Miracle-dz/UniFAR-FTUs huggingface dataset:
A Gel-Free Quantitative Proteomics Analysis of Factors Released From Hypoxic-Conditioned Placentae

Characterizing the protein factors released from placentae during pathogenesis remains a key objective toward understanding preeclampsia and related pregnancy disorders. Gel-free proteomics technologies applied to placental explant-conditioned media offers the potential of identifying these factors. Relative quantification mass spectrometry using isobaric tagging for relative and absolute quantification (iTRAQ) labeling was employed to compare the ‘‘secretome’’ between healthy term placental tissue cultured under both normoxic and hypoxic oxygen tensions. Of the 499 proteins identified, 45 were differentially expressed (P < .01 level), including interleukin 8 (IL-8) which was significantly upregulated under hypoxia. Global protein level changes are suggestive of decreased extracellular matrix remodeling under the same conditions. A significant enrichment of soluble liberated placental factors is achieved using this model system. Identifying these changes resulting from hypoxic conditioning is hypothesis generating and may provide new mechanistic insights into preeclampsia.
Adenosine and Dopamine Receptors Coregulate Photoreceptor Coupling via Gap Junction Phosphorylation in Mouse Retina

Gap junctions in retinal photoreceptors suppress voltage noise and facilitate input of rod signals into the cone pathway during mesopic vision. These synapses are highly plastic and regulated by light and circadian clocks. Recent studies have revealed an important role for connexin36 (Cx36) phosphorylation by protein kinase A (PKA) in regulating cell–cell coupling. Dopamine is a light-adaptive signal in the retina, causing uncoupling of photoreceptors via D4 receptors (D4R), which inhibit adenylyl cyclase (AC) and reduce PKA activity. We hypothesized that adenosine, with its extracellular levels increasing in darkness, may serve as a dark signal to coregulate photoreceptor coupling through modulation of gap junction phosphorylation. Both D4R and A2a receptor (A2aR) mRNAs were present in photoreceptors, inner nuclear layer neurons, and ganglion cells in C57BL/6 mouse retina, and showed cyclic expression with partially overlapping rhythms. Pharmacologically activating A2aR or inhibiting D4R in light-adapted daytime retina increased photoreceptor coupling. Cx36 among photoreceptor terminals, representing predominantly rod–cone gap junctions but possibly including some rod–rod and cone–cone gap junctions, was phosphorylated in a PKA-dependent manner by the same treatments. Conversely, inhibiting A2aR or activating D4R in daytime dark-adapted retina decreased Cx36 phosphorylation with similar PKA dependence. A2a-deficient mouse retina showed defective regulation of photoreceptor gap junction phosphorylation, fairly regular dopamine release, and moderately downregulated expression of D4R and AC type 1 mRNA. We conclude that adenosine and dopamine coregulate photoreceptor coupling through opposite action on the PKA pathway and Cx36 phosphorylation. In addition, loss of the A2aR hampered D4R gene expression and function.
Wiener model based nonlinear predictive control

This paper addresses the problem of discrete-time nonlinear predictive control of W iener systems. Wiener-model-based nonlinear predictive control combines the advantages of linear-model-based predictive control and gain scheduling while retaining a moderate level of computational complexity. A clear relation is shown between an iteration in the optimization of the nonlinear control problem and the control problem of the underlying linear-model-based method. This relation has a simple form of gain scheduling, thus the properties of the nonlinear control system can be analysed from the comprehensible linear control aspect. Several disturbance rejection techniques are proposed and compared. The method was tested on a simulated model of a pH neutralization process. The performance was excellent also in the case of a considerable plant-tomodel mismatch. The method can be applied as a first next step in cases where the performance of linear control is unsatisfactory owing to process nonlinearity.
Collective intertemporal choice: time consistency vs. time invariance

We study collective choice when individuals have heterogeneous discounted utilitarian preferences. Two attractive properties of intertemporal preferences are indistinguishable for individuals, but have dramatically different implications for collective choice. Time Consistency requires a plan that is optimal at one evaluation date to be optimal at all later evaluation dates, while Time Invariance requires preferences to be unchanged under translations of the time axis. We study the implications of these two properties in a tractable dynamic model that captures both common resource and public goods problems. Utilitarian social planners implement the first best if collective preferences are time consistent, but not if they are time invariant. Decentralized alternatives { property rights (for common resources) and voting (for public goods) { can strictly improve on the planning equilibrium if social preferences are time invariant. We reflect on the implications of these fndings for dynamic welfare economics. Revealed preference cannot determine which property we should adopt, but each property is normatively attractive in some contexts.
An ethno-medicinal study of medicinal plants used for the treatment of diabetes

Background: Diabetes is the greatest public health problem and is considered as the silent epidemic of the 21st century. In Iran, there are approximately 1.5 million diabetic patients. Before the discovery of insulin, medicinal plants were widely used for the treatment of diabetes in Iran. Objectives: This study aimed to determine the indigenous plants used for the treatment of diabetes in Shiraz, southwest of Iran. Materials and Methods: Semi-structured direct interviews were conducted with 25 herbalists to identify medicinal plants used to treat diabetes. Questionnaires were included herbalist personal information, plant local name, growth season, plant parts used, preparation methods, and traditional therapies. Results: The interview data indicated that, 24 medicinal plants from 19 families are used for the treatment of diabetes in Shiraz. The families with most antidiabetic species were Compositae (13%), Rosaceae (13%) and Cucurbitaceae (8%). The most frequently used plant parts were fruits (38%) and the most common preparation method was decoction (62%). For 45% of reported plants, pharmaceutical studies approved antidiabetic effects in animal or humane model of diabetes. Results of this study showed that the plants recommended by Shirazian herbalists have potential antidiabetic effects. Conclusions: It is suggested that the ingredients of indigenous plants be studied to determine therapeutic effects and mechanism of action. If they were safe and effective, they can be refined and processed to produce natural drugs.
Determining the effects of films with suicidal content: A laboratory experiment

Background Media stories on suicide can increase suicidal ideation, but little is known about variations in media effects with regard to audience vulnerability and story contents. Aims We investigated the impact of three drama films with suicidal content that varied with regard to the final outcome (suicide completion, mastery of crisis and death by natural causes) and tested the moderating effect of baseline suicidality of the participants on the effects. Method Within a laboratory setting, we randomly assigned 95 adults to three film groups. We used questionnaires to analyse the effects of the films on mood, depression, life satisfaction, self-worth, assumed benevolence of the world and suicidality, as well as identification with the protagonist. We stratified the sample into participants with suicidal tendencies above and below the sample median. Results The film that ended with the protagonist's suicide led to a deterioration of mood particularly in individuals with baseline suicidality below the median, who also experienced an increase in self-worth. Participants with stronger suicidal tendencies experienced a rise in suicidality that depended on their level of identification with the protagonist. The film featuring the main character positively coping with his crisis increased life satisfaction particularly among participants with higher suicidal tendencies. Conclusions The effects of suicide-related media material seem to vary with individual vulnerability and with type of media portrayal. Individuals with lower vulnerability experience more emotional reactions when exposed to a film culminating in suicide, but individuals with higher vulnerability experience a rise in suicidal tendencies particularly if they identify with the protagonist who died by suicide. In contrast, portrayals of individual mastery of crisis may have beneficial effects in more vulnerable individuals.
Acute alcohol consumption is associated with increased interatrial electromechanical delay in healthy men.

BACKGROUND Acute alcohol consumption can cause atrial fibrillation in patients with, and without, heart disease. Increased atrial electromechanical delay (EMD) has been associated with atrial fibrillation. We evaluated the atrial conduction properties by tissue Doppler imaging (TDI) echocardiography in healthy men following acute alcohol intake. METHODS Thirty healthy male volunteers were included in this study. Baseline ECG, heart rate, blood pressure, and TDI echocardiographic findings were compared to readings taken one hour after drinking six 12-oz cans of beer (76.8 g of ethanol). RESULTS Although the blood pressure and heart rate remained similar before and one hour after alcohol intake, Pmax and Pd values were significantly prolonged (114.2 ± 10.4 vs 100.8 ± 10.6, p = 0.002; 50.6 ± 9.6 vs 34.5 ± 8.8, p < 0.0001). Interatrial EMD was significantly increased after drinking alcohol compared to the baseline (19.8 ± 9.2 vs 14.0 ± 5.5 ms, p < 0.0002). CONCLUSIONS Acute moderate alcohol intake was associated with an increased interatrial EMD obtained by TDI echocardiography. This finding may help explain how these patients express increased susceptibility to atrial fibrillation.
A Mobile Internet Service for Self-Management of Physical Activity in People With Rheumatoid Arthritis: Challenges in Advancing the Co-Design Process During the Requirements Specification Phase

Background User involvement in the development of health care services is important for the viability, usability, and effectiveness of services. This study reports on the second step of the co-design process. Objective The aim was to explore the significant challenges in advancing the co-design process during the requirements specification phase of a mobile Internet service for the self-management of physical activity (PA) in rheumatoid arthritis (RA). Methods A participatory action research design was used to involve lead users and stakeholders as co-designers. Lead users (n=5), a clinical physiotherapist (n=1), researchers (n=2) with knowledge in PA in RA and behavioral learning theories, an eHealth strategist (n=1), and an officer from the patient organization (n=1) collaborated in 4 workshops. Data-collection methods included video recordings and naturalistic observations. Results The inductive qualitative video-based analysis resulted in 1 overarching theme, merging perspectives, and 2 subthemes reflecting different aspects of merging: (1) finding a common starting point and (2) deciding on design solutions. Seven categories illustrated the specific challenges: reaching shared understanding of goals, clarifying and handling the complexity of participants’ roles, clarifying terminology related to system development, establishing the rationale for features, negotiating features, transforming ideas into concrete features, and participants’ alignment with the agreed goal and task. Conclusions Co-designing the system requirements of a mobile Internet service including multiple stakeholders was a complex and extensive collaborative decision-making process. Considering, valuing, counterbalancing, and integrating different perspectives into agreements and solutions (ie, the merging of participants’ perspectives) were crucial for moving the process forward and were considered the core challenges of co-design. Further research is needed to replicate the results and to increase knowledge on key factors for a successful co-design of health care services.
Circular RNA ITCH has inhibitory effect on ESCC by suppressing the Wnt/β-catenin pathway

Circular RNAs with exonic sequences represent a special form of non-coding RNAs, discovered by analyzing a handful of transcribed genes. It has been observed that circular RNAs function as microRNA sponges. In the present study, we investigated whether the expression of circular RNAs is altered during the development of esophageal squamous cell carcinoma (ESCC). Using a TaqMan-based reverse transcriptase polymerase chain reaction assay, the relationship between cir-ITCH and ESCC was analyzed in a total of 684 ESCC and paired adjacent non-tumor tissue samples from eastern and southern China. We found that cir-ITCH expression was usually low in ESCC compared to the peritumoral tissue. The functional relevance of cir-ITCH was further examined by biochemical assays. As sponge of miR-7, miR-17, and miR-214, cir-ITCH might increase the level of ITCH. ITCH hyper expression promotes ubiquitination and degradation of phosphorylated Dvl2, thereby inhibiting the Wnt/β-catenin pathway. These results indicate that cir-ITCH may have an inhibitory effect on ESCC by regulating the Wnt pathway.
Biomimetic Titanium Alloy with Sparsely Distributed Nanotubes Could Enhance Osteoblast Functions

Designing the bone implant surface by mimicking the structure of natural tissue is an intriguing means to achieve better osseointegration. In this study, a biomimetic surface with sparsely distributed 80 nm diameter nanotubes (SNT) with a spacing of about 20–80 nm from each other, contrary to the closely distributed nanotubes on pure titanium, is fabricated by anodization of near β titanium alloy Ti‐5Zr‐3Sn‐5Mo‐15Nb (TLM). The structure is more similar to the cross‐section of collagen fibrils than commonly reported nanotubes on pure titanium. The SNT‐textured Ti‐alloy also shows good wettability and low elastic modulus more compatible with bone tissues. The surface bioactivity is evaluated in vitro by primary osteoblast cultures. Compared with the polished non‐textured TLM, the SNT texture exhibits satisfactory bioactivity with protein adsorption, initial cell adhesion, cell differentiation as revealed by ALP activity and osteogenesis‐related gene expression. Although cell proliferation is slightly suppressed, ECM deposition is enhanced. The enhanced cell functions are probably related to the biomimetic structure, biochemical characteristics, and mechanical properties of SNT‐textured Ti‐alloy as well as the potential fluid exchange effect among the nanotubes. The SNT texture which constitutes a bio‐interface with fluid supply from the implant surface can be tailored to enhance biological properties such as cell immigration and differentiation.
Cross-generational vowel change in American English

Abstract This study examines cross-generational changes in the vowel systems in central Ohio, southeastern Wisconsin, and western North Carolina. Speech samples from 239 speakers, males and females, were divided into three age groups: grandparents (66–91 years old), parents (35–51), and children (8–12). Acoustic analysis of vowel dynamics (i.e., formant movement) was undertaken to explore variation in the amount of spectral change for each vowel. A robust set of cross-generational changes in /ɪ, ɛ, æ, ɑ/ was found within each dialect-specific vowel system, involving both their positions and dynamics. With each successive generation, /ɪ, ɛ, æ/ become increasingly monophthongized and /ɑ/ is diphthongized in children. These changes correspond to a general anticlockwise parallel rotation of vowels (with some exceptions in /ɪ/ and /ɛ/). Given the widespread occurrence of these parallel chainlike changes, we term this development the “North American Shift,” which conforms to the general principles of chain shifting formulated by Labov (1994) and others.
Recessive cardiac phenotypes in induced pluripotent stem cell models of Jervell and Lange-Nielsen syndrome: Disease mechanisms and pharmacological rescue

Significance There are few laboratory models that recapitulate human cardiac disease. Here, we created human cell models for Jervell and Lange-Nielsen syndrome (JLNS) in vitro, based on human induced pluripotent stem cells (hiPSCs). JLNS is one of the most severe disorders of heart rhythm and can cause sudden death in young patients. JLNS is inherited recessively and is caused by homozygous mutations in the slow component of the delayed rectifier potassium current, IKs. Cardiomyocytes (CMs) from two independent sets of patient-derived and engineered hiPSCs showed electrophysiological defects that reflect the severity of the condition in patients. Our work allowed better understanding of the mechanisms of recessive inheritance. Furthermore, JLNS-CMs showed increased sensitivity to proarrhythmic drugs, which could be rescued pharmacologically, demonstrating the potential of hiPSC-CMs in drug testing. Jervell and Lange-Nielsen syndrome (JLNS) is one of the most severe life-threatening cardiac arrhythmias. Patients display delayed cardiac repolarization, associated high risk of sudden death due to ventricular tachycardia, and congenital bilateral deafness. In contrast to the autosomal dominant forms of long QT syndrome, JLNS is a recessive trait, resulting from homozygous (or compound heterozygous) mutations in KCNQ1 or KCNE1. These genes encode the α and β subunits, respectively, of the ion channel conducting the slow component of the delayed rectifier K+ current, IKs. We used complementary approaches, reprogramming patient cells and genetic engineering, to generate human induced pluripotent stem cell (hiPSC) models of JLNS, covering splice site (c.478-2A>T) and missense (c.1781G>A) mutations, the two major classes of JLNS-causing defects in KCNQ1. Electrophysiological comparison of hiPSC-derived cardiomyocytes (CMs) from homozygous JLNS, heterozygous, and wild-type lines recapitulated the typical and severe features of JLNS, including pronounced action and field potential prolongation and severe reduction or absence of IKs. We show that this phenotype had distinct underlying molecular mechanisms in the two sets of cell lines: the previously unidentified c.478-2A>T mutation was amorphic and gave rise to a strictly recessive phenotype in JLNS-CMs, whereas the missense c.1781G>A lesion caused a gene dosage-dependent channel reduction at the cell membrane. Moreover, adrenergic stimulation caused action potential prolongation specifically in JLNS-CMs. Furthermore, sensitivity to proarrhythmic drugs was strongly enhanced in JLNS-CMs but could be pharmacologically corrected. Our data provide mechanistic insight into distinct classes of JLNS-causing mutations and demonstrate the potential of hiPSC-CMs in drug evaluation.
Insulation characteristics of gas mixtures including perfluorocarbon gas

This paper describes discharge properties of N<sub>2</sub> and CO<sub>2</sub>-based gas mixtures including a perfluorocarbon (PFC) gas such as CF<sub>4</sub>, C<sub>3</sub>F<sub>8</sub> and c-C<sub>4</sub>F<sub>8</sub> under non-uniform field. The mixture ratio between a base gas of N<sub>2</sub> or CO<sub>2</sub> and the additive PFC gas was fixed as 9:1; namely, 90%N<sub>2</sub>/10%PFC or 90%CO<sub>2</sub>/10%PFC gas mixture. The PFC gases have even smaller global warming potential (GWP) than SF<sub>6</sub> gas and have good insulation properties as SF<sub>6</sub> gas. Thus, PFC gas mixture is expected to be a SF<sub>6</sub> substitute without highly pressurizing the gas over the conventional pressure of 0.5 to 0.6 MPa. In this study, in order to compare the partial discharge (PD) inception voltage V<sub>PD</sub> and breakdown voltage V<sub>B</sub> properties between N<sub>2</sub> and CO<sub>2</sub>-based gas mixtures, as well as between the additive gas of PFC and SF<sub>6</sub> gas, we investigated these properties of the gas mixtures with a needle to plane electrode under ac high voltage application. The gas pressure was changed from 0.1 to 0.6 MPa. As a result, it was found that V<sub>PD</sub> and V<sub>B</sub> characteristics of N<sub>2</sub> and CO<sub>2</sub>-based gas mixtures differed considerably, especially the gas pressure dependence of V<sub>B</sub> (so-called the N shape characteristics). V<sub>B</sub> characteristics of N<sub>2</sub>-based gas mixture including c-C<sub>4</sub>F<sub>8</sub> proved to be excellent within the test conditions over the wide gas pressure region, showing the maximum breakdown voltage. In terms of V<sub>PD</sub> properties, CO<sub>2</sub>-based gas mixture had an advantage over N<sub>2</sub>-based gas mixture due to higher V<sub>PD</sub>. Furthermore, we discussed the synergy effects of V<sub>PD</sub> and V<sub>B</sub> for N<sub>2</sub> and CO<sub>2</sub>-based gas mixtures using the index R<sub>n</sub> which was defined to quantify the degree of the effect. R<sub>n</sub> for CO<sub>2</sub>-based gas mixture was higher than that of N<sub>2</sub>-based gas mixture.
Minimum Waist and Visceral Fat Values for Identifying Japanese Americans at Risk for the Metabolic Syndrome

Hayashi et al. (1) reported from cross-sectional data that the optimal cut points of intra-abdominal fat area, waist circumference, and BMI were 96 cm2, 90 cm, and 25 kg/m2, respectively, for Japanese men and 75 cm2, 84 cm, and 23 kg/m2, respectively, for Japanese women, identifying subjects with two or more nonadipose components of the metabolic syndrome (1). They criticized the arbitrary and inconsistent methodology used by the Examination Committee of Criteria for Obesity Disease in Japan to derive the peculiar cut points of waist circumference (85 cm for men and 90 cm for women) …