Miracle-dz/UniFAR-FTUs huggingface dataset:
Allosteric modulation of the mouse kir6.2 channel by intracellular H+ and ATP

The ATP‐sensitive K+ (KATP) channels are regulated by intracellular H+ in addition to ATP, ADP, and phospholipids. Here we show evidence for the interaction of H+ with ATP in regulating a cloned KATP channel, i.e. Kir6.2 expressed with and without the SUR1 subunit. Channel sensitivity to ATP decreases at acidic pH, while the pH sensitivity also drops in the presence of ATP. These effects are more evident in the presence of the SUR1 subunit. In the Kir6.2 + SUR1, the pH sensitivity is reduced by about 0.4 pH units with 100 μM ATP and 0.6 pH units with 1 mm ATP, while a decrease in pH from 7.4 to 6.8 lowers the ATP sensitivity by about fourfold. The Kir6.2 + SUR1 currents are strongly activated at pH 5.9‐6.5 even in the presence of 1 mm ATP. The modulations appear to take place at His175 and Lys185 that are involved in proton and ATP sensing, respectively. Mutation of His175 completely eliminates the pH effect on the ATP sensitivity. Similarly, the K185E mutant‐channel loses the ATP‐dependent modulation of the pH sensitivity. Thus, allosteric modulations of the cloned KATP channel by ATP and H+ are demonstrated. Such a regulation allows protons to activate directly the KATP channels and release channel inhibition by intracellular ATP; the pH effect is further enhanced with a decrease in ATP concentration as seen in several pathophysiological conditions.
Coexisting conformations of fibronectin in cell culture imaged using fluorescence resonance energy transfer

Fluorescence resonance energy transfer (FRET) between fluorophores attached to single proteins provides a tool to study the conformation of proteins in solution and in cell culture. As a protein unfolds, nanometer-scale increases in distance between donor and acceptor fluorophores cause decreases in FRET. Here we demonstrate the application of FRET to imaging coexisting conformations of fibronectin (Fn) in cell culture. Fn is a flexible 440-kDa extracellular matrix protein, with functional sites that are regulated by unfolding events. Fn was labeled with multiple donor and acceptor fluorophores such that intramolecular FRET could be used to distinguish a range of Fn conformations. The sensitivity of FRET to unfolding was tested by progressively denaturing labeled Fn using guanidium chloride. To investigate Fn conformation changes during cell binding and matrix assembly, we added labeled Fn to the culture medium of NIH 3T3 fibroblasts. Coexisting conformations of Fn were visualized using fluorescence microscopy, and spectra from specific features were measured with an attached spectrometer. Using FRET as an indicator of Fn conformation, Fn diffusely bound to cells was in a compact state, whereas Fn in matrix fibrils was highly extended. Matrix fibrils exhibited a range of FRET that suggested some degree of unfolding of Fn's globular modules. Fn in cell-associated clusters that preceded fibril formation appeared more extended than diffuse cell-bound Fn but less extended than fibrillar Fn, suggesting that Fn undergoes extension after cell binding and before polymerization. FRET thus provides an approach to gain insight into the integrin-mediated pathway of Fn fibrillogenesis.
Reliability and procedural validity of UM-CIDI DSM-III-R phobic disorders

Synopsis We evaluate the long-term test–retest reliability and procedural validity of phobia diagnoses in the UM-CIDI, the version of the Composite International Diagnostic Interview, used in the US National Co-morbidity Survey (NCS) and a number of other ongoing large-scale epidemiological surveys. Test–retest reliabilities of lifetime diagnoses of simple phobia, social phobia, and agoraphobia over a period between 16 and 34 months were K = 0·46, 0·47, and 0·63, respectively. Concordances with the Structured Clinical Interview for DSM-III-R (SCID) were K = 0·45, 0·62, and 0·63, respectively. Diagnostic discrepancies with the SCID were due to the UM-CIDI under-diagnosing. Post hoc analysis demonstrated that modification of UM-CIDI coding rules could dramatically improve cross-sectional procedural validity for both simple phobia (K = 0·57) and social phobia (K = 0·95). Based on these results, it seems likely that future modification of CIDI questions and coding rules could lead to substantial improvements in diagnostic validity.
Controversies in iron management.

BACKGROUND Iron therapy is required in hemodialysis patients receiving erythropoietic stimulators in order to achieve the target hemoglobin in the most efficient way. While oral iron has been disappointing in this regard, parenteral iron has been widely used, despite a significant incidence of severe side effects when iron dextran is used. The recent availability of a more effective form of oral iron (heme-iron), and safer forms of parenteral iron (iron sucrose and iron gluconate) has made iron management in this population simpler. Many questions remain, however, about the use, efficacy, and safety of these compounds in hemodialysis patients. METHODS Current literature was reviewed and combined with the authors' clinical experience to address a number of current questions regarding the use of iron in hemodialysis patients. RESULTS Although oral non-heme iron is infrequently sufficient to maintain iron stores in hemodialysis patients, recent studies suggest that heme-iron may be more useful in this regard. Heme-iron is absorbed to a greater extent than non-heme iron, and is better tolerated. Small studies have shown that when heme-iron is administered, less parenteral iron and lower doses of erythropoietin (EPO) are needed to maintain target hemoglobin. Current evidence suggests that both iron sucrose and iron gluconate are safer than iron dextran, and the latter should only be used in extraordinary circumstances. While in vitro studies have demonstrated some differences in the effects of iron sucrose and iron gluconate on cellular toxicity, the clinical importance of these has not been determined. Both compounds can be used safely for repletion and maintenance therapy, and doses of up to 300 mg of either are generally well tolerated when such higher doses are needed, as in peritoneal dialysis (PD) patients or chronic kidney disease (CKD) patients not on dialysis. CONCLUSION A number of questions remain regarding the appropriate use, efficacy, and potential toxicity of iron therapy in dialysis patients. Further prospective research should address the myriad questions raised in this review.
Pulmonary hypertension and elevated transpulmonary gradient in patients with mitral stenosis.

BACKGROUND AND AIM OF THE STUDY Pulmonary hypertension frequently complicates mitral stenosis, with a subset of these patients exhibiting pressures well in excess of their mitral valve hemodynamics. The prevalence of this condition and its impact on clinical outcome following percutaneous balloon mitral commissurotomy (PBMC) is unknown. METHODS The transpulmonary gradient (TPG) was measured in 317 patients undergoing PBMC; patients were subsequently defined as having either an appropriate or excessive TPG (< or =15 mmHg or >15 mmHg, respectively). Twenty-two patients were excluded due to valvuloplasty-related significant mitral regurgitation. The remaining 295 patients (250 females, 45 males; mean age 52 +/- 13 years) were prospectively followed up, with each patient underwent serial echocardiography. RESULTS Among the patients, 214 (73%) had pulmonary hypertension (pulmonary artery pressure >25 mmHg) and 55 (19%) also had an elevated TPG. Females were almost fivefold more likely than males to have an elevated TPG (p = 0.003). Patients with an elevated TPG had a worse mean NYHA functional class than those with a normal TPG (3.0 +/- 0.5 versus 2.7 +/- 0.6, p = 0.01), while the mitral valve area (MVA) was slightly smaller in patients with an elevated TPG (1.0 +/- 0.2 versus 1.1 +/- 0.2 cm2, p = 0.003). All patients demonstrated a significant increase in MVA after commissurotomy (final MVA 1.7 +/- 0.6 cm2, p < 0.001 for elevated TPG; 1.8 +/- 0.4 cm2, p < 0.001 for normal TPG), and the NYHA class at six months was improved for all patients (2.8 +/- 0.6 versus 1.6 +/- 0.7, p < 0.001). The improvements in NYHA class, TPG and MVA were sustained at 36 months. CONCLUSION Pulmonary hypertension with elevated TPG occurs in patients with mitral stenosis, and is significantly more common in females. Despite worse symptoms and higher right-sided pressures, PBMC is equally successful in patients with a normal TPG, and provides sustained benefit for up to 36 months after the procedure.
Complications and Management of Polymethylmethacrylate (PMMA) Injections to the Midface.

BACKGROUND Polymethylmethacrylate (PMMA) has been used as an injectable filler to treat hollows and reduce rhytids. PMMA injections have been associated with several side effects, however, the literature is scarce on periorbital complications and their treatments. OBJECTIVES The purpose of this study is to report a series of complications after periorbital PMMA injections to the midface and to describe their management. METHODS Retrospective chart review, including photography and histopathology when available. RESULTS The authors identified 11 cases of complications of PMMA injections to the midface. Patient ages ranged from 36 to 62 years (mean, 47 years; median, 44 years). Two (18%) were males and 9 (82%) were females. Adverse effects began between 2 to 24 months after injection (mean, 7.2 months; median, 6 months). All patients had edema, erythema, and contour irregularity. Seven (64%) patients had nodules, 4 (36%) had yellow, xanthomatous skin changes, and 2 (18%) had eyelid malposition. Histopathology demonstrated a giant cell inflammation in 5 of 6 cases. Corticosteroid injection was tried in 6 cases but was associated with minimal clinical improvement. Surgical debulking of the implanted material was performed in 9 (82%) cases and was effective in improving edema, erythema, and nodularity. CONCLUSIONS PMMA injection to the midface may be associated with chronic inflammation, fibrotic nodules, yellowing of the skin, and eyelid malposition. Intralesional corticosteroid injections yielded minimal or no improvement; surgical debulking achieved favorable results. LEVEL OF EVIDENCE 4: Therapeutic.
T2 and DWI in Pilocytic and Pilomyxoid Astrocytoma with Pathologic Correlation

Objective: To quantify and compare T2 signal and apparent diffusion coefficient (ADC) in pilocytic and pilomyxoid astrocytoma (PA and PMA) and correlate results with myxoid content. Methods: Echo-planar diffusion weighted images (DWI) and standard magnetic resonance imaging (MRI) findings were reviewed retrospectively in patients with PA (n=34) and PMA (n=8). Regions of interest (ROIs) were drawn on ADC maps within tumor parts with lowest ADC values. Apparent diffusion coefficient values in tumor were normalized to those in cerebrospinal fluid (ADC/CSF). The ratio of T2 signal intensity in solid tumor parts to CSF (T2/CSF) was registered. Myxoid matrix was histologically quantified retrospectively in 8 PMAs and 17 PAs and correlated with imaging findings. Results: Mean ADC/CSF for PA and PMA was 0.53±0.10 and 0.69±0.10 (p<0.01). Mean T2/CSF for PA and PMA was 0.78±0.19 and 0.93±0.09 (p<0.01). Mean proportion of myxoid tumor matrix in PA was 50% (range, 10-100%) and 93% (range, 90-100%) in PMA (p=0.004). Eight patients (32%; all PA) had less than 50% myxoid content and 17 (68%; 8 PA; 9 PMA) had more. There was positive correlation of ADC/CSF, T2/CSF and ADC (r2=0.61, 0.65 and 0.60 respectively) and significant difference between the groups with more and less than 50% myxoid content (p=0.01 for ADC/CSF and T2/CSF and p=0.02 for ADC). Conclusions: General imaging features of PA and PMA are non-specific, ADC values and T2 signal intensity are generally higher in the latter, reflecting the proportion of myxoid matrix in these tumors.
Activity-Dependent Anchoring of Importin α at the Synapse Involves Regulated Binding to the Cytoplasmic Tail of the NR1-1a Subunit of the NMDA Receptor

Synaptic plasticity, the capacity of neurons to change the strength of their connections with experience, provides a mechanism for learning and memory in the brain. Long-term plasticity requires new transcription, indicating that synaptically generated signals must be transported to the nucleus. Previous studies have described a role for importin nuclear transport adaptors in mediating the retrograde transport of signals from synapse to nucleus during plasticity. Here, we investigated the possibility that stimulus-induced translocation of importins from synapse to nucleus involves activity-dependent anchoring of importins at the synapse. We show that importin α binds to a nuclear localization signal (NLS) present in the cytoplasmic tail of NR1-1a. This interaction is disrupted by activation of NMDA receptors in cultured neurons and by stimuli that trigger late-phase, but not early-phase, long-term potentiation of CA3–CA1 synapses in acute hippocampal slices. In vitro PKC phosphorylation of GST-NR1-1a abolishes its ability to bind importin α in brain lysates, and the interaction of importin α and NR1 in neurons is modulated by PKC activity. Together, our results indicate that importin α is tethered at the postsynaptic density by binding to the NLS present in NR1-1a. This interaction is activity dependent, with importin α being released following NMDA receptor activation and phosphorylation rendering it available to bind soluble cargoes and transport them to the nucleus during transcription-dependent forms of neuronal plasticity.
La atenuación en el habla de Madrid: patrones sociopragmáticos

The study of attenuation has experienced a considerable but still limited development in the last decades. It has been tackled, especially, within the disciplines that work with the spoken language, such as pragmatics or discourse analysis, which have broadened the scope of study. So far, one of the least addressed issues in the use of attenuation strategies in Spanish is the variation conditioned by social factors. Hence, with the final aim of gaining deeper knowledge about the use Spanish speakers make of attenuation devices, the discursive functions these fulfi ll and the incidence that given social factors (e.g. gender, age and level of instruction) have on their use, solid sociopragmatic research is being carried out within the framework of the research project entitled “Sociolinguist Study on the Spanish from Spain and Latin America Project (PRESEEA)”. In this article the more signifi cant results obtained after the analysis of the Madrid corpus and the more relevant conclusions reached are presented.
Early scrotal approximation after hemiscrotectomy in patients with Fournier's gangrene prevents scrotal reconstruction with skin graft.

OBJECTIVE We report the outcomes of an early loose closure of the scrotum with a modified U-stitch to minimize use of split thickens skin graft for patients with hemiscrotal tissue loss after surgical debridement. METHODS From January 2006 to August 2011, 28 male patients presented with Fournier's gangrene, requiring major urological surgical care and scrotal debridement at Denver Health Medical Center. Surgical outcomes were compared between patients receiving a novel U-Stitch approximation and those treated by traditional management. RESULTS The mean age of the patients was 47.1 ± 10.2 years. In total 8 patients (2.2%) developed bacteremia and 3 (0.1%) had methicillin-resistant staphylococcus aureus (MRSA) infection. There was conversion from the U-Stitch approximation patients to traditional management. U-stitch patients required less hospitalization than patients requiring split-thickness skin graft (STSG) due to loss of >50% of the total scrotal tissue (11 vs. 35 days, p = 0.081). The U-stitch demonstrated non-inferiority to traditional treatment. CONCLUSION Immediate loose scrotal wound approximation with efficient surgical debridement for Fournier's gangrene may prevent testis exposure facilitating local wound treatment, decreasing the length of hospital stay in patients with Fournier's gangrene involving the scrotum. Future randomized trials may validate these findings.
An intensive study on rule acquisition in formal decision contexts based on minimal closed label concept lattices

AbstractRule acquisition is one of the main purposes in the analysis of formal decision contexts. Up to now, there have been several types of rules in formal decision contexts. However, these existing rules were investigated independently and are, to some extent, unsatisfactory for making better decision analysis since some of them (e.g. decision implications) are computationally expensive and others (e.g. decision rules and granular rules) are short of compactness. Motivated by these problems, minimal closed label concept lattice is defined to present limitary decision implications, which not only are easier to be extracted than decision implications, but also have more concise premises than decision rules and granular rules. Moreover, we discuss the pairwise inclusion and inference relationships among limitary decision implications, decision implications, decision rules and granular rules. Finally, some numerical experiments are conducted to demonstrate that the proposed limitary decision implications a.
Gas phase atmospheric bromine photochemistry

This paper reviews the current knowledge of gas phase bromine photochemistry and presents a budget study of atmospheric bromine species. The effectiveness of the ozone catalytic loss cycles involving bromine is quantified by considering their chain length and effectiveness. The chain effectiveness is a new variable defined as the chain length multiplied by the rate of the cycle's rate-limiting step. The chain effectiveness enables a fair comparison of different catalytic cycles involving species which have very different concentrations. This analysis clearly shows that below 25 km the BrO/ClO and BrO/HO2 cycles are among the most important ozone destruction cycles.
Enhancing the quality of case studies in health services research.

OBJECTIVE To provide guidance on improving the quality of case studies in health services research. DATA SOURCES Secondary data, drawing from previous case study research. RESEARCH DESIGN Guidance is provided to two audiences: potential case study investigators (eight items) and reviewers of case study proposals (four additional items). PRINCIPAL FINDINGS The guidance demonstrates that many operational steps can be undertaken to improve the quality of case studies. These steps have been a hallmark of high-quality case studies in related fields but have not necessarily been practiced in health services research. CONCLUSIONS Given higher-quality case studies, the case study method can become a valuable tool for health services research.
Deep Learning for Experimental Physics

Author(s): Sadowski, Peter | Advisor(s): Baldi, Pierre | Abstract: Experimental physicists explore the fundamental nature of the universe by probing the properties of subatomic particles using specialized detectors. These detectors generate vast quantities of data that must undergo multiple stages of processing, such as dimensionality-reduction and feature extraction, before statistical analysis and interpretation. The processing steps are typically designed by physicists, using expert knowledge and intuition. However, this approach is human-limited and costly --- useful information is inevitably lost. Machine learning offers an alternative approach in which processing steps are instead learned from data. In particular, deep learning is the approach of learning many processing steps simultaneously. In this dissertation, we apply deep learning to a number of data analysis pipelines in experimental physics. We demonstrate that human-engineered processing steps can instead be learned from data, and that the deep learning approach can retain useful information from low-level data that is otherwise lost. Ultimately, this has the potential to both streamline data analysis pipelines and increase the statistical power of experiments, speeding up scientific discoveries.
Frequency synchronization for carrier allocation in uplink OFDMA systems

One of the most prominent issues in the design and implementation of OFDMA based systems is the need for a very fine frequency synchronization due to the fact that OFDMA, like OFDM, is extremely sensitive to carrier frequency offsets (CFO). The task of frequency synchronization becomes more challenging in the uplink OFDMA-based systems where one OFDMA symbol is generated by the contribution of many different users. Our goals include the study and analysis of problems resulting from frequency mismatches provide solution to combat these problems. We first look at the interference resulting from CFOs, resulting from user terminal oscillator mismatch. We demonstrate that one must take into account the cyclic prefix while analyzing interference resulting from CFO. A new analytical expression of the ICI that takes into account the effect of CFO on the cyclic prefix is proposed. Then we focus our attention on analysis of the trade-off between channel frequency diversity and robustness against CFO and show that there exists a contradiction between the two. We propose a trade-off in the form of a Threshold blocksize, to allow a good compromise between the channel diversity and robustness for CFO for the case when no CSI is available. For system where CSI is available, we propose an optimal block carrier allocation scheme through which both robustness to CFO and channel frequency diversity can be achieved with small blocksize for small CFO. We also propose a Critical CFO value, above which the performance of the optimal block carrier allocation loses interest. Next we propose solutions for two important issues encountered in an uplink OFDMA system. First, we propose an efficient method for joint estimation of channel impulse responses and carrier frequency at the receiver based on polynomial approximation. Our proposed joint estimation method is simpler than the existing methods without any performance degradation. Next we propose a CFO compensation method based on successive interference cancellation. The proposed cancellation method reduces the implementation complexity faced in case of large DFT matrices.
A Review of Ultrastructural and Ultracytochemical Studies of Infection Processes in Some Plant Wilt Diseases: The Opaque Matter Extensively Involved, Its Links with Pathogen Elements, Insights into Its Nature

Abstract The present review is based on results of several years of investigation on the pathogenesis of plant wilt diseases using for one of the main aspects, several labeling techniques at the ultrastructural level: autoradiography with 3H-thymidine; gold-tagged lectins, enzymes, polyclonal, and monoclonal antibodies. Thus, opaque matter (OM), labeling for DNA with the appropriate markers, can be abundant in and associated with host tissue reactions and pronounced alterations (particularly in newly differentiated xylem). The presence of structures (called P-elements) in OM, paralleled by a similar occurrence in nuclei of both the host and pathogen cells, is considered as being also indicative of a cytoplasmic nature for this OM and most likely originating from fungal elements.