Miracle-dz/UniFAR-FTUs huggingface dataset:
pH Sensing by the Calcium-sensing Receptor*

The calcium-sensing receptor (CaR) is activated by small changes in the ionic extracellular calcium concentration (Cao) within the physiological range, allowing the parathyroid gland to regulate serum Cao; however, the CaR is also distributed in a number of other tissues where it may sense other endogenous agonists and modulators. CaR agonists are polycationic molecules, and our previous studies suggest that charged residues in the extracellular domain of the CaR are critical for receptor activation through electrostatic interactions. Therefore, pH could also potentially modulate CaR activation by its polycationic agonists. Changes in the concentration of extracellular H+ substantially altered the activation of the CaR by Cao and other CaR agonists. The effects of external pH on the CaR's sensitivity to its agonists were observed for both acidic and basic deviations from physiological pH of 7.4, with increases in pH rendering the receptor more sensitive to activation by Cao and decreases in pH producing the converse effect. At pH values more acidic than 5.5, CaR sensitivity to its agonists showed some recovery. Changes in the intracellular pH could not account for the effects of external pH on CaR sensitivity to its agonists. Other G-protein-coupled receptors, which are endogenously expressed in human embryonic kidney 293 cells, showed little change in activity with alterations in external pH or effects opposite those found for the CaR. Extracellular pH directly alters the CaR in the case of Cao and Mgo activation; however, the charges on many organic and inorganic agonists are pH-dependent. Activating CaR mutations show reduced pHo modulation, suggesting a molecular mechanism for increased CaR activity at physiological pHo. Several CaR-expressing tissues, including regions of the stomach, the kidney, bone, and the brain, could potentially use the CaR as a sensor for pH and acid-base status.
Patient-centered outcomes comparing digital and conventional implant impression procedures: a randomized crossover trial.

OBJECTIVES The aim of this randomized controlled trial was to compare patient-centered outcomes during digital and conventional implant impressions. MATERIAL AND METHODS In a crossover study design, intraoral scanning (IOS) [test] as well as classical polyether impressions [control] were both performed on 20 patients for single-tooth replacement with implant-supported crowns. The sequential distribution of either starting with the test or the control procedure was randomly selected. Patients' perception and satisfaction on the level of convenience-related factors were assessed with visual analogue scale (VAS) questionnaires. In addition, clinical work time was separately recorded for test and control procedures. Statistical analyses were performed with Wilcoxon signed-rank tests and corrected for multiple testing by the method of Holm. RESULTS On VAS ranging from 0 to 100, patients scored a mean convenience level of 78.6 (SD ± 14.0) in favor of IOS compared to conventional impressions with 53.6 (SD ± 15.4) [P = 0.0001]. All included patients would prefer the digital workflow if in the future they could choose between the two techniques. Secondary, IOS was significantly faster with 14.8 min (SD ± 2.2) compared to the conventional approach with 17.9 min (SD ± 1.1) [P = 0.0001]. CONCLUSION Based on the findings of this investigation, both impression protocols worked successfully for all study participants capturing the 3D implant positions. However, the digital technique emerges as the most preferred one according to patient-centered outcomes and was more time-effective compared to conventional impressions.
Direct real-time PCR with ethidium monoazide: a method for the rapid detection of viable Cronobacter sakazakii in powdered infant formula.

The goal of this study was to establish a rapid assay for the specific detection of viable Cronobacter sakazakii in powdered infant formula (PIF). Samples were subjected to treatment multiple times with ethidium monoazide with a concentration gradient (gEMA) prior to PCR to discriminate viable from dead C. sakazakii cells. To improve the current detection limits, we developed a new buffer for direct quantitative real-time PCR (DqPCR) without DNA isolation. Using 17 PIF samples, our rapid assay was compared with the new U.S. Food and Drug Administration (FDA) method published in the Bacteriological Analytical Manual in 2012. Although both the new FDA method and our rapid assay, which consists of DqPCR combined with gEMA (gEMA-DqPCR), produced negative results for all 17 PIF samples, 5 of the 17 PIFs were positive by DqPCR when they were not treated with EMA. Furthermore, for PIF samples artificially contaminated with viable C. sakazakii, gEMA-DqPCR successfully detected between 1 and 9 CFU of viable C. sakazakii in 300 g of PIF within 9 h, including a 6-h preincubation. Our results indicate that multiple EMA treatments are required to avoid false-positive results due to the contamination of commercial PIF with dead or injured C. sakazakii cells. Our rapid assay may also improve the sensitivity of the screening portion required by the new FDA method published in the Bacteriological Analytical Manual in 2012.
Disruption and mutagenesis of the Saccharomyces cerevisiae PDX1 gene encoding the protein X component of the pyruvate dehydrogenase complex.

Disruption of the PDX1 gene encoding the protein X component of the mitochondrial pyruvate dehydrogenase (PDH) complex in Saccharomyces cerevisiae did not affect viability of the cells. However, extracts of mitochondria from the mutant, in contrast to extracts of wild-type mitochondria, did not catalyze a CoA- and NAD(+)-linked oxidation of pyruvate. The PDH complex isolated from the mutant cells contained pyruvate dehydrogenase (E1 alpha + E1 beta) and dihydrolipoamide acetyltransferase (E2) but lacked protein X and dihydrolipoamide dehydrogenase (E3). Mutant cells transformed with the gene for protein X on a unit-copy plasmid produced a PDH complex that contained protein X and E3, as well as E1 alpha, E1 beta, and E2, and exhibited overall activity similar to that of the wild-type PDH complex. These observations indicate that protein X is not involved in assembly of the E2 core nor is it an integral part of the E2 core. Rather, protein X apparently plays a structural role in the PDH complex; i.e., it binds and positions E3 to the E2 core, and this specific binding is essential for a functional PDH complex. Additional evidence for this conclusion was obtained with deletion mutations. Deletion of most of the lipoyl domain (residues 6-80) of protein X had little effect on the overall activity of the PDH complex. This observation indicates that the lipoyl domain, and its covalently bound lipoyl moiety, is not essential for protein X function. However, deletion of the putative subunit binding domain (residues approximately 144-180) of protein X resulted in loss of high-affinity binding of E3 and concomitant loss of overall activity of the PDH complex. (ABSTRACT TRUNCATED AT 250 WORDS)
Competition between native and introduced salmonid fishes: cutthroat trout have lower growth rate in the presence of cutthroat-rainbow trout hybrids.

When nonnative species become established within new communities, competition may play a role in determin- ing the persistence of ecologically similar native species. In western North America, many native cutthroat trout (Onco- rhynchus clarkii) populations have been replaced by nonnative rainbow trout (Oncorhynchus mykiss). Superior competitive ability of rainbow trout and cutthroat-rainbow trout hybrids is often cited for this replacement; however, few studies have tested for mechanisms that might allow introduced rainbow trout to out-compete native trout species. Our previous work found individual-based differences in swimming and foraging ability among cutthroat trout, rainbow trout, and their hy- brids. In this study, we tested for the presence and strength of competition between cohorts of cutthroat trout, rainbow trout, and their reciprocal hybrids. We assayed the growth rate of juvenile cutthroat trout in allopatry versus cutthroat trout when sympatric with rainbow trout and each hybrid cross. After controlling for size and density of trout, cutthroat trout co- horts in stream channels that contained hybrid genotypes experienced lower growth than cutthroat trout in allopatry. Aver- aged across heterospecific treatments, cutthroat trout growth was also lower than that of cutthroat trout cohorts in allopatry. Our study suggests that juvenile cutthroat trout experience a growth disadvantage when competing against cutthroat-rainbow hybrids.
An Empirical Study of Factors Affecting Software Package Selection

Evidence suggests that information centers (ICs) have significantly more interest in evaluating software packages and assisting in the selection of software packages than end users have. However, the selection of software packages by the information center product specialists (ICPSs) can compromise their usage. Ease of use and usefulness are believed to be fundamental predictors of usage. The question of whether ICPSs are able to correctly evaluate ease of use and usefulness of software packages for end users is posed. An insight into this issue could enhance end-user computing (EUC) policy and lead to a more effective partnership between end users and information systems (IS) professionals. A search for this insight provided the motivation for our empirical investigation of the perception of ICPSs and end users in assessing the ease of use and usefulness of thirty different software packages. Our investigation was performed in an organization with an IC that had evolved to the formalization stage. The findings show that the perceptions of the end users and ICPSs were similar in terms of assessing the ease of use of software packages. However, end users found the software packages less useful than did IC product specialists. Therefore, in sophisticated environments, end users should be empowered to develop their own user groups and suggest to IC personnel which useful software packages to acquire. Otherwise, selection of software packages without end-user participation could have an adverse effect on their usage.
Quantitative analysis and effect of attenuation correction on lymph node staging of non-small cell lung cancer on SPECT and CT.

OBJECTIVE The purpose of our study was to assess quantitative indexes and the effect of attenuation correction on the evaluation of lymph node metastasis in the staging of non-small cell lung cancer (NSCLC) using fused thallium-201 SPECT/CT images. MATERIALS AND METHODS We evaluated 156 lymph nodes (66 metastatic, 90 nonmetastatic) from 29 patients with NSCLC. Using our combined SPECT/CT system, all patients underwent 201Tl SPECT and CT examinations immediately (early images) and 3 hr after (delayed images) the injection of 201Tl. SPECT images were reconstructed with and without attenuation correction. For the quantitative evaluation of lymph node metastasis, we calculated the early ratio, the delayed ratio, and the washout ratio for SPECT images and the short-axis diameter for CT images. Receiver operating characteristic (ROC) analysis was performed in each index for the differentiation between metastatic and nonmetastatic lymph nodes. Visual analysis was also performed by two experienced radiologists. RESULTS The area under the ROC curve (A(z)) showed that early ratio and delayed ratio were superior to short-axis diameter for the assessment of lymph node metastasis. In addition, early and delayed ratios on attenuation-corrected images were superior to those ratios on images without attenuation correction. However, the A(z) value for washout ratio was smaller than that for short-axis diameter. Early ratio on attenuation-corrected images was the most useful index (A(z) = 0.94). The sensitivity, specificity, and accuracy for early ratio on attenuation-corrected images were 78.8%, 94.4%, and 87.8% for the diagnosis of lymph node metastasis and 84.6%, 100%, and 93.1% for clinical staging (N0-N1 vs N2-N3), respectively. Fused images showed significantly higher diagnostic accuracy than CT images on visual analysis. CONCLUSION Quantitative assessment using fused SPECT/CT images is useful for the diagnosis of lymph node metastasis in patients with NSCLC.
Consonant clusters in child phonology and the directionality of syllable structure assignment

ABSTRACT The production of target consonant clusters at early stages of acquisition is analysed from a phonological representational perspective. The data stem from five normal monolingual German and four normal monolingual Spanish children at ages from 0;9 to 2;1, observed in naturalistic settings. At the beginning stages, target clusters are reduced to a single consonantal position, due to lack of branching of the syllabic constituents. This finding coincides with other results in the literature, which have in general been explained by means of universal principles. Nevertheless, there is an essential difference between the German and the Spanish data: German children tend to prefer the first consonant and Spanish children the second one. This difference can only be explained in terms of parameterization of syllabification, which in German takes place from left to right and in Spanish from right to left. At later stages, when clusters begin to be produced with two consonantal positions, they offer evidence for the beginning of branching of syllabic constituents, due to parameterization, and for the chronological order of the setting of the subsyllabic parameters. Our data offer evidence in favour of the following acquisitional hierarchy: CV > CVC > CVCC > CCVCC.
A phase I clinical and pharmacokinetic study (LIPOTEC - GP PHARM/DOXO 01) of a new liposomal doxorubicin given as 3-week schedule in patients with solid tumors

As a dose-finding phase I study of a new liposomal formulation of doxorubicin (LipD), patients (n = 39; median age: 60 years; range, 41–75; median ECOG performance status, 1; range, 0–2) with refractory cancer had a starting dose of LipD administered at 30 mg/m2 as a 1-hour iintravenous infusion. Cycle duration was 21 days. At the recommended dose (RD), patients received a first cycle of nonliposomal doxorubicin (non-LipD) to evaluate intrapatient pharmacokinetic differences between non-LipD and LipD. The most frequent diagnosis was head and neck tumor (7 patients). Tolerance and safety of dose levels of 30, 40, 50, 60, 70, 80, and 90 mg/m2 were evaluated. A total of 131 cycles were administered (median per patient, 3; range, 1–6). Of the 39 patients, 8 completed the planned six cycles. Febrile neutropenia was dose limiting and defined the toxic dose of LipD as 70 mg/m2. Other significant toxicities included asthenia (G2: 31%; G3: 8%), neutropenia (G3: 35%; G4: 29%), thrombopenia (G3: 15%; G4: 2%), anemia (G1–G2: 67%; G3–G4: 5%), mucositis (G1–G2: 32%, G3: 4%), and acute allergic reactions (G1–G2: 36%). Comparison of pharmacokinetic profiles of non-LipD and LipD showed that higher exposure was achieved with LipD. Stable disease was observed in 14 patients. We conclude that the LipD regimen, given as a 1-hour infusion every 3 weeks, is well tolerated and has a favorable pharmacokinetic profile. The recommended dose is 70 mg/m2 with prophylactic antihistamines and corticoids to preempt allergic reaction.
Discovering Potential Pathogens among Fungi Identified as Nonsporulating Molds

ABSTRACT Fungal infections are increasing, particularly among immunocompromised hosts, and a rapid diagnosis is essential to initiate antifungal therapy. Often fungi cannot be identified by conventional methods and are classified as nonsporulating molds (NSM). We sequenced internal transcribed spacer regions from 50 cultures of NSM and found 16 potential pathogens that can be associated with clinical disease. In selected clinical settings, identification of NSM could prove valuable and have an immediate impact on patient management.
An ion‐channel forming protein produced by Entamoeba histolytica.

We have identified a remarkable ion‐channel forming material in virulent strains of Entamoeba histolytica that may be responsible for many of the symptoms associated with amoebic dysentery. A polypeptide that we refer to as amoebapore is shed into the growth media and is also found within the amoeba in a high speed sedimentable fraction. Amoebapore has the distinctive property of spontaneously incorporating into lipid bilayers, liposomes, and cells, leading to progressive and irreversible changes in the ion conductance of the target membranes. Exposure of planar lipid bilayers to amoebapore ‐containing fractions under voltage clamp conditions results in an almost immediate and progressive incorporation of ion channels which continues in an irreversible manner leading to a fall in membrane impedance of up to five orders of magnitude. The ion‐channel conductance is moderately cation‐selective, voltage dependent, and displays a unit size of 1.6 +/‐ 0.2 nanoSiemens in 1 M KCl at ‐10 mV. In the bilayer, the amoebapore ‐induced conductance exhibits an in situ sensitivity to protease. Amoebapore is mainly concentrated in a fraction sedimenting at 150 000 g. It is insoluble in Triton X‐100 but can be dissociated in an active state in 1% SDS. Under these conditions it has an apparent mol. wt. of 13 000 daltons.
The scl +18/19 Stem Cell Enhancer Is Not Required for Hematopoiesis: Identification of a 5′ Bifunctional Hematopoietic-Endothelial Enhancer Bound by Fli-1 and Elf-1

ABSTRACT Analysis of cis-regulatory elements is central to understanding the genomic program for development. The scl/tal-1 transcription factor is essential for lineage commitment to blood cell formation and previous studies identified an scl enhancer (the +18/19 element) which was sufficient to target the vast majority of hematopoietic stem cells, together with hematopoietic progenitors and endothelium. Moreover, expression of scl under control of the +18/19 enhancer rescued blood progenitor formation in scl−/− embryos. However, here we demonstrate by using a knockout approach that, within the endogenous scl locus, the +18/19 enhancer is not necessary for the initiation of scl transcription or for the formation of hematopoietic cells. These results led to the identification of a bifunctional 5′ enhancer (−3.8 element), which targets expression to hematopoietic progenitors and endothelium, contains conserved critical Ets sites, and is bound by Ets family transcription factors, including Fli-1 and Elf-1. These data demonstrate that two geographically distinct but functionally related enhancers regulate scl transcription in hematopoietic progenitors and endothelial cells and suggest that enhancers with dual hematopoietic-endothelial activity may represent a general strategy for regulating blood and endothelial development.
Treatment of inflammatory myopathies

The treatment of the immune‐mediated inflammatory myopathies remains largely empirical. Corticosteroids are usually effective in polymyositis and dermatomyositis but may need to be combined with methotrexate or azathioprine in some patients. Intravenous immunoglobulin (IVIg) is effective as add‐on therapy in some patients not adequately controlled with steroids or immunosuppressive agents, but further controlled trials of IVIg are necessary to define the indications and optimal dose regimens. Cyclophosphamide, cyclosporin, or chlorambucil may be effective in patients with refractory polymyositis or dermatomyositis. Low‐dose whole body or lymphoid irradiation is a last option in severely disabled patients resistant to all other treatments. As a small proportion of patients with inclusion body myositis respond to corticosteroid or immunosuppressive therapy, a 3–6‐month trial of such therapy is justified in this condition. More specific immunotherapy for these disorders awaits identification of the target antigens and further clarification of the immunopathogenetic mechanisms. © 1997 John Wiley & Sons, Inc. Muscle Nerve 20:651–664, 1997.
The Cytochrome P450 Enzyme CYP96A15 Is the Midchain Alkane Hydroxylase Responsible for Formation of Secondary Alcohols and Ketones in Stem Cuticular Wax of Arabidopsis1[W][OA]

Most aerial surfaces of plants are covered by cuticular wax that is synthesized in epidermal cells. The wax mixture on the inflorescence stems of Arabidopsis (Arabidopsis thaliana) is dominated by alkanes, secondary alcohols, and ketones, all thought to be formed sequentially in the decarbonylation pathway of wax biosynthesis. Here, we used a reverse-genetic approach to identify a cytochrome P450 enzyme (CYP96A15) involved in wax biosynthesis and characterized it as a midchain alkane hydroxylase (MAH1). Stem wax of T-DNA insertional mutant alleles was found to be devoid of secondary alcohols and ketones (mah1-1) or to contain much lower levels of these components (mah1-2 and mah1-3) than wild type. All mutant lines also had increased alkane amounts, partially or fully compensating for the loss of other compound classes. In spite of the chemical variation between mutant and wild-type waxes, there were no discernible differences in the epicuticular wax crystals on the stem surfaces. Mutant stem wax phenotypes could be partially rescued by expression of wild-type MAH1 under the control of the native promoter as well as the cauliflower mosaic virus 35S promoter. Cauliflower mosaic virus 35S-driven overexpression of MAH1 led to ectopic accumulation of secondary alcohols and ketones in Arabidopsis leaf wax, where only traces of these compounds are found in the wild type. The newly formed leaf alcohols and ketones had midchain functional groups on or next to the central carbon, thus matching those compounds in wild-type stem wax. Taken together, mutant analyses and ectopic expression of MAH1 in leaves suggest that this enzyme can catalyze the hydroxylation reaction leading from alkanes to secondary alcohols and possibly also a second hydroxylation leading to the corresponding ketones. MAH1 expression was largely restricted to the expanding regions of the inflorescence stems, specifically to the epidermal pavement cells, but not in trichomes and guard cells. MAH1-green fluorescent protein fusion proteins localized to the endoplasmic reticulum, providing evidence that both intermediate and final products of the decarbonylation pathway are generated in this subcellular compartment and must subsequently be delivered to the plasma membrane for export toward the cuticle.
One for Sure or Maybe Three: Empirical Evidence for Overtime Play from a Comparison of Swiss Ice Hockey and the NHL

In order to avoid too many tied games after playing the five-minute overtime period, the National Hockey League (NHL) introduced two rule changes in the 1999-2000 season. First, a team that loses in overtime receives one point instead of zero points. Second, the number of skaters in overtime is reduced from five to four. The theoretical literature analyzing these rule changes predicted that they would also produce the unintended side-effect that more games would reach overtime and recommended that a team that wins in regulation should receive three points (instead of two) in order to counterbalance the converse effect. We are the first to empirically support this theoretical prediction using NHL data and data from Swiss ice hockey, in which the rule changes of the NHL were copied in the 2006–2007 season and in which the three-point rule was also introduced.