gebhart/patrepeval huggingface dataset:
Differences in complexity of isolated brachydactyly type C cannot be attributed to locus heterogeneity alone (2001)

Hereditary isolated brachydactyly type C (OMIM 113100) mostly follows an autosomal dominant pattern of inheritance with a marked variability in expression. This phenotype has been mapped to two different loci on chromosomes 12q24 and 20q11.2. The latter locus contains the cartilage-derived morphogenetic protein (CDMP)1 gene, in which a null mutation has been found in patients with malformations restricted to the upper limbs. A more complex brachydactyly type C phenotype has been mapped to chromosome 12q24. Differences in complexity of these phenotypes have been attributed to locus heterogeneity. Clinical subclassification based on the degree of complexity of the phenotype has therefore been suggested. We present patients with a complex brachydactyly type C phenotype in whom there is considerable intra- and interfamilial variability in expression. We show that clinical subclassification based on the complexity of the brachydactyly type C phenotype related to the genetic defect is not feasible. We present evidence that differences in complexity are not only due to locus heterogeneity, but that genetic modifiers and/or environmental factors must also play a role.
Biological Applications of Chromophores With Large Two-Photon Cross Sections (1999)

Abstract One current limitation of two-photon technology is the lack of optimized fluorochromes for Two-Photon Laser Scanning Microscopy (TPLSM). Recently, Albota et al. (1998) have reported the design and synthesis of a number of bis(styryl)benzene derivatives that have large fluorescence quantum yields and greater two-photon absoption cross sections than any of fluorochromes that are currently used for TPLSM. As a first step in understanding how such molecules could be used in biological experiments, we have tagged a donor-πdonor molecule with biotin. We have successfully used this dye to detect quail nuclei in 2- 4 day old fixed embryos that have been reacted with QCPN, a quail specific monoclonal antibody. We have observed that this molecule gives a very intense signal, among the most intense signals we have been able to measure in our immunoassay. In particular, the brightness was about a factor of four higher than Rhodamine B-labelled streptavidin (containing 3.3 moles of dye per streptavidin tetramer).
Cache Write Generate for High Performance Parallel Processing (2005)

We present, Generate, a new cache write handling scheme that avoids unnecessary reads from main memory, reduces bus contention, and increases the available bandwidth of the memory. Cache Write Generate increases the amount of CPU execution and memory load/store overlap, and decreases the memory cycle time. We compare the performance of cache write generate with write around and write allocate in single processor and shared bus multiprocessors and demonstrate a speedup of 1.2 to 1.5 over allocate and write around.
Residual Pulse Morphology Visualization and Analysis in Pressure Signals (2005)

We describe a new method to determine whether there is additional information contained in the intracranial pulse morphology that cannot be explained by covariation with the mean intracranial pressure (ICP) alone. Our procedure calculates and displays the difference between the actual pulse morphology and the expected morphology given a predictor variable, such as the mean ICP. The display is intuitive and permits easy recognition of changes in morphology unaccounted for by the given predictor variable. This method can be applied to any signal that consists of a series of events that generate a consistent morphology that is correlated to other predictor variables. Our exploratory analysis of ICP signals revealed examples of changes in pulse morphology that were independent of mean ICP. This suggests the need for further work that examines the underlying physiology responsible for pulse morphology.
Design and Analysis of a Novel Reversible Airfoil Mechanism (2023)

Stop-rotor aircraft, which utilize a central lifting surface capable of transitioning between rotation and fixed configurations, offer a promising option for improving the efficiency of vertical take-off and landing aircraft. However, across the transition between rotation and fixed configurations, the necessary airfoil directionality for efficient aerodynamic performance changes. This work presents the design and experimental analysis of a novel reversible morphing airfoil capable of altering the airfoil directionality necessitated for stop-rotor aircraft. Inspired by roll-up chair design by Uros Vitas, the proposed morphing reversible airfoil, henceforth referred to as the folding slat method, takes shape primarily through a flexible strip that is symmetric about the center and consists of a series of rigid trapezoidal extrusions, forming slats, that are mounted on a flexible substrate. The directionality of the airfoil is switched by altering the compression and tension of each side of the strip, thereby pressing and releasing the contact points between the trapezoidal sections. While the proposed folding slat successfully morphed the leading and trailing edge, the experimental evaluation of the morphing airfoil was critical to justify its usage in a real system. As such, a suite of tests evaluating the compression, bending, and fatigue behaviors were performed. From this testing, it was shown that the folding slat could transfer up to a 150 N load without any added electrical energy usage and was able to switch the orientation of the leading and trailing edge at least 1,000 times, while still maintaining adequate stiffness.
Right ventricular systolic pressure load alters myocyte maturation in fetal sheep (2000)

The effects of right ventricular (RV) systolic pressure (RVSP) load on fetal myocyte size and maturation were studied. Pulmonary artery (PA) pressure was increased by PA occlusion from mean 47.4 +/- 5.0 (+/-SD) to 71 +/- 13.6 mmHg (P < 0.0001) in eight RVSP-loaded near-term fetal sheep for 10 days. The maximal pressure generated by the RV with acute PA occlusion increased after RVSP load: 78 +/- 7 to 101 +/- 15 mmHg (P < 0.005). RVSP-load hearts were heavier (44.7 +/- 8.4 g) than five nonloaded hearts (31.8 +/- 0.2 g; P < 0.03); heart-to-body weight ratio (10.9 +/- 1.1 and 6.5 +/- 0.9 g/kg, respectively; P < 0.0001). RVSP-RV myocytes were longer (101.3 +/- 10.2 microm) than nonloaded RV myocytes (88.2 +/- 8.1 microm; P < 0. 02) and were more often binucleated (82 +/- 13%) than nonloaded myocytes (63 +/- 7%; P < 0.02). RVSP-loaded myocytes had less myofibrillar volume than did nonloaded hearts (44.1 +/- 4.4% and 56. 1 +/- 2.6%; P < 0.002). We conclude that RV systolic load 1) leads to RV myocyte enlargement, 2) has minor effects on left ventricular myocyte size, and 3) stimulates maturation (increased RV myocyte binucleation). Myocyte volume data suggest that RV systolic loading stimulates both hyperplastic and hypertrophic growth.
Combining electrokinetics with deterministic lateral displacement (2016)

We make Deterministic Lateral Displacement (DLD) flexible by combining it with AC electrokinetics.
Rupture Processes in the Presence of Creep Zones (2011)

This paper describes a model of stress and slip distribution on a strike-slip fault with strength heterogeneity depthwise and along strike. The 3-D problem is analyzed by means of a “line-spring' procedure which is numerically implemented in an Indirect Boundary Element Program. The model is applied to study the effect of a creep zone on the stressing of the adjacent fault segments. Results include the thickness averaged slip rate in the creep zone, and stressing rate and slip zone penetration in the adjacent segments. Temporal and spatial variation of surface strain rate profiles are also computed. Order of magnitude comparisons of these and other parameters with geodetic measurements on the San Andreas fault in central California suggests that the model may be fine tuned for future site-specific studies. Simplification in boundary conditions, however, are expected to limit the model accuracy in the preseismic period. The ‘line-spring' procedure itself is known to become inadequate in the limit when strength heterogeneities vary with wavelengths less than a plate thickness.
Safety and pharmacokinetic (PK) study of perifosine plus capecitabine (P-CAP) in patients (pts) with refractory metastatic colorectal cancer (mCRC). (2010)

e14086 Background: Perifosine (P), a synthetic alkylphospholipid, inhibits or modifies multiple signal transduction pathways, including AKT, MAPK and JNK. A small randomized phase II study of P 50 mg PO QD d1-21 + CAP 825 mg/m2 PO BID d1-14 (P-CAP) vs. placebo + CAP 825 mg/m2 PO BID d1-14 in pts with advanced mCRC showed improved TTP and OS of P-CAP vs. placebo + CAP. A more commonly used dose of CAP in the U.S. is 1,000 mg/m2 PO BID. This study evaluated the safety and PK of P 50 mg PO QD d1-21 + CAP 1,000 mg/m2 BID d1-14. Methods: Pts with refractory mCRC received P 50 mg PO QD d 1-21 + CAP 1,000 mg/m2 BID d1- 14. Pts were enrolled in a 3+3 fashion, with a total of 9 patients treated if the dose was tolerated for further safety and PK data. PK of P and CAP were evaluated C1D1 and C1D11 (steady-state). Plasma concentrations were evaluated by a validated LCMS assay with PK parameters determined with Win Non Lin version 5.2. Results: 10 pts were enrolled. Median age 65 (54-72); 70% female. Median prior Rx = 3 (2-4). Prior Rx: FOLFOX (100%); FOLFIRI (100%); bevacizumab (100%); EGFR antibody (60%); progressed on prior 5-FU-based Rx (100%). 9 pts were evaluable for DLT; no DLTs were observed. 1 pt was inevaluable after stopping study drug after 2d for non-related AE. G 3/4 AE's ≥ 10%: dyspnea (10%), rash (10%), hyperkalemia (10%) and abdominal pain (10%). Perifosine PK results show a mean half-life of 5.66 ± 4.06 hours, Cmax of 2.66 ug/mL, AUC(0- 8) (C1D1) of 9.73 hr*ug/mL, CL of 5.66 mL/hr and a V of 26.5 L. Steady state AUC(0-8) was 21.8 hr*ug/mL. These data are consistent with single agent perifosine PK data, suggesting no perifosine PK change with the addition of capecitabine. Capecitabine PK evaluation is underway. As of Jan 2010, 3/10 pts have had one response assessment (9 wk scan). One pt had a 13% decrease in disease, and 1 pt had SD. 7/10 pts remain on study treatment. Conclusions: P 50 mg PO QD d1-21 + CAP 1,000 mg/m2 PO BID d 1-14 is a well-tolerated regimen for pts with mCRC. Updated PK, safety and efficacy results will be presented. A randomized phase III trial of P-CAP vs. placebo + CAP is planned for refractory colorectal cancer pts. Author Disclosure Employment or Leadership Position Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Keryx Biopharmaceuticals Keryx Biopharmaceuticals
Folic Acid‐Modified Mesoporous Silica Nanoparticles for Cellular and Nuclear Targeted Drug Delivery (2012)

Folic acid-modified mesoporous silica nanoparticles are designed for cellular and nuclear targeted drug delivery. Camptothecin is efficiently delivered to human cancer cells resulting in apoptosis without premature leakage. The folic acid moiety is an integral part of a rotaxane structure, which locks the drug molecules in the pores, preventing premature release. Upon folate receptor-mediated cell uptake, esterases cleave the rotaxane valves and camptothecin is released, resulting in apoptosis. As a service to our authors and readers, this journal provides supporting information supplied by the authors. Such materials are peer reviewed and may be re-organized for online delivery, but are not copy-edited or typeset. Technical support issues arising from supporting information (other than missing files) should be addressed to the authors. Please note: The publisher is not responsible for the content or functionality of any supporting information supplied by the authors. Any queries (other than missing content) should be directed to the corresponding author for the article.
Tree-based Secure Comparison of Secret Shared Data (2018)

A secure integer comparison protocol is one of the most fundamental building blocks to construct protocols of rich functionality in multi-party computation. It allows parties to compute the less-than functionality on shared values in privacy preserving manner. In this paper, we present a tree-based secure two-party comparison protocol in the client-aided client-server model, which outperforms existing approaches in terms of round complexity when it is used for 64-bit data. Our proposed protocol requires only 9 communication rounds to compare 64-bit data, which is at least 3 times fewer rounds than existing protocols. This suggests that our protocol is adequate to be used in low-latency networks such as WAN.
Outcome of Cochlear Implantation in Prelingually Deafened Children According to Molecular Genetic Etiology (2017)

Current molecular genetic testing including deafness panel sequencing helps to predict the 2-year follow-up outcomes after CI in prelingually deafened children. GD cochlear implantees show better functional outcomes after CI than undiagnosed cochlear implantees as determined by deafness panel sequencing, suggesting a genotype-functional outcome correlation. The genetic testing may provide a customized optimal window period in terms of CI timing for favorable outcome according to genetic etiology.
Mechanisms of Antisense Drug Action, an Introduction (2007)

The antisense concept derives from an understanding of nucleic acid structure and function and depends on Watson-Crick hybridization [1]. Thus, arguably, the demonstration that nucleic acid hybridization is feasible [2] and the advances in situ hybridization and diagnostic probe technology [3] lay the most basic elements of the foundation supporting the antisense concept.
Benefits of quantum well intermixing in high power diode lasers (2004)

Quantum well intermixing (QWI) can bring considerable benefits to the reliability and performance of high power laser diodes by intermixing the facet regions of the device to increase the band-gap and hence eliminate absorption, avoiding catastrophic optical damage (COD). The non-absorbing mirror (NAM) regions of the laser cavity can be up to ~20% of the cavity length, giving an additional benefit on cleave tolerances, to fabricate very large element arrays of high power, individually addressable, single mode lasers. As a consequence, large arrays of single mode lasers can bring additional benefits for packaging in terms of hybrization and integration into an optics system. Our QWI techniques have been applied to a range of material systems, including GaAs/AlGaAs, (Al)GaAsP/AlGaAs and InGaAs/GaAs.
Preclinical Development of LNA Antimir-155 (MRG-106) in Acute Myeloid Leukemia (2015)

Abstract Introduction MicroRNAs (miRs) are deregulated in AML and play a key role in leukemogenesis. MiR-155 is one of the most frequently overexpressed miRs in AML. Higher expression of miR-155 is associated with FLT3 internal tandem duplication (FLT3-ITD) and is associated with worse outcome, independent of FLT3-ITD status. Preliminary data shows that silencing of miR-155 induces strong antileukemic effects in AML cell lines. Altogether these data support a therapeutic role for miR-155 antagonism in AML. Here, we show the in vitro and in vivo activity of MRG-106, a novel LNA antimiR-155 compound that we are developing as a potential treatment for hematological malignancies. Methods Unconjugated, LNA-modified oligonucleotide against miR-155 (MRG-106) was developed by miRagen Therapeutics, Inc. MRG-106 was evaluated in FLT3-ITD+ AML cell lines and primary FLT3-ITD+ AML samples for impact on apoptosis and cellular proliferation using Annexin V and MTS assays. Predicted and validated targets of miR-155 were measured by qPCR and Western Blotting to assess the efficacy of miR-155 silencing. The in vivo antileukemic effect of MRG-106 was evaluated in NOD/SCID gamma mice engrafted with MV4-11 AML cells that have elevated miR-155 expression. One week after leukemic cell inoculation, the mice were separated in 3 cohorts and received either MRG-106 (n=12); LNA-scramble control (n=12); or saline (n=6). Results Inhibition of miR-155 decreased cell proliferation in MV-4-11 and MOLM-13 cells at 48hrs (Absorbance 450 nM (A450nM): 0.5 and 0.4 vs controls 2.4 and 2.5, respectively, p&lt;0.01). These effects were associated with increased apoptosis (2-fold increase in Annexin staining) and re-expression of the validated miR-155 target WEE1 protein. MRG-106 produced a 4-6 fold increase in apoptosis in primary samples from 3 newly diagnosed AML patients with FLT3 -ITD cytogenetically normal AML (p&lt;0.01). In addition, inhibition of miR-155 reduced the colony forming ability of the primary blasts (average # of colonies; controls=90 vs. MRG-106=55,p&lt;0.01). In an MV4-11 xenograft model, MRG-106 significantly increased survival compared to controls (p&lt;0.01). Biodistribution studies confirmed adequate MRG-106 distribution to bone marrow. GLP preclinical safety studies have been completed in rats and non-human primates, demonstrating an acceptable safety profile for MRG-106. Conclusions Inhibition of miR-155 in AML cell lines and primary AML samples in vitro and in vivo induces significant antileukemic effects. These studies validate miR-155 as a therapeutic target in AML and support the testing of MRG-106 in AML patients in the context of a phase 1 clinical trial. Disclosures Dickinson: miRagen Therapeutics: Employment, Equity Ownership. Jackson:miRagen Therapeutics: Employment, Equity Ownership. Rodman:miRagen Therapeutics: Employment, Equity Ownership.
SPARTA: Sparse phase retrieval via Truncated Amplitude flow (2017)

A linear-time algorithm termed SPARse Truncated Amplitude flow (SPARTA) is developed for the phase retrieval (PR) of sparse signals. Upon formulating the sparse PR as a non-convex empirical loss minimization task, SPARTA emerges as an iterative solver consisting of two components: s1) a sparse orthogonality-promoting initialization leveraging support recovery and principal component analysis; and, s2) a series of refinements by hard thresholding based truncated gradient iterations. SPARTA is simple, scalable, and fast. It recovers any k-sparse n-dimensional signal (k ≪ n) of large enough minimum (in modulus) nonzero entries from about k <sup xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">2</sup> log n measurements with high probability; this is achieved at computational complexity of order k <sup xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">2</sup> n log n, improving upon the state-of-the-art by at least a factor of k. SPARTA is robust against bounded additive noise. Simulated tests corroborate the merits of SPARTA relative to existing alternatives.
Input-specific control of reward and aversion in the ventral tegmental area (2012)

Ventral tegmental area (VTA) dopamine neurons have important roles in adaptive and pathological brain functions related to reward and motivation. However, it is unknown whether subpopulations of VTA dopamine neurons participate in distinct circuits that encode different motivational signatures, and whether inputs to the VTA differentially modulate such circuits. Here we show that, because of differences in synaptic connectivity, activation of inputs to the VTA from the laterodorsal tegmentum and the lateral habenula elicit reward and aversion in mice, respectively. Laterodorsal tegmentum neurons preferentially synapse on dopamine neurons projecting to the nucleus accumbens lateral shell, whereas lateral habenula neurons synapse primarily on dopamine neurons projecting to the medial prefrontal cortex as well as on GABAergic (γ-aminobutyric-acid-containing) neurons in the rostromedial tegmental nucleus. These results establish that distinct VTA circuits generate reward and aversion, and thereby provide a new framework for understanding the circuit basis of adaptive and pathological motivated behaviours.
MoS2 on topological insulator Bi2Te3 thin films: Activation of the basal plane for hydrogen reduction (2021)

2H-MoS2 is a well-studied and promising non-noble metal electrocatalyst for heterogeneous reactions, such as the hydrogen evolution reaction (HER). The performance is largely limited by the chemically inert basal plane, which is unfavorable for surface adsorption and reactions. Herein, we report a facile method to boost the HER activities of 2H-MoS2 by coupling with epitaxial Bi2Te3 topological insulator films. The as-obtained MoS2/ Bi2Te3/SrTiO3 catalyst exhibits prominent HER catalytic activities compared to that of pure MoS2 structures, with a 189 mV decrease in the overpotential required to reach a current density of 10 mA cm−2 and a low Tafel slope of 58 mV dec−1. Theoretical investigations suggest that the enhanced catalytic activity originates from the charge redistribution at the interface between the Bi2Te3topological insulator films and the MoS2 layer. The delocalized sp-derived topological surface states could denote electrons to the MoS2 layer and activate the basal plane for hydrogen adsorption. This study demonstrates the potential of manipulating topological surface states to design high-performance electrocatalysts.
Modeling the Polymeric Microstructure of LDPE in Tubular and Autoclave Reactors with a Coupled Deterministic and Stochastic Simulation Approach (2014)

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