Miracle-dz/UniFAR-FTUs huggingface dataset:
The clinical significance of K-Cl cotransport activity in red cells of patients with HbSC disease

HbSC disease is the second commonest form of sickle cell disease, with poorly understood pathophysiology and few treatments. We studied the role of K-Cl cotransport activity in determining clinical and laboratory features, and investigated its potential role as a biomarker. Samples were collected from 110 patients with HbSC disease and 41 with sickle cell anemia (HbSS). K-Cl cotransport activity was measured in the oxygenated (K-Cl cotransport100) and deoxygenated (K-Cl cotransport0) states, using radioactive tracer studies. K-Cl cotransport activity was high in HbSC and decreased significantly on deoxygenation. K-Cl cotransport activity correlated significantly and positively with the formation of sickle cells. On multiple regression analysis, K-Cl cotransport increased significantly and independently with increasing reticulocyte count and age. K-Cl cotransport activity was increased in patients who attended hospital with acute pain in 2011 compared to those who did not (K-Cl cotransport100: mean 3.87 versus 3.20, P=0.009, independent samples T-test; K-Cl cotransport0: mean 0.96 versus 0.68, P=0.037). On logistic regression only K-Cl cotransport was associated with hospital attendance. Increased K-Cl cotransport activity was associated with the presence of retinopathy, but this effect was confounded by age. This study links variability in a fundamental aspect of cellular pathology with a clinical outcome, suggesting that K-Cl cotransport is central to the pathology of HbSC disease. Increased K-Cl cotransport activity is associated with increasing age, which may be of pathophysiological significance. Effective inhibition of K-Cl cotransport activity is likely to be of therapeutic benefit.
HCN Channels Are Not Required for Mechanotransduction in Sensory Hair Cells of the Mouse Inner Ear

The molecular composition of the hair cell transduction channel has not been identified. Here we explore the novel hypothesis that hair cell transduction channels include HCN subunits. The HCN family of ion channels includes four members, HCN1-4. They were orginally identified as the molecular correlates of the hyperpolarization-activated, cyclic nucleotide gated ion channels that carry currents known as If, IQ or Ih. However, based on recent evidence it has been suggested that HCN subunits may also be components of the elusive hair cell transduction channel. To investigate this hypothesis we examined expression of mRNA that encodes HCN1-4 in sensory epithelia of the mouse inner ear, immunolocalization of HCN subunits 1, 2 and 4, uptake of the transduction channel permeable dye, FM1-43 and electrophysiological measurement of mechanotransduction current. Dye uptake and transduction current were assayed in cochlear and vestibular hair cells of wildtype mice exposed to HCN channel blockers or a dominant-negative form of HCN2 that contained a pore mutation and in mutant mice that lacked HCN1, HCN2 or both. We found robust expression of HCNs 1, 2 and 4 but little evidence that localized HCN subunits in hair bundles, the site of mechanotransduction. Although high concentrations of the HCN antagonist, ZD7288, blocked 50–70% of the transduction current, we found no reduction of transduction current in either cochlear or vestibular hair cells of HCN1- or HCN2- deficient mice relative to wild-type mice. Furthermore, mice that lacked both HCN1 and HCN2 also had normal transduction currents. Lastly, we found that mice exposed to the dominant-negative mutant form of HCN2 had normal transduction currents as well. Taken together, the evidence suggests that HCN subunits are not required for mechanotransduction in hair cells of the mouse inner ear.
Osteopontin: a protein with diverse functions

In this review most of the various known, suspected, or postulated functions of osteopontin, a secreted highly acidic phosphoprotein, are discussed in terms of what we currently know about the protein. These include 1) binding of OPN both to cells via a GRGDS cell adhesion sequence that recognizes the αvβ3 integrin and to extracellular matrix components via poorly characterized motifs, 2) regulation of the formation and remodeling of mineralized tissue, 3) recruiting and stimulating macrophages and lymphocytes as part of a nonspecific response to microbial infections, 4) multiple interactions with Ca2+ that likely influence OPN protein conformation and may be important in Ca2+‐mediated or Ca2+‐dependent processes, 5) inhibiting the growth of calcium oxalate crystals by disruption of the growing crystal lattice, 6) effects on gene expression, Ca2+ regulation, and nitric oxide production, and 7) involvement in cell migration. OPN production is frequently augmented when cell signaling pathways are activated by any of a variety of stimuli, for example in cancer cells. — Denhardt, D. T. , Guo, X. Osteopontin: a protein with diverse functions. FASEB J. 7: 1475‐1482; 1993.
Mutation-Specific Phenotypes in hiPSC-Derived Cardiomyocytes Carrying Either Myosin-Binding Protein C Or α-Tropomyosin Mutation for Hypertrophic Cardiomyopathy

Hypertrophic cardiomyopathy (HCM) is a genetic cardiac disease, which affects the structure of heart muscle tissue. The clinical symptoms include arrhythmias, progressive heart failure, and even sudden cardiac death but the mutation carrier can also be totally asymptomatic. To date, over 1400 mutations have been linked to HCM, mostly in genes encoding for sarcomeric proteins. However, the pathophysiological mechanisms of the disease are still largely unknown. Two founder mutations for HCM in Finland are located in myosin-binding protein C (MYBPC3-Gln1061X) and α-tropomyosin (TPM1-Asp175Asn) genes. We studied the properties of HCM cardiomyocytes (CMs) derived from patient-specific human induced pluripotent stem cells (hiPSCs) carrying either MYBPC3-Gln1061X or TPM1-Asp175Asn mutation. Both types of HCM-CMs displayed pathological phenotype of HCM but, more importantly, we found differences between CMs carrying either MYBPC3-Gln1061X or TPM1-Asp175Asn gene mutation in their cellular size, Ca2+ handling, and electrophysiological properties, as well as their gene expression profiles. These findings suggest that even though the clinical phenotypes of the patients carrying either MYBPC3-Gln1061X or TPM1-Asp175Asn gene mutation are similar, the genetic background as well as the functional properties on the cellular level might be different, indicating that the pathophysiological mechanisms behind the two mutations would be divergent as well.
l-Leucine Supplementation Worsens the Adiposity of Already Obese Rats by Promoting a Hypothalamic Pattern of Gene Expression that Favors Fat Accumulation

Several studies showed that l-leucine supplementation reduces adiposity when provided before the onset of obesity. We studied rats that were exposed to a high-fat diet (HFD) for 10 weeks before they started to receive l-leucine supplementation. Fat mass was increased in l-leucine-supplemented rats consuming the HFD. Accordingly, l-leucine produced a hypothalamic pattern of gene expression that favors fat accumulation. In conclusion, l-leucine supplementation worsened the adiposity of rats previously exposed to HFD possibly by central mechanisms.
Agency and communion in spontaneous self-descriptions: Occurrence and situational malleability†

This study investigated agency and communion in self-descriptions using a free-response format as well as an established rating scale. I hypothesized that agency and communion as fundamental dimensions of social judgment also emerge in spontaneous self-descriptions; that self-descriptions comprise more communal than agentic content; and that self-descriptions vary intraindividually with context (work vs. family). In accord with these predictions, more than two-thirds of participants' (N = 73) self-descriptions could reliably be coded in terms of agency and communion. Participants generally used more communal than agentic attributes to describe themselves, but they did not rate the former as more important. Participants used more agentic characteristics to describe themselves in a work context than in a family context; conversely, they used more communal characteristics to describe themselves in a family context than in a work context. The correlations between spontaneous self-descriptions and rating-scale answers were low. Copyright © 2008 John Wiley & Sons, Ltd.
Trust in Organizational Superiors: Systemic and Collective Considerations

The social-psychological literature on trust in organizational superiors implies that it is an interpersonal phenomenon, based on the superior’s behaviours and on subordinates’ perceptions of the superior’s behaviours and qualities. The sociological literature, in contrast, implies that trust in a superior is a property of the system in which the superior-subordinate relationship is embedded. In this article, we suggest that trust is both an interpersonal and a collective phenomenon and focus on the linkages between three levels of trust: the system level, the group level, and the individual level. We use a longitudinal quantitative analysis of cadets’ trust in their team commanders and a qualitative analysis of critical incidents of trust building and erosion to develop and support three propositions. First, trust in a superior reflects subordinates’ trust in the system that the superior represents. Second, subordinates employ criteria derived from systemic properties such as collective identities and values to evaluate the trustworthiness of their superior. Third, team processes play a major role in the social construction of trust in a superior and in translating systemic considerations into criteria for evaluating superiors’ trustworthiness.
Epidemiologic and viral factors associated with cervical neoplasia in HPV‐16‐positive women

While infection with high‐risk HPV is the most important risk factor for cervical cancer, HPV alone is insufficient. Our purpose was to identify viral and epidemiologic factors associated with cervical disease in HPV‐16 DNA‐positive women referred to colposcopy. We used a standardized interview to collect epidemiologic data from consenting women. Total nucleic acids from exfoliated cervical cells were used for all viral assays (HPV detection and typing using L1 consensus PCR with line probe hybridization, variant classification by sequencing, viral load and transcript copy determination by quantitative PCR and transcript pattern by nested RT‐PCR). Cervical disease was based on colposcopic biopsy. Logistic regression was used to calculate ORs with 95% CIs. There were 115 HPV‐16 positive women among 839 enrollees. By univariate analyses, age >25 years (OR = 3.05, 95% CI 1.20–7.76), smoking (OR = 3.0, 95% CI 1.19–7.56), high viral load (OR = 5.27, 95% CI 2.05–13.60), detection of both E6 and E6*I transcripts (OR = 10.0, 95% CI 2.1–47.58) and high transcript copies (OR = 5.56, 95% CI 2.05–13.60) were significant risk factors for CIN III with reference to No CIN/CIN I. Less than a third of the women (31.5%) had prototype HPV‐16 detected, and variants showed no association with disease, viral load or transcription. Viral DNA and transcript copies were highly correlated, and the ratio of transcript copies to DNA copies was not changed with disease status. While viral load, transcript copies and transcript pattern were statistically associated with CIN III, none of these measures effectively discriminated between HPV‐16 women with disease requiring treatment and those who could be followed. Cellular proliferation and differentiation pathways affected by HPV should be investigated as biomarkers for cervical cancer screening. © 2005 Wiley‐Liss, Inc.
Volume decorrelation effects in polarimetric SAR interferometry

Volume decorrelation is an aspect of synthetic aperture radar interferometry that is currently at stake. It stems from the distribution in height of the backscattering cross section in a imaged scene, and it widely affects interferometric coherence images, e.g., in the presence of forests or buildings. The interest in its reduction lies on the fact that "resolving" volume decorrelation and fixing the exact position of the scattering centers in a resolution cell may lead to an estimation of the height of the observed distributed scatterers. Indeed, the determination of the volume scattering contribution is determinant in digital elevation model generation as well as in biomass estimation. However, volume decorrelation itself may be a source of information on the mechanisms that originate it. In this paper, a distinction is made between the behavior of volume decorrelation due to random volumes and stationary distributed targets. The two cases are then studied by means of polarimetry: the response of such targets to different polarizations is considered by applying a series of decompositions of the scattering matrix, and a systematic analysis of the interferometric coherence characteristics is reported.
Screening and Identifying Erosive Esophagitis in Children with Non-cardiac Chest Pain

Non-cardiac chest pain is a common disorder that leads to costly evaluations to distinguish it from cardiac pain. The present study aimed to clarify the clinical characteristics of erosive esophagitis in children with non-cardiac chest pain. Ninety nine patients (mean age, 9.55 ± 2.95 years, 49 girls) with non-cardiac chest pain were enrolled. Patients were classified into two groups: erosive esophagitis and non-erosive esophagitis-related non-cardiac chest pain by esophagogastroduodenoscopy. Children in the erosive esophagitis-related non-cardiac chest pain group were significantly older (10.95 ± 2.54 years vs. 8.52 ± 2.83 years). Multivariate logistic regression analysis identified the following predictors of gastroesophageal reflux: chest pain related to sleep (odds ratio = 18.05, 95% confidence interval: 3.18–102.49); unfavorable dietary habits (odds ratio = 7.11, 95% confidence interval: 1.53–32.87); chest pain related to food (odds ratio = 5.09, 95% confidence interval: 1.37–18.86); epigastric pain (odds ratio = 3.73, 95% confidence interval: 1.12–12.33); and nausea, vomiting, and/or regurgitation (odds ratio = 4.35, 95% confidence interval: 1.22–15.54). Gastroesophageal reflux disease should be considered first in children with non-cardiac chest pain. Children with gastroesophageal reflux disease should receive medical treatment and lifestyle modifications.
Protein phosphatase 1‐dependent dephosphorylation of Akt is the prime signaling event in sphingosine‐induced apoptosis in Jurkat cells

Sphingosine (SPH) is an important bioactive lipid involved in mediating a variety of cell functions including apoptosis. However, the signaling mechanism of SPH‐induced apoptosis remains unclear. We have investigated whether SPH inhibits survival signaling in cells by inhibiting Akt kinase activity. This study demonstrates that treatment of Jurkat cells with SPH leads to Akt dephosphorylation as early as 15 min, and the cells undergo apoptosis after 6 h. This Akt dephosphorylation is not mediated through deactivation of upstream kinases, since SPH does not inhibit the upstream phosphoinositide‐dependent kinase 1 (PDK1) phosphorylation. Rather, sensitivity to the Ser/Thr protein phosphatase inhibitors (calyculin A, phosphatidic acid, tautomycin, and okadaic acid) indicates an important role for protein phosphatase 1 (PP1) in this process. In vitro phosphatase assay, using Akt immunoprecipitate following treatment with SPH, reveals an increase in Akt‐PP1 association as determined by immunoprecipitation analysis. Moreover, SPH‐induced dephosphorylation of Akt at Ser473 subsequently leads to the activation of GSK‐3β, caspase 3, PARP cleavage, and ultimately apoptosis. Pre‐treatment with caspase 3 inhibitor z‐VAD‐fmk and Ser/Thr phosphatase inhibitor abrogates the effect of SPH on facilitating apoptosis. Altogether, these results demonstrate that PP1‐mediated inhibition of the key anti‐apoptotic protein, Akt, plays an important role in SPH‐mediated apoptosis in Jurkat cells. J. Cell. Biochem. 112: 1138–1153, 2011. © 2011 Wiley‐Liss, Inc.
Photoperiodic Regulation of Florigen Function in Arabidopsis thaliana

One mechanism through which flowering in response to seasonal change is brought about is by sensing the fluctuation in day-length; the photoperiod. Flowering induction occurs through the production of the florigenic protein FLOWERING LOCUS T (FT) and its movement from the phloem companion cells in the leaf vasculature into the shoot apex, where meristematic reprogramming occurs. FT activation in response to photoperiod condition is accomplished largely through the activity of the transcription factor CONSTANS (CO). Regulation of CO expression and protein stability, as well as the timing of other components via the circadian clock, is a critical mechanism by which plants are able to respond to photoperiod to initiate the floral transition. Modulation of FT expression in response to external and internal stimuli via components of the flowering network is crucial to mediate a fluid flowering response to a variety of environmental parameters. In addition, the regulated movement of FT protein from the phloem to the shoot apex, and interactions that determine floral meristem cell fate, constitute novel mechanisms through which photoperiodic information is translated into flowering time.
Comparison of 13CO line and far-infrared continuum emission as a diagnostic of dust and molecular gas physical conditions – III. Systematic effects and scientific implications

Far-infrared continuum data from the COBE/DIRBE instrument were combined with Nagoya 4-m 13 CO J = 1 → 0 spectral line data to infer the multiparsec-scale physical conditions in the OrionA and B molecular clouds, using 140 � m/240 � m dust color temperatures and the 240 � m/ 13 CO J = 1 → 0 intensity ratios. In theory, the ratio of far-IR, submillimeter, or millimeter continuum to that of a 13 CO (or C 18 O) rotational line can place reliable upper limits on the temperature of the dust and molecular gas on multi-parsec scales; on such scales, both the line and continuum emission are optically thin, resulting in a continuum-to-line ratio that suffers no loss of temperature sensitivity in the high-temperature limit as occurs for ratios of CO rotational lines or ratios of continuum emission in different wavelength bands. Two-component models fit the Orion data best, where one has a fixedtemperature and the other has a spatially varying temperature. The former represents gas and dust towards the surface of the clouds that are heated primarily by a very large-scale (i.e. ∼ 1kpc) interstellar radiation field. The latter represents gas and dust at greater depths into the clouds and are shielded from this interstellar radiation field and heated by local stars. The inferred physical conditions are consistent with those determined from previously observed maps of 12 CO J = 1 → 0 and J = 2 → 1 that cover the entire OrionA and B molecular clouds. The models require that the dust-gas temperature difference is 0±2K. If this surprising result applies to much of the Galactic ISM, except in
Speaking up, being heard: registered nurses' perceptions of workplace communication.

AIMS The aim of the present study was to explore nurses' perceptions of their own ability to speak up and be heard in the workplace. BACKGROUND Nurses are central to patient care and patient safety in hospitals. Their ability to speak up and be heard greatly impacts their own work satisfaction, team work as well as patient safety. METHOD The present study utilized a qualitative approach, consisting of focus group interviews of 33 registered nurses (RNs), in staff or management positions from a variety of healthcare settings in California, USA. Data were analysed using thematic content analysis. RESULTS Findings were organized into three categories: influences on speaking up, transmission and reception of a message and outcomes or results. The present study supported the importance of the manager in setting the culture of open communication. IMPLICATIONS FOR NURSE MANAGERS It is anticipated that findings from the present study may increase understandings of nurse views of communication within healthcare settings. The study highlights the importance of nurse managers in creating the communication culture that will allow nurses to speak up and be heard. These open communication cultures lead to better patient care, increased safety and better staff satisfaction.
Methylation Profiling of Archived Non–Small Cell Lung Cancer: A Promising Prognostic System

Purpose: Enhanced prognostication power is becoming more desirable in clinical oncology. In this study, we explored the prognostic potential of multigene hypermethylation profiling in non–small-cell lung cancer. Experimental Design: We evaluated a panel of eight genes (p16, APC, ATM, hMLH1, MGMT, DAPK, ECAD, and RASSF1A) using methylation-specific PCR in 105 archived specimens of non–small-cell lung cancer representing all stages of the illness. We analyzed the effect of gene methylation status on outcome individually in a cumulative manner and in a combinatorial approach using recursive partitioning to identify methylation profiles, which affect overall survival. Results: In this data set, tumors harboring promoter hypermethylation at two or more genes exhibit similar survival trends to others in the cohort. Using recursive partitioning, three genes (APC, ATM, and RASSF1A) emerged as determinants of prognostic groups. This designation retained its statistical significance even when disease stage and age were entered into a multivariate analysis. Using this approach, patients whose tumors were hypermethylated at APC and those hypermethylated at only ATM (not also at APC or RASSF1A) enjoyed substantially longer 1- and 2-year survival than patients in the remaining groups. In 32 adjacent histologically normal lung tissue specimens, we detected similar methylation abnormalities. Conclusion: Assessment of promoter hypermethylation aberrations may facilitate prognostic profiling of lung tumors, but validation in independent data sets is needed to verify these profiles. This system uses material that is abundantly available with linked outcome data and can be used to generate reliable epigenetic determinants.
ARMA lattice model for phoneme feature extraction

In this paper, the result of a study on phoneme feature extraction, under a noisy environment, using an auto-regressive moving average (ARMA) lattice model, is presented. The phoneme characteristics are modeled and expressed in the form of ARMA lattice reflection coefficients for classification. Experimental results, based on the TIMIT speech database and NoiseX-92 noise database, indicate that the ARMA lattice model achieves an improved noise-resistant capability on vowel phonemes and fricative phonemes as compared to those of the conventional mel-frequency cepstral coefficient (MFCC) method.