Dependence of Self-Assembled Peptide Hydrogel Network Structure on Local Fibril Nanostructure

Physically cross-linked, fibrillar hydrogel networks are formed by the self-assembly of β-hairpin peptide molecules with varying degrees of strand asymmetry. The peptide registry in the self-assembled state can be used as a design element to generate fibrils with twisting, nontwisting, or laminated morphology. The mass density of the networks varies significantly, and can be directly related to the local fibrillar morphology as evidenced by small angle neutron scattering (SANS) and in situ substantiation using cryogenic transmission electron microscopy (cryo-TEM) under identical concentrations and conditions. Similarly, the density of the network is dependent on changes in the peptide concentration. Bulk rheological properties of the hydrogels can be correlated to the fibrillar nanostructure, with the stiffer, laminated fibrils forming networks with a higher G′ as compared to the flexible, singular fibrillar networks

A Note on Fermion and Gauge Couplings in Field Theory Models for Tachyon Condensation

We study soliton solutions in supersymmetric scalar field theory with a class of potentials. We study both bosonic and fermionic zero-modes around the soliton solution. We study two possible couplings of gauge fields to these models. While the Born-Infeld like coupling has one normalizable mode (the zero mode), the other kind of coupling has no normalizable modes. We show that quantum mechanical problem which determines the spectrum of fluctuation modes of the scalar, fermion and the gauge field is identical. We also show that only the lowest lying mode, i.e., the zero mode, is normalizable and the rest of the spectrum is continuous.Comment: 10 pages, 2 figures, LaTe

Timing and characteristics of cumulative evidence available on novel therapeutic agents receiving Food and Drug Administration accelerated approval

Context: Therapeutic agents treating serious conditions are eligible for Food and Drug Administration (FDA) accelerated approval. The clinical evidence accrued on agents receiving accelerated approval has not been systematically evaluated. Our objective was to assess the timing and characteristics of available studies. Methods: We first identified clinical studies of novel therapeutic agents receiving accelerated approval. We then (1) categorized those studies as randomized or non-randomized; (2) explored whether or not they evaluated the FDA-approved indications; and (3) documented the available treatment comparisons. We also meta-analyzed the difference in start times between randomized studies that (1) did or did not evaluate approved indications and (2) were or were not designed to evaluate the agent’s effectiveness. Findings: In total, 37 novel therapeutic agents received accelerated approval between 2000 and 2013. Our search identified 7,757 studies including 1,258,315 participants. Only one third of identified studies were randomized controlled trials. Of 1,631 randomized trials with advanced recruitment status, 906 were conducted in therapeutic areas for which agents received initial accelerated approval, 202 were in supplemental indications, and 523 were outside approved indications. Only 411/906 (45.4%) trials were designed to test the effectiveness of agents that received accelerated approval (“evaluation” trials); others used these agents as common background treatment in both arms (“background” trials). There was no detectable lag between average start times of trials conducted within and outside initially approved indications. “Evaluation” trials started on average 1.52 years, (95% CI: 0.87 to 2.17) earlier than “background” trials. Conclusions: Cumulative evidence on agents with accelerated approvals has major limitations. Most clinical studies including these agents are small and non-randomized, and about a third are conducted in unapproved areas, typically concurrently with those conducted in approved areas. Most randomized trials including these therapeutic agents are not designed to evaluate directly their clinical benefits but incorporate them as standard treatment

PHARMACEUTICO THERAPEUTICS OF SHADBINDU THAILA - A CASE STUDY ON EFFICACY IN TIMIRA W.S.R. TO MYOPIA

Nasyakarma is one among the Panchakarma procedures in which, the medicated drugs are administered through the nasal route and is indicated specially for the treatment of Urdhwajathrugatharogas i.e., the disorders of head and neck. Prathimarsha nasya is a type of Nasya wherein the medicament is administered in smaller dosage and advisable in all age groups and conditions. Material and methods: Shadbindhu taila containing different Vatahara and Kaphahara drugs processed along with Ajakshira was prepared in the laboratory of Rasashatra and Bhaishajyakalpana of SDM college of Ayurveda, Udupi, as per the classical reference and with all precautions. Single case study was taken up in a patient diagnosed of Timira viz myopia. Results and discussion: Shadbindhu taila is Tikta – katu rasa, Madhuravipaka, having Ushnathikshnaguna. It helps in decreasing the excessive secretions from the mucus membrane of nose, dryness as well as the inflammation of the nose. It is useful in strengthening the functions of eyes, growth of hair, maintaining the integrity of the teeth. A single case study was taken up to access its efficacy in Timira w.s.r. myopia and it is found to have promising results. Conclusion: Shadbindhu taila has shown improvement in the patient when used in the form of Prathimarsha nasya. Further study with larger sample size has to be done and with different stages of myopia can be done for further evaluation

Synthesis and Characterization of Ruthenium (II) Complexes and their Applications to Atom Transfer Radical Addition Reactions

A series of mixed-phosphine ruthenium complexes of the type Cp#Ru(PR3)(PPh3)Cl, ,here Cp# 0 Cp*, Dp, Ind, Cp, Tp; PR3 = PTA or PMe3 have been synthesized by lichan<e reactions ,ith Cp#Ru(PPh3)2Cl, and characterized by multinuclear NMR spectroscopy and X-ray crystallography. We have explored the efficiency of these complexes as catalysts for the atom transfer radical addition (ATRA) of various chloro-substrates (CCl4, CHCl3, p-TsCl, CCl3CO2Et, and CH2ClCO2Et) to styrene in the presence of AIBN as a radical source. For comparison purposes, we also investi<ated the activity of Cp#Ru(PPh3)2Cl and Cp#Ru(PTA)2Cl complexes towards ATRA. In general, these complexes efficiently catalyzed the radical addition reactions affording the 1:1 adduct in almost quantitative yields. Catalyst performance was found to depend mainly on the electron-donatin< ability of the Cp# ancillary li<ands and on the nature of the phosphines. Among the ruthenium (II) complexes studied Cp*Ru(PTA)(PPh3)Cl and Cp*Ru(PMe3)(PPh3)Cl were very active at 60° C with TOFs of 1060 h-1 and 933 h-1 , respectively; Cp*Ru(PPh3)2Cl was the most active for the addition of CCl4 to styrene with a TOF >960 h-1 at room temperature. The reactivity decreased significantly upon substitution of the labile PPh3 with stronger binding phosphines such as PTA or PMe3 (Cp#Ru(PPh3)2Cl F Cp#Ru(PR3)(PPh3)Cl > Cp#Ru(PTA)2Cl)G Based on the Cp# ancillary li<and, the order of reactivity was found to be: Cp*Ru >> DpRu > IndRu > CpRu > TpRu. The activity of Cp*Ru(PTA)(PPh3)Cl, Cp*Ru(PMe3)(PPh3)Cl, and Cp*Ru(PPh3)2Cl was further explored for the addition of CCl4 to more challenging ii olefins. Both terminal and internal olefins were utilized for the addition reactions. All the three complexes exhibited high reactivity towards CCl4 addition to terminal olefins. Total turnovers (TTO) in excess of 80,000 were obtained for the addition of CCl4 to hexene, making the Cp* complexes the most active and robust catalysts for ATRA reported to date. Contrary to this, the internal olefins were less prone to CCl4 addition whatever the catalytic system may be. These results indicate that the rate of the reaction depends not only on the type of catalyst, but also on the nature of substrate employed. The synthesis and characterization of the air-sensitive hydride, IndRu(PTA)(PPh3)H, is also described. The rate of H/D exchange of the hydride complex was found to be very low (t1/2 ~ 5.5 d). We explored the activity of IndRu(PTA)(PPh3)Cl for the selective transfer hydrogenation of ,-unsaturated carbonyl compounds in aqueous-biphasic mediaG Jlectrochemical studies on some of the Cp#Ru(PR3)(PPh3)Cl complexes in dichloromethane are also reported

Insulin Dynamics In African Americans And European Americans: Mechanistic Aspects, And Association With Inflammation

Identification and characterization of ethnic differences in insulin dynamics, insulin sensitivity (SI), and inflammation may shed light on the greater risk for type 2 diabetes in African Americans (AA), relative to European Americans (EA). Ideally, such studies should take into account the potential confounding roles of adiposity, fat distribution, genetic background, and socioeconomic status (SES). The objectives of this study were, 1) to evaluate ethnic differences in insulin dynamics in AA and EA children and adults using robust measures of insulin secretion and clearance; 2) to identify the contributions of genetic admixture and SES to insulin dynamics; 3) to examine ethnic differences in markers of inflammation (CRP, IL6, TNF-α, and TNFRII) in AA and EA adults; and 4) to examine the association of markers of inflammation with SI after adjusting for measures of adiposity and fat distribution. Measures of SI and insulin dynamics were obtained via intravenous glucose tolerance test and mathematical modeling. Body composition was assessed with dual-energy X-ray absorptiometry, and fat distribution with computed tomography scanning. Subjects were genotyped for African and European genetic admixture. In children, African genetic admixture was independently associated with greater first-phase insulin secretion, and tended to be associated with lower insulin extraction. Total body fat masked the effect of genetic admixture on firstphase secretion. Children with lower SES have greater total insulin secretion. In adults, iii AA vs. EA women had greater early-phase β-cell responsivity, compensated by lower total-β-cell responsivity, and similar insulin extraction. AA had lower TNF-α and TNFRII, relative to EA. Significant independent associations of SI with IL6 and TNFRII were present, after adjusting for confounding variables. The greater first phase secretion in AA may serve as a risk factor for development of type 2 diabetes, by facilitating early β-cell exhaustion. While this study highlights the independent association between SI and inflammation, it is unclear whether the role of inflammation in chronic disease is similar in AA and EA. Future studies should aim at understanding the physiologic significance of greater first phase insulin secretion, and lower TNF-α and TNFRII, in AA with respect to implication for chronic disease