gebhart/patrepeval huggingface dataset:
cDNA, deduced polypeptide structure and chromosomal assignment of human pulmonary surfactant proteolipid, SPL(pVal). (1988)

In hyaline membrane disease of premature infants, lack of surfactant leads to pulmonary atelectasis and respiratory distress. Hydrophobic surfactant proteins of Mr = 5,000-14,000 have been isolated from mammalian surfactants which enhance the rate of spreading and the surface tension lowering properties of phospholipids during dynamic compression. We have characterized the amino-terminal amino acid sequence of pulmonary proteolipids from ether/ethanol extracts of bovine, canine, and human surfactant. Two distinct peptides were identified and termed SPL(pVal) and SPL(Phe). An oligonucleotide probe based on the valine-rich amino-terminal amino acid sequence of SPL(pVal) was utilized to isolate cDNA and genomic DNA encoding the human protein, termed surfactant proteolipid SPL(pVal) on the basis of its unique polyvaline domain. The primary structure of a precursor protein of 20,870 daltons, containing the SPL(pVal) peptide, was deduced from the nucleotide sequence of the cDNAs. Hybrid-arrested translation and immunoprecipitation of labeled translation products of human mRNA demonstrated an Mr = 22,000 precursor protein, the active hydrophobic peptide being produced by proteolytic processing to Mr = 5,000-6,000. Two classes of cDNAs encoding SPL(pVal) were identified. mRNA of approximately 900 bases was identified on Northern analysis of fetal and adult RNA. Human SPL(pVal) mRNA was more abundant in the adult than in fetal lung. The SPL(pVal) gene locus was assigned to chromosome 8.
A uniform approach to accelerated PageRank computation (2005)

In this note we consider a simple reformulation of the traditional power iteration algorithm for computing the stationary distribution of a Markov chain. Rather than communicate their current probability values to their neighbors at each step, nodes instead communicate only changes in probability value. This reformulation enables a large degree of flexibility in the manner in which nodes update their values, leading to an array of optimizations and features, including faster convergence, efficient incremental updating, and a robust distributed implementation.While the spirit of many of these optimizations appear in previous literature, we observe several cases where this unification simplifies previous work, removing technical complications and extending their range of applicability. We implement and measure the performance of several optimizations on a sizable (34M node) web subgraph, seeing significant composite performance gains, especially for the case of incremental recomputation after changes to the web graph.
An HSV-2 Trivalent Vaccine Is Immunogenic in Rhesus Macaques and Highly Efficacious in Guinea Pigs (2017)

A genital herpes vaccine is urgently needed to prevent pain and suffering, reduce the incidence of neonatal herpes, and decrease the risk of HIV acquisition and transmission that accompanies genital infection. We evaluated a trivalent HSV-2 subunit antigen vaccine administered with CpG and alum in rhesus macaques and guinea pigs. The vaccine contains glycoproteins C, D and E (gC2, gD2, gE2) to block virus entry by gD2 and immune evasion by gC2 and gE2. In rhesus macaques, the trivalent vaccine induced plasma and mucosa neutralizing antibodies, antibodies that block gC2 and gE2 immune evasion activities, and stimulated CD4 T cell responses. After intravaginal challenge, a self-limited vaginal infection of brief duration was detected by histopathology and immunohistochemistry in naïve, but not in trivalent immunized macaques. Vaccine efficacy was evaluated in female guinea pigs. Animals were mock immunized, or immunized with gD2, the trivalent vaccine or the trivalent vaccine followed by a booster dose of gD2 (trivalent + gD2). The trivalent and trivalent + gD2 groups were 97% and 99% efficacious, respectively in preventing genital lesions and both outperformed gD2 alone. As a marker of transmission risk, vaginal swabs were evaluated daily for HSV-2 DNA and replication competent virus between five and seven weeks after challenge. HSV-2 DNA shedding was reduced in all groups compared with mock. Shedding of replication competent virus occurred on fewer days in the trivalent than gD2 immunized animals while the trivalent + gD2 group had no shedding of replication competent virus. Overall, the trivalent group had genital lesions on < 1% days and shedding of replication competent virus on 0.2% days. The vaccine has outstanding potential for prevention of genital herpes in humans.
Reviving Lonidamine and 6-Diazo-5-oxo-L-norleucine to Be Used in Combination for Metabolic Cancer Therapy (2015)

Abnormal metabolism is another cancer hallmark. The two most characterized altered metabolic pathways are high rates of glycolysis and glutaminolysis, which are natural targets for cancer therapy. Currently, a number of newer compounds to block glycolysis and glutaminolysis are being developed; nevertheless, lonidamine and 6-diazo-5-oxo-L-norleucine (DON) are two old drugs well characterized as inhibitors of glycolysis and glutaminolysis, respectively, whose clinical development was abandoned years ago when the importance of cancer metabolism was not fully appreciated and clinical trial methodology was less developed. In this review, a PubMed search using the words lonidamine and 6-diazo-5-oxo-L-norleucine (DON) was undertaken to analyse existing information on the preclinical and clinical studies of these drugs for cancer treatment. Data show that they exhibit antitumor effects; besides there is also the suggestion that they are synergistic. We conclude that lonidamine and DON are safe and potentially effective drugs that need to be reevaluated in combination as metabolic therapy of cancer.
α-Tocopherol encapsulation and in vitro release from wheat gliadin nanoparticles (2002)

Alpha-tocopherol, or vitamin E (VE), is widely used as a strong antioxidant in many medical and cosmetic applications, but is rapidly degraded, because of its light, heat and oxygen sensitivity. Thus, all of its formulation has to avoid contact with light, heat or air. Drug loaded carriers are an attractive opportunity, especially if they are made for bioacceptable macromolecules such as vegetal proteins. For instance, gliadins, extracted from wheat gluten, generate nanoparticles by a desolvatation method and may interact with epidermal keratin for therapeutic or cosmetic formulations. Their lipophilic drug loading capacities have been investigated. The VE loaded gliadin nanoparticles have been characterized by their size, by their zeta potential, by their VE payload, and by their entrapment efficiency. When VE loaded, the gliadin particle size is approximately 900 nm and their charge is close to zero. They are suitable VE drug carriers with an optimum encapsulation rate approximately 100 VE microg/gliadin mg with an efficiency of more than 77%. The release behaviour of VE loaded nanoparticles may be interpreted as a 'burst effect', followed by a diffusion process through an homogeneous sphere.
Multiple molecular logic functions and molecular calculations facilitated by surfactant’s versatility (2008)

Two isomeric compounds and , combining intramolecular charge transfer (ICT) and photoinduced electron transfer (PET) mechanisms together, were designed and used as logic gates with configurable multiple outputs; ten different logic functions (AND, NAND, OR, NOR, XNOR, INHIBIT, YES, NO, PASS 1 and PASS 0) were achieved by varying the inputs threshold or by altering the inputs; furthermore, half addition and half subtraction were performed within (or ); the concept demonstrated here may provide a strategy for constructing more integrated molecular level devices with multiple functions.
An experimental evaluation of rate-adaptation algorithms in adaptive streaming over HTTP (2011)

Adaptive (video) streaming over HTTP is gradually being adopted, as it offers significant advantages in terms of both user-perceived quality and resource utilization for content and network service providers. In this paper, we focus on the rate-adaptation mechanisms of adaptive streaming and experimentally evaluate two major commercial players (Smooth Streaming, Netflix) and one open source player (OSMF). Our experiments cover three important operating conditions. First, how does an adaptive video player react to either persistent or short-term changes in the underlying network available bandwidth. Can the player quickly converge to the maximum sustainable bitrate? Second, what happens when two adaptive video players compete for available bandwidth in the bottleneck link? Can they share the resources in a stable and fair manner? And third, how does adaptive streaming perform with live content? Is the player able to sustain a short playback delay? We identify major differences between the three players, and significant inefficiencies in each of them.
Amylin-insulin relationships in insulin resistance with and without diabetic hyperglycemia (1993)

To determine if increased secretion of amylin can be implicated in the pathogenesis of non-insulin-dependent diabetes mellitus (NIDDM) in vitro and in vivo, we studied its relationships to insulin in insulin-resistant rats with and without NIDDM. In obesity-associated and dexamethasone-induced insulin resistance without diabetes, basal and stimulated secretion of amylin and insulin by isolated pancreata were proportionately elevated, leaving the amylin-to-insulin ratio (A/I) unchanged. By contrast, whenever diabetes occurred in dexamethasone-treated rats or in spontaneously diabetic obese insulin-resistant ZDF-drt male rats, a doubling of A/I was invariably observed due to an increase in amylin without a proportional increase in insulin secretion. Correction of dexamethasone-induced hyperglycemia with the glucocorticord receptor antagonist RU-486 was accompanied by a decline in A/I. Longitudinal in vivo studies demonstrated in both spontaneous and dexamethasone-induced models of NIDDM an increase in plasma A/I at the onset of hyperglycemia. In dexamethasone-induced diabetes, the increased A/I was associated with a high proamylin mRNA relative to proinsulin mRNA. We conclude that amylin and insulin expression and secretion rise in concert in compensated insulin-resistant states, but when hyperglycemia is present the increase in amylin exceeds that of insulin. Although a role of an increased A/I in the pathogenesis of NIDDM has not been established directly, these studies indicate that such a role could be possible.
Denosumab for Prevention of Fractures in Postmenopausal Women with Osteoporosis (2009)

Denosumab given subcutaneously twice yearly for 36 months was associated with a reduction in the risk of vertebral, nonvertebral, and hip fractures in women with osteoporosis. (ClinicalTrials.gov number, NCT00089791.)
Macrocycles Are Great Cycles: Applications, Opportunities, and Challenges of Synthetic Macrocycles in Drug Discovery (2011)

ADVERTISEMENT RETURN TO ISSUEPREVPerspectiveNEXTMacrocycles Are Great Cycles: Applications, Opportunities, and Challenges of Synthetic Macrocycles in Drug DiscoveryEric Marsault*† and Mark L. Peterson*‡View Author Information† Institut de Pharmacologie de Sherbrooke, Université de Sherbrooke, Sherbrooke Québec, J1H5N4, Canada‡ Tranzyme Pharma Inc., 3001 12e Avenue Nord, Sherbrooke, Québec, J1H5N4, Canada*For E.M.: phone, +819.820.6868, extension 12433; fax, +819.820.6841; e-mail, [email protected]. For M.L.P.: phone, +819.820.6845; fax, 819.820.6841; e-mail, [email protected]Cite this: J. Med. Chem. 2011, 54, 7, 1961–2004Publication Date (Web):March 7, 2011Publication History Received23 September 2010Published online7 March 2011Published inissue 14 April 2011https://pubs.acs.org/doi/10.1021/jm1012374https://doi.org/10.1021/jm1012374review-articleACS PublicationsCopyright © 2011 American Chemical SocietyRequest reuse permissionsArticle Views18103Altmetric-Citations695LEARN 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 SUBJECTS:Chemical structure,Inhibitors,Macrocycles,Macrocyclization,Peptides and proteins Get e-Alerts
Gene (mRNA) expression in canine atopic dermatitis: microarray analysis (2008)

Genes potentially involved in the pathology of canine atopic dermatitis (AD) were identified using gene expression microarrays. Total RNA extracted from skin biopsies was hybridized to an Agilent Technologies custom-designed 22K canine array. The arrays were analysed using Genedata Analyst software. Data were corrected for multiple hypothesis testing and tested for significance using the National Institute on Aging array analysis tool. For comparison, data were divided into separate groups: lesional atopic (n = 16), nonlesional atopic (n = 17) and healthy controls (n = 9). Fifty-four genes were differentially expressed at a significance level of 0.05 in canine AD compared to healthy controls. Sixteen genes were differentially expressed in both nonlesional and lesional atopic skin, 26 genes only in nonlesional skin and 12 only in lesional skin. These genes were associated with innate immune and inflammatory responses, cell cycle, apoptosis, barrier formation and transcriptional regulation. The most dysregulated gene in lesional skin was S100A8, which showed an almost 23-fold increase in expression. This is a pro-inflammatory cytokine located in the epidermal differentiation complex. Microarray analysis is a novel technique in canine AD. Significant changes in gene expression were identified in atopic skin. These were relevant to skin barrier formation and the immune response, suggesting that they both participate in AD. Gene expression restricted to lesional skin may be involved in inflammatory changes, whereas those shared or restricted to nonlesional skin may reflect the atopic phenotype. Investigating gene polymorphisms in the targets identified in this study will help improve our understanding of the genetic basis of this disease.
Pimobendan Increases Survival of Cardiomyopathic Hamsters (1989)

We investigated the effect of the new cardiotonic drug pimobendan on survival of hereditary cardiomyopathic hamsters. Untreated cardiomyopathic hamsters served as controls. A 50% mortality was observed after 280 days for the control group and after 318 days for the pimobendan-treated animals. After 340 days, survival was 0% for the untreated cardiomyopathic hamsters and 27% in the pimobendan-treated group. We conclude that pimobendan slows the progression of heart failure in cardiomyopathic hamsters.
DNA-launched RNA replicon vaccines induce potent anti-SARS-CoV-2 immune responses in mice (2021)

The outbreak of the SARS-CoV-2 virus and its rapid spread into a global pandemic made the urgent development of scalable vaccines to prevent coronavirus disease (COVID-19) a global health and economic imperative. Here, we characterized and compared the immunogenicity of two alphavirus-based DNA-launched self-replicating (DREP) vaccine candidates encoding either SARS-CoV-2 spike glycoprotein (DREP-S) or a spike ectodomain trimer stabilized in prefusion conformation (DREP-S<sup>ecto</sup>). We observed that the two DREP constructs were immunogenic in mice inducing both binding and neutralizing antibodies as well as T cell responses. Interestingly, the DREP coding for the unmodified spike turned out to be more potent vaccine candidate, eliciting high titers of SARS-CoV-2 specific IgG antibodies that were able to efficiently neutralize pseudotyped virus after a single immunization. In addition, both DREP constructs were able to efficiently prime responses that could be boosted with a heterologous spike protein immunization. These data provide important novel insights into SARS-CoV-2 vaccine design using a rapid response DNA vaccine platform. Moreover, they encourage the use of mixed vaccine modalities as a strategy to combat SARS-CoV-2.
Regulation of Interleukin 12 p40 Expression through an NF-κB Half-Site (1995)

Interleukin 12 (IL-12) is an inducible cytokine composed of 35- and 40-kDa subunits that is critical for promoting T helper type 1 development and cell-mediated immunity against pathogens. The 40-kDa subunit, expressed by activated macrophages and B cells, is induced by several pathogens in vivo and in vitro and is augmented or inhibited by gamma interferon (IFN-gamma) or IL-10, respectively. Control of IL-12 p40 expression is therefore important for understanding resistance and susceptibility to a variety of pathogens, including Leishmania major and perhaps human immunodeficiency virus. In this report, we provide the first characterization of IL-12 p40 gene regulation in macrophages. We localize inducible activity of the promoter to the sequence -122GGGGAATTTTA-132 not previously recognized to bind Rel family transcription factors. We demonstrate binding of this sequence to NF-kappa B (p50/p65 and p50/c-Rel) complexes in macrophages activated by several p40-inducing pathogens and provide functional data to support a role for NF-kappa B family members in IL-12 p40 activation. Finally, we find that IFN-gamma treatment of cells enhances this binding interaction, thus potentially providing a mechanism for IFN-gamma augmentation of IL-12 production by macrophages.
IP over optical networks: architectural aspects (2000)

The Internet transport infrastructure is moving toward a model of high-speed routers interconnected by intelligent optical core networks. A consensus is emerging in the industry on utilizing an IP-centric control plane within optical networks to support dynamic provisioning and restoration of lightpaths. At the same time, there are divergent views on how IP routers must interact with optical core networks to achieve end-to-end connectivity. This article describes the architectural alternatives for interconnecting IP routers over optical networks, considering the routing and signaling issues. Also, the application of IP-based protocols for dynamic provisioning and restoration of lightpaths, as well as the interworking of multivendor optical networks is described.
Ultra-high speed semiconductor lasers (1985)

Recent progress on semiconductor lasers having a very high direct modulation bandwidth of beyond 10 GHz will be described. Issues related to application of these lasers in actual systems will be addressed. Possibilities of further extending the bandwidth of semiconductor lasers will be examined.
Interleukin-7 gene transfer in non-small-cell lung cancer decreases tumor proliferation, modifies cell surface molecule expression, and enhances antitumor reactivity. (1997)

Cytokine gene transfer to tumor cells can augment host antitumor responses and modify tumor phenotype. To evaluate the immunoregulatory and antitumor capacities of lung tumor-derived interleukin-7 (IL-7), we transduced non-small-cell lung cancer (NSCLC) cell lines with the IL-7/HyTK internal ribosomal entry site (IRES) retroviral vector and evaluated modifications in tumor phenotype and cocultured effector activities. In vitro proliferation of IL-7-transduced tumor cells was significantly less than control vector-transduced and parental tumor cells. The decreased proliferation rates of IL-7-transduced cells could be reproduced by adding high concentrations of recombinant IL-7 to the parental cells. Anti-IL-7 monoclonal antibody significantly increased the proliferation of the IL-7-transduced cells (P < .05). Parental NSCLC cells were found to express the IL-7 receptor, and IL-7 gene transduction did not alter expression of the IL-7 receptor. IL-7 transduction significantly altered tumor cell expression of intracellular adhesion molecule 1, major histocompatibility complex 1, lymphocyte function-related antigen 3, very late activation antigen beta 1, and p185neu. Peripheral blood lymphocytes cocultured with either IL-7-transduced tumor cells or tumor supernatants had enhanced cytolytic and proliferative capacities compared with coculture with control vector-transduced or parental cells. Our findings indicate that IL-7 gene transfer in NSCLC significantly augments cocultured effector activities in vitro, inhibits tumor cell proliferation, and modifies tumor cell surface phenotype. These findings suggest that IL-7 gene therapy may be effective in modifying host antitumor responses in NSCLC.
Metformin in obesity, cancer and aging: addressing controversies (2012)

Metformin, an oral anti-diabetic drug, is being considered increasingly for treatment and prevention of cancer, obesity as well as for the extension of healthy lifespan. Gradually accumulating discrepancies about its effect on cancer and obesity can be explained by the shortage of randomized clinical trials, differences between control groups (reference points), gender- and age-associated effects and pharmacogenetic factors. Studies of the potential antiaging effects of antidiabetic biguanides, such as metformin, are still experimental for obvious reasons and their results are currently ambiguous. Here we discuss whether the discrepancies in different studies are merely methodological or inherently related to individual differences in responsiveness to the drug.
A 3D implantable microsystem for intraocular pressure monitoring using a glass-in-silicon reflow process (2011)

This paper describes an implantable microsystem being developed to continuously monitor intraocular pressure. The glass-in-silicon reflow process allows the formation of an embedded cavity and a variety of device shapes. A 0.18μm CMOS circuit fits within the cavity and uses vertical feedthroughs in the glass to interface with other components. An optical trigger wakes up the IC to take data, reducing idle-mode power consumption to 50pW. The glass package allows the possibility of solar energy harvesting and provides haptics that facilitate implantation and allow explantation without tissue damage. The final microsystem will incorporate a microprocessor, microbattery, pressure sensor, and antenna.
Design considerations for a multihop wireless network testbed (2005)

Limited fidelity of simulators has prompted researchers to build wireless network testbeds for realistic testing. Unlike simulators, which have broad applicability, most of these testbeds are tailored to specific projects and cannot be used by a wider research community. Recognizing the growing importance of testbeds, this article is one of the first attempts to identify a comprehensive set of requirements for a general-purpose multihop wireless network testbed and the challenges therein. The issues range from initial testbed deployment and routine management to individual experimental configuration and data collection. We survey state-of-the-art wireless testbeds and highlight their salient features. The article is intended to provide an initial reference for researchers, application developers, and administrators dealing with various aspects of wireless network testbeds.