gebhart/patrepeval huggingface dataset:
AIDS as a Zoonosis: Scientific and Public Health Implications (2000)

Evidence of simian immunodeficiency virus (SIV) infection has been reported for 26 different species of African nonhuman primates. Two of these viruses, SIVcpz from chimpanzees and SIVsm from sooty mangabeys, are the cause of acquired immunodeficiency syndrome (AIDS) in humans. Together, they have been transmitted to humans on at least seven occasions. The implications of human infection by a diverse set of SIVs and of exposure to a plethora of additional human immunodeficiency virus-related viruses are discussed.
Nighttime Driving in Older Adults: Effects of Glare and Association With Mesopic Visual Function (2017)

Glare reduced several aspects of nighttime driving performance. Mesopic tests of visual function, including motion sensitivity and mesopic high contrast VA, were more strongly associated with nighttime driving performance than photopic high-contrast VA. These results highlight the potential importance of nonstandard vision tests for assessing older drivers' visual capacity to drive at night.
Phosphorylation of C/EBPα Inhibits Granulopoiesis (2003)

CCAAT/enhancer-binding protein alpha (C/EBPalpha) is one of the key transcription factors that mediate lineage specification and differentiation of multipotent myeloid progenitors into mature granulocytes. Although C/EBPalpha is known to induce granulopoiesis while suppressing monocyte differentiation, it is unclear how C/EBPalpha regulates this cell fate choice at the mechanistic level. Here we report that inducers of monocyte differentiation inhibit the alternate cell fate choice, that of granulopoiesis, through inhibition of C/EBPalpha. This inhibition is mediated by extracellular signal-regulated kinases 1 and/or 2 (ERK1/2), which interact with C/EBPalpha through an FXFP docking site and phosphorylate serine 21. As a consequence of C/EBPalpha phosphorylation, induction of granulocyte differentiation by C/EBPalpha or retinoic acid is inhibited. Our analysis of C/EBPalpha by fluorescent resonance energy transfer revealed that phosphorylation induces conformational changes in C/EBPalpha, increasing the distance between the amino termini of C/EBPalpha dimers. Thus, myeloid development is partly regulated by an ERK1/2-mediated change in the conformation of C/EBPalpha that favors monocyte differentiation by blocking granulopoiesis.
Sulfation of tyrosine residues increases activity of the fourth component of complement. (1989)

Sulfation of tyrosine residues recently has been recognized as a biosynthetic modification of many plasma proteins and other secretory proteins. Effects of this site-specific modification on protein function are not known, but the activity of several peptides such as cholecystokinin is greatly augmented by sulfation. Here, we examine the role of sulfation in the processing and activity of C4 (the fourth component of complement), one of the few proteins in which sites and stoichiometry of tyrosine sulfation have been characterized. Our results, with C4 as a paradigm, suggest that sulfation of tyrosine residues can have major effects on the activity of proteins participating in protein-protein interactions. Sulfation of C4 synthesized by Hep G2 cells was blocked by incubating the cells with NaClO3 and guaiacol. These sulfation inhibitors did not alter secretion or other steps in the processing of C4. However, hemolytic activity of C4 was decreased more than 50%. The inhibitors' effect on C4 activity was prevented by adding Na2SO4 to restore sulfation of C4. Activity of C3, a complement component homologous to C4 but lacking tyrosine sulfate residues, was minimally reduced (19%) by the inhibitors. Decreased hemolytic activity of nonsulfated C4 apparently resulted from impaired interaction with complement subcomponent C1s (EC 3.4.21.42), the protease that physiologically activates C4. Purified C1s was able to cleave nonsulfated C4, but approximately 10-fold higher concentrations of C1s were required for that cleavage than to yield equivalent cleavage of sulfated C4. Our results suggest that activation of C4, a central component in the classical pathway of complement activation, is influenced by the level of sulfation of the protein. Thus, sulfation of C4 provides a potential locus for physiological or pharmacological modulation of complement-mediated opsonization and inflammation.
Gaussian multiaccess channels with ISI: capacity region and multiuser water-filling (1993)

The capacity region of a two-user Gaussian multiaccess channel with intersymbol interference (ISI) in which the inputs pass through respective linear systems and are superimposed before being corrupted by an additive Gaussian noise process is discussed. A geometrical method for obtaining the optimal input power spectral densities and the capacity region is presented. This method can be viewed as a nontrivial generalization of the single-user water-filling argument. It is shown that, as in the traditional memoryless multiaccess channel, frequency-division multiaccess (FDMA) with optimally selected frequency bands for each user achieves the total capacity of the multiuser Gaussian multiaccess channel with ISI. However, the capacity region of the two-user channel with memory is, in general, not a pentagon unless the channel transfer functions for both users are identical.< <ETX xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">&gt;</ETX>
Graph-based surface reconstruction from stereo pairs using image segmentation (2005)

This paper describes a novel stereo matching algorithm for epipolar rectified images. The method applies colour segmentation on the reference image. The use of segmentation makes the algorithm capable of handling large untextured regions, estimating precise depth boundaries and propagating disparity information to occluded regions, which are challenging tasks for conventional stereo methods. We model disparity inside a segment by a planar equation. Initial disparity segments are clustered to form a set of disparity layers, which are planar surfaces that are likely to occur in the scene. Assignments of segments to disparity layers are then derived by minimization of a global cost function via a robust optimization technique that employs graph cuts. The cost function is defined on the pixel level, as well as on the segment level. While the pixel level measures the data similarity based on the current disparity map and detects occlusions symmetrically in both views, the segment level propagates the segmentation information and incorporates a smoothness term. New planar models are then generated based on the disparity layers' spatial extents. Results obtained for benchmark and self-recorded image pairs indicate that the proposed method is able to compete with the best-performing state-of-the-art algorithms.
Bootstrap Analysis of DT-MRI Tractography Techniques: Streamlines and Tensorlines (2001)

Introduction Diffusion tensor MRI has been used to reconstruct white matter connections in the human brain [1,2]. The common approach in tracking the white matter fibers trajectories through the brain has been the use of the tensor major eigenvector in order to assess the propagation direction. As an alternative approach, tensorlines [3,4] was developed using the entire tensor, D, by defining a deflected vector:
Optimising TNFRSF agonism and checkpoint blockade with a novel CD137/PD-L1 bispecific antibody (2018)

Background: PD-1/L1 axis blockade shows durable responses and extended overall survival across cancer types in a subset of patients. Tumour Necrosis Factor Receptor (TNFR) superfamily activation is also being tested clinically to improve patient responses. Current interventions using therapeutic CD137 agonists to activate T cells are limited by adverse safety effects and poor efficacy as monotherapies. The generation of a bispecific agonist of CD137 following PD-L1 crosslinking allows a greater therapeutic window with improved safety and efficacy. Methods: An anti-CD137/PD-L1 mAb2 was generated by introducing a CD137-binding specificity into the Fc-region of a human IgG1 targeting PD-L1 mAb. FcgR binding was decreased by introducing a LALA mutation. Binding characterisation was assessed and in vitro activity measured in a mouse primary OT-1 CD8+ T cell assay. The anti-tumour activity and PK/PD of anti-CD137/PD-L1 mAb2 was tested in mouse tumour models. Results: An anti-CD137/PD-L1 mAb2 was developed, which binds to mouse PD-L1 enabling CD137 agonism (in vitro EC50: 3 pM in primary antigen-specific OT-1 assay). The mAb2 significantly reduced tumour growth in 3 syngeneic mouse tumour models (MC38, CT26 and B16-F10) with dose-dependent inhibition seen in CT26, resulting in a significant survival benefit at concentrations of 0.3 mg/kg or above. This growth inhibition was coincident with increases in tumour and peripheral activated CD8 T cells. Liver pharmacology was minimal as defined by histopathology. Conclusions: We report intra-tumoural and peripheral PD changes leading to an increase in the proliferative CD8+ T cell response following dosing with an anti-CD137/PD-L1 bispecific mAb2. These changes were dose dependent and coincident with tumour growth inhibition. In in vitro T cell activation assays the bispecific was superior to control antibodies and relevant combinations. Minimal liver pharmacology and no toxicity was observed with the anti-CD137/PD-L1 mAb2 unlike with other monoclonal antibodies targeting CD137. This warrants the development of a first-in-class anti-human CD137/PD-L1 bispecific antibody with a novel mode of action and improved therapeutic index for the treatment of human cancer. Legal entity responsible for the study: The authors. Funding: Has not received any funding. Disclosure: All authors have declared no conflicts of interest.
Evolutionary parameters of the transcribed mammalian genome: An analysis of 2,820 orthologous rodent and human sequences (1998)

We have rigorously defined 2,820 orthologous mRNA and protein sequence pairs from rats, mice, and humans. Evolutionary rate analyses indicate that mammalian genes are evolving 17-30% more slowly than previous textbook values. Data are presented on the average properties of mRNA and protein sequences, on variations in sequence conservation in coding and noncoding regions, and on the absolute and relative frequencies of repetitive elements and splice sites in untranslated regions of mRNAs. Our data set contains 1,880 unique human/rodent sequence pairs that represent about 2-4% of all mammalian genes. Of the 1,880 human orthologs, 70% are present on a new gene map of the human genome, thus providing a valuable resource for cross-referencing human and rodent genomes. In addition to comparative mapping, these results have practical applications in the interpretation of noncoding sequence conservation between syntenic regions of human and mouse genomic sequence, and in the design and calibration of gene expression arrays.
Smad2 and 3 transcription factors control muscle mass in adulthood (2009)

Loss of muscle mass occurs in a variety of diseases, including cancer, chronic heart failure, aquired immunodeficiency syndrome, diabetes, and renal failure, often aggravating pathological progression. Preventing muscle wasting by promoting muscle growth has been proposed as a possible therapeutic approach. Myostatin is an important negative modulator of muscle growth during myogenesis, and myostatin inhibitors are attractive drug targets. However, the role of the myostatin pathway in adulthood and the transcription factors involved in the signaling are unclear. Moreover, recent results confirm that other transforming growth factor-beta (TGF-beta) members control muscle mass. Using genetic tools, we perturbed this pathway in adult myofibers, in vivo, to characterize the downstream targets and their ability to control muscle mass. Smad2 and Smad3 are the transcription factors downstream of myostatin/TGF-beta and induce an atrophy program that is muscle RING-finger protein 1 (MuRF1) independent. Furthermore, Smad2/3 inhibition promotes muscle hypertrophy independent of satellite cells but partially dependent of mammalian target of rapamycin (mTOR) signaling. Thus myostatin and Akt pathways cross-talk at different levels. These findings point to myostatin inhibitors as good drugs to promote muscle growth during rehabilitation, especially when they are combined with IGF-1-Akt activators.
Antisense Sequence-Directed Cross-Linking of DNA Oligonucleotides by Mitomycin C (1996)

Oligodeoxyribonucleotides (ODNs) conjugated with mitomycin C (MC) via (-CH2-)n tethers of different lengths (n = 6, 12) to their terminal 5'-phosphate were synthesized, and their interaction with target complementary single-stranded DNA oligonucleotides was investigated. MC, a clinically used natural anticancer drug, is known to act as a bioreductive alkylating agent of duplex DNA with a remarkable preference for 5'-d(CG) sequences. The usual enzymatic bioreductive techniques known to trigger MC to alkylate DNA were employed in the reaction between the MC-oligonucleotide conjugates and their targets radiolabeled by 32P at their 5'-phosphate. A slow-moving radiolabeled product, detected by polyacrylamide gel electrophoresis using phosphorimaging techniques, was obtained in 15-25% yield with complementary DNA as target. Formation of these products was dependent upon complementary duplex formation. Evidence is presented that the DNA target is alkylated by the mitomycin C moiety of the ODN conjugate at the 2-amino group of a guanine base. These findings suggest that the MC-ODN conjugates may be useful specific inhibitors of cellular or viral gene expression. To our knowledge this is the first report on ODN conjugates of a reductively activated drug of known therapeutic value.
Murine thymocytes proliferate in direct response to interleukin-7 (1989)

The ability of interleukin-7 (IL-7) to stimulate murine thymocyte proliferation was investigated. IL-7, either alone or in concert with lectin, induced proliferation of adult thymocytes as well as day 13 fetal and adult CD4-/CD8-thymocytes. The IL-7-induced proliferative response of unfractionated thymocytes could not be inhibited by antibodies to IL-2, or IL-4, IL-6, or the IL-2 receptor. In addition, IL-2, IL-4, and IL-6 were not produced by thymocytes activated with IL-7, as judged by the absence of biologically active cytokine in IL-7-stimulated culture supernatants. IL-7 could act in concert with IL-2 and IL-4 or with IL-4 to enhance the proliferative response of thymocyte cultures. Thus, IL-7 may cause proliferation of thymocytes directly, not indirectly, through production of IL-2, IL-4, or IL-6. IL-7 may then play a significant role in differentiation of T lymphocytes.
Characterization of functionally distinct subpopulations of CD34+ cord blood cells in serum-free long-term cultures supplemented with hematopoietic cytokines (1993)

We have previously identified, based on the expression of the CD45RA and CD71 antigens, three major subpopulations of CD34+ cells derived from human umbilical cord blood: CD34+ CD45RAloCD71lo cells (up to 42% multipotent progenitors), CD34+ CD45RA+ CD71lo cells (90% myeloid progenitors), and CD34+ CD45RAloCD71+ cells (70% erythroid progenitors). In the present study, we have investigated the long-term proliferation and differentiation of these subpopulations in response to hematopoietic cytokines. Cells from each subpopulation were cultured for 38 days in serum- and stroma-free liquid cultures supplemented with cytokine combinations that favor either erythropoiesis or myelopoiesis. In keeping with their high content of primitive progenitors, CD34+ CD45RAloCD71lo cells showed the highest CD34+ cell expansion (up to 532- fold) throughout the culture period, followed by CD34+ CD45RA+ CD71lo (130-fold) and CD34+ CD45RAloCD71+ (28-fold) cells. Interestingly, the cytokine combination favoring myelopoiesis was always more efficient in inducing CD34+ cell expansion than the one favoring erythropoiesis. In all but one of the cultures, a predominance of myelopoiesis was observed after 2 weeks, even in those supplemented with the cytokine mixture that favors erythropoiesis. Only when CD34+ CD45RAloCD71+ cells were cultured in the presence of erythroid cytokine mixture, erythropoiesis was evident at all time points. However, such cultures could be sustained for only 29 days. The results of this study demonstrate that the cord blood-derived CD34+ cell compartment consists of functionally distinct cell subpopulations that possess different proliferative capacities in vitro. Our results also show that the cytokine combinations used here were able to modulate proliferation and, to a much lesser extent, differentiation of such subpopulations, probably by favoring the expansion of committed progenitors rather than by acting on uncommitted cells.
Synthesis of 9-Benzyl-6-aminopurines from 5-Amino-1-benzyl-4-cyanoimidazoles (2003)

Purine, purine nucleosides and their analogues have been extremely useful as anti-cancer agents. Robines, in 1964, reviewed the anti-tumour activity of purine and purine nucleosides from a structure-activity stand-point. Subsequently, several reviews on this subject have been published. The chemotherapeutic uses of purines and purine analogues have prompted tremendous efforts towards their synthesis, both in academia and in the pharmaceutical industry. As the purine ring system is a fusion of two aromatic heterocyclces, pyrimidine and imidazole, a logical starting point for ring synthesis is an appropriately substituted pyrimidine or imidazole from which the second ring can be constructed by a cyclization process. 5-amino-4-cyanoimidazoles are useful intermediates for purine synthesis. There are few reports of 9-aminopurine derivatives and most of the routes described are from 5amino-4-hydrazinopyrimidine precursors, substituted in the 2and 6-position. We therefore decided to investigate the reactions of 9benzyl-6-aminopurines 5a-b were prepared via a multistep synthesis from ethyl (Z)-N-(2-amino-1,2-dicyanovinyl)formimidate 1, by treatment with a benzyl-amine in a 1 : 1 molar ratio in ethanol in the presence of a catalytic amount of aniline hydrochloride to give the corresponding formamidine. (Scheme 1). Cyclisation of the formamidines in the presence of a strong base, aqueous KOH solution, provided the corresponding 5-amino-1-benzyl-4-cyanoimidazoles 3a-b, which are readily converted to 1-amino-9benzyl-6-aminopurines 5a-b by treatment with HC(OEt)3 and Ac2O followed by reaction with ammonia. The initial step involved conversion of the 5-amino-4cyanoimidazoles 3 to the corresponding ethoxyimidates 4. These were achieved by a modification of the procedure
Immune Response to Cholera Toxin Epitope Inserted in Salmonella Flagellin (1989)

Bacterial flagella are potent immunogens and aromatic-dependent (aro) Salmonella as live vaccines evoke humoral and cellular immune responses. Such strains expressing epitopes of protective antigens as inserts in flagellin would provide a novel way to vaccinate against diseases caused by unrelated pathogens. A synthetic oligonucleotide specifying an epitope of cholera toxin subunit B was inserted in a Salmonella flagellin gene. The chimeric flagellin functioned normally and the epitope was expressed at the flagellar surface. Parenteral administration to mice of an aro A flagellin-negative strain of S. dublin expressing the chimeric flagellin gene evoked antibody to cholera toxin.
Plasma sources based on the propagation of electromagnetic surface waves (1991)

Microwave and RF plasmas are finding increasing use in materials processing, plasma chemistry, chemical analysis, and other fields. This is stimulating the search for suitable plasma sources. In the 1970s, electromagnetic surface waves were put to use to sustain plasmas and an efficient microwave device, called a surfatron, was developed for this purpose. Recent work has shown that such discharges can also operate at radio frequencies. A large number of on surface-wave plasmas experimental data have been accumulated-their modelling is well advanced and they have found applications in various fields of research and technology. This paper reviews the physical principles of operation and the design of surface-wave plasma sources. Since the wave launcher is the central component of the source, this review presents a unified description of several compact, efficient, and easy to operate launchers specifically intended for plasma generation that have been developed over the past fifteen years. It is now possible to sustain such plasmas at frequencies ranging from 1 MHz to 10 GHz, in a pressure domain extending from 10-5 Torr up to few times atmospheric pressure, and in a rich variety of plasma vessels and reaction chambers.
Microsatellite analysis of loss of heterozygosity on chromosomes 9q, 11 p and 17p in medulloblastomas (1994)

Medulloblastoma (MB) is a primitive neuroectodermal tumour of the cerebellum whose pathogenesis is poorly understood. Previous studies suggest a role for loci on chromosomes 11p and 17p in the pathogenesis of MB. Evidence for another potential MB locus has recently emerged from studies on Gorlin syndrome (GS), an autosomal dominant syndrome with multiple basal cell carcinomas, epithelial jaw cysts, and skeletal anomalies. Since GS can be associated with MB, we examined sporadic (non-GS) cases of MB for evidence of loss of heterozygosity (LOH) on chromosome 9 where a putative GS locus has been localized to band q31. Nineteen paired blood and MB DNA specimens from 16 patients (11 primary tumours, two primary with recurrent tumours, one primary tumour and cell line, two cell lines) were studied by PCR analysis of microsatellites at D9S55 (9p12), D9S15 (9q13-q21.1), D9S127 (9q21.1-21.3), D9S12 (9q22.3), D9S58 (9q22.3-q31), D9S109 (9q31), D9S53 (9q31), GSN (9q33), D9S60 (9q33-q34), D9S65 (9q33-q34), ASS (9q34), D9S67 (9q34.3), TH (11p15.5), D11S490 (11q23.3), D17S261 (17p11.2-12), D17S520 (17p12), TP53 (17p13.1), D17S5 (17p13.3), D17S515 (17q22-qter), and by RFLP analysis at the WT-1 locus (11p13). Only two tumours had LOH on 9q. One was non-informative at D9S15, D9S65, and GSN but showed LOH at D9S127, D9S12, D9S58, D9S109, D9S53, D9S60, ASS, and D9S67. The other was uninterpretable at D9S65 and non-informative at D9S15, D9S58, D9S53, and D9S67 but exhibited LOH at D9S127, D9S12, D9S109, GSN, D9S60, and ASS. Both these cases were informative at D9S55 without LOH.(ABSTRACT TRUNCATED AT 250 WORDS)
Low power 50 Gb/s silicon traveling wave Mach-Zehnder modulator near 1300 nm (2013)

The wavelength band near 1300 nm is attractive for many telecommunications applications, yet there are few results in silicon that demonstrate high-speed modulation in this band. We present the first silicon modulator to operate at 50 Gbps near 1300 nm. We demonstrate an open eye at this speed using a differential 1.5 V(pp) signal at 0 V reverse bias, achieving an energy efficiency of 450 fJ/bit.