The crystal structure of dGTPase reveals the molecular basis of dGTP selectivity.

Deoxynucleotide triphosphohydrolases (dNTPases) play a critical role in cellular survival and DNA replication through the proper maintenance of cellular dNTP pools. While the vast majority of these enzymes display broad activity toward canonical dNTPs, such as the dNTPase SAMHD1 that blocks reverse transcription of retroviruses in macrophages by maintaining dNTP pools at low levels, Escherichia coli (Ec)-dGTPase is the only known enzyme that specifically hydrolyzes dGTP. However, the mechanism behind dGTP selectivity is unclear. Here we present the free-, ligand (dGTP)- and inhibitor (GTP)-bound structures of hexameric Ec-dGTPase, including an X-ray free-electron laser structure of the free Ec-dGTPase enzyme to 3.2 Å. To obtain this structure, we developed a method that applied UV-fluorescence microscopy, video analysis, and highly automated goniometer-based instrumentation to map and rapidly position individual crystals randomly located on fixed target holders, resulting in the highest indexing rates observed for a serial femtosecond crystallography experiment. Our structures show a highly dynamic active site where conformational changes are coupled to substrate (dGTP), but not inhibitor binding, since GTP locks dGTPase in its apo- form. Moreover, despite no sequence homology, Ec-dGTPase and SAMHD1 share similar active-site and HD motif architectures; however, Ec-dGTPase residues at the end of the substrate-binding pocket mimic Watson-Crick interactions providing guanine base specificity, while a 7-Å cleft separates SAMHD1 residues from dNTP bases, abolishing nucleotide-type discrimination. Furthermore, the structures shed light on the mechanism by which long distance binding (25 Å) of single-stranded DNA in an allosteric site primes the active site by conformationally "opening" a tyrosine gate allowing enhanced substrate binding.

Design and Implementation of Low Power High-Efficient Transceiver for Body Channel Communications.

Body channel communications (BCC) have been researched while an allowing technology to improve necessities for the low power and high reconfiguration power in wireless telemetry systems used at wireless communication purpose. Conventional features on BCC are concentrated mostly on modeling of channels by using of an efficient measurement technique, wireless transceiver design and then by means of a transmission technique. Particularly, the wireless digital transmitting, developed as a personalized method intended for the body channel, offers wanted to develop flexible and low power BCC systems. With the developing level of wearable communication protocol and applications, there may be an increasingly reliable on an adaptable BCC transmitter that helps both data reconfigure power and power reduction condition. In this paper, an extremely reconfigurable Hamming Encoding Digital Transmitter (HEDT) which works with both reconfigurable data and power reduction condition that supports from two innovative operation conditions is suggested. In a HEDT device, the overall data rate is controlled by the level of Hamming codes designed to make use of in the perfect BCC band of 20-100 MHz. The proposed Hamming Encoded Transmission method achieves seven times improved data rate when compared with conventional BCC processors. The next unique implementation technique is based on the usage of Frequency Shift Keying (FSK) of a Hamming encoded HEDT approach. This approach permits the BCC transceiver to use the perfect channel with bandwidth among 40-100 MHz. Thereby half the clock rate reduces 40% of overall power utilization. The HEDT system is completely designed in a 65 nm CMOS procedure. It uses a primary area of 0.14 × 0.2 mm. When functioning below a data-rate of 60 Mb/s (low power) condition, the BCC transmitter utilizes only 1.00 mW.

Efficient Image De-Noising Technique Based on Modified Cuckoo Search Algorithm.

The image restoration has emerged as a very vital investigation technique in the domain of the image processing. The underlying motive behind the image restoration is devoted to the augmentation of the perceived visual impact of image so as to make it almost identical to the original image. A host of exploration approaches are now in vogues which are intended to steer clear of the noise, thereby regaining the images with original quality. In our earlier research, two distinct noise elimination methods like the (OGHP) and SURE shrinkage were effectively employed for the purpose of denoising, though the relative PSNR and SSIM efficiencies did not come up to the desired level. In the innovative approach envisaged in the document, at the outset, the noise is included by means of two processes like the salt and pepper and impulse noise. Subsequently, the pre-processing methods are performed with the able assistance of two novel filters such as the adaptive median filter and adaptive fuzzy switching. Thereafter, the preprocessed image is furnished to the succeeding function of noise elimination like the (OGHP) and SURE shrinkage. In the course of the OGHP noise elimination technique, the GHP constraints are optimized by employing the Cuckoo Search Algorithm. Thereafter, the noise-eliminated image is effectively estimated with the help of the Discrete Wavelet Transform (DWT). The consequential noiseless images are subjected to the image restoration procedure by efficiently employing the AGA approach. The cheering performance outcomes chant the success stories of the novel image restoration method, highlighting its superlative efficiency. Moreover, the efficacy of the innovative approach is assessed by means of a set of noise-polluted images and contrasted with the modern noiseless image restoration technique.

Obesity paradox in group 1 pulmonary hypertension: analysis of the NIH-Pulmonary Hypertension registry.

BACKGROUND: The 'obesity paradox' refers to the fact that obese patients have better outcomes than normal weight patients. This has been observed in multiple cardiovascular conditions, but evidence for obesity paradox in pulmonary hypertension (PH) remains sparse. METHODS: We categorized 267 patients from the National Institute of Health-PH registry into five groups based on body mass index (BMI): underweight, normal weight, overweight, obese and morbidly obese. Mortality was compared in BMI groups using the χ2 statistic. Five-year probability of death using the PH connection (PHC) risk equation was calculated, and the model was compared with BMI groups using Cox proportional hazards regression and Kaplan-Meier (KM) survival curves. RESULTS: Patients had a median age of 39 years (interquartile range 30-50 years), a median BMI of 23.4 kg m-2 (21.0-26.8 kg m-2) and an overall mortality at 5 years of 50.2%. We found a U-shaped relationship between survival and 1-year mortality with the best 1-year survival in overweight patients. KM curves showed the best survival in the overweight, followed by obese and morbidly obese patients, and the worst survival in normal weight and underweight patients (log-rank P=0.0008). In a Cox proportional hazards analysis, increasing BMI was a highly significant predictor of improved survival even after adjustment for the PHC risk equation with a hazard ratio for death of 0.921 per kg m-2 (95% confidence interval: 0.886-0.954) (P<0.0001). CONCLUSION: We observed that the best survival was in the overweight patients, making this more of an 'overweight paradox' than an 'obesity paradox'. This has implications for risk stratification and prognosis in group 1 PH patients.

Mechanical stress-induced switching kinetics of ferroelectric thin films at the nanoscale.

We investigate ferroelectric domain structure and piezoelectric response under variable mechanical compressive stress in Pb(Zr0.2TiO0.8)O3 (PZT) thin films using high-resolution piezoresponse force microscopy (PFM) and an in situ sample bending stage. Measurements reveal a drastic change in the ferroelectric domain structure which is presented along with details of the mediating switching process involving domain wall motion, nucleation, and domain wall roughening under an applied external mechanical stimulus. Furthermore, local PFM hysteresis loops reveal significant changes in the observed coercive biases under applied stress. The PFM hysteresis loops become strongly imprinted under increasing applied compressive stress.

Use of transmission electron microscopy to identify nanocrystals of challenging protein targets.

The current practice for identifying crystal hits for X-ray crystallography relies on optical microscopy techniques that are limited to detecting crystals no smaller than 5 µm. Because of these limitations, nanometer-sized protein crystals cannot be distinguished from common amorphous precipitates, and therefore go unnoticed during screening. These crystals would be ideal candidates for further optimization or for femtosecond X-ray protein nanocrystallography. The latter technique offers the possibility to solve high-resolution structures using submicron crystals. Transmission electron microscopy (TEM) was used to visualize nanocrystals (NCs) found in crystallization drops that would classically not be considered as "hits." We found that protein NCs were readily detected in all samples tested, including multiprotein complexes and membrane proteins. NC quality was evaluated by TEM visualization of lattices, and diffraction quality was validated by experiments in an X-ray free electron laser.

A systematic review of tobacco use among adolescents with physical disabilities.

OBJECTIVE: To provide a systematic review of tobacco use among adolescents with physical disabilities. STUDY DESIGN: A systematic review. METHODS: A search was performed of English articles published prior to December 2014 in the PubMed database for studies examining smoking rates among adolescents with and without physical disabilities. Ten studies were retrieved (all cross-sectional surveys) of which six compared adolescent populations from nationally representative samples and four examined those based on convenience sampling. Pooled analyses of smoking rates by disability status were performed. RESULTS: In studies from nationally representative samples (n = 6 studies), adolescents with physical disabilities were significantly more likely to use tobacco as compared to adolescents without (pooled analyses = 29.7% vs 23.3%). However, in studies from non-representative samples, adolescents with physical disabilities were less likely to use tobacco as compared to adolescents without (pooled analyses = 22.7% vs 39.1%). CONCLUSIONS: Adolescents with physical disabilities may have an increased risk of tobacco use relative to those without disabilities. Tailored tobacco use prevention and cessation strategies may be appropriate for this high-risk population. Future longitudinal studies which determine factors associated with tobacco use among adolescents with different disabilities should be considered to reduce the disproportionate tobacco use in this population.

Increasing prevalence and incidence rates of multiple sclerosis in Kuwait.

BACKGROUND: Kuwait was considered as low to intermediate risk area for MS. OBJECTIVES: To determine the prevalence and incidence rates of MS among Kuwaiti nationals based on 2011 population census. METHODS: This cross-sectional study was conducted between October 2010 and April 2013 using the newly developed national MS registry in Kuwait. Patients with a diagnosis of MS according to 2010 revised McDonald criteria were identified. The crude, age- and sex-specific prevalence and incidence rates among Kuwaiti patients were calculated. RESULTS: 1176 MS patients were identified of which 927 (78.8%) were Kuwaitis and 249 (21.2%) were expatriates. Among Kuwaiti patients, female to male ratio was 1.8:1 with a mean age of 35.40 ± 10.99 years. The prevalence rate of MS was 85.05 per 100,000 persons (95% CI: 82.80 - 87.04). There was a peak in prevalence among patients aged 30-39 years. The incidence of MS was 6.88 per 100,000 persons (95% CI 5.52-8.55). Between 2003 and 2011, the incidence increased 3.22 and 2.54 times in women and men respectively. CONCLUSION: Kuwait is considered a high-risk area for MS. The significant increase in prevalence and incidence rates may represent a true increase despite the improvement in case ascertainment and case definition.

pKa Modulation in rhodamine based probes for colorimetric detection of picric acid.

Tuning the pKa in acid sensitive rhodamine spirolactam derivatives as a function of the solvent medium resulted in the selective detection of picric acid from its lower nitro phenolic analogues and a few other carboxylic acids.

Self-similar nested flux closure structures in a tetragonal ferroelectric.

In specific solid-state materials, under the right conditions, collections of magnetic dipoles are known to spontaneously form into a variety of rather complex geometrical patterns, exemplified by vortex and skyrmion structures. While theoretically, similar patterns should be expected to form from electrical dipoles, they have not been clearly observed to date: the need for continued experimental exploration is therefore clear. In this Letter we report the discovery of a rather complex domain arrangement that has spontaneously formed along the edges of a thin single crystal ferroelectric sheet, due to surface-related depolarizing fields. Polarization patterns are such that nanoscale "flux-closure" loops are nested within a larger mesoscale flux closure object. Despite the orders of magnitude differences in size, the geometric forms of the dual-scale flux closure entities are rather similar.

Diethylbenzene and ethyltoluene adsorption studies on novel beta antimonide phosphorus nanosheets-a first-principle study.

CONTEXT: In the present work, we examined the sensing behavior of monolayer beta antimonide phosphorus (ß-SbP) sheets towards toxic volatile organic compounds (VOCs) namely, 1,2-diethylbenzene and 2-ethyltoluene using density functional theory (DFT) method. At first, using cohesive energy structural stability of the monolayer ß-SbP is confirmed. The calculated energy band gap value of monolayer ß-SbP is 2.168 eV, which is a semiconductor. Furthermore, the adsorption properties of 1,2-diethylbenzene and 2-ethyltoluene on ß-SbP are studied through key factors, such as adsorption energy, Mulliken charge transfer, and relative band gap variation. The adsorption energy clearly shows (- 0.335 to - 0.903 eV) that both 1,2-diethylbenzene and 2-ethyltoluene are physisorbed on ß-SbP monolayer. Besides, Mulliken charge transfer falls in the range of - 0.465 to 0.933 e; this information clearly shows that the ß-SbP monolayer is a potential candidate for sensing 1,2-diethylbenzene and 2-ethyltoluene molecules. METHODS: The structural firmness including electronic and adsorption properties of 1,2-diethylbenzene and 2-ethyltoluene on ß-SbP monolayer are investigated with the support of the DFT method. Particularly, the hybrid generalized gradient approximation (hybrid GGA) along with Beck's three-parameter + Lee-Yang-Parr (B3LYP) exchange-correlation functional is utilized for relaxing the ß-SbP monolayer. In the present work, all calculations are performed using the Quantum Atomistic Tool Kit (ATK) simulation package. In the present work, we utilized ß-SbP monolayer as a chief sensing element to detect 1,2-diethylbenzene and 2-ethyltoluene to safeguard humans from toxic environments.

Novel chair graphene nanotubes as adsorbing medium for alanine and asparagine amino acids - A DFT outlook.

Amino acids are required to make protein. The deficiency of amino acids leads to a lack of sleep and mood. Among various amino acids, we conducted the adsorption studies of alanine and asparagine amino acids on a novel one-dimensional material, chair graphene nanotube. The stability of the chair graphene nanotube is ensured with the negative formation energy, which is -6.490 eV/atom. The energy band gap of bare chair graphene nanotube is 1.022 eV, which possesses a semiconductor nature. The stable chair graphene nanotube is used as adsorbing material for alanine and asparagine amino acids. Besides, alanine and asparagine are physisorbed on chair graphene nanotubes that are confirmed by the range of adsorption energy from -0.107 eV to -0.718 eV. Upon adsorption of amino acids, the charge transfer outcome shows that chair graphene nanotubes behave as donors of electrons to alanine and asparagine. Further, the changes in the band gap of the chair graphene nanotube are noticed from the results of band structure and PDOS spectrum. The changes in the electron density also reveal the changes in the electronic properties of the chair graphene nanotube owing to alanine and asparagine sorption. The proposed report portrays the adsorption attributes of alanine and asparagine amino acids on 1D chair graphene nanotubes.

Comparative Evaluation of Volume and Homogeneity of Obturation with Four Different Obturation Systems Using Micro-Computed Tomography: An In vitro Study.

Aim: To evaluate and compare volume and homogeneity of the three different root canal obturation systems. Materials and Methods: Single-rooted premolar (n = 24) teeth samples were selected, and crowns were removed for standardization. Four groups are divided randomly as (n = 6), namely: For group I (single-cone gutta-percha obturation), group II (Beefill 2 in 1 obturation), group III (GuttaCore obturation), group IV (GuttaFlow bioseal obturation) and the root canal were subjected to prepare till X3 (protaper next) and subjected to micro-CT imaging. After completion of obturation, the image was taken by using micro-CT imaging. This is to evaluate the volume of filled obturation material in the canal space and the voided area sections, viz. the apical, middle, coronal, and third sections. Results: Group III (GuttaCore obturation) showed the least significant mean of the difference in relation to the volume of the canal obturation (81.148). The least mean significant difference in area of voids in the canal region for apical (0.00133), middle (0.00233), and coronal thirds (0.00533). The most statistically significant difference is in the apical and middle thirds root canal space. Conclusion: All the experimental groups showed significant differences in volume and voids in the obturation at three different levels, and the GuttaCore obturation systems occupied more of the volume with less voids in the prepared root canal space.

The role of platelet-rich plasma in androgenetic alopecia: A systematic review.

BACKGROUND: Androgenetic alopecia (AGA), also referred to as male or female pattern hair loss, is the commonest cause of chronic hair loss and affects up to 80% of men by the age of 70. Despite a high prevalence, there are few approved therapies, which show minimal efficacy. OBJECTIVES: This systematic review aims to evaluate the efficacy of platelet-rich plasma (PrP) in the treatment of AGA in male patients. METHODS: MEDLINE, EMBASE, Cochrane (CENTRAL), CINAHL, clinicaltrials.gov, Google Scholar and the Science Citation Index database were searched to identify eligible studies. All randomized controlled trials (RCTs) and prospective cohort studies related to PrP use in AGA were included. Primary outcomes included changes in hair density and hair count. Methodological quality was assessed using bias assessment tools. RESULTS: Eight RCTs and one cohort study were included in the review with a total of 291 participants. Six studies reported a statistically significant increase in hair density in the PrP group versus the control. Five studies reported a statistically significant increase in hair count with PrP. Seven studies showed moderate risk and two showed low risk of bias. CONCLUSION: In a methodologically robust review on the effectiveness of PrP on male AGA, PrP demonstrated some potential to be used therapeutically. However, the low quality of evidence, moderate risk of bias, and high heterogeneity of included studies limit inferences and call for more robust designs to investigate this further.

Domain wall geometry controls conduction in ferroelectrics.

A new paradigm of domain wall nanoelectronics has emerged recently, in which the domain wall in a ferroic is itself an active device element. The ability to spatially modulate the ferroic order parameter within a single domain wall allows the physical properties to be tailored at will and hence opens vastly unexplored device possibilities. Here, we demonstrate via ambient and ultrahigh-vacuum (UHV) scanning probe microscopy (SPM) measurements in bismuth ferrite that the conductivity of the domain walls can be modulated by up to 500% in the spatial dimension as a function of domain wall curvature. Landau-Ginzburg-Devonshire calculations reveal the conduction is a result of carriers or vacancies migrating to neutralize the charge at the formed interface. Phase-field modeling indicates that anisotropic potential distributions can occur even for initially uncharged walls, from polarization dynamics mediated by elastic effects. These results are the first proof of concept for modulation of charge as a function of domain wall geometry by a proximal probe, thereby expanding potential applications for oxide ferroics in future nanoscale electronics.

Adsorption studies of camphene and eucalyptol molecules on orthorhombic germanane nanosheet - A first-principles investigation.

In the present work, we deployed a novel orthorhombic germanane nanosheet (ortho-GeNS) as a sensing material to detect camphene and eucalyptol molecules, the indoor air pollutants in the ambient environment. In the beginning, the structural and dynamical permanency of ortho-GeNS is confirmed with cohesive energy (-4.164eV/atom) and phonon-band maps. Successively, the electronic features of ortho-GeNS are conferred using band structure along with the projected density of states maps. The energy gap of ortho-GeNS at the hybrid GGA/B3LYP level of theory is computed to be 3.948 eV. Mainly, the adsorption properties of terpinene molecules, namely camphene and eucalyptol on ortho-GeNS are investigated via ascertaining adsorption energy, Mulliken population analysis, and relative band gap variations. Besides, the scope of adsorption energy values (-0.405eVto-0.669eV) exemplifies that the target molecules are physisorbed on ortho-GeNS. Overall results suggested that the ortho-GeNS can be deployed as a worthy chemiresistive sensor to sense indoor air pollutants for monitoring indoor air quality.

N-Nitrosamine sensing properties of novel penta-silicane nanosheets-a first-principles outlook.

CONTEXT: N-Nitrosamine is one of the highly toxic carcinogenic compounds that are found almost in the entire environment. In the present work, novel penta-silicene (penta-Si) and penta-silicane (penta-HSi) are utilised to sense the N-nitrosamine in the air environment. Initially, structural firmness of penta-Si and penta-HSi is confirmed using cohesive energy. Subsequently, the electronic properties of penta-Si and penta-HSi are discussed with the aid of electronic band structure and projected density of states (PDOS) maps. The calculated band gap of penta-Si and penta-HSi is 0.251 eV and 3.117 eV, correspondingly. Mainly, the adsorption property of N-nitrosamine on the penta-Si and penta-HSi is studied based on adsorption energy, Mulliken population analysis along with relative energy gap changes. The computed adsorption energy range is in physisorption (- 0.101 to - 0.619 eV), which recommends that the proposed penta-Si and penta-HSi can be employed as a promising sensor to detect the N-nitrosamine in the air environment. METHODS: The structural, electronic and adsorption behaviour of N-nitrosamine on penta-Si and penta-HSi are studied based on the density functional theory (DFT) approach. The hybrid generalized gradient approximation (GGA) with Becke's three-parameter (B3) + Lee-Yang-Parr (LYP) exchange correlation functional is used to optimise the base material. All calculations in the present work are carried out in Quantum-ATK-Atomistic Simulation Software.

Interaction studies of propylene and butadiene on tricycle graphane nanosheet - A DFT outlook.

In this research work, we employed a tricycle graphane nanosheet as a chemical sensor to monitor the toxic hydrocarbon molecules, namely propylene, and 1,3-butadiene, which are emitted from automobile industries. At first, the structural stability and dynamical permanency of tricycle graphane is ascertained based on cohesive energy and phonon-band-spectrum. Sequentially, the electronic properties of tricycle graphane are conferred with the results of the projected density of states spectrum and band structure. The computed band gap of tricycle graphane is 5.53 eV. Chiefly, the adsorption behaviour of target propylene and 1, 3-butadiene on tricycle graphane is explored by determining adsorption energy, relative band gap variation, and Mulliken population analysis. Furthermore, the range of adsorption energy magnitudes (-0.16 eV to -1.03 eV) demonstrates that the target hydrocarbon molecules are physically adsorbed on tricycle graphane material. The overall outcome endorses that the tricycle graphane can be utilised as a prominent sensor to sense the hydrocarbon molecules released from automobiles and monitor air pollutants.

Recent progress on the synthesis, properties and applications of antimonene - A mini-review.

The recent advancement in group VA monolayer and few-layer materials leads to fascinating applications. In this mini-review, we present the state-of-the-art in the synthesis of antimonene, its properties and various applications. Besides, the electronic properties of antimonene depend on its allotropes. Furthermore, we studied the electronic properties of δ, ε, and twisted-θ antimonene nanosheets, nanoribbons, and nanoring, and the results are reported. Moreover, the structural stability and electronic properties of antimonene is influenced by its allotrope and nanostructure. The report will give insights into the synthesis, properties, applications, and future outlook of antimonene.

Interaction networks of lithium and valproate molecular targets reveal a striking enrichment of apoptosis functional clusters and neurotrophin signaling.

The overall neurobiological mechanisms by which lithium and valproate stabilize mood in bipolar disorder patients have yet to be fully defined. The therapeutic efficacy and dissimilar chemical structures of these medications suggest that they perturb both shared and disparate cellular processes. To investigate key pathways and functional clusters involved in the global action of lithium and valproate, we generated interaction networks formed by well-supported drug targets. Striking functional similarities emerged. Intersecting nodes in lithium and valproate networks highlighted a strong enrichment of apoptosis clusters and neurotrophin signaling. Other enriched pathways included MAPK, ErbB, insulin, VEGF, Wnt and long-term potentiation indicating a widespread effect of both drugs on diverse signaling systems. MAPK1/3 and AKT1/2 were the most preponderant nodes across pathways suggesting a central role in mediating pathway interactions. The convergence of biological responses unveils a functional signature for lithium and valproate that could be key modulators of their therapeutic efficacy.