Fracture Diodes: Directional Asymmetry of Fracture Toughness.

Toughness describes the ability of a material to resist fracture or crack propagation. It is demonstrated here that fracture toughness of a material can be asymmetric, i.e., the resistance of a medium to a crack propagating from right to left can be significantly different from that to a crack propagating from left to right. Such asymmetry is unknown in natural materials, but we show that it can be built into artificial materials through the proper control of microstructure. This paves the way for control of crack paths and direction, where fracture-when unavoidable-can be guided through predesigned paths to minimize loss of critical components.

Genome wide association study (GWAS) and identification of candidate genes for yield and oil yield related traits in oil palm (Eleaeis guineensis) using SNPs by genotyping-based sequencing.

The genotyping-based sequencing (GBS) method used for GWAS of four yield and seven oil yield related traits on highly diverse African oil palm germplasm. GBS generated 325 million-reads covering 50.78Gb of sequence data, with an average of 3.4 million-reads per sample. Finally, 4031 fully informative SNPs with a range between 157 on chromosome 15 to 455 on chromosome 1 were used for GWAS. Association mapping resulted in identification of 40 highly significant loci, where more genetic loci were found to be associated with oil to bunch (OB), followed by average bunch weight (ABW). The loci, SGI|593,593|linked to QTNOB3 explained high amount of phenotypic variance (25.3%). The nucleotide sequences of linked genetic loci for OB were found to be similar to mitogen activated protein kinase-5 (MAPK-5) protein which is an early flowering protein. The significant loci identified can be used to select desirable palms at early stage through marker assisted selection.

Phenomics, genomics of oil palm (Elaeis guineensis Jacq.): way forward for making sustainable and high yielding quality oil palm.

Oil palm (Elaeis guineensis Jacq.) is a heterogeneous, perennial crop having long breeding cycle with a genome size of 1.8 Gb. The demand for vegetable oil is steadily increasing, and expected that nearly 240-250 million tons of vegetable oil may be required by 2050. Genomics and next generation technologies plays crucial role in achieving the sustainable availability of oil palm with good yield and high quality. A successful breeding programme in oil palm depends on the availability of diverse gene pool, ex-situ conservation and their proper utilization for generating elite planting material. The major breeding methods adopted in oil palm are either modified recurrent selection or the modified reciprocal recurrent selection method. The QTLs of yield and related traits are chiefly located on chromosome 4, 10, 12 and 15 which is discussed in the current review. The probable chromosomal regions influencing the less height increment is observed to be on chromosomes 4, 10, 14 and 15. Advanced genomic approaches together with bioinformatics tools were discussed thoroughly for achieving sustainable oil palm where more efforts are needed. Major emphasis is given on oil palm crop improvement using holistic approaches of various genomic tools. Also a road map given on the milestones in the genomics and way forward for making oil palm to high yielding quality oil palm.

Three-dimensional analysis of the effect of epidermal growth factor on cell-cell adhesion in epithelial cell clusters.

The effect that growth factors such as epidermal growth factor (EGF) have on cell-cell adhesion is of interest in the study of cellular processes such as epithelial-mesenchymal transition. Because cell-cell adhesions cannot be measured directly, we use three-dimensional traction force microscopy to measure the tractions applied by clusters of MCF-10A cells to a compliant substrate beneath them before and after stimulating the cells with EGF. To better interpret the results, a finite element model, which simulates a cluster of individual cells adhered to one another and to the substrate with linear springs, is developed to better understand the mechanical interaction between the cells in the experiments. The experiments and simulations show that the cluster of cells acts collectively as a single unit, indicating that cell-cell adhesion remains strong before and after stimulation with EGF. In addition, the experiments and model emphasize the importance of three-dimensional measurements and analysis in these experiments.

Toughening and asymmetry in peeling of heterogeneous adhesives.

The effective adhesive properties of heterogeneous thin films are characterized through a combined experimental and theoretical investigation. By bridging scales, we show how variations of elastic or adhesive properties at the microscale can significantly affect the effective peeling behavior of the adhesive at the macroscale. Our study reveals three elementary mechanisms in heterogeneous systems involving front propagation: (i) patterning the elastic bending stiffness of the film produces fluctuations of the driving force resulting in dramatically enhanced resistance to peeling; (ii) optimized arrangements of pinning sites with large adhesion energy are shown to control the effective system resistance, allowing the design of highly anisotropic and asymmetric adhesives; (iii) heterogeneities of both types result in front motion instabilities producing sudden energy releases that increase the overall adhesion energy. These findings open potentially new avenues for the design of thin films with improved adhesion properties, and motivate new investigations of other phenomena involving front propagation.

Efficacy and safety comparison of combination of 0.04% tretinoin microspheres plus 1% clindamycin versus their monotherapy in patients with acne vulgaris: a phase 3, randomized, double-blind study.

BACKGROUND AND OBJECTIVES: There is an unmet need for topical treatments with good tolerability in management of acne vulgaris. The present study aimed to evaluate efficacy and safety of a novel tretinoin (microsphere, 0.04%) formulation in combination with clindamycin (1%) gel for treatment of acne vulgaris. MATERIALS AND METHODS: This phase 3 randomized, double-blind study included patients with moderate-to-severe acne. Patients were treated with tretinoin (microsphere, 0.04%) + clindamycin (1%) or one of the monotherapies (tretinoin, 0.025%; clindamycin, 1%). Key endpoints included percent change in lesion counts, and improvement in Investigator's Static Global Assessment (ISGA) score. RESULTS: 750 patients were randomized (combination, n = 300; tretinoin and clindamycin, each n = 150). At week 12, reductions in inflammatory (77%), non-inflammatory (71%) and total lesions (73%) were significantly greater with combination treatment versus either monotherapy (p < .03). Proportion of patients rated 'clear' or 'almost clear' with ≥2-grade ISGA improvement was higher with combination (46%) versus monotherapies (p < .02). Adverse events occurred in 20 patients, most were mild-moderate; no deaths or serious adverse events were reported. The discontinuation rates due to adverse events with combination therapy were low (≤1%). CONCLUSION: The once-daily, microsphere-based formulation was generally tolerable with a positive impact on therapeutic outcomes and patients' compliance. CLINICALTRIAL REGISTRATION NO.: CTRI/2014/08/004830.

Genome-wide association study for leaf area, rachis length and total dry weight in oil palm (Eleaeisguineensis) using genotyping by sequencing.

The marker-trait association for complex traits using genotyping by sequencing (GBS) method is being widely spread in plants. The study aimed to identify significant single nucleotide polymorphism (SNP) associations for rachis length (RL), leaf area (LA) and total dry weight (TrDW) in oil palm among diverse African germplasm. The Illumina NextSeq platform has been used for SNP genotyping and retained 4031 fully informative SNPs after applying the filter criterion. These 4031 SNPs were used for genome wide association study for the above three traits. The LD decay rates of the African germplasm using GBS data of SNP is observed to be 25 Kb at 0.45 of average pair wise correlation coefficient (r2). Association mapping led to the identification of seven significant associations for three traits using MLM approach at a P value of ≤ 0.001. Three associations were identified for total dry weight, two each for leaf area index and rachis length. The qtlLA1 was found to be highly significant at a P value of 7.39E-05 (18.4% phenotypic variance) which is located on chromosome 4. Two QTLs (qtlLA2 and qtlRL1) were located on chromosome 1, which explained 11.9% and 12.4% of phenotypic variance respectively. Three QTLs for total dry weight were located on chromosome 2, 14 and 16, all-together explained 40% phenotypic variance. The results showed that the SNP-trait associations identified in the present study could be used in selection of elite oil palm germplasm for higher yields.

Expert consensus on the management of Androgenetic Alopecia in India.

Androgenetic alopecia (AGA), also known as androgenic or pattern alopecia, is a frequently reported disorder that affects both the sexes, with a higher incidence generally reported in men. AGA has immense psychological effects on the patient, irrespective of the age or stage of baldness. This consensus document has been developed taking into account the opinions of leading experts in the field of dermatology. The objective of this article is to provide the dermatologists with an evidence-based platform for choosing efficacious and safe therapy for patients with AGA. This review articulately summarizes the key opinions of the experts on all aspects of treatment for the effective management of AGA.

Expert consensus on the management of Telogen Effluvium in India.

Alopecia, a frequently reported problem, severely impacts the quality of life of patients and is often associated with loss of confidence and low self-esteem. Several conditions such as telogen effluvium (TE), anagen effluvium, diffuse type of alopecia areata, female pattern hair loss, hair shaft abnormalities, loose anagen hair syndrome, and congenital atrichia or hypotrichosis are associated with hair loss. The actual prevalence rate of TE is not reported since most cases are subclinical in nature. Further, since women get more distressed by hair fall and promptly seek treatment, they tend to be over-represented. However, both genders can suffer from this condition if triggering factors are present. This consensus paper was developed by taking into account opinions of renowned experts in the field and is hoped to serve as an evidence-based platform for selecting efficacious and safe therapy for patients with TE. This review presents a synopsis of the key opinions of experts on all aspects of treatment and effective management of this condition.

Medicinal Plant Using Ground State Stabilization of Natural Antioxidant Curcumin by Keto-Enol Tautomerisation.

Curcumin is a medicinal agent that exhibits anti-cancer properties and bioactive pigment in Turmeric has a huge therapeutic value. It has a keto-enol moiety that gives rise to many of its chemical properties. A recent study has shown that keto-enol tautomerisation at this moiety is implicated the effect of curcumin. The tautomerisation of curcumin in methanol, acetone and acetonitrile are used in nuclear magnetic resonance (1H, 13C) spectroscopy. It was characterized using UV, IR and Raman spectral values. The molecular electrostatic potential surface of the Curcumin has been visualized in electropositive potential in the region of the CH3+ group and most electronegative potential in the two oxygen atom has very strong binding group. In the following, the modality of structural and thermo dynamical parameters, electrophilicity (ω), chemical potential (µ), chemical hardness (η) and electronic charge transfer confirms the local reactivity. The rate constant of tautomerisation of curcumin shows strong temperature dependence. Molecular electrostatic potential and Temperature dependence of various thermodynamic properties like [Formula: see text] is increase with increase in temperature for monomer and dimer of various electrical fields.

Development, identification and validation of CAPS marker for SHELL trait which governs dura, pisifera and tenera fruit forms in oil palm (Elaeis guineensis Jacq.).

The oil palm fruit forms (dura, pisifera and tenera) governed by the shell thickness gene (Sh) plays a major role in identification of fruit type and also influences palm oil yield. Identification of desired fruit type is a major asset to the breeders and oil palm workers for applications in breeding, seed certification and to reduce time, space and money spent on identification of fruit form. In the present study, we developed Sh gene specific primer pairs and bulk segregant analysis was done using 300 genomic and 8 genic SSR markers. We identified one cleaved amplified polymorphic site (CAPS) marker for differentiation of oil palm fruit type which produced two alleles (280 and 250bp) in dura genotypes, three alleles in tenera genotypes (550, 280, and 250bp) and one allele in pisifera genotypes (550bp). The shell allele sequencing results showed that two SNPs were present, of which SNP2 contributed for variation of fruit forms. The nucleotide 'A' was present in only dura genotypes, where as 'T' was present only in pisifera genotypes, which in turn led to the change of amino acid lysine to aspargine. The identified CAPS marker was validated on 300 dura, 25 pisifera and 80 tenera genotypes, 80 dura/ pisifera cross progenies and 60 lines of tenera/ tenera cross progeny. Association mapping of marker data with phenotypic data of eight oil yield related traits resulted in identification of seven significant QTLs by GLM approach, four by MLM approach at a significant threshold (P) level of 0.001. Significant QTLs were identified for fruit to bunch and oil to bunch traits, which explained R2 of 12.9% and 11.5% respectively. The CAPS marker used in the present study facilitate selection and timely distribution of desirable high yielding tenera sprouts to the farmers instead of waiting for 4-5 years. This saves a lot of land, time and money which will be a major breakthrough to the oil palm community.

Medical Management of Melasma: A Review with Consensus Recommendations by Indian Pigmentary Expert Group.

Melasma is one of the most common hyperpigmentary disorders found mainly in women and dark-skinned patients. Sunlight, hormones, pregnancy, and genetics remain the most implicated in the causation of melasma. Although rather recalcitrant to treatment, topical agents such as hydroquinone, modified Kligman's Regime, azelaic acid, kojic acid, Vitamin C, and arbutin still remain the mainstay of therapy with sun protection being a cornerstone of therapy. There are several new botanical and non botanical agents and upcoming oral therapies for the future. There is a lack of therapeutic guidelines, more so in the Indian setup. The article discusses available evidence and brings forward a suggested treatment algorithm by experts from Pigmentary Disorders Society (PDS) in a collaborative discussion called South Asian Pigmentary Forum (SPF).

Chemical Peels in Melasma: A Review with Consensus Recommendations by Indian Pigmentary Expert Group.

Melasma is a notorious dermatosis, often resistant to treatment. Chemical peeling constitutes an acceptable option of management of melasma (of any type and duration). In this article, as a group of experts from Pigmentary Disorders Society (PDS) in collaboration with South Asian Pigmentary Forum (SPF), we have tried to elaborate the various chemical peeling agents for the treatment of melasma. Besides, we have reviewed the indications, mechanism of action, rationality and the detailed procedure of peeling. The evidence in favor of various peeling agents have been summarized as well.

Lasers in Melasma: A Review with Consensus Recommendations by Indian Pigmentary Expert Group.

Lasers have come up as the newest therapeutic modality in dermatological conditions including melasma. In this article, as a group of experts from Pigmentary Disorders Society in collaboration with South Asian Pigmentary Disorders Forum (SPF), we have tried to discuss the lasers which have been used in melasma and formulate simple consensus guidelines. Following thorough literature search, we have summarised the rationale of using the lasers and the supporting evidences have also been provided. It is clear that laser cannot be the first line treatment for melasma. However, it can be used as an adjuvant therapy in resistant cases, provided the selection of patient and counselling has been done properly.

Abnormalities of brain structure and density in schizophrenia.

Quantitative and qualitative measures of brain morphology were derived through CT scans using computer-assisted methodology in patients with schizophrenia or schizo-affective psychosis and headache controls. Schizophrenics had significantly higher density of white matter, together with greater right vs. left asymmetry in density of white matter than controls. Schizophrenics tended to have larger widths of cortical sulci than headache patients. In our sample of schizophrenics, however, no significant differences were found on measures of lateral ventricle (LV) width, LV area, VBR, or other measures of ventricular size compared to headache controls. There were no differences between CT scan measures taken in patients with schizophrenia vs. schizo-affective psychosis.

Comparative efficacy of red cell and plasma haloperidol as predictors of clinical response in schizophrenia.

The relative utility of steady-state (SS), plasma (Pl), and red blood cell (RBC) haloperidol levels for predicting clinical response was evaluated in a fixed-dose study in schizophrenic inpatients. There were significant curvilinear relationships between the decrease in BPRS Psychosis Factor Scores by day 24 of haloperidol treatment and both Pl (R2 = 0.34) and RBC (R2 = 0.38) haloperidol levels. Although SS RBC haloperidol levels consistently showed a slightly stronger relationship to clinical response than Pl levels in several comparisons, the differences in R2s between Pl and RBC haloperidol were not statistically significant. Ninety percent confidence intervals for the blood level ranges associated with optimal clinical response in our sample of patients were: 6.5-16.5 ng/ml Pl haloperidol and 2.2-6.8 ng/ml RBC haloperidol.

Lateral ventricular enlargement and clinical response in schizophrenia.

The relationship between enlargement of the lateral ventricles in the brains of schizophrenic patients and clinical response to neuroleptic treatment, as assessed by the ventricle-brain ratio (VBR) and psychopathology scores, was studied in a sample of 39 patients with schizophrenia or schizoaffective psychosis during a drug-free washout and after 3 1/2 weeks of treatment with either haloperidol or thioridazine. There was a weak, but statistically significant positive relationship between VBR and improvement on BPRS Psychosis factor scores after 3 1/2 weeks of treatment, and a negative correlation between VBR and baseline (washout) scores on the BPRS Anergia factor. Patients with enlarged VBRs, as defined by two criteria, also tended to show a better response to neuroleptics than patients below these criterion values.

Nuclear magnetic resonance in schizophrenia: a preliminary study.

Nuclear magnetic resonance (NMR) scans were performed in nine patients with schizophrenia and five control subjects. NMR scans allowed multiple-plane views of the brains of schizophrenic patients and demonstrated much greater detail of morphological structure than computed tomographic (CT) scans. This small sample of subjects, however, showed no significant differences in several quantitative measurements between schizophrenic patients and control subjects. Problems in the interpretation of image intensity measures of NMR scans are discussed.

Prolactin response to single and multiple doses of haloperidol in schizophrenic patients.

Serum prolactin and blood levels of haloperidol were assessed in schizophrenic patients after single acute oral doses of haloperidol and during fixed dose treatment with this medication. Although significant intrapatient correlations between prolactin responses to different doses of haloperidol were found, no statistically significant interpatient relationship between haloperidol dose and prolactin response emerged. There were statistically significant relationships between steady-state plasma and red cell haloperidol levels (measured by radioreceptor or gas liquid chromatographic techniques) and serum prolactin response, but not between blood levels after the acute haloperidol dose and prolactin response.

Plasma and red cell levels of thioridazine and clinical response in schizophrenia.

The relationship of plasma and red blood cell (RBC) levels of thioridazine to clinical response in schizophrenia was evaluated in a fixed-dose study. Steady-state plasma and RBC levels of thioridazine, mesoridazine, and sum of thioridazine and mesoridazine, determined by gas-liquid chromatography, were not significantly correlated with clinical response as measured by improvement on the Brief Psychiatric Rating Scale. RBC thioridazine levels were not substantially more strongly correlated with clinical response than plasma levels.