gebhart/patrepeval huggingface dataset:
Integrated Deviance Information Criterion for Latent Variable Models (2018)

Deviance information criterion (DIC) has been widely used for Bayesian model comparison, especially after Markov chain Monte Carlo (MCMC) is used to estimate candidate models. This paper studies the problem of using DIC to compare latent variable models after the models are estimated by MCMC together with the data augmentation technique. Our contributions are twofold. First, we show that when MCMC is used with data augmentation, it undermines theoretical underpinnings of DIC. As a result, by treating latent variables as parameters, the widely used way of constructing DIC based on the conditional likelihood, although facilitating computation, should not be used. Second, we propose two versions of integrated DIC (IDIC) to compare latent variable models without treating latent variables as parameters. The large sample properties of IDIC are studied and an asymptotic justi fication of IDIC is provided. Some popular algorithms such as the EM, Kalman and particle filtering algorithms are introduced to compute IDIC for latent variable models. IDIC is illustrated using asset pricing models, dynamic factor models, and stochastic volatility models.
Schizophrenia susceptibility gene locus at Xp22.3 (1999)

Multiple genetic loci have been implicated in the search for schizophrenia susceptibility genes, none having been proven as causal. Genetic heterogeneity is probable in the polygenic etiology of schizophrenia. We report on two unrelated Caucasian women with paranoid schizophrenia (meeting Diagnostic and Statistical Manual of Mental Disorders (DSM IV) criteria) who have an Xp22.3 overlapping deletion characterized by fluorescence in situ hybridization (FISH). Patient 1 was previously reported by us (Wyandt HE, Bugeau-Michaud L, Skare JC, Milunsky A. Partial duplication of Xp: a case report and review of previously reported cases. Amer J Med Genet 1991: 40: 280-283) to have a de novo partial duplication of Xp. At that time, she was a 24-year-old woman with short stature, irregular menses, other abnormalities suggestive of Turner syndrome, and paranoid schizophrenia. Recently, FISH analysis demonstrated that she has an inverted duplication (X)(p22.1p11.2) and a microscopic deletion (X)(p22.2p22.3) between DXS1233 and DXS7108 spanning approximately 16-18 cM. Patient 2 is a 14-year-old girl with short stature, learning disabilities, and paranoid schizophrenia. High-resolution chromosome analysis revealed a de novo deletion involving Xp22. FISH analysis showed that the deletion (X)(p22.2p22.3) spanned 10-12 cM between AFMB290XG5 and DXS1060. Given that deletions of Xp22 are not common events, the occurrence of two unrelated schizophrenia patients with an overlapping deletion of this region would be extraordinarily rare. Hence, the deletion within Xp22.3 almost certainly contains a gene involved in the pathogenesis of paranoid schizophrenia.
Novel Replication-Competent Circular DNA Molecules from Healthy Cattle Serum and Milk and Multiple Sclerosis-Affected Human Brain Tissue (2014)

Epidemiological data point to the involvement of a cow milk factor in the etiology of multiple sclerosis (MS). Eleven circular DNA molecules closely related to transmissible spongiform encephalopathy (TSE)-associated isolate Sphinx 1.76 were isolated from healthy cattle serum, cow milk, and serum and brain tissue from MS patients.
Consensus Nomenclature for <i>in vivo</i> Imaging of Reversibly Binding Radioligands (2007)

An international group of experts in pharmacokinetic modeling recommends a consensus nomenclature to describe in vivo molecular imaging of reversibly binding radioligands.
Thin-Film PZT Lateral Actuators With Extended Stroke (2008)

Many microelectromechanical system applications require large in-plane actuation forces, with stroke lengths ranging from submicrometer to tens of micrometers in distance. Piezo electric thin films are capable of generating very large actuation forces, but their motion is not easily directed into lateral displacement in microscale devices. A new piezoelectric thin-film actuator that uses a combination of piezoelectric unimorph beams to generate lateral displacement has been developed. The piezoelectric actuators were fabricated using chemical-solution-derived lead zirconate titanate thin films. These actuators have demonstrated forces greater than 7 mN at displacements of nearly 1 mum, with maximum stroke lengths at 20 V greater than 5 mum in a 500-mum-long by 100-mum-wide actuator. Force and displacement capabilities can be manipulated through simple changes to the actuator design, while actuator nonlinearity can produce dramatic gains in work capacity and stroke length for longer actuators.
Order-disorder effects in the magneto-optical properties of evaporated Fe-Co alloy films (1981)

The magneto-optical properties of evaporated films of Fe-Co alloys have been studied as a function of composition using ellipsometric techniques to obtain the components of the index of refraction N = n-ik and the magneto-optical coefficient Q = Q <inf xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">1</inf> -iQ <inf xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">2</inf> at the He-Ne laser wavelengths of λ = 1.15μm and 0.63μm. The results indicate a very sharply defined compositional range between Fe <inf xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">.5</inf> Co <inf xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">.5</inf> and Fe <inf xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">.6</inf> Co <inf xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">.4</inf> in which the order-disorder transition affects the optical properties by increasing both n and k, as well as increasing |Q| to values larger than any previously reported except for the compound MnBi.
Synergistic drug combination GC7/DFMO suppresses hypusine/spermidine-dependent eIF5A activation and induces apoptotic cell death in neuroblastoma (2018)

The eukaryotic initiation factor 5A (eIF5A), which contributes to several crucial processes during protein translation, is the only protein that requires activation by a unique post-translational hypusine modification. eIF5A hypusination controls cell proliferation and has been linked to cancer. eIF5A hypusination requires the enzymes deoxyhypusine synthase (DHPS) and deoxyhypusine hydroxylase and uniquely depends on the polyamine (PA) spermidine as the sole substrate. Ornithine decarboxylase (ODC) is the rate-limiting enzyme in PA biosynthesis. Both ODC and PAs control cell proliferation and are frequently dysregulated in cancer. Since only spermidine can activate eIF5A, we chose the hypusine-PA nexus as a rational target to identify new drug combinations with synergistic antiproliferative effects. We show that elevated mRNA levels of the two target enzymes DHPS and ODC correlate with poor prognosis in a large cohort of neuroblastoma (NB) tumors. The DHPS inhibitor GC7 (<i>N</i><sup>1</sup>-guanyl-1,7-diaminoheptane) and the ODC inhibitor α-difluoromethylornithine (DFMO) are target-specific and in combination induced synergistic effects in NB at concentrations that were not individually cytotoxic. Strikingly, while each drug alone at higher concentrations is known to induce p21/Rb- or p27/Rb-mediated G<sub>1</sub> cell cycle arrest, we found that the drug combination induced caspase 3/7/9, but not caspase 8-mediated apoptosis, in NB cells. Hypusinated eIF5A levels and intracellular spermidine levels correlated directly with drug treatments, signifying specific drug targeting effects. This two-pronged GC7/DFMO combination approach specifically inhibits both spermidine biosynthesis and post-translational, spermidine-dependent hypusine-eIF5A activation, offering an exciting clue for improved NB drug therapy.
The pathogenesis of experimental bladder cancer. (1977)

The pathogenesis of signal morphological lesions of the urinary bladder induced in several species following administration of N-butyl-N-(4-hydroxybutyl)nitrosamine, bracken fern, or N-[4-(5-nitro-2-furyl)-2-thiazolyl]formamide is presented. Incidences of bladder neoplasia exceeding 80% were generated in the rat by each compound. Bladder neoplasia was induced in the following species by each substance: by N-butyl-N-(4-hydroxybutyl)nitrosamine in the mouse, hamster, guinea pig, and dog; by bracken fern in the guinea pig, mouse, and cow; and by N-[4-(5-nitro-2-furyl)-2-thiazolyl]formamide in mouse, hamster, and dog. The guinea pig appeared resistant to the bladder oncogenicity of N-[4-(5-nitro-2-furyl)-2-thiazolyl]formamide. Different species displayed a gradient of bladder neoplastic responsiveness. Hyperplasia was a consistent early lesion and was usually focal. Early hyperplastic lesions regressed following removal of the carcinogenic stimulus, but later lesions appeared to be irreversible. These animal systems appear useful in providing opportunities for investigations relevant to human bladder cancer.
APT‐weighted and NOE‐weighted image contrasts in glioma with different RF saturation powers based on magnetization transfer ratio asymmetry analyses (2013)

The APT and nuclear Overhauser enhancement image signals in tumor are maximized at different saturation powers. The saturation power of roughly 2 μT is ideal for APT-weighted imaging at clinical B0 field strengths.
Modulation of Major Histocompatibility Complex Protein Expression by Human Gamma Interferon Mediated by Cysteine Proteinase-Adhesin Polyproteins of<i>Porphyromonas gingivalis</i> (1999)

Cysteine proteinases have been emphasized in the virulence of Porphyromonas gingivalis in chronic periodontitis. These hydrolases may promote the degradation of extracellular matrix proteins and disrupt components of the immune system. In this study it was shown that purified Arg-gingipain and Lys-gingipain inhibited expression of class II major histocompatibility complex (MHC) proteins in response to the stimulation of endothelial cells with human gamma interferon (IFN-gamma). Treatment with the cysteine proteinases resulted in a rapid shift in the apparent molecular size of IFN-gamma from 17 to 15 kDa, as shown by Western blot analysis, a response which also occurred in the presence of serum. Further, glycosylated natural IFN-gamma from human leukocytes and unglycosylated recombinant IFN-gamma from Escherichia coli were both digested by the cysteine proteinases. Immunoblot analysis indicated that cleavage within the carboxyl terminus of recombinant IFN-gamma correlated with the loss of induction of MHC class II expression as monitored by analytical flow cytometry. No hydrolysis of MHC class II molecules or human IFN-gamma receptor by these proteinases was detected by Western blot analysis. These findings suggest that P. gingivalis cysteine proteinases may alter the cytokine network at the point of infection through the cleavage of IFN-gamma. Degradation of IFN-gamma could have important consequences for the recruitment and activation of leukocytes and therefore may contribute significantly to the destruction of the periodontal attachment.
ChemInform Abstract: Coordination Versatility of sp<sup>3</sup>‐Hybridized Pincer Ligands Toward Ligand—Metal Cooperative Catalysis (2013)

Abstract Review: 105 refs.
Detection of Symptomatic Carotid Plaque Using Source Data from MR and CT Angiography: A Correlative Study (2015)

<b><i>Background:</i></b> Carotid plaque MRI has been a useful method to characterize vulnerable atherosclerotic plaque elements. Recent investigations have suggested that source images from CT angiography (CTA) and MR angiography (MRA) can identify the simple high-risk features of symptom-producing carotid artery plaque. We studied the correlation and relative diagnostic accuracies of CTA and MRA source images in detecting symptomatic carotid artery plaque. <b><i>Methods:</i></b> Subjects were eligible if they had carotid stenosis between 50 and 99% and had MRA and CTA exams performed within 10 days of one another. We measured the soft (non-calcified) plaque and hard (calcified) plaque thickness on CTA axial source images and intraplaque high-intensity signal (IHIS) on 3D-time-of-flight MRA source images in subjects. We assessed whether a correlation existed between increasing CTA soft plaque thicknesses and the presence of MRA IHIS using the Student's t-test. We calculated the differences in sensitivity and specificity measures of CTA and MRA source-imaging data with the occurrence of recent ipsilateral stroke or transient ischemic attack (TIA) as the reference standard. We also performed logistic regression analyses to evaluate the predictive strength of plaque showing both IHIS and increased CTA soft plaque thickness in predicting symptomatic disease status. <b><i>Results:</i></b> Of 1994 screened patients, 48 arteries met the final inclusion criteria with MRA and CTA performed within 10 days of one another. The mean and median time between CTA and MRA exams were 2.0 days and 1 day, respectively. A total of 34 of 48 stenotic vessels (70.8%) were responsible for giving rise to ipsilateral stroke or TIA. CTA mean soft plaque thickness was significantly greater (4.47 vs. 2.30 mm, p < 0.0001) in patients with MRA-defined IHIS, while CTA hard plaque thickness was significantly greater (2.09 vs. 1.16 mm, p = 0.0134) in patients without MRA evidence of IHIS. CTA soft plaque thickness measurements were more sensitive than MRA IHIS (91.2 vs. 67.6%, p = 0.011) in detecting symptomatic plaque, while differences in specificity were not significantly different (p = 0.1573). In the subset of patients with both IHIS on MRA and plaque thickness >2.4 mm on CTA, the odds ratio of detecting symptomatic plaque, corrected for stenosis severity, was 45.3 (p < 0.0005). <b><i>Conclusions:</i></b> Unprocessed source images from CTA and MRA, which are routinely evaluated for clinical studies demonstrate the highly correlated presence of IHIS and increasing soft plaque thickness. In particular, plaque that shows high-risk features on both MRA and CTA are very strongly associated with symptom-producing carotid plaque. With further validation, such techniques are promising practical methods of extracting risk information from routine neck angiographic imaging.
Direct simulation of the sedimentation of elliptic particles in Oldroyd-B fluids (1998)

Cross-stream migration and stable orientations of elliptic particles falling in an Oldroyd-B fluid in a channel are studied. We show that the normal component of the extra stress on a rigid body vanishes; lateral forces and torques are determined by the pressure. Inertia turns the long side of the ellipse across the stream and elasticity turns it along the stream; tilted off-centre falling is unstable. There are two critical numbers: the elasticity and Mach numbers. When the elasticity number is smaller than critical the fluid is essentially Newtonian with broadside-on falling at the centreline of the channel. For larger elasticity numbers the settling turns the long side of the particle along the stream in the channel centre for all velocities below a critical one, identified with a critical Mach number of order one. For larger Mach numbers the ellipse flips into broadside-on falling again. The critical numbers are functions of the channel blockage ratio, the particle aspect ratio and the retardation/relaxation time ratio of the fluid. Two ellipses falling near to each other, attract, line-up vertically and straighten-out with long sides vertical. Stable, off-centre tilting is found for ellipses falling in shear-thinning fluids and for cylinders with flat ends in which particles tend to align their longest diameter with gravity.
MR1-Restricted T Cells Are Unprecedented Cancer Fighters (2020)

Non-polymorphic MHC class I-related molecule MR1 presents antigenic bacterial metabolites to mucosal-associated invariant T (MAIT) cells and self-antigens to MR1-restricted T (MR1T) cells. Both MR1-restricted T cell populations are readily identified in healthy individuals, with MAIT cells accounting for 1-10% of circulating T cells, while MR1T cells have frequencies comparable to peptide-specific T cells (<0.1%). Self-reactive MR1T cells display a heterogeneous phenotype, and are capable of releasing both T<sub>H1</sub> and T<sub>H2</sub> cytokines, supporting not only activation of inflammation but also contributing to its regulation. Importantly, MR1T cells recognize and kill a diverse range of MR1-expressing tumor cells. On the other hand, evidence suggests MAIT cells augment cancer growth and metastases. This review addresses the potential role of MR1-restricted T cells in controlling tumor cells, facilitating their elimination and regulating cancer immunity. We also discuss therapeutic opportunities surrounding MR1-restricted T cells in cancer.
Analog integrated 2-D optical flow sensor with programmable pixels (2004)

We present a framework for real-time visual motion perception consisting of an analog VLSI optical flow sensor with reconfigurable pixels, connected in feedback with a controlling processor. The 2-D sensor array is composed of motion processing pixels that can be individually recruited to form dynamic ensembles that collectively compute visual motion. The flexible framework lends itself to the emulation of multi-layer recurrent network architectures for high-level processing of visual motion. In particular, attentional modulation can easily be incorporated in the visual motion processing. We show a simple example of visual tracking that demonstrates the potential of the framework.
Frequent Closed Sequence Mining without Candidate Maintenance (2007)

Previous studies have presented convincing arguments that a frequent pattern mining algorithm should not mine all frequent patterns but only the closed ones because the latter leads to not only a more compact yet complete result set but also better efficiency. However, most of the previously developed closed pattern mining algorithms work under the candidate maintenance-and- test paradigm, which is inherently costly in both runtime and space usage when the support threshold is low or the patterns become long. In this paper, we present BIDE, an efficient algorithm for mining frequent closed sequences without candidate maintenance. It adopts a novel sequence closure checking scheme called Bl-Directional Extension and prunes the search space more deeply compared to the previous algorithms by using the BackScan pruning method. A thorough performance study with both sparse and dense, real, and synthetic data sets has demonstrated that BIDE significantly outperforms the previous algorithm: It consumes an order(s) of magnitude less memory and can be more than an order of magnitude faster. It is also linearly scalable in terms of database size.
Single‐Dose Pharmacokinetics and Safety of Ubrogepant in Adults With Hepatic Impairment: Results From an Open‐Label, Phase 1 Trial (2022)

Ubrogepant is an oral calcitonin gene-related peptide receptor antagonist approved for the treatment of acute migraine headaches. Ubrogepant demonstrated efficacy and safety in 2 pivotal phase 3 studies (N = 2240) that led to its approval. Here, we report the pharmacokinetics and safety results from a phase 1 study in which participants with severe (n = 4), moderate (n = 8), or mild (n = 8) hepatic impairment and matched participants with normal hepatic function (n = 8) were administered a single dose of 100 mg of ubrogepant. Twenty-eight participants aged 36 to 70 years were enrolled and completed the study. In participants with mild, moderate, or severe hepatic impairment, ubrogepant systemic exposure (area under the plasma concentration-time curve) increased by 7%, 52%, and 115%, respectively, compared with participants with normal hepatic function (≈1600 ng • h/mL). Peak exposure increased by 1%, 18%, and 26%, respectively, in participants with mild, moderate, or severe hepatic impairment compared to those with normal hepatic function (≈400 ng/mL). Plasma protein binding did not change significantly across groups. No dose adjustment is recommended for patients with mild or moderate hepatic impairment. Dose adjustment (50 mg) is recommended for patients with severe hepatic impairment. Single doses of ubrogepant 100 mg were safe, and all the enrolled participants, regardless of hepatic function, completed the study.
Polymers from Fatty Acids: Poly(ω-hydroxyl tetradecanoic acid) Synthesis and Physico-Mechanical Studies (2011)

This Article describes the synthesis and physicomechanical properties of bioplastics prepared from methyl ω-hydroxytetradecanoic acid (Me-ω-OHC14), a new monomer available by a fermentation process using an engineered Candida tropicalis strain. Melt-condensation experiments were conducted using titanium tetraisopropoxide (Ti[OiPr](4)) as a catalyst in a two-stage polymerization (2 h at 200 °C under N(2), 4 h at 220 °C under 0.1 mmHg). Poly(ω-hydroxytetradecanoate), P(ω-OHC14), M(w), determined by SEC-MALLS, increased from 53K to 110K as the Ti(OiPr)(4) concentration increased from 50 to 300 ppm. By varying the polymerization conditions (catalyst concentration, reaction time, second-stage reaction temperature) a series of P(ω-OHC14) samples were prepared with M(w) values from 53K to 140K. The synthesized polyesters with M(w) ranging from 53K to 140K were subjected to characterization by DSC, TGA, DMTA, and tensile testing. Influences of P(ω-OHC14) molecular weight, melting point, and enthalpies of melting/crystallization on material tensile properties were explored. Cold-drawing tensile tests at room temperature for P(ω-OHC14) with M(w) 53K-78K showed a brittle-to-ductile transition. In contrast, P(ω-OHC14) with M(w) 53K undergoes brittle fracture. Increasing P(ω-OHC14) M(w) above 78K resulted in a strain-hardening phenomena and tough properties with elongation at break ~700% and true tensile strength of ~50 MPa. Comparisons between high density polyethylene and P(ω-OHC14) mechanical and thermal properties as a function of their respective molecular weights are discussed.
The nonspecific DNA-binding and -bending proteins HMG1 and HMG2 promote the assembly of complex nucleoprotein structures. (1993)

The mammalian high mobility group proteins HMG1 and HMG2 are abundant, chromatin-associated proteins whose cellular function is not known. In this study we show that these proteins can substitute for the prokaryotic DNA-bending protein HU in promoting the assembly of the Hin invertasome, an intermediate structure in Hin-mediated site-specific DNA inversion. Formation of this complex requires the assembly of the Hin recombinase, the Fis protein, and three cis-acting DNA sites, necessitating the looping of intervening DNA segments. Invertasome assembly is strongly stimulated by HU or HMG proteins when one of these segments is shorter than 104 bp. By use of ligase-mediated circularization assays, we demonstrate that HMG1 and HMG2 can bend DNA extremely efficiently, forming circles as small as 66 bp, and even 59-bp circles at high HMG protein concentrations. In both invertasome assembly and circularization assays, substrates active in the presence of HMG1 contain one less helical turn of DNA compared with substrates active in the presence of HU protein. Analysis of different domains of HMG1 generated by partial proteolytic digestion indicate that DNA-binding domain B is sufficient for both bending and invertasome assembly. We suggest that an important biological function of HMG1 and HMG2 is to facilitate cooperative interactions between cis-acting proteins by promoting DNA flexibility. A general role for HMG1 and HMG2 in chromatin structure is also suggested by their ability to wrap DNA duplexes into highly compact forms.