Miracle-dz/UniFAR-FTUs huggingface dataset:
Dual Inhibition of Src and GSK3 Maintains Mouse Embryonic Stem Cells, Whose Differentiation Is Mechanically Regulated by Src Signaling

Recent studies reveal that the mechanical environment influences the behavior and function of various types of cells, including stem cells. However, signaling pathways involved in the mechanical regulation of stem cell properties remain largely unknown. Using polyacrylamide gels with varying Young's moduli as substrates, we demonstrate that mouse embryonic stem cells (mESCs) are induced to differentiate on substrates with defined elasticity, involving the Src‐ShcA‐MAP kinase pathway. While the dual inhibition of mitogen‐activated protein (MAP) kinase and glycogen synthase kinase 3 (GSK3), termed “2i,” was reported to sustain the pluripotency of mESCs, we find it to be substrate elasticity dependent. In contrast, Src inhibition in addition to 2i allows mESCs to retain their pluripotency independent of substrate elasticity. The alternative dual inhibition of Src and GSK3 (“alternative 2i”) retains the pluripotency and self‐renewal of mESCs in vitro and is instrumental in efficiently deriving mESCs from preimplantation mouse embryos. In addition, the transplantation of mESCs, maintained under the alternative 2i condition, to immunodeficient mice leads to the formation of teratomas that include differentiation into three germ layers. Furthermore, mESCs established with alternative 2i contributed to chimeric mice production and transmitted to the germline. These results reveal a role for Src‐ShcA‐MAP kinase signaling in the mechanical regulation of mESC properties and indicate that alternative 2i is a versatile tool for the maintenance of mESCs in serum‐free conditions as well as for the derivation of mESCs. Stem Cells2012;30:1394–1404
Guidelines for evaluating chronic cough in pediatrics: ACCP evidence-based clinical practice guidelines.

OBJECTIVES To review relevant literature and present evidence-based guidelines to assist general and specialist medical practitioners in the evaluation and management of children who present with chronic cough. METHODOLOGY The Cochrane, MEDLINE, and EMBASE databases, review articles, and reference lists of relevant articles were searched and reviewed by a single author. The date of the last comprehensive search was December 5, 2003, and that of the Cochrane database was November 7, 2004. The authors' own databases and expertise identified additional articles. RESULTS/CONCLUSIONS Pediatric chronic cough (ie, cough in children aged <15 years) is defined as a daily cough lasting for >4 weeks. This time frame was chosen based on the natural history of URTIs in children and differs from the definition of chronic cough in adults. In this guideline, only chronic cough will be discussed. Chronic cough is subdivided into specific cough (ie, cough associated with other symptoms and signs suggestive of an associated or underlying problem) and nonspecific cough (ie, dry cough in the absence of an identifiable respiratory disease of known etiology). The majority of this section focuses on nonspecific cough, as specific cough encompasses the entire spectrum of pediatric pulmonology. A review of the literature revealed few randomized controlled trials for treatment of nonspecific cough. Management guidelines are summarized in two pathways. Recommendations are derived from a systematic review of the literature and were integrated with expert opinion. They are a general guideline only, do not substitute for sound clinical judgment, and are not intended to be used as a protocol for the management of all children with a coughing illness. Children (aged <15 years) with cough should be managed according to child-specific guidelines, which differ from those for adults as the etiologic factors and treatments for children are sometimes different from those for adults. Cough in children should be treated based on etiology, and there is no evidence for using medications for the symptomatic relief of cough. If medications are used, it is imperative that the children are followed up and therapy with the medications stopped if there is no effect on the cough within an expected time frame. An evaluation of the time to response is important. Irrespective of diagnosis, environmental influences and parental expectations should be discussed and managed accordingly. Cough often impacts the quality of life of both children and parents, and the exploration of parental expectations and fears is often valuable in the management of cough in children.
The US adoption system: media depictions and why they are ignored

This study investigated the U.S. adoption system, media influence, and welfare spending. It was undertaken to understand how the media frames adoption and the U.S. adoption system and how certain factors influence how the public views welfare spending (welfare spending including foster care and adoption programs). The media presents the adoption process as long and complex, suggesting that social welfare programs that handle adoption and foster care may be underfunded. However, such presentation has not prompted a response from the public, suggesting that opinions about adoption are influenced by factors other than media portrayal. This research suggests that political leanings, family income, and confidence in the media are all partially influential to how people view how much money is spent on welfare programs. This research also suggests that other avenues would be more successful than the media in raising awareness about problems in adoptions, such as using conservative-leaning NGOs to inform conservative-leaning citizens.
Analysis of Tipping Points in Social Networks for Diffusion of Innovations

Tipping point phenomena (events that had rarely observed becomes suddenly common) for diffusion of innovations have received huge attention from academia and industry [4,6,12]. Understanding tipping point phenomena has numerous applications including viral marketing and minimizing the spread of contamination. Depending on the characteristics of the information and social network structures, the information either cascades globally or terminates quickly. For example, sometimes new technologies become widespread over the network (a global cascade), but in some cases they simply disappear in a short time. In this work, we identify conditions for the occurrence of tipping points for general classes of network structures and provide a novel proof for its correctness. Various models of information spreading have been studied. These models are established based on the common assumption that the neighbors play significant roles for the spread of information. The SIR (Susceptible-Infected-Recover) model is one of those popular models applied to the cases when accepting the information requires low costs, such as the epidemics of contagious diseases [1, 2, 8]. Under the SIR model, some sufficient conditions for a global cascade have been studied [2, 3, 9]. On the other hand, for the diffusion of new technologies or innovations which requires relatively high costs to adopters, the linear threshold model is widely used [7, 12, 13]. However, general conditions for a global cascade under the linear threshold model are known for restricted cases. In the linear threshold model, individuals make their decisions based on the decisions of their neighbors. Each node has its own threshold value and if the fraction of neighbors who have already adopted the innovation is greater than the threshold, it will adopt the innovation. The mechanism of this model is originated from the utility maximization of individuals in game theory. A tipping point is defined as the number of initial adopters x so that the cascade size becomes suddenly large as the number increases from x to x+ δ for a small δ. Under the linear threshold model, the mechanism how a tipping point arises in a complete graph is well known [5]. When the thresholds of all nodes are homogeneous, the average cascade size and the number of initial adopters that triggers a global cascade have been predicted in the case of Erdös-Rényi random graph networks [13]. However, it is known that distributions of thresholds usually follow diverse unimodal distributions such as the normal distribution [10,11]. In this work, we consider any distributions of thresholds and assume that each node takes its threshold value from the distribution independently. We first analyze that in a social networks including Facebook and Myspace, tipping points occur almost always if certain conditions on the distribution of thresholds are met. We provide a novel proof that under those conditions, a tipping point occurs almost surely for
Explaining Variation in the Social Performance of Lean Production: A Comparative Case Study of the Role Played by Workplace Unions' Framing of the System and Institutions

Several studies have acknowledged that lean production is implemented in diverse ways across workplaces, thereby generating different outcomes for workers. However, explanations for this variability needs further development. The present article addresses this issue by considering the role played by workplace unions' framing of lean production. It finds that unions' framing is derived from their identities in interaction with available resources in institutional and organisational terms. A case study comparison of the automotive parts industry in Italy and the United States was conducted.
FAT10 mediates the effect of TNF-α in inducing chromosomal instability

Tumor necrosis factor-alpha (TNF-α) plays important roles in chronic inflammation-associated tumorigenesis but the mechanisms involved remain poorly understood. Previously, we reported that high levels of FAT10 led to chromosomal instability that is mediated by an abbreviated mitotic phase. Here, we show that TNF-α induces FAT10 gene expression through TNF receptor 1 (TNFR1) and activates the NF-κB pathway in HCT116 and SW620 cells. TNF-α treatment also leads to an abbreviated mitotic phase that can be reversed by inhibiting FAT10 expression. This abbreviated mitotic phase is correlated with a TNF-α-induced reduction in the kinetochore localization of MAD2 during prometaphase which, again, can be reversed by inhibiting FAT10 gene expression. There is greater variability of chromosome numbers in HCT116 and SW620 cells treated with TNF-α than in untreated cells, which can be reversed by the introduction of short hairpin RNA (shRNA) against FAT10. The more stable chromosome numbers in HCT116 cells expressing FAT10 shRNA can revert to greater variability with the addition of a mutant FAT10 that is not recognized by the FAT10 shRNA. Upon TNF-α stimulation, higher cell death is observed when FAT10 expression is inhibited by shRNA. These data strongly suggest that FAT10 plays an important role in mediating the function of TNF-α during tumorigenesis by inducing cell cycle deregulation and chromosomal instability, and by inhibiting apoptosis.
Outcomes After Warfarin Initiation in a Cohort of Hemodialysis Patients With Newly Diagnosed Atrial Fibrillation.

BACKGROUND Although warfarin is indicated to prevent ischemic strokes in most patients with atrial fibrillation (AF), evidence supporting its use in hemodialysis patients is limited. Our aim was to examine outcomes after warfarin therapy initiation, relative to no warfarin use, following incident AF in a large cohort of hemodialysis patients who had comprehensive prescription drug coverage through Medicare Part D. STUDY DESIGN Retrospective observational cohort study. SETTING & PARTICIPANTS Patients in the US Renal Data System undergoing maintenance hemodialysis who had AF newly diagnosed in 2007 to 2011, with Medicare Part D coverage, who had no recorded history of warfarin use. PREDICTOR Warfarin therapy initiation, identified by a filled prescription within 30 days of the AF event. OUTCOMES Death, ischemic stroke, hemorrhagic stroke, severe gastrointestinal bleeding, and composite outcomes. MEASUREMENTS HRs estimated by applying Cox regression to an inverse probability of treatment and censoring-weighted cohort. RESULTS Of 12,284 patients with newly diagnosed AF, 1,838 (15%) initiated warfarin therapy within 30 days; however, ∼70% discontinued its use within 1 year. In intention-to-treat analyses, warfarin use was marginally associated with a reduced risk of ischemic stroke (HR, 0.68; 95% CI, 0.47-0.99), but not with the other outcomes. In as-treated analyses, warfarin use was associated with reduced mortality (HR, 0.84; 95% CI, 0.73-0.97). LIMITATIONS Short observation period, limited number of nonfatal events, limited generalizability of results to more affluent patients. CONCLUSIONS In hemodialysis patients with incident AF, warfarin use was marginally associated with reduced risk of ischemic stroke, and there was a signal toward reduced mortality in as-treated analyses. These results support clinical equipoise regarding the use of warfarin in hemodialysis patients and underscore the need for randomized trials to fill this evidence gap.
Typing of Histoplasma capsulatum by restriction fragment length polymorphisms in a nuclear gene

We previously described yps-3, a Histoplasma-specific nuclear gene probe useful in the identification of Histoplasma capsulatum. By using restriction fragment length polymorphisms (RFLPs) of DNA detected by the yps-3 gene and mitochondrial DNA, 76 clinical and soil isolates of H. capsulatum were classified. The majority of North American isolates obtained from endemic regions of the midwestern United States were members of the previously characterized class 2, although four clinical isolates from different patients with AIDS from that region were grouped in class 1 with the temperature-sensitive Downs strain. A Florida soil isolate (FLS1) was placed in class 4 on the basis of RFLP with both probes. Two American Type Culture Collection strains (G184B and G186B) from Panama were grouped into class 3 by this analysis. A group of five H. capsulatum isolates obtained from patients with AIDS in New York City were typed into a new class 5 on the basis of yps-3 polymorphisms; those organisms fell into two broad mitochondrial DNA patterns, designated 5b and 5c. Two new isolates from Panama were also members of this broad yps-3 class 5 group, but they exhibited a distinct mitochondrial DNA profile (class 5a). A sixth class was detected in DNA obtained from a patient with AIDS from Panama; that DNA had unique RFLP profiles with respect to both probes. These observations suggest that the Histoplasma-specific yps-3 gene probe is a sensitive tool for typing H. capsulatum in clinical specimens. Additionally, these studies provide molecular support for the hypothesis that AIDS-associated histoplasmosis in nonendemic areas is due to reactivation of a previously acquired infection.
SOS: Software-based out-of-order scheduling for high-performance NAND flash-based SSDs

We propose an efficient software-based out-of-order scheduling technique, called SOS, for high-performance NAND flash-based SSDs. Unlike an existing hardware-based out-of-order technique, our proposed software-based solution, SOS, can make more efficient out-of-order scheduling decisions by exploiting various mapping information and I/O access characteristics obtained from the flash translation layer (FTL) software. Furthermore, SOS can avoid unnecessary hardware-level operations and manage I/O request rearrangements more efficiently, thus maximizing the multiple-chip parallelism of SSDs. Experimental results on a prototype SSD show that SOS is effective in improving the overall SSD performance, lowering the average I/O response time by up to 42% over a hardware-based out-of-order flash controller.
Maternal prepregnancy obesity and cause-specific stillbirth.

BACKGROUND In high-income countries, maternal obesity is one of the most important modifiable causes of stillbirth, yet the pathways underpinning this association remain unclear. OBJECTIVE We estimated the association between maternal prepregnancy body mass index (BMI) and the risk of stillbirth defined by pathophysiologic contributors or causes. DESIGN Using a case-cohort design, we randomly sampled 1829 singleton deliveries from a cohort of 68,437 eligible deliveries at Magee-Womens Hospital in Pittsburgh, Pennsylvania (2003-2010), and augmented it with all remaining cases of stillbirth for a total of 658 cases. Stillbirths were classified based on probable cause(s) of death (maternal medical conditions, obstetric complications, fetal abnormalities, placental diseases, and infection). A panel of clinical experts reviewed medical records, placental tissue slides and pathology reports, and fetal postmortem reports of all stillbirths. Causes of fetal death were assigned by using the Stillbirth Collaborative Research Network Initial Causes of Fetal Death protocol from the Eunice Kennedy Shriver National Institute of Child Health and Human Development. Proportional hazards models were used to estimate the BMI-stillbirth association after adjustment for confounders. RESULTS The rate of stillbirth among lean, overweight, obese, and severely obese women was 7.7, 10.6, 13.9, and 17.3 per 1000 live-born and stillborn infants, respectively. Adjusted stillbirth HRs (95% CIs) were 1.4 (1.1, 1.8) for overweight, 1.8 (1.3, 2.4) for obese, and 2.0 (1.5, 2.8) for severely obese women, respectively, compared with lean women; associations strengthened when limited to antepartum stillbirths. Obesity and severe obesity were associated with stillbirth resulting from placental diseases, hypertension, fetal anomalies, and umbilical cord abnormalities. BMI was not related to stillbirth caused by placental abruption, obstetric conditions, or infection. CONCLUSIONS Multiple mechanisms appear to link obesity to stillbirth. Interventions to reduce stillbirth among obese mothers should consider targeting stillbirth due to hypertension and placental diseases-the most common causes of fetal death in this at-risk group.
Diamond Radio Receiver: Nitrogen-Vacancy Centers as Fluorescent Transducers of Microwave Signals

The nitrogen-vacancy (N-$V$) center is a lattice defect in diamond, consisting of a substitutional nitrogen atom and an adjacent vacancy. This study exploits the electron-spin-dependent photoluminescence of N-$V$ centers to use them as radio receivers. The centers transduce frequency-modulated (FM) microwave radio signals to amplitude-modulated (AM) optical fluorescence signals. This effect has potential for photonics, quantum information processing, microwave applications, and wireless communication, even in extreme environments.
Aluminum forms in drinking water and risk of Alzheimer's disease.

The objective of this study was to assess the relation between long-term exposure to different aluminum (Al) forms in drinking water and Alzheimer's disease (AD). The study participants were selected from a random sample of the elderly population (> or = 70 years of age) of the Saguenay-Lac-Saint-Jean region (Quebec). Sixty-eight cases of Alzheimer's disease diagnosed according to recognized criteria were paired for age (+/-2 years) and sex with nondemented controls. Aluminum speciation was assessed using established standard analytical protocols along with quality control procedures. Exposure to Al forms (total Al, total dissolved Al, monomeric organic Al, monomeric inorganic Al, polymeric Al, Al(3+), AlOH, AlF, AlH(3)SiO(2+)(4), AlSO(4)) in drinking water was estimated by juxtaposing the subject's residential history with the physicochemical data of the municipalities. The markers of long-term exposures (1945 to onset) to Al forms in drinking water were not significantly associated with AD. On the other hand, after adjustment for education level, presence of family cases, and ApoE varepsilon4 allele, exposure to organic monomeric aluminum estimated at the onset of the disease was associated with AD (odds ratio 2.67; 95% CI 1.04-6.90). On average, the exposure estimated at the onset had been stable for 44 years. Our results confirm prime the importance of estimation of Al speciation and consideration of genetic characteristics in the assessment of the association between aluminum exposure and Alzheimer's disease.
Course and Recurrence of Postnatal Depression

Background It is unclear whether the causative factors of non-psychotic postnatal depression are the same as those of depression at other times. Method The course and recurrence of postnatal depression was studied in two groups of primiparous women experiencing an index episode of postnatal depression: those for whom the mood disorder had arisen de novo (n = 34), and those for whom it was a recurrence of previous affective disturbance (n = 21). The mental state of these two groups, together with a psychiatrically well control group (n = 40), was studied for five years. Results It was found that those for whom the index episode was a recurrence of depression were at raised risk of further non-postpartum episodes but not postpartum episodes, and that those for whom the index episode had arisen de novo were at raised risk for further episodes of postnatal depression but not for non-postpartum episodes. Conclusion These findings suggest a specific nosologic reference for the concept of postnatal depression.
Expression of Immunomodulatory Genes in Human Monocytes Induced by Voriconazole in the Presence of Aspergillus fumigatus

ABSTRACT We assessed the effect of voriconazole (VRC) on the expression and release of selected cytokines and chemokines in the THP-1 human monocytic cell line in response to Aspergillus fumigatus hyphal fragments (HF) by cDNA microarray analysis, reverse transcriptase (RT) PCR, and enzyme-linked immunosorbent assay. Stimulation of THP-1 cells by HF alone caused a significant up-regulation of CCL4 (MIP1B) and CCL16, while CCL2 (MCP1) was down-regulated. By comparison, in the presence of VRC, a large number of genes such as CCL3 (MIP1A), CCL4 (MIP1B), CCL5 (RANTES), CCL7 (MCP3), CCL11 (EOTAXIN), CCL15 (MIP1Δ), CXCL6, and CXCL13 were strongly up-regulated in THP-1 cells challenged by HF, whereas CCL20 (MIP3A) and CCL21 (MIP2) were down-regulated. Among five genes differentially expressed in THP-1 cells, IL12A, IL12B, and IL-16 were down-regulated whereas IL-11 and TGFB1 were significantly up-regulated in the presence of VRC. The inflammation-related genes IFNγ, IL1R1, and TNFA were also up-regulated in THP-1 cells exposed to HF only in the presence of VRC. RT-PCR of four selected genes validated the results of microarrays. The release of interleukin 1β (IL-1β) and IL-12 was significantly increased from monocytes stimulated either by HF alone (P < 0.05) or in the presence of VRC (P < 0.01 and P < 0.05, respectively). In contrast, tumor necrosis factor alpha release from monocytes was enhanced only in the presence of VRC (P < 0.01). The chemokines monocyte chemoattractant protein 1 and macrophage inflammatory protein 1β were decreased under both conditions (P < 0.01). These results demonstrate that in the presence of VRC, HF induces a more pronounced profile of gene expression in THP-1 cells than HF alone, potentially leading to more-efficient host resistance to A. fumigatus.