gebhart/patrepeval huggingface dataset:
5’UTR point substitutions and N-terminal truncating mutations of ANKRD26 in acute myeloid leukemia (2017)

Thrombocytopenia 2 (THC2) is an inherited disorder caused by monoallelic single nucleotide substitutions in the 5'UTR of the ANKRD26 gene. Patients have thrombocytopenia and increased risk of myeloid malignancies, in particular, acute myeloid leukemia (AML). Given the association of variants in the ANKRD26 5'UTR with myeloid neoplasms, we investigated whether, and to what extent, mutations in this region contribute to apparently sporadic AML. To this end, we studied 250 consecutive, non-familial, adult AML patients and screened the first exon of ANKRD26 including the 5'UTR. We found variants in four patients. One patient had the c.-125T>G substitution in the 5'UTR, while three patients carried two different variants in the 5' end of the ANKRD26 coding region (c.3G>A or c.105C>G). Review of medical history showed that the patient carrying the c.-125T>G was actually affected by typical but unrecognized THC2, highlighting that some apparently sporadic AML cases represent the evolution of a well-characterized familial predisposition disorder. As regards the c.3G>A and the c.105C>G, we found that both variants result in the synthesis of N-terminal truncated ANKRD26 isoforms, which are stable and functional in cells, in particular, have a strong ability to activate the MAPK/ERK signaling pathway. Moreover, investigation of one patient with the c.3G>A showed that mutation was associated with strong ANKRD26 overexpression in vivo, which is the proposed mechanism for predisposition to AML in THC2 patients. These data provide evidence that N-terminal ANKRD26 truncating mutations play a potential pathogenetic role in AML. Recognition of AML patients with germline ANKRD26 pathogenetic variants is mandatory for selection of donors for bone marrow transplantation.
Serum Uric Acid and Plasma Norepinephrine Concentrations Predict Subsequent Weight Gain and Blood Pressure Elevation (2003)

It has been reported that hypertension and obesity often coexist with hyperuricemia. To clarify the relations between serum uric acid, plasma norepinephrine, and insulin or leptin levels in subjects with weight gain-induced blood pressure elevation, we conducted the present longitudinal study. In 433 young, nonobese, normotensive men, body mass index, blood pressure, and levels of serum uric acid, fasting plasma norepinephrine, insulin, and leptin were measured every year for 5 years. Subjects were stratified by significant weight gain and/or blood pressure elevation (>10% in body mass index or mean blood pressure) for 5 years. At entry, blood pressure, uric acid, and norepinephrine values in subjects with blood pressure elevation were greater than in those without it, although body mass index, insulin, and leptin were similar. At entry, body mass index, blood pressure, uric acid, and norepinephrine in subjects with weight gain were greater than in those without weight gain. The increases in body mass index, mean blood pressure, uric acid, norepinephrine, insulin, and leptin for 5 years were greater in subjects with blood pressure elevation and/or weight gain than in subjects without, and those increases were greatest in subjects with weight gain whose blood pressure was elevated. By multiple regression analysis, basal mean blood pressure, norepinephrine, and uric acid were significant determinant factors of changes in mean blood pressure over 5 years, and basal body mass index, norepinephrine, and uric acid were significant determinant factors of changes in body mass index. These results demonstrate that serum uric acid and plasma norepinephrine concentrations predict subsequent weight gain and blood pressure elevation.
Growth Hormone Induces Resistance to the Mitogenic Action of Insulin Through Local IGF-I: Studies in Normal and Pygmy T-Cell Lines (1994)

Growth hormone (GH) and insulin have both mitogenic and metabolic actions. The growth-promoting effects of GH in vivo are thought to be mediated by insulin-like growth factor-I (IGF-I), whereas the metabolic effects of GH are thought to be either direct or mediated by factors other than IGF-I. In previous studies using HTLV-II-transformed T-lymphoblast cell lines established from normal individuals, we have shown that GH preincubation induces resistance to the growth-promoting (mitogenic) action of insulin. In this study, using T-cell lines from 3 American control subjects, 1 African control subject, and 1 African Pygmy (the latter previously shown to be resistant to the growth-promoting actions of both IGF-I and GH), we examined the role of local IGF-I in the mediation of GH-induced resistance to the mitogenic action of insulin. In these studies, we quantified the stimulation of T-cell colony formation in response to insulin in the presence and absence of either GH or IGF-I.(ABSTRACT TRUNCATED AT 250 WORDS)
A DFT Loopback Scheme for ADC ENOB Testing Using an All-Digital ATE (2013)

This article presents a design-for-test (DFT) loopback scheme for testing the analog portion of a mixed-signal chip using an all- digital tester. In fact, the proposed approach is used to assess the ENOB of a high-speed 6-bit ADC without the need for an external signal generator. Using an on-chip PLL with a programmable divider, a divided version of the 16GHz clock is passed through an on-chip buffer network where the output driver amplitude is programmable to achieve the desired fill ratio (~80%). The test PLL is coherent to the system PLL as they are driven from the same reference clock; hence, no windowing needs to be applied to the ADC output prior to performing the FFT for ENOB assessment. The on-chip output driver has an open-drain configuration that is far- end terminated through 50Ω pull-up resistors connected to a 2.0V external supply on the device interface board (DIB). The output is then applied to a 5th order external filter on the DIB with a 3dB cutoff frequency of 2.4GHz to filter out the high order harmonics prior to looping back the stimulus to the ADC front-end. The proposed scheme is implemented within a CMOS 32nm ADC macro and is experimentally validated using a commercial all-digital automated-test-equipment (ATE). A 4.5 bit ENOB was experimentally measured using the ADC under test. Unlike conventional loopback schemes, the proposed architecture is not susceptible to fault masking.
Phosphorylation-Dependent Assembly of a 14-3-3 Mediated Signaling Complex During Red Blood Cell Invasion by Plasmodium falciparum Merozoites (2020)

Abstract Red blood cell (RBC) invasion by Plasmodium merozoites requires multiple steps that are regulated by signaling pathways. Exposure of P. falciparum merozoites to the physiological signal of low K + , as found in blood plasma, leads to a rise in cytosolic Ca 2+ , which mediates microneme secretion, motility, and invasion. We have used global phosphoproteomic analysis of merozoites to identify signaling pathways that are activated during invasion. Using quantitative phosphoproteomics we found 394 protein phosphorylation site changes in merozoites subjected to different ionic environments (high K + / low K + ) out of which 143 were Ca 2+ -dependent. These included a number of signaling proteins such as catalytic and regulatory subunits of protein kinase A (PfPKAc and PfPKAr) and calcium-dependent protein kinase 1 (PfCDPK1). Proteins of the 14-3-3 family interact with phosphorylated target proteins to assemble signaling complexes. Here, using co-immunoprecipitation and gel filtration chromatography, we demonstrate that Pf14-3-3I binds phosphorylated PfPKAr and PfCDPK1 to mediate the assembly of a multi-protein complex in P. falciparum merozoites. A phospho-peptide, P1, based on the Ca 2+ dependent phosphosites of PKAr, binds Pf14-3-3I and disrupts assembly of the Pf14-3-3I-mediated multi-protein complex. Disruption of the multi-protein complex with P1 inhibits microneme secretion and RBC invasion. This study thus identifies a novel signaling complex that plays a key role in merozoite invasion of RBCs. Disruption of this signaling complex could serve as a novel approach to inhibit blood stage growth of malaria parasites. Importance Invasion of red blood cells (RBCs) by Plasmodium falciparum merozoites is a complex process that is regulated by intricate signaling pathways. Here, we have used phosphoproteomic profiling to identify the key proteins involved in signaling events during invasion. We found changes in the phosphorylation of various merozoite proteins including multiple kinases previously implicated in the process of invasion. We also found that a phosphorylation dependent multi-protein complex including signaling kinases assembles during the process of invasion. Disruption of this multi-protein complex impairs merozoite invasion of RBCs providing a novel approach for the development of inhibitors to block the growth of blood stage malaria parasites.
Theoretical analysis of trapping and emission of photons by a single defect in a 2D photonic crystal slab (2002)

Trapping and emission of photons by a single defect in a 2D photonic crystal slab is analyzed. We show that the tuning of emission wavelength is possible by selecting appropriate geometry of structure while keeping the high emission efficiency.
Dicloxacillin and erythromycin at high concentrations increase ICAM-1 expression by endothelial cells: a possible factor in the pathogenesis of infusion phlebitis (2004)

The results of this study support the theory that endothelial cells that are affected by high concentrations of antibiotics may initiate an inflammatory response through expression of ICAM-1. This is a novel finding in the pathogenesis of infusion phlebitis.
Biological approaches to artificial photosynthesis: general discussion (2019)

Jenny Zhang opened the discussion of the paper by Shelley Minteer: Was the vision of this study to produce salinity adapted microorganisms in the lab and then release them into the environment? Or was it mainly to try to understand how salinity adaptation can occur in the natural environment, u
50.3: A Pseudo‐Photopic Light Sensor Control System for AMLCD Fluorescent Back Lights (2000)

Abstract A pseudo‐photopic feedback back light control system has been developed for automotive AMLCD's which utilizes two low cost surface mount photodiodes. By utilizing a subtraction process, a pseudo‐photopic feedback signal is produced which can be used to control the back light inverter to the desired brightness level.
Pure phase-encoded MRI and classification of solids (1995)

Here, the authors combine a pure phase-encoded magnetic resonance imaging (MRI) method with a new tissue-classification technique to make geometric models of a human tooth. They demonstrate the feasibility of three-dimensional imaging of solids using a conventional 11.7-T NMR spectrometer. In solid-state imaging, confounding line-broadening effects are typically eliminated using coherent averaging methods. Instead, the authors circumvent them by detecting the proton signal at a fixed phase-encode time following the radio-frequency excitation. By a judicious choice of the phase-encode time in the MRI protocol, the authors differentiate enamel and dentine sufficiently to successfully apply a new classification algorithm. This tissue-classification algorithm identifies the distribution of different material types, such as enamel and dentine, in volumetric data. In this algorithm, the authors treat a voxel as a volume, not as a single point, and assume that each voxel may contain more than one material. They use the distribution of MR image intensities within each voxel-sized volume to estimate the relative proportion of each material using a probabilistic approach. This combined approach, involving MRI and data classification, is directly applicable to bone imaging and hard-tissue contrast-based modeling of biological solids.
OP014 Histological remission is predictive of improved clinical outcomes in patients with ulcerative colitis: results from the TOUCHSTONE open-label extension (2017)

Background: Histological remission (HR) has been reported as a positive prognostic indicator of clinical activity in ulcerative colitis (UC). The TOUCHSTONE open-label extension (OLE) is an opportunity to examine the impact of histologic remission on UC activity during a long-term evaluation of efficacy and safety of ozanimod 1 mg. TOUCHSTONE was a randomized, double-blind, placebo-controlled phase 2 trial designed to assess the efficacy and safety of ozanimod 0.5 mg and 1 mg versus placebo during induction and maintenance in patients with moderate to severe UC [1], and established that ozanimod induced and maintained clinical response, clinical remission (CR), endoscopic mucosal healing, and HR through weeks 8 and 32. Methods: A total of 197 patients were randomized (1:1:1) and treated with daily ozanimod at 0.5 mg, 1 mg, or placebo in TOUCHSTONE. Of the initial 197 patients randomized, 170 (86%) entered OLE and received daily ozanimod 1 mg, and 131 (77%) and 105 (62%) completed assessments at weeks 44 and 80. In this analysis, HR was defined as a Geboes score <2 and CR was defined as rectal bleeding score =0 and stool frequency score ≤1. Results: Of the patients who entered OLE, 27% showed histologic remission at the time of OLE entry and 34% were in CR. Clinical remission increased to 62% at OLE week 32, with 62%, and 55% in CR at OLE weeks 44 and 80. At OLE weeks 44 and 80, CR was seen in 83% and 80% of those in HR at OLE entry compared to 55% and 46% of those not in HR at OLE entry. The proportion of patients in CR increased throughout OLE while receiving 1 mg of ozanimod, regardless of prior treatment in the TOUCHSTONE study or HR status at OLE entry. The highest rates of CR were seen in patients in HR at OLE entry who had received ozanimod for 32 weeks prior to OLE entry, with CR rates at OLE weeks 4 and 8, with over 90% in CR. The lowest CR rates were seen in patients naïve to ozanimod and not in HR at OLE entry, with CR increasing from 13% at entry to 50% at OLE week 8, reaching a peak of 56% at OLE week 32. Overall, treatment with ozanimod for 32 to 36 weeks resulted in CR in 80% of patients. Most common adverse events seen in OLE were UC flare, back pain, URTI, anemia, and nasopharyngitis. Transient asymptomatic elevations in ALT or AST >3× ULN were seen in 3% of patients. Conclusions: Histological remission is predictive of CR in patients with UC receiving ozanimod 1 mg in OLE. All patients, whether naïve to or having received ozanimod in TOUCHSTONE, showed additional improvements in CR upon continued treatment with ozanimod 1 mg in OLE. Patients naïve to ozanimod had a rapid improvement in CR over the first 8 weeks of treatment with ozanimod 1 mg in OLE. References: [1] Sandborn WJ, Feagan BG, Wolf DC, et al. (2016), Ozanimod induction and maintenance treatment for ulcerative colitis. N Engl J Med, 1754–62
Epithelial Interactions and Local Engraftment of Lung-Resident Mesenchymal Stem Cells (2011)

Multipotent mesenchymal progenitor cells, termed "mesenchymal stem cells" (MSCs), have been demonstrated to reside in human adult lungs. However, there is little information regarding the associations of these local mesenchymal progenitors with other resident somatic cells and their potential for therapeutic use. Here we provide in vivo and in vitro evidence for the ability of human adult lung-resident MSCs (LR-MSCs) to interact with the local epithelial cells. The in vivo retention and localization of human LR-MSCs in an alveolar microenvironment was investigated by placing PKH-26 or DsRed lentivirus-labeled human LR-MSCs in the lungs of immunodeficient (SCID) mice. At 3 weeks after intratracheal administration, 19.3 ± 3.21% of LR-MSCs were recovered, compared with 3.47 ± 0.51% of control fibroblasts, as determined by flow cytometry. LR-MSCs were found to persist in murine lungs for up to 6 months and demonstrated preferential localization to the corners of the alveoli in close proximity to type II alveolar epithelial cells, the progenitor cells of the alveolar epithelium. In vitro, LR-MSCs established gap junction communications with lung alveolar and bronchial epithelial cells and demonstrated an ability to secrete keratinocyte growth factor, an important modulator of epithelial cell proliferation and differentiation. Gap junction communications were also demonstrable between LR-MSCs and resident murine cells in vivo. This study demonstrates, for the first time, an ability of tissue-specific MSCs to engraft in their organ of origin and establishes a pathway of bidirectional interaction between these mesenchymal progenitors and adult somatic epithelial cells in the lung.
Broadband AlGaN/GaN MMIC amplifier (2011)

A broadband Monolithic Microwave Integrated Circuit (MMIC) amplifier, with 12 ± 2 dB gain across the 0.1–27 GHz band has been demonstrated using the AlGaN/GaN on SiC technology. The amplifier design employs a non-conventional, series-DC/RF-High Electron Mobility Transistor (HEMT) configuration. This configuration provides an alternative design to the conventional traveling-wave amplifier (TWA). It results in a smaller MMIC chip size, and extends amplifier gain to the low-frequency region. The amplifier MMIC utilizes four HEMT devices in series and could be biased at voltages up to 120 V.
Persufflation (gaseous oxygen perfusion) as a method of heart preservation (2013)

Persufflation (PSF; gaseous oxygen perfusion) is an organ preservation technique with a potential for use in donor heart preservation. Improved heart preservation with PSF may improve outcomes by maintaining cardiac tissue quality in the setting of longer cold ischemia times and possibly increasing the number of donor hearts available for allotransplant. Published data suggests that PSF is able to extend the cold storage times for porcine hearts up to 14 hours without compromising viability and function, and has been shown to resuscitate porcine hearts following donation after cardiac death. This review summarizes key published work on heart PSF, including prospective implications and future directions for PSF in heart transplantation. We emphasize the potential impact of extending preservation times and expanding donor selection criteria in heart allotransplant. Additionally, the key issues that need to be addressed before PSF were to become a widely utilized preservation strategy prior to clinical heart transplantation are summarized and discussed.
Autoimmune hearing loss (1997)

Immune-mediated inner ear disease describes a variety of clinical conditions associated with unilateral or bilateral rapidly progressive sensorineural hearing loss. Typically, the hearing loss occurs over weeks to months. Although it may affect both sexes and all ages, it occurs most commonly in middle-aged female patients. Frequently, the patient may experience Meniere's disease-like symptoms including episodic vertigo, aural fullness, otalgia and disequilibrium, although the hearing loss is more progressive. A history of systemic autoimmune disorders (eg, systemic lupus erythematosis, Wegener's granulomatosis, or rheumatoid arthritis) can be elicited in less than one-third of the time. Recent experimental evidence supports the existence of a group of organ-specific and nonspecific antibodies that target the inner ear tissues, leading to inflammatory insults of the cochlea. This class of cochleovestibular disorder is unique because it represents one of the few forms of sensorineural hearing loss that can be treated with immunosuppressive therapy. Therefore, it is important that the clinician maintains a high index of suspicion, obtain laboratory validation, and promptly initiate therapy to preserve cochleovestibular function.
Bounding switching activity in CMOS circuits using constraint resolution (1996)

This paper deals with the problem of estimating the average power consumption (per clock cycle) of CMOS digital circuits. A new pattern-independent method is proposed for computing an upper bound on the switching activity, and therefore the average power, of a combinational circuit described at the gate level. The method is based on the propagation of abstract waveform sets, described down to the level of individual transitions. The view of a gate as a relation between input and output signals, described by forward and partial inverse functions, permits the determination of a tight upper bound on the power using a constraint resolution method based on waveform narrowing. A fully scalable, case analysis-based algorithm provides at any step an upper bound and, with enough resources (CPU time), it can continue up to the exact solution. The paper presents the theoretical background, a description of the implementation, and results on benchmark circuits.
Black-Box Superconducting Circuit Quantization (In Russian) (2019)

We present a semi-classical method for determining the effective low-energy quantum Hamiltonian of weakly anharmonic superconducting circuits containing mesoscopic Josephson junctions coupled to electromagnetic environments made of an arbitrary combination of distributed and lumped elements. A convenient basis, capturing the multi-mode physics, is given by the quantized eigenmodes of the linearized circuit and is fully determined by a classical linear response function. The method is used to calculate numerically the low-energy spectrum of a 3D-transmon system, and quantitative agreement with measurements is found.
Induction Machine Modeling Approach Based on 3-D Magnetic Equivalent Circuit Framework (2010)

Developments in power electronics technology, materials, and changing application requirements are driving advances in electric machines. Limitations of standard motor design, particularly for induction machines, restrict performance capabilities in drive applications. Current computer-aided design tools are inadequate to overcome these limitations. Lumped-parameter and finite-element models have limited accuracy and heavy computational effort, respectively. Magnetic equivalent circuits (MEC) avoid these limitations. This paper presents an induction machine MEC model geared toward design and based on a 3-D MEC framework introduced in previous work. A matrix formulation suitable for computation is described. Details of mesh generation for the MEC approach are provided. Force and performance estimation are discussed. Simulations based on this approach are able to track dynamic effects, such as rotor slot torque ripple contributions. Comparisons are made to a 500 W purpose-built machine. Results from lumped-parameter and finite-element models and measurements indicate that MECs, corrected for local saturation, are a promising option for design tools.