Miracle-dz/UniFAR-FTUs huggingface dataset:
Gene replacement reveals a specific role for E-cadherin in the formation of a functional trophectoderm

During mammalian embryogenesis the trophectoderm represents the first epithelial structure formed. The cell adhesion molecule E-cadherin is ultimately necessary for the transition from compacted morula to the formation of the blastocyst to ensure correct establishment of adhesion junctions in the trophectoderm. Here, we analyzed to what extent E-cadherin confers unique adhesion and signaling properties in trophectoderm formation in vivo. Using a gene replacement approach, we introduced N-cadherin cDNA into the E-cadherin genomic locus. We show that the expression of N-cadherin driven from the E-cadherin locus reflects the expression pattern of endogenous E-cadherin. Heterozygous mice co-expressing E- and N-cadherin are vital and show normal embryonic development. Interestingly, N-cadherin homozygous mutant embryos phenocopy E-cadherin-null mutant embryos. Upon removal of the maternal E-cadherin, we demonstrate that N-cadherin is able to provide sufficient cellular adhesion to mediate morula compaction, but is insufficient for the subsequent formation of a fully polarized functional trophectoderm. When ES cells were isolated from N-cadherin homozygous mutant embryos and teratomas were produced, these ES cells differentiated into a large variety of tissue-like structures. Importantly, different epithelial-like structures expressing N-cadherin were formed, including respiratory epithelia, squamous epithelia with signs of keratinization and secretory epithelia with goblet cells. Thus, N-cadherin can maintain epithelia in differentiating ES cells, but not during the formation of the trophectoderm. Our results point to a specific and unique function for E-cadherin during mouse preimplantation development.
Familial Hypertension and Albuminuria in Normotensive Type I Diabetic Patients

An inherited predisposition to hypertension may increase susceptibility to nephropathy in type I diabetes. We evaluated the influence of a family history of essential hypertension on albuminuria in normotensive, normoalbuminuric type I diabetic patients. Forty-two diabetics (12.9±2.04 years) were divided into three groups according to tertiles of albumin excretion rate (group 1,1.27±0.35; group 2, 2.43±0.49; group 3, 6.37±3.43 μg/min; P<.001). Familial hypertension was considered to be present if the patient had one parent or grandparent on antihypertensive therapy. The three groups did not differ concerning age, diabetes duration, insulin requirement, body mass index, blood pressure, and urinary glucose excretion. Albumin excretion rate did not correlate with any parameter studied. The frequency of hypertension was significantly lower among the relatives of the patients from group 1 compared with those from groups 2 and 3 (28.6% versus 64.3% versus 78.6%, P<.03). Our data suggest that a familial antecedent of hypertension in normoalbuminuric type I diabetic patients is associated with a high normal albumin excretion rate not related to increases in blood pressure. Early changes in renal hemodynamics, seen in patients with a predisposition to hypertension, may contribute to increments in albuminuria even within the normal range.
The Impact of Educational Attainment on Observed Race/Ethnic Disparities in Inflammatory Risk in the 2001–2008 National Health and Nutrition Examination Survey

Inflammation has shown to be an independent predictor of cardiovascular disease (CVD) and growing evidence suggests Non-Hispanic Blacks (NHBs) and certain Hispanic subgroups have higher inflammation burden compared to Non-Hispanic Whites (NHWs). Socioeconomic status (SES) is a hypothesized pathway that may account for the higher inflammation burden for race/ethnic groups yet little is known about the biological processes by which SES “gets under the skin” to affect health and whether income and education have similar or distinct influences on elevated inflammation levels. The current study examines SES (income and education) associations with multiple levels of C-Reactive Protein (CRP), an important biomarker of inflammation, in a sample of 13,362 NHWs, 7696 NHBs and 4545 Mexican Americans (MAs) in the United States from the 2001 to 2008 National Health and Nutrition Examination Survey. After adjusting for age, sex, and statin use, NHBs and MAs had higher intermediate and high CRP levels compared to NHWs. Income lessened the magnitude of the association for both race/ethnic groups. The greater intermediate and high CRP burden for NHBs and MAs was strongly explained by educational attainment. MAs were more vulnerable to high CRP levels for the lowest (i.e., less than nine years) and post high school (i.e., associates degree) educational levels. After additional adjustment for smoking, heavy drinking, high waist circumference, high blood pressure, diabetes and statin use, the strength of the association between race/ethnicity and inflammation was reduced for NHBs with elevated intermediate (RR = 1.31; p ≤ 0.001) and high CRP levels (RR = 1.14; p ≤ 0.001) compared to NHWs but the effect attenuated for MAs for both intermediate (RR = 0.74; p ≤ 0.001) and high CRP levels (RR = 0.38; p ≤ 0.001). These findings suggest educational attainment is a powerful predictor of elevated CRP levels in race/ethnic populations and challenges studies to move beyond examining income as a better predictor in the SES-inflammation pathway.
Platelet function in sepsis

ObjectiveTo evaluate platelet function in sepsis. Data SourcesThe MEDLINE database and bibliographies of selected articles. Data SynthesisThe common occurrence of thrombocytopenia in critically ill patients has been recognized for many years and is known to be associated with an increased mortality rate. Platelet function can be divided into four areas: activation, adhesion, aggregation, and secretion. Studies have found that activated platelets secrete key components of the coagulation and inflammatory cascades and are involved in the regulation of vascular tone. However, studies on platelet function in sepsis have been scarce, and their data are often conflicting. In sepsis, aggregation of circulating platelets seems to be reduced, yet platelet receptors are present in normal amounts. ConclusionsPlatelets play a complex role in sepsis; they are able to modulate not only their own function but also that of cells around them. Further study is needed to better define the precise mechanisms and effects of platelet activation in sepsis and to determine the benefits and risks of inhibiting platelet function.
Atomic Structures and Energies of Σ7 Symmetrical Tilt Grain Boundaries in Alumina Bicrystals

Symmetrical Σ7 tilt grain boundaries of alumina (Al2O3) were studied using bicrystals. Three types of Σ7 boundaries were successfully fabricated, that is, rhombohedral twin (Σ7{1[Onemacr]02}) and two types of [0001] symmetrical tilt grain boundaries with grain-boundary planes {4[Fivemacr]10} and {2[Threemacr]10} (Σ7{4[Fivemacr]10} and Σ7{2[Threemacr]10}). Their atomic structures and grain-boundary energies were investigated using high-resolution transmission electron microscopy (HRTEM) and a thermal grooving technique, respectively. HRTEM observations showed that the Σ7{1[Onemacr]02} boundary had a completely symmetrical atomic arrangement with respect to the grain-boundary plane. In contrast, Σ7{2[Threemacr]10} and Σ7{4[Fivemacr]10} boundaries exhibited asymmetrical atomic structures, which were confirmed by analyzing the atomic configurations using static lattice calculations. Thermal grooving experiments showed that the grain-boundary energies strongly depended on the properties of the grain-boundary planes.
Collecting Duct Renin Is Upregulated in Both Kidneys of 2-Kidney, 1-Clip Goldblatt Hypertensive Rats

Renin in collecting duct cells is upregulated in chronic angiotensin II–infused rats via angiotensin II type 1 receptors. To determine whether stimulation of collecting duct renin is a blood pressure–dependent effect; changes in collecting duct renin and associated parameters were assessed in both kidneys of 2-kidney, 1-clip Goldblatt hypertensive (2K1C) rats. Renal medullary tissues were used to avoid the contribution of renin from juxtaglomerular cells. Systolic blood pressure increased to 184±9 mm Hg in 2K1C rats (n=19) compared with sham rats (121±6 mm Hg; n=12). Although renin immunoreactivity markedly decreased in juxtaglomerular cells of nonclipped kidneys (NCK: 0.2±0.0 versus 1.0±0.0 relative ratio) and was augmented in clipped kidneys (CK: 1.7±1.0 versus 1.0±0.0 relative ratio), its immunoreactivity increased in cortical and medullary collecting ducts of both kidneys of 2K1C rats (CK: 2.8±1.0 cortex; 2.1±1.0 medulla; NCK: 4.6±2.0 cortex, 3.2±1.0 medulla versus 1.0±0.0 in sham kidneys). Renal medullary tissues of 2K1C rats showed greater levels of renin protein (CK: 1.4±0.2; NCK: 1.5±0.3), renin mRNA (CK: 5.8±2.0; NCK: 4.9±2.0), angiotensin I (CK: 120±18 pg/g; NCK: 129±13 pg/g versus sham: 67±6 pg/g), angiotensin II (CK: 150±32 pg/g; NCK: 123±21 pg/g versus sham: 91±12 pg/g; P<0.05), and renin activity (CK: 8.6 &mgr;g of angiotensin I per microgram of protein; NCK: 8.3 &mgr;g of angiotensin I per microgram of protein; sham: 3.4 &mgr;g of angiotensin I per microgram of protein) than sham rats. These data indicate that enhanced collecting duct renin in 2K1C rats occurs independently of blood pressure. Upregulation of distal tubular renin helps to explain how sustained intrarenal angiotensin II formation occurs even during juxtaglomerular renin suppression, thus allowing maintained effects on tubular sodium reabsorption that contribute to the hypertension.
How much does transmit correlation affect the sum-rate scaling of MIMO gaussian broadcast channels?

This paper considers the effect of spatial correlation between transmit antennas on the sum-rate capacity of the MIMO Gaussian broadcast channel (i.e., downlink of a cellular system). Specifically, for a system with a large number of users n, we analyze the scaling laws of the sum-rate for the dirty paper coding and for different types of beamforming transmission schemes. When the channel is i.i. d. , it has been shown that for large n, the sum rate is equal to M log log n + M log P/M + o(1) where M is the number of transmit antennas, P is the average signal to noise ratio, and o(1) refers to terms that go to zero as n rarr infin. When the channel exhibits some spatial correlation with a covariance matrix R (non-singular with tr(R) = M), we prove that the sum rate of dirty paper coding is M log log n + M log P/M + log det(R) + o(1). We further show that the sum-rate of various beamforming schemes achieves M log log n + M log P/M + M log c + o(1) where c les 1 depends on the type of beamforming. We can in fact compute c for random beamforming proposed in and more generally, for random beamforming with preceding in which beams are pre-multiplied by a fixed matrix. Simulation results are presented at the end of the paper.
Cell signaling pathways elicited by asbestos.

In recent years, it has become apparent that minerals can trigger alterations in gene expression by initiating signaling events upstream of gene transactivation. These cascades may be initiated at the cell surface after interaction of minerals with the plasma membrane either through receptorlike mechanisms or integrins. Alternatively, signaling pathways may be stimulated by active oxygen species generated both during phagocytosis of minerals and by redox reactions on the mineral surface. At least two signaling cascades linked to activation of transcription factors, i.e., DNA-binding proteins involved in modulating gene expression and DNA replication, are stimulated after exposure of lung cells to asbestos fibers in vitro. These include nuclear factor kappa B (NF kappa B) and the mitogen-activated protein kinase (MAPK) cascade important in regulation of the transcription factor, activator protein-1 (AP-1). Both NF kappa B and AP-1 bind to specific DNA sequences within the regulatory or promoter regions of genes that are critical to cell proliferation and inflammation. Unraveling the cell signaling cascades initiated by mineral dusts and pharmacologic inhibition of these events may be important for the control and treatment of mineral-associated occupational diseases. ImagesFigure 2. BFigure 3. AFigure 3. B
Additive Pressures of Elevated Sea Surface Temperatures and Herbicides on Symbiont-Bearing Foraminifera

Elevated ocean temperatures and agrochemical pollution individually threaten inshore coral reefs, but these pressures are likely to occur simultaneously. Experiments were conducted to evaluate the combined effects of elevated temperature and the photosystem II (PSII) inhibiting herbicide diuron on several types of symbiotic algae (diatom, dinoflagellate or rhodophyte) of benthic foraminifera in hospite. Diuron was shown to evoke a direct effect on photosynthetic efficiency (reduced effective PSII quantum yield ΔF/F′m), while elevated temperatures (>30°C, only 2°C above current average summer temperatures) were observed to impact photosynthesis more indirectly by causing reductions in maximum PSII quantum yield (Fv/Fm), interpreted as photodamage. Additionally, elevated temperatures were shown to cause bleaching through loss of chlorophyll a in foraminifera hosting either diatoms or dinoflagellates. A significant linear correlation was found between reduced Fv/Fm and loss of chlorophyll a. In most cases, symbionts within foraminifera proved more sensitive to thermal stress in the presence of diuron (≥1 µg L−1). The mixture toxicity model of Independent Action (IA) described the combined effects of temperature and diuron on the photosystem of species hosting diatoms or dinoflagellates convincingly and in agreement with probabilistic statistics, so a response additive joint action can be assumed. We thus demonstrate that improving water quality can improve resilience of symbiotic phototrophs to projected increases in ocean temperatures. As IA described the observed combined effects from elevated temperature and diuron stress it may therefore be employed for prediction of untested mixtures and for assessing the efficacy of management measures.
IPOG/IPOG‐D: efficient test generation for multi‐way combinatorial testing

This paper presents two strategies for multi‐way testing (i.e. t‐way testing with t>2). The first strategy generalizes an existing strategy, called in‐parameter‐order, from pairwise testing to multi‐way testing. This strategy requires all multi‐way combinations to be explicitly enumerated. When the number of multi‐way combinations is large, however, explicit enumeration can be prohibitive in terms of both the space for storing these combinations and the time needed to enumerate them. To alleviate this problem, the second strategy combines the first strategy with a recursive construction procedure to reduce the number of multi‐way combinations that have to be enumerated. Both strategies are deterministic, i.e. they always produce the same test set for the same system configuration. This paper reports a multi‐way testing tool called FireEye, and provides an analytic and experimental evaluation of the two strategies. Copyright © 2007 John Wiley & Sons, Ltd.
Time and money: a retrospective evaluation of the inputs, outputs, efficiency, and incomes of physicians.

BACKGROUND Physicians' concerns with the health care system focus on having less time with their patients and needing to work harder to maintain incomes. We sought to determine whether physicians are working longer hours and whether their incomes are declining. METHODS Using survey data, we conducted a retrospective analysis of physician inputs, outputs, efficiency, and incomes for generalists, general internists, general surgeons, pediatricians, and obstetrician-gynecologists from 1987 to 1998. RESULTS Physician inputs (as measured by the average hours worked in professional activities) showed little absolute change across specialties over time. Outputs (as measured by the total number of patient visits per week) decreased between 9% and 28%, depending on the specialty. Efficiency (the proportion of time spent in direct patient care and the amount of time spent during a typical office visit) remained stable over the time examined. Consumer price index inflation-adjusted annual incomes increased considerably over the time period examined (42% for general internists, 28% for pediatricians, 13% for generalists, and 8% for general surgeons); only obstetricians-gynecologists showed a net loss of annual income when adjusting for inflation (a 6% loss). CONCLUSIONS Our findings do not confirm the prevailing concern that physicians are working harder or longer or that their incomes are declining, but they offer an explanation of how physicians are maintaining incomes without increasing work inputs. There is a great deal of dissatisfaction with the health care system among physicians; exploration of perceptual reasons for that dissatisfaction may outline a course of action needed to resolve it.
The critical role of the routing scheme in simulating peak river discharge in global hydrological models

Global hydrological models (GHMs) have been applied to assess global flood hazards, but their capacity to capture the timing and amplitude of peak river discharge—which is crucial in flood simulations—has traditionally not been the focus of examination. Here we evaluate to what degree the choice of river routing scheme affects simulations of peak discharge and may help to provide better agreement with observations. To this end we use runoff and discharge simulations of nine GHMs forced by observational climate data (1971–2010) within the ISIMIP2a project. The runoff simulations were used as input for the global river routing model CaMa-Flood. The simulated daily discharge was compared to the discharge generated by each GHM using its native river routing scheme. For each GHM both versions of simulated discharge were compared to monthly and daily discharge observations from 1701 GRDC stations as a benchmark. CaMa-Flood routing shows a general reduction of peak river discharge and a delay of about two to three weeks in its occurrence, likely induced by the buffering capacity of floodplain reservoirs. For a majority of river basins, discharge produced by CaMa-Flood resulted in a better agreement with observations. In particular, maximum daily discharge was adjusted, with a multi-model averaged reduction in bias over about 2/3 of the analysed basin area. The increase in agreement was obtained in both managed and near-natural basins. Overall, this study demonstrates the importance of routing scheme choice in peak discharge simulation, where CaMa-Flood routing accounts for floodplain storage and backwater effects that are not represented in most GHMs. Our study provides important hints that an explicit parameterisation of these processes may be essential in future impact studies.
Campylobacter Colonization of the Turkey Intestine in the Context of Microbial Community Development

ABSTRACT Patterns of microbial community dynamics in the turkey intestine were examined. Every week of the 18-week production cycle, cecal bacterial communities and Campylobacter loads were examined from five birds for each of two flocks. Molecular fingerprinting via the automated ribosomal intergenic spacer analysis (ARISA) and terminal restriction fragment length polymorphism (T-RFLP) of the cecal samples revealed that microbial communities changed in a time-dependent manner, and during both trials they developed via transition through three phases during the production cycle. A core component of the microbiota consisting of 11 Bacteroidetes types was present throughout both trials. In contrast, constant succession was detected in the Clostridiales populations until week 10 or 11, with few shared sequences between the flocks. Changes in Campylobacter jejuni and Campylobacter coli loads were correlated to, but not dependent on, the two acute transitions delimiting the three developmental phases.
Evidence of Substantial Carbon Isotope Fractionation among Substrate, Inorganic Carbon, and Biomass during Aerobic Mineralization of 1,2-Dichloroethane byXanthobacter autotrophicus

ABSTRACT Carbon isotope fractionation during aerobic mineralization of 1,2-dichloroethane (1,2-DCA) by Xanthobacter autotrophicusGJ10 was investigated. A strong enrichment of 13C in residual 1,2-DCA was observed, with a mean fractionation factor α ± standard deviation of 0.968 ± 0.0013 to 0.973 ± 0.0015. In addition, a large carbon isotope fractionation between biomass and inorganic carbon occurred. A mechanistic model that links the fractionation factor α to the rate constants of the first catabolic enzyme was developed. Based on the model, it was concluded that the strong enrichment of 13C in 1,2-DCA arises because the first irreversible step of the initial enzymatic transformation of 1,2-DCA consists of an SN2 nucleophilic substitution. SN2 reactions are accompanied by a large kinetic isotope effect. The substantial carbon isotope fractionation between biomass and inorganic carbon could be explained by the kinetic isotope effect associated with the initial 1,2-DCA transformation and by the metabolic pathway of 1,2-DCA degradation. Carbon isotope fractionation during 1,2-DCA mineralization leads to 1,2-DCA, inorganic carbon, and biomass with characteristic carbon isotope compositions, which may be used to trace the process in contaminated environments.
Types of cervical disk lesions and their surgical approaches.

Cervical disk lesions fall into five distinct categories differing widely in numerical composition, in symptomatology, and in operative approaches. Lateral disk lesions constitute 95% of all operable lesions and simple "keyhole" facetectomy or foraminotomy with slow and high-speed drills constitutes the treatment of choice. Central ridge or bar defects, misnamed "spondylosis," may be approached by either the anterior or posterior approach, providing decompression from the infolded ligamentum flavum, the calcified central ridge, and the lateral osteophytes. Central soft disk lesions are so rare as to constitute only 1% of cervical disk surgery. They should be approached anteriorly but the posterior combined intradural and extradural approach is advocated when there is need to differentiate from a tumor. Patients with fracture-dislocations with disk protrusion should be operated on through an anterior approach. There is rarely improvement, but it is occasionally advocated to permit earlier rehabilitation.
Children Making Faces : The Effect of age and Prompts on Children's Facial Composites of Unfamiliar Faces

The police do not usually ask child witnesses (under 10-years) to construct facial composites, as it is believed that they could not create images of sufficient accuracy. The main aim of the current experiment was to evaluate whether this age limit is a suitable threshold by comparing composites made by children of age 6-, 8- and 10-years and adults. Additionally, as children's lack of vocabulary to describe faces was considered a likely factor, a technique based on visual prompts was devised to obtain facial descriptions, and compared to construction based on verbal prompting. The experiment involved participants' construction of composites, which were subsequently evaluated subjectively (ranking and rating tasks) and objectively (matching task). Although adults' and older children's composites were, on average, more accurate than those of the younger children, the results demonstrated that children from the age of 6-years were able to produce facial composites of an unfamiliar face. Copyright © 2007 John Wiley & Sons, Ltd.