Revealing an unusual transparent phase of superhard iron tetraboride under high pressure

First principles–based electronic structure calculations of superhard iron tetraboride (FeB₄) under high pressure have been undertaken in this study. Starting with a “conventional” superconducting phase of this material under high pressure leads to an unexpected phase transition toward a semiconducting one. This transition occurred at 53.7 GPa, and this pressure acts as a demarcation between two distinct crystal symmetries, metallic orthorhombic and semiconducting tetragonal phases, with Pnnm and I4₁/acd space groups, respectively. In this work, the electron–phonon coupling-derived superconducting T_c has been determined up to 60 GPa and along with optical band gap variation with increasing pressure up to 300 GPa. The dynamic stability has been confirmed by phonon dispersion calculations throughout this study.The shorter interatomic distances of metal under external pressure consequently increase the valence and conduction band widths, which leads to the enhancement of free electron-like behavior. The development of creating immensely substantial pressure at laboratories enables us to observe the core electrons overlapping under enormous compression and dramatically influences the electronic properties of normally free electron metals such as Li and Na (1–3). The metal-to-insulating phase transformation has been contrived both experimentally and theoretically for both the normal metals while exerting pressure on them. This observation propelled us to investigate the electronic and structural phase transformation of the experimentally synthesized superhard material iron tetraboride (FeB₄) under high pressure (4–8). The intriguing factor of choosing FeB₄ is that the material was proposed as a “conventional” Fe-based superconductor, in contradiction to the discovery of an “unconventional” Fe-based superconductor because of its large electron–phonon coupling. Here we report the exotic phase transition of FeB₄ from metal to semiconductor at 53.7 GPa, even though we started with the metallic orthorhombic phase Pnnm of FeB₄, which shows the superconducting temperature T_c up to 60 GPa. The new phase after 53.7 GPa has I4₁/acd space group symmetry with a finite fundamental band gap, which increases along with pressure monotonically. All of the considered structures have been tested to have a thermodynamic stability from phonon dispersion calculations. The reason behind the phenomena could be the overlap of atomic cores at higher pressure ranges, which increases the hybridization of valence electrons and their repulsive interactions with core electrons. The immediate technological outcome of this scenario of metal-to-semiconducting phase transition could be to search for a transparent state of a material that is a metal under ambient conditions. This drastic change of electronic and structural properties can be observed in other materials as well, and hence this can open a field of studying them from a high-pressure perspective.     

Action capability constrains visuo-motor complexity during planning and performance in on-sight climbing

The capability to adapt to changing conditions is crucial for safe and successful performance in physical activities and sports. According to the affordance-based control perspective, individuals act in such a way as to take into account the limits of their capability to act. However, it is not clear how strength interacts with skill in shaping performer-environment interactions. We, therefore, determined whether fingertip strength influences patterns of gaze and climbing behavior on new routes of ever-increasing difficulty. We expected that comparatively weaker climbers would show less complex behavior because of an inability to perceive and act. Stronger climbers would show more complex visuo-motor behavior because more opportunities for action remain, even as route difficulty increases. For very strong climbers the route would not be challenging enough, and less complex patterns suffice. Twenty climbers, ranging from lower grade to elite level participated. Maximum fingertip strength was obtained. Participants previewed and then climbed two separate 3 m long traverses, gradually decreasing in edge depth. Gaze and hip positions were collected for subsequent computation of gaze transition entropy (during preview) and hip displacement entropy (during climbing). Data revealed statistically significant curvilinear relationships between both fingertip strength and gaze transition entropy, and fingertip strength, and hip displacement entropy. Visuo-motor complexity is scaled by how close the individual must act relative to boundaries of what the environment affords and does not afford for action given the individual constraints. Future research should examine in greater detail relationships between action capabilities and functional movement variability.     

Ceramides are associated with inflammatory processes in human mediastinal adipose tissue

Background and AimCeramides are poorly characterized in human adipose tissue. The aim of this study was to investigate concentrations of different ceramide species in human subcutaneous and visceral adipose tissue depots and to determine associations between ceramides and global gene expression profiles.Methods and ResultsConcentrations of six ceramide species were determined in plasma and in subcutaneous and mediastinal adipose tissue from 10 overweight subjects (BMI 29.4 ± 4.9 kg/m²). In the adipose tissue biopsies gene expression arrays were performed and relationships between ceramides and gene expression analyzed. Immunostaining of the two adipose tissue depots was performed in an independent group of 10 patients. Mediastinal adipose tissue contained significantly higher concentrations (p < 0.05) of all six ceramide species than the subcutaneous depot. Of the six ceramides in plasma, concentrations of only two (Cer d18:1/18:0 and Cer d18:1/22:0) correlated significantly (p < 0.05) with the corresponding species in mediastinal adipose tissue, but there were no significant correlations between ceramides in plasma and subcutaneous adipose tissue. Multivariate analysis identified significant correlations between the total ceramide concentration and global gene expression within mediastinal, but not subcutaneous adipose tissue, according to cross-validation. Gene ontology analysis of genes related to ceramides in the mediastinal depot revealed that genes positively correlated with ceramides were associated mainly with immune and inflammatory categories, while genes negatively correlated with ceramides were associated mainly with lipid and carbohydrate metabolism.ConclusionsCeramides in human mediastinal adipose tissue may be involved in inflammation and lipid and carbohydrate metabolism.     

Time Interval of Two Injections and First-Dose Dependent of Accelerated Blood Clearance Phenomenon Induced by PEGylated Liposomal Gambogenic Acid: The Contribution of PEG-Specific IgM

Repeated injection of PEGylated liposomes can cause the disappearance of long circulating property because of the induction of anti-PEG IgM antibody referred to as “accelerated blood clearance (ABC) phenomenon.” Although ABC phenomenon typically occurs when entrapped drugs are chemotherapeutic agent with low cytotoxic, there is little evidence of accelerated blood clearance of PEGylated herbal-derived compound on repeated injection. Herein, we investigated the blood concentration of PEGylated liposomal gambogenic acid (PEG-GEA-L), a model PEGylated liposomal herbal extract, on its repeated injection to rats. We found time interval between injections had considerable impact on the magnitude of ABC phenomenon induced by PEG-GEA-L. When time interval was prolonged from 3 days to 7 days, ABC phenomenon could be attenuated. Furthermore, its magnitude was enhanced accompanied by a marked rise in the accumulation of PEG-GEA-L in the liver and spleen in a first-dose–dependent manner. Consistently, the level of anti-PEG IgM significantly increased with the first dose of PEG-GEA-L and decreased with the extended time interval between injections, which implies anti-PEG IgM is a major contributor to the ABC phenomenon. Notably, the increased expression of liver anti-PEG IgM was accompanied by an increased expression of efflux transporters in the induction process of the ABC phenomenon.     

Evaluating the Effects of Hinge Flexibility on the Solution Structure of Antibodies at Concentrated Conditions

Employing 2 different coarse-grained models, we evaluated the effect of intramolecular domain-domain distances and hinge flexibility on the general solution structure of monoclonal antibodies (mAbs), within the context of protein-protein steric repulsion. These models explicitly account for the hinge region, and represent antibodies at either domain or subdomain levels (i.e., 4-bead and 7-bead representations, respectively). Additionally, different levels of mAb flexibility are also considered. When evaluating mAbs as rigid structures, analysis of small-angle scattering profiles showed that changes in the relative internal distances between Fc and Fab domains significantly alter the local arrangement of neighboring molecules, as well as the molecular packing of the concentrated mAb solutions. Likewise, enabling hinge flexibility in either of the mAb models led to qualitatively similar results, where flexibility increases the spatial molecular arrangement at elevated concentrations. This occurs because fluctuations in mAb quaternary structure are modulated by the close proximity between molecules at elevated concentrations (>50 mg mL^?1), yielding an increased molecular packing and osmotic compressibility. However, our results also showed that the mechanism behind this synergy between flexibility and packing strongly depends on both the level of structural detail and the number of degrees-of-freedom considered in the coarse-grained model.     

Effects of sitagliptin therapy on markers of low-grade inflammation and cell adhesion molecules in patients with type 2 diabetes

Inflammation and endothelial dysfunction are increasingly being recognized as key etiological factors in the development of atherosclerosis and subsequent cardiovascular disease. These pro-atherogenic factors are strongly correlated and are often found to co-segregate in patients with type 2 diabetes. The impact of sitagliptin, a selective inhibitor of dipeptidyl peptidase-4, on inflammation and markers of endothelial function remains to be fully characterized.     

The one year exercise and lifestyle intervention program KLAKS: Effects on anthropometric parameters,cardiometabolic risk factors and glycemic control in childhood obesity

Objective

Regular physical exercise within structured lifestyle programs may improve weight status and minimize metabolic risk factors in childhood obesity. The aim of this study was to evaluate the effect of the one-year combined physical exercise/lifestyle program KLAKS on anthropometric and metabolic parameters and glycemic control in childhood obesity.

Materials and Methods

142 overweight/obese (BMI > 90th percentile) candidates (7–18 years) were enrolled, 115 participants completed the program. Anthropometrics and biochemical parameters were obtained at beginning and completion. An oral glucose tolerance test (OGTT) was performed in a subgroup of participants. Course of glucose and insulin levels within OGTT was correlated with several parameters and is reported here for those who completed the program.

Results

The mean standard deviation scores (SDS) decreased significantly for BMI, waist circumference, waist-to-height ratio (WHtR) and percentage body fat (all p ≤ 0.01). Improved metabolic risk markers included mean glucose levels within an OGTT at follow-up compared to baseline (p < 0.0001) and HbA1c (p = 0.05) as well as indications of improvement for gamma-glutamyl-transferase and free fatty acids.

Conclusions

The one-year combined exercise/lifestyle program KLAKS significantly improves markers of obesity and glycemic control. Impaired cardiometabolic risk markers, even subclinical, are also favorably influenced by program participation.