Weak localization effects in granular metals

The weak localization correction to the conductivity of a granular metal is calculated using the diagrammatic technique in the reciprocal grain lattice representation. The properties of this correction are very similar to that one in disordered metal, with the replacement of the electron mean free path $\ell$ by the grain diameter $d$ and the dimensionless conductance $g$ by the tunnelling dimensionless conductance $g_{T}$. In particular, we demonstrate that at zero temperature no conducting phase can exist for dimensions $D\leq 2$. We also analyze the WL correction to magnetoconductivity in the weak field limit.Comment: 4 pages, 3 figures; minor corrections adde

Association of a homozygous GCK missense mutation with mild diabetes

Background: Homozygous inactivating GCK mutations have been repeatedly reported to cause severe hyperglycemia, presenting as permanent neonatal diabetes mellitus (PNDM). Conversely, only two cases of GCK homozygous mutations causing mild hyperglycemia have been so far described. We here report a novel GCK mutation (c.1116G>C, p.E372D), in a family with one homozygous member showing mild hyperglycemia. Methods: GCK mutational screening was carried out by Sanger sequencing. Computational analyses to investigate pathogenicity and molecular dynamics (MD) were performed for GCK-E372D and for previously described homozygous mutations associated with mild (n = 2) or severe (n = 1) hyperglycemia, used as references. Results: Of four mildly hyperglycemic family-members, three were heterozygous and one, diagnosed in the adulthood, was homozygous for GCK-E372D. Two nondiabetic family members carried no mutations. Fasting glucose (p = 0.016) and HbA1c (p = 0.035) correlated with the number of mutated alleles (0–2). In-silico predicted pathogenicity was not correlated with the four mutations’ severity. At MD, GCK-E372D conferred protein structure flexibility intermediate between mild and severe GCK mutations. Conclusions: We present the third case of homozygous GCK mutations associated with mild hyperglycemia, rather than PNDM. Our in-silico analyses support previous evidences suggesting that protein stability plays a role in determining clinical severity of GCK mutations

Lectin staining shows no evidence of involvement of glycocalyx/mucous layer carbohydrate structures in development of celiac disease

The presence of unique carbohydrate structures in the glycocalyx/mucous layer of the intestine may be involved in a susceptibility to celiac disease (CD) by serving as attachment sites for bacteria. This host-microbiota interaction may influence the development of CD and possibly other diseases with autoimmune components. We examined duodenal biopsies from a total of 30 children, of which 10 had both celiac disease (CD) and type 1 diabetes (T1D); 10 had CD alone; and 10 were suspected of having gastrointestinal disease, but had normal duodenal histology (non-CD controls). Patients with both CD and T1D were examined before and after remission following a gluten-free diet. We performed lectin histochemistry using peanut agglutinin (PNA) and Ulex europaeus agglutinin (UEA) staining for Gal-β(1,3)-GalNAc and Fucα1-2Gal-R, respectively, of the glycocalyx/mucous layer. The staining was scored based on dissemination of stained structures on a scale from 0 to 3. Evaluation of the scores revealed no difference between biopsies obtained before and after remission in the group of children with both CD and T1D. A comparison of this pre-remission group with the children who had CD alone or the non-CD controls also showed no significant differences. Based on our material, we found no indication that the presence of Gal-β(1,3)-GalNAc or Fucα1-2Gal-R is involved in the susceptibility to CD, or that the disease process affects the expression of these carbohydrates

Many-Body Effects on Tunneling of Electrons in Magnetic-Field-Induced Quasi One-Dimensional Electron Systems in Semiconductor Nanowhiskers

Effects of the electron-electron interaction on tunneling in a semiconductor nanowhisker are studied in a magnetic quantum limit. We consider the system with which bulk and edge states coexist. In bulk states, the temperature dependence of the transmission probability is qualitatively similar to that of a one-dimensional electron system. We investigate contributions of edge states on transmission probability in bulk states. Those contributions can be neglected within our approximation which takes into account only most divergent terms at low temperatures.Comment: 9 pages, 6 figure

MitImpact 3: modeling the residue interaction network of the Respiratory Chain subunits

Numerous lines of evidence have shown that the interaction between the nuclear and mitochondrial genomes ensures the efficient functioning of the OXPHOS complexes, with substantial implications in bioenergetics, adaptation, and disease. Their interaction is a fascinating and complex trait of the eukaryotic cell that MitImpact explores with its third major release. MitImpact expands its collection of genomic, clinical, and functional annotations of all non-synonymous substitutions of the human mitochondrial genome with new information on putative Compensated Pathogenic Deviations and co-varying amino acid sites of the Respiratory Chain subunits. It further provides evidence of energetic and structural residue compensation by techniques of molecular dynamics simulation. MitImpact is freely accessible at http://mitimpact.css-mendel.it

A low-cost internal standard loader for solid-phase sorbing tools

Solid-phase sorption is widely used for the analysis of gaseous specimens as it allows at the same time to preconcentrate target analytes and store samples for relatively long periods. The addition of internal standards (ISs) in the analytical workflow can greatly reduce the variability of the analyses and improve the reliability of the protocols. In this work, we describe the development and testing of a portable system for the reliable production of gaseous mixture of( 8)D-Toluene in a 1L Silonite canister as well as its reproducible loading into solid-phase sorbing tools as ISs. The portable system was tested using needle trap microextraction, solid-phase extraction, and thin-film microextraction techniques commonly employed for the analysis of gaseous samples. Even though our specific interest is in breath analysis, the system can also be used for the collection of any kind of gaseous specimen. A microcontroller allows the fine control of the sampling flow by a digital mass flow controller. Flow rate and sample volume could be set either through a rotary encoder mounted onto the control board or through a dedicated android app. The variability of the airflow is in the range 5-200 ml min(-1) and it is lower than 1%, whereas the variability of the IS (D-8-Toluene) concentration dispensed over time by the loader measured by selected-ion flow-tube mass spectrometry (MS) is <3%. This combination resulted in intra- and inter-day precision of the amount loaded in the sorbent tools lower than 15%. No carry-over was detected in the loader after the delivery of the D-8-Toluene measured by gas chromatography-MS. The 8D-Toluene concentration in the canister was stable for up to three weeks at room temperature

Mechanisms of pathogenesis of missense mutations on the KDM6A-H3 interaction in type 2 Kabuki Syndrome

Mutations in genes encoding for histone methylation proteins are associated with several developmental disorders. Among them, KDM6A is the disease causative gene of type 2 Kabuki Syndrome, a rare multisystem disease. While nonsense mutations and short insertions/deletions are known to trigger pathogenic mechanisms, the functional effects of missense mutations are still uncharacterized. In this study, we demonstrate that a selected set of missense mutations significantly hamper the interaction between KDM6A and the histone H3, by modifying the dynamics of the linker domain, and then causing a loss of function effect

Supramolecular behaviour and fluorescence of rhodamine-functionalised ROMP polymers

Inherently fluorescent polymers are of interest in materials and medicine. We report a ring-opening metathesis polymerisation (ROMP) platform for creation of amphiphilic block copolymers in which one block is formed from rhodamine B-containing monomers. The polymers self-assemble into well-defined micelles which are able to sequester molecular dyes and further interact with them by energy transfer. Despite incorporating a cationic dye known to bind DNA, the polymer micelles do not interact with DNA, indicating that they are potentially safe for use in bioanalytical applications

Prognostic stratification of obese patients by stress ^99mTc- tetrofosmin myocardial perfusion imaging

Obesity is a major heath problem associated with increased cardiovascular mortality. There are currently no data to support a role for stress imaging techniques in the risk stratification of obese patients. The aim of this study was to assess the independent value of stress 99mTc-tetrofosmin SPECT in predicting mortality and hard cardiac events in obese patients. Methods: We studied 265 patients with a body mass index greater than 30 kg/m2 by exercise or dobutamine stress 99mTc-tetrofosmin myocardial perfusion tomography. Endpoints during follow-up were cardiac death and death of any cause. Results: The mean patient age (±SD) was 59 ± 10 y, and 110 of the patients were men (42%). The mean body mass index was 37 ± 7 kg/m2. Scan findings were normal in 113 patients (43%). Myocardial perfusion abnormalities were fixed in 62 patients (23%) and reversible in 90 patients (34%). During a mean follow-up period of 5.5 ± 2 y, 41 patients (15%) died. Death was considered cardiac in 22 patients (8%). Nonfatal myocardial infarction occurred in 20 patients (7.5%). The annual cardiac death rate was 0.6% in patients with normal perfusion and 3.3% in patients with abnormal perfusion. Patients with a multiple-vessel distribution of abnormalities had a higher cardiac death rate than did patients with a single-vessel distribution (4.1%vs. 2.5%, P &lt; 0.05). The annual mortality rate was 1.3% in patients with normal perfusion and 4.2% in patients with abnormal perfusion. In a multivariate analysis, perfusion abnormalities were independently predictive of cardiac mortality (risk ratio, 3.2; 95% confidence interval, 1.5-6.7) and overall mortality (risk ratio, 2.7; 95% confidence interval, 1.4-4.3). Conclusion: Stress 99mTc-tetrofosmin myocardial perfusion imaging is a useful tool for predicting cardiac and overall mortality in obese patients.</p