gebhart/patrepeval huggingface dataset:
Single-molecule genome-wide mutation profiles of cell-free DNA for non-invasive detection of cancer (2023)

Somatic mutations are a hallmark of tumorigenesis and may be useful for non-invasive diagnosis of cancer. We analyzed whole-genome sequencing data from 2,511 individuals in the Pan-Cancer Analysis of Whole Genomes (PCAWG) study as well as 489 individuals from four prospective cohorts and found distinct regional mutation type-specific frequencies in tissue and cell-free DNA from patients with cancer that were associated with replication timing and other chromatin features. A machine-learning model using genome-wide mutational profiles combined with other features and followed by CT imaging detected >90% of patients with lung cancer, including those with stage I and II disease. The fixed model was validated in an independent cohort, detected patients with cancer earlier than standard approaches and could be used to monitor response to therapy. This approach lays the groundwork for non-invasive cancer detection using genome-wide mutation features that may facilitate cancer screening and monitoring.
Pathogenicity of Shigella fiexneri and Its Regulation. (1995)

赤痢菌の病原性発現には,菌の腸上皮への侵入とその後の細胞内・細胞間拡散が不可欠である。細胞侵入と拡散は,本菌の大プラスミドがコードするIpa(IpaB,IpaC,IpaD)とVirG蛋白により各々行なわれる。Ipa蛋白の菌体表層分泌は大プラスミドのコードするMixとSpa蛋白群により行なわれるが,細胞侵入を発揮するためには菌体からIpaが遊離しIpaBC複合体を形成する事が必要である。Ipa蛋白の遊離は赤痢菌と細胞外マトリックス(フィブロネクチン等)の接触が引き金となり起こり,生じたIpa複合体は上皮細胞レセプターに作用し,最終的にアクチン系細胞骨格繊維を再構築し食作用を誘起する。ファゴゾームからの菌の脱離にもIpa蛋白が関与している。細胞質内では,赤痢菌は菌体の一極にVirG蛋白を分泌し,そこでアクチンの重合を行ない,これを原動力として菌は細胞内及び隣接細胞へ感染を行なう。これら赤痢菌の感染に重要な蛋白の発現は,その機能が合目的に働くよう厳密な調節系の元に置かれている。さらに染色体上にも多数のビルレンスに必要な遺伝子群が存在し,菌の細胞内増殖,細胞間感染,大プラスミド上の遺伝子発現調節など様々な機能に関与していることが知られている。
On Singular Moduli (2013)

The modular j-function plays an important role in number theory: its values at quadratic imaginary integers are called singular moduli. Singular moduli can be interpreted as an invariant of CM elliptic curves and play a role in explicit class eld theory. In 1985, Gross and Zagier gave an elegant formula for the factorization of norms of dierences of singular moduli associated to a pair of imaginary quadratic discriminants d1 and d2, under the assumption that d1 and d2 are fundamental and relatively prime. Their theorem was one of the ingredients in the proof of the only known case of the Birch-Swinnerton Dyer Conjecture. This talk will present a generalization of their result to give a complete factorization for any two fundamental discriminants which are not necessarily coprime, and obtain at least a partial factorization for any two quadratic imaginary discriminants. We will discuss the motivation for this generalization arising in cryptography and give an application to proving an intersection formula on Hilbert modular surfaces related to the work of Bruinier and Yang. This is joint work with Bianca Viray.
Single-shot error mitigation by coherent Pauli checks (2022)

Generating samples from the output distribution of a quantum circuit is a ubiquitous task used as a building block of many quantum algorithms. Here we show how to accomplish this task on a noisy quantum processor lacking full-blown error correction for a special class of quantum circuits dominated by Clifford gates. Our approach is based on Coherent Pauli Checks (CPCs) that detect errors in a Clifford circuit by verifying commutation rules between random Pauli-type check operators and the considered circuit. Our main contributions are as follows. First, we derive a simple formula for the probability that a Clifford circuit protected by CPCs contains a logical error. In the limit of a large number of checks, the logical error probability is shown to approach the value ${\approx}7εn/5$, where $n$ is the number of qubits and $ε$ is the depolarizing error rate. Our formula agrees nearly perfectly with the numerical simulation results. Second, we show that CPCs are well-suited for quantum processors with a limited qubit connectivity. For example, the difference between all-to-all and linear qubit connectivity is only a 3X increase in the number of CNOT gates required to implement CPCs. Third, we describe simplified one-sided CPCs which are well-suited for mitigating measurement errors in the single-shot settings. Finally, we report an experimental demonstration of CPCs with up to 10 logical qubits and more than 100 logical CNOT gates. Our experimental results show that CPCs provide a marked improvement in the logical error probability for the considered task of sampling the output distribution of quantum circuits.
The Association Between Retinal Neuronal Layer and Brain Structure is Disrupted in Patients with Cognitive Impairment and Alzheimer’s Disease (2016)

Both healthy and pathological aging due to Alzheimer's disease (AD) are associated with decreased brain grey matter volume (GMV) and disrupted white matter (WM) microstructure. Thinner macular ganglion cell-inner plexiform layer (GC-IPL) measured by spectral-domain optical coherence tomography has been reported in patients with AD and mild cognitive impairment. Emerging evidence suggested a link between thinner GC-IPL and lower GMV in subjects with no dementia using region-of-interest-based approach. However, it remains unknown whether GC-IPL thickness is associated with brain WM microstructure and how such association differed between normal and cognitively impaired subjects. Here, for subjects with no cognitive impairment (NCI), thinner GC-IPL was associated with lower WM microstructure integrity in the superior longitudinal fasciculus, inferior fronto-occipital fasciculus, corticospinal tracts, anterior thalamic radiation, and cingulum regions, while it was weakly associated with lower GMV in visual cortex and cerebellum. Nevertheless, these retina-brain associations were disrupted in the presence of cognitive impairment. Correlations between GMV and GC-IPL were lost in patients with cognitive impairment but no dementia (CIND) and AD patients. GC-IPL was related to WM microstructural disruption in similar regions with decreased significance. In contrast, lower WM microstructure integrity in the fornix showed a trend of correlation with thinner GC-IPL in both CIND and AD but not NCI. Collectively, our findings suggest the possible physiological retina-brain relationship in healthy aging, which might be disrupted by disease-induced changes in patients with cognitive impairment. Longitudinal study with larger patient sample should follow to confirm the disease mechanism behind these retina-brain relationship changes.
Socio-economic position at three points in life in association with type 2 diabetes and impaired glucose tolerance in middle-aged Swedish men and women (2007)

The association between type 2 diabetes and low SEP during childhood and adolescence in middle-aged Swedish subjects disappeared after adjustment for adult SEP and adult risk factors of diabetes.
PyCARL: A PyNN Interface for Hardware-Software Co-Simulation of Spiking Neural Network (2020)

We present PyCARL, a PyNN-based common Python programming interface for hardware-software cosimulation of spiking neural network (SNN). Through PyCARL, we make the following two key contributions. First, we provide an interface of PyNN to CARLsim, a computationally- efficient, GPU-accelerated and biophysically-detailed SNN simulator. PyCARL facilitates joint development of machine learning models and code sharing between CARLsim and PyNN users, promoting an integrated and larger neuromorphic community. Second, we integrate cycle-accurate models of state-of-the-art neuromorphic hardware such as TrueNorth, Loihi, and DynapSE in PyCARL, to accurately model hardware latencies, which delay spikes between communicating neurons, degrading performance of machine learning models. PyCARL allows users to analyze and optimize the performance difference between software-based simulation and hardware-oriented simulation. We show that system designers can also use PyCARL to perform design-space exploration early in the product development stage, facilitating faster time-to-market of neuromorphic products.
The elevated blood pressure of humanGRK4γA142Vtransgenic mice is not associated with increased ROS production (2007)

G protein-coupled receptor (GPCR) kinases (GRKs) regulate the sensitivity of GPCRs, including dopamine receptors. The GRK4 locus is linked to, and some of its polymorphisms are associated with, human essential hypertension. Transgenic mice overexpressing human (h) GRK4gamma A142V on a mixed genetic background (C57BL/6J and SJL/J) have impaired renal D(1)-dopamine receptor (D(1)R) function and increased blood pressure. We now report that hGRK4gamma A142V transgenic mice, in C57BL/6J background, are hypertensive and have higher blood pressures than hGRK4gamma wild-type transgenic and nontransgenic mice. The hypertensive phenotype is stable because blood pressures in transgenic founders and F6 offspring are similarly increased. To determine whether the hypertension is associated with increased production of reactive oxygen species (ROS), we measured renal NADPH oxidase (Nox2 and Nox4) and heme oxygenase (HO-1 and HO-2) protein expressions and urinary excretion of 8-isoprostane and compared the effect of Tempol on blood pressure in hGRK4gamma A142V transgenic mice and D(5)R knockout (D(5)(-/-)) mice in which hypertension is mediated by increased ROS. The expressions of Nox isoforms and HO-2 and the urinary excretion of 8-isoprostane were similar in hGRK4gamma A142V transgenic mice and their controls. HO-1 expression was increased in hGRK4gamma A142V relative to hGRK4gamma wild-type transgenic mice. In contrast with the hypotensive effect of Tempol in D(5)(-/-) mice, it had no effect in hGRK4gamma A142V transgenic mice. We conclude that the elevated blood pressure of hGRK4gamma A142V transgenic mice is due mainly to the effect of hGRK4gamma A142V transgene acting via D(1)R and increased ROS production is not a contributor.
On-farm performance and farmers’ participatory assessment of new stress-tolerant maize hybrids in Eastern Africa (2019)

The development and deployment of high-yielding stress tolerant maize hybrids are important components of the efforts to increase maize productivity in eastern Africa. This study was conducted to: i) evaluate selected, stress-tolerant maize hybrids under farmers' conditions; ii) identify farmers' selection criteria in selecting maize hybrids; and iii) have farmers evaluate the new varieties according to those criteria. Two sets of trials, one with 12 early-to-intermediate maturing and the other with 13 intermediate-to-late maturing hybrids, improved for tolerance to multiple stresses common in farmers' fields in eastern Africa (drought, northern corn leaf blight, gray leaf spot, common rust, maize streak virus), were evaluated on-farm under smallholder farmers' conditions in a total of 42 and 40 environments (site-year-management combinations), respectively, across Kenya, Uganda, Tanzania and Rwanda in 2016 and 2017. Farmer-participatory variety evaluation was conducted at 27 sites in Kenya and Rwanda, with a total of 2025 participating farmers. Differential performance of the hybrids was observed under low-yielding (<3 t ha<sup>-1</sup>) and high-yielding (>3 t ha<sup>-1</sup>) environments. The new stress-tolerant maize hybrids had a much better grain-yield performance than the best commercial checks under smallholder farmer growing environments but had a comparable grain-yield performance under optimal conditions. These hybrids also showed better grain-yield stability across the testing environments, providing an evidence for the success of the maize-breeding approach. In addition, the new stress- tolerant varieties outperformed the internal genetic checks, indicating genetic gain under farmers' conditions. Farmers gave high importance to grain yield in both farmer-stated preferences (through scores) and farmer-revealed preferences of criteria (revealed by regressing the overall scores on the scores for the individual criteria). The top-yielding hybrids in both maturity groups also received the farmers' highest overall scores. Farmers ranked yield, early maturity, cob size and number of cobs as the most important traits for variety preference. The criteria for the different hybrids did not differ between men and women farmers. Farmers gave priority to many different traits in addition to grain yield, but this may not be applicable across all maize-growing regions. Farmer-stated importance of the different criteria, however, were quite different from farmer- revealed importance. Further, there were significant differences between men and women in the revealed-importance of the criteria. We conclude that incorporating farmers' selection criteria in the stage-gate advancement process of new hybrids by the breeders is useful under the changing maize-growing environments in sub-Saharan Africa, and recommended to increase the turnover of new maize hybrids.
Cationic Covalent Organic Polymer Thin Film for Label-free Electrochemical Bacterial Cell Detection (2022)

Numerous species of bacteria pose a serious threat to human health and cause several million deaths annually. It is therefore essential to have quick, efficient, and easily operable methods of bacterial cell detection. Herein, we synthesize a novel cationic covalent organic polymer (COP) named <b>CATN</b> through the Menshutkin reaction and evaluate its potential as an impedance sensor for <i>Escherichia coli</i> cells. On account of its positive surface charge (ζ-potential = +21.0 mV) and pyridinium moieties, <b>CATN</b> is expected to interact favorably with bacteria that possess a negatively charged cell surface through electrostatic interactions. The interdigitated electrode arrays were coated with <b>CATN</b> using a simple yet non-traditional method of electrophoresis and then used in two-electrode electrochemical impedance spectroscopy (EIS) measurements. The impedance response showed a linear relationship with the increasing concentration of <i>E. coli</i>. The system was sensitive to bacterial concentrations as low as ∼30 CFU mL<sup>-1</sup>, which is far below the concentration considered to cause illnesses. The calculated limit of detection was as low as 2 CFU mL<sup>-1</sup>. This work is a rare example of a COP used in this type of bacteria sensing and is anticipated to stimulate further interest in the synthesis of organic polymers for EIS-based sensors.
Ultrathin fiber-taper coupling with nitrogen vacancy centers in nanodiamonds at cryogenic temperatures (2015)

We demonstrate cooling of ultrathin fiber tapers coupled with nitrogen vacancy (NV) centers in nanodiamonds to cryogenic temperatures. Nanodiamonds containing multiple NV centers are deposited on the subwavelength 480-nm-diameter nanofiber region of fiber tapers. The fiber tapers are successfully cooled to 9 K using our home-built mounting holder and an optimized cooling speed. The fluorescence from the nanodiamond NV centers is efficiently channeled into a single guided mode and shows characteristic sharp zero-phonon lines (ZPLs) of both neutral and negatively charged NV centers. The present nanofiber/nanodiamond hybrid systems at cryogenic temperatures can be used as NV-based quantum information devices and for highly sensitive nanoscale magnetometry in a cryogenic environment.
Increased expression of intrinsic antiviral genes in HLA-B*57-positive individuals (2013)

The genetic background of HIV-1-infected subjects, particularly the HLA class I haplotype, appears to be critical in determining disease progression rates, thought to be a result of the role of HIV-1-specific CD8(+) T cell responses. The HLA-B*57 allele is strongly associated with viremic suppression and slower disease progression. However, there is considerable heterogeneity in HIV-1 disease progression rates among HLA-B*57-positive subjects, suggesting that additional factors may help to contain viral replication. In this report, we investigated the association between host restriction factors, other established immunological parameters, and HLA type in HIV-1-seronegative individuals. Our results demonstrate that healthy, uninfected HLA-B*57-positive individuals exhibit significantly higher gene-expression levels of host restriction factors, such as APOBEC3A, APOBEC3B, BST-2/tetherin, and ISG15. Interestingly, HLA-B*57 individuals have significantly lower CD4(+) T cell frequencies but harbor slightly more activated CD4(+) T cells compared with their HLA-B*35 counterparts. We detected significant correlations between CD4(+) T cell activation and expression of several APOBEC3 family members, BST-2/tetherin, SAMHD1, and TRIM5α in HLA-B*57-positive individuals. To our knowledge, this is the first report showing distinct associations between host restriction factors and HLA class I genotype. Our results provide insights into natural protection mechanisms and immunity against HIV-1 that fall outside of classical HLA-mediated effects.
Conductive Two-Dimensional Titanium Carbide ‘Clay’ with High Volumetric Capacitance (2023)

Safe and powerful energy storage devices are becoming increasingly important. Charging times of seconds to minutes, with power densities exceeding those of batteries, can in principle be provided by electrochemical capacitors in particular, pseudocapacitors. The best volumetric capacitances of carbonbased electrodes are around 300 farads per cubic centimetre. MXenes have proved to be promising candidates for electrodes in lithium-ion batteries and super-capacitors, exhibiting volumetric capacitances. The activated carbon electrodes were prepared by mechanical processing of a pre-mixed slurry, containing ethanol, YP-50 activated carbon powder, and polytetrafluoroethynene binder. Cyclic voltammetry, electrochemical impedance spectroscopy, and galvanostatic cycling were performed using a VMP3 potentiostat. Transmission electron microscopy of the MXene flakes was performed on a JEM-2100 using an accelerating voltage of 200 kV.
RNA splicing regulates the temporal order of TNF-induced gene expression (167.5) (2012)

Abstract When cells are induced to express inflammatory genes by treatment with TNF the mRNAs for the induced genes appear in three distinct waves, defining gene Groups I, II and III or early, intermediate and late genes. To examine the basis for these different kinetic classes, we developed a PCR-based procedure to distinguish pre-mRNA synthesis from mRNA synthesis. It showed that the three Groups initiate transcription virtually simultaneously but that delays in splicing characterize Groups II and III. We examined the elongation times and polyadenylation timing, concluding that pre-mRNA synthesis is coordinate but splicing differences directly regulate the timing of mRNA production. Coupled to previous measurements of the half-life of mRNAs, the kinetic parameters can be combined in a general mathematical model of pre-mRNA conversion to mRNA that reproduces the experimental kinetics without recourse to differences in transcription.This model could be a generally relevant description of sequential transcriptional events in response to inducers.
SAEMIX, an R version of the SAEM algorithm (2010)

) 1.57 (19%) 0.39 (45%) CL (L.hr 1 ) 1.58 (64%) 0.07 (49%) βBW;CL (-) 0.008 (110%) - V (L) 31.5 (4%) 0.02 (59%)
Deep silicon etching: current capabilities and future directions (2014)

Deep Reactive Ion Etching (DRIE) has revolutionized a wide variety of MEMS applications since its inception nearly two decades ago. The DRIE technology has been largely responsible for allowing lab scale technology demonstrations to become manufacturable and profitable consumer products. As applications which utilize DRIE technologies continue to expand and evolve, they continue to spawn a range of new requirements and open up exciting opportunities for advancement of DRIE. This paper will examine a number of current and emerging DRIE applications including nanotechnology, and DRIE related packaging technologies such as Through Silicon Via (TSV) and plasma dicing. The paper will discuss a number of technical challenges and solutions associated with these applications including: feature profile control at high aspect ratios, causes and elimination of feature tilt/skew, process options for fragile device structures, and problems associated with through substrate etching. The paper will close with a short discussion around the challenges of implementing DRIE in production environments as well as looking at potentially disruptive enhancements / substitutions for DRIE.
CHFR promoter methylation indicates poor prognosis in stage II microsatellite stable colorectal cancer. (2013)

e14503 Background: Data on the prognostic significance of promoter CpG island methylation in colorectal cancer (CRC) are conflicting, possibly due to associations between methylation and other factors affecting survival such as genetic alterations and use of adjuvant therapy. Here we examine the prognostic impact of promoter methylation in CRC patients treated with surgery alone in the context of microsatellite instability (MSI), BRAF- and KRAS mutations. Methods: 173 CRCs were analyzed for promoter methylation of 19 tumor suppressor- and DNA repair genes, the CpG island methylator phenotype (CIMP), MSI, the exon 15 V600E BRAF mutation and KRAS codon 12 and 13 mutations. Results: Unsupervised hierarchical clustering based on methylation status of 19 genes revealed three subgroups: cluster 1 (CL1, 57% (98/173) of CRCs), cluster 2 (CL2, 25% (43/173) of CRCs) and cluster 3 (CL3, 18% (32/173) of CRCs). CL3 had the highest methylation index (0.25, 0.49 and 0.69 respectively, p=&lt;0.01) and was strongly associated with CIMP (p&lt;0.01). After stratification for tumor stage, MSI and BRAF status, no statistically significant differences in survival between CL1, CL2 and CL3 nor between CIMP and non-CIMP CRCs were detected. Analyzing genes separately revealed that CHFR promoter methylation was associated with a poor prognosis in stage II, MSS, BRAF wild-type CRCs: HR=3.89 (95% CI =1.58-9.60, p=0.003) and HR=2.21 (95% CI =1.09-4.48, p=0.03) in a second population-based study (n=151). Conclusions: CHFR promoter CpG island methylation, which is associated with MSI, also occurs frequently in MSS CRCs and is a promising prognostic marker in stage II, MSS, BRAF wild-type CRCs.
Murine model of genetic demyelinating disease: The twitcher mouse (1995)

Twitcher mouse is an authentic murine model of human genetic demyelinating disease, globoid cell leukodystrophy (GLD), or Krabbe disease. Since its discovery at the Jackson Laboratory (Bar Harbor, ME) this model has been used extensively for the morphological, biochemical-enzymatic studies to clarify pathogenesis and also for therapeutic manipulation of genetic demyelinating disease in humans. As a result of these studies, now we know that (1) GLD is caused by a deficiency of lysosomal enzyme galactosylceramidase, and a toxic metabolite, psychosine, accumulates in the tissue, including the nervous system, damaging myelin forming cells and resulting in secondary demyelination; (2) morphological features of demyelination and associated cellular reactions in demyelination in this mutant are similar to those seen in autoimmune or toxic demyelination; and (3) with enzyme supplementation provided by bone marrow transplantation, remyelination occurs to some extent in demyelinated fibers in both central and peripheral nervous systems of twitcher mouse.
Un modèle computationnel pour simuler des données EEG chez les patients implantés cochléaires : vers le développement de mesures objectives (2015)

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