Miracle-dz/UniFAR-FTUs huggingface dataset:
Extracellular potassium effects are conserved within the rat erg K+ channel family

The biophysical properties of native cardiac erg1 and recombinant HERG1 channels have been shown to be influenced by the extracellular K+ concentration ([K+]o). The erg1 conductance, for example, increases dramatically with a rise in [K+]o. In the brain, where local [K+]o can change considerably with the extent of physiological and pathophysiological neuronal activity, all three erg channel subunits are expressed. We have now investigated and compared the effects of an increase in [K+]o from 2 to 10 mm on the three rat erg channels heterologously expressed in CHO cells. Upon increasing [K+]o, the voltage dependence of activation was shifted to more negative potentials for erg1 (ΔV0.5=−4.0 ± 1.1 mV, n= 28) and erg3 (ΔV0.5=−8.4 ± 1.2 mV, n= 25), and was almost unchanged for erg2 (ΔV0.5=−2.0 ± 1.3 mV, n= 6). For all three erg channels, activation kinetics were independent of [K+]o, but the slowing of inactivation by increased [K+]o was even more pronounced for erg2 and erg3 than for erg1. In addition, with increased [K+]o, all three erg channels exhibited significantly slower time courses of recovery from inactivation and of deactivation. Whole‐cell erg‐mediated conductance was determined at the end of 4 s depolarizing pulses as well as with 1 s voltage ramps starting from the fully activated state. The rise in [K+]o resulted in increased conductance values for all three erg channels which were more pronounced for erg2 (factor 3–4) than for erg1 (factor 2.5–3) and erg3 (factor 2–2.5). The data demonstrate that most [K+]o‐dependent changes in the biophysical properties are well conserved within the erg K+ channel family, despite gradual differences in the magnitude of the effects.
Vascular-related NAC-DOMAIN7 is involved in the differentiation of all types of xylem vessels in Arabidopsis roots and shoots.

SUMMARY The Arabidopsis thaliana NAC domain transcription factor, vascular-related NAC-DOMAIN7 (VND7), plays a pivotal role in regulating the differentiation of root protoxylem vessels. In order to understand the mechanisms underscoring the function of VND7 in vessel differentiation in more detail, we conducted extensive molecular analyses in yeast (Saccharomyces cerevisiae), Arabidopsis, and Nicotiana tabacum L. cv. Bright Yellow 2 (tobacco BY-2) cells. The transcriptional activation activity of VND7 was confirmed in yeast and Arabidopsis, and the C-terminal region was shown to be required for VND7 transcriptional activation. Expression of the C-terminus-truncated VND7 protein under the control of the native VND7 promoter resulted in inhibition of the normal development of metaxylem vessels in roots and vessels in aerial organs, as well as protoxylem vessels in roots. The expression pattern of VND7 overlapped that of VND2 to VND5 in most of the differentiating vessels. Furthermore, a yeast two-hybrid assay revealed the ability of VND7 to form homodimers and heterodimers with other VND proteins via their N-termini, which include the NAC domain. The heterologous expression of VND7 in tobacco BY-2 cells demonstrated that the stability of VND7 could be regulated by proteasome-mediated degradation. Together these data suggest that VND7 regulates the differentiation of all types of vessels in roots and shoots, possibly in cooperation with VND2 to VND5 and other regulatory proteins.
Meiotic Parthenogenesis in a Root-Knot Nematode Results in Rapid Genomic Homozygosity

Many isolates of the plant-parasitic nematode Meloidogyne hapla reproduce by facultative meiotic parthenogenesis. Sexual crosses can occur, but, in the absence of males, the diploid state appears to be restored by reuniting sister chromosomes of a single meiosis. We have crossed inbred strains of M. hapla that differ in DNA markers and produced hybrids and F2 lines. Here we show that heterozygous M. hapla females, upon parthenogenetic reproduction, produce progeny that segregate 1:1 for the presence or absence of dominant DNA markers, as would be expected if sister chromosomes are rejoined, rather than the 3:1 ratio typical of a Mendelian cross. Codominant markers also segregate 1:1 and heterozygotes are present at low frequency (<3%). Segregation patterns and recombinant analysis indicate that a homozygous condition is prevalent for markers flanking recombination events, suggesting that recombination occurs preferentially as four-strand exchanges at similar locations between both pairs of non-sister chromatids. With this mechanism, meiotic parthenogenesis would be expected to result in rapid genomic homozygosity. This type of high negative crossover interference coupled with positive chromatid interference has not been observed in fungal or other animal systems in which it is possible to examine the sister products of a single meiosis and may indicate that meiotic recombination in this nematode has novel features.
Ectopic pregnancy—a diagnostic challenge in the emergency department

&NA; The aim of ths study was to elucidate the clinical presentation of ectopic pregnancy in the emergency department and highlight the atypical presentations and pitfalls in its diagnosis. This was a 4‐year retrospective descriptive study carried out at a tertiary teaching hospital. Two hundred and seven cases of ectopic pregnancy treated in a tertiary teaching hospital were reviewed Among the risk factors, 4.9% had a history of tubal ligation. Two patients developed ectopic pregnancy while breastfeeding. Of the patients, 43.7% did not have the triad symptoms of lower abdominal pain, vaginal bleeding and amenorrhoea, One patient presented with rectal bleeding while three patients presented with epigastric pain and central abdominal pain instead of lower abdominal pain. All who had tachycardia (10.4% of all cases) had ruptured ectopic pregnancy. Of the cases, 30% and 49% did not have abdominal pain and rebound tenderness respectively; 37.5% had negative cervical motion tenderness; 3.1% and 2.6% of cases had negative urine HCG and plasma &bgr;HCG tests respectively. Ultrasound missed 1.6% of ectopic pregnancies. Missed pregnancy, normal ultrasound study and diagnosis of other gynaecological conditions were reasons for the delayed diagnosis of 5.8% of cases. There was one mortality Any female in the reproductive age group with syncope, abdominal symptoms or any of the components of the classical triad must have ectopic pregnancy excluded. Patients with normal ultrasound studies should have their serum &bgr;HCG levels and ultrasound scans repeated until the condition can be completely excluded Transabdominal or transvaginal ultrasound studies done within the emergency department would enable earlier diagnosis and management
Selection of multiple antibiotic resistance by quinolones, beta-lactams, and aminoglycosides with special reference to cross-resistance between unrelated drug classes

The ability of three quinolones, two beta-lactams, and one aminoglycoside to select resistant mutants was examined in tests with 30 isolates of commonly encountered nosocomial pathogens. Ciprofloxacin and norfloxacin, two new quinolone derivatives, were no more likely to select resistant mutants than amikacin, whereas nalidixic acid, an older quinolone derivative, was the most likely of the six drugs examined to select resistant mutants. Mutational frequencies of 10(-7) to 10(-8) were observed in most instances. In general, the mutants were 8 to 16 times less susceptible to the drug used for selection. Although most quinolone-selected mutants were cross-resistant only to other drugs within this class, certain mutants of Klebsiella pneumoniae selected by nalidixic acid, ciprofloxacin, or norfloxacin were also less susceptible to beta-lactam antibiotics. This unusual pattern of multiple drug resistance was associated with changes in outer membrane proteins of the organism. Multiple drug resistance was also observed in beta-lactam-selected mutants of Enterobacter cloacae and Pseudomonas aeruginosa (beta-lactams), amikacin-selected mutants of Providencia stuartii and P. aeruginosa (aminoglycosides), and beta-lactam- or amikacin-selected mutants of Serratia marcescens (beta-lactams plus aminoglycosides). These results underscore the need to examine carefully the frequency with which resistance to any new antibiotic develops, as well as the patterns of multiple drug resistance which may occur simultaneously.
Analytical Surface Potential and Drain Current Models of Dual-Metal-Gate Double-Gate Tunnel-FETs

In this paper, a new 2-D analytical model for the surface potential of a dual-metal-gate double-gate tunnel field-effect transistor is presented. It takes into account the effects of the drain and gate voltages, gate metal work function, insulator thickness, silicon film thickness, and source and drain depletions. The surface potential thus obtained is used to calculate the tunneling widths at both the source and drain junctions, which are subsequently used as the limits for the integration of the band-to-band generation rate in order to arrive at the tunneling current. In this paper, the band-to-band tunneling is considered to take place through both the source as well as the drain depletion regions. Our model accounts for the variable drain doping through a fitting function, which is postulated based on the theory of generation current, and the results have been found to predict the correct ambipolar behavior of the tunneling field-effect transistors. The results of our model, both for the surface potential and the tunneling current, match very well with those obtained through the TCAD simulations.
A Clinical Study on Temporomandibular Joint Ankylosis in Children

Temporomandibular joint (TMJ) ankylosis is a disabling condition of the masticatory system and is most commonly due to trauma, infections, and some systemic diseases. Hypomobility affects the surrounding structures as well as the joint itself. Ankylosis arising in early childhood usually leads to facial asymmetry. Ankylosis in children usually occurs from an intracapsular compression fracture or rarely from a suppurative arthritis of middle ear infection. Treatment of the ankylosis is probably one of the greatest challenges in TMJ surgery, and the treatment of TMJ ankylosis in children is much more challenging than in adults because of high recurrence and the probable change in the unpredictable growth of the mandible. In treatment of TMJ ankylosis in children, to maintain a normal growth and the development of the face is as important as to provide a satisfactory mouth opening with free movement of the mandible. A variety of techniques and various success rates in the treatment of TMJ ankylosis both in adults and in children have been reported. However, no single method has produced uniformly successful results. In this study, gap arthroplasty was applied in 6 patients, and 2 different types of fossa implants were used as interpositional material in the other 8 patients, and the results of the treatments have been evaluated retrospectively.
Stressor-Induced Increase in Microbicidal Activity of Splenic Macrophages Is Dependent upon Peroxynitrite Production

ABSTRACT Exposing mice to a social stressor called social disruption (SDR) that involves repeated social defeat during intermale aggression results in increased circulating cytokines, such as interleukin-1α (IL-1α) and IL-1β, and increased reactivity of splenic CD11b+ macrophages to inflammatory stimuli. For example, upon lipopolysaccharide stimulation, macrophages from stressor-exposed mice produce higher levels of cytokines than do cells from nonstressed controls. Moreover, the SDR stressor enhances the ability of these macrophages to kill Escherichia coli both in vitro and in vivo, through a Toll-like receptor 4-dependent mechanism. The present study tested the hypothesis that stressor-enhanced bacterial killing is due to increases in the production of peroxynitrite. Male mice were exposed to the SDR stressor or were left undisturbed. Upon stimulation with E. coli, splenic macrophages from SDR-exposed mice expressed significantly increased levels of inducible nitric oxide synthase mRNA and produced higher levels of peroxynitrite. Blocking the production of peroxynitrite abrogated the SDR-induced increase in microbicidal activity. Studies in IL-1 receptor type 1 knockout mice indicated that the increased microbicidal activity and peroxynitrite production was dependent upon IL-1 signaling. These data confirm and extend the importance of IL-1 signaling for stressor-induced immunopotentiation; the finding that inhibiting superoxide or nitric oxide production inhibits both peroxynitrite production and killing of E. coli demonstrates that peroxynitrite mediates the stressor-induced increase in bacterial killing.
Sterol Carrier Protein-2, a New Fatty Acyl Coenzyme A-binding Protein*

The ability of sterol carrier protein-2 (SCP-2) to interact with long chain fatty acyl-CoAs was examined. SCP-2 bound fluorescent fatty acyl-CoAs at a single site with high affinity. Kd values for cis- and trans-parinaroyl-CoA were 4.5 and 2.8 nM, respectively. Saturated 10-18-carbon and unsaturated 14-20-carbon fatty acyl-CoAs displaced SCP-2-bound fluorescent ligand. Oleoyl-CoA and oleic acid (but not coenzyme A) significantly altered SCP-2 Trp50 emission and anisotropy decay, thereby increasing SCP-2 rotational correlation time, SCP-2 hydrodynamic radius, and SCP-2 Trp50 remaining anisotropy up to 1.7-, 1.2-, and 1.3-fold, respectively. These changes were not accompanied by significant alterations in protein secondary structure as determined by circular dichroism. Finally, SCP-2 differentially altered the fluorescence emission and anisotropy decays of bound cis- and trans-parinaroyl-CoA. Both fluorescent fatty acyl-CoAs were located within a very ordered (limited cone angle of rotation) environment within SCP-2, as shown by a remaining anisotropy of 0.365 and 0.361 and a wobbling cone angle of 12 and 13°, respectively. These anisotropy values were very close to those of such ligands in a propylene glass. However, the rotational relaxation times exhibited by SCP-2-bound cis- and trans-parinaroyl-CoA, 8.4-8.8 ns, were longer than those for the corresponding free fatty acid, 7.5-6.6 ns. These data show for the first time that SCP-2 is a fatty acyl-CoA-binding protein.
Hitler, Germans, and the Jewish Question

This book probes the background of the ultimately unexplainable evil of our century, the deliberate and unprovoked murder of millions of European Jews--and goes on to explore German reactions to that evil. Depicting the emergence in Weimar Germany of a new type of extreme anti-Semite, of which Hitler was the paramount example, Sarah Gordon discusses a number of related questions about the role of anti-Semitism in the rise of the Nazis and draws on hitherto unexamined Gestapo files, new data on court sentences, and a variety of other sources to describe the tiny numbers of courageous Germans who opposed Nazi anti-Semitism. She analyzes Hitler's own deranged world view, his use of his feelings about Jews as a political tool, and the extent of the German people's knowledge of his intentions and actions; she examines the history of German anti-Semitism from 1870 through the Nazi years; and she indicates several reasons for thinking that anti-Semitism, however virulent in certain individuals and groups, was not the major reason for Nazi electoral successes. No apologia for the German people, this work shows how a minority of extreme anti-Semites coexisted in Germany with the indifferent or fearfully disapproving majority, while the heroic few assumed the extreme risks of opposition. It offers a clear picture of the kinds of people who aided the Jews or publicly criticized their persecution, including surprising evidence of opposition in the Nazi party itself. In addition, it questions widely held beliefs that older Germans, males, Protestants, and the middle classes were disproportionately anti-Semitic; that bluecollar workers were basically immune to anti-Semitism; and that most Nazis were radical anti-Semites. It also discusses such subjects as the attitudes of German churches, the role of the military, and the socio-economic characteristics of Jews in Germany.
Method for assessment of volume of trapped gas in infants during multiple‐breath inert gas washout

A breath‐by‐breath inert gas washout method for assessment of the volume of trapped gas in the lungs (VTG) in sedated sleeping infants is described. It is based on washin using a gas mixture containing 4% sulfur hexafluoride (VTG,SF6) and washout with air. A mass spectrometer was used for continuous gas concentration measurements, and a Fleisch no. 0 pneumotachometer for flow measurement. When equilibration of the tracer gas was achieved with tidal breathing washin, five passive inflations with a maximum positive airway pressure of 20 cm of H2O were performed to ensure filling of lung spaces not communicating during tidal breathing. After tidal washout of the tracer gas by air until the end‐tidal concentration was 1/40th of its starting concentration, five passive inflations with air were instituted again. The VTG,SF6 was calculated from the volume of SF6 mobilized by these large breaths, and expressed as the corresponding volume of air.
Analysis of the prevalence and associated factors of overactive bladder in adult Korean men

Overactive bladder (OAB) is a prevalent condition characterized by lower urinary tract symptoms (LUTS). Age, education, income, marital status, sleep, and emotional problems have been associated with OAB; however, conflicting results exist. The present study was conducted to estimate the prevalence of OAB and comprehensively analyze its associated factors in a large cross-sectional, population-based study. The data of 94,554 participants aged 19–107 were analyzed from the Korean Community Health Survey (KCHS) of 2012. Data on marital status, physical activity, education level, occupation, body mass index (BMI), income level, sleep time, and stress level were retrieved for all enrolled participants. The overactive bladder symptom score (OABSS) was used to evaluate the presence and degree of OAB. Simple and multiple logistic regression analyses with complex sampling were used for the associations between various factors and the presence of OAB. Overall, OAB was present in approximately 2.9% of the participants. The prevalence of OAB increased with age and steeply increased after 60 years of age (adjusted odds ratio [AOR] for each 10 years = 1.70, 95% confidence interval [CI] = 1.61–1.80, P<0.001). The prevalence of OAB was lower in married than unmarried subjects (AOR = 0.59, 95% CI = 0.48–0.72, P<0.001). The prevalence of OAB was significantly different according to occupation Compared to manager, expert, specialist, clerk group, the prevalence of OAB was highest in unemployed group (AOR = 1.90, 95% CI = 1.55–2.32, P < 0.001). Being underweight was correlated with OAB (AOR = 1.29, 95% CI = 1.08–1.55, P = 0.018). Inadequate sleep showed a significant association with OAB (AOR = 1.13, 95% CI = 1.02–1.25 for ≤6 hours of sleep time and AOR = 1.53, 95% CI = 1.27–1.86 for ≥9 hours of sleep, P<0.001). Stress level showed a dose-dependent positive association with OAB [AOR (95% CI) = 3.91 (3.13–4.89) > 2.16 (1.88–2.48) > 1.39 (1.23–1.57) for severe stress > moderate stress > some stress, respectively, P<0.001]. A medical history of diabetes mellitus, hyperlipidemia, and/or cerebral stroke was significantly related to OAB. Approximately 2.9% of adult Korean men experienced OAB based on the OABSS. Unmarried status; occupation; being underweight; inadequate sleep; stress; and medical history of diabetes mellitus, hyperlipidemia, or cerebral stroke were significantly correlated with OAB.
Lens Epithelium-derived Growth Factor/p75 Prevents Proteasomal Degradation of HIV-1 Integrase*

The transcriptional coactivator lens epithelium-derived growth factor (LEDGF)/p75 acts as a chromatin tethering factor for human immunodeficiency virus type 1 (HIV-1) integrase protein, determining its nuclear localization and its tight association with nuclear DNA. Here we identify a second function for the LEDGF/p75-integrase interaction. We observed that stable introduction of HIV-1 integrase (IN) transcription units into cells made stringently LEDGF/p75-deficient by RNAi resulted in much lower steady state levels of IN protein than introduction into LEDGF/p75 wild type cells. The same LEDGF/p75-dependent disparity was observed for feline immunodeficiency virus IN. However, IN mRNA levels were equivalent in the presence and absence of LEDGF/p75. A post-translational mechanism was confirmed when the half-life of HIV-1 IN protein was found to be much shorter in LEDGF/p75-deficient cells. Proteasome inhibition fully countered this extreme instability, increasing IN protein levels to those seen in LEDGF/p75 wild type cells and implicating proteasomal destruction as the main cause of IN instability. Consistent with these data, increased ubiquitinated HIV-1 IN was found in the LEDGF/p75 knock-down cells. Moreover, restoration of LEDGF/p75 to knocked down clones rescued HIV-1 IN stability. Subcellular fractionation showed that HIV-1 IN is exclusively cytoplasmic in LEDGF/p75-deficient cells, but mainly nuclear in LEDGF/p75 wild type cells, and that cytoplasmic HIV-1 IN has a shorter half-life than nuclear HIV-1 IN. However, using LEDGF proteins defective for nuclear localization and IN interaction, we further determined that protection of HIV-1 IN from the proteasome requires neither chromatin tethering nor nuclear residence. Protection requires only interaction with LEDGF/p75, and it is independent of the subcellular localization of the IN-LEDGF complex.
Immune and Clinical Outcomes in Patients with Stage IV Melanoma Vaccinated with Peptide-Pulsed Dendritic Cells Derived From CD34+ Progenitors and Activated with Type I Interferon

Twenty-two HLA A*0201+ patients with stage IV melanoma were enrolled in a phase 1 safety and feasibility trial using a composite dendritic cell (DC) vaccine generated by culturing CD34+ hematopoietic progenitors and activated with IFN-α. The DC vaccine was loaded with peptides derived from four melanoma tissue differentiation antigens (MART-1, tyrosinase, MAGE-3, and gp100) and influenza matrix peptide (Flu-MP). Twenty patients were evaluable, 14 of whom received vaccination with peptide-pulsed DCs without keyhole limpet hemocyanin (KLH) and 6 of whom received vaccination with KLH-loaded DCs. Patients were vaccinated until disease progression or until they had received eight vaccinations. None of the analyzed patients showed the expansion of melanoma-peptide-specific circulating effector memory T cells that secrete IFN-γ in direct ELISPOT. Melanoma-peptide-specific recall memory CD8+ T cells able to secrete IFN-γ and to proliferate could be detected in six of the seven analyzed patients. There were no objective clinical responses. The estimated median overall survival was 12 months (range 2-38), and the median event-free survival was 4 months (range 1-12). There was no statistically significant survival advantage in patients who received KLH-loaded vaccines. As of March 2005, four patients remained alive, 26+, 28+, 28+, and 36+ months. Three of them had received KLH-loaded vaccines and all of them had had additional therapy. Overall, these results suggest that IFN-α-activated CD34-DCs are safe but elicit only limited immune responses, underscoring the need to test different DC maturation factors.