Thermoelectric power of MgB2−x_{2-x}Bex_x

We investigated thermoelectric power $S(T)$ of MgB$_{2-x}$Be$_{x}$ ($x=0$, 0.2, 0.3, 0.4, and 0.6). $S(T)$ decreases systematically with $x$, suggesting that the hole density increases. Our band calculation shows that the increase occurs in the $\sigma$-band. With the hole-doping, $T_{c}$ decreases. Implication of this phenomenon is discussed within the BCS framework. While the Mott formula explains only the linear part of $S(T)$ at low temperature, incorporation of electron-phonon interaction enables us to explain $S(T)$ over wide temperature range including the anomalous behavior at high temperature.Comment: 4 pages, 4 figure

Review: A Meta-Analysis of GWAS Studies and Age-Associated Diseases

Genome-Wide Association studies (GWAS) offer an unbiased means to understand the genetic basis of traits by identifying single nucleotide polymorphisms (SNPs) linked to causal variants of complex phenotypes. GWAS have identified a host of susceptibility SNPs associated with many important human diseases, including diseases associated with aging. In an effort to understand the genetics of broad resistance to age-associated diseases (i.e. ‘wellness’), we performed a meta-analysis of human GWAS. Toward that end, we compiled 372 GWAS that identified 1,775 susceptibility SNPs to 105 unique diseases and used these SNPs to create a genomic landscape of disease susceptibility. This map was constructed by partitioning the genome into 200 kb ‘bins’ and mapping the 1,775 susceptibility SNPs to bins based on their genomic location. Investigation of these data revealed significant heterogeneity of disease association within the genome, with 92% of bins devoid of disease-associated SNPs. In contrast, 10 bins (0.06%) were significantly (pINK4/ARF (CDKN2a/b) tumor suppressor locus on 9p21.3. Provocatively, all 10 significantly enriched bins contained genes linked to either inflammation or cellular senescence pathways, and SNPs near regulators of senescence were particularly associated with disease of aging (e.g. cancer, atherosclerosis, type 2 diabetes, glaucoma). This analysis suggests that germline genetic heterogeneity in the regulation of immunity and cellular senescence influences the human health span

Skeletal Ring Contractions via I(I)/I(III) Catalysis: Stereoselective Synthesis of cis-α,α-Difluorocyclopropanes

The clinical success of α,α-difluorocyclopropanes, combined with limitations in the existing synthesis portfolio, inspired the development of an operationally simple, organocatalysis-based strategy to access cis-configured derivatives with high levels of stereoselectivity (up to >20:1 cis:trans). Leveraging an I(I)/I(III)-catalysis platform in the presence of an inexpensive HF source, it has been possible to exploit disubstituted bicyclobutanes (BCBs) as masked cyclobutene equivalents for this purpose. In situ generation of this strained alkene, enabled by Brønsted acid activation, facilitates an unprecedented 4 → 3 fluorinative ring contraction, to furnish cis-α,α-difluorinated cyclopropanes in a highly stereoselective manner (up to 88% yield). Mechanistic studies are disclosed together with conformational analysis (X-ray crystallography and NMR) to validate cis-α,α-difluorocyclopropanes as isosteres of the 1,4-dicarbonyl moiety. Given the importance of this unit in biology and the foundational no → π* interactions that manifest themselves in this conformation (e.g., collagen), it is envisaged that the title motif will find application in focused molecular design

Fructose transport-deficient Staphylococcus aureus reveals important role of epithelial glucose transporters in limiting sugar-driven bacterial growth in airway surface liquid.

Hyperglycaemia as a result of diabetes mellitus or acute illness is associated with increased susceptibility to respiratory infection with Staphylococcus aureus. Hyperglycaemia increases the concentration of glucose in airway surface liquid (ASL) and promotes the growth of S. aureus in vitro and in vivo. Whether elevation of other sugars in the blood, such as fructose, also results in increased concentrations in ASL is unknown and whether sugars in ASL are directly utilised by S. aureus for growth has not been investigated. We obtained mutant S. aureus JE2 strains with transposon disrupted sugar transport genes. NE768(fruA) exhibited restricted growth in 10 mM fructose. In H441 airway epithelial-bacterial co-culture, elevation of basolateral sugar concentration (5-20 mM) increased the apical growth of JE2. However, sugar-induced growth of NE768(fruA) was significantly less when basolateral fructose rather than glucose was elevated. This is the first experimental evidence to show that S. aureus directly utilises sugars present in the ASL for growth. Interestingly, JE2 growth was promoted less by glucose than fructose. Net transepithelial flux of D-glucose was lower than D-fructose. However, uptake of D-glucose was higher than D-fructose across both apical and basolateral membranes consistent with the presence of GLUT1/10 in the airway epithelium. Therefore, we propose that the preferential uptake of glucose (compared to fructose) limits its accumulation in ASL. Pre-treatment with metformin increased transepithelial resistance and reduced the sugar-dependent growth of S. aureus. Thus, epithelial paracellular permeability and glucose transport mechanisms are vital to maintain low glucose concentration in ASL and limit bacterial nutrient sources as a defence against infection

The femoral insertions of the anteromedial and posterolateral bundles of the anterior cruciate ligament: a radiographic evaluation

The aim of this radiographic study was to visualize the femoral insertion sites of the anteromedial (AM) and posterolateral (PL) bundle of the anterior cruciate ligament (ACL) on lateral radiographs in different angles of knee flexion to gain better understanding for arthroscopic femoral tunnel placement in ACL double bundle reconstruction. Four fresh cadaveric knees with an intact ACL were dissected to isolate the AM and PL bundle of the ACL. We obtained lateral radiographs of each knee over the range of 0°–90° flexion in 30° increments after painting the bundles with a radiopaque tantalum powder. The center of the radiographically marked femoral insertion was defined for each bundle on the lateral roentgenogram. We analyzed the relationship of knee flexion and the projection of the relative position of the femoral insertion sites of both bundles of the ACL on the lateral roentgenogram. The centre of the PL bundle visualized more anterior and distal than the centre of the AM bundle with the knee held in 90° flexion. The centers of the AM and PL bundle were horizontally aligned when the knee was flexed over 90°. The resulting images allow a radiographic description of the femoral insertion sites of both bundles in different angles of knee flexion. It is essential to be aware of the degree of knee flexion when drilling the femoral tunnels

Fixation of osteochondral fragments in the human knee using Meniscus Arrows®

The aim of this study is to compare the hold in bone of Meniscus Arrows® and Smart Nails®, followed by the report of the results of the clinical application of Meniscus Arrows® as fixation devices. First, pull-out tests were performed to analyse the holdfast of both nails in bone. Statistical analysis showed no significant difference; therefore, the thinner Meniscus Arrow® was chosen as fixation device in the patient series of two patients with a symptomatic Osteochondritis dissecans fragment and three patients with an osteochondral fracture of a femur condyle. The cartilage margins were glued with Tissuecoll®. All fragments consolidated. Second look arthroscopy in three patients showed fixed fragments with stable, congruent cartilage edges. At an average follow-up period of 5 years no pain, effusion, locking, restricted range of motion or signs of osteoarthritis were reported. Based on the results of the pull-out tests and available clinical studies, Meniscus Arrows® and Smart Nails® are both likely to perform adequately as fixation devices in the treatment of Osteochondritis dissecans and osteochondral fractures in the knee. They both provide the advantage of one stage surgery. However, based on their smaller diameter, the Meniscus Arrows® should be preferred for this indication