gebhart/patrepeval huggingface dataset:
The bruton tyrosine kinase inhibitor ibrutinib (PCI‐32765) blocks hairy cell leukaemia survival, proliferation and B cell receptor signalling: a new therapeutic approach (2014)

B cell receptor (BCR) signalling plays a critical role in the progression of several B-cell malignancies, but its role in hairy cell leukaemia (HCL) is ambiguous. Bruton tyrosine kinase (BTK), a key player in BCR signalling, as well as B cell migration and adhesion, can be targeted with ibrutinib, a selective, irreversible BTK inhibitor. We analysed BTK expression and function in HCL and analysed the effects of ibrutinib on HCL cells. We demonstrated uniform BTK protein expression in HCL cells. Ibrutinib significantly inhibited HCL proliferation and cell cycle progression. Accordingly, ibrutinib also reduced HCL cell survival after BCR triggering with anti-immunoglobulins and abrogated the activation of kinases downstream of the BCR (PI3K and MAPK). Ibrutinib also inhibited BCR-dependent secretion of the chemokines CCL3 and CCL4 by HCL cells. Interestingly, ibrutinib inhibited also CXCL12-induced signalling, a key pathway for bone marrow homing. Collectively, our data support the clinical development of ibrutinib in patients with HCL.
Purification and characterization of extremely thermophilic and thermostable 5'-methylthioadenosine phosphorylase from the archaeon Sulfolobus solfataricus. Purine nucleoside phosphorylase activity and evidence for intersubunit disulfide bonds. (1994)

5'-Methylthioadenosine phosphorylase from Sulfolobus solfataricus, a thermoacidophilic archaeon optimally growing at 87 degrees C, has been purified to homogeneity. Reducing agents are not required for catalytic activity. The enzyme has a molecular mass of 160 kDa and is composed of six apparently identical subunits of 27 kDa. The NH2-terminal sequence shows high homology (50%) with the NH2-terminal sequence of Escherichia coli purine nucleoside phosphorylase. Physicochemical and kinetic features are reported. 5'-Methylthioadenosine phosphorylase is highly thermophilic, with an optimum temperature of 120 degrees C. The enzyme is characterized by extreme thermal stability, remaining completely active after 2 h at 100 degrees C and showing half-inactivation times of 15 and 5 min when incubated at 130 and 140 degrees C, respectively. An apparent melting temperature of 132 degrees C has been calculated. After 24 h of incubation at room temperature no loss of activity is detected in the presence of 9 M urea, 4 M guanidine hydrochloride, 0.075% SDS, 50% methanol, 50% ethanol, 50% dimethylformamide, 1 M NaCl, and 1% Triton X-100. Data are also reported on the enzyme's resistance to proteolysis and on the effect of salts, detergents, solvents, and reducing agents on enzyme thermostability. Labeling experiments with iodo[2-14C]acetic acid resulted in the incorporation of approximately 12 mol of labeled iodoacetate/mol of protein, indicating the presence of six disulfide bonds that, on the basis of SDS-polyacrylamide gel electrophoresis, are probably positioned intersubunits, resulting in the organization of the enzyme into two trimers. 5'-Methylthioadenosine (MTA) phosphorylase is endowed with a broad substrate specificity, being able to phosphorolytically cleave inosine, guanosine, and adenosine with a better efficiency than MTA, allowing us to hypothesize that in S. solfataricus the same enzyme is responsible for the catabolism of MTA and of these purine nucleosides.
Efficient vaccination strategies for epidemic control using network information (2019)

Using even partial network information to prioritize vaccines at either the village or individual level, i.e. determine the optimal order of communities or individuals within each village, substantially improved epidemic outcomes. Such approaches may be feasible and effective in outbreak settings, and full ascertainment of network structure may not be required.
Pocket Oxford English dictionary (2002)

This is a reissue of the ninth edition of the world's longest-established and best-selling pocket English dictionary. It is one of the new generation Oxford dictionaries derived from the database of the highly-acclaimed New Oxford Dictionary of English and is particularly user friendly with its elegant open design, with different elements starting on new lines. It offers excellent coverage of English as an international language, the defining style is straightforward and non-technical, and thousands of examples illustrate idiomatic usage. All irregular noun, verb, and adjectival inflections are spelled out in full, while guidance on grammar and good usage is provided by in-text notes. Additional features include Wordbuilder boxes giving information on related words and thematic tables on subjects such as countries, chemical elements, and nationalities. This title replaces ISBN: 0-19-861334-2.
Genetic and Mutational Analysis of the T-Cell Antigen Receptor (1990)

The studies reviewed here exploit the fact that the TCR is a multisubunit complex whose perturbation initiates an assortment of biochemical pathways and diverse biological responses. The creation and analysis of T cells bearing aberrant TCRs has led to a number of important conclusions and provided a framework for some educated speculation about T-cell biology. The assembly of the TCR is a highly regulated process in which the majority of the synthesized material is rapidly degraded. Partial complexes, which potentially might interfere with ligand binding by, or the function of, complete receptor molecules, are not tolerated; this "architectural editing" is performed in a compartment(s) associated with the ER or, in some cases, lysosomes. The individual chains of the TCR can be separated into subgroups that are, perhaps, functionally autonomous. The disulfide-linked variable chains bind ligand. The zeta eta heterodimer appears to be largely responsible for coupling receptor occupancy to PI hydrolysis, the zeta 2 heterodimer may couple to tyrosine kinase activation and/or other signaling pathways. The zeta 2-containing receptors are fully capable of transducing signals leading to IL-2 production and growth inhibition, while the presence of the zeta eta heterodimer is associated with the autolytic response of T-cell hybridomas to activation. Finally, an intact and functional TCR must be present for optimal expression of some, although not all, manifestations of activation that are initiated via independent cell-surface molecules such as Thy-1, Ly-6, and CD2. Future experiments in which TCR chains that incorporate site-directed mutations are transfected into T and non-T cells are certain to enhance our appreciation of how the structure of this receptor determines its many biological attributes.
Inhibition of neuronal acetylcholine sensitivity by α-toxins from Bungarus multicinctus venom (1979)

Bungarus multicinctus venom contains several alpha-toxins in addition to the widely used alpha-bungarotoxin (Bgt 2.2). We have found that two of the alpha-toxins (Bgt 3.1 and 3.3) inhibit neuronal acetylcholine (AcCho) sensitivity when tested on ciliary ganglion neurons in cell culture. Over 90% of the AcCho sensitivity recorded in response to iontophoretic application of AcCho was blocked when the neurons were incubated with either of the toxins at 10(-7) M for 1 hr at 37 degrees C. The blockade could be partially reversed by incubating the neurons for 1-2 hr in medium lacking the toxins. The neurons also had a high-affinity binding site for Bgt 2.2, as indicated by binding studies with rhodamine-labeled Bgt 2.2. Concentrations of Bgt 2.2(10(-7) M) that should be nearly adequate to saturate the high-affinity site, however, had no detectable effect on AcCho sensitivity of the neurons. Higher concentrations of Bgt 2.2(10(-5) M) produced a partial inhibition of AcCho sensitivity, suggesting either that the neurons had two classes of binding sites for Bgt 2.2 (with the low-affinity site affecting AcCho sensitivity) or that the preparation of Bgt 2.2 contained minor components (e.g., Bgt 3.1 or 3.3) that were responsible for the blockade. The mechanisms by which Bgt 3.1 and 3.3 inhibit neuronal AcCho sensitivity remain unknown. If they bind specifically to the AcCho receptor, they will be useful agents for studying the distribution and regulation of this membrane component.
Advanced Optical Modulation Formats (2006)

Fiber-optic communication systems form the high-capacity transport infrastructure that enables global broadband data services and advanced Internet applications. The desire for higher per-fiber transport capacities and, at the same time, the drive for lower costs per end-to-end transmitted information bit has led to optically routed networks with high spectral efficiencies. Among other enabling technologies, advanced optical modulation formats have become key to the design of modern wavelength division multiplexed (WDM) fiber systems. In this paper, we review optical modulation formats in the broader context of optically routed WDM networks. We discuss the generation and detection of multigigabit/s intensity- and phase-modulated formats, and highlight their resilience to key impairments found in optical networking, such as optical amplifier noise, multipath interference, chromatic dispersion, polarization-mode dispersion, WDM crosstalk, concatenated optical filtering, and fiber nonlinearity
Effects of Oligonucleotide Immobilization Density on Selectivity of Quantitative Transduction of Hybridization of Immobilized DNA (2000)

Immobilized single-stranded DNA (ssDNA) can be used as a selective “reagent” to bind complementary nucleic acids for applications including detection of pathogenic organisms and genetic mutations. The density of ssDNA on a surface will determine nearest neighbor interactions, surface interactions, and charge density due to ionizable phosphate groups. This may result in a local ionic strength, pH, and dielectric constant at the surface that is substantially different from that in bulk electrolyte solution. It is the local conditions that influence the thermodynamics of hybridization, and this can be studied by the melt temperature (Tm) of double-stranded DNA (dsDNA). Organosilane chemistry has been used to covalently immobilize hexaethylene glycol linkers and to control the subsequent density of dT20 that was prepared by automated synthesis. Fiber-optic biosensors based on fused silica optical fibers that were coated with DNA were used in a total internal reflection fluorescence instrument to determine Tm from the dissociation of duplexes of mixtures of fluorescein-labeled and unlabeled dA20 and d(A9GA10). Each thermal denaturation of dsDNA at the surface of the optical fibers was accompanied by a 2−3-fold reduction in standard enthalpy change, relative to values determined for denaturation in bulk solution. The experimental results suggest that the thermodynamic stability of duplexes that are immobilized on a surface is dependent on the density of immobilized DNA. Additionally, the deviation in Tm arising as a result of the presence of a centrally located single base-pair mismatch was significantly larger for thermal denaturation occurring at the surface of the optical fibers (ΔTm = 6−10 °C) relative to that observed in bulk solution (ΔTm = 3.8−6.1 °C). These results suggest that hybridization at an interface occurs in a significantly different physical environment in comparison to hybridization in bulk solution, and that surface density can be tuned to design analytical figures of merit.
αvβ3-dependent cross-presentation of matrix metalloproteinase–2 by melanoma cells gives rise to a new tumor antigen (2005)

A large array of antigens that are recognized by tumor-specific T cells has been identified and shown to be generated through various processes. We describe a new mechanism underlying T cell recognition of melanoma cells, which involves the generation of a major histocompatibility complex class I-restricted epitope after tumor-mediated uptake and processing of an extracellular protein--a process referred to as cross-presentation-which is believed to be restricted to immune cells. We show that melanoma cells cross-present, in an alpha v beta3-dependent manner, an antigen derived from secreted matrix metalloproteinase-2 (MMP-2) to human leukocyte antigen A*0201-restricted T cells. Because MMP-2 activity is critical for melanoma progression, the MMP-2 peptide should be cross-presented by most progressing melanomas and represents a unique antigen for vaccine therapy of these tumors.
Giving applications access to Gb/s networking (1993)

Operating systems (OSs) used in high-speed networks must reduce copying to deliver maximal throughput to applications and must deliver this throughput while preserving the capability of the host to perform applications processing. One way to reduce copying by enabling data transfers directly to and from buffers located in application-process address spaces is presented. The method has been demonstrated experimentally and is shown to deliver high throughputs. OS support must also include scheduling, which allows bandwidth-allocated traffic streams to be delivered. The implementation described provides resource scheduling for network users, and considerably reduces interrupt overhead.< <ETX xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">&gt;</ETX>
Rethinking optimal control of human movements (2012)

The complex bio-mechanics of human body is capable of generating an unlimited repertoire of movements, which on one hand yields highly versatile motor behavior but on the other hand presents a formidable control problem for the brain. Understanding the computational process that allows us to easily perform various motor tasks with a high degree of coordination is of central interest to both neuroscience and robotics control. In recent decades, it became widely accepted that the observed movement features can be understood as a result of the brain's effort of optimizing the motor behaviors. However, a major challenge for the optimal control models is deciding how the motor task should be represented. In this thesis, (1) I compare the existing representations in literature (2) derive a novel formulation using the principles and analytic tools from physics, (3) predict previously unreported features of human movements, and (4) conrm them in psychophysics experiments. I also explore implementing the optimal controller with articial neural networks, which may potentially lead to a deeper understanding of neural computation. The obtained controller generates realistic target-directed hand movements in real-time, and reproduces many of reported neuro-physiology data in primary motor cortex
The formation of autoantibodies and antibodies to TNF-α blocking agents in relation to clinical response in patients with ankylosing spondylitis. (2010)

This study indicates that antibody formation to IFX or ADA is related to a decrease in efficacy and early discontinuation of anti-TNF-α treatment in AS patients. Furthermore, autoantibody formation does not seem to be associated with antibody formation to TNF-α blocking agents.
Cyclin D Expression Is Controlled Post-transcriptionally via a Phosphatidylinositol 3-Kinase/Akt-dependent Pathway (1998)

Cyclin D expression is regulated by growth factors and is necessary for the induction of mitogenesis. Herbimycin A, a drug that binds to Hsp90, induces the destruction of tyrosine kinases and causes the down-regulation of cyclin D and an Rb-dependent growth arrest in the G1 phase of the cell cycle. We find that the induction of D-cyclin expression by serum and its repression by herbimycin A are regulated at the level of mRNA translation. Induction of cyclin D by serum occurs prior to the induction of its mRNA and does not require transcription. Herbimycin A repression is characterized by a decrease in the synthetic rate of D-cyclins prior to changes in mRNA expression and in the absence of changes in the half-life of the protein. This effect on D-cyclin translation is mediated via a phosphatidylinositol 3-kinase (PI 3-kinase)-dependent pathway. PI 3-kinase inhibitors such as wortmannin and LY294002, and rapamycin, an inhibitor of FRAP/TOR, cause a decline in the level of D-cyclins, whereas inhibitors of mitogen-activated protein kinase kinase and farnesyltransferase do not. Cells expressing the activated, myristoylated form of Akt kinase, a target of PI 3-kinase, are refractory to the effects of herbimycin A or serum starvation on D-cyclin expression. These data suggest that serum induction of cyclin D expression results from enhanced translation of its mRNA and that this results from activation of a pathway that is dependent upon PI 3-kinase and Akt kinase.
Palmitoylation-dependent association with CD63 targets the Ca2+ sensor synaptotagmin VII to lysosomes (2010)

Syt VII is a Ca(2+) sensor that regulates lysosome exocytosis and plasma membrane repair. Because it lacks motifs that mediate lysosomal targeting, it is unclear how Syt VII traffics to these organelles. In this paper, we show that mutations or inhibitors that abolish palmitoylation disrupt Syt VII targeting to lysosomes, causing its retention in the Golgi complex. In macrophages, Syt VII is translocated simultaneously with the lysosomal tetraspanin CD63 from tubular lysosomes to nascent phagosomes in a Ca(2+)-dependent process that facilitates particle uptake. Mutations in Syt VII palmitoylation sites block trafficking of Syt VII, but not CD63, to lysosomes and phagosomes, whereas tyrosine replacement in the lysosomal targeting motif of CD63 causes both proteins to accumulate on the plasma membrane. Complexes of CD63 and Syt VII are detected only when Syt VII palmitoylation sites are intact. These findings identify palmitoylation-dependent association with the tetraspanin CD63 as the mechanism by which Syt VII is targeted to lysosomes.
Tourette’s Syndrome (2008)

Tourette’s syndrome (TS) is a neuropsychiatric disorder of childhood onset characterized by the presence of motor and vocal tics for a duration of at least 1 year. Tics are typically brief and stereotypical movements (eg, eye blinking, head jerks) or vocalizations (eg, throat clearing, grunting), but they can also be more complex movements involving multiple muscle groups and combinations of movements and sounds. There is a great range of tic severity. Tics can be so subtle or occur so infrequently as to be unnoticeable, even to the person with the tics. However, tics can also be so intense and frequent that they are readily noticeable by others, and they can be disruptive of daily activities. Indeed, in some cases (eg, severe head jerks), tics can cause pain or physical injury (eg, cervical disc and spine damage). Tics usually begin in childhood; the average age at diagnosis is 7 years. They reach peak severity in the early teen years and then lessen in intensity and frequency during young adulthood (Leckman et al., 2001). Tics wax and wane in severity, worsening with excitement and stress and improving during calm, focused activities. Coprolalia and its motor counterpart copropraxia (uttering obscene words or making obscene gestures, respectively) are uncommon symptoms, occurring in less than 10% of patients with TS and are not required for a diagnosis of TS (Robertson and Stern, 1998). Many patients describe a sensation or urge prior to tic occurrence, commonly referred to as a premonitory sensation or urge (Miguel et a1., 2000). Even though tics are considered involuntary, they can be voluntarily suppressed for short periods of time. Prevalence estimates of TS have varied and depend a great deal on the threshold for diagnosis and setting in which cases are identified. A review of the many epidemiologic studies suggests that 0.1% to 1% of people are affected with TS (Scahill et al., 2005). Despite this variability in specific rates, epidemiologic studies have consistently identified that males are more commonly affected than females, children are more frequently affected than adults, and that milder forms of TS are more common than severe forms.
Endocrinology (1991)

Journal Article Endocrinology Get access M A Baxter, M A Baxter Department of Medicine, University of Birmingham, Queen Elizabeth Hospital, Edgbaston, Birmingham B15 2TH, UK Search for other works by this author on: Oxford Academic Google Scholar M C Sheppard M C Sheppard Department of Medicine, University of Birmingham, Queen Elizabeth Hospital, Edgbaston, Birmingham B15 2TH, UK Correspondence: Professor M.C. Sheppard, Ph.D., F.R.C.P. Search for other works by this author on: Oxford Academic Google Scholar Postgraduate Medical Journal, Volume 67, Issue 783, January 1991, Pages 23–32, https://doi.org/10.1136/pgmj.67.783.23 Published: 01 January 1991
Diversity in Gold- and Silver-Catalyzed Cycloisomerization of Epoxide−Alkyne Functionalities (2008)

We report Au(I)- and Ag(I)-catalyzed cycloisomerizations of epoxide-alkyne functionalities in both aromatic and nonaromatic systems, leading to diversified carbocyclic and heterocyclic frameworks with high chemoselectivities. The use of such cycloisomerizations is reflected by a facile access to the cores of natural pallidol and gibberic acid.
Direct Gene Transfer into Skeletal Muscle In Vivo : Factors Affecting Efficiency of Transfer and Stability of Expression (1993)

Striated muscle is the only tissue found to be capable of taking up and expressing reporter genes that are transferred in the form of plasmid DNA. Thus, direct gene transfer is a potential method of gene therapy for the primary inherited myopathies. However, results to date have had insufficient and too variable expression to consider using direct gene transfer in human trials. We have determined that much of the variability of expression is due to nonuniform distribution of substances injected into skeletal muscle in vivo, and have developed a model to ameliorate this. Preinjection of muscles with a relatively large volume of hypertonic sucrose improves the distribution of injected substances and results in significantly less variable expression of reporter genes for luciferase or beta-galactosidase; the coefficient of variation for mean luciferase activity was reduced from about 120% to 25%. Expression is not directly proportional to dose, but is more so if the muscles are preinjected with sucrose than not. Expression is higher and less variable if DNA is injected in a larger than a smaller volume. The choice of promoter appears to be particularly important. Luciferase reporter gene expression from the SV40 promoter was transient and low, whereas expression driven by the Rous sarcoma virus (RSV) promoter was high and sustained, such that a 1,000-fold difference in expression could be observed. The mechanism of gene uptake is still unknown, but our findings indicate that fibers damaged by the injection procedure do not take up and express plasmid DNA.