A Generalized Nomenclature Scheme for Graphene Pores, Flakes, and Edges, and an Algorithm for Their Generation and Numbering.

In the present study, we generalize our recently proposed nomenclature scheme for porous graphene structures to include graphene flakes and (periodic) edges, i.e., nanographenes and graphene nanoribbons. The proposed nomenclature scheme is a complete scheme that similarly treats all these structures. Beyond this generalization, we study the geometric features of graphene flakes and edges based on ideas from the graph theory, as well as the pore-flake duality. Based on this study, we propose an algorithm for the systematic generation, identification, and numbering of graphene pores, flakes, and edges. The algorithm and the nomenclature scheme can also be used for flakes and edges of similar honeycomb systems.

Evaluating the performance of ReaxFF potentials for sp2 carbon systems (graphene, carbon nanotubes, fullerenes) and a new ReaxFF potential.

We study the performance of eleven reactive force fields (ReaxFF), which can be used to study sp2 carbon systems. Among them a new hybrid ReaxFF is proposed combining two others and introducing two different types of C atoms. The advantages of that potential are discussed. We analyze the behavior of ReaxFFs with respect to 1) the structural and mechanical properties of graphene, its response to strain and phonon dispersion relation; 2) the energetics of (n, 0) and (n, n) carbon nanotubes (CNTs), their mechanical properties and response to strain up to fracture; 3) the energetics of the icosahedral C60 fullerene and the 40 C40 fullerene isomers. Seven of them provide not very realistic predictions for graphene, which made us focusing on the remaining, which provide reasonable results for 1) the structure, energy and phonon band structure of graphene, 2) the energetics of CNTs versus their diameter and 3) the energy of C60 and the trend of the energy of the C40 fullerene isomers versus their pentagon adjacencies, in accordance with density functional theory (DFT) calculations and/or experimental data. Moreover, the predicted fracture strain, ultimate tensile strength and strain values of CNTs are inside the range of experimental values, although overestimated with respect to DFT. However, they underestimate the Young's modulus, overestimate the Poisson's ratio of both graphene and CNTs and they display anomalous behavior of the stress - strain and Poisson's ratio - strain curves, whose origin needs further investigation.

Crystal structure of human NADK2 reveals a dimeric organization and active site occlusion by lysine acetylation.

NAD+ kinases (NADKs) are metabolite kinases that phosphorylate NAD+ molecules to make NADP+, a limiting substrate for the generation of reducing power NADPH. NADK2 sustains mitochondrial NADPH production that enables proline biosynthesis and antioxidant defense. However, its molecular architecture and mechanistic regulation remain undescribed. Here, we report the crystal structure of human NADK2, revealing a substrate-driven mode of activation. We find that NADK2 presents an unexpected dimeric organization instead of the typical tetrameric assemblage observed for other NADKs. A specific extended segment (aa 325-365) is crucial for NADK2 dimerization and activity. Moreover, we characterize numerous acetylation events, including those on Lys76 and Lys304, which reside near the active site and inhibit NADK2 activity without disrupting dimerization, thereby reducing mitochondrial NADP(H) production, proline synthesis, and cell growth. These findings reveal important molecular insight into the structure and regulation of a vital enzyme in mitochondrial NADPH and proline metabolism.

CanVaS: Documenting the genetic variation spectrum of Greek cancer patients.

National genetic variation registries vastly increase the level of detail for the relevant population, while directly affecting patient management. Herein, we report CanVaS, a Cancer Variation reSource aiming to document the genetic variation of cancer patients in Greece. CanVaS comprises germline genetic data from 7,363 Greek individuals with a personal and/or family history of malignancy. The data set incorporates approximately 24,000 functionally annotated rare variants in 97 established or suspected cancer susceptibility genes. For each variant, allele frequency for the Greek population, interpretation for clinical significance, anonymized family and segregation information, as well as phenotypic traits of the carriers, are included. Moreover, information on the geographic distribution of the variants across the country is provided, enabling the study of Greek population isolates. Direct comparisons between Greek (sub)populations with relevant genetic resources are supported, allowing fine-grain localized adjustment of guidelines and clinical decision-making. Most importantly, anonymized data are available for download, while the Leiden Open Variation Database schema is adopted, enabling integration/interconnection with central resources. CanVaS could become a stepping-stone for a countrywide effort to characterize the cancer genetic variation landscape, concurrently supporting national and international cancer research. The database can be accessed at: http://ithaka.rrp.demokritos.gr/CanVaS.

High temperature stability, metallic character and bonding of the Si2BN planar structure.

The family of monolayered Si2BN structures constitute a new class of 2D materials exhibiting metallic character with remarkable stability. Topologically, these structures are very similar to graphene, forming a slightly distorted honeycomb lattice generated by a union of two basic motifs with AA and AB stacking. In the present work we study in detail the structural and electronic properties of these structures in order to understand the factors which are responsible for their structural differences as well as those which are responsible for their metallic behavior and bonding. Their high temperature stability is demonstrated by the calculations of finite temperature phonon modes which show no negative contributions up to and beyond 1000 K. Presence of the negative thermal expansion coefficient, a common feature of one-atom thick 2D structures, is also seen. Comparison of the two motifs reveal the main structural differences to be the differences in their bond angles, which are affected by the third nearest neighbor interactions ofcis-transtype. On the other hand, the electronic properties of these two structures are very similar, including the charge transfers occurring between orbitals and between atoms. Their metallicity is mainly due to thepzorbitals of Si with a minor contribution from thepzorbitals of B, while the contribution from thepzorbitals of N atoms is negligible. There is almost no contributions from the Npzelectrons to the energy states near the Fermi level, and they form a band well below it. I.e., thepzelectrons of N are localized mostly at the N atoms and therefore cannot be considered as mobile electrons of thepzcloud. Moreover, we show that due to the relative positions in the energy axis of the atomic energies of thepzorbitals of B, N and Si atoms, the density of states (DOS) of Si2BN can be considered qualitatively as a combination of the DOS of planar hexagonal BN (h-BN) and hypothetically planar silicene (ph-Si). As a result, the Si2BN behaves electronically at the Fermi level as slightly perturbed ph-Si, having very similar electronic properties as silicene, but with the advantage of having kinetic stability in planar form. As for the bonding, the Si-Si bonds are covalent, while theπback donation mechanism occurs for the B-N bonding, in accordance with the B-N bonding in h-BN.

The Coming of Age for Big Data in Systems Radiobiology, an Engineering Perspective.

As high-throughput approaches in biological and biomedical research are transforming the life sciences into information-driven disciplines, modern analytics platforms for big data have started to address the needs for efficient and systematic data analysis and interpretation. We observe that radiobiology is following this general trend, with -omics information providing unparalleled depth into the biomolecular mechanisms of radiation response-defined as systems radiobiology. We outline the design of computational frameworks and discuss the analysis of big data in low-dose ionizing radiation (LDIR) responses of the mammalian brain. Following successful examples and best practices of approaches for the analysis of big data in life sciences and health care, we present the needs and requirements for radiation research. Our goal is to raise awareness for the radiobiology community about the new technological possibilities that can capture complex information and execute data analytics on a large scale. The production of large data sets from genome-wide experiments (quantity) and the complexity of radiation research with multidimensional experimental designs (quality) will necessitate the adoption of latest information technologies. The main objective was to translate research results into applied clinical and epidemiological practice and understand the responses of biological tissues to LDIR to define new radiation protection policies. We envisage a future where multidisciplinary teams include data scientists, artificial intelligence experts, DevOps engineers, and of course radiation experts to fulfill the augmented needs of the radiobiology community, accelerate research, and devise new strategies.

Investigating the impact of overnight fasting on intrinsic functional connectivity: a double-blind fMRI study.

The human brain depends mainly on glucose supply from circulating blood as an energy substrate for its metabolism. Most of the energy produced by glucose catabolism in the brain is used to support intrinsic communication purposes in the absence of goal-directed activity. This intrinsic brain function can be detected with fMRI as synchronized fluctuations of the BOLD signal forming functional networks. Here, we report results from a double-blind, placebo controlled, cross-over study addressing changes in intrinsic brain activity in the context of very low, yet physiological, blood glucose levels after overnight fasting. Comparison of four major resting state networks in a fasting state and a state of elevated blood glucose levels after glucagon infusion revealed altered patterns of functional connectivity only in a small region of the posterior default mode network, while the rest of the networks appeared unaffected. Furthermore, low blood glucose was associated with changes in the right frontoparietal network after cognitive effort. Our results suggest that fasting has only limited impact on intrinsic brain activity, while a detrimental impact on a network related to attention is only observable following cognitive effort, which is in line with ego depletion and its reliance on glucose.

Atomistic potential for graphene and other sp2 carbon systems.

We introduce a torsional force field for sp2 carbon to augment an in-plane atomistic potential of a previous work [G. Kalosakas et al., J. Appl. Phys., 2013, 113, 134307] so that it is applicable to out-of-plane deformations of graphene and related carbon materials. The introduced force field is fit to reproduce density-functional-theory calculation data of appropriately chosen structures. The aim is to create a force field that is as simple as possible so it can be efficient for large scale atomistic simulations of various sp2 carbon structures without significant loss of accuracy. We show that the complete proposed potential reproduces characteristic properties of fullerenes and carbon nanotubes. In addition, it reproduces very accurately the out-of-plane acoustic and optical modes of graphene's phonon dispersion as well as all phonons with frequencies up to 1000 cm-1.

Physiological parameters regulating circulating levels of the IGFBP-4/Stanniocalcin-2/PAPP-A axis.

BACKGROUND: Insulin Growth Factor Binding Protein 4 (IGFBP-4), Stanniocalcin-2 (STC-2) and Pregnancy-Associated Plasma Protein-A (PAPP-A) have a well-documented involvement in several physiological functions in humans but predictors of their circulating levels remain largely unknown. We aimed to identify anthropometric and biochemical parameters associated with circulating levels of IGFBP-4/STC-2/PAPP-A axis (ISPa) cross-sectionally and to study their day-night variation and their regulation in response to mixed meal and exercise. METHODS: One hundred twenty two healthy individuals were evaluated cross-sectionally. Subgroups were subjected to standardized mixed meal ingestion in increasing quantities of 125mL or 250mL, or aerobic exercise for 30min, or day-night rhythm study. Main outcome measurements were circulating IGFBP-4 (total and intact), STC-2 and PAPP-A levels. RESULTS: In multivariate models, the main predictors of serum total IGFBP-4 were PAPP-A and female gender. Intact IGFBP-4 was positively associated with serum creatinine. Height was inversely and female gender and % of total body fat were positively correlated with STC-2. PAPP-A decreased after ingesting both the 125mL (p=0.03) and 250mL quantities (p=0.001), while total IGFBP-4 was reduced after the 250mL quantity (p=0.001). Exercise increased STC-2 and PAPP-A levels (p<0.001 for both). Intact, and to a lesser extent total, IGFBP-4 displayed a cortisol-like day/night variation. CONCLUSIONS: We report for the first time anthropometric and physiological modulators of ISPa serum levels in healthy humans.

Structural deformations of two-dimensional planar structures under uniaxial strain: the case of graphene.

In the present work, a method for the study of the structural deformations of two dimensional planar structures under uniaxial strain is presented. The method is based on molecular mechanics using the original stick and spiral model and a modified one which includes second nearest neighbor interactions for bond stretching. As we show, the method allows an accurate prediction of the structural deformations of any two dimensional planar structure as a function of strain, along any strain direction in the elastic regime, if structural deformations are known along specific strain directions, which are used to calculate the stick and spiral model parameters. Our method can be generalized including other strain conditions and not only uniaxial strain. We apply this method to graphene and we test its validity, using results obtained from ab initio density functional theory calculations. What we find is that the original stick and spiral model is not appropriate to describe accurately the structural deformations of graphene in the elastic regime. However, the introduction of second nearest neighbor interactions provides a very accurate description.

A Time-Calibrated Mitogenome Phylogeny of Catfish (Teleostei: Siluriformes).

A very significant part of the world's freshwater ichthyofauna is represented by ancient, exceptionally diverse and cosmopolitan ray-finned teleosts of the order Siluriformes. Over the years, catfish have been established as an exemplary model for probing historical biogeography at various scales. Yet, several tantalizing gaps still exist in their phylogenetic history, timeline and mode of diversification. Here, we re-examine the phylogeny of catfish by assembling and analyzing almost all publicly available mitogenome data. We constructed an ingroup matrix of 62 full-length mitogenome sequences from 20 catfish families together with four cypriniform outgroups, spanning 15,557 positions in total. Partitioned maximum likelihood analyses and Bayesian relaxed clock dating using fossil age constraints provide some useful and novel insights into the evolutionary history of this group. Loricarioidei are recovered as the first siluriform group to diversify, rendering Neotropics the cradle of the order. The next deepest clade is the South American Diplomystoidei placed as a sister group to all the remaining Siluroidei. The two multifamilial clades of "Big Asia" and "Big Africa" are also recovered, albeit nodal support for the latter is poor. Within "Big Asia", Bagridae are clearly polyphyletic. Other interfamilial relationships, including Clariidae + Heteropneustidae, Doradidae + Auchenipteridae and Ictaluridae + Cranoglanididae are robustly resolved. Our chronogram shows that siluriforms have a Pangaean origin, at least as far back as the Early Cretaceous. The inferred timeline of the basal splits corroborates the "Out-of-South America" hypothesis and accords well with the fossil record. The divergence of Siluroidei most likely postdated the final separation of Africa and South America. An appealing case of phylogenetic affinity elaborated by biogeographic dispersal is exemplified by the Early Paleogene split between the Southeast Asian Cranoglanididae and Ictaluridae, with the latter radiating into North America's freshwater realm by Eocene. The end of Cretaceous probably concludes the major bout of diversification at the family level while with the dawn of the Cenozoic a prolific radiation is evident at the generic level.

Glutamatergic Agents as Add-On Medication for the Treatment of Obsessive-Compulsive Disorder: A Systematic Review and Meta-Analysis.

OBJECTIVE: The aim of the present study was to review the existing literature on clinical trials with glutamatergic agents in adults with obsessive-compulsive disorder (OCD) and to perform a meta-analysis to estimate the overall effect size. DATA SOURCES: We searched in MEDLINE, Embase, and the Cochrane Library for eligible studies, using the following search terms: (glutamate OR glutaminergic OR glutamatergic OR NMDA OR AMPA OR kainate) AND (obsessive-compulsive disorder OR obsessive OR compulsive OR OCD). A separate search was performed for generally known glutamatergic agents. The databases were searched for articles published by May 31, 2015. STUDY SELECTION: Eligible studies were double-blind, randomized controlled trials that tested the efficacy of add-on treatment with a glutamatergic agent in patients with OCD. DATA EXTRACTION: Data were extracted independently by 2 reviewers. We extracted dichotomous data (number of patients with response and remission) to estimate relative risk ratios (RRs), as well as continuous data (scores in Yale-Brown Obsessive Compulsive Scale and Clinical Global Impressions-Severity of Illness and -Improvement scales), which were used to estimate standardized mean differences. Effect sizes were estimated using a random-effects model. RESULTS: Eight randomized controlled trials were identified. The overall ratio for response was RR = 3.71 (95% CI, 2.35-5.83; P < .001). When limited to the studies with treatment-resistant patients, the effect size remained significant (RR = 4.30; 95% CI, 2.19-8.43; P < .001). Secondary outcomes, such as the standardized mean differences for continuous data, showed the statistically significant superiority (P < .001) of glutamatergic agents over placebo. The risk of dropouts was RR = 1.18 (95% CI, 0.83-1.69; P = .361) and the risk of dropouts due to adverse effects was RR = 3.04 (95% CI, 1.57-5.89; P = .001). CONCLUSIONS: Glutamatergic agents are effective as add-on treatment for OCD in general and especially for treatment-refractory OCD.

Circulating follistatin displays a day-night rhythm and is associated with muscle mass and circulating leptin levels in healthy, young humans.

PURPOSE: Follistatin may affect lean and fat mass and be implicated in metabolic diseases. We aimed to elucidate physiological predictors of circulating follistatin variation in healthy young humans. PROCEDURES: This was an observational, cross-sectional study with two additional prospective observational arms (circadian, seasonal sub-studies) and one prospective interventional arm (mixed meal sub-study). Healthy, young individuals of both sexes (n=122) were subjected to anthropometric and body composition measurements and their eating and exercise behavior profiles were assessed by validated questionnaires. Sub-groups were subjected to standardized meal ingestion (n=36), day-night rhythm (n=20) and seasonal variation (n=20) studies. Main outcome of the study were circulating follistatin levels. RESULTS: At baseline follistatin levels were correlated with creatinine (r=0.24; p=0.01), creatine phosphokinase (rs=0.22; p=0.02), and with lean body mass (rs=0.19; p=0.04) and were higher in males than females (p=0.004) after adjustment for leptin, which was its major predictor. Follistatin levels showed a circadian (p<0.001), but not a seasonal, variation, and were also affected by the phase of menstrual cycle in females (p=0.034). Follistatin levels were not affected by dietary or exercise habits but levels increased after a standardized meal ingestion (250kcal) (p=0.002). CONCLUSIONS: In healthy young individuals circulating follistatin levels are correlated with muscle mass. Follistatin levels are associated with circulating leptin levels and display a day-night rhythm and a menstrual cycle, but not a seasonal, variation.

Brain Radiation Information Data Exchange (BRIDE): integration of experimental data from low-dose ionising radiation research for pathway discovery.

BACKGROUND: The underlying molecular processes representing stress responses to low-dose ionising radiation (LDIR) in mammals are just beginning to be understood. In particular, LDIR effects on the brain and their possible association with neurodegenerative disease are currently being explored using omics technologies. RESULTS: We describe a light-weight approach for the storage, analysis and distribution of relevant LDIR omics datasets. The data integration platform, called BRIDE, contains information from the literature as well as experimental information from transcriptomics and proteomics studies. It deploys a hybrid, distributed solution using both local storage and cloud technology. CONCLUSIONS: BRIDE can act as a knowledge broker for LDIR researchers, to facilitate molecular research on the systems biology of LDIR response in mammals. Its flexible design can capture a range of experimental information for genomics, epigenomics, transcriptomics, and proteomics. The data collection is available at: .

Graphene allotropes under extreme uniaxial strain: an ab initio theoretical study.

Using density functional theory calculations, we study the response of three representative graphene allotropes (two pentaheptites and octagraphene) as well as graphene, to uniaxial strain up to their fracture limit. Those allotropes can be seen as distorted graphene structures formed upon periodically arranged Stone-Walles transformations. We calculate their mechanical properties (Young's modulus, Poisson's ratio, speed of sound, ultimate tensile strength and the corresponding strain), and we describe the pathways of their fracture. Finally, we study strain as a factor for the conversion of graphene into those allotropes upon Stone-Walles transformations. For specific sets of Stone-Walles transformations leading to an allotrope, we determine the strain directions and the corresponding minimum strain value, for which the allotrope is more favorable energetically than graphene. We find that the minimum strain values which favor those conversions are of the order of 9-13%. Moreover, we find that the energy barriers for the Stone-Walles transformations decrease dramatically under strain, however, they remain prohibitive for structural transitions. Thus, strain alone cannot provide a synthetic route to these allotropes, but could be a part of composite procedures for this purpose.

Successive spin polarizations underlying a new magnetic coupling contribution in diluted magnetic semiconductors.

We propose a new type of magnetic coupling (MC) that is found in diluted magnetic semiconductors (DMSs). The origin of this is found to be the result of charge transfer processes followed by successive spin polarizations (SSPs) along successive cation-anion segments which include the impurities. The basic process underlying the SSP-based MC (SSP-MC) is the sharing of a single spin orbital by two neighboring impurities. As such, it can be considered as a localized double exchange as it is not mediated by free carriers. SSP-MC can be either ferromagnetic (SSP-FMC) or antiferromagnetic (SSP-AFMC) and, as demonstrated here, the SSP-FMC can be significantly enhanced via codoping; it can act in competition with superexchange and/or double and/or p-d exchange interactions. While the SSP-MC is not directly related to the magnitude of the magnetic moments of the impurities, it depends strongly on the energy difference of the host and impurity d-band centers, the difference of their electronegativities and rather weakly on the coupling interactions between them as well as between the cations and their mediating anions. The validity of the proposed SSP-MC as a new type of magnetic coupling is demonstrated by ab initio results for DMSs, namely ZnO, GaN, GaP, TiO2 and MoS2 monodoped (with Co, Cu and Mn) and codoped (with Co-Cu-Co and Mn-Cu-Mn).

Effects of overnight fasting on working memory-related brain network: an fMRI study.

Glucose metabolism serves as the central source of energy for the human brain. Little is known about the effects of blood glucose level (BGL) on higher-order cognitive functions within a physiological range (e.g., after overnight fasting). In this randomized, placebo-controlled, double blind study, we assessed the impact of overnight fasting (14 h) on brain activation during a working memory task. We sought to mimic BGLs that occur naturally in healthy humans after overnight fasting. After standardized periods of food restriction, 40 (20 male) healthy participants were randomly assigned to receive either glucagon to balance the BGL or placebo (NaCl). A parametric fMRI paradigm, including 2-back and 0-back tasks, was used. Subclinically low BGL following overnight fasting was found to be linked to reduced involvement of the bilateral dorsal midline thalamus and the bilateral basal ganglia, suggesting high sensitivity of those regions to minimal changes in BGLs. Our results indicate that overnight fasting leads to physiologically low levels of glucose, impacting brain activation during working memory tasks even when there are no differences in cognitive performance.

Antipsychotic-induced elevation of creatine kinase: a systematic review of the literature and recommendations for the clinical practice.

RATIONALE: The primary antipsychotic-induced creatine kinase elevation (i.e., not due to neuroleptic malignant syndrome, extrapyramidal symptoms, etc.) is a poorly studied condition. OBJECTIVES: The aims of the present study were to provide an overview of published cases with antipsychotic-induced creatine kinase elevation and give recommendations for the clinical practice. METHODS: PubMed and EMBASE were searched for eligible trials, case series, and case reports. We set a threshold at ten times the upper normal limit of the creatine kinase value in order to define an elevation as significant. RESULTS: The prevalence of significant creatine kinase elevation ranged between 2 and 7%. We found a total of 42 eligible cases. Men were overrepresented in our sample (81%). Patients with myoglobinuria were more likely to be symptomatic (Fisher's exact test, p = 0.006), whereas neither myoglobinuria (Mann-Whitney test, p > 0.10) nor symptoms (Mann-Whitney test, p = 0.64) were related to the magnitude of the creatine kinase (CK) elevation. In the majority of the cases, the antipsychotic medication was discontinued (86%). Forced diuresis was given in 36% of the patients. Eighty-three percent of the patients had no further complications. Only one case was found with a de novo acute renal failure. CONCLUSIONS: The discontinuation of the antipsychotic medication was a sufficient measure for the CK elevation to subside in the majority of the cases. Cases with myoglobinuria should eventually be treated more aggressively. Further recommendations for the clinical practice are presented.

Circulating irisin in healthy, young individuals: day-night rhythm, effects of food intake and exercise, and associations with gender, physical activity, diet, and body composition.

CONTEXT: The myokine irisin may increase energy expenditure and affect metabolism. OBJECTIVE: The objective of the study was to elucidate predictors of irisin and study whether circulating irisin may have day-night rhythm in humans. DESIGN: This was an observational, cross-sectional study with an additional 24-hour prospective observational arm (day-night rhythm substudy) and two prospective interventional arms (mixed meal substudy and exercise substudy). SETTING: The study was conducted at the Hellenic Military School of Medicine (Thessaloniki, Greece). PATIENTS AND INTERVENTIONS: One hundred twenty-two healthy, young individuals were subjected to anthropometric and body composition measurements, and their eating and exercise behavior profiles were assessed with validated questionnaires. Subgroups were subjected to day-night rhythm, standardized meal ingestion, and 30-minute aerobic exercise studies. MAIN OUTCOME MEASURES: Circulating irisin levels were measured. RESULTS: Ιrisin levels were lower in males than females (P = .02) after adjustment for lean body mass, which was its major determinant. Irisin levels followed a day-night rhythm (P < .001) with peak at 9:00 pm. Irisin levels were increased at the end of exercise (84.1 ± 10.0 vs 105.8 ± 14.3 ng/mL; P < .001). Irisin levels were not affected by intake of a standardized meal and were not associated with caloric intake or diet quality. CONCLUSIONS: In healthy, young individuals, circulating irisin displays a day-night rhythm, is correlated with lean body mass, and increases acutely after exercise.