This article studies the interplay of U.S. primary and general elections. I examine how the nomination of an extremist changes general-election outcomes and legislative behavior in the U.S. House, ...1980–2010, using a regression discontinuity design in primary elections. When an extremist—as measured by primary-election campaign receipt patterns—wins a “coin-flip” election over a more moderate candidate, the party’s general-election vote share decreases on average by approximately 9–13 percentage points, and the probability that the party wins the seat decreases by 35–54 percentage points. This electoral penalty is so large that nominating the more extreme primary candidate causes the district’s subsequent roll-call representation to reverse, on average, becoming more liberal when an extreme Republican is nominated and more conservative when an extreme Democrat is nominated. Overall, the findings show how general-election voters act as a moderating filter in response to primary nominations.
The level of body-mass index (BMI) associated with the lowest risk of death remains unclear. Although differences in muscle mass limit the utility of BMI as a measure of adiposity, no study has ...directly examined the effect of muscle mass on the BMI-mortality relationship.
Body composition was measured by dual-energy x-ray absorptiometry in 11,687 participants of the National Health and Nutrition Examination Survey 1999-2004. Low muscle mass was defined using sex-specific thresholds of the appendicular skeletal muscle mass index (ASMI). Proportional hazards models were created to model associations with all-cause mortality.
At any level of BMI ≥22, participants with low muscle mass had higher body fat percentage (%TBF), an increased likelihood of diabetes, and higher adjusted mortality than other participants. Increases in %TBF manifested as 30-40% smaller changes in BMI than were observed in participants with preserved muscle mass. Excluding participants with low muscle mass or adjustment for ASMI attenuated the risk associated with low BMI, magnified the risk associated with high BMI, and shifted downward the level of BMI associated with the lowest risk of death. Higher ASMI was independently associated with lower mortality. Effects were similar in never-smokers and ever-smokers. Additional adjustment for waist circumference eliminated the risk associated with higher BMI. Results were unchanged after excluding unintentional weight loss, chronic illness, early mortality, and participants performing muscle-strengthening exercises or recommended levels of physical activity.
Muscle mass mediates associations of BMI with adiposity and mortality and is inversely associated with the risk of death. After accounting for muscle mass, the BMI associated with the greatest survival shifts downward toward the normal range. These results provide a concrete explanation for the obesity paradox.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Starch is a nutritionally important carbohydrate in feeds that is increasingly measured and used for formulation of animal diets. Discontinued production of the enzyme Rhozyme-S required for AOAC ...Method 920.40 invalidated this method for starch in animal feeds. The objective of this study was to compare methods for the determination of starch as potential candidates as a replacement method and for an AOAC collaborative study. Many starch methods are available, but they vary in accuracy, replicability, and ease of use. After assays were evaluated that differed in gelatinization method, number of reagents, and sample handling, and after assays with known methodological defects were excluded, 3 enzymatic-colorimetric assays were selected for comparison. The assays all used 2-stage, heat-stable, α-amylase and amyloglucosidase hydrolyses, but they differed in the gelatinization solution (heating in water, 3-(N-morpholino) propanesulfonic acid buffer, or acetate buffer). The measured values included both starch and maltooligosaccharides. The acetate buffer-only method was performed in sealable vessels with dilution by weight; it gave greater starch values (2-6 percentage units of sample dry matter) in the analysis of feed/food substrates than did the other methods. This method is a viable candidate for a collaborative study.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Breast tumor interleukin-6 (IL-6) levels increase with tumor grade, and elevated serum IL-6 correlates with poor breast cancer patient survival. Epithelial-mesenchymal transition (EMT) phenotypes ...such as impaired E-cadherin expression or aberrant Vimentin induction are associated with enhanced metastasis and unfavorable clinical outcome in breast cancer. Despite this fact, few tumor microenvironment-derived extracellular signaling factors capable of provoking such a phenotypic transition have been identified. In this study, we showed that IL-6 promoted E-cadherin repression among a panel of estrogen receptor-alpha-positive human breast cancer cells. Furthermore, ectopic stable IL-6 expressing MCF-7 breast adenocarcinoma cells (MCF-7(IL-6)) exhibited an EMT phenotype characterized by impaired E-cadherin expression and induction of Vimentin, N-cadherin, Snail and Twist. MCF-7(IL-6) cells formed xenograft tumors that displayed loss of E-cadherin, robust Vimentin induction, increased proliferative indices, advanced tumor grade and undifferentiated histology. Finally, we showed aberrant IL-6 production and STAT3 activation in MCF-7 cells that constitutively express Twist, a metastatic regulator and direct transcriptional repressor of E-cadherin. To our knowledge, this is the first study that shows IL-6 as an inducer of an EMT phenotype in breast cancer cells and implicates its potential to promote breast cancer metastasis.
The NiFe hydrogenase (H2ase) has been characterized in the Ni-R state with a hydride bridging between Fe and Ni but displaced toward the Ni. In nearly all of the synthetic Ni-R models reported so ...far, the hydride ligand is either displaced toward Fe, or terminally bound to Fe. Recently, a structural and functional NiFe-H2ase mimic ( Nat. Chem. 2016, 8, 1054−1060 ) was reported to produce H2 catalytically via EECC mechanism through a Ni-centered hydride intermediate like the enzyme. Here, a comprehensive DFT study shows a much lower energy route via an EECEC mechanism through an Fe-centered hydride intermediate. Although catalytic H2 production occurs at the potential corresponding to the complex’s second reduction, a third electron is needed to induce the second proton addition from the weak acid. The first two-electron reductions and a proton addition produce a semibridging hydride with a short Fe–H bond like other structured NiFe-biomimetics, but this species is not basic enough to add another proton from the weak acid without the third electron. The calculated mechanism provides insight into the origin of this structure in the enzyme.
Human epithelial tissues accumulate cancer-driver mutations with age
, yet tumour formation remains rare. The positive selection of these mutations suggests that they alter the behaviour and fitness ...of proliferating cells
. Thus, normal adult tissues become a patchwork of mutant clones competing for space and survival, with the fittest clones expanding by eliminating their less competitive neighbours
. However, little is known about how such dynamic competition in normal epithelia influences early tumorigenesis. Here we show that the majority of newly formed oesophageal tumours are eliminated through competition with mutant clones in the adjacent normal epithelium. We followed the fate of nascent, microscopic, pre-malignant tumours in a mouse model of oesophageal carcinogenesis and found that most were rapidly lost with no indication of tumour cell death, decreased proliferation or an anti-tumour immune response. However, deep sequencing of ten-day-old and one-year-old tumours showed evidence of selection on the surviving neoplasms. Induction of highly competitive clones in transgenic mice increased early tumour removal, whereas pharmacological inhibition of clonal competition reduced tumour loss. These results support a model in which survival of early neoplasms depends on their competitive fitness relative to that of mutant clones in the surrounding normal tissue. Mutant clones in normal epithelium have an unexpected anti-tumorigenic role in purging early tumours through cell competition, thereby preserving tissue integrity.
Annual influenza epidemics in the United States result in an average of >36,000 deaths and 114,000 hospitalizations. Influenza can spread rapidly to patients and health care personnel in health care ...settings after influenza is introduced by visitors, staff, or patients. Influenza outbreaks in health care facilities can have potentially devastating consequences, particularly for immunocompromised persons. Although vaccination of health care personnel and patients is the primary means to prevent and control outbreaks of influenza in health care settings, antiviral influenza medications and isolation precautions are important adjuncts. Although droplet transmission is thought to be the primary mode of influenza transmission, limited evidence is available to support the relative clinical importance of contact, droplet, and droplet nuclei (airborne) transmission of influenza. In this article, the results of studies on the modes of influenza transmission and their relevant isolation precautions are reviewed.
The SARS-CoV-2 nucleocapsid (N) protein is an abundant RNA-binding protein critical for viral genome packaging, yet the molecular details that underlie this process are poorly understood. Here we ...combine single-molecule spectroscopy with all-atom simulations to uncover the molecular details that contribute to N protein function. N protein contains three dynamic disordered regions that house putative transiently-helical binding motifs. The two folded domains interact minimally such that full-length N protein is a flexible and multivalent RNA-binding protein. N protein also undergoes liquid-liquid phase separation when mixed with RNA, and polymer theory predicts that the same multivalent interactions that drive phase separation also engender RNA compaction. We offer a simple symmetry-breaking model that provides a plausible route through which single-genome condensation preferentially occurs over phase separation, suggesting that phase separation offers a convenient macroscopic readout of a key nanoscopic interaction.
Abstract
We analyze Very Large Telescope/UVES observations of the quasar SDSS J024221.87+004912.6. We identify four absorption outflow systems: a C
iv
broad absorption line (BAL) at
v
≈ −18,000 km s
...−1
and three narrower low-ionization systems with centroid velocities ranging from –1200 to –3500 km s
−1
. These outflows show similar physical attributes to the O
iii
outflows studied by Liu et al. (2013). We find that two of the systems are energetic enough to contribute to active galactic nucleus feedback, with one system reaching above 5% of the quasar’s Eddington luminosity. We also find that this system is at a distance of 67 kpc away from the quasar, the farthest detected mini-BAL absorption outflow from its central source to date. In addition, we examine the time-variability of the BAL and find that its velocity monotonically increases, while the trough itself becomes shallower over time.
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