gebhart/patrepeval huggingface dataset:
Role of Inhibitory BCR Co-Receptors in Immunity (2012)

B lymphocytes (B cells) express a variety of membrane molecules containing immunoreceptor tyrosine-based inhibition motifs (ITIMs) in the cytoplasmic region such as FcγRIIB, FCRLs, CD22, mouse Siglec-G/human Siglec-10, PECAM-1, mouse PIR-B/human LIRB1 and LIRB2PD-1 and CD72. When phosphorylated, ITIMs in these molecules recruit and activate phosphatases such as SH2 domain-containing protein tyrosine phosphatase 1 (SHP-1), SHP-2, SH2 domain- containing inositol 5-phosphatase 1 (SHIP1) and SHIP2 depending on receptors. These phosphatases then negatively regulate B cell antigen receptor (BCR) signaling. Because of their ability to inhibit BCR signaling, these ITIMcontaining molecules are called inhibitory BCR co-receptors. Studies on mice deficient in an inhibitory co-receptor have demonstrated that the inhibitory co-receptors regulate B cell development, antibody responses and development of autoimmune diseases. Moreover, polymorphisms in some inhibitory co-receptors such as FcγRIIB, FCRL3 and CD72 are associated with autoimmune diseases, suggesting a crucial role of inhibitory co-receptor polymorphisms in the regulation of autoimmune diseases. The ligands for inhibitory co-receptors regulate their inhibitory activity by inducing co-ligation of the co-receptors with BCR or some other regulatory mechanisms. Inhibitory co-receptors and their ligands are therefore good targets for controlling antibody responses and autoimmune diseases.
Selection of DNA binding sites by regulatory proteins: the LexA protein and the arginine repressor use different strategies for functional specificity (1988)

The DNA sequences in the operator sites of the arginine regulon and of the SOS regulon have been subject to a statistical analysis. A quantitative correlation is found between the statistics of sequence choice and the activity at individual operator sites in both systems, as expected from theoretical considerations [Berg & von Hippel, J.Mol.Biol. (1987) 193, 723-750]. Based on these correlations it is possible to predict the effect of various sequence mutations. There is a significant difference in the slopes of the correlation lines between sequence and activity for the two systems. From this difference it can be expected that individual point mutations in the ARG boxes will have a much smaller effect on activity than similar changes in the SOS boxes. This difference may be related to a strong cooperative activity at tandem ARG boxes while the binding at SOS boxes appears to be mostly noncooperative.
Update on the biomarker core of the Alzheimer's Disease Neuroimaging Initiative subjects (2010)

Here, we review progress by the Penn Biomarker Core in the Alzheimer's Disease Neuroimaging Initiative (ADNI) toward developing a pathological cerebrospinal fluid (CSF) and plasma biomarker signature for mild Alzheimer's disease (AD) as well as a biomarker profile that predicts conversion of mild cognitive impairment (MCI) and/or normal control subjects to AD. The Penn Biomarker Core also collaborated with other ADNI Cores to integrate data across ADNI to temporally order changes in clinical measures, imaging data, and chemical biomarkers that serve as mileposts and predictors of the conversion of normal control to MCI as well as MCI to AD, and the progression of AD. Initial CSF studies by the ADNI Biomarker Core revealed a pathological CSF biomarker signature of AD defined by the combination of Abeta1-42 and total tau (T-tau) that effectively delineates mild AD in the large multisite prospective clinical investigation conducted in ADNI. This signature appears to predict conversion from MCI to AD. Data fusion efforts across ADNI Cores generated a model for the temporal ordering of AD biomarkers which suggests that Abeta amyloid biomarkers become abnormal first, followed by changes in neurodegenerative biomarkers (CSF tau, F-18 fluorodeoxyglucose-positron emission tomography, magnetic resonance imaging) with the onset of clinical symptoms. The timing of these changes varies in individual patients due to genetic and environmental factors that increase or decrease an individual's resilience in response to progressive accumulations of AD pathologies. Further studies in ADNI will refine this model and render the biomarkers studied in ADNI more applicable to routine diagnosis and to clinical trials of disease modifying therapies.
Inductive and Ultrasonic Multi-Tier Interface for Low-Power, Deeply Implantable Medical Devices (2012)

We report the development of a novel multi-tier interface which enables the wireless, noninvasive transfer of sufficient amounts of power as well as the collection and transmission of data from low-power, deeply implantable analog sensors. The interface consists of an inductive coupling subsystem and an ultrasonic subsystem. The designed and experimentally verified inductive subsystem ensures that 5 W of power is transferred across 10 mm of air gap between a single pair of PCB spiral coils with an efficiency of 83% using our prototype CMOS logic gate-based driver circuit. The implemented ultrasonic subsystem, based on ultrasonic PZT ceramic discs driven in their low-frequency, radial/planar-excitation mode, further ensures that 29 μW of power is delivered 70 mm deeper inside a homogenous liquid environment-with no acoustic matching layer employed-with an efficiency of 1%. Overall system power consumption is 2.3 W. The implant is intermittently powered every 800 msec; charging a capacitor which provides sufficient power for a duration of ~ 18&nbsp;msec; sufficient for an implant μC operating at a frequency of 500 KHz to transmit a nibble (4 bits) of digitized sensed data.
Circulating Concentrations of the Adipocyte Protein Adiponectin Are Decreased in Parallel With Reduced Insulin Sensitivity During the Progression to Type 2 Diabetes in Rhesus Monkeys (2001)

Adiponectin is an adipose-specific plasma protein whose plasma concentrations are decreased in obese subjects and type 2 diabetic patients. This protein possesses putative antiatherogenic and anti-inflammatory properties. In the current study, we have analyzed the relationship between adiponectin and insulin resistance in rhesus monkeys (Macaca mulatta), which spontaneously develop obesity and which subsequently frequently progress to overt type 2 diabetes. The plasma levels of adiponectin were decreased in obese and diabetic monkeys as in humans. Prospective longitudinal studies revealed that the plasma levels of adiponectin declined at an early phase of obesity and remained decreased after the development of type 2 diabetes. Hyperinsulinemic-euglycemic clamp studies revealed that the obese monkeys with lower plasma adiponectin showed significantly lower insulin-stimulated peripheral glucose uptake (M rate). The plasma levels of adiponectin were significantly correlated to M rate (r = 0.66, P < 0.001). Longitudinally, the plasma adiponectin decreased in parallel to the progression of insulin resistance. No clear association was found between the plasma levels of adiponectin and its mRNA levels in adipose tissue. These results suggest that reduction in circulating adiponectin may be related to the development of insulin resistance.
Knockdown of Human &lt;italic&gt;p53&lt;/italic&gt; Gene Expression in 293-T Cells by Retroviral Vector-mediated Short Hairpin RNA (2005)

RNA interference (RNAi) is an evolutionarily conserved process of gene silencing in multiple organisms, which has become a powerful tool for investigating gene function by reverse genetics. Recently, many groups have reported to use synthesized oligonucleotides or siRNA encoding plasmids to induce RNAi in mammalian cells by transfection, but this is still limited in its application, especially when it is necessary to generate long-term gene silencing in vivo. To circumvent this problem, retrovirus- or lentivirus-delivered RNAi has been developed. Here, we described two retroviral systems for delivering short hairpin RNA (shRNA) transcribed from the H1 promoter. The results showed that retroviral vector-mediated RNAi can substantially downregulate the expression of human p53 in 293-T cells. Furthermore, the retroviral vector-mediated RNAi in our transduction system can stably inactivate the p53 gene for a long time. Compared to shRNAs transcribed from the U6 promoter, H1-driven shRNA also dramatically reduced the expression of p53. The p53 downregulation efficiencies of H1- and U6-driven shRNAs were almost identical. The results indicate that retroviral vector-delivered RNAi would be a useful tool in functional genomics and gene therapy.
A peer-to-peer agent auction (2002)

In this work we examine a peer-to-peer agent continuous double auction. We compare agents trading using peer-to-peer communications with agents using the same trading strategy in an auction that makes use of a centralized auctioneer to disseminate information. We present simulation data for these two auctions running with 2,500 to 160,000 agents. We find that the peer-to-peer auction is able to display price convergence behavior similar to that of the centralized auction. Further, the data shows that the peer-to-peer system has a constant cost in the number of message rounds needed to find the market equilibrium price as the number of traders is increased, in contrast to the linear cost incurred by the central auctioneer. Considering the above message costs, the peer-to-peer system outperformed the simple central auction by at least 100 times in our simulations. We further calculate that for a distributed hierarchical set of auctioneers, for which the message rounds cost of finding equilibrium are reduced to logarithmic in the number of traders, the peer-to-peer system will still produce better performance for systems with more than 5,000 traders.
Intelligent agents for matching information providers and consumers on the World-Wide-Web (2002)

We discuss the various issues in designing intelligent software systems to assist World Wide Web users in locating relevant information. We identify a number of key components in such intelligent systems. These include a Web document database management system, a client based goal directed search engine, an intelligent learning agent which discovers users' topics of interest by studying their browsing behavior, and an intelligent agent which monitors "hot" Web sites. We give examples and suggestions on how these components are designed and implemented. We also describe the architecture of a prototype system that integrates the various components.
HLA transgenic mice as humanized mouse models of disease and immunity. (1998)

The application of molecular genetics to human disease in the past decade has been helpful in elucidating the genetic influences involved in the induction and pathogenesis of various autoimmune diseases. Among the numerous genes studied for their role in disease development, polymorphisms within HLA class I and class II loci play a significant role in predisposition to disease. HLA molecules are encoded by genes on the short arm of chromosome 6. Crystal structures of MHC molecules show a peptide binding cleft which contains the variable region of MHC molecules. Genetic polymorphism at the MHC determines the specificity and affinity of peptide binding and T cell recognition. HLA molecules play a pivotal role in T cell repertoire selection in the thymus and antigen presentation in the periphery. Analysis of T cell responses in humans has involved the use of T cell lines or clones in vitro from naturally primed individuals. On the other hand, MHC restriction, mapping of epitope recognition, and T cell function in murine systems have been determined by in vivo studies. Various experimental animal models of autoimmune diseases have been studied, contributing greatly to our basic understanding of the disease. For example, type II collagen‐induced arthritis (CIA) 1 in mice and rats has been used as an experimental model for RA. Even though the model differs in the manner polyarthritis is induced, disease expression is broadly similar to RA, with the occurrence of symmetrical peripheral polyarthritis and systemic inflammation. Although growing knowledge of the functions of T and B cells in the immune response has shed light on their role in disease induction, the pathogenic mechanisms of most autoimmune diseases remain unresolved. There are many unanswered questions as to how tolerance to self is usually maintained, because autoreactive T cells can be found in normal as well as diseased individuals. How is tolerance broken in autoimmunity? Do specific autoantigens trigger the immune system to mount tissue-destructive responses? These questions need to be solved for most of the autoimmune diseases. Although the strongest MHC association with an autoimmune disease is between HLA class I B27 and spondyloarthropathies, class II alleles are implicated in most other cases. For example, RA is strongly associated with alleles of the DRB1 locus, whereas diabetes shows a stronger association with DQB1 alleles. HLA-DR and -DQ alleles are inherited en bloc and are known to occur in linkage disequilibrium. To better understand the role of HLA molecules in autoimmune diseases, transgenic animals expressing human HLA genes associated with disease have been developed. The generation of transgenic mice expressing functional HLA molecules has been an important step toward the creation of an in vivo model for enhancing our understanding of the function of human molecules in disease induction and predisposition. The potential value of HLA transgenic animals as a “humanized” disease model was first illustrated in the HLA-B27
Fast and scalable packet classification (2003)

Emerging Internet applications create the need for advanced packet classifiers. We propose a novel multifield classification scheme, called P <sup xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">2</sup> C, which exploits the strengths of state-of-the-art memory technologies to provide wire-speed classification performance for OC-192 and beyond, in combination with very high storage efficiency and the support of fast incremental updates. Key features of the new scheme are its ability to adapt to the complexity of a classification rule set, whereas the storage requirements and update dynamics can be tuned at the granularity of individual rules. This makes P <sup xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">2</sup> C suitable for a broad spectrum of applications.
A novel cadherin cell adhesion molecule: its expression patterns associated with implantation and organogenesis of mouse embryos. (1986)

The Ca2+-dependent cell adhesion molecules, termed cadherins, were previously divided into two subclasses, E- and N-types, with different adhesive specificity. In this study, we identified a novel class of cadherin, termed P-cadherin, using a visceral endoderm cell line PSA5-E. This cadherin was a 118,000-D glycoprotein and distinct from E- and N-cadherins in immunological specificity and molecular mass. In accord with these findings, cells with P-cadherin did not cross-adhere with cells with E-cadherin. P-Cadherin first appeared in developing mouse embryos in the extraembryonic ectoderm and the visceral endoderm at the egg cylinder stage and later was expressed in various tissues. The placenta and the uterine decidua most abundantly expressed this cadherin. The expression of P-cadherin was transient in many tissues, and its permanent expression was limited to certain tissues such as the epidermis, the mesothelium, and the corneal endothelium. When the tissue distribution of P-cadherin was compared with that of E-cadherin, we found that: each cadherin displayed a unique spatio-temporal pattern of expression; P-cadherin was co-expressed with E-cadherin in local regions of various tissues; and onset or termination of expression of P-cadherin was closely associated with connection or segregation of cell layers, as found with other cadherins. These results suggested that differential expression of multiple classes of cadherins play a role in implantation and morphogenesis of embryos by providing cells with heterogenous adhesive specificity.
Defining Non-International Armed Conflict: A Historically Difficult Task (2012)

A s the initial speaker on the first panel of the Newport conference dealing with non-international armed con flict (NIAC) in the twenty-first century, was asked to do two things. First, establish the framework for a broad and comprehensivediscussion ofNIAC by assessing, historically. the wayin which the international community has attempted to define this particular form of conflict, to include the issue of whether there now exist various types ofNIAC. Second, speak to the U.S. practice with respect to the manner in which the United States has determined whether to designate certain hostilities as NlACs. In undertaking that mandate, was reminded of the words of Sir Hersch Lauterpacht: [ Jf international law is. in some ways, at the vanishing point oflaw, the law of war is, perhaps even more conspicuously, at the vanishing point of international law. I And, given the nuances of our current subject matter, would think it appropriate to add to this statement If the law of war is at the vanishing point of international law, then, surely, the law related to non-international armed conflict is at the vanishing point of the law of war.
From single molecules to life: microscopy at the nanoscale (2016)

Super-resolution microscopy is the term commonly given to fluorescence microscopy techniques with resolutions that are not limited by the diffraction of light. Since their conception a little over a decade ago, these techniques have quickly become the method of choice for many biologists studying structures and processes of single cells at the nanoscale. In this review, we present the three main approaches used to tackle the diffraction barrier of ∼200 nm: stimulated-emission depletion (STED) microscopy, structured illumination microscopy (SIM), and single-molecule localization microscopy (SMLM). We first present a theoretical overview of the techniques and underlying physics, followed by a practical guide to all of the facets involved in designing a super-resolution experiment, including an approachable explanation of the photochemistry involved, labeling methods available, and sample preparation procedures. Finally, we highlight some of the most exciting recent applications of and developments in these techniques, and discuss the outlook for this field. Graphical Abstract Super-resolution microscopy techniques. Working principles of the common approaches stimulated-emission depletion (STED) microscopy, structured illumination microscopy (SIM), and single-molecule localization microscopy (SMLM).
Deepwater Chemical Injection Systems: The Balance Between Conservatism and Flexibility (2006)

Abstract The chemical dosing requirements of any deepwater subsea tieback are always difficult to define. Well bore samples are rarely representative of the oil in place so there is a need for the design of the chemical injection system to be conservative. The system must be adaptable to any potential technical hurdles that may arise. This, combined with the need to define and then stay within a budget, makes for a dilemma that will neither lay down nor go away. Insight is presented into mixing new and proven technology to achieve a comprehensive solution. The paper covers the challenges of extrapolating the data samples, which indicated the presence of asphaltenes, paraffins and hydrates in the oil, and determining the types of chemical inhibitors required. It details the lessons learned from the K2 project during and following the design of the delivery systems used for the chemicals, including the umbilical design, tube materials, and specialist valves. The innovative method for controlling the dosing rates of chemicals, using the new technology of multiphase flowmeters to measure the oil volumes, combined with the unique use of a mathematical model of the flowline to determine the potential for deposition, is a first for the Gulf of Mexico. Introduction One of the objectives of the K2 development operated by ENI Petroleum was to optimize the chemicals used for the mitigation of flow assurance concerns. The conventional solution for chemical dosing is to add the chemicals into the system based on the data collected at the topside facility. Due to the time delay in obtaining results, more chemicals are added than necessary. The K2 Project hoped to achieve a system that would use a mixture of conventional measuring devices combined with newer technologies to produce a control system that could dose chemicals and monitor the total flowline system in order to identify potential problems to the operators. The chemical injection system was made up of a number of different elements:Mechanical EquipmentChemical injection skidUmbilicalSubsea umbilical termination unitsFlying leadsChemical metering valvesValves for chemical isolation downholeDownhole tubingInjection mandrelsMeasuring InstrumentationFlowmeters for total chemicalFlowmeters at chemical metering valvesMultiphase flowmeters for total oil/gas/waterSystem instrumentationControl SystemA mathematical model of the whole systemThe chemical injection system was fault tolerant as far as was technically possible, but equipment reliability is still a challenge. Oil Samples Prior to production sample acquisition there is a lot of planning for the analysis of the fluid samples. The planning also determines the amount of sampling attempted and the priority of obtaining the reservoir samples. The planning includes the Pressure, Volume, Temperature (PVT) analysis for the oil characterization required for project sanctioning to the flow assurance analysis for the production and chemical injection issues.
Post-transfusion Hepatitis Following the Use of Prothrombin Complex Concentrates (1975)

Summary The incidence of post-transfusion hepatitis in patients receiving concentrates containing the prothrombin complex factors is reviewed. A survey of the literature indicates a high incidence of hepatitis in such patients.
T-cell responses to human papillomavirus type 16 among women with different grades of cervical neoplasia (2005)

Infection with high-risk genital human papillomavirus (HPV) types is a major risk factor for the development of cervical intraepithelial neoplasia (CIN) and invasive cervical carcinoma. The design of effective immunotherapies requires a greater understanding of how HPV-specific T-cell responses are involved in disease clearance and/or progression. Here, we have investigated T-cell responses to five HPV16 proteins (E6, E7, E4, L1 and L2) in women with CIN or cervical carcinoma directly ex vivo. T-cell responses were observed in the majority (78%) of samples. The frequency of CD4+ responders was far lower among those with progressive disease, indicating that the CD4+ T-cell response might be important in HPV clearance. CD8+ reactivity to E6 peptides was dominant across all disease grades, inferring that E6-specific CD8+ T cells are not vitally involved in disease clearance. T-cell responses were demonstrated in the majority (80%) of cervical cancer patients, but are obviously ineffective. Our study reveals significant differences in HPV16 immunity during progressive CIN. We conclude that the HPV-specific CD4+ T-cell response should be an important consideration in immunotherapy design, which should aim to target preinvasive disease.