gebhart/patrepeval huggingface dataset:
The impact of tobacco on lung health in China (2003)

China has the largest production and consumption of tobacco worldwide. It has witnessed a dramatic increase in tobacco consumption over the past two decades, with more than 34.8 million cartons of cigarettes being produced and 34.7 million sold annually. Approximately 67% of males and 4% of females aged over 15 years in China are smokers, and the total of over 320 million Chinese smokers represents about one-third of all smokers worldwide. The continuous, rapid increase in the number of Chinese smokers is largely due to teenagers taking up smoking. Among teenagers aged 15-19 years, 18% of men and 0.28% of women (making a total of 9 million teenagers) are smokers. The prevalence of passive smoking is very high at 53.5%, about 0.3 billion people aged above 15 years were affected. The average daily consumption of tobacco per person in China rose from one cigarette in 1952 to 10 cigarettes in 1990, a rate similar to that of the USA 40 years earlier. It seems inevitable that China will witness a substantial increase in mortality following this increase in smoking. Based on current smoking rates, the predicted deaths attributed to smoking in China will rise to 3 million in 2050. If the current smoking pattern in China remains unchanged, 100 million men now under 30 years will die from smoking-related diseases. The respiratory system is harmed most by tobacco smoke. Over two-thirds of all deaths related to smoking in China are attributed to chronic obstructive pulmonary disease (COPD), lung cancer and pulmonary tuberculosis. The morbidity of COPD alone in China is estimated at over 3%, or 25 million people, of whom 72% were smokers. The Chinese government consistently supports smoking control and advocates smoking abstinence via laws to restrain the sale and advertising of tobacco. These actions have been successful in some aspects, and in particular, more people are aware that 'cigarette smoking is harmful to health'. In future, the emphasis of smoking control should be directed at restraining teenagers and adolescents from smoking. Cigarette smoking has already caused significant ill-health to the Chinese population with over 1 million people dying each year of various disorders caused by smoking. However, the peak of smoking-induced diseases is still to come and therefore, it is very important to strengthen anti-smoking measures so as to have a far-reaching effect on the future health of the Chinese population.
Immune defense against pneumonic plague (2008)

Yersinia pestis is one of the world's most virulent human pathogens. Inhalation of this Gram-negative bacterium causes pneumonic plague, a rapidly progressing and usually fatal disease. Extensively antibiotic-resistant strains of Y. pestis exist and have significant potential for exploitation as agents of terrorism and biowarfare. Subunit vaccines comprised of the Y. pestis F1 and LcrV proteins are well-tolerated and immunogenic in humans but cannot be tested for efficacy, because pneumonic plague outbreaks are uncommon and intentional infection of humans is unethical. In animal models, F1/LcrV-based vaccines protect mice and cynomolgus macaques but have failed, thus far, to adequately protect African green monkeys. We lack an explanation for this inconsistent efficacy. We also lack reliable correlate assays for protective immunity. These deficiencies are hampering efforts to improve vaccine efficacy. Here, I review the immunology of pneumonic plague, focusing on evidence that humoral and cellular defense mechanisms collaborate to defend against pulmonary Y. pestis infection.
HEALTH MAINTENANCE ORGANIZATIONS VERSUS FEE FOR SERVICE: PATIENT SATISFACTION WITH COST AND QUALITY. (1992)

This study examines the tradeoff between consumer evaluations of cost and quality of HMOs using ordered profits. The results indicate that consumers may prefer HMOs if out-of-pocket costs are reduced without greatly sacrificing quality.
Pharmacokinetics and Oral Bioavailability of Hydrocortisone (1991)

The pharmacokinetics of 20 mg hydrocortisone were studied after IV and oral administration. Endogenous hydrocortisone was suppressed by dexamethasone administration. Hydrocortisone concentrations were measured in plasma and saliva. After IV administration, hydrocortisone was eliminated with a total body clearance of 18 L/hr and a half-life of 1.7 hr. The volume of distribution was 34 L. Oral bioavailability averaged 96%. Absorption was rapid, achieving maximum hydrocortisone levels of 300 ng/mL after 1 hour. Saliva levels were not proportional to plasma levels, but could be shown to reflect free, non-protein bound hydrocortisone concentrations in plasma.
Isolation of a glutamate synthase (GOGAT)-negative, pleiotropically N utilization-defective mutant of Azospirillum brasilense: cloning and partial characterization of GOGAT structural gene (1993)

An Azospirillum brasilense mutant (N12) pleiotropically defective in the assimilation of nitrogenous compounds (Asm-) was isolated and found lacking in the glutamate synthase (GOGAT-). The glt (GOGAT) locus of A. brasilense was identified by isolating a broad-host-range pLAFR1 cosmid clone from a gene library of the bacterium that rectified Asm- and GOGAT- defects (full recovery of activities of the nitrogenase, the assimilatory nitrate and nitrite reductases, and the glutamate synthase). A 7.5-kb EcoRI fragment of the cosmid clone that also complemented N12 was partially sequenced to identify the open reading frame for the alpha-subunit of GOGAT. The amino acid sequences deduced from the partial nucleotide sequences of the glt locus of A. brasilense showed considerable homology with that of the alpha-subunit of GOGAT coded by the gltB gene of Escherichia coli. The genetic lesion of N12 was found within the gltB gene of A. brasilense. The gltB promoter of A. brasilense showed the presence of a consensus sigma-70-like recognition site (as in E. coli) in addition to potential NtrA-RNA polymerase, IHF, and NifA binding sites.
Differential Labeling of Closely Spaced Biosensor Electrodes via Electrochemical Lithography (2006)

Electrochemical biosensors offer the promise of exceptional scalability and parallelizability. To achieve this promise, however, will require the development of new methods for the differential labeling of closely spaced electrodes with specific biomolecules such as DNA or proteins. Here we report a simple, highly selective method for passivating and differentially labeling closely separated gold electrodes with oligonucleotides or other biomolecules. Analogous to photolithography, where a light-sensitive resist is selectively removed to expose specific surfaces to further modification, we passivate gold electrodes with a self-assembled alkanethiol monolayer that protects them from modification. The monolayer is then electrochemically desorbed at relatively low potentials, allowing for the subsequent labeling of the now exposed array element with a specific sensing biomolecule. The observed passivation is highly efficient: using a C11-OH monolayer as the passivating agent, we do not observe any detectable cross-contamination of adjacent electrodes (95 microm separation) upon labeling with a stem-loop DNA probe. Critically, the conditions employed are sufficiently gentle that depassivation reduces the DNA load on adjacent electrodes by only approximately 1%, allowing for the sequential labeling of multiple, closely spaced electrodes. This technology paves the way for labeling multiple array elements sequentially without observable cross-contamination in a fast and controlled manner.
A single step purification for recombinant proteins Characterization of a microtubule associated protein (MAP 2) fragment which associates with the type II cAMP‐dependent protein kinase (1992)

A 167 base pair DNA cassette has been constructed to facilitate the detection and purification of recombinant proteins. This cassette, kfc, encodes three distinct peptide units: a phosphorylation site for the cAMP-dependent protein kinase (PKA), called kemptide, a factor Xa cleavage site, and a calmodulin-binding peptide. Expressed kfc fusion proteins can be purified from bacterial lysates in one step by affinity chromatography on calmodulin-agarose using EGTA as eluant. As a test of this system, we describe the expression, purification and characterization of the PKA binding domain of the microtubule associated protein (MAP 2).
Stem Cell Microenvironments ‐ Unveiling the Secret of How Stem Cell Fate is Defined (2010)

Stem cells are defined as unspecialized cells that are capable of long term self-renewal and differentiation into specialized cell types. These unique properties make them an attractive cell source for regenerative medicine applications. Although the functions of various stem cells have been extensively studied in the development of organisms and in diseases, the specific factors and conditions that control stem cell fate, specifically the conditions that allow them to remain unspecialized, are not well studied. It has been suggested that adult stem cell survival and maintenance, as well as proliferation and differentiation, are controlled by the three-dimensional (3D) microenvironment, the so-called niche. Major functional niche components include supporting niche cells, growth-modulating soluble factors stored within the niches, and the extracellular matrix (ECM). In this article, we review work highlighting the growing complexity of stem cell-ECM interactions and their impact on the fields of biomaterials research and regenerative medicine.
Suppression assays with human T regulatory cells: A technical guide (2011)

The suppression of inappropriate immune responses by Treg cells is one of the major ways that the body maintains immune tolerance and homeostasis. Since defects in the suppressive capacity of Treg cells underlie many different immune-mediated diseases, there is great interest in developing ways to track the number and function of Treg cells as biomarkers of tolerance and in devising ways to enhance their function therapeutically. However, the methods of studying human Treg cells are fraught with technical challenges that can often lead to misinterpretation. The most common way to determine the suppressive capacity of human Treg cells is to measure their ability to suppress the proliferation of responding CD4(+) T cells. Here, we discuss the technical considerations that must be taken into account when performing suppression of T-cell proliferation assays with human Treg cells. We also consider how T cells may falsely appear suppressive because of dying cells in the system, improper resting of T-cell lines prior to the assay, or insufficient proliferation of the responding T cells. We propose that, in the future, classification of a population of cells as "regulatory" should rely on more than a simple test for blockade of CD4(+) T-cell proliferation.
Identification of T-cell Receptors Targeting KRAS-Mutated Human Tumors (2016)

KRAS is one of the most frequently mutated proto-oncogenes in human cancers. The dominant oncogenic mutations of KRAS are single amino acid substitutions at codon 12, in particular G12D and G12V present in 60% to 70% of pancreatic cancers and 20% to 30% of colorectal cancers. The consistency, frequency, and tumor specificity of these "neoantigens" make them attractive therapeutic targets. Recent data associate T cells that target mutated antigens with clinical immunotherapy responses in patients with metastatic melanoma, lung cancer, or cholangiocarcinoma. Using HLA-peptide prediction algorithms, we noted that HLA-A*11:01 could potentially present mutated KRAS variants. By immunizing HLA-A*11:01 transgenic mice, we generated murine T cells and subsequently isolated T-cell receptors (TCR) highly reactive to the mutated KRAS variants G12V and G12D. Peripheral blood lymphocytes (PBL) transduced with these TCRs could recognize multiple HLA-A*11:01(+) tumor lines bearing the appropriate KRAS mutations. In a xenograft model of large established tumor, adoptive transfer of these transduced PBLs reactive with an HLA-A*11:01, G12D-mutated pancreatic cell line could significantly reduce its growth in NSG mice (P = 0.002). The success of adoptive transfer of TCR-engineered T cells against melanoma and other cancers supports clinical trials with these T cells that recognize mutated KRAS in patients with a variety of common cancer types.
Dappled photography (2007)

We describe a theoretical framework for reversibly modulating 4D light fields using an attenuating mask in the optical path of a lens based camera. Based on this framework, we present a novel design to reconstruct the 4D light field from a 2D camera image without any additional refractive elements as required by previous light field cameras. The patterned mask attenuates light rays inside the camera instead of bending them, and the attenuation recoverably encodes the rays on the 2D sensor. Our mask-equipped camera focuses just as a traditional camera to capture conventional 2D photos at full sensor resolution, but the raw pixel values also hold a modulated 4D light field. The light field can be recovered by rearranging the tiles of the 2D Fourier transform of sensor values into 4D planes, and computing the inverse Fourier transform. In addition, one can also recover the full resolution image information for the in-focus parts of the scene. We also show how a broadband mask placed at the lens enables us to compute refocused images at full sensor resolution for layered Lambertian scenes. This partial encoding of 4D ray-space data enables editing of image contents by depth, yet does not require computational recovery of the complete 4D light field.
Recently Approved and Upcoming Treatments for Narcolepsy (2020)

Narcolepsy is a chronic, disabling neurologic disorder characterised by excessive daytime sleepiness (EDS) and, in up to 60% of patients, cataplexy. Treatments for narcolepsy are aimed at improving wakefulness (e.g. modafinil, armodafinil, stimulants), reducing cataplexy attacks (e.g. sodium oxybate, venlafaxine), and treating the symptoms of disturbed nocturnal sleep, sleep paralysis and sleep-related hallucinations (e.g. sodium oxybate). In general, medications that increase the release, or inhibit the reuptake, of norepinephrine or dopamine have wake-promoting effects and are useful in managing EDS, whereas medications that inhibit serotonin or norepinephrine reuptake have anticataplectic effects. Modulation of γ-aminobutyric acid B (GABA<sub>B</sub>) receptors or histamine H<sub>3</sub> receptors (H3Rs) has effects on both EDS and cataplexy. Pitolisant, an H3R antagonist, and solriamfetol, a dopamine and norepinephrine reuptake inhibitor, are the most recently approved treatments for EDS associated with narcolepsy in the European Union (pitolisant) and the USA (pitolisant and solriamfetol). Several new agents are being developed and tested as potential treatments for EDS and cataplexy associated with narcolepsy; these agents include novel oxybate formulations (once-nightly [FT218]; low sodium [JZP-258]), a selective norepinephrine reuptake inhibitor (AXS-12), and a product combining modafinil and an astroglial connexin inhibitor (THN102). This review summarises the mechanisms of action, pharmacokinetics, efficacy, and safety/tolerability of recently approved and emerging treatments for narcolepsy.
Autophosphorylation of the Focal Adhesion Kinase, ppl25FAK, Directs SH2-Dependent Binding of pp60src (1994)

The phosphorylation of protein tyrosine kinases (PTKs) on tyrosine residues is a critical regulatory event that modulates catalytic activity and triggers the physical association of PTKs with Src homology 2 (SH2)-containing proteins. The integrin-linked focal adhesion kinase, pp125FAK, exhibits extracellular matrix-dependent phosphorylation on tyrosine and physically associates with two nonreceptor PTKs, pp60src and pp59fyn, via their SH2 domains. Herein, we identify Tyr-397 as the major site of tyrosine phosphorylation on pp125FAK both in vivo and in vitro. Tyrosine 397 is located at the juncture of the N-terminal and catalytic domains, a novel site for PTK autophosphorylation. Mutation of Tyr-397 to a nonphosphorylatable residue dramatically impairs the phosphorylation of pp125FAK on tyrosine in vivo and in vitro. The mutation of Tyr-397 to Phe also inhibits the formation of stable complexes with pp60src in cells expressing Src and FAK397F, suggesting that autophosphorylation of pp125FAK may regulate the association of pp125FAK with Src family kinases in vivo. The identification of Tyr-397 as a major site for FAK autophosphorylation provides one of the first examples of a cellular protein containing a high-affinity binding site for a Src family kinase SH2 domain. This finding has implications for models describing the mechanisms of action of pp125FAK, the regulation of the Src family of PTKs, and signal transduction through the integrins.
WWOX protein expression varies among ovarian carcinoma histotypes and correlates with less favorable outcome (2005)

These data indicate that WWOX protein expression is highly variable among ovarian carcinoma histotypes. It was also observed that subsets of ovarian tumors demonstrated loss of WWOX expression and is potentially associated with patient outcome.
New Paradigms for HIV/AIDS Vaccine Development (2011)

HIV-1 and its simian counterpart SIV have been exquisitely tailored by evolution to evade host immunity. By virtue of specific adaptations that thwart individual innate or adaptive immune mechanisms, and an overall replication strategy that provides for rapid establishment of a large, systemic viral population, capable of dynamic adaptation to almost all immune selection pressures, these viruses, once established, almost invariably stay one step ahead of the host's immune system, and in the vast majority of infected individuals, replicate indefinitely. Although many vaccine approaches tested to date have been able to enhance the magnitude of the immune responses to HIV/SIV infection, most of these responses, whether cellular or humoral, have largely failed to be both effectively antiviral and targeted to prevent the emergence of fully functional escape variants. Recent advances, however, have provided strong evidence that the initial stages of infection following mucosal transmission of these viruses are more vulnerable to immune intervention, and have led to the development of vaccine strategies that elicit responses able to effectively intervene in these early stages of infection, either preventing acquisition of infection or establishing early, stringent, and durable control. Here, we place HIV/AIDS vaccine development in the context of the basic immunobiology of HIV and SIV, review the evidence for their vulnerability to immune responses immediately after mucosal transmission, and discuss how this newly recognized vulnerability might be exploited for the development of an effective HIV/AIDS vaccine.
Chiral synthesis via organoboranes. 24. B-allylbis(2-isocaranyl)borane as a superior reagent for the asymmetric allylboration of aldehydes (1990)

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTChiral synthesis via organoboranes. 24. B-allylbis(2-isocaranyl)borane as a superior reagent for the asymmetric allylboration of aldehydesHerbert C. Brown, Ramnarayan S. Randad, Krishna S. Bhat, Marek Zaidlewicz, and Uday S. RacherlaCite this: J. Am. Chem. Soc. 1990, 112, 6, 2389–2392Publication Date (Print):March 1, 1990Publication History Published online1 May 2002Published inissue 1 March 1990https://pubs.acs.org/doi/10.1021/ja00162a047https://doi.org/10.1021/ja00162a047research-articleACS PublicationsRequest reuse permissionsArticle Views1133Altmetric-Citations116LEARN 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
Corneal collagen crosslinking: new horizons (2010)

Corneal collagen crosslinking using the photosensitzer riboflavin and UVA light has been introduced recently as an effective means of stabilizing the cornea in keratoconus and is currently entering mainstream use; the 6-year results have confirmed earlier positive results. Preoperative pachymetry to ensure a stromal thickness of at least 400 µm and individual control of the UVA irradiance of 3 mW/cm2 before each treatment are both mandatory to avoid serious risks. Complications such as keratitis, perforation or scarring are extremely rare. New applications of the technique are currently being explored, such as the treatment of post-laser in situ keratomileusis ectasia, pellucid marginal degeneration, therapy-refractive keratitis or bullous keratopathy. Thanks to crosslinking, the need for corneal transplantation should be reduced significantly in the future in various corneal disorders.
A primary undifferentiated pleomorphic sarcoma of the lumbosacral region harboring a LMNA-NTRK1 gene fusion with durable clinical response to crizotinib: a case report (2018)

The LMNA-NTRK1 fusion was likely the molecular driver of tumorigenesis and metastasis in this patient, and the observed effectiveness of crizotinib treatment provides clinical validation of this molecular target. Molecular and cytogenetic evaluations are critical to accurate prognosis and treatment planning in cases of UPS, especially when treatment options are limited or otherwise exhausted. Molecularly targeted therapy of these rare but aggressive lesions represents a novel treatment option that may lead to fewer toxic side effects and better clinical outcomes.