gebhart/patrepeval huggingface dataset:
Multiple Peptides Homologous to Herpes Simplex Virus Type 1 Glycoprotein B Inhibit Viral Infection (2008)

The 773-residue ectodomain of the herpes simplex virus type 1 (HSV-1) glycoprotein B (gB) has been resistant to the use of mutagenic strategies because the majority of the induced mutations result in defective proteins. As an alternative strategy for the identification of functionally important regions and novel inhibitors of infection, we prepared a library of overlapping peptides homologous to the ectodomain of gB and screened for the ability of the peptides to block infection. Seven of 138 15-mer peptides inhibited infection by more than 50% at a concentration of 100 microM. Three peptides (gB94, gB122, and gB131) with 50% effective concentrations (EC(50)s) below 20 microM were selected for further studies. The gB131 peptide (residues 681 to 695 in HSV-1 gB [gB-1]) was a specific entry inhibitor (EC(50), approximately 12 microM). The gB122 peptide (residues 636 to 650 in gB-1) blocked viral entry (EC(50), approximately 18 microM), protected cells from infection (EC(50), approximately 72 microM), and inactivated virions in solution (EC(50), approximately 138 microM). We were unable to discern the step or steps inhibited by the gB94 peptide, which is homologous to residues 496 to 510 in gB-1. Substitution of a tyrosine in the gB122 peptide (Y640 in full-length gB-1) reduced the antiviral activity eightfold, suggesting that this residue is critical for inhibition. This peptide-based strategy could lead to the identification of functionally important regions of gB or other membrane proteins and identify novel inhibitors of HSV-1 entry.
Consequences of Cell Death (2000)

Cell death by necrosis is typically associated with inflammation, in contrast to apoptosis. We have identified additional distinctions between the two types of death that occur at the level of dendritic cells (DCs) and which influence the induction of immunity. DCs must undergo changes termed maturation to act as potent antigen-presenting cells. Here, we investigated whether exposure to apoptotic or necrotic cells affected DC maturation. We found that immature DCs efficiently phagocytose a variety of apoptotic and necrotic tumor cells. However, only exposure to the latter induces maturation. The mature DCs express high levels of the DC-restricted markers CD83 and lysosome-associated membrane glycoprotein (DC-LAMP) and the costimulatory molecules CD40 and CD86. Furthermore, they develop into powerful stimulators of both CD4(+) and CD8(+) T cells. Cross-presentation of antigens to CD8(+) T cells occurs after uptake of apoptotic cells. We demonstrate here that optimal cross-presentation of antigens from tumor cells requires two steps: phagocytosis of apoptotic cells by immature DCs, which provides antigenic peptides for major histocompatibility complex class I and class II presentation, and a maturation signal that is delivered by exposure to necrotic tumor cells, their supernatants, or standard maturation stimuli, e.g., monocyte-conditioned medium. Thus, DCs are able to distinguish two types of tumor cell death, with necrosis providing a control that is critical for the initiation of immunity.
Target testing and the PicHunter Bayesian multimedia retrieval system (2002)

We address how the effectiveness of a content-based, multimedia information retrieval system can be measured, and how such a system should best use response feedback in performing searches. We propose a simple, quantifiable measure of an image retrieval system's effectiveness, "target testing", in which effectiveness is measured as the average number of images that a user must examine in searching for a given random target. We describe an initial version of PicHunter, a retrieval system designed to test a novel approach to relevance-feedback. This approach is based on a Bayesian framework that incorporates an explicit model of the user's selection process. PicHunter is intentionally designed to have a minimal, "queryless" user interface, so that its performance reflects only the performance of the relevance feedback algorithm. The algorithm, however, can easily be incorporated into more traditional, query-based systems. Employing no explicit query, and only a small amount of image processing, PicHunter is able to locate randomly selected targets in a database of 4522 images after displaying an average of only 55 groups of 4 images. This is more than 10 times better than random chance.
Learning and Predicting User Behavior for Particular Resource Use (2001)

On the basis of the examination covering 30 young children (aged 2 months to 3.5 years), three variants of motor psychogenic disorders were specified. Group I included elementary, stereotypic motor phenomena expressed as special poses, rocking, jack-knifing, finger sucking and other stereotypes of motor acts. Group II was characterized by more complicated motor and psychomotor disorders in the form of various manifestations of motor infantilism. Group III comprised children with neurotic motor monosymptomatic and ritual-behavioural obsessive actions. The above disorders are assessed from the evolutional-dynamic point of view.
Use of the Controlled Adverse Environment (CAE) in Clinical Research: A Review (2017)

The many internal and external factors that contribute to the pathophysiology of dry eye disease (DED) create a difficult milieu for its study and complicate its clinical diagnosis and treatment. The controlled adverse environment (CAE<sup>®</sup>) model has been developed to minimize the variability that arises from exogenous factors and to exacerbate the signs and symptoms of DED by stressing the ocular surface in a safe, standardized, controlled, and reproducible manner. By integrating sensitive, specific, and clinically relevant endpoints, the CAE has proven to be a unique and adaptable model for both identifying study-specific patient populations with modifiable signs and symptoms, and for tailoring the evaluation of interventions in clinical research studies.
The soothing function of touch: affective touch reduces feelings of social exclusion (2017)

The mammalian need for social proximity, attachment and belonging may have an adaptive and evolutionary value in terms of survival and reproductive success. Consequently, ostracism may induce strong negative feelings of social exclusion. Recent studies suggest that slow, affective touch, which is mediated by a separate, specific C tactile neurophysiological system than faster, neutral touch, modulates the perception of physical pain. However, it remains unknown whether slow, affective touch, can also reduce feelings of social exclusion, a form of social pain. Here, we employed a social exclusion paradigm, namely the Cyberball task (N = 84), to examine whether the administration of slow, affective touch may reduce the negative feelings of ostracism induced by the social exclusion manipulations of the Cyberball task. As predicted, the provision of slow-affective, as compared to fast-neutral, touch led to a specific decrease in feelings of social exclusion, beyond general mood effects. These findings point to the soothing function of slow, affective touch, particularly in the context of social separation or rejection, and suggest a specific relation between affective touch and social bonding.
CD20-induced lymphoma cell death is independent of both caspases and its redistribution into triton X-100 insoluble membrane rafts. (2003)

Rituximab is routinely used for the treatment of neoplasia, although the mechanism of action remains uncertain. In the current study, CD20-induced apoptosis was investigated with a panel of anti-CD20 monoclonal antibodies (mAb) in a wide range of cell lines. A hierarchy of mAb activity was apparent, with the B1 mAb generally the most potent. Apoptosis through CD20 was dependent on the nature of mAb binding and correlated with the extent of homotypic cell adhesion induced. However, using anti-CD20 mAb, which vary in the extent to which they redistribute wild-type and mutant CD20 molecules to membrane rafts, we showed that CD20-induced apoptosis was independent of translocation to TX-100 insoluble rafts. Using crmA-transfected cells and caspase inhibitors, we showed that phosphatidylserine translocation and mitochondrial permeability transition evoked during CD20-induced apoptosis appeared caspase independent. Furthermore, in cytoplasts which lack mitochondria and in Bcl(2)-transfected cells, phosphatidylserine was still translocated to the cell surface after CD20 stimulation. Together, these data imply that CD20 can evoke apoptosis without the involvement of mitochondria and caspases and irrespective of redistribution into TX-100 insoluble membrane rafts.
Treatment of Cancer Weight Loss in Patients with Advanced Lung Cancer (1992)

Megestrol acetate, a semisynthetic gestagen, is effective not only for endocrine therapy of advanced breast carcinomas, but also in the treatment of cachectic patients with aggressive, hormone-independent tumors. Sixty-six patients with therapy-resistant, advanced bronchogenic carcinomas of different histologic types, who had lost more than 10% of their regular body weight within a prospective, randomized trial, were treated with megestrol acetate at a dose of either 160 or 480 mg/day for 3-4 months. The mean weight gain for all patients was 2.5 kg. Nearly all of them (80%) reported improved appetite and well-being. The mean weight gain in the group of patients receiving 480 mg/day was higher (3.0 kg) than in the group receiving 160 mg/day (2.0 kg).
Phosphodiesterase 4 Inhibitors Augment Levels of Glucocorticoid Receptor in B Cell Chronic Lymphocytic Leukemia but Not in Normal Circulating Hematopoietic Cells (2007)

Type 4 cyclic AMP (cAMP) phosphodiesterase (PDE4) inhibitors, a class of compounds in clinical development that activate cAMP-mediated signaling by inhibiting cAMP catabolism, offer a feasible means by which to potentiate glucocorticoid-mediated apoptosis in lymphoid malignancies such as B-cell chronic lymphocytic leukemia (B-CLL). In this study, we show that PDE4 inhibitors up-regulate glucocorticoid receptor (GRalpha) transcript levels in B-CLL cells but not T-CLL cells or Sezary cells or normal circulating T cells, B cells, monocytes, or neutrophils. Because GRalpha transcript half-life does not vary in CLL cells treated with the prototypic PDE4 inhibitor rolipram, the 4-fold increase in GRalpha mRNA levels observed within 4 h of rolipram treatment seems to result from an increase in GRalpha transcription. Rolipram treatment increases levels of transcripts derived from the 1A3 promoter to a greater extent than the 1B promoter. Treatment of B-CLL cells with two other PDE4 inhibitors currently in clinical development also augments GR transcript levels and glucocorticoid-mediated apoptosis. Washout studies show that simultaneous treatment with both drug classes irreversibly augments apoptosis over the same time frame that GR up-regulation occurs. Although treatment of B-CLL cells with glucocorticoids reduces basal GRalpha transcript levels in a dose-related manner, cotreatment with rolipram maintained GRalpha transcript levels above baseline. Our results suggest that as a result of their unusual sensitivity to PDE4 inhibitor-mediated up-regulation of GRalpha expression, treatment of B-CLL patients with combined PDE4 inhibitor/glucocorticoid therapy may be of therapeutic benefit in this disease.
Effect of Rifampin on the Pharmacokinetics of Rosiglitazone in Healthy Subjects (2004)

This study showed that rifampin affected the disposition of rosiglitazone in humans, probably by the induction of cytochrome P450 (CYP) 2C8 and, to a lesser extent, CYP2C9. Therefore caution should be exercised during the coadministration of rifampin and rosiglitazone.
Tau Protein Phosphorylation as a Therapeutic Target in Alzheimers Disease (2002)

Neurofibrillary tangles (NFTs) are a distinguishing neuropathological feature found in postmortem brains of Alzheimer s disease (AD) and tauopathy patients. The density of these lesions correlates with severity of AD and their distribution follows a characteristic pattern of expansion as the disease progresses. The principle components of NFTs are highly phosphorylated forms of the microtubule-associated protein, tau. Tau phosphorylation is believed to initiate or facilitate dissociation from microtubules leading to microtubule destabilization, decay of cellular transport properties, and cell death. This review summarizes recent data and prevailing views on the roles of protein kinases and phosphatases in the regulation of tau phosphorylation in vitro and in vivo, taking into account data from human neurodegenerative diseases and from transgenic rodent models. Small molecule inhibitors of tau phosphorylation that serve as important research tools and possibly the basis of potential new therapeutics, are also described. Key challenges in developing effective therapeutic agents include identification of the relevant kinase(s) responsible for aberrant tau phosphorylation in AD, synthesis of inhibitors selectively targeting those kinases and establishment of appropriate animal models.
Hyper-Rayleigh scattering in solution (1992)

The experimental setup for the implementation of a new technique to determine the hyperpolarizability of nonlinear optical molecules in solution is presented. The new technique, hyper-Rayleigh scattering in solution [K. Clays and A. Persoons, Phys. Rev. Lett. 66, 2980 (1991)], has the advantage over the electric-field-induced second-harmonic generation technique that the dipole moment μ and the second hyperpolarizability γ do not have to be independently determined to obtain the first hyperpolarizability β. No electric field is needed to lower the intrinsic symmetry of the isotropic solution, leading to a simpler cell design and a simpler local field factor. The internal reference method, when applicable, completely eliminates the local field factor. With the technique presented, values of the first hyperpolarizability β of 23×10−30 esu for para-nitroaniline (PNA), 105×10−30 esu for 4-methoxy-4′-nitrostilbene (MONS), and 95×10−30 esu for 4-hydroxy-4′-nitrostilbene (HONS) dissolved in chloroform have been obtained.
On Political Order and the “Arab Spring” (2012)

A year has passed since a young vegetable vendor, Mohamed Bouazizi, immolated himself after his cart and dignity were taken away by police in the provincial Tunisian town of Sidi Bouzid. Since the death of the 26-year-old, millions of similarly disenfranchised, poor, and prospect-less Arabs have risen in revolt across North Africa and the Middle East in a phenomenon widely dubbed the “Arab Spring.”
Effects of granulocyte colony-stimulating factor and interferon-γ on antifungal activity of human polymorphonuclear neutrophils against pseudohyphae of different medically important Candida species (1995)

Polymorphonuclear neutrophils (PMNs) are the major host defense against pseudohyphae, the invasive form of Candida species. We studied the effects of granulocyte colony-stimulating factor (G-CSF) and interferon-gamma (IFN-gamma) on the PMN-induced damage of pseudo-hyphae of Candida albicans, Candida tropicalis, and Candida parapsilosis in vitro by using two antifungal assays: a modified limiting dilution assay and a colorimetric metabolic 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay. PMNs from healthy volunteers were incubated with either G-CSF (100-10,000 U/ml) or IFN-gamma (10-5000 U/ml) or buffer at 37 degrees C for 90 min and their capacity to damage nonopsonized pseudohyphae was then measured. C. tropicalis appeared to be the most susceptible species, whereas C. parapsilosis showed the highest rate of resistance to PMN damage. G-CSF (500-10,000 U/ml) and IFN-gamma (100-1000 U/ml) enhanced the antifungal activity of PMNs against C. albicans pseudo-hyphae (P < .01 and P < .05). Among the others, G-CSF enhanced PMN-induced damage of C. parapsilosis at concentrations 500-10,000 U/ml (P < .05), whereas it enhanced damage of C. tropicalis only at 10,000 U/ml (P < .01). IFN-gamma (100-1000 U/ml)-primed PMNs also caused augmented damage of C. parapsilosis (P < .05) but not of C. tropicalis at the same concentrations. Species-dependent differences exist in the responses of PMNs to Candida pseudohyphae and G-CSF as well as IFN-gamma are important immunomodulators of phagocytic host defenses against them.
Macaque Lymphocytes Transduced by a Constitutively Expressed Interferon beta Gene Display an Enhanced Resistance to SIVmac251 Infection (1999)

We are developing a method of gene therapy of HIV infection based on the low constitutive expression of an interferon beta (IFN-beta) gene in HIV target cells. Herein we report the first step in the development of a relevant animal model, provided by the macaque (Macaca fascicularis) infected with a pathogenic SIVmac251 isolate. To avoid the possibility of in vivo rejection of macaque lymphocytes expressing Hu IFN-beta, we have PCR-amplified and sequenced the Ma IFN-beta-coding sequence, and placed it under the control of a PstI-NruI 0.6-kb fragment of the murine H-2Kb gene promoter in the MFG-K(b)MaIFNbeta retroviral vector. Lymphocytic CEMX174 cells, transduced by coculture on packaging cells with this construct, harbored a mean of 0.07 to 1.2 copies of the IFN-beta transgene per cell, and were characterized by an IFN production ranging from 75 to 750 units per 5 x 10(5) cells per 3 days. The IFN-beta-transduced populations displayed an enhanced resistance against the pathogenic SIVmac251 isolate. Control experiments showed that the enhanced resistance could not be ascribed to the Ma IFN-beta released during the 3 days of coculture by the packaging cells, or to the mere transduction with a retroviral vector. Macaque lymphocytes transduced by the MFG-K(b)MaIFNbeta retroviral vector by coculture on packaging cells, acquired a mean number of IFN-beta transgene copies per cell ranging from 0.03 to 0.1. Such transduction led to the release of IFN-beta into the culture medium, ranging from 10 to 20 units per 5 x 10(5) cells per 3 days. This increased the anti-SIV resistance of the lymphocytes, as demonstrated by a decreased p27 antigen release into the culture medium, without affecting lymphocyte proliferation.
Organic Synthesis with .alpha.-Diazo Carbonyl Compounds (1994)

ADVERTISEMENT RETURN TO ISSUEPREVArticleOrganic Synthesis with .alpha.-Diazo Carbonyl CompoundsTao Ye and M. Anthony McKerveyCite this: Chem. Rev. 1994, 94, 4, 1091–1160Publication Date (Print):June 1, 1994Publication History Published online1 May 2002Published inissue 1 June 1994https://pubs.acs.org/doi/10.1021/cr00028a010https://doi.org/10.1021/cr00028a010research-articleACS PublicationsRequest reuse permissionsArticle Views17581Altmetric-Citations1352LEARN ABOUT THESE METRICSArticle Views are the COUNTER-compliant sum of full text article downloads since November 2008 (both PDF and HTML) across all institutions and individuals. These metrics are regularly updated to reflect usage leading up to the last few days.Citations are the number of other articles citing this article, calculated by Crossref and updated daily. Find more information about Crossref citation counts.The Altmetric Attention Score is a quantitative measure of the attention that a research article has received online. Clicking on the donut icon will load a page at altmetric.com with additional details about the score and the social media presence for the given article. Find more information on the Altmetric Attention Score and how the score is calculated. Share Add toView InAdd Full Text with ReferenceAdd Description ExportRISCitationCitation and abstractCitation and referencesMore Options Share onFacebookTwitterWechatLinked InRedditEmail Other access optionsGet e-Alertsclose Get e-Alerts
Enabling robust information accountability in E-healthcare systems (2012)

In the United States, the transition from traditional paperbased healthcare records to electronic healthcare record (EHR) systems is being promoted aggressively. While EHR systems offer a number of benefits, they will introduce new security and privacy concerns. A significant fraction of such threats, at least in part, arise due to actions of insiders of healthcare organizations, either accidentally or intentionally. We believe information accountability, which allows us to securely identify how a health record reached a certain consumer and who was involved in its sharing or transfer, is a key to discourage such threats. In this work, we propose a patient-centric scheme to establish robust information accountability in electronic healthcare record sharing systems. We also present a prototype implementation and show that it does not impose unacceptable performance overhead.
Role of the Methoxy Group in Immune Responses to mPEG-Protein Conjugates (2012)

Anti-PEG antibodies have been reported to mediate the accelerated clearance of PEG-conjugated proteins and liposomes, all of which contain methoxyPEG (mPEG). The goal of this research was to assess the role of the methoxy group in the immune responses to mPEG conjugates and the potential advantages of replacing mPEG with hydroxyPEG (HO-PEG). Rabbits were immunized with mPEG, HO-PEG, or t-butoxyPEG (t-BuO-PEG) conjugates of human serum albumin, human interferon-α, or porcine uricase as adjuvant emulsions. Assay plates for enzyme-linked immunosorbent assays (ELISAs) were coated with mPEG, HO-PEG, or t-BuO-PEG conjugates of the non-cross-reacting protein, porcine superoxide dismutase (SOD). In sera from rabbits immunized with HO-PEG conjugates of interferon-α or uricase, the ratio of titers of anti-PEG antibodies detected on mPEG-SOD over HO-PEG-SOD ("relative titer") had a median of 1.1 (range 0.9-1.5). In contrast, sera from rabbits immunized with mPEG conjugates of three proteins had relative titers with a median of 3.0 (range 1.1-20). Analyses of sera from rabbits immunized with t-BuO-PEG-albumin showed that t-butoxy groups are more immunogenic than methoxy groups. Adding Tween 20 or Tween 80 to buffers used to wash the assay plates, as is often done in ELISAs, greatly reduced the sensitivity of detection of anti-PEG antibodies. Competitive ELISAs revealed that the affinities of antibodies raised against mPEG-uricase were c. 70 times higher for 10 kDa mPEG than for 10 kDa PEG diol and that anti-PEG antibodies raised against mPEG conjugates of three proteins had >1000 times higher affinities for albumin conjugates with c. 20 mPEGs than for analogous HO-PEG-albumin conjugates. Overall, these results are consistent with the hypothesis that antibodies with high affinity for methoxy groups contribute to the loss of efficacy of mPEG conjugates, especially if multiply-PEGylated. Using monofunctionally activated HO-PEG instead of mPEG in preparing conjugates for clinical use might decrease this undesirable effect.