gebhart/patrepeval huggingface dataset:
Combining Incretin-Based Therapies With Insulin (2013)

### What is the rationale for adding incretin-based therapies to insulin?

The combination of the incretin-based therapies, i.e., the dipeptidyl peptidase (DPP)-4 inhibitors and glucagon-like peptide (GLP)-1 receptor agonists (GLP-1RAs), with basal insulin has, in theory, logical appeal. While basal insulin primarily improves fasting plasma glucose (FPG) control, the glucose-dependent effect of incretins will additionally benefit postprandial plasma glucose (PPG) control. This should enable improved control of A1C with the expectation of relatively stable blood glucose concentrations, and the combination of incretins with basal insulin might reduce insulin dose requirement and, consequently, weight gain. This also supports the concept that combining the incretin-based therapies with basal insulin should enable tight glycemic control with a low risk of hypoglycemia. Furthermore, a reciprocal benefit of this combination is that the basal insulin will theoretically supplement endogenous insulin production and “rest” the β-cell, enabling greater recovery of the endogenous insulin response when required. The basis of this theory is formed from research showing benefits with incretin therapies for β-cell function (1) and β-cell mass in experimental systems (2–4).

In addition to their antihyperglycemic properties, GLP-1RAs also reduce gastrointestinal motility, which, together with increased satiety, produces a weight-sparing effect (2). This quality could mitigate the weight gain associated with insulin therapy and might be further enhanced through any reductions in insulin dose.

### Evidence to date: how do the data from insulin plus incretin clinical studies meet with expectations?

#### Glycemic control.

Using basal insulin to reduce FPG is an effective way of improving glycemic control; however, the second component of glycemic control, PPG, requires additional consideration. This is one area where incretin-based therapies and basal insulin should have complementary actions.

##### Adding incretin-based therapies to insulin.

In an uncontrolled, retrospective investigation involving a cohort of 188 patients receiving insulin, the addition of exenatide produced an A1C reduction of –0.66% ( P < 0.001) from a baseline value of 8.05% after 6 months of combination therapy—an improvement that was maintained at 27 months (5). Moreover, the patients in this …
Interference of a four-hole aperture for on-chip quantitative two-dimensional differential phase imaging (2007)

We present a novel on-chip method for quantitative two-dimensional differential phase imaging. This technique uses four circular holes (600 nm diameter, 1.2 mum spacing) arranged in a 'plus' pattern that are fabricated in a layer of metal above a complementary metal-oxide semiconductor (CMOS) imaging sensor. The interference pattern of the aperture shifts position with respect to the differential phase of the incident light. By imaging the interference pattern with the CMOS sensor, this method measures amplitude and differential phase (1 degrees /microm sensitivity for signal-to-noise ratio >/=16 dB) of the incident light field simultaneously. An application to optical beam profiling is presented; we show the amplitude and differential phase profiles of a Gaussian laser beam and an optical vortex.
Contrastive Analysis with Predictive Power: Typology Driven Estimation of Grammatical Error Distributions in ESL (2015)

This work examines the impact of crosslinguistic transfer on grammatical errors in English as Second Language (ESL) texts. Using a computational framework that formalizes the theory of Contrastive Analysis (CA), we demonstrate that language specific error distributions in ESL writing can be predicted from the typological properties of the native language and their relation to the typology of English. Our typology driven model enables to obtain accurate estimates of such distributions without access to any ESL data for the target languages. Furthermore, we present a strategy for adjusting our method to low-resource languages that lack typological documentation using a bootstrapping approach which approximates native language typology from ESL texts. Finally, we show that our framework is instrumental for linguistic inquiry seeking to identify first language factors that contribute to a wide range of difficulties in second language acquisition.
Regulatory T Cell Responses in Participants with Type 1 Diabetes after a Single Dose of Interleukin-2: A Non-Randomised, Open Label, Adaptive Dose-Finding Trial (2016)

ISRCTN Registry ISRCTN27852285; ClinicalTrials.gov NCT01827735.
Interaction of a human FcγRIIb1 (CD32) isoform with murine and human IgG subclasses (1993)

A group of Fc receptor molecules, classified CD32, recognize the Fc moiety of IgG with low affinity. We report the isolation and identification of different hFc gamma RIIb cDNA clones, amongst which are cDNA clones encoding hFc gamma RIIb1 and hFc gamma RIIb2. Two hFc gamma RIIb1 encoding cDNA clones (pIP9 and pIP14) were isolated, which differed by three nucleotides, probably because of allelic variation. The nucleotide differences result in one amino acid change between the allelic hFc gamma RIIb1 variants. This substitution is located at amino acid position 11 of the cytoplasmic tail; a tyrosine in hFc gamma RIIb1 (clone pIP9) was replaced by an aspartic acid in clone pIP14 (encoding hFc gamma RIIb1*). A complication in studying ligand specificity of Fc receptors is the potential co-expression of different classes, subclasses, or polymorphic forms of FcR on the same cell. We therefore used murine fibroblasts transfected with cDNA clone pIP14, encoding a hFc gamma RIIb1* isoform, as our model system. These fibroblasts were found to interact with erythrocytes sensitized with mIgG2a and mIgG2b in rosetting assays performed at 4 and 37 degrees C. Interestingly, hFc gamma RIIb1* transfectants bound mIgG1 sensitized erythrocytes only weakly at 4 degrees C, whereas profound binding was observed at 37 degrees C. The ligand specificity for human (h) IgG isotypes was found to be hlgG3 > or = hlgG1 > hlgG4 > hlgG2, as determined at 4 degrees C with hlgG dimeric complexes. However, when assayed at 37 degrees C, the binding of hlgG2 dimers increased significantly. Next, we evaluated whether these transfectants were capable of supporting anti-CD3 induced T cell proliferation.(ABSTRACT TRUNCATED AT 250 WORDS)
Partial discharge. XIII. Acoustic partial discharge detection-fundamental considerations (1992)

An overview of the basic acoustics theory required to understand the finer points of acoustic partial discharge (PD) detection systems is given. PD and acoustic test methods are discussed, and acoustic wave motion, impedance, and intensity are described. Wave propagation and signal absorption, and the velocity of sound are discussed. Acoustic characteristics of media gases, liquids, and solid materials are described.< <ETX xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">&gt;</ETX>
Statistical analysis of observed and simulated hourly surface wind in the vicinity of the Panama Canal (2010)

Abstract Surface wind patterns at the Panama Canal vicinity are identified on the basis of 6 years of observed hourly surface wind data and with the use of high‐resolution numerical model simulations. Statistical analysis of the observed wind at various stations in the Panama Canal is presented, together with the analysis of simulated surface wind fields that are obtained from the MM5 mesoscale meteorological model using surface wind assimilation and forced by North American regional reanalysis data. The performance analysis indicates that the 2‐km‐resolution MM5 model surface wind simulations have skill when compared with the observations at the measurement sites. The analysis of the wind fields for the period 2002–2007 shows that the dry season (January to April) is more spatially and temporally coherent than the wet season in the region. The simulated wind shows that the average wind speed reaches up to 7–8 m s −1 and the frequency of exceeding 5 m s −1 reaches up to 0.7–0.8 in Lake Gatun, the entrance/exit of the Canal in the Caribbean and Pacific coasts, and at high elevations. The dry season exhibits higher climatological wind speeds and exceedence frequencies than the wet season but the wet season shows greater spatial variability. For both seasons, the morning hours have lower average winds than the evening hours. The analysis underlines the significant influence of convection, sea breeze and local conditions (elevation gradients and land surface cover) in the observed and simulated surface wind patterns. The information presented herein, particularly as regards the Canal centerline results, may be useful for identifying the effects of air pollution from sources aboard transiting cargo ships on large communities in the Canal vicinity (e.g. Panama City). Information presented is also relevant to regional wind energy studies and fog formation analyses. Copyright © 2010 Royal Meteorological Society
Recombinant Sindbis/Venezuelan Equine Encephalitis Virus Is Highly Attenuated and Immunogenic (2003)

Venezuelan equine encephalitis virus (VEEV) is an important, naturally emerging zoonotic virus. VEEV was a significant human and equine pathogen for much of the past century, and recent outbreaks in Venezuela and Colombia (1995), with about 100,000 human cases, indicate that this virus still poses a serious public health threat. The live attenuated TC-83 vaccine strain of VEEV was developed in the 1960s using a traditional approach of serial passaging in tissue culture of the virulent Trinidad donkey (TrD) strain. This vaccine presents several problems, including adverse, sometimes severe reactions in many human vaccinees. The TC-83 strain also retains residual murine virulence and is lethal for suckling mice after intracerebral (i.c.) or subcutaneous (s.c.) inoculation. To overcome these negative effects, we developed a recombinant, chimeric Sindbis/VEE virus (SIN-83) that is more highly attenuated. The genome of this virus encoded the replicative enzymes and the cis-acting RNA elements derived from Sindbis virus (SINV), one of the least human-pathogenic alphaviruses. The structural proteins were derived from VEEV TC-83. The SIN-83 virus, which contained an additional adaptive mutation in the nsP2 gene, replicated efficiently in common cell lines and did not cause detectable disease in adult or suckling mice after either i.c. or s.c. inoculation. However, SIN-83-vaccinated mice were efficiently protected against challenge with pathogenic strains of VEEV. Our findings suggest that the use of the SINV genome as a vector for expression of structural proteins derived from more pathogenic, encephalitic alphaviruses is a promising strategy for alphavirus vaccine development.
The Origins and development of ground stone assemblages in Late Pleistocene Southwest Asia (1991)

La technologie du mobilier en pierre est généralement considérée comme une condition préalable à la domestication des céréales. Les assemblages du Levant datant du Pléistocène récent et de l'Holocène ancien révèlent plusieurs tendances : 1) les outils en pierre polie sont attestés pour la première fois au Paléolithique ancien; 2) les récipients/mortiers apparaissent au cours du maximum glaciaire et coïncident ainsi avec les échantillons les plus anciens de céréales sauvages connus à ce jour en provenance de sites archéologiques; 3) les assemblages connus sont peu nombreux et restent pauvres jusqu'au Natoufien ancien; 4) les assemblages du Natoufien ancien sont nombreux; certains sont riches et beaucoup présentent une dominante de récipients/mortiers et de pilons; 5) le nombre de meules et de molettes s'accroît au Natoufien récent et plus particulièrement au PPNA et au PPNB, époques où sont documentées les plus anciennes céréales domestiques. Les données ethnographiques et expérimentales semblent montrer que la décortication des céréales sauvages au moyen des outils épipaléolithiques devait être ardue, ce qui pose la question de savoir si les céréales constituaient une source de nourriture "attrayante". Les mortiers et les pilons du Natoufien ancien suggèrent une décortication simple des céréales, ainsi que la préparation de nombreux aliments à base d'autres plantes. Ces ustensiles apparaissent dans des rituels funéraires, ce qui pourrait constituer dans le domaine de la nourriture des indices indirects de choix culturels, à une époque où la pression de l'environnement se fait plus forte. Les meules et les molettes du Natoufien récent-PPNA suggèrent l'intensification de modes d'exploitation pré-existants lors des modifications du milieu qui caractérisent la fin du Pléistocène.
Lightweight Email Signatures (2006)

Abstract. We present Lightweight Email Signatures (LES), a simple cryptographic architecture for authenticating email. LES is an extension of DKIM, the recent IETF effort to standardize domain-based email signatures. LES shares DKIM’s ease of deployment: they both use the DNS to distribute a single public key for each domain. Importantly, LES supports common uses of email that DKIM jeopardizes: multiple email personalities, firewalled ISPs, incoming-only email forwarding services, and other common uses that often require sending email via a thirdparty SMTP server. In addition, LES does not require DKIM’s implied intra-domain mechanism for authenticating users when they send email. LES provides these features using identity-based signatures. Each domain authority generates a master keypair, publishes the public component in the DNS, and stores the private component securely. Using this private component, the authority delivers to each of its users, via email, an individual secret key whose identity string corresponds to the user’s email address. A sender then signs messages using this individual secret key. A recipient verifies such a signature by querying the appropriate master public key from the DNS, computing the sender’s public key, and verifying the signature accordingly. As an added bonus, the widespread availability of user-level public keys enables deniable authentication, such as ring signatures. Thus, LES provides email authentication with optional repudiability. We built a LES prototype to determine its practicality. Basic user tests show that the system is relatively easy to use, and that cryptographic performance, even when using deniable authentication, is well within acceptable range.
Mitochondrial Dysregulation of Osteoarthritic Human Articular Chondrocytes Analyzed by Proteomics (2008)

Mitochondria are involved in many cellular processes; mitochondrial dysfunctions have been associated with apoptosis, aging, and a number of pathological conditions, including osteoarthritis (OA). Mitochondrial proteins are attractive targets for the study of metabolism of the chondrocyte, the unique cell type present in mature cartilage, and its role in tissue degradation. Using a proteomics approach based on two-dimensional DIGE and MALDI-TOF/TOF mass spectrometric identification of mitochondria- enriched protein fractions from human articular chondrocytes, we analyzed mitochondrial protein changes that are characteristic of OA chondrocytes. A total of 73 protein forms were unambiguously identified as significantly altered in OA; 23 of them have been previously described as mitochondrial. An extensive statistical and cluster analysis of the data revealed a mitochondrial protein profile characteristic for OA. This pattern includes alterations in energy production, maintenance of mitochondrial membrane integrity, and free radical detoxification. Real time PCR, Western blot, and immunohistofluorescence assays confirmed a significant decrease of the major mitochondrial antioxidant protein manganese-superoxide dismutase (SOD2) in the superficial layer of OA cartilage. As possible outputs for this antioxidant deficiency, we found an increase of intracellular reactive oxygen species generation in OA chondrocytes and also verified an OA-dependent increase in the mitochondrial tumor necrosis factor-alpha receptor-associated protein 1 (TRAP1), a chaperone with a reported reactive oxygen species antagonist role. Our results describe the differences between the mitochondrial protein profiles of normal and OA chondrocytes, demonstrating that mitochondrial dysregulation occurs in cartilage cells during OA and highlighting redox imbalance as a key factor in OA pathogenesis.
Molecular Genetic Insights into Cardiovascular Disease (1996)

The recent application of molecular genetic tools to inherited forms of cardiovascular disease has provided important insight into the molecular mechanisms underlying cardiac arrhythmias, cardiomyopathies, and vascular diseases. These studies point to defects in ion channels, contractile proteins, structural proteins, and signaling molecules as key players in disease pathogenesis. Genetic testing is now available for a subset of inherited cardiovascular diseases, and new mechanism-based therapies may be available in the near future. This remarkable progress and the implications it may have for more common forms of cardiovascular disease are reviewed here.
PPARs, Insulin Resistance and Type 2 Diabetes (2001)

It is clear that the PPAR receptors are exciting targets for therapeutic compounds likely to impact on insulin sensitivity, lipid and glucose homeostasis and vascular disease. The PPARgamma receptor agonists rosiglitazone and pioglitazone are very useful additions to the treatment options for type 2 diabetes. Currently they have limited licences, particularly in Europe, and hopefully as further clinical trial data becomes available these will be extended. Clinical outcome studies are important to ensure that the surrogate effects on glucose and other parameters translate into improved outcomes. There is exciting potential for these agents with the possibility of a combination of effects not only on glucose and lipid homeostasis but also on coagulation and thrombosis, blood pressure and microalbuminuria, which are likely to impact on vascular disease. If the current lack of evidence of serious hepatic toxicity persists they have an advantage over metformin in terms of tolerability and can be used in patients with impaired renal function. In addition to potential effects on diabetic outcome it will be of tremendous interest to determine whether these compounds, which improve insulin sensitivity and beta-cell function, will impact on the natural history of the disease. From what is known of the PPAR receptor systems it is likely that compounds acting as agonists or partial agonists for these receptors will have differing effects and it is possible to envisage the tailoring of compounds to enhance wanted effects and diminish unwanted effects, particularly fluid retention and weight gain. The future certainly looks exciting in this area.
European Thyroid Association (2014)

This issue is a dedicated supplement published in addition to the regular issues of 'European Thyroid Journal' containing congress abstracts. 'European Thyroid Journal' is a well-respected, international peer-reviewed journal in 'Endocrinology'. Supplement issues are included in the subscription.
Characterization of fibronectin-binding antigens released by Mycobacterium tuberculosis and Mycobacterium bovis BCG (1988)

Fibronectin (FN)-binding antigens are prominent components of short-term culture supernatants of Mycobacterium tuberculosis. In 3-day-old supernatants, a 30-kilodalton (kDa) protein was identified as the major FN-binding molecule. In 21-day-old supernatants, FN bound to a double protein band of 30 and 31 kDa, as well as to a group of antigens of larger molecular mass (57 to 60 kDa). FN-binding molecules in this size range, but not of 30 to 31 kDa, were also found in sonicates. We showed that the 31- and 30-kDa FN-binding bands correspond to components A and B of the BCG85 complex, previously shown to be abundant in culture supernatants of Mycobacterium bovis BCG. Thus, a polyclonal antibody to the BCG85 complex bound to the 30- and 31-kDa antigens and inhibited binding of FN to them on immunoblots of the culture filtrates. Similarly, FN bound to the purified components of the BCG85 complex, and this binding was blocked by the antibody. A monoclonal antibody, HYT27, also bound both to the BCG85 components A and B and to the 30- and 31-kDa FN-binding molecules of M. tuberculosis, but it did not block the binding of FN. Related molecules appear to be present on the surface of BCG and to mediate the binding of BCG to FN-coated plastic surfaces, since this binding could also be blocked by the polyclonal anti-BCG85 antibody and by the purified components of BCG85, particularly component A, but not by monoclonal antibody HYT27. The binding of these mycobacterial antigens to FN appears to be of very high affinity, and we suggest that this property of major secreted antigens of M. tuberculosis indicates an important role in mycobacterial disease and in the binding of BCG to tumor cells during immunotherapy of bladder cancer.
Evaluation of HBs, HBc, and frCP Virus-Like Particles for Expression of Human Papillomavirus 16 E7 Oncoprotein Epitopes (2002)

The HBs and HBc, but not frCP carriers support an efficient outcome for VLPs carrying the HPV16 E7 epitopes. All chimeric proteins may be regarded as potential vaccine candidates.
Does the suggestion that respondents recall events chronologically significantly influence the data collected (2001)

This paper is about estimating a salience scale for trip reporting. The measurement project began as a way of establishing the affects of methodological changes between 1994 and 1997 in the Canadian Travel Survey. This is a survey that Canada uses to study the travel of its residents. There were several changes in methodology that could be expected to influence how trips are recalled. A key change was that in 1994 the interviewers were encouraged to suggest to the respondents that they report chronologically but in 1996 and 1997 they were told not to use the prompt during interviews. It is likely that other changes resulted in response burden being higher in 1996 and 1997 than in 1994. For people reporting two or more trips, chronological reporting should result in trips being reported in random order. It was found that the order in which trips were reported changed with the change in memory cue. The change may have been exacerbated by some trips not being reported because of response burden. The data were analyzed using paired-comparison. The effect of the methodology change is found to be significant. The implications for future research as well as general implications for survey methodology are reported.