Miracle-dz/UniFAR-FTUs huggingface dataset:
A recently evolved novel trophoblast-enriched secreted form of fms-like tyrosine kinase-1 variant is up-regulated in hypoxia and preeclampsia.

CONTEXT Recent published studies indicate a possible role for sFlt1 in the development of preeclampsia. OBJECTIVE The objective of the study was to investigate the expression and regulation of sFlt1-e15a, a recently described novel C-terminal variant isoform of sFlt1. DESIGN The studies included a computational comparative analysis of the genomic locus of sFlt1 across vertebrate species; an assessment of sFlt1 variants in human and rhesus cells and tissues; an analysis of sFlt1 variants transiently expressed in HeLa and COS-7 cells; an evaluation of the effect of hypoxia on sFlt1 expression in trophoblasts; and a comparison of placental sFlt1 expression between pregnancies complicated by preeclampsia and control pregnancies. RESULT AND CONCLUSIONS sFlt1-e15a emerged as an alternate transcript of Flt1 late in evolution with the insertion of an AluSq sequence into the primate genome after the emergence of the simian infraorder about 40 million years ago. sFlt1-e15a is particularly abundant in human placenta and trophoblasts and is also highly expressed in nonhuman primate placenta. The expressed protein has a C-terminal polyserine tail and, like reference sequence sFlt1 (sFlt1-i13), is glycosylated and secreted. Consistent with a role in placental pathophysiology, hypoxia stimulates sFlt1-e15a expression in isolated cytotrophoblasts and a trophoblast cell line, and differentiation into syncytiotrophoblasts further enhances the effect of hypoxia. Placental levels of sFlt1-e15a and sFlt1-i13 transcripts are significantly elevated in patients with preeclampsia compared with normal pregnancies. We speculate that sFlt1-e15a may contribute to the pathophysiology of preeclampsia.
A robot fish encapsulated by an electromagnetic wave-transmitting plastic film

This manuscript describes a robot fish, the surface of which is composed of a flexible thin plastic film. Its internal mechanism, including an actuator (e.g. a servomotor), is encapsulated in the plastic film by a vacuum packaging machine. This plastic film has electromagnetic wave-transmitting properties, allowing sensors, wireless charging modules, and communication devices to be arranged within the device. To simplify the waterproofing and pressure resistance properties of the robot, the inner portion of the robot fish is filled with insulating fluid, such as industrial oil. The transmission performances of these devices, which utilize electromagnetic waves, may worsen due to the tendency of water or insulating fluids to attenuate the electromagnetic waves. This study therefore experimentally investigated the transmission performance of these devices, while taking into account the effects of water or insulating fluid. These devices were subsequently applied to our fish robot; enabling us to verify its performance by using infrared sensors to assess its autonomous locomotion.
G Protein‐Independent Inhibition of GIRK Current by Adenosine in Rat Atrial Myocytes Overexpressing A1 Receptors after Adenovirus‐Mediated Gene Transfer

G protein‐activated inwardly rectifying K+ (GIRK) channels, important regulators of membrane excitability in the heart and central nervous system, are activated by interaction with βγ subunits from heterotrimeric G proteins upon receptor stimulation. In atrial myocytes various endogenous receptors couple to GIRK channels, including the canonical muscarinic M2 receptor (M2AChR) and the A1 adenosine receptor (A1AdoR). Saturating stimulation of A1AdoR in atrial myocytes activates only a fraction of the GIRK current that is activated via M2AChR, which reflects a lower density of A1AdoR. In the present study A1AdoR were overexpressed by means of adenovirus‐mediated gene transfer using green fluorescent protein (GFP) as the reporter. Confirmatory to a previous study, this resulted in an increased sensitivity of macroscopic GIRK current (ACh‐activated K+ current (IK(ACh))) to stimulation by Ado. However, in the majority of GFP‐positive myocytes, exposure to Ado at concentrations ≥ 1 μm resulted in activation of IK(ACh) followed by a rapid inhibition. In those cells a rebound activation of current was recorded upon washout of Ado. The inhibitory component could be recorded in isolation when IK(ACh) was activated by M2AChR‐stimulation and brief pulses of Ado were superimposed. In myocytes loaded with GTP‐γ‐S, IK(ACh), irreversibly activated by brief exposure to agonist, was still reversibly inhibited by Ado, suggesting that inhibition is independent of G protein cycling. In myocytes co‐transfected with adenoviral vectors encoding A1AdoR and GIRK4 subunit, no inhibition of GIRK current by Ado was observed. As acute desensitization of atrial GIRK current, which is reminiscent of the inhibition described here, has been shown to be absent in myocytes overexpressing GIRK4, this suggests that acute desensitization and the novel inhibition might share a common pathway whose target is the GIRK channel complex or its GIRK1 subunit.
An application of the behavioral model to the utilization of health care services in Turkey: A focus on equity

The aim of this study is to investigate the equity phenomenon, which can be defined as an equal treatment for equal need irrespective of socio-economic status, in the utilization of health care services in Turkey (for out-patient and in-patient treatment services, separately) in the context of the behavioral model. We have used the “Health Surveys” obtained from the Turkish Statistical Institute for 2010, 2012 and 2014. The equity phenomenon and the determinants of the health care utilization are investigated by using the probit model. The findings indicate that the need variable has the largest marginal effect in magnitude for all types of health care. This implies that the health system structure in Turkey is based on need and, therefore, equity exists in the utilization of health care services. We have also found that health insurance has the second largest marginal effect after the need variable. This means that policy makers should focus on enabling factors, especially the coverage of health insurance and the level of income to increase health care utilization of the disadvantaged segments of the population. Key words: Equity, Health care utilization, Behavioral model.JEL: I12, I14.
Gate-all-around Si nanowire array tunnelling FETs with high on-current of 75 µA/µm @ VDD=1.1V

Gate-all-around Si nanowire array p-type tunneling field effect transistors (GAA NW p-TFETs) have been fabricated on thin SOI. High on-current of 75 μA/μm at V<sub>D</sub>=V<sub>G</sub>=1.1V (=V<sub>DD</sub>) was observed. Asymmetric junctions were formed to suppress ambipolar switching typical for all silicon TFETs. Nickel aluminum silicide NiAl<sub>0.2</sub>Si<sub>1.8</sub> was used to create high quality single crystalline metal source/drain contacts with matched lattice parameter to the silicon substrate. Implantation into silicide (IIS) method created the n<sup>++</sup>-junctions after outdiffusion of the dopants with a low temperature thermal anneal at 500°C in forming gas (FG). TCAD simulations confirm TFET operation and qualitatively demonstrate the suppression of ambipolarity by optimization of the drain contact.
Feasibility of 7 Tesla Breast Magnetic Resonance Imaging Determination of Intrinsic Sensitivity and High-Resolution Magnetic Resonance Imaging, Diffusion-Weighted Imaging, and 1H-Magnetic Resonance Spectroscopy of Breast Cancer Patients Receiving Neoadjuvant Therapy

Objectives:To evaluate the feasibility of 7T breast magnetic resonance imaging (MRI) by determining the intrinsic sensitivity gain compared with 3T in healthy volunteers and to explore clinical application of 7T MRI in breast cancer patients receiving neoadjuvant chemotherapy (NAC). Materials and Methods:In 5 volunteers, the signal-to-noise ratio (SNR) was determined on proton density MRI at 3T using a conventional 4-channel bilateral breast coil and at 7T using a dedicated 2-channel unilateral breast coil, both obtained at identical scan parameters. Subsequently, consecutive breast cancer patients on NAC were included. The 7T breast MRI protocol consisted of diffusion-weighted imaging, 3D high-resolution (450 &mgr;m isotropic) T1-weighted fat-suppressed gradient-echo sequences and quantified single voxel 1H-magnetic resonance spectroscopy. Morphology was scored according to the MRI Breast Imaging-Reporting and Data System (BI-RADS)-lexicon, and the images were compared with 3T and histopathologic findings. Image quality was evaluated using a 5-point scale. Results:A 5.7-fold higher SNR was measured at 7T than at 3T, which reflects the advantages of a higher field strength and the use of optimized radiofrequency coils. Three breast cancer patients were included and received a total of 13 7T MRI examinations. The image quality of the high-resolution examinations was at least satisfactory, and good to excellent in 9 of the 13 examinations performed. More anatomic detail was depicted at 7T than at 3T. In 1 case, a fat plane between the muscle and tumor was visible at 7T, but not at the clinically performed 3T examination, suggesting that there was no muscle invasion, which was confirmed by pathology. Changes in tumor apparent diffusion coefficient values could be monitored in 2 patients and were found to increase during NAC, consistent with published results from studies at lower field strengths. Apparent diffusion coefficient values increased respectively from 0.33 × 10−3 mm2/s to 1.78 × 10−3 mm2/s after NAC and from 1.20 × 10−3 mm2/s to 1.44 × 10−3 mm2/s during NAC. Choline concentrations as low as 0.77 mMol/kgwater could be detected. In 1 patient, choline levels showed an overall decrease from 4.2 mMol/kwwater to 2.6 mMol/kgwater after NAC and the tumor size decreased correspondingly from 3.9 × 4.1 × 5.6 cm3 to 2.0 × 2.7 × 2.4 cm3. All 7T MRI findings were consistent with pathology analysis. Conclusion:Dedicated 7T breast MRI is technically feasible, can provide more SNR than at 3T, and has diagnostic potential.
Somatotopic mapping of sensory neurons innervating mechanosensory hairs on the larval prolegs of Manduca sexta

The abdominal prolegs are the principal locomotory appendages of the larval tobacco hornworm, Manduca sexta. The prolegs bear numerous mechanosensory bristle sensilla, each innervated by an afferent neuron that arborizes within the central nervous system (CNS). Based on their positions on the proleg, we have divided the sensilla into planta hairs (PHs), lateral hairs (LHs), and medial hairs (MHs). Previously, we found that PH afferents produce monosynaptic excitatory postsynaptic potentials (EPSPs) in proleg retractor muscle motoneurons, the size of which depends on the position of the hair in the PH array. In this paper we examined the central arbors of the proleg afferents to determine whether there was an anatomical correlate to the pattern of synaptic strengths. We found that the afferent arbors are arranged somatotopically within the CNS in a pattern similar to that for bristle afferents elsewhere on the abdomen; i.e., the anterior‐posterior and medial‐lateral position of a hair on the proleg was reflected in the location of the afferent arbor along the corresponding axes within sensory neuropil. All afferents terminated within a similar ventral region of neuropil. The arbors of PH, MH, and to a lesser extent, LH afferents, were enlarged as compared to afferents innervating hairs elsewhere on the abdomen. This feature, combined with the dense innervation of the proleg, causes the proleg region to be relatively overrepresented in sensory neuropil. We also examined the afferents innervating a pair of ventral midline hairs (VMHs) present in each abdominal segment, which, unlike the other afferents, showed segment‐specific central arbors. We conclude that the somatotopic mapping of afferent arbors may contribute to the specificity of synaptic connections in this system.
DNA Damage and the Activation of the p53 Pathway Mediate Alterations in Metabolic and Secretory Functions of Adipocytes

Activation of the p53 pathway in adipose tissue contributes to insulin resistance associated with obesity. However, the mechanisms of p53 activation and the effect on adipocyte functions are still elusive. Here we found a higher level of DNA oxidation and a reduction in telomere length in adipose tissue of mice fed a high-fat diet and an increase in DNA damage and activation of the p53 pathway in adipocytes. Interestingly, hallmarks of chronic DNA damage are visible at the onset of obesity. Furthermore, injection of lean mice with doxorubicin, a DNA damage-inducing drug, increased the expression of chemokines in adipose tissue and promoted its infiltration by proinflammatory macrophages and neutrophils together with adipocyte insulin resistance. In vitro, DNA damage in adipocytes increased the expression of chemokines and triggered the production of chemotactic factors for macrophages and neutrophils. Insulin signaling and effect on glucose uptake and Glut4 translocation were decreased, and lipolysis was increased. These events were prevented by p53 inhibition, whereas its activation by nutlin-3 reproduced the DNA damage-induced adverse effects. This study reveals that DNA damage in obese adipocytes could trigger p53-dependent signals involved in alteration of adipocyte metabolism and secretory function leading to adipose tissue inflammation, adipocyte dysfunction, and insulin resistance.
Bayesian Versus Orthodox Statistics: Which Side Are You On?

Researchers are often confused about what can be inferred from significance tests. One problem occurs when people apply Bayesian intuitions to significance testing—two approaches that must be firmly separated. This article presents some common situations in which the approaches come to different conclusions; you can see where your intuitions initially lie. The situations include multiple testing, deciding when to stop running participants, and when a theory was thought of relative to finding out results. The interpretation of nonsignificant results has also been persistently problematic in a way that Bayesian inference can clarify. The Bayesian and orthodox approaches are placed in the context of different notions of rationality, and I accuse myself and others as having been irrational in the way we have been using statistics on a key notion of rationality. The reader is shown how to apply Bayesian inference in practice, using free online software, to allow more coherent inferences from data.
Use of Bone Morphogenetic Protein-2 in the Rabbit Ulnar Nonunion Model

The ability of the osteoinductive protein and recombinant human bone morphogenetic protein-2, combined with polylactic glycolic acid porous microspheres and autologous blood clot to heal a large segmental defect was tested in a rabbit diaphyseal defect model. Two centimeter nonuniting defects were surgically created in the bilateral ulnae of 50 male New Zealand white rabbits. Each defect was then implanted with a pastelike polylactic glycolic acid/blood clot combination that was mixed with 5 different concentrations of recombinant human bone morphogenetic protein-2. The forearms were radiographically assessed on a biweekly schedule for 8 weeks. At 8 weeks, all animals were sacrificed and forearms radiographed. Radiographs were then scored by 3 independent observers for bone formation and union rates. United limbs were tested in torsion for mechanical strength using a Burstein torsion tester. All nonunited limbs were analyzed histologically as were 2 united limbs from each dosage group. Radiographic evaluation revealed that there was a dose dependent response in healing of the ulnar defect with a higher bone formation rate in the 2 higher dose limbs than in the lower dose limbs. Union was achieved in 100% of the highest dose limbs, whereas only 50% of the lowest dose limbs achieved bony union. No defects implanted with carrier alone achieved union. Biomechanical studies revealed significantly stiffer bone than age matched controls. Histologic analysis demonstrated normal bone formation with abundant normal appearing osteoid. These dose response data further support the role of recombinant human bone morphogenetic protein-2 as a potent morphogen in bone regeneration.
Outcomes of Anterior Cruciate Ligament Reconstruction in Obese and Overweight Patients: A Systematic Review.

OBJECTIVE To evaluate the mechanism of injury, outcomes, and complications of anterior cruciate ligament (ACL) reconstruction in overweight and obese patients. DATA SOURCES MEDLINE, EMBASE, and OVID electronic libraries were systematically searched from inception to December, 2017 for any eligible articles using a combination of the phrases "anterior cruciate ligament," "ACL," "overweight," "obese," and "BMI. " RESULTS Studies that evaluated patients with primary ACL reconstruction, classified patients as overweight or obese, and reported a minimum of 1-year follow-up data were included. Eight cohorts from 9 studies fulfilled the inclusion criteria. There were no significant differences for mechanism of injury, Lysholm scores, Knee injury and Osteoarthritis Outcome Scores values, or return to sports with a body mass index (BMI) above or below 25 kg/m. A significant difference was described in International Knee Documentation Committee (IKDC) scores when comparing obese patients (BMI >30 kg/m) to patients with BMI <25 kg/m (P <0.01). In patients with BMI >25 kg/m, the risk for arthritis was significantly higher but the risk for revision surgery or contralateral ACL tear was lower (P <0.05). There was no significant difference in complication rates (P = 0.77). CONCLUSION Patient-reported outcome measures were similar for patients with BMI above and below 25 kg/m, but there is evidence that obese patients have lower IKDC scores. There is a consistent association between overweight status and developing arthritis among patients having an ACL reconstruction. Overweight and obese patients have a lower risk of revision ACL reconstruction and contralateral ACL tear. There is insufficient data to make any conclusions regarding mechanism of injury or complications. More research is needed to better understand what is the appropriate counsel and treatment for overweight or obese patients with ACL tears. PROSPERO REGISTRATION NUMBER CRD42017055594.
Chemical regulation of epigenetic modifications: Opportunities for new cancer therapy

Epigenetics is concerned about heritable changes in gene expression without alteration of the coding sequence. Epigenetic modification of chromatin includes methylation of genomic DNA as well as post‐translational modification of chromatin‐associated proteins, in particular, histones. The spectrum of histone and non‐histone modifications ranges from the addition of relatively small groups such as methyl, acetyl and phosphoryl groups to the attachment of larger moieties such as poly(ADP‐ribose) and small proteins ubiquitin or small ubiquitin‐like modifier (SUMO). The combinatorial nature of DNA methylation and histone modifications constitutes a significant pathway of epigenetic regulation and considerably extends the information potential of the genetic code. Chromatin modification has emerged as a new fundamental mechanism for gene transcriptional activity control associated with many cellular processes like proliferation, growth, and differentiation. Also it is increasingly recognized that epigenetic modifications constitute important regulatory mechanisms for the pathogenesis of malignant transformations. We review here the recent progress in the development of chemical inhibitors/activators that target different chromatin modifying enzymes. Such potent natural or synthetic modulators can be utilized to establish the quantitative contributions of epigenetic modifications in DNA regulated pathways including transcription, replication, recombination and repair, as well as provide leads for developing new cancer therapeutics. © 2008 Wiley Periodicals, Inc. Med Res Rev, 28, No. 5, 645–687, 2008
Forecasting the Real Price of Oil Under Alternative Specifications of Constant and Time-Varying Volatility

This paper constructs a monthly real-time oil price dataset using backcasting and compares the forecast performance of alternative models of constant and timevarying volatility based on the accuracy of point and density forecasts of real oil prices of both real-time and ex-post revised data. The paper considers Bayesian autoregressive and autoregressive moving average models with respectively, constant volatility and two forms of time-varying volatility: GARCH and stochastic volatility. In addition to the standard time-varying models, more flexible models with volatility in mean and moving average innovations are used to forecast the real price of oil. The results show that timevarying volatility models dominate their counterparts with constant volatility in terms of point forecasting at longer horizons and density forecasting at all horizons. The inclusion of a moving average component provides a substantial improvement in the point and density forecasting performance for both types of time-varying models while stochastic volatility in mean is superfluous for forecasting oil prices.
Characterizing flow distributions in AV fistulae for haemodialysis access.

BACKGROUND The arteriovenous fistula is the most widely used means of enabling vascular access for chronic haemodialysis. When interest in vascular access was at its height, in the 1970s, a substantial amount of work was carried out on the physiology of arteriovenous fistulae and on the relationship between fistula flow and patency. One omission in the catalogue of studies was research into the distribution of flow in the fistula and the effects on surgical outcome. METHOD To address this issue, 30 patients with end-to-side radiocephalic fistulae were studied. Flow measurements were made intraoperatively, and at various intervals postoperatively using colour-flow ultrasonography. RESULTS In 22 cases, the development of the fistula was monitored at regular intervals for periods of up to 27 months. In seven of the 30 fistulae, flow in the distal artery was antegrade, while in the remaining 23, distal artery flow was retrograde. The proportion of fistula flow supplied by the proximal and distal arteries varied considerably. CONCLUSION Despite the wide range of flow distributions in the fistulae studied, flow distribution did not appear to affect fistula maturation or long-term function.
Professional Development Needs of Beginning Agricultural Education Teachers in Idaho.

The continuing shortage of agricultural education instructors has been documented across the state and nation. Secondary instructor retention may help reduce the shortage and position changes each year. Identifying the challenges facing beginning teachers as perceived by beginning teachers, veteran teachers, and building administrators can help identify the professional development and mentoring needs to assist in teacher retention. Establishing consensus among the target groups through this Delphi study will allow Idaho Team Ag Ed to be specific and purposeful in long term professional development planning. Through this study, 21 professional development areas were agreed upon in three areas: Teacher Skills and Knowledge (8); Personal Skills and Professional Development (6); and Program Area Concerns (7). Volume of work was the area of highest concern (n = 92, 90.11%) followed by classroom management skills and teaching experience (n = 81, 89.01%) and 79 of the 91 respondents (86.81%) agreed that finding alternative funding sources was an area of concern followed closely by overall program funding (n = 79 of 90 responses, 87.78%). The consensus supported previous research across the country and will provide a guide for targeted professional development, mentorship, and long-term retention for beginning teachers (0-5 years’ experience) in Idaho.