gebhart/patrepeval huggingface dataset:
Rare variant detection using family-based sequencing analysis (2013)

Next-generation sequencing is revolutionizing genomic analysis, but this analysis can be compromised by high rates of missing true variants. To develop a robust statistical method capable of identifying variants that would otherwise not be called, we conducted sequence data simulations and both whole-genome and targeted sequencing data analysis of 28 families. Our method (Family-Based Sequencing Program, FamSeq) integrates Mendelian transmission information and raw sequencing reads. Sequence analysis using FamSeq reduced the number of false negative variants by 14-33% as assessed by HapMap sample genotype confirmation. In a large family affected with Wilms tumor, 84% of variants uniquely identified by FamSeq were confirmed by Sanger sequencing. In children with early-onset neurodevelopmental disorders from 26 families, de novo variant calls in disease candidate genes were corrected by FamSeq as mendelian variants, and the number of uniquely identified variants in affected individuals increased proportionally as additional family members were included in the analysis. To gain insight into maximizing variant detection, we studied factors impacting actual improvements of family-based calling, including pedigree structure, allele frequency (common vs. rare variants), prior settings of minor allele frequency, sequence signal-to-noise ratio, and coverage depth (∼20× to >200×). These data will help guide the design, analysis, and interpretation of family-based sequencing studies to improve the ability to identify new disease-associated genes.
Increased soluble TREM2 in cerebrospinal fluid is associated with reduced cognitive and clinical decline in Alzheimer’s disease (2019)

Loss of function of TREM2, a key receptor selectively expressed by microglia in the brain, contributes to the development of Alzheimer's disease (AD). We therefore examined whether soluble TREM2 (sTREM2) concentrations in cerebrospinal fluid (CSF) were associated with reduced rates of cognitive decline and clinical progression in subjects with AD or mild cognitive impairment (MCI). We measured sTREM2 in CSF samples from 385 elderly subjects, including cognitively normal controls, individuals with MCI, and subjects with AD dementia (follow-up period: mean, 4 years; range 1.5 to 11.5 years). In subjects with AD defined by evidence of CSF Aβ<sub>1-42</sub> (amyloid β-peptide 1 to 42; A+) and CSF p-tau<sub>181</sub> (tau phosphorylated on amino acid residue 181; T+), higher sTREM2 concentrations in CSF at baseline were associated with attenuated decline in memory and cognition. When analyzed in clinical subgroups, an association between higher CSF sTREM2 concentrations and subsequent reduced memory decline was consistently observed in individuals with MCI or AD dementia, who were positive for CSF Aβ<sub>1-42</sub> and CSF p-tau<sub>181</sub> (A+T+). Regarding clinical progression, a higher ratio of CSF sTREM2 to CSF p-tau<sub>181</sub> concentrations predicted slower conversion from cognitively normal to symptomatic stages or from MCI to AD dementia in the subjects who were positive for CSF Aβ<sub>1-42</sub> and CSF p-tau<sub>181.</sub> These results suggest that sTREM2 is associated with attenuated cognitive and clinical decline, a finding with important implications for future clinical trials targeting the innate immune response in AD.
A Simple “New” Method to Accelerate Clearance of Carbon Monoxide (2000)

The currently recommended prehospital treatment for carbon monoxide (CO) poisoning is administration of 100% O(2). We have shown in dogs that normocapnic hyperpnea with O(2) further accelerates CO elimination. The purpose of this study was to examine the relation between minute ventilation (V E) and the rate of elimination of CO in humans. Seven healthy male volunteers were exposed to CO (400 to 1,000 ppm) in air until their carboxyhemoglobin (COHb) levels reached 10 to 12%. They then breathed either 100% O(2) at resting V E (4.3 to 9.0 L min) for 60 min or O(2) containing 4.5 to 4.8% CO(2) (to maintain normocapnia) at two to six times resting V E for 90 min. The half-time of the decrease in COHb fell from 78 +/- 24 min (mean +/- SD) during resting V E with 100% O(2) to 31 +/- 6 min (p < 0. 001) during normocapnic hyperpnea with O(2). The relation between V E and the half-time of COHb reduction approximated a rectangular hyperbola. Because both the method and circuit are simple, this approach may enhance the first-aid treatment of CO poisoning.
Newborn Screening for Congenital Adrenal Hyperplasia: Additional Steroid Profile using Liquid Chromatography-Tandem Mass Spectrometry (2007)

Our liquid chromatography-tandem mass spectrometry procedure as a second-tier test can be used to reduce false-positive results of standard 21-CAH screening. The short total run time of 6 min allows for immediate reanalysis of all immunoassay results above the cutoff.
Rolling neutrophils form tethers and slings under physiologic conditions in vivo (2017)

Human and mouse neutrophils are known to form tethers when rolling on selectins in vitro. Tethers are ∼0.2 μm thin, ∼5-10 μm-long structures behind rolling cells that can swing around to form slings that serve as self-adhesive substrates. Here, we developed a mouse intravital imaging method, where the neutrophil surface is labeled by injecting fluorescently labeled mAb to Ly-6G. Venules in the cremaster muscle of live mice were imaged at a high frame rate using a confocal microscope equipped with a fast resonant scanner. We observed 270 tethers (median length 3.5 μm) and 31 slings (median length 6.9 µm) on 186 neutrophils of 15 mice. Out of 199 tether break events, 123 were followed by immediate acceleration of the rolling cell, which shows that tethers are load-bearing structures in vivo. In venules with a high wall shear stress (WSS; > 12 dyn/cm<sup>2</sup> ), median rolling velocity was higher (19 μm/s), and 43% of rolling neutrophils had visible tethers. In venules with WSS < 12 dyn/cm<sup>2</sup> , only 26% of rolling neutrophils had visible tethers. We conclude that neutrophil tethers are commonly present and stabilize rolling in vivo.
Genetic analysis of the connexin-26 M34T variant: identification of genotype M34T/M34T segregating with mild-moderate non-syndromic sensorineural hearing loss (2001)

Mutations in the human gap junction beta-2 gene (GJB2) that encodes connexin-26 have been shown to cause non-syndromic sensorineural hearing loss (NSSNHL) at the DFNB1 locus on 13q11. Functional and genetic data regarding the disease causing potential of one particular GJB2 sequence variant, 101 T-->C (M34T), have proven contradictory. In this study, we found the prevalence of the M34T allele in a cohort of white sib pairs and sporadic cases with NSSNHL from the United Kingdom and Ireland to be 3.179% of chromosomes screened. Significantly, we identified the first M34T/M34T genotype cosegregating in a single family with mid to high frequency NSSNHL. Screening a control population of 630 subjects we identified 25 M34T heterozygotes; however, no M34T homozygotes were detected. Surprisingly, the majority of M34T alleles (88%) were in cis with a 10 bp deletion in the 5' non-coding sequence. This non-coding deletion was also homozygous in the homozygous M34T subjects. Microsatellite analysis of flanking loci in M34T heterozygotes and controls does not define an extensive ancestral haplotype but preliminary data suggest two common alleles in subjects with the M34T allele. In summary, we provide data that support M34T acting as a recessive GJB2 allele associated with mild-moderate prelingual hearing impairment.
A novel harmonic selection technique based on the injection of a periodically repeated oscillations train into an oscillator (2014)

A new concept based on the injection of a periodically repeated oscillations train into an oscillator is presented. It is based on a phenomenon named pseudo-locking, leading to a novel harmonic selection technique. Theoretical description of the concept is presented, in particular an analytical condition is carried out, paving the way of design rules. For a proof of concept, an oscillator fabricated on a 40 nm CMOS technology was measured. The concept was validated by measured phase noise equivalent to classical fundamental injection locking phase noise performance.
Teneur en plomb et en oxyde de carbone dans le sang des chauffeurs de taxi de Londres (1973)

H. J. Teneur en plomb et en oxyde de carbone dans le sang des chauffeurs de taxis de Londres. In: Population, 28ᵉ année, n°1, 1973. pp. 141-142.
The Last Judgment (1953)

The historic significance and aesthetic merits of an anonymous Chinese painting which is part of the Ethnographic Collection in the Department of History at the University of Melbourne are discussed. The technical, compositional and artistic details of the painting, which depict the last judgement are analysed, and it is suggested that the picture could have been painted during the Ming dynasty at the beginning of the 17th century.
Slit2/Robo1 signaling promotes intestinal tumorigenesis through Src-mediated activation of the Wnt/β-catenin pathway (2014)

Slit2 is often overexpressed in cancers. Slit2 is a secreted protein that binds to Roundabout (Robo) receptors to regulate cell growth and migration. Here, we employed several complementary mouse models of intestinal cancers, including the Slit2 transgenic mice, the ApcMin/+ spontaneous intestinal adenoma mouse model, and the DMH/DSS-induced colorectal carcinoma model to clarify function of Slit2/Robo1 signaling in intestinal tumorigenesis. We showed that Slit2 and Robo1 are overexpressed in intestinal tumors and may contribute to tumor generation. The Slit2/Robo1 signaling can induce precancerous lesions of the intestine and tumor progression. Ectopic expression of Slit2 activated Slit2/Robo1 signaling and promoted tumorigenesis and tumor growth. This was mediated in part through activation of the Src signaling, which then down-regulated E-cadherin, thereby activating Wnt/β-catenin signaling. Thus, Slit2/Robo1 signaling is oncogenic in intestinal tumorigenesis.
Regional hemodynamic effects of antihypertensive renomedullary lipids in conscious rats. (1984)

Renomedullary tissue has been proposed to exert an antihypertensive endocrine-like action. The antihypertensive polar renomedullary lipids (APRL) and neutral renomedullary lipids (ANRL) are potential mediators of this action. We evaluated the blood pressure and regional hemodynamic responses to APRL administered peripherally (i.v.) and to the central nervous system (CNS) in normal rats and rats with sinoaortic deafferentation (SAD) to remove baroreflex buffering. Rats were chronically instrumented with Doppler flow probes for measurement of mesenteric, renal, and hind-quarter vascular resistance, with arterial pressure and intravenous catheters, and with lateral cerebroventricular cannuli for intracerebroventricular (i.c.v.) administration. Intravenous APRL (0.01 to 1.0 micrograms) produced a dose-dependent decrease in blood pressure, tachycardia, and dilation of all vascular beds studied. The dose-response relationships were shifted to the left in SAD animals. APRL administered i.c.v. had no effect on intact or SAD rats. Pressor and regional vasoconstrictor responses to norepinephrine, angiotensin, and vasopressin were markedly reduced in SAD animals during constant infusion of APRL. In a second group of conscious SAD animals instrumented for blood pressure and heart rate measurements, intravenous ANRL (500 micrograms) decreased both arterial pressure (-45 +/- 16 mm Hg) and heart rate (-50 +/- 16 bpm). When given i.c.v., however, ANRL (10-100 micrograms) had no significant effect on resting blood pressure or heart rate. These studies suggest that APRL and ANRL produce no significant cardiovascular effects that are mediated through the CNS. However, both lipids are potent depressor agents, and APRL exhibits a strong peripheral vasodilator action and nonspecifically reduces reactivity to vasoconstrictor agents.
The Effect of Reference Microphone Placement on Sound Pressure Levels at an Ear Level Hearing Aid Microphone (1990)

The present study was designed to investigate the effects of reference microphone location on probe tube microphone measures of hearing aid response. The reference microphone of a clinical probe tube microphone system was located either at a position on the cheek (position A) or in close proximity to the microphone of an ear level hearing aid (position B). With sound pressure level (SPL) held constant at the reference microphone, the SPL at the position of the hearing aid microphone was measured at 14 test frequencies using a 1/8-inch condenser microphone. Measures were obtained on ten male and ten female subjects. Results indicated large frequency-dependent deviations in SPL at the hearing aid microphone, compared to that measured at the reference microphone, when the reference microphone was at position A. In the 1200 to 2000 Hz range, the SPL at the hearing aid microphone was as much as 9.5 dB higher than at the reference microphone. There were no large frequency-dependent variations with the reference microphone in position B, but the SPL at the hearing aid microphone location was approximately 3 dB higher than at the reference microphone. Results suggest that estimates of hearing aid output can be affected markedly by the reference microphone location. Clinical implications of the impact of reference microphone location on probe microphone measures of hearing aid gain and saturation sound pressure levels are discussed.
Graphene Nanosheets and Graphite Oxide as Promising Adsorbents for Removal of Organic Contaminants from Aqueous Solution (2013)

Graphenes are an emerging class of carbon nanomaterials whose adsorption properties toward organic compounds have not been well understood. In the present study, graphene nanosheets were prepared by reoxidation and abrupt heating of graphite oxide, which was prepared by sequential chemical oxidation of commercial nonporous graphite powder. Adsorption properties of three aromatic compounds (naphthalene, 2-naphthol, and 1-naphthylamine) and one pharmaceutical compound (tylosin) on graphene nanosheets and graphite oxide were examined to explore the potential of these two adsorbents for the removal of organic contaminants from aqueous solutions. Compared with the literature data of adsorption on carbon nanotubes, adsorption of bulky, flexible tylosin on graphene nanosheets exhibited markedly faster adsorption kinetics, which can be attributed to their opened-up layer structure. Graphene nanosheets and graphite oxide showed similar sequences of adsorption affinity: 1-naphthylamine > 2-naphthol > tylosin > naphthalene (with much larger differences observed on graphite oxide). It was proposed that the strong adsorption of the three aromatic compounds was mainly due to π-π electron donor-acceptor interactions with the graphitic surfaces of adsorbents. Additionally, Lewis acid-base interaction was likely an important factor contributing to the strong adsorption of 1-naphthylamine and tylosin, especially for the O-functionality-abundant graphite oxide. After being normalized on the basis of adsorbent surface area, adsorption affinities of all four tested adsorbates on graphene nanosheets were very close to those on nonporous graphite powder, reflecting complete accessibility of the adsorbent surface area in adsorption.
Reducing negativity artifacts in emission tomography: post-processing filtered backprojection solutions (1993)

The problem of negative artifacts in emission tomography reconstructions computed by filtered backprojection (FBP) is of practical concern particularly in low count studies. Statistical reconstruction methods based on maximum likelihood (ML) are automatically constrained to be non-negative but their excessive computational overhead (orders of magnitude greater than FBP) has limited their use in operational settings. Motivated by the statistical character of the negativity artifact, the authors develop a simple post-processing technique that iteratively adjusts negative values by cancellation with positive values in a surrounding local neighborhood. The compute time of this approach is roughly equivalent to 2 applications of FBP. The approach was evaluated by numerical simulation in 1- and 2-dimensional (2D) settings. In 2D, the source distributions included the Hoffman, the Shepp and Vardi, and a digitized version of the Jaszczak cold spheres phantoms. The authors' studies compared smoothed versions of FBP, the post-processed FBP, and ML implemented by the expectation-maximization algorithm. The root mean square (RMS) error between the true and estimated source distribution was used to evaluate performance; in 2D, additional region-of-interest-based measures of reconstruction accuracy were also employed. In making comparisons between the different methods, the amount of smoothing applied to each reconstruction method was adapted to minimize the RMS error-this was found to be critical.
Intramuscular hepatitis B immune globulin combined with lamivudine for prophylaxis against hepatitis B recurrence after liver transplantation (1999)

Immunoprophylaxis using intravenous (IV) hepatitis B immune globulin (HBIG) decreases the recurrence of hepatitis B virus (HBV) infection after orthotopic liver transplantation (OLT). However, IV HBIG is expensive, has significant side effects, and is inconvenient to administer. An alternative approach for prophylaxis using intramuscular (IM) HBIG and oral lamivudine was prospectively evaluated in this study. Ten consecutive patients with cirrhosis with HBV infection who underwent OLT were included in this study. Nine of 10 patients received lamivudine, 150 mg/d, for an average duration of 8.6 months before OLT. Two of 10 patients with detectable HBV DNA at the time of OLT received 10,000 U (45 mL) of IV HBIG daily for 7 consecutive days, followed by 5 mL of IM HBIG weekly for the next 3 weeks, then every 3 weeks. The other 8 patients were HBV DNA negative at OLT and received one dose of IV HBIG (45 mL) during surgery, followed by 5 mL of IM HBIG weekly for 4 weeks, then every 3 weeks. All patients received lamivudine, 150 mg/d, after OLT. During a mean follow-up of 15.6 months, 9 of 10 patients achieved a protective hepatitis B surface antibody (HBsAb) titer greater than 200 IU/L and had no evidence of HBV recurrence. One patient failed to develop an adequate HBsAb titer and developed histological and virological evidence of recurrence. One patient died unrelated to HBV recurrence. Our preliminary data suggest that this combination prophylaxis with IM HBIG and lamivudine is effective and potentially cost saving.
Corneal Endothelial Damage by Air Bubbles During Phacoemulsification (1997)

Air bubbles in intraocular fluids with a high surface tension can cause a ring-shaped pattern of damage to the corneal endothelium. The mechanism that caused this pattern of damage appears to be a surface tension phenomenon.
Two- to one-dimensional transition of self-assembled coordination networks at surfaces by organic ligand addition (2009)

Two-dimensional metal–organic coordination networks at a Cu(100) surface are transformed to a new supramolecular structure with one-dimensional coordination character by the addition of a second organic ligand.
The preparation and properties of a new polymorphic form of (a-bromoisovaleryl)urea. (1980)

(α-Bromoisovaleryl) urea has two polymorphic forms (I and II : leaflet crystals and needle crystals, respectively) but another form (III) of fine crystals, which shows different transition and melting properties from the conventional forms, was found in commercial (α-bromoisovaleryl) urea of JP grade. These fine crystals are transformed to parallelogramic plates at about 110° and melt at 142°. Suitable conditions for the preparation of form III were examined and its properties were studied. Form III was obtained as columnar crystals from methanol on standing for 2 days at -20°. The crystals are very fragile and show an X-ray diffraction pattern and infrared spectrum different from those of the conventional polymorphs. The transition and melting properties of these columnar crystals are the same as those of the fine crystals found in commercial (α-bromoisovaleryl) urea. It was found that form III is more stable at 4° or below than the conventional leaflet crystals (form I), though the relative stability of these polymorphic forms is reversed at room temperature.
Blockade of metastasis formation by CD44-receptor globulin (1998)

CD44 standard as well as variant isoforms have been frequently reported to be involved in the process of metastasis formation. Whereas in the rat system, but also in some human tumours, the variant exon v6 is of importance in the lymphatic spread of carcinomas, in human malignant melanoma CD44s and, possibly, CD44v10 appear to facilitate local invasion and haematogenous spread. This has been tested in the B16F10 murine melanoma model by treating B16F10-bearing C57BL/6 mice either with a CD44s-/ CD44v10-specific antibody, or with receptor globulins (Rg) containing the extracellular part of CD44s or CD44v10 linked to the constant region of the immunoglobulin kappa light chain. Prior characterization of the CD44s and CD44v10 Rg had shown that both Rgs bound to components of the extracellular matrix, CD44s in particular to hyaluronic acid. Immunohistological screening of organ sections from adult C57BL/6 mice revealed additional evidence for both Rgs binding to elements of the extracellular matrix, particularly in bone marrow, intestine and lung. In the absence of any further treatment, the CD44s Rg reduced the number of lung colonies by 70%, while application of the CD44v10 Rg resulted in 60% reduction. CD44-specific antibodies were equally efficient with regard to B16F10 settlement in the lung. However, only the CD44 Rgs prevented spread and settlement of melanoma cells in distant organs. The finding confirms the involvement of both CD44s and CD44v10 in melanoma progression, and is suggestive for the use of Rgs as therapeutic reagents.
Measurement of Industrial and Commercial Employment in the United States (1956)

The United States has become a land with annual gross national output of nearly $400 billion; a land in which more than 65 million persoins are at work. The already extensive range, scope, and variety of activities continue to expand. To describe this situation analysts seek a common denominator, and find it in the yardstick of numbers of workers employed, classified into appropriate categories.