and alter the composition of flavonoids produced in forage. Lc constructs included a full-length gene and a gene with a shortened 5'-untranslated region. Lc RNA was strongly expressed in Lc transgenic alfalfa foliage, but accumulation of red-purple anthocyanin was observed only under conditions of high light intensity or low temperature. These stress conditions induced chalcone synthase and flavanone 3-hydroxylase expression in Lc transgenic alfalfa foliage compared with non-transformed plants. Genotypes containing the Lc transgene construct with a full-length 5'-untranslated region responded more quickly to stress conditions and with a more extreme phenotype. High-performance liquid chromatography analysis of field-grown tissue indicated that flavone content was reduced in forage of the Lc transgenic plants. Leucocyanidin reductase, the enzyme that controls entry of metabolites into the proanthocyanidin pathway, was activated both in foliage and in developing seeds of the Lc transgenic alfalfa genotypes. Proanthocyanidin polymer was accumulated in the forage, but (+)-catechin monomers were not detected. B-Peru transgenic and C1 transgenic populations displayed no visible phenotypic changes, although these transgenes were expressed at detectable levels. These results support the emerging picture of Lc transgene-specific patterns of expression in different recipient species. These results demonstrate that proanthocyanidin biosynthesis can be stimulated in alfalfa forage using an myc-like transgene, and they pave the way for the development of high quality, bloat-safe cultivars with ruminal protein bypass.
Metabolic engineering of cultured tobacco cells (1998)

Construction of a gene expression system in tobacco cultured cells (BY2) was studied. A 925 bp promoter fragment of a heat-shock protein gene (HSP18.2) of Arabidopsis thaliana showed clear heat-shock response of expression of the beta-glucuronidase (GUS) reporter gene in BY2 cells. Similar results were observed in a 500 mL flask and 3-L jar fermentor. Isolation of strong promoters in BY2 cells was tried. cDNA clones, in which the mRNA level is high in log-phase cells and the copy number in the genome is low, were isolated. These clones showed high homology with F1-ATPase (mitochondria type), elongation factor 1-alpha, and a gene with an unknown function of A. thaliana (clone 27), respectively. A 5'-flanking region of clone 27 showed 6.2 times the promoter activity of the CaMV35S promoter in BY2 cells. Three cDNA clones, which are expressed in the stationary growth phase of BY2 cells, were isolated by a differential screening. These clones showed high sequence homologies to alcohol dehydrogenase, pectin esterase, and extensin. Promoters of these genes will be useful in gene expression in high cell-density culture.
Learning-Dependent Increases in Sleep Spindle Density (2002)

Declarative memory consolidation is enhanced by sleep. In the investigation of underlying mechanisms, mainly rapid eye movement (REM) sleep and slow-wave sleep have been considered. More recently, sleep stage 2 with sleep spindles as a most prominent feature has received increasing attention. Specifically, in rats hippocampal ripples were found to occur in temporal proximity to cortical sleep spindles, indicating an information transfer between the hippocampus and neocortex, which is supposed to underlie the consolidation of declarative memories during sleep. This study in humans looks at the changes in EEG activity during nocturnal sleep after extensive training on a declarative learning task, as compared with a nonlearning control task of equal visual stimulation and subjectively rated cognitive strain. Time spent in each sleep stage, spindle density, and EEG power spectra for 28 electrode locations were determined. During sleep after training, the density of sleep spindles was significantly higher after the learning task as compared with the nonlearning control task. This effect was largest during the first 90 min of sleep (p < 0.01). Additionally, spindle density was correlated to recall performance both before and after sleep (r = 0.56; p < 0.05). Power spectra and time spent in sleep stages did not differ between learning and nonlearning conditions. Results indicate that spindle activity during non-REM sleep is sensitive to previous learning experience.
Characterization and Properties of Dominant-negative Mutants of the Ras-specific Guanine Nucleotide Exchange Factor CDC25Mm (1999)

Ras proteins are small GTPases playing a pivotal role in cell proliferation and differentiation. Their activation depends on the competing action of GTPase activating proteins and guanine nucleotide exchange factors (GEF). The properties of two dominant-negative mutants within the catalytic domains of the ras-specific GEF, CDC25 Mm , are described. In vitro, the mutant GEF W1056E and GEF T1184E proteins are catalytically inactive, are able to efficiently displace wild-type GEF from p21 ras , and strongly reduce affinity of the nucleotide-free rasGEF complex for the incoming nucleotide, thus resulting in the formation of a stable rasGEF binary complex. Consistent with their in vitro properties, the two mutant GEFs bring about a dramatic reduction in ras-dependent fos-luciferase activity in mouse fibroblasts. The stable ectopic expression of the GEF W1056E mutant in smooth muscle cells effectively reduced growth rate and DNA synthesis with no detectable morphological changes.
X-Linked Lymphoproliferative Disease: A Progressive Immunodeficiency (2001)

Our understanding of the X-linked lymphoproliferative syndrome (XLP) has advanced significantly in the last two years. The gene that is altered in the condition (SAP/SH2D1A) has been cloned and its protein crystal structure solved. At least two sets of target molecules for this small SH2 domain-containing protein have been identified: A family of hematopoietic cell surface receptors, i.e. the SLAM family, and a second molecule, which is a phosphorylated adapter. A SAP-like protein, EAT-2, has also been found to interact with this family of surface receptors. Several lines of evidence, including structural studies and analyses of missense mutations in XLP patients, support the notion that SAP/SH2D1A is a natural inhibitor of SH2-domain-dependent interactions with members of the SLAM family. However, details of its role in signaling mechanisms are yet to be unravelled. Further analyses of the SAP/SH2D1A gene in XLP patients have made it clear that the development of dys-gammaglobulinemia and B cell lymphoma can occur without evidence of prior EBV infection. Moreover, preliminary results of virus infections of a mouse in which the SAP/SH2D1A gene has been disrupted suggest that EBV infection is not per se critical for the development of XLP phenotypes. It appears therefore that the SAP/SH2D1A gene controls signaling via the SLAM family of surface receptors and thus may play a fundamental role in T cell and APC interactions during viral infections.
Chenodeoxycholic Acid and Ursodeoxycholic Acid Effects in Endogenous Hypertriglyceridemias. A Controlled Double‐Blind Trial (1981)

A double-blind controlled trial was carried out to compare the effects of chenodeoxycholic acid (CDCA), ursodeoxycholic acid (UDCA), and placebo on cholesterol and triglyceride levels in patients with endogenous hypertriglyceridemias. The dose of both bile acids was four 150-mg capsules day. Total serum cholesterol levels did not show appreciable changes with any of the treatments. HDL cholesterol was significantly increased after CDCA but not after UDCA or placebo. CDCA feeding was associated with a significant decrease in serum triglyceride levels, whereas the other treatments failed to show an effect. It is concluded that UDCA does not affect serum lipid levels, whereas CDCA lowers serum triglycerides and may be useful in the treatment of endogenous hypertriglyceridemia.
A novel human HER2-derived peptide homologous to the mouse Kd-restricted tumor rejection antigen can induce HLA-A24-restricted cytotoxic T lymphocytes in ovarian cancer patients and healthy individuals (2000)

A mouse HER2-derived peptide, HER2p63 (A) (TYLPANASL), can induce K(d)-restricted mouse cytotoxic T lymphocytes (CTL) and also function as a tumor rejection antigen in an in vivo assay. Since the anchor motif of mouse K(d) for peptide binding has much similarity to that of human HLA-A2402, we asked if human HER2p63 (T) (TYLPTNASL) could induce HER2-specific CTL in HLA-A2402-positive individuals. Peripheral blood mononuclear cells (PBMC) of HLA-A2402-positive individuals were sensitized in vitro with HER2p63-pulsed autologous dendritic cells prepared from PBMC. CTL clone derived from these specifically lysed HER2-expressing cell lines bearing HLA-A2402. Cytotoxic activity of the CTL clone against the HER2-expressing cell line bearing HLA-A2402 was blocked by antibodies against CD3, CD8, HLA-A24 or MHC class I, and was also inhibited by the addition of excess HER2p63-pulsed C1R bearing HLA-A2402. Killer cells were generated from PBMC of seven healthy individuals and five ovarian cancer patients, all of HLA-A2402 type, by in vitro sensitization with HER2p63-pulsed autologous antigen presenting cells. These killer cells selectively lysed HER2-expressing SKOV3 transfected with HLA-A2402 cDNA, indicating high immunogenicity of HER2p63 in all 12 individuals examined.