54 research outputs found
\u3ci\u3eFisons\u3c/i\u3e: Will It Tame the Beast of Discovery Abuse?
In WSPIEA v. Fisons, the Washington Supreme Court held that evasive and misleading discovery tactics violate Civil Rule 26(g). This Note examines the discovery tactics used in Fisons against the backdrop of the historic failure of courts to impose adequate sanctions for discovery abuse. It argues that courts must do more to deter discovery abuse by clearly articulating the requirements of the rules governing discovery, imposing severe sanctions for discovery abuse, and closely monitoring discovery in large, complex cases
Visualization of microbe-dietary remnant interactions in digesta from pigs, by fluorescence in situ hybridization and staining methods; effects of a dietary arabinoxylan-rich wheat fraction
This study investigated how the addition of a specific hydrocolloid, arabinoxylan (AX), to the pig diets containing red meat, affected the gut microbiota in terms of changes to the bacterial community dynamics. Fluorescence in situ hybridization (FISH) was used to enumerate both broad groups and particular bacterial species, and showed systematic differences in pigs fed AX. In addition, the role of bacteria in the fermentation of dietary substrates was studied by visualizing direct associations between the bacteria and substrate particles. To achieve this, novel methods of combining histological staining or enzymatic labelling with FISH protocols were established. In this way, undigested and/or unfermented remnants of meat, endogenous mucin, and several plant cell wall hydrocolloids (cellulose, lignin and arabinoxylan) were distinguished, together with large intestine microbiota under brightfield and/or confocal laser scanning microscopy (CLSM). It was evident that no apparent direct associations occurred between specific classes or groups of bacteria and meat, mucin, lignin or AX remnants. In contrast, bacteria belonging to Clostridium clusters XIVa and XIVb formed a strong (P < 0.01) direct association with cellulose remnants in the pig digesta in the caecum
Damaging variants in FOXI3 cause microtia and craniofacial microsomia
Q1Q1Pacientes con Microtia y MicrosomĂa craneofacialPurpose:
Craniofacial microsomia (CFM) represents a spectrum of craniofacial malformations, ranging from isolated microtia with or without aural atresia to underdevelopment of the mandible, maxilla, orbit, facial soft tissue, and/or facial nerve. The genetic causes of CFM remain largely unknown.
Methods:
We performed genome sequencing and linkage analysis in patients and families with microtia and CFM of unknown genetic etiology. The functional consequences of damaging missense variants were evaluated through expression of wild-type and mutant proteins in vitro.
Results:
We studied a 5-generation kindred with microtia, identifying a missense variant in FOXI3 (p.Arg236Trp) as the cause of disease (logarithm of the odds = 3.33). We subsequently identified 6 individuals from 3 additional kindreds with microtia-CFM spectrum phenotypes harboring damaging variants in FOXI3, a regulator of ectodermal and neural crest development. Missense variants in the nuclear localization sequence were identified in cases with isolated microtia with aural atresia and found to affect subcellular localization of FOXI3. Loss of function variants were found in patients with microtia and mandibular hypoplasia (CFM), suggesting dosage sensitivity of FOXI3.
Conclusion:
Damaging variants in FOXI3 are the second most frequent genetic cause of CFM, causing 1% of all cases, including 13% of familial cases in our cohort.https://orcid.org/0000-0003-3822-7780https://orcid.org/0000-0002-0729-6866Revista Internacional - IndexadaA1N
Measurement of the cosmic ray spectrum above eV using inclined events detected with the Pierre Auger Observatory
A measurement of the cosmic-ray spectrum for energies exceeding
eV is presented, which is based on the analysis of showers
with zenith angles greater than detected with the Pierre Auger
Observatory between 1 January 2004 and 31 December 2013. The measured spectrum
confirms a flux suppression at the highest energies. Above
eV, the "ankle", the flux can be described by a power law with
index followed by
a smooth suppression region. For the energy () at which the
spectral flux has fallen to one-half of its extrapolated value in the absence
of suppression, we find
eV.Comment: Replaced with published version. Added journal reference and DO
Energy Estimation of Cosmic Rays with the Engineering Radio Array of the Pierre Auger Observatory
The Auger Engineering Radio Array (AERA) is part of the Pierre Auger
Observatory and is used to detect the radio emission of cosmic-ray air showers.
These observations are compared to the data of the surface detector stations of
the Observatory, which provide well-calibrated information on the cosmic-ray
energies and arrival directions. The response of the radio stations in the 30
to 80 MHz regime has been thoroughly calibrated to enable the reconstruction of
the incoming electric field. For the latter, the energy deposit per area is
determined from the radio pulses at each observer position and is interpolated
using a two-dimensional function that takes into account signal asymmetries due
to interference between the geomagnetic and charge-excess emission components.
The spatial integral over the signal distribution gives a direct measurement of
the energy transferred from the primary cosmic ray into radio emission in the
AERA frequency range. We measure 15.8 MeV of radiation energy for a 1 EeV air
shower arriving perpendicularly to the geomagnetic field. This radiation energy
-- corrected for geometrical effects -- is used as a cosmic-ray energy
estimator. Performing an absolute energy calibration against the
surface-detector information, we observe that this radio-energy estimator
scales quadratically with the cosmic-ray energy as expected for coherent
emission. We find an energy resolution of the radio reconstruction of 22% for
the data set and 17% for a high-quality subset containing only events with at
least five radio stations with signal.Comment: Replaced with published version. Added journal reference and DO
Measurement of the Radiation Energy in the Radio Signal of Extensive Air Showers as a Universal Estimator of Cosmic-Ray Energy
We measure the energy emitted by extensive air showers in the form of radio
emission in the frequency range from 30 to 80 MHz. Exploiting the accurate
energy scale of the Pierre Auger Observatory, we obtain a radiation energy of
15.8 \pm 0.7 (stat) \pm 6.7 (sys) MeV for cosmic rays with an energy of 1 EeV
arriving perpendicularly to a geomagnetic field of 0.24 G, scaling
quadratically with the cosmic-ray energy. A comparison with predictions from
state-of-the-art first-principle calculations shows agreement with our
measurement. The radiation energy provides direct access to the calorimetric
energy in the electromagnetic cascade of extensive air showers. Comparison with
our result thus allows the direct calibration of any cosmic-ray radio detector
against the well-established energy scale of the Pierre Auger Observatory.Comment: Replaced with published version. Added journal reference and DOI.
Supplemental material in the ancillary file
Cells of the adult human heart
Abstract: Cardiovascular disease is the leading cause of death worldwide. Advanced insights into disease mechanisms and therapeutic strategies require a deeper understanding of the molecular processes involved in the healthy heart. Knowledge of the full repertoire of cardiac cells and their gene expression profiles is a fundamental first step in this endeavour. Here, using state-of-the-art analyses of large-scale single-cell and single-nucleus transcriptomes, we characterize six anatomical adult heart regions. Our results highlight the cellular heterogeneity of cardiomyocytes, pericytes and fibroblasts, and reveal distinct atrial and ventricular subsets of cells with diverse developmental origins and specialized properties. We define the complexity of the cardiac vasculature and its changes along the arterio-venous axis. In the immune compartment, we identify cardiac-resident macrophages with inflammatory and protective transcriptional signatures. Furthermore, analyses of cell-to-cell interactions highlight different networks of macrophages, fibroblasts and cardiomyocytes between atria and ventricles that are distinct from those of skeletal muscle. Our human cardiac cell atlas improves our understanding of the human heart and provides a valuable reference for future studies
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Cells of the adult human heart
Abstract: Cardiovascular disease is the leading cause of death worldwide. Advanced insights into disease mechanisms and therapeutic strategies require a deeper understanding of the molecular processes involved in the healthy heart. Knowledge of the full repertoire of cardiac cells and their gene expression profiles is a fundamental first step in this endeavour. Here, using state-of-the-art analyses of large-scale single-cell and single-nucleus transcriptomes, we characterize six anatomical adult heart regions. Our results highlight the cellular heterogeneity of cardiomyocytes, pericytes and fibroblasts, and reveal distinct atrial and ventricular subsets of cells with diverse developmental origins and specialized properties. We define the complexity of the cardiac vasculature and its changes along the arterio-venous axis. In the immune compartment, we identify cardiac-resident macrophages with inflammatory and protective transcriptional signatures. Furthermore, analyses of cell-to-cell interactions highlight different networks of macrophages, fibroblasts and cardiomyocytes between atria and ventricles that are distinct from those of skeletal muscle. Our human cardiac cell atlas improves our understanding of the human heart and provides a valuable reference for future studies
Mothers construct fathers: Destabilized patriarchy in La Leche League
This paper examines changing masculine ideals from the point of view of women homemakers through a case study of La Leche League, a maternalist organization dedicated to breastfeeding and mother primacy. We suggest two reasons for studying the League: first, an emerging literature suggests that changing norms are seeping into many such seemingly conservative groups, and second, the League continues to be highly successful among white, middle-class, married women. The paper looks at two aspects of masculinity, examining changes in the League through fieldwork, interviews, and content analysis, and finds that new norms of increased father involvement and decreased rights over women's bodies have both influenced League philosophy. We conclude that while in some respects a measure of the decline of men's patriarchal privileges, the League's changes also may contribute to a ârestabilizationâ of male dominance in a modified, partial form.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/43548/1/11133_2004_Article_BF00990071.pd
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