gebhart/patrepeval huggingface dataset:
The development of dermatitis infiltrated by γ<sup>δ</sup> T cells in IL-7 transgenic mice (1993)

Transgenic mice constitutively expressing IL-7 developed severe dermatitis with erythroderma and alopecia. The skin lesions were characterized by massive infiltration of mononuclear cells. Immunofluorescence staining showed that most of the infiltrating cells were T cells with the majority bearing the gamma delta TCR other than the V gamma 5 moiety. Furthermore, the number of gamma delta T cells had increased in the lymphoid organs of the dermatitis animals. These findings indicate the strong relationship between the expression of IL-7 and the development of gamma delta T cells in vivo and the pathological involvement of proliferated and/or activated gamma delta T cells in skin disease.
<p>Lenvatinib for the treatment of unresectable hepatocellular carcinoma: evidence to date</p> (2019)

During the last 10 years, the multikinase inhibitor sorafenib has emerged as the only systemic treatment for unresectable hepatocellular carcinoma (HCC). More recently, data from the Phase III REFLECT trial showed that another multikinase inhibitor, namely, lenvatinib, was non-inferior to sorafenib in terms of overall survival (OS). In contrast, with respect to OS, previous randomized Phase III trials have been negative, and several agents tested have failed to prove non-inferiority (or superiority) when compared with sorafenib in a first-line setting. Furthermore, the REFLECT trial demonstrated that lenvatinib, in comparison with sorafenib, significantly increased progression-free survival, time to progression, and objective response rate. Overall, the incidence of grade ≥3 treatment-emergent adverse events (TEAEs) was similar in the two treatment arms of the trial, with a higher incidence of serious TEAEs in the lenvatinib arm. Encouraging efficacy signals had already been reported for immune checkpoint inhibitors in HCC, and different synergisms have been postulated in the frame of interplay between vascular endothelial growth factor receptor-2 inhibitors and immunotherapy. Given these premises, future approaches are being developed in Phase I trials testing lenvatinib in combination with pembrolizumab or nivolumab. As the treatment landscape of HCC is expanding with novel agents being approved for patients who are intolerant or are progressing on prior sorafenib, we will discuss current challenges pertaining to the optimal sequencing of active agents in first- and second-line setting.
Flavone and isoflavone phytoestrogens are agonists of estrogen-related receptors. (2003)

While estrogen-related receptors (ERRalpha, ERRbeta, and ERRgamma) share a high amino acid sequence homology with estrogen receptors (ERs), estrogens are not ligands of ERRs. Structure-function studies from this and other laboratories have revealed that ERRs have small ligand-binding pockets and have provided evidence to show that these receptors can activate gene transcription in a constitutive manner. To address the question as to whether there is any agonist for ERRs, our laboratory recently performed virtual ligand screening on ERRalpha that predicted flavone and isoflavone phytoestrogens to be ligands of this receptor. Our mammalian cell transfection and mammalian two-hybrid experiments revealed that three isoflavones (genistein, daidzein, and biochanin A) and one flavone (6,3',4'-trihydroxyflavone) behaved as agonists of ERRs. These phytoestrogens induced the activity of ERRalpha at concentrations that are comparable to those for the activation of ERalpha and ERbeta. In this study, we also used the results of ERRalpha ligand-binding site mutant, F232A, to verify our ERRalpha hypothetical computer model. Our recent ERR research has determined for the first time that flavone and isoflavone phytoestrogens are agonists of ERRs. In addition, our studies have demonstrated that an approach that combines structure-based virtual screening and receptor functional assays can identify novel ligands of orphan nuclear receptors.
Comparing Reconstruction Algorithms for Electrical Impedance Tomography (1987)

An improved electrical impedance tomographic reconstruction algorithm is presented that is generally guaranteed to converge. The algorithm is attractive for several reasons. A modified Newton-Raphson method varies a finite-element model of resistivities to fit a set of voltage measurements in a least-squared sense. Two procedures for calculating the Jacobian matrix are derived. One is standard, while the other is based on the compensation theorem. This second procedure is more efficient for computations, and just as accurate as the standard one. The inherent ill-conditioning in the approximate Hessian matrix of the linearized system is eliminated using the Marquardt method. Results from two-dimensional computer simulations are compared to four other reconstruction algorithms, which are based on methods proposed by other authors. The modified Newton-Raphson method provided significantly better reconstructions than any of the other methods. The algorithms compared are the perturbation, equipotential, iterative-equipotential, and the double-constraint methods. The modified Newton-Raphson method was found to be sensitive to measurement error, but future work in designing electrode-probing configurations is expected to reduce this sensitivity.
Exocyclic Carbons Adjacent to the<i>N</i><sup>6</sup>of Adenine are Targets for Oxidation by the Escherichia coli Adaptive Response Protein AlkB (2012)

The DNA and RNA repair protein AlkB removes alkyl groups from nucleic acids by a unique iron- and α-ketoglutarate-dependent oxidation strategy. When alkylated adenines are used as AlkB targets, earlier work suggests that the initial target of oxidation can be the alkyl carbon adjacent to N1. Such may be the case with ethano-adenine (EA), a DNA adduct formed by an important anticancer drug, BCNU, whereby an initial oxidation would occur at the carbon adjacent to N1. In a previous study, several intermediates were observed suggesting a pathway involving adduct restructuring to a form that would not hinder replication, which would match biological data showing that AlkB almost completely reverses EA toxicity in vivo. The present study uses more sensitive spectroscopic methodology to reveal the complete conversion of EA to adenine; the nature of observed additional putative intermediates indicates that AlkB conducts a second oxidation event in order to release the two-carbon unit completely. The second oxidation event occurs at the exocyclic carbon adjacent to the N(6) atom of adenine. The observation of oxidation of a carbon at N(6) in EA prompted us to evaluate N(6)-methyladenine (m6A), an important epigenetic signal for DNA replication and many other cellular processes, as an AlkB substrate in DNA. Here we show that m6A is indeed a substrate for AlkB and that it is converted to adenine via its 6-hydroxymethyl derivative. The observation that AlkB can demethylate m6A in vitro suggests a role for AlkB in regulation of important cellular functions in vivo.
Antibody responses to non-immunogenic synthetic peptides induced by co-immunization with immunogenic peptides. (1992)

Chimeric peptides comprising B- and T-helper cell epitopes from the proteins of infectious agents represent immunogens with potential for use as new vaccines. However, it has become clear that the orientation of the epitopes, the presence of spacer residues and the number of copies of the epitopes influence the specificity, levels and affinity of the antibody produced following immunization with such constructs. Furthermore, the response to peptides is under genetic control leading to major histocompatibility complex (MHC)-linked non-responsiveness. In this study, we have investigated the potential of co-immunization of immunogenic peptides (to provide T-cell help) with non-immunogenic peptides (representing B-cell epitopes) to overcome the non-response to the latter. For this purpose, we have employed peptides representing T- and B-cell epitopes derived from the sequences of the fusion and haemagglutinin glycoproteins of measles virus. The results obtained show that simple co-immunization of a B-cell epitope with a T-cell epitope results in the production of antibody to the B-cell epitope without the requirement for covalent linkage of the two peptides. This approach could thus be used to overcome the problem of poor immunogenicity of peptides and will be of potential value in the design of immunization strategies using synthetic immunogens.
奥尔罕·帕慕克：跨越东西方的桥梁 (2007)

在2006年诺贝尔文学奖公布以前,帕慕克这个名字对于中国读者来说也许还十分陌生。其实此时的他已经是享誉国际的作家,被认为是欧洲当代最杰出的小说家之一。从去年起,这位土耳其文坛巨擘的作品被陆续介绍到中国,并在国内掀起了一股读书热潮,延续至今。以下是帕慕克获诺贝尔奖前的一篇采访记。通过这篇文章,我们不难发现东西方文明给这位作家的人生及其作品留下的不可磨灭的印记。
Hydraulic Conductivity Tests on Compacted Clay (1985)

Permeability tests were performed in the laboratory on compacted clay to study the effects of type of permeameter, hydraulic anisotropy, diameter of test specimens, storage time, and desiccation cracking. Essentially identical hydraulic conductivities were measured with compaction‐mold, consolidation‐cell, and flexible‐wall permeameters. With good bonding between lifts, hydraulic conductivity was isotropic. Test specimens having a diameter of 15 cm were twice as permeable as specimens having a diameter of 4 cm, but this difference is too small to be of any consequence. There was no tendency for hydraulic conductivity to increase with increasing storage time. Desiccation cracks in compacted clay close only partially when the clay is moistened and permeated, unless substantial effective stresses are applied to aid in closing the cracks.
Harnessing “A Billion Years of Experimentation”: The Ongoing Exploration and Exploitation of CRISPR–Cas Immune Systems (2018)

The famed physicist-turned-biologist, Max Delbrück, once remarked that, for physicists, "the field of bacterial viruses is a fine playground for serious children who ask ambitious questions." Early discoveries in that playground helped establish molecular genetics, and half a century later, biologists delving into the same field have ushered in the era of precision genome engineering. The focus has of course shifted-from bacterial viruses and their mechanisms of infection to the bacterial hosts and their mechanisms of immunity-but it is the very same evolutionary arms race that continues to awe and inspire researchers worldwide. In this review, we explore the remarkable diversity of CRISPR-Cas adaptive immune systems, describe the molecular components that mediate nucleic acid targeting, and outline the use of these RNA-guided machines for biotechnology applications. CRISPR-Cas research has yielded far more than just Cas9-based genome-editing tools, and the wide-reaching, innovative impacts of this fascinating biological playground are sure to be felt for years to come.
An efficient way to enable prognostics in an onboard system (2015)

Prognostics and Health Management (PHM) systems are becoming increasingly important for monitoring and maintaining high value assets. In order to enable real time onboard diagnostic and prognostic capabilities, mechanisms for reading, manipulating and analyzing the data need to be architected into the onboard system. Machine learning and statistical algorithms provide tools to develop data models for enabling prognostics that are typically developed off-board by mining historical data. Once trained, the logic of processing real time data is then embedded on a real time onboard system. A straightforward approach for incorporating the knowledge and intelligence for real time data processing is to add the needed logic and algorithms as an integral part of the onboard software. While this method can serve the purpose of enabling real time health assessment and analysis, it is very restrictive in nature. Every time the analytics need to be updated or algorithms need refinement, it requires a refresh of the complete onboard software. The ability to fine tune onboard embedded logic for the purpose of making the analysis smarter is crucial for creating a successful and sound health monitoring system. In addition, it is desired that the process of encoding logic and algorithms should be simple and easy to incorporate into the system. User friendliness of the process of embedding intelligent logic is critical for long term maintenance of the system as well. This paper discusses an approach to build algorithms and logic into an onboard system such that they are programmatically decoupled from the onboard software. The approach described in this paper allows users the ease of use and flexibility in building knowledge into the system. In addition, as more historical data is collected and richer knowledge is discovered from mining the data, algorithms can be improved over time without having to update the onboard software.
Chip Scale 12-Channel 10 Gb/s Optical Transmitter and Receiver Subassemblies Based on Wet Etched Silicon Interposer (2017)

In this paper, compact optical subassemblies are demonstrated based on a novel silicon interposer, which is designed and fabricated in a wafer scale process. The interposer includes the design of optical and electrical connections. A low-cost fabrication method, wet etching, is used to define light inputs and outputs as well as create the required recesses in the interposer to embed the chips into the silicon wafer at the same time. Impedance matched traces, for the high speed signals of the CMOS and opto-electronic ICs, are designed using advanced design system software and transferred onto the interposer by photolithography and electro-plating, which are accomplished on the deeply etched topology. The whole process flow of the silicon interposer patterning is designed and demonstrated, and the challenges are discussed. After the process, the optoelectronic dies and their complimentary CMOS parts are flipped and bonded on the interposer in close proximity, and a mechanical optical interface (MOI) is mounted for light coupling. Both transmitter and receiver subassemblies provide 12 parallel optical interconnections, and are scaled down to an area measuring 6 by 8 mm. Signal integrity testing is performed on a probe station for 10 Gb/s data signal delivering clear eye patterns for all channels (in both Rx and Tx subassemblies). The performance is further characterized using bit error rate (BER) testing. Both transmitter and receiver assemblies outperform a reference SFP+, with receiver sensitivity of -10 dBm at a BER lower than 10 <sup xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">-12</sup> after compensating for the MOI insertion loss. Finally, we also test the assemblies for crosstalk and demonstrate that the current design has a maximal additional penalty lower than 0.2 and 0.8 dB for transmitter and receiver, respectively.
Folic Acid for the Prevention of Neural Tube Defects: US Preventive Services Task Force Recommendation Statement (2009)

Description: In 1996, the U. S. Preventive Services Task Force (USPSTF) recommended that all women planning or capable of pregnancy take a multivitamin supplement containing folic acid for the prevention of neural tube defects. This recommendation is an update of the 1996 USPSTF recommendation. Methods: The USPSTF reviewed the evidence on folic acid supplementation in women of childbearing age published since the 1996 USPSTF recommendation. The USPSTF did not review the evidence on folic acid food fortification, counseling to increase dietary intake, or screening for neural tube defects. Recommendation: The USPSTF recommends that all women planning or capable of pregnancy take a daily supplement containing 0.4 to 0.8 mg (400 to 800 mu g) of folic acid. (Grade A recommendation).
Treatment of tuberculosis (2003)

Concordance is a key step 

The importance of people taking medicines extends beyond individuals to communities when medicines are crucial for treatment of communicable diseases and prevention of transmission. In this editorial we discuss the relevance of the concept of concordance (a term introduced to emphasise patients' beliefs about treatment)1 to the treatment of communicable disease, taking tuberculosis as an example. Tuberculosis is one of the leading causes of death due to an infectious agent, and the control of tuberculosis depends on effective treatment of the infectious patients, and therefore on people taking medicines.

The likelihood of successful treatment of tuberculosis depends on the extent to which patients complete the prescribed treatment regimen (usually called compliance with, or adherence to, treatment). Interrupted treatment of tuberculosis results in ongoing transmission of disease. Without support throughout the full course of treatment, many patients with tuberculosis adhere to treatment until symptoms have resolved and then stop, since patients may equate disease and therefore the need to continue treatment with illness (symptoms).2 The consequent risks of failure of …
Paclitaxel Formulations: Challenges and Novel Delivery Options (2014)

Paclitaxel (PTX), a taxane plant product, is one of the most effective broad-spectrum anti-cancer agents and approved for the treatment of a variety of cancers including ovarian, breast, lung, head and neck as well as Kaposi's sarcoma. Poor aqueous solubility and serious side effects associated with commercial preparation of PTX (Taxol®) triggered the development of alternative PTX formulations. Over past three decades, plethora of research work has been published towards the development of cremophor free and efficient formulations. Various nanocarrier systems including nanoparticles, liposomes, micelles, bioconjugates and dendrimers have been employed in order to improve PTX solubility and eliminate undesired side effects. These nanocarriers offer the advantage of high degree of encapsulation and cellular uptake, escape from elimination by P-glycoprotein (P-gp) mediated efflux, and can be explored for targeted drug delivery. The potential of these nanocarriers is reflected by the fact that various nanocarriers of PTX are in different stages of clinical trials and a few have already been commercialized including Abraxane®, Lipusu and Genexol PM®. This review focuses on the various challenges associated with PTX formulation development, limitations of existing formulations and novel approaches for the development of alternative formulations for PTX and also highlights the development of novel formulations in clinical settings.
Efficient test-based model generation for legacy reactive systems (2004)

We present the effects of using an efficient algorithm for behavior-based model synthesis which is specifically tailored to reactive (legacy) system behaviors. Conceptual backbone is the classical automata learning procedure L*, which we adapt according to the considered application profile. The resulting learning procedure L*Meal , which directly synthesizes generalized Mealy automata from behavioral observations gathered via an automated test environment, drastically outperforms the classical learning algorithm for deterministic finite automata. Thus it marks a milestone towards opening industrial legacy systems to model-based test suite enhancement, test coverage analysis, and online testing.
Rapid lateral flow immunoassay for the fluorescence detection of SARS-CoV-2 RNA (2020)

The coronavirus disease 2019 (COVID-19) pandemic has highlighted the need for rapid and accurate nucleic acid detection at the point of care. Here, we report an amplification-free nucleic acid immunoassay, implemented on a lateral flow strip, for the fluorescence detection of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) RNA in less than one hour. The assay uses DNA probes that are designed to bind to the conserved open reading frame 1ab (ORF1ab), envelope protein (E) and the nucleocapsid (N) regions of the SARS-CoV-2 genome, and a fluorescent-nanoparticle-labelled monoclonal antibody that binds to double-stranded DNA-RNA hybrids. In a multi-hospital randomized double-blind trial involving 734 samples (593 throat swabs and 141 sputum) provided by 670 individuals, the assay achieved sensitivities of 100% and specificities of 99% for both types of sample (ground truth was determined using quantitative PCR with reverse transcription). The inexpensive amplification-free detection of SARS-CoV-2 RNA should facilitate the rapid diagnosis of COVID-19 at the point of care.
Gastric Ulcer Healing (1991)

Enprostil is a synthetic prostaglandin E2 analogue with gastric antisecretory and mucosal protective properties. We compared the effects of enprostil and ranitidine on the healing of gastric ulcers and the subsequent relapse rates over 6 months. Patients (N = 156) were recruited for a double-blind study from 12 centers in Europe; 71 were randomly assigned to oral treatment with 35 micrograms enprostil twice daily and 85 to 150 mg ranitidine twice daily for up to 8 weeks. Both groups were of similar demography; their healing rates were also similar. Cumulative intent-to-treat healing rates were at 4 weeks enprostil 48%, ranitidine 41%: at 6 weeks enprostil 65%, ranitidine 68%; and at 8 weeks enprostil 72%, ranitidine 80%. Of those patients who met all protocol criteria and completed treatment, and were endoscoped at the prescribed times, healing rates were at 4 weeks enprostil 55%, ranitidine 54%, at 6 weeks enprostil 75%, ranitidine 84%; and at 8 weeks enprostil 80%, ranitidine 90%. Relief of pain was rapid and similar in both groups. The incidence of adverse events was low and similar in the two groups. The treatment-free relapse rate at 6 months was enprostil 64%, ranitidine 49%; the median times to relapse were 169 and 203 days, respectively. Enprostil and ranitidine appear to be equally effective in healing gastric ulcers.
The gene encoding tobacco gibberellin 3β‐hydroxylase is expressed at the site of GA action during stem elongation and flower organ development (1999)

Gibberellin 3beta-hydroxylase catalyzes the final step in the biosynthetic pathway leading to the plant hormone gibberellin (GA) and, therefore, the in vivo localization of this enzyme should give a direct indication of the site of synthesis of bioactive GAs in plants. We have isolated a cDNA clone, Nty (Nicotiana tabacum GA 3beta-hydroxylase), which encodes a putative GA 3beta-hydroxylase, by RT-PCR using RNA from tobacco shoot apices. Functional analysis, using an NTY protein expressed in Escherichia coli, revealed that Nty encoded an active GA 3beta-hydroxylase. A high expression level of Nty was observed in shoot apices, flowers, roots, young internodes but not in leaves or seeds. We performed more detailed expression analyses using in situ hybridization and histochemical analyses of the GUS activity in transgenic tobacco plants carrying an Nty promoter:GUS fusion gene. These studies revealed that expression of Nty was restricted to specific regions, including actively dividing and elongating cells in the various organs; rib meristem and elongation zones of shoot apices, tapetum and pollen grains in developing anthers and root tips, which are consistent with the sites of GA action. It is proposed that GA actions depend on the modulation of endogenous bioactive GA levels through the regulation of GA 3beta-hydroxylase expression in situ.
Helicon wave plasma doping system (2002)

A new concept of Plasma Doping (PD) equipment is demonstrated. Shallow profiles and low resistance will be required for sub 50 nm MOS transistor. Dose control by changing plasma doping time is shown in this paper.
Lifting Strategy and Stability in Strength-Impaired Elders (2001)

Subjects apparently chose their lift strategy based on their hip and knee extensor strength. Weaker elders using a less stable back dominant strategy could be susceptible to falls and subsequent long bone and vertebral body fractures. Clinicians could identify at-risk elders by muscle testing. Beyond emphasizing strength and endurance exercise in elderly patients, weak elders should be taught to use a leg dominant lifting strategy, or if they are not physically able, to use a combined back/leg strategy.