Miracle-dz/UniFAR-FTUs huggingface dataset:
Graphene‐Modified Interface Controls Transition from VCM to ECM Switching Modes in Ta/TaOx Based Memristive Devices

By modification of the electrode-solid-electrolyte interface with graphene, transit from valence change memories (VCM) to electrochemical metallization memories (ECM) in the cell Ta(C)/Ta2 O5 /Pt is demonstrated, thus, bridging both mechanisms. The ECM operation is discussed in the light of Ta-cation mobility in TaOx . The crucial role of electrochemical processes and moisture in the resistive switching process is also highlighted.
A cage without a view increases stress and impairs cognitive performance in rats

Single housing is believed to be chronically stressful and to have a negative impact on welfare and cognition in rats (Rattus norvegicus). However, single housing does not consistently evoke stress-like responses nor does it consistently impair cognitive performance. In an experiment in which all cages were separated by an opaque barrier, single- and pair-housed pigmented (dark-eyed) rats performed equally in a cognitive test and displayed similar levels of anxiety during testing. Additionally, bar biting in the home cage did not differ between the two groups. Stress levels both during cognitive testing and in the home cage were higher than those we have previously reported when rats were housed without opaque barriers between the cages. We conclude that visual interactions between rats in different cages may be of sufficient significance that single housing in a cage with a view to neighbouring rats and to the rest of the laboratory holding room may be preferable to pair housing in a cage without this view.
Nuclease activity of Saccharomyces cerevisiae Dna2 inhibits its potent DNA helicase activity

Significance The integrity of DNA must be preserved to pass genetic information onto the next generation and to prevent genomic instability. One of the key enzymes involved in DNA metabolism is the nuclease-helicase Dna2, which is required for both DNA replication and the repair of broken DNA. Our work revealed that Dna2 from Saccharomyces cerevisiae possesses a potent but cryptic helicase capacity, which is controlled by the nuclease activity of the same polypeptide. Regulating the interplay between both enzymatic activities might explain how Dna2 can take on its distinct cellular roles. Dna2 is a nuclease-helicase involved in several key pathways of eukaryotic DNA metabolism. The potent nuclease activity of Saccharomyces cerevisiae Dna2 was reported to be required for all its in vivo functions tested to date. In contrast, its helicase activity was shown to be weak, and its inactivation affected only a subset of Dna2 functions. We describe here a complex interplay of the two enzymatic activities. We show that the nuclease of Dna2 inhibits its helicase by cleaving 5′ flaps that are required by the helicase domain for loading onto its substrate. Mutational inactivation of Dna2 nuclease unleashes unexpectedly vigorous DNA unwinding activity, comparable with that of the most potent eukaryotic helicases. Thus, the ssDNA-specific nuclease activity of Dna2 limits and controls the enzyme's capacity to unwind dsDNA. We postulate that regulation of this interplay could modulate the biochemical properties of Dna2 and thus license it to carry out its distinct cellular functions.
Functional interplay between a virus and the ESCRT machinery in Archaea

Recently it has been discovered that a number of eukaryotic viruses, including HIV, coopt the cellular Endosomal Sorting Complex Required for Transport (ESCRT) machinery to affect egress from infected cells. Strikingly, the ESCRT apparatus is conserved in a subset of Archaea, including members of the genus Sulfolobus where it plays a role in cytokinesis. In the current work, we reveal that the archaeal virus Sulfolobus turreted icosahedral virus isolated from Yellowstone National Park's acidic hot springs also exploits the host ESCRT machinery in its replication cycle. Moreover, perturbation of normal ESCRT function abrogates viral replication and, thus, prevents establishment of a productive Sulfolobus turreted icosahedral virus infection. We propose that the Sulfolobus ESCRT machinery is involved in viral assembly within the cytoplasm and in escape from the infected cell by using a unique lysis mechanism. Our results support an ancient origin for viruses “hijacking” ESCRT proteins to complete their replication cycle and thus identify a critical host–virus interaction conserved between two domains of life.
The effect of static and dynamic stretching exercises on the maximal isokinetic strength of the knee extensors and flexors

Warm-up and stretching exercises constitute an essential part of physical preparation before any athletic event. The aim of this study was to examine the acute effect of static and dynamic stretching exercises on maximal isokinetic torque of knee extensor and flexor muscles. Thirty-two (n = 32) physical education students aged 19-22 years were asked to perform three different protocols consisting of A) warm-up, B) warm-up and static stretching and C) warm-up and dynamic stretching exercises, on three non-consecutive days. Each treatment was followed by measurements of knee extensor and flexor muscles maximal concentric torque on an isokinetic dynamometer at 60 and 180 ◦ /s. ANOVA for repeated-measures revealed significant differences in maximal torque following the different protocols. Tukey's post hoc tests showed a reduced torque for knee extensor ( p< 0.01) and knee flexor muscles ( p< 0.01) at both velocities when static stretching exercises preceded the test. These findings indicate the negative influence of the static stretching exercises on maximal isokinetic torque production, while dynamic stretching approach does not seem to have any inhibitory effect.
Conserved microRNA pathway regulates developmental timing of retinal neurogenesis

Significance The sequential generation of different types of neurons and glia is a fundamental property of neurogenesis, but little is known about the mechanisms controlling this phenomenon. Conditional deletion of Dicer prevents progenitors from progressing in their competence to generate late cell types, indefinitely generating early cell types. We now elucidate the molecular mechanism for this phenomenon. Three microRNAs, let-7, microRNA-125, and microRNA-9, serve as key regulators of the early to late developmental transition in retinal progenitors. These results show how progenitor temporal identity is controlled, a finding that will impact efforts to generate specific neural types from pluripotent stem cells. Most regions of the vertebrate central nervous system develop by the sequential addition of different classes of neurons and glia. This phenomenon has been best characterized in laminated structures like the retina and the cerebral cortex, in which the progenitor cells in these structures are thought to change in their competence as development proceeds to generate different types of neurons in a stereotypic sequence that is conserved across vertebrates. We previously reported that conditional deletion of Dicer prevents the change in competence of progenitors to generate later-born cell types, suggesting that specific microRNAs (miRNAs) are required for this developmental transition. In this report, we now show that three miRNAs, let-7, miR-125, and miR-9, are key regulators of the early to late developmental transition in retinal progenitors: (i) members of these three miRNA families increase over the relevant developmental period in normal retinal progenitors; (ii) inhibiting the function of these miRNAs produces changes in retinal development similar to Dicer CKO; (iii) overexpression of members of these three miRNA families in Dicer-CKO retinas can rescue the phenotype, allowing their progression to late progenitors; (iv) overexpression of these miRNAs can accelerate normal retinal development; (v) microarray and computational analyses of Dicer-CKO retinal cells identified two potential targets of the late-progenitor miRNAs: Protogenin (Prtg) and Lin28b; and (vi) overexpression of either Lin28 or Prtg can maintain the early progenitor state. Together, these data demonstrate that a conserved miRNA pathway controls a key step in the progression of temporal identity in retinal progenitors.
mitoBKCa is encoded by the Kcnma1 gene, and a splicing sequence defines its mitochondrial location

The large-conductance Ca2+- and voltage-activated K+ channel (BKCa, MaxiK), which is encoded by the Kcnma1 gene, is generally expressed at the plasma membrane of excitable and nonexcitable cells. However, in adult cardiomyocytes, a BKCa-like channel activity has been reported in the mitochondria but not at the plasma membrane. The putative opening of this channel with the BKCa agonist, NS1619, protects the heart from ischemic insult. However, the molecular origin of mitochondrial BKCa (mitoBKCa) is unknown because its linkage to Kcnma1 has been questioned on biochemical and molecular grounds. Here, we unequivocally demonstrate that the molecular correlate of mitoBKCa is the Kcnma1 gene, which produces a protein that migrates at ∼140 kDa and arranges in clusters of ∼50 nm in purified mitochondria. Physiological experiments further support the origin of mitoBKCa as a Kcnma1 product because NS1619-mediated cardioprotection was absent in Kcnma1 knockout mice. Finally, BKCa transcript analysis and expression in adult cardiomyocytes led to the discovery of a 50-aa C-terminal splice insert as essential for the mitochondrial targeting of mitoBKCa.
Renal cell cancer--a multimodal approach to preserving renal function and improving survival.

Renal cancer comprises ~3% of all malignancies and in the past decade, the incidence has grown from 2.3 to 4.3% per year [1]. In Germany, the estimated number of newly diagnosed cases of renal cell cancer is 21.3 per 100 000 for men and 10 per 100 000 for women [2]. Renal cell cancer accounts for the top 10 cancer-associated mortalities in the Western world [3]. The size of renal cancer tumours has decreased in the past decade mainly due to the widespread use of ultrasonography [4, 5]. Within the past 10 years, tumour size at initial diagnosis has decreased from 4.1 cm in 1998 to 3.1 cm in 2008. In addition, the majority of patients diagnosed with renal cell cancer are in the 701 to 85 age group, with considerable comorbidity [3]. Despite early diagnosis and a smaller tumor size, the overall survival in patients with renal cell cancer has not improved significantly in the past years. In contrast to other parenchymal malignancies, reduction of organ mass in renal cell cancer and the partial loss of renal function influence the survival of patients with kidney-associated malignancy considerably [6].
Assessment of difficult airway predictors for predicting difficult laryngoscopy and intubation

Objectives: The aims and objectives of this study was to study and compare the sensitivity, specificity, positive predictive value, negative predictive value, odds ratio, relative risk, likelihood ratio and accuracy of the following parameters, modified Mallampati grading, interincisor gap, thyromental distance (TMD), ratio of height to thyromental distance (RHTMD), sternomental distance, neck movements, mandibular length and mentohyoid distance for predicting difficult laryngoscopy and/or intubation. Methods: A single blinded prospective observational study involving 100 patients of both gender between 20-70 years of age belonging to ASA physical status I, II and III scheduled to undergo elective surgery under general anaesthesia with endotracheal intubation were recruited for the study. All patients were subjected to the preoperative airway assessment and the above 8 airway parameters were recorded and analysed. The number of intubation attempts were noted. Use of intubation aids were also noted. Conclusion: Upper lip bite test can be used as a simple bedside screening test for prediction of difficult laryngoscopy/intubation but it should be combined with other airway assessment tests. RHTMD is a more accurate test than TMD. Inspite of various airway assessment tests no single test is 100% accurate. So it is advisable to use combination of different tests or the use various scoring systems for predict predicting difficult laryngoscopy/intubation.
Synthesis of Functional Nanomaterials in Ionic Liquids

Utilization of ionic liquids (ILs) in material synthesis is a promising field. The unusual properties of ILs provide new opportunities for the design of functional materials, and much excellent work has been reported. Here, the progress in material design and synthesis using ILs, especially nanomaterials, is discussed, including the unitization of ILs as synthetic media, templates, precursors, or components in the synthesis of various categories of nanomaterials. The challenges and opportunities in this interesting and rapid developing area are also discussed.
Effect of mean arterial pressure, haemoglobin and blood transfusion during cardiopulmonary bypass on post-operative acute kidney injury.

BACKGROUND Acute kidney injury (AKI) after cardiac surgery is a common and serious condition carrying significant costs. During cardiopulmonary bypass (CPB) surgery, modifiable factors may contribute to post-operative AKI. Their avoidance might be a potential target for nephroprotection. METHODS The objective of the present study was to identify and determine whether intraoperative hypotension, anaemia, or their combination, red blood cell transfusion or vasopressor use are independent risk factors for post-operative AKI defined by the RIFLE (renal Risk, Injury, Failure, Loss of renal function and End-stage renal disease) classification and other thresholds using a mixed logistic multivariate model. RESULTS We analysed 381 468 mean arterial pressure (MAP) measurements from 920 consecutive on-pump cardiac surgery patients. Overall, 19.5% developed AKI which was associated with an 8.2-fold increase in-hospital mortality. Haemoglobin concentration was an independent risk factor for AKI {odds ratio [OR] 1.16 per g/dL decrease [95% confidence interval (CI) 1.05-1.31]; P = 0.018} with systemic arterial oxygen saturation and pressure values not adding further strength to such an association. MAP alone or vasopressor administration was not independently associated with AKI but volume of red blood cell transfusion was, with its effect being apparent at a haemoglobin level of >8 g/dL (>5 mmol/L). In patients with severe anaemia (<25th percentile of lowest haemoglobin), the independent effect of hypotension (>75th percentile of area under the curve MAP <50 mmHg) on AKI was more pronounced [OR 3.36 (95% CI 1.34-8.41); P = 0.010]. CONCLUSION Intraoperative avoidance of the extremes of anaemia, especially during severe hypotension and avoidance of transfusion in patients with haemoglobin levels >8 g/dL (>5 mmol/L) may help decrease AKI in patients undergoing cardiac surgery and represent targets for future controlled interventions.
Recent Developments in p‐Type Oxide Semiconductor Materials and Devices

The development of transparent p‐type oxide semiconductors with good performance may be a true enabler for a variety of applications where transparency, power efficiency, and greater circuit complexity are needed. Such applications include transparent electronics, displays, sensors, photovoltaics, memristors, and electrochromics. Hence, here, recent developments in materials and devices based on p‐type oxide semiconductors are reviewed, including ternary Cu‐bearing oxides, binary copper oxides, tin monoxide, spinel oxides, and nickel oxides. The crystal and electronic structures of these materials are discussed, along with approaches to enhance valence‐band dispersion to reduce effective mass and increase mobility. Strategies to reduce interfacial defects, off‐state current, and material instability are suggested. Furthermore, it is shown that promising progress has been made in the performance of various types of devices based on p‐type oxides. Several innovative approaches exist to fabricate transparent complementary metal oxide semiconductor (CMOS) devices, including novel device fabrication schemes and utilization of surface chemistry effects, resulting in good inverter gains. However, despite recent developments, p‐type oxides still lag in performance behind their n‐type counterparts, which have entered volume production in the display market. Recent successes along with the hurdles that stand in the way of commercial success of p‐type oxide semiconductors are presented.
Unique drug screening approach for prion diseases identifies tacrolimus and astemizole as antiprion agents

Prion diseases such as Creutzfeldt–Jakob disease (CJD) are incurable and rapidly fatal neurodegenerative diseases. Because prion protein (PrP) is necessary for prion replication but dispensable for the host, we developed the PrP–FRET-enabled high throughput assay (PrP–FEHTA) to screen for compounds that decrease PrP expression. We screened a collection of drugs approved for human use and identified astemizole and tacrolimus, which reduced cell-surface PrP and inhibited prion replication in neuroblastoma cells. Tacrolimus reduced total cellular PrP levels by a nontranscriptional mechanism. Astemizole stimulated autophagy, a hitherto unreported mode of action for this pharmacophore. Astemizole, but not tacrolimus, prolonged the survival time of prion-infected mice. Astemizole is used in humans to treat seasonal allergic rhinitis in a chronic setting. Given the absence of any treatment option for CJD patients and the favorable drug characteristics of astemizole, including its ability to cross the blood–brain barrier, it may be considered as therapy for CJD patients and for prophylactic use in familial prion diseases. Importantly, our results validate PrP-FEHTA as a method to identify antiprion compounds and, more generally, FEHTA as a unique drug discovery platform.
Hiperlipidemik Olgularda Azalmış Serum Adiponektin Düzeyi ve Atorvastatin Tedavisinin Etkisi

Objectives: Atherosclerotic diseases such as coronary heart disease, myocardial infarction and stroke are leading causes of morbidity and mortality. Hyperlipidemia is among the major risk factors for atherosclerotic diseases. Atorvastatin, a member of statins wich is a potent lipid lowering drugs is used widely in hyperlipidemia. Serum levels of adiponectin that is produced in adipose tissue and that regressed atherosclerosis were shown to fall down in the presence of such atherosclerosis risk factors as hypertension, diabetes and hyperlipidemia. In the present study we aimed to examine serum adiponectin levels in hyperlipidemia and at the end of atorvastatin treatment. Material and Methods: The study enrolled 26 non-diabetic hyperlipidemic patients and 10 healthy individuals matching hyperlipidemia group in terms of age, sex, body mass index and blood pressure. The 26 hyperlipidemic patients were treated with 20 mg/day atorvastatin for 8 weeks. Serum lipid and adiponectin levels were examined at the beginning of the treatment and after 8 weeks. Results: Adiponectin levels were found 18.8±6.8 µg/mL in healthy individuals and 3.7±1.3 µg/mL in hyperlipidemic patients, the difference between them being statistically significant (p
Interpretation of serum PTH concentrations with different kits in dialysis patients according to the KDIGO guidelines: importance of the reference (normal) values.

BACKGROUND The recommended target range for serum parathyroid hormone (PTH) in dialysis patients has changed from 150 to 300 pg/mL in the KDOQI guidelines to two to nine times the upper normal limit in the KDIGO ones. Although inclusion/exclusion criteria for the reference population are highly important, they are usually not mentioned in the commercial kits. In this study, we used the same reference population of vitamin D-replete normal subjects to establish reference values for 10 commercial PTH kits. We evaluated whether this may improve the classification of dialysis patients according to the KDIGO compared to the use of reference values proposed by the manufacturers. METHODS We measured serum PTH with 10 different kits in 149 haemodialysis patients, and 240 25-OH-vitamin D-replete (>75 nmol/L) individuals with an estimated glomerular filtration rate >60 mL/min/1.73 m(2). RESULTS For the 10 kits, our upper normal limit was lower than those of the manufacturers. The difference was, however, variable from one kit to another. The two kits that yielded the lowest and the highest absolute concentrations classified differently 84/149 patients (56.4%) according to the KDOQI and 53/149 (36.2%) according to the KDIGO using the manufacturers' normal values. Using our normal values significantly decreased the discrepancies with 24/149 patients (16.1%) being still classified differently. Taking the measurement uncertainty into consideration, 8% of the patients only remained differently classified by these two kits. CONCLUSIONS Using the same vitamin-D-replete population to establish the reference range for 10 commercial PTH kits significantly improved the classification of haemodialysis patients according to the KDIGO target range.
Synthesis and dissolution of hemicatenanes by type IA DNA topoisomerases

Significance A hemicatenane conjoins two DNA duplexes through a single-strand interlock. It has been proposed that hemicatenanes are important intermediates for replication, repair, and recombination. However, the biochemical analysis of hemicatenanes is hampered by the relative inaccessibility of such structures. We report here that a DNA topoisomerase III (Top3) from a hyperthermophilic archaeum can carry out synthesis and dissolution of hemicatenanes. We also show that a complex of human Top3α, Bloom helicase (Blm), and RecQ-mediated genome instability protein 1 and 2 has a biochemical function of reversing this hemicatenation. Our results demonstrate that type IA topoisomerases can regulate the formation of hemicatenane structures. Type IA DNA topoisomerases work with a unique mechanism of strand passage through an enzyme-bridged, ssDNA gate, thus enabling them to carry out diverse reactions in processing structures important for replication, recombination, and repair. Here we report a unique reaction mediated by an archaeal type IA topoisomerase, the synthesis and dissolution of hemicatenanes. We cloned, purified, and characterized an unusual type IA enzyme from a hyperthermophilic archaeum, Nanoarchaeum equitans, which is split into two pieces. The recombinant heterodimeric enzyme has the expected activities in its preference of relaxing negatively supercoiled DNA. Its amino acid sequence and cleavage site sequence analysis suggest that it is topoisomerase III, and therefore we named it “NeqTop3. ” At high enzyme concentrations, NeqTop3 can generate high-molecular-weight DNA networks. Biochemical and electron microscopic data indicate that the DNA networks are connected through hemicatenane linkages. The hemicatenane formation likely is mediated by the single-strand passage through denatured bubbles in the substrate DNA under high temperature. NeqTop3 at lower concentrations can reverse hemicatenanes. A complex of human topoisomerase 3α, Bloom helicase, and RecQ-mediated genome instability protein 1 and 2 can partially disentangle the hemicatenane network. Both the formation and dissolution of hemicatenanes by type IA topoisomerases demonstrate that these enzymes have an important role in regulating intermediates from replication, recombination, and repair.