gebhart/patrepeval huggingface dataset:
Discovery and Preclinical Characterization of INCB018424, a Selective JAK2 Inhibitor for the Treatment of Myeloproliferative Disorders. (2007)

Abstract Activating mutations in Janus kinase 2 (JAK2) have recently been identified in the majority of Philadelphia chromosome negative (Ph-) myeloproliferative disorders (MPDs). Importantly, constitutive JAK2 activation is oncogenic and, in murine models, recapitulates much of the pathobiology observed in MPD patients, suggesting that JAK2 inhibition may be of therapeutic benefit. Here we describe the identification and preclinical characterization of INCB018424, a potent, selective, and orally bioavailable inhibitor of the JAK2 now in clinical trials. INCB018424 was identified through an extensive medicinal chemistry effort designed to optimize potency, selectivity, pharmaceutical and pharmacokinetic properties. INCB018424 inhibits JAK2 at <1 nM and demonstrated >500–fold selectivity against a broad sampling of the kinome. The potency and selectivity of INCB018424 translated to exceptional cellular activity where it inhibited the proliferation of FDCP cells and BaF/3 cells expressing JAK2V617F with an IC50 of 100–130 nM, but not the proliferation of cell lines expressing activating mutations in either BCR-Abl or cKit (IC50 > 25 and 4 mM, respectively). The effect of INCB18424 on cell proliferation correlated well with reduced levels of phosphorylated JAK2 and STAT5 in the BaF/3 cell model, suggesting that the effect is mediated by pharmacological inhibition of JAK-STAT pathway. Interestingly, the activation of endogenous wild-type JAKs - by the addition of IL-3 - shifted the potency of INCB018424 in the BaF/3 model greater than five fold suggesting that cells expressing the mutated form of JAK2 may be more sensitive to INCB018424. Indeed, using cells harvested from patients with Jak2V617F-positive polycythemia vera (PV) in colony forming assays, we observed that INCB018424 inhibited the cytokine-independent formation of erythroid progenitor colonies (n=3) with an IC50 of 67nM while normal colony formation from healthy donors (n=3) was inhibited 50% at > 400 nM. Further, INCB018424 inhibited proliferation of PV patient samples (n=3) following ex vivo expansion of erythroid progenitors in serum free media, with an IC50 of 60 nM, similar to that observed in semi-solid media. In a mouse model of MPD, where implantation of BaF/3 cells expressing JAK2V617F results in rapid organomegaly and reduced survival, oral administration of INCB018424 was well tolerated and markedly reduced the splenomegaly. Using this animal model, we also demonstrated that selective JAK inhibition eliminates neoplastic cells from the spleen, liver, and bone marrow normalizing the histology of affected organs and significantly prolongs survival. As such, potent and selective JAK inhibitors such as INCB018424 hold great promise for the treatment of MPDs and other disease states associated with elevated JAK activity - a concept currently being tested clinically.
Visual speaker authentication by ensemble learning over static and dynamic lip details (2016)

This paper presents a new visual speaker authentication scheme which can extract the most representative details of a speaker's lip feature. For each speaker, the entire utterance pronouncing a specific prompt text is divided into several word-level segments and a mute segment. Three kinds of lip feature details are investigated including: i) lip movements in each word segment; ii) lip movements in each word transition; and iii) lip appearance in the mute segment. An HMM with model adaptation is adopted to depict each dynamic details and a linear SVM is used to differentiate the static details. A confident measure is introduced to evaluate the discriminative ability of each details between the speaker and other speakers. Finally, an ensemble learning structure is proposed which focuses on the discriminative details and provides a reliable authentication result. Experimental results have demonstrated that our scheme achieves better performance compared with some traditional approaches investigated.
The Practice of Ministry (1972)

Ferment in the ministry today requires an understanding of ministry that focuses upon the effect on the lives of people of what a minister does rather than upon the role functions he performs. The practice of ministry may be defined, therefor, under four categories: (1) the minister as a guarantor of continuity, (2) the minister as a celebrator of change, (3) the minister as a negotiator of structure, and (4) the minister as a facilitator of meaning. Any concept of ministry must be linked to an empirical understanding of man as a developing person, and Erikson's schema serves the purpose well. Whatever model of ministry one employs, it must be flexible in dealing with the realities of change.
New features of wave propagation not subject to cutoff between two parallel guiding surfaces (1967)

Wave propagation not subject to cutoff between two parallel guiding surfaces is generally described in terms of the so-called TEM mode. Although this is recognised to be an over simplification, it is nevertheless very close to the truth in many cases when bare copper conductors are used to form the guiding surfaces. However, at high frequencies, such surfaces, having very nearly equal resistive and reactive components which are not entirely insignificant, tend to require the support of a hybrid TEM-dual-surface-wave mode, and this can be readily accentuated by deliberately enhancing the surface reactances. Investigation shows that the accompanying redistribution of power flow over the cross-section of the guide can, in appropriate circumstances, lead to a very significant reduction of the attenuation suffered by the wave. The technique is applicable both to striplines and to coaxial cables.
Observation of Electromagnetic Angular Momentum within Magnetite (1979)

A hollow cylinder of magnetite at 4 K has been subjected to the simultaneous action of constant axial magnetic field $\stackrel{\ensuremath{\rightarrow}}{\mathrm{B}}$ and low-frequency radial electric field $\stackrel{\ensuremath{\rightarrow}}{\mathrm{E}}$. The reaction torque, which appears in the magnetite as the electromagnetic angular momentum changes, has been observed for the first time. Preliminary results favor the Livens' reaction-force density $\frac{\ensuremath{-}\ensuremath{\partial}({\ensuremath{\epsilon}}_{0}\stackrel{\ensuremath{\rightarrow}}{\mathrm{E}}\ifmmode\times\else\texttimes\fi{}\stackrel{\ensuremath{\rightarrow}}{\mathrm{B}})}{\ensuremath{\partial}t}$ and contradict the alternative $\frac{\ensuremath{-}\ensuremath{\partial}({\ensuremath{\epsilon}}_{0}{\ensuremath{\mu}}_{0}\stackrel{\ensuremath{\rightarrow}}{\mathrm{E}}\ifmmode\times\else\texttimes\fi{}\stackrel{\ensuremath{\rightarrow}}{\mathrm{H}})}{\ensuremath{\partial}t}$ of Einstein and Laub which was followed by Abraham and is widely accepted by modern authors.
Investigation of Ca3TaGa3Si2O14 piezoelectric crystals for high temperature sensors (2011)

The dielectric and electromechanical properties of fully ordered Ca3TaGa3Si2O14 (CTGS) crystals were investigated over the temperature range of −60∼700 °C. The highest electromechanical coupling factor, k26 (18.9%) and piezoelectric coefficient, d26 (−11.5 pC/N) were obtained for (YXl)-25° cuts. The temperature dependent behavior of resonance frequency (fr) was investigated in single-rotated thickness shear mode (TSM) (YXl)θ cuts (θ = −35°∼10°). The turnover temperatures of resonance frequency were found to increase from 20 °C to 330 °C, as the rotation angle θ varied from −22.5° to −35°. Bulk acoustic wave (BAW) resonators based on Y(−30°) monolithic disks with a fundamental frequency ∼2.87 MHz were fabricated, where the in air mechanical quality factor Q was found to be on the order of 24000 and 10000 at 20 °C and 700 °C, respectively. The high coupling k26, high mechanical Q, and high electrical resistivity (16 MΩ·cm) at 700 °C, together with the near zero TCF characteristics at elevated temperatures, demonstrate the potential of CTGS crystals for high temperature sensor applications.
Design of a Hexahedron-Octahedron Based Spherical Stepping Motor (2008)

A spherical stepping motor with a hexahedron based rotor and an octahedron based stator is designed. The motor has a rotor supported by six spherical bearings and a stator. Eight NdFeB permanent magnets are attached at the vertexes of the virtual hexahedron inscribed in the rotor so that the North and the South poles are located alternately. Six iron cores are also attached on the spherical shell at the center of the faces of the virtual hexahedron inscribed in the rotor. Six, twelve, and seven armature coils are attached at the vertexes, center of the edges, and the center of the faces of the virtual octahedron inscribed in the stator respectively. The motor will be driven in almost any direction by the combination of the conventional motor driver and a switch. The designed motor will be easy controlled high-torque motor with wide working area.
Prognostic value of PD-L1 expression in tumor infiltrating immune cells in cancers: A meta-analysis (2017)

Programmed death-ligand 1 (PD-L1) is a promising target of cancer immune therapy. It not only expressed in tumor cells (TCs) but also up regulated in tumor infiltrating immune cells (TIICs). Although the previous meta-analysis have shown that PD-L1 expression in TCs was a valuable biomarker in predicting cancer prognosis, but few researches systematic evaluated the association between its expression in TIICs and survival of cancer patients. Thus, we performed this meta-analysis to evaluate the prognostic value of PD-L1 expression in TIICs in different types of cancers. Our results are valuable supplements when using PD-L1 expression to predict the survival of cancer patients and to select the beneficial patients from PD-L1 target therapy. PubMed, Embase, Web of Science and the Cochrane Central Search Library were used to perform our systematic literature search. Overall survival (OS) at 5th years and hazard ratios (HRs) were calculated using random effects models. Eighteen studies involving 3674 patients were included. The median positive rate of PD-L1 staining in TIICs was 36.37%. PD-L1 positive expression in TIICs related to a lower risk of death (HR = 0.784, 95%CI: 0.616-0.997, P = 0.047). Subgroup analyses found that PD-L1 positive expression in TIICs indicated a better prognosis especially in breast cancer patients (HR = 0.359, P = 0.041). When using whole tissue section slides, or using 'any expression in TIICs' as a cutoff value to assessing the results of IHC staining, PD-L1 expression in TIICs had a good prognostic value in cancer prognosis (HR = 0.587, P = 0.001 and HR = 0.549, P = 0.002). Our findings suggested that PD-L1 expression in TIICs was related to a better survival of cancer. The comprehensive evaluation of tumor cells and tumor infiltrating immune cells are required when evaluating the effect of PD-L1 expression on prognosis of cancer in future research.
Polarizing beam splitters for infrared and millimeter waves using single-layer-coated dielectric slab or unbacked films (1986)

Get PDF Email Share Share with Facebook Tweet This Post on reddit Share with LinkedIn Add to CiteULike Add to Mendeley Add to BibSonomy Get Citation Copy Citation Text R. M. A. Azzam, "Polarizing beam splitters for infrared and millimeter waves using single-layer-coated dielectric slab or unbacked films," Appl. Opt. 25, 4225-4227 (1986) Export Citation BibTex Endnote (RIS) HTML Plain Text Citation alert Save article
Rapid optimization method of the strong stray light elimination for extremely weak light signal detection (2017)

The strong stray light has huge interference on the detection of weak and small optical signals, and is difficult to suppress. In this paper, a miniaturized baffle with angled vanes was proposed and a rapid optimization model of strong light elimination was built, which has better suppression of the stray lights than the conventional vanes and can optimize the positions of the vanes efficiently and accurately. Furthermore, the light energy distribution model was built based on the light projection at a specific angle, and the light propagation models of the vanes and sidewalls were built based on the Lambert scattering, both of which act as the bias of a calculation method of stray light. Moreover, the Monte-Carlo method was employed to realize the Point Source Transmittance (PST) simulation, and the simulation result indicated that it was consistent with the calculation result based on our models, and the PST could be improved by 2-3 times at the small incident angles for the baffle designed by the new method. Meanwhile, the simulation result was verified by laboratory tests, and the new model with derived analytical expressions which can reduce the simulation time significantly.
THE BIOLOGY OF ANTI-FERTILITY STEROIDS (1966)

The literature on the hormonal control of fertility is complicated because all of the agents used clinically are mixtures of oestrogens and progestogens. Clinical reports generally refer to the additive effects of these two hormonal types, whereas biological studies are frequently performed with either the progestational or oestrogenic agent alone. The contribution of each of these components to the effectiveness of the oral contraceptives has not been fully summarized and there has been little attempt to correlate available biological and clinical information. We have undertaken such an evaluation to evolve a mechanistic concept of the action of these steroid hormones in the control of female fertility. In the female, the chain of events which results in fertility is dependent on a balanced interaction of the humoral agents of the hypothalamus, trophic hormones secreted by the pituitary gland and gonadal steroid hormones which have an ultimate effect on egg
Increase in Testicular Androgen Receptor during Sexual Maturation in the Rat1 (1988)

Androgen receptor concentration was measured by exchange with 3H-dimethylnortestosterone (DMNT) in cytosol and nuclear extracts from testes of rats 15-90 days of age. Dissociation kinetics verified the necessity of an extended incubation (86 h) for maximum exchange at 4 degrees C. Nuclear androgen receptor concentration per mg DNA decreased between 15 and 25 days of age, from 375 to 146 fmol per mg DNA, then increased to 584 fmol per mg DNA at 90 days. Testicular receptor content also increased between 25 and 90 days of age. Cytosol receptor concentration patterns were similar to nuclear androgen receptor patterns. The affinity of the receptor for the ligand did not change with age (mean Kd = 0.88 nM). No significant difference in androgen receptor concentration per cell was detected between cultured peritubular cells from animals 25 and 45 days of age. Androgen receptor concentrations in freshly isolated peritubular cells could not be determined. There also was no difference in receptor concentration per cell in a Leydig cell-enriched fraction from animals between 25 and 45 days of age. Although androgen receptor concentrations per Sertoli cell increased between 15 and 35 days of age, the increase in Leydig cell number over the same period probably accounted for approximately 75% of the increase in receptor per testis between 25 and 45 days of age.
Determination of Noise Immission From Sound Sources Close to the Ears (2008)

Udgivelsesdato: JAN
How well does B-type natriuretic peptide predict death and cardiac events in patients with heart failure: systematic review (2005)

Although systematic reviews of prognostic studies have inherent difficulties, including the possibility of publication bias, the results of the studies in this review show that BNP is a strong prognostic indicator for both asymptomatic patients and for patients with heart failure at all stages of disease.
Effect of gamma radiation on resting B lymphocytes. II. Functional characterization of the antigen-presentation defect. (1988)

The effect of radiation on three discrete Ag-presentation functions in resting B cells was examined: 1) Ag uptake and processing, 2) expression of processed Ag in the context of functional class II molecules, and 3) provision of necessary co-stimulatory, or "second," signals. Analysis of radiation's effect on B cell presentation of intact vs fragmented Ag or its effect on presentation by Ag-pulsed B cells indicated that damage to Ag uptake and processing could not account for the bulk of the radiation-induced Ag-presentation defect. Experiments with phosphatidylinositol hydrolysis as an indirect measure of TCR occupancy suggested that irradiation caused a fairly rapid (within 1 to 2 h) decrease in the ability of the B cell APC to display a stimulatory combination of Ag and class II molecule. Ag dose-response analyses demonstrated that when presenting a fragment of the Ag pigeon cytochrome c to a T cell clone, 3000 rad-treated B cell APC were able to stimulate approximately 50% as much phosphatidylinositol turnover as unirradiated B cells. It was also found that, in contrast to their inability to initiate T cell proliferation, and similarly to chemically cross-linked splenocytes, heavily irradiated resting B cells plus Ag induced a state of Ag hyporesponsiveness in T cell clones. This effect on T cells had the same Ag- and MHC-specificity as did receptor occupancy required for proliferation, indicating that heavily irradiated resting B cells bear functional class II molecules. Co-culture of T cells with allogeneic B cells and syngeneic heavily irradiated B cells or chemically cross-linked splenic APC plus Ag resulted in T cell proliferation and interfered with the induction of the hyporesponsive state. This co-stimulatory function was radiosensitive in resting allogeneic B cells. Together, these data support the hypothesis that the major functional consequences of radiation to resting B cell APC are a reduction in the effective display of Ag plus class II molecules and, probably what is more important, a loss in the ability to provide APC-derived co-stimulatory signals.
Cytotoxic Effect of the Pine needle extracts (1998)

This study was performed to observe cytotoxic effect of the pine needle extracts against cancer cell lines including human gastric carcinoma (KATOIII), human lung carcinoma (A549), human hepatocellular carcinoma (Hep3B) and human breast adenocarcinoma (MCF-7) using MTT (3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyl tetrazolium bromide) and SRB (sulforhodamine B) method. The extracts were prepared by step-wise fractionation of ethanol extract of pine needles using diethylether, chloroform, ethylacetate, butanol and water. The growth of the cancer cells in medium containing pine needle extracts were significantly inhibited degree in proportion to the increase of the extract concentration. A significant shrinkage of Hep3B cells was observed when the cells were exposed into 0.5, 1 mg/mL of pinus rigida extract.
Pattern control for adaptive antenna processing with overlapped sub-arrays (2004)

This paper deals with the optimization of adaptive techniques operating with partially overlapped sub-arrays. Three new adaptive schemes are introduced that properly cancel jamming signals when present, but give exactly the desired quiescent pattern in the absence of jammers. These schemes solve the problem of the antenna pattern control under adaptive operation even for the case of overlapped sub-arrays.
Sustained Cellular Immune Dysregulation in Individuals Recovering from SARS-CoV-2 Infection (2020)

ABSTRACT SARS-CoV-2 causes a wide spectrum of clinical manifestations and significant mortality. Studies investigating underlying immune characteristics are needed to understand disease pathogenesis and inform vaccine design. In this study, we examined immune cell subsets in hospitalized and non-hospitalized individuals. In hospitalized patients, many adaptive and innate immune cells were decreased in frequency compared to healthy and convalescent individuals, with the exception of B lymphocytes which increased. Our findings show increased frequencies of T-cell activation markers (CD69, Ox40, HLA-DR and CD154) in hospitalized patients, with other T-cell activation/exhaustion markers (CD25, PD-L1 and TIGIT) remaining elevated in hospitalized and non-hospitalized individuals. B cells had a similar pattern of activation/exhaustion, with increased frequency of CD69 and CD95 during hospitalization, followed by an increase in PD1 frequencies in non-hospitalized individuals. Interestingly, many of these changes were found to increase over time in non-hospitalized longitudinal samples, suggesting a prolonged period of immune dysregulation following SARS-CoV-2 infection. Changes in T-cell activation/exhaustion in non-hospitalized patients were found to positively correlate with age. Severely infected individuals had increased expression of activation and exhaustion markers. These data suggest a prolonged period of immune dysregulation following SARS-CoV-2 infection highlighting the need for additional studies investigating immune dysregulation in convalescent individuals.
New Approaches in the Treatment of Critical‐Size Segmental Defects in Long Bones (2007)

Abstract Summary : The treatment of large segmental diaphyseal bone deficiencies presents a formidable challenge. The standard treatment modalities such as cancellous bone grafting, cortical allografts, vascularized bone transfer, or distraction osteogenesis exhibit extremely high complication rates, and can culminate in limb amputation or major functional deficits. Recent efforts to develop new treatment modalities for segmental bone loss have resulted in designing new biodegradable polymeric and metallic mesh implants that can incorporate novel osteogenic, osteoinductive, and/or osteoconductive bone healing augmentation materials. These biologic implant composites are capable of further enhancing the efficacy of the treatment applied. This paper briefly reviews the limitations of the currently applied standard treatment modalities for segmental critical size bone defects, provides insight into the specific treatment challenges, and presents the animal and initial clinical results of new alterative treatment approaches that involve the application of cylindrical mesh implants consisting of biodegradable polylactide membranes or titanium cages as a means of potentiating the efficacy of bone graft.
A New Quantitative Method for Analysis of Drill Cuttings and Core for Geologic, Diagenetic and Reservoir Evaluation (2009)

Summary Drill cuttings have traditionally been utilized as a first look, qualitative tool but are often not re-examined once wireline logs are run. The advent of advanced technology from the mining industry has broad applications for quantitative rock analysis of oil and gas reservoirs. The automated, high resolution data provided from QEMSCAN ® analysis of drill cuttings provides much more information than conventional
A power efficient W-CDMA smart power amplifier with emitter area adjusted for output power levels (2004)

We demonstrate a power efficient HBT MMIC smart power amplifier to provide improved power efficiency for W-CDMA mobile terminals. A small part of amplifier transistors is activated selectively to deliver output power with improved efficiency for low power mode of 16 dBm, and the PAE (power added efficiency) is increased by a factor of 1.8 using 21 mA of a quiescent current. At a high power mode, the MMIC reveals 27 dBm output power with the PAE of 33.4%. From this approach the battery lifetime can be extended as much as 2.5 times through calculating overall average power usage efficiency. The fabricated chip size is as small as 0.95/spl times/1 mm/sup 2/ including input/inter-stage matching network and all active bias circuits.