Miracle-dz/UniFAR-FTUs huggingface dataset:
Structural Determinants of M-Type KCNQ (Kv7) K+ Channel Assembly

The ability of KCNQ (Kv7) channels to form hetero-oligomers is of high physiological importance, because heteromers of KCNQ3 with KCNQ2 or KCNQ5 underlie the neuronal M-current, which modulates neuronal excitability. In KCNQ channels, we recently identified a C-terminal subunit interaction (si) domain that determines their subunit-specific assembly. Within this si domain, there are two motifs that comprise ∼30 amino acid residues each and that exhibit a high probability for coiled-coil formation. Transfer of the first or the second coiled-coil (TCC) domain from KCNQ3 into the KCNQ1 scaffold resulted in chimeras KCNQ1(TCC1)Q3 and KCNQ1(TCC2)Q3, both of which coimmunoprecipitated with KCNQ2. However, only KCNQ1(TCC2)Q3 enhanced KCNQ2 currents and surface expression or exerted a strong dominant-negative effect on KCNQ2. Deletion of TCC2 within KCNQ2 yielded functional homomeric channels but prevented the current augmentation measured after coexpression of KCNQ2 and KCNQ3. In contrast, deleting TCC1 within KCNQ2 did not give functional homomeric KCNQ2 or heteromeric KCNQ2/KCNQ3 channels. Mutations that disrupted the predicted coiled-coil structure of TCC1 in KCNQ2 or KCNQ3 abolished channel activity after expressing these constructs singly or in combination, whereas helix-breaking mutations in TCC2 of KCNQ2 gave functional homomeric channels but prevented the heteromerization with KCNQ3. In contrast, KCNQ3 carrying a coiled-coil disrupting mutation in TCC2 hetero-oligomerized with KCNQ2. Our data suggest that the TCC1 domains of KCNQ2 and KCNQ3 are required to form functional homomeric as well as heteromeric channels, whereas both TCC2 domains facilitate an efficient transport of heteromeric KCNQ2/KCNQ3 channels to the plasma membrane.
Protein-thiol oxidation and cell death: regulatory role of glutaredoxins.

SIGNIFICANCE Glutaredoxin (Grx) is the primary enzyme responsible for catalysis of deglutathionylation of protein-mixed disulfides with glutathione (GSH) (protein-SSG). This reversible post-translational modification alters the activity and function of many proteins important in regulation of critical cellular processes. Aberrant regulation of protein glutathionylation/deglutathionylation reactions due to changes in Grx activity can disrupt both apoptotic and survival signaling pathways. RECENT ADVANCES Grx is known to regulate the activity of many proteins through reversible glutathionylation, such as Ras, Fas, ASK1, NFκB, and procaspase-3, all of which play important roles in control of apoptosis. Reactive oxygen species and/or reactive nitrogen species mediate oxidative modifications of critical Cys residues on these apoptotic mediators, facilitating protein-SSG formation and thereby altering protein function and apoptotic signaling. CRITICAL ISSUES Much of what is known about the regulation of apoptotic mediators by Grx and reversible glutathionylation has been gleaned from in vitro studies of discrete apoptotic pathways. To relate these results to events in vivo it is important to examine changes in protein-SSG status in situ under natural cellular conditions, maintaining relevant GSH:GSSG ratios and using appropriate inducers of apoptosis. FUTURE DIRECTIONS Apoptosis is a highly complex, tightly regulated process involving many different checks and balances. The influence of Grx activity on the interconnectivity among these various pathways remains unknown. Knowledge of the effects of Grx is essential for developing novel therapeutic approaches for treating diseases involving dysregulated apoptosis, such as cancer, heart disease, diabetes, and neurodegenerative diseases, where alterations in redox homeostasis are hallmarks for pathogenesis.
Micro-Scale Genomic DNA Copy Number Aberrations as Another Means of Mutagenesis in Breast Cancer

Introduction In breast cancer, the basal-like subtype has high levels of genomic instability relative to other breast cancer subtypes with many basal-like-specific regions of aberration. There is evidence that this genomic instability extends to smaller scale genomic aberrations, as shown by a previously described micro-deletion event in the PTEN gene in the Basal-like SUM149 breast cancer cell line. Methods We sought to identify if small regions of genomic DNA copy number changes exist by using a high density, gene-centric Comparative Genomic Hybridizations (CGH) array on cell lines and primary tumors. A custom tiling array for CGH (244,000 probes, 200 bp tiling resolution) was created to identify small regions of genomic change, which was focused on previously identified basal-like-specific, and general cancer genes. Tumor genomic DNA from 94 patients and 2 breast cancer cell lines was labeled and hybridized to these arrays. Aberrations were called using SWITCHdna and the smallest 25% of SWITCHdna-defined genomic segments were called micro-aberrations (<64 contiguous probes, ∼ 15 kb). Results Our data showed that primary tumor breast cancer genomes frequently contained many small-scale copy number gains and losses, termed micro-aberrations, most of which are undetectable using typical-density genome-wide aCGH arrays. The basal-like subtype exhibited the highest incidence of these events. These micro-aberrations sometimes altered expression of the involved gene. We confirmed the presence of the PTEN micro-amplification in SUM149 and by mRNA-seq showed that this resulted in loss of expression of all exons downstream of this event. Micro-aberrations disproportionately affected the 5′ regions of the affected genes, including the promoter region, and high frequency of micro-aberrations was associated with poor survival. Conclusion Using a high-probe-density, gene-centric aCGH microarray, we present evidence of small-scale genomic aberrations that can contribute to gene inactivation. These events may contribute to tumor formation through mechanisms not detected using conventional DNA copy number analyses.
Management control and public sector performance management

Purpose The purpose of this paper is to investigate whether and how evolving ideas about management control (MC) emerge in research about public sector performance management (PSPM). Design/methodology/approach This is a literature review on PSPM research through using a set of key terms derived from a review of recent developments in MC. Findings MC research, originating in the management accounting discipline, is largely disconnected from PSPM research as part of public administration and public management disciplines. Overlaps between MC and PSPM research are visible in a cybernetic control approach, control variety and contingency-based reasoning. Both academic communities share an understanding of certain issues, although under diverging labels, especially enabling controls or, in a more general sense, usable performance controls, horizontal controls and control packaging. Specific MC concepts are valuable for future PSPM research, i.e. trust as a complement of performance-based controls in complex settings, and strategy as a variable in contingency-based studies. Research limitations/implications Breaking the boundaries between two currently remote research disciplines, on the one hand, might dismantle “would-be” innovations in one of these disciplines, and, on the other hand, may provide a fertile soil for mutual transfer of knowledge. A limitation of the authors’ review of PSPM research is that it may insufficiently cover research published in the public sector accounting journals, which could be an outlet for MC-inspired PSPM research. Originality/value The paper unravels the “apparent” and “real” differences between MC and PSPM research, and, in doing so, takes the detected “real” differences as a starting point for discussing in what ways PSPM research can benefit from MC achievements.
The preparation of magnetic nanoparticles and their decoration towards bifunctional nanoparticles

A novel coprecipitate reaction happens on the oil/water interface was utilized to fabricate magnetite nanoparticles (MNPs). Then a mercapto-silane molecule was decorated on the surface of nanoparticles, and thiol-capped quantum dots (QDs) was linked on by these molecules with silane group binding to MNPs and thiol group connecting with QDs. In addition, the MNPs were coated by a layer of silica, and their application in magnetic resonance image (MRI) was evaluated.
Exploration of delayed-onset posttraumatic stress disorder after severe injury.

OBJECTIVE The first aim of this work was to conduct a rigorous longitudinal study to identify rates of delayed-onset posttraumatic stress disorder (PTSD) in a sample of patients with severe injury. The second aim was to determine what variables differentiated delayed-onset PTSD from chronic PTSD. METHODS Randomly selected patients with injury who were admitted to four hospitals around Australia were recruited to the study (N = 834) and assessed in the acute care hospital, at 3 months, and at 12 months. A structured clinical interview was used to assess PTSD at each time point. RESULTS Seventy-three patients (9%; n = 73) had PTSD at 12 months. Of these, 39 (53%) were classified as having delayed-onset PTSD. Furthermore, 22 (56%) patients with delayed-onset PTSD had minimal PTSD symptoms at 3 months (i.e., they did not have partial/subsyndromal PTSD at 3 months). The variables that differentiated delayed-onset PTSD from chronic PTSD were greater injury severity (odds ratio [OR] = 1.13; 95% confidence interval [CI] = 1.02-1.26), lower anxiety severity at 3 months (OR = 0.73; 95% CI = 0.61-0.87), and greater pain severity at 3 months (OR = 1.39; 95% CI = 1.06-1.84). CONCLUSIONS Delayed-onset PTSD occurred frequently in this sample. Approximately half of the patients with delayed-onset PTSD had minimal PTSD symptoms at 3 months; therefore, their delayed-onset PTSD could not be accounted for by a small number of fluctuating symptoms. As we move toward DSM-V, it is important that research continues to explore the factors that underpin the development of delayed-onset PTSD.
Impaired Glucose Sensitivity of ATP-Sensitive K+ Channels in Pancreatic β-cells in Streptozotocin-Induced NIDDM Rats

ATP-sensitive K+ channels (KATP channels) are known to play a key role in the cellular mechanism of insulin secretion from pancreatic β cells. In order to examine the possible impairment of KATP channel function in non-insulin-dependent diabetes mellitus (NIDDM), we have studied the properties of the KATP channels in single β cells of neonatally streptozotocin-induced diabetic rats (NSZ rats) using the patch-clamp technique. The unitary conductance of the channel in diabetic β-cells was virtually identical to that in control beta cells and there was no difference in the sensitivity to ATP and glibenclamide of KATP channels between the NIDDM and control groups. In response to glucose, the activity of the KATP channels was diminished in a dose-dependent manner in both control and diabetic cells. However, the inhibition of the KATP channels in β-cells of NSZ rats was significantly < that in control cells. Even in the presence of 11.1 mM glucose, the openings of a few single KATP channels were consistently observed in cell-attached patch membranes of diabetic, but not control, β-cells. Thus, it appears that the impaired insulinotropic action of glucose in β-cells in NSZ rats is associated with a reduced sensitivity of the KATP channel to glucose, but not to ATP, presumably due to a deficiency in glucose metabolism.
Effects of folic acid fortification on orofacial clefts prevalence: a meta-analysis

Abstract Objective Orofacial clefts (OFC) are the most prevalent craniofacial birth defect. Folic acid (FA) supplementation has been demonstrated as an effective intervention to reduce risk of OFC occurrence. However, the effect of mandatory FA fortification of wheat and/or maize flour on OFC prevalence has shown controversial results among countries adopting this policy. Thus, we performed a meta-analysis to synthesize the available evidence evaluating the global impact of this mandatory policy on OFC occurrence. Design Literature search in conventional and grey medical/scientific databases showed fifteen studies considering OFC prevalence in pre- and post-fortification periods with FA. The effect of this policy was evaluated by computing relative risk (RR) and separating samples into total OFC, non-syndromic forms, cleft lip with or without cleft palate (CL/P) and cleft palate only (CPO). Results We found a significant effect of FA fortification only on non-syndromic CL/P (RR=0·88; 95 % CI 0·81, 0·96), whereas neutral effects were detected for total OFC (syndromic plus non-syndromic) and CPO. Conclusions Our results may reflect the different aetiology of syndromic OFC with respect to non-syndromic forms and the CL/P related to CPO. Although the number of non-syndromic CL/P samples was lower than that for total OFC, the absence of both between-study heterogeneity and publication bias leads us to conclude that FA fortification may have beneficial effects on non-syndromic CL/P.
The motivation and actions of Australians concerning brain health and dementia risk reduction.

ISSUE ADDRESSED Alzheimer's disease and dementia are recognised as critical public health priorities. This study investigated intentions and behaviours concerning brain health and dementia risk reduction among Australians. METHODS A cross-sectional survey of 1000 persons aged 20-75 years measured knowledge, beliefs, intentions and behaviours concerning brain health and dementia. The demographic, experiential and cognitive factors associated with intentions and actions were examined. RESULTS Around half of respondents were motivated to improve brain health. Behaviours most often reported were mental activity (19%), physical activity (9.6%) and dietary action (6.5%). Actions were most likely among women (OR 1.59, 95% CI 1.19-2.14), those aged 60 years and over (OR 3.07, 95% CI 2.01-2.58), with university education (OR 1.67, 95% CI 1.08-2.58) or with prior contact with a person with dementia (OR 1.99, 95% CI 1.12-3.56). Both intentions and actions were associated with moderate to high knowledge, and beliefs and confidence that favoured dementia risk reduction. CONCLUSIONS A lower proportion of Australians reported taking action to improve brain health than who expressed intentions in this regard. Strategies are needed to improve knowledge about the range of behaviours that contribute to dementia risk reduction and to increase confidence that this outcome is personally achievable. SO WHAT? The burden of disease due to Alzheimer's disease and dementia is growing dramatically. It is essential to promote awareness that dementia is not an inevitable result of ageing and to increase understanding that action can be taken throughout the life course to promote brain health.
A Simplified Method for (Circular) Transmission Line Model Simulation and Ultralow Contact Resistivity Extraction

The metal resistance in the transmission line model (TLM) structures creates a serious obstacle to determine precisely the intrinsic contact resistivity. To tackle this problem, we propose a new model, the lump model, to evaluate the metal resistance influence in both TLM and circular TLM (CTLM) test structures. In this letter, we demonstrate the high simplicity, great robustness, and flexibility of the lump model. The previous reported contact resistivity values extracted with CTLM are usually above 1 χ 10-7Ω · cm2 because the metal resistance impact is commonly neglected. This is the first time that the role of the metal in CTLM is appropriately analyzed. Low contact resistivity, 3. 6χ10-8Ω · cm2, of standard NiSi/n-Si contact has been extracted and this shows the high sensitivity of this method.
Dynamic Bias-Current Boosting Technique for Ultralow-Power Low-Dropout Regulator in Biomedical Applications

A dynamic bias-current boosting technique that concurrently enables ultralow-power operation and fast-transient behavior is presented in this brief. It is applied to an ultralow-power output-capacitor-free low-dropout regulator (LDO) to demonstrate the bandwidth extension provided during the transient periods. The proposed LDO is capable of providing 50 mA of output current with a minimum dropout voltage of 0.1 V. The ultralow-power LDO is implemented in a commercial 0.13-μm CMOS process, with power consumption of 1.20 μW only. Experimental results verify that both the load- and line-transient responses of the proposed LDO are significantly improved, and the settling times during load and line transients are shortened by as much as 33 and 3 times, respectively.
Quantitative measurement of mitochondrial membrane potential in cultured cells: calcium‐induced de‐ and hyperpolarization of neuronal mitochondria

• Within cells, mitochondria oxidize carbohydrates, and fatty and amino acids to use the released energy to form ATP, and in the process, they also generate reactive oxygen species. Their maximal rates are linked to the magnitude of the mitochondrial membrane potential. • Here we derive a model of fluorescent potentiometric probe dynamics, and on these principles we introduce an absolute quantitative method for assaying mitochondrial membrane potential in millivolts in individual cultured cells. • This is the first micro‐scale method to enable measurement of differences in mitochondrial membrane potential between cells with different properties, e.g. size, mitochondrial density and plasma membrane potential, including cases when plasma membrane potential fluctuates. • Mitochondrial membrane potential in cultured rat cortical neurons is −139 mV at rest. In response to electrical stimulation of the cells, it is regulated between −108 mV and −158 mV by concerted increases in energy demand and metabolic activation.
Cutaneous Adverse Events during Vemurafenib Therapy

Background: Vemurafenib, an oral agent that selectively targets the BRAF V600E mutation, has recently emerged as the mainstay of treatment in patients with BRAF-positive stage IV melanoma. A spectrum of cutaneous adverse events has been associated with vemurafenib, ranging from benign rashes to malignant side effects such as keratoacanthoma and squamous cell carcinoma. Objective: In this article, we review clinical data regarding the frequency and severity of the common dermatologic side effects associated with vemurafenib; case series and noncontrolled studies evaluating the safety of vemurafenib therapy are used to further characterize these adverse events. Conclusion: Benign vemurafenib-induced side effects generally tend not to be severe or life threatening, with most patients managed by dose interruptions, dose reductions, or topical therapies. Squamous cell carcinomas and keratoacanthomas associated with vemurafenib therapy are easily treated by simple excision of the lesion without discontinuation of vemurafenib. Thus, awareness of potential adverse events coupled with routine dermatologic assessment and timely management will allow for optimal therapeutic benefit in patients receiving vemurafenib therapy.
A novel coil winding technique applicable to multiple strands concentrated wound electric motors for low voltage-high torque applications

A new coil winding technique is developed for multiple strands concentrated wound electric motors. This coil winding method simplifies the winding steps, eradicates the requirement of having multiple spools for multiple strands winding and increases the slot fill factor. Low voltage-high current motor designs necessitate the use of multiple strands winding. Bending the end turns with multiple strands in hand is cumbersome with present day's coil winding technology. The developed technique uses multiple layers of single strand wires instead of multiple strands of wires, thus, making the end windings to bend easier. The balance of inductance and resistance among different layers is achieved by 'layer transposition'. While this technique is mostly suitable for segmented electromagnetic architecture, it can also be used in conventional twin pole electromagnetic designs having concentrated winding.
A Quantitative Method to Determine ICT Delay Requirements for Wide-Area Power System Damping Controllers

This paper presents a quantitative method to determine delay requirements of the information and communication technology (ICT) system supporting wide-area power oscillation damping (WAPOD) controllers. An allowable time delay for the ICT infrastructure named “equivalent time delay (ETD)” is defined. The ETD is calculated by numerically comparing the damping behavior of the system when local input signals (LI) and remote input signals (RI) are used in the damping controller. The use of a WAPOD is only justified when its response outperforms that of a controller using local inputs. Therefore, the total time delay in the control loop must be below the calculated ETD. As such, the ETD serves as a design criteria to determine ICT latency requirements. The selection of an effective RI signal can be carried out by considering the maximum delays (ETDs) of different wide-area measurements. A damping improvement ETDx % has been proposed using the same methodology indicating a minimum outperformance of the remote signals. The proposed method is demonstrated using the well-known Klein-Rogers-Kundur multi-machine power system and the Vietnamese power system model.
Adventitial remodeling after coronary arterial injury.

BACKGROUND Intraluminal thrombus formation and medial smooth muscle (SM) cell proliferation are recognized responses of the arterial system to injury. In contrast to these well-characterized processes during vascular repair, changes involving the adventitia have been largely neglected in previous studies. Hence, the goal of this investigation was to assess the response of the adventitia to coronary arterial injury. METHODS AND RESULTS Adventitial changes in porcine coronary arteries subjected to medial injury were characterized by immunohistochemistry, histochemistry, and microscopic morphometry. The rapid development of a hypercellular response in the adventitia was evident 3 days after balloon-induced medial injury. Cell proliferation, as assessed by proliferating cell nuclear antigen immunostaining, reached the maximum level in the adventitia at 3 days, whereas at 14 and 28 days, the number of replicating cells reverted toward the baseline. The proliferating activity in the adventitia exceeded that seen in the media at all times after injury. To further define the changes in the phenotype of adventitial cells, the expression of three cytoskeletal proteins (vimentin, alpha-SM actin, and desmin) was characterized. Fibroblasts in normal adventitia expressed vimentin but no alpha-SM actin or desmin. After injury, these cells acquired characteristics of myofibroblasts expressing alpha-SM actin, which peaked at 7 and 14 days. Desmin expression was patchy in the adventitia, as opposed to its homogeneous distribution in medial SM cells. The modulation of fibroblast phenotype was transient, inasmuch as alpha-SM actin immunostaining declined at 28 days after injury, when dense, collagen-rich scar was evident within the adventitia. The above-described changes involving hypercellularity of the adventitia, myofibroblast formation, and fibrosis were associated with a significant focal adventitial thickening at 3, 7, 14, and 28 days after injury (P < .01 versus uninjured coronary arteries). CONCLUSIONS This study demonstrates the involvement of the adventitia in the vascular repair process after medial injury. The hypercellularity of the adventitial layer, proliferation of fibroblasts, and modulation of their phenotype to myofibroblasts are associated with the development of the thickened adventitia. It is postulated that these phenomena affect vascular remodeling and may provide an important insight into the mechanisms of vascular disorders.