gebhart/patrepeval huggingface dataset:
Expression of functional replication protein from tomato golden mosaic virus in transgenic tobacco plants. (1990)

The A component of the bipartite genome of the geminivirus tomato golden mosaic virus (TGMV) encodes the viral protein (AL1) that is required for viral DNA replication. We have constructed transgenic Nicotiana benthamiana plants in which the AL1 open reading frame is transcribed under the control of the cauliflower mosaic virus 35S promoter. The transgenic plants, which were phenotypically normal, produced a single transcript from the 35S-AL1 construct and a 40-kDa protein that cross-reacted with a polyclonal antiserum raised against AL1 protein overproduced in Escherichia coli. Six of nine transgenic lines complemented a TGMV A variant with a mutation in AL1 when coinoculated with the B component of the TGMV genome. Single- and double-stranded forms of the B component were synthesized in leaf discs from a complementing, transgenic line in the absence of TGMV A. These results establish that the transgenic plants express functional AL1 protein and show that this viral protein is not only required, but sufficient, for single- and double-stranded replication of TGMV DNA in the presence of host proteins. These results also show that the AL1 protein is not by itself a determinant of disease or pathogenesis.
BIOSYNTHESIS AND FUNCTION OF THE SULFOLIPID SULFOQUINOVOSYL DIACYLGLYCEROL (1998)

▪ Abstract The sulfolipid sulfoquinovosyl diacylglycerol is an abundant sulfur-containing nonphosphorous glycerolipid that is specifically associated with photosynthetic membranes of higher plants, mosses, ferns, algae, and most photosynthetic bacteria. The characteristic structural feature of sulfoquinovosyl diacylglycerol is the unique head group constituent sulfoquinovose, a derivative of glucose in which the 6-hydroxyl is replaced by a sulfonate group. While there is growing evidence for the final assembly of the sulfolipid by the transfer of the sulfoquinovosyl moiety from UDP-sulfoquinovose to the sn-3 position of diacylglycerol, very little is known about the biosynthesis of the precursor UDP-sulfoquinovose. Recently, a number of mutants deficient in sulfolipid biosynthesis and the corresponding sqd genes have become available from different organisms. These provide novel tools to analyze sulfolipid biosynthesis by a combination of molecular and biochemical approaches. Furthermore, the analysis of sulfolipid-deficient mutants has provided novel insights into the function of sulfoquinovosyl diacylglycerol in photosynthetic membranes.
Overview of FTY720 Clinical Pharmacokinetics and Pharmacology (2004)

Drug discovery programs are actively exploring for therapeutic agents targeting enzymes and receptors regulating sphingolipid metabolism and biologic functions. FTY720 is a close structural analogue of sphingosine with immunomodulatory properties. After oral administration, FTY720 is phosphorylated by sphingosine kinase to form the active moiety FTY720-phosphate, which subsequently binds to the sphingosine-1-phosphate receptor. In characterizing the safety and pharmacological effects of FTY720, detailed clinical pharmacology studies in healthy subjects and renal transplant recipients have focused on cardiac responses and lymphocyte trafficking. After the first dose, FTY720 causes a mild, transient decrease in heart rate that returns to baseline in approximately 1 to 2 weeks despite continued administration of the drug. FTY720 elicits a prompt and dose-dependent decrease in peripheral blood lymphocytes by redirecting them from the circulation to the lymph nodes without impairing lymphocyte functions. An association among FTY720 blood concentration, decrease in lymphocyte counts, and freedom from acute rejection episodes has been observed in early clinical development trials in de novo kidney transplantation.
Cardiac blood-pool scintigraphy using technetium-99m DTPA-HSA: comparison with in vivo technetium-99m RBC labeling. (1989)

We performed cardiac blood-pool scintigraphy using technetium-99m diethylenetriaminepentaacetic acid human serum albumin [( 99mTc] DTPA-HSA), a newly developed blood-pool agent, in 31 patients with various heart diseases and evaluated its clinical usefulness in comparison with the conventional in vivo 99mTc red blood cell (RBC) labeling. Excellent cardiac blood-pool images were obtained by [99mTc]DTPA-HSA method. Biodistribution studies showed higher accumulation of [99mTc]DTPA-HSA than that of 99mTc RBC in the lungs and liver, but similar count ratios of the cardiovascular blood pool to whole body between the two methods. In ECG-gated end-diastolic images, no quantitatively significant difference was observed in left ventricular target-to-background ratios between these two methods. Left ventricular ejection fraction (LVEF) calculated by [99mTc]DTPA-HSA MUGA method was correlated well with that by contrast LVEF (r = 0.91). No side effects were observed in any patient. In conclusion, cardiac blood-pool scintigraphy using [99mTc] DTPA-HSA is readily performed by single i.v. injection and useful for the assessment of cardiac function.
Involuntary Emotional Expression Disorder: Definition, Diagnosis, and Measurement Scales (2007)

Involuntary emotional expression disorder (IEED) is a syndrome in which emotional or affective motor control becomes dysregulated as a result of brain damage from neurological disease or as a result of brain injury. A debilitating disorder with persistent symptoms, IEED has a significant impact upon the lives of patients and caregivers, but is often overlooked or misdiagnosed. IEED is a clinically well-defined disorder, and specific criteria may be used when making a diagnosis. It must be distinguished from depression or other psychological and neurological conditions. Several assessment scales have been validated for use in IEED, in order to evaluate the baseline severity and to track the course of the disorder and response to treatment.
Comparison of tumor growth inhibitory and toxic effects of a new fluorouracil--nitrosourea derivative (B-3839). (1992)

The toxic effect and anti-tumor activity of B-3839, a new molecular combination of pyrimidine antimetabolite 5-fluorouracil (5-FU) with the alkylating agent N-Chloroethyl-N-nitrosourea (BCNU), was compared to that of BCNU and 5-FU given alone and in physical combination. The tumor inhibitory effect of B-3839 was similar to that of BCNU given alone or combined with a low dose of 5-FU in the i.m. Walker tumor model. Furthermore, the bone marrow toxicity of BCNU was not significantly altered by either form of combination with 5-FU. The intestinal side effects, evaluated by measuring the decrease of marker enzyme (thymidine kinase, xanthine oxidase, alkaline phosphatase, sucrase, maltase) activities in isolated enterocytes, were dose-dependent and moderate. A significant, more than 30%, decrease occurred only if BCNU and 5-FU were given simultaneously or as B-3839. The molecular combination of the two drugs does not provide any additional advantage over their physical combination.
Immune checkpoint inhibitors: recent progress and potential biomarkers (2018)

Cancer growth and progression are associated with immune suppression. Cancer cells have the ability to activate different immune checkpoint pathways that harbor immunosuppressive functions. Monoclonal antibodies that target immune checkpoints provided an immense breakthrough in cancer therapeutics. Among the immune checkpoint inhibitors, PD-1/PD-L1 and CTLA-4 inhibitors showed promising therapeutic outcomes, and some have been approved for certain cancer treatments, while others are under clinical trials. Recent reports have shown that patients with various malignancies benefit from immune checkpoint inhibitor treatment. However, mainstream initiation of immune checkpoint therapy to treat cancers is obstructed by the low response rate and immune-related adverse events in some cancer patients. This has given rise to the need for developing sets of biomarkers that predict the response to immune checkpoint blockade and immune-related adverse events. In this review, we discuss different predictive biomarkers for anti-PD-1/PD-L1 and anti-CTLA-4 inhibitors, including immune cells, PD-L1 overexpression, neoantigens, and genetic and epigenetic signatures. Potential approaches for further developing highly reliable predictive biomarkers should facilitate patient selection for and decision-making related to immune checkpoint inhibitor-based therapies.
Platinum- and Acid-Catalyzed Enyne Metathesis Reactions:  Mechanistic Studies and Applications to the Syntheses of Streptorubin B and Metacycloprodigiosin (1998)

Formal total syntheses of the antibiotics metacycloprodigiosin (2) and streptorubin B (3) are described, which are known to exhibit promising immunomodulating properties. The key step en route to their meta-bridged pyrrole core structures 5 and 7, respectively, consists of a metathesis reaction of electron-deficient enynes catalyzed by either platinum halides, hard Lewis acids, or HBF4. This transformation expands the pre-existing cycloalkene of the substrates by two C atoms, forges the bicyclic pyrrolophane structure of the targets, and simultaneously forms a bridgehead alkene function. The products of this skeletal rearrangement are converted into the targets by a sequence comprising (i) a stepwise reduction of their enone entity to the corresponding saturated alcohols and (ii) an aromatization of the N-tosylated dihydropyrroles 20 and 34 thus obtained via elimination of potassium sulfinate on exposure to KAPA (potassium 3-aminopropylamide). A careful analysis of the minor byproducts formed in the enyne metathesis reactions allows a mechanistic rationale to be proposed for this operationally trivial yet highly attractive transformation which involves “nonclassical” cyclopropylmethyl−homoallyl−cyclobutyl cations as key intermediates. This cationic pathway is distinctly different from mechanistic interpretations of other enyne metathesis reactions previously reported in the literature.
The Epstein–Barr virus oncoprotein, latent membrane protein‐1, reprograms germinal centre B cells towards a Hodgkin's Reed–Sternberg‐like phenotype (2008)

Although the latent membrane protein-1 (LMP1) of the Epstein-Barr virus (EBV) is believed to be important for the transformation of germinal centre (GC) B cells, the precise contribution of this viral oncogene to lymphoma development is poorly understood. In this study, we used a non-viral vector-based method to express LMP1 in primary human GC B cells. Gene expression profiling revealed that LMP1 induced in GC B cells transcriptional changes characteristic of Hodgkin's lymphoma cell lines. Strikingly, LMP1 down-regulated the expression of B-cell-specific genes including B-cell receptor components such as CD79A, CD79B, CD19, CD20, CD22, and BLNK. LMP1 also induced the expression of ID2, a negative regulator of B-cell differentiation. Our data suggest that in EBV-positive cases, LMP1 is likely to be a major contributor to the altered transcriptional pattern characteristic of Hodgkin/Reed-Sternberg cells, including the loss of B-cell identity.
Retroviruses and human pathology (1985)

This book contains four sections, each consisting of several papers. The section headings are: Retroviruses and the Murine Model System;Retroviruses and the Vertebrate Model System;Retroviruses and Human Pathology;and Retroviruses and Oncogenes.
Alloactivated cytotoxic T cells recognize the carboxy‐terminal domain of human immunodeficiency virus‐1 gp120 envelope glycoprotein (1993)

Infection with the human immunodeficiency virus (HIV) virus leads to clinical disease in humans but not in chimpanzees. Progression to disease is associated with activation of the immune system followed by loss of T helper cell function and a slow decline in CD4-positive lymphocytes. The presence of autoreactive and cytotoxic cells in humans but not chimpanzees suggests that mechanisms other than, or in addition to, direct virus-induced cell killing, are required for disease to develop. The observed changes are similar to those seen in chronic allogeneic disease. Here we show that a peptide from the carboxy terminus of gp120, predicted to have a structure similar to the major alpha-helices of major histocompatibility complex (MHC) class I and class II, acts as a cytolytic target when presented on syngeneic cells for alloactivated cytotoxic T effector cells. These data add further evidence to the hypothesis that HIV can act as an allostimulant due to its dual properties of CD4 binding and MHC mimicry. The ability to signal nonspecifically through the T cell receptor could explain the initially paradoxical responses of proliferation, anergy and apoptosis.
<title>Pyramid broadcasting for video-on-demand service</title> (1995)

The proposed scheme of pyramid broadcasting is a new way of rendering Video On Demand service. In pyramid broadcasting, the most frequently requested movies are multiplexed on the broadcast network, resulting in radical improvement of access time and efficient bandwidth utilization. This is achieved by using storage at the receiving end. As the available bandwidth increases, the improvement in access time is exponential as opposed to just linear improvement as in the case of conventional broadcasting. The larger the bandwidth of the network, the better the access time gain due to pyramid broadcasting. As the access time requirement decreases, the bandwidth requirement in the case of conventional broadcasting increases linearly while the bandwidth requirement in the case of pyramid broadcasting increases only logarithmically. We provide analytical and experimental evaluations of pyramid broadcasting based on its implementation on ethernet LAN, illustrating its advantages.
The Serine-rich Entamoeba histolytica Protein Is a Phosphorylated Membrane Protein Containing O-Linked Terminal N-Acetylglucosamine Residues (1995)

Previously, we described the isolation of a cDNA clone and the gene encoding a protective antigen of the protozoan parasite Entamoeba histolytica, the serine-rich Entamoeba histolytica protein (SREHP). The derived amino acid sequence of the SREHP cDNA clone was remarkable for a high serine content (52/233 amino acids), a putative signal sequence, multiple hydrophilic dodecapeptide and octapeptide tandem repeats, and a hydrophobic C-terminal putative membrane-spanning region. Here, we show that SREHP is modified by the addition of phosphate at serine residues, O-linked terminal N-acetylglucosamine residues, and by acylation. When the SREHP gene is expressed in baculovirus transformed Sf-9 cells, the product is also phosphorylated and glycosylated and is localized to the plasma membrane of the insect cells. The native SREHP molecule also serves as a potent chemoattractant for amebic trophozoites. The data presented here suggest that SREHP is a unique membrane protein with phosphorylation and glycosylation patterns usually associated with nuclear or cytoplasmic proteins.
A clinico‐pathological approach to the classification of human demodicosis (2005)

We suggest that demodicosis be divided into both primary and secondary types. The usual etiological agent of primary demodicosis is D. folliculorum, which causes an erythemato-squamous eruption in the facial T-zone. The rash starts on unaltered skin and covers 8 - 15 % of the face. Pruritus accompanies the onset of the rash, while erythema is first apparent after papulo-pustules are seen and disappears after treatment. Half the patients show seasonal exacerbations. Secondary demodicosis is usually caused by D. brevis and characterized by a symmetrical malar papulo-pustular eruption. It develops on diseased skin and covers 30 - 40 % of the face. Pruritus starts after the lesion exacerbation, but erythema precedes the papulo-pustular phase and persists after treatment. Most patients flare during the summer. The facial distribution, seasonality and pathogenesis, as well as the species of mite involved, must be taken into consideration in separating the various forms of demodicosis.
[Construction and expression of recombinant adenovirus containing human thymic stromal lymphopoietin gene]. (2005)

The construction of recombinant adenovirus bearing human TSLP gene and its expression mediated by this adenovirus pave a foundation for the study on the biological function of this novel cytokine.
N-Acylated and d Enantiomer Derivatives of a Nonamer Core Peptide of Lactoferricin B Showing Improved Antimicrobial Activity (1999)

N-acylated or D enantiomer peptide derivatives based on the sequence RRWQWRMKK in lactoferricin B demonstrated antimicrobial activities greater than those of lactoferricin B against bacteria and fungi. The most potent peptide, conjugated with an 11-carbon-chain acyl group, showed two to eight times lower MIC than lactoferricin B.
Inkjet-printed, flexible, and photoactive thin film strain sensors (2014)

In an effort to improve the resilience and reliability of infrastructure systems, many advanced sensors have been developed for structural health monitoring. However, these sensors often suffer from high energy demand, large form factors, and have difficulties conforming to complex structural surfaces. Recently, a self-sensing poly(3-hexylthiophene)–based thin film sensor was proposed, and it was shown that light illumination generates an electrical current that was also proportional to applied strains. However, its strain sensing range was limited largely due to the brittleness of the electrodes. In this study, inkjet printing was employed for printing flexible polymer electrodes that enhanced fabrication scalability and its strain sensing range. First, a commercial off-the-shelf Canon inkjet printer was customized for electrode fabrication. Second, a conductive ink solution was prepared for printing the conductive and transparent thin film electrodes. Then, the printed thin film electrodes were characterized for their electrical conductivity, optical transmittance, profile (i.e. roughness and thickness), and piezoresistivity. Finally, poly(3-hexylthiophene)–based strain sensors were fabricated using these electrodes, and strain sensing was validated to 2% tensile strains.
Cumulative effect of five genetic variants on prostate cancer risk in multiple study populations (2008)

These results provide an important confirmation for the cumulative effect of five genetic risk variants on prostate cancer risk. The more stable OR estimates of the cumulative effect of these six risk factors are a major step toward individual risk characterization for this disease.
Design and Implementation of a Prototype PC Based Graphical and Interactive Milsatcom Requirements Database System (1993)

This thesis develops a prototype PC based Military Satellite Communications MILSATCOM) Requirements Database (MRDB) application for U.S. Space Command, using Microsoft's Access relational database management system (DBMS) for Windows. It demonstrates the advantages of using the proposed database system over the existing one and shows how U.S. Space Command can save both time and money by using a PC based interactive, graphical, and user friendly database system. A rapid prototyping approach in concert with a six phase database design process was used to develop the prototype. The first two chapters of the thesis provide a background of the application and describe database management systems in general and Microsoft Access in particular. The applications of Access - tables, queries, forms, reports, macros, and modules - to the design of the MRDB are then discussed in the succeeding five chapters. The Conclusions describe the advantages and benefits of using the prototype MRDB database system and make recommendations for future improvements. MILSATCOM requirements database, MRDB, Databases, Database design, Microsoft access
Individual domains of connective tissue growth factor regulate fibroblast proliferation and myofibroblast differentiation (2005)

All members of the Ctgf, Cyr61, and Nov (CCN) family share a high degree of sequence homology and conservation of structural motifs and domains. Here, we present data about a structure function analysis of connective tissue growth factor (CTGF), a prototypic member of the CCN family, which has been shown to be a downstream mediator of transforming growth factor-beta activities on fibroblasts. Our findings demonstrate the two domains of CTGF function to mediate two distinct biological effects. The N-terminal domain of CTGF mediates myofibroblast differentiation and collagen synthesis. The C-terminal domain of CTGF mediates fibroblast proliferation. These data provide a molecular basis for the divergence of CTGF actions on connective tissue cell types and suggest a model for functional analysis of all of the CCN family gene products.
Chimera of IL-2 Linked to Light Chain of anti-IL-2 mAb Mimics IL-2/anti-IL-2 mAb Complexes Both Structurally and Functionally (2013)

IL-2/anti-IL-2 mAb immunocomplexes were described to have dramatically higher activity than free IL-2 in vivo. We designed protein chimera consisting of IL-2 linked to light chain of anti-IL-2 mAb S4B6 through flexible oligopeptide spacer (Gly(4)Ser)(3). This protein chimera mimics the structure of IL-2/S4B6 mAb immunocomplexes but eliminates general disadvantages of immunocomplexes like possible excess of either IL-2 or anti-IL-2 mAb and their dissociation to antibody and IL-2 at low concentrations. This novel kind of protein chimera is characterized by an intramolecular interaction between IL-2 and binding site of S4B6 mAb similarly as in IL-2/S4B6 mAb immunocomplexes. Our protein chimera has biological activity comparable to IL-2/S4B6 mAb immunocomplexes in vitro, as shown by stimulation of proliferation of purified and activated OT-I CD8(+) T cells. The protein chimera exerts higher stimulatory activity to drive expansion of purified CFSE-labeled OT-I CD8(+) T cells activated by an injection of a low dose of SIINFEKL peptide than IL-2/S4B6 mAb immunocomplexes in vivo.
Computer-supported routing for intelligent networks and personalized wired communications (2002)

We present the architecture, capabilities, and applications of CSTA, a European ISDN-OSI interface for routing in intelligent networks. It allows computer-supported routing of all types of telephony calls: voice, video, image, and data. This enhances routing in telephony networks in terms of speed, throughput, reliability, support of call priorities, and customization of routing to users requirements. We conclude by highlighting some areas for future research and standardization.< <ETX xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">&gt;</ETX>
Batch Tuning Strategies for Statistical Machine Translation (2012)

There has been a proliferation of recent work on SMT tuning algorithms capable of han-dling larger feature sets than the traditional MERT approach. We analyze a number of these algorithms in terms of their sentence-level loss functions, which motivates several new approaches, including a Structured SVM. We perform empirical comparisons of eight different tuning strategies, including MERT, in a variety of settings. Among other results, we find that a simple and efficient batch ver-sion of MIRA performs at least as well as training online, and consistently outperforms other options. 1