3,708 research outputs found

    Surgical resection and survival of patients with unsuspected single node positive lung cancer (NSCLC) invading the descending aorta

    Get PDF
    Background: Surgical treatment of non-small cell lung cancer (NSCLC) with aortic invasion is still debated

    The Sodium/Proline Transporter PutP of Helicobacter pylori

    Get PDF
    Helicobacter pylori is cause of chronic gastritis, duodenal ulcer and gastric carcinoma in humans. L-proline is a preferred energy source of the microaerophilic bacterium. Previous analyses revealed that HpputP and HpputA, the genes that are predicted to play a central role in proline metabolism as they encode for the proline transporter and proline dehydrogenase, respectively, are essential for stomach colonization. Here, the molecular basis of proline transport in H. pylori by HpPutP was investigated experimentally for the first time. Measuring radiolabeled substrate transport in H. pylori and E. coli heterologously expressing HpputP as well as in proteoliposomes reconstituted with HpPutP, we demonstrate that the observed proline transport in H. pylori is mediated by HpPutP. HpPutP is specific and exhibits a high affinity for L-proline. Notably, L-proline transport is exclusively dependent on Na+ as coupling ion, i.e., Na+/L-proline symport, reminiscent to the properties of PutP of E. coli even though H. pylori lives in a more acidic environment. Homology model-based structural comparisons and substitution analyses identified amino acids crucial for function. HpPutP-catalyzed proline uptake was efficiently inhibited by the known proline analogs 3,4-dehydro-D,L-proline and L-azetidine-2-carboxylic acid

    Kondo effect in nanostructures

    Full text link
    Kondo effect arises whenever a coupling to the Fermi gas induces transitions within the otherwise degenerate ground state multiplet of an interacting system. Both coupling to the Fermi gas and interactions are naturally present in any nanoscale transport experiment. At the same time, many nanostructures can easily be tuned to the vicinity of a degeneracy point. This is why the Kondo effect in its various forms often influences the low temperature transport in meso- and nanoscale systems. In this short review we discuss the basic physics of the Kondo effect and its manifestations in the low-temperature electronic transport through a single electron transistor

    Predicting the earliest deviation in weight gain in the course towards manifest overweight in offspring exposed to obesity in pregnancy: a longitudinal cohort study

    Get PDF
    BACKGROUND: Obesity in pregnancy and related early-life factors place the offspring at the highest risk of being overweight. Despite convincing evidence on these associations, there is an unmet public health need to identify “high-risk” offspring by predicting very early deviations in weight gain patterns as a subclinical stage towards overweight. However, data and methods for individual risk prediction are lacking. We aimed to identify those infants exposed to obesity in pregnancy at ages 3 months, 1 year, and 2 years who likely will follow a higher-than-normal body mass index (BMI) growth trajectory towards manifest overweight by developing an early-risk quantification system. METHODS: This study uses data from the prospective mother-child cohort study Programming of Enhanced Adiposity Risk in CHildhood–Early Screening (PEACHES) comprising 1671 mothers with pre-conception obesity and without (controls) and their offspring. Exposures were pre- and postnatal risks documented in patient-held maternal and child health records. The main outcome was a “higher-than-normal BMI growth pattern” preceding overweight, defined as BMI z-score >1 SD (i.e., World Health Organization [WHO] cut-off “at risk of overweight”) at least twice during consecutive offspring growth periods between age 6 months and 5 years. The independent cohort PErinatal Prevention of Obesity (PEPO) comprising 11,730 mother-child pairs recruited close to school entry (around age 6 years) was available for data validation. Cluster analysis and sequential prediction modelling were performed. RESULTS: Data of 1557 PEACHES mother-child pairs and the validation cohort were analyzed comprising more than 50,000 offspring BMI measurements. More than 1-in-5 offspring exposed to obesity in pregnancy belonged to an upper BMI z-score cluster as a distinct pattern of BMI development (above the cut-off of 1 SD) from the first months of life onwards resulting in preschool overweight/obesity (age 5 years: odds ratio [OR] 16.13; 95% confidence interval [CI] 9.98–26.05). Contributing early-life factors including excessive weight gain (OR 2.08; 95% CI 1.25–3.45) and smoking (OR 1.94; 95% CI 1.27–2.95) in pregnancy were instrumental in predicting a “higher-than-normal BMI growth pattern” at age 3 months and re-evaluating the risk at ages 1 year and 2 years (area under the receiver operating characteristic [AUROC] 0.69–0.79, sensitivity 70.7–76.0%, specificity 64.7–78.1%). External validation of prediction models demonstrated adequate predictive performances. CONCLUSIONS: We devised a novel sequential strategy of individual prediction and re-evaluation of a higher-than-normal weight gain in “high-risk” infants well before developing overweight to guide decision-making. The strategy holds promise to elaborate interventions in an early preventive manner for integration in systems of well-child care. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s12916-022-02318-z

    PLANNING OF HUMAN RESOURCE COMPETENCY DEVELOPMENT IN PT.XYZ WITH TAGUCHI METHOD

    Get PDF
    The problem of human resources is still a concern within the company to remain competitive in this globalization world. This shows that the problem of human resources greatly affect the implementation and success of the company in achieving goals and objectives. The company demand to obtain the development process and get quality human resources more urgent. And the development of human resource competence is necessary. This study uses experimental testing with several parameters of validity and reliability testing. For testing analysis using Taguchi Method. Based on the Response Table for Signal to Noise Ratios Nominal is best obtained taguchi test results obtained values obtained from the effect plot for means with the approach of table of means, then the intellectual competence is needed for the improvement of HR performance

    Mutational Analysis of the SOX9 Gene in Campomelic Dysplasia and Autosomal Sex Reversal: Lack of Genotype/Phenotype Correlations

    Get PDF
    It has previously been shown that, in the heterozygous state, mutations in the SOX9 gene cause campomelic dysplasia (CD) and the often associated autosomal XY sex reversal. In 12 CD patients, 10 novel mutations and one recurrent mutation were characterized in one SOX9 allele each, and in one case, no mutation was found. Four missense mutations are all located within the high mobility group (HMG) domain. They either reduce or abolish the DNA-binding ability of the mutant SOX9 proteins. Among the five nonsense and three frameshift mutations identified, two leave the C-terminal transactivation (TA) domain encompassing residues 402-509 of SOX9 partly or almost completely intact. When tested in cell transfection experiments, the recurrent nonsense mutation Y440X, found in two patients who survived for four and more than 9 years, respectively, exhibits some residual transactivation ability. In contrast, a frameshift mutation extending the protein by 70 residues at codon 507, found in a patient who died shortly after birth, showed no transactivation. This is apparently due to instability of the mutant SOX9 protein as demonstrated by Western blotting. Amino acid substitutions and nonsense mutations are found in patients with and without XY sex reversal, indicating that sex reversal in CD is subject to variable penetrance. Finally, none of 18 female patients with XY gonadal dysgenesis (Swyer syndrome) showed an altered SOX9 banding pattern in SSCP assays, providing evidence that SOX9 mutations do not usually result in XY sex reversal without skeletal malformation

    Immune Markers and Tumor-Related Processes Predict Neoadjuvant Therapy Response in the WSG-ADAPT HER2-Positive/Hormone Receptor-Positive Trial in Early Breast Cancer

    Get PDF
    Prognostic or predictive biomarkers in HER2-positive early breast cancer (EBC) may inform treatment optimization. The ADAPT HER2-positive/hormone receptor-positive phase II trial (NCT01779206) demonstrated pathological complete response (pCR) rates of ~40% following de-escalated treatment with 12 weeks neoadjuvant ado-trastuzumab emtansine (T-DM1) ± endocrine therapy. In this exploratory analysis, we evaluated potential early predictors of response to neoadjuvant therapy. The effects of PIK3CA mutations and immune (CD8 and PD-L1) and apoptotic markers (BCL2 and MCL1) on pCR rates were assessed, along with intrinsic BC subtypes. Immune response and pCR were lower in PIK3CA-mutated tumors compared with wildtype. Increased BCL2 at baseline in all patients and at Cycle 2 in the T-DM1 arms was associated with lower pCR. In the T-DM1 arms only, the HER2-enriched subtype was associated with increased pCR rate (54% vs. 28%). These findings support further prospective pCR-driven de-escalation studies in patients with HER2-positive EBC
    corecore