New pairing scheme to overhaul BCS theory

In a superconductor pair occupancy probabilities are doubly defined with conflicting values when normal and umklapp scattering coexist with the same destination momentum. To resolve this issue a new pairing scheme is introduced to assert normal–umklapp frustration under such circumstances. Superconductivity then arises solely from residual umklapp scattering to destination momenta not reached by normal scattering. Consequent Tc calculations from first principles for niobium, tantalum, lead and aluminum turn out to be accurate within a few percent. A new perspective is revealed to support Matthias׳ rule. New light is also shed relevant to the future study of metallic hydrogen.

PEG-based solid dispersions enhanced the solubility and dissolution of eprosartan mesylate in-vitro

Abstract - This study investigates the effect of solid dispersions prepared from of polyethylene glycol (PEG) 3350 and 6000 Da alone or combined with the non-ionic surfactant Tween 80 on the solubility and dissolution rate of a poorly soluble drug eprosartan mesylate (ESM) in attempt to improve its bioavailability following its oral administration.

INTRODUCTION

ESM is a potent anti-hypertension [1]. It has low water solubility and is classified as a Class II drug as per the Biopharmaceutical Classification Systems (BCS) leading to low and variable oral bioavailability (approximately 13%). [2]. Thus, improving ESM solubility and/or dissolution rate would eventually improve the drug bioavailability. Solid dispersion is widely used technique to improve the water solubility of poorly water-soluble drugs employing various biocompatible polymers. In this study, we aimed to enhance the solubility and dissolution of EMS employing solid dispersion (SD) formulated from two grades of poly ethylene glycol (PEG) polymers (i.e. PEG 3350 & PEG 6000 Da) either individually or in combination with Tween 80.

MATERIALS AND METHODS

ESM SDs were prepared by solvent evaporation method using either PEG 3350 or PEG 6000 at various (drug: polymer, w/w) ratios 1:1, 1:2, 1:3, 1:4, 1:5 alone or combined with Tween 80 added at fixed percentage of 0.1 of drug by weight?. Physical mixtures (PMs) of drug and carriers were also prepared at same ratios. Drug solid dispersions and physical mixtures were characterized in terms of drug content, drug dissolution using dissolution apparatus USP II and assayed using HPLC method. Drug dissolution enhancement ratio (ER %) from SD in comparison to the plain drug was calculated. Drug-polymer interactions were evaluated using Differential Scanning Calorimetry (DSC) and FT-IR.

RESULTS AND DISCUSSION

The in vitro solubility and dissolution studies showed SDs prepared using both polymers produced a remarkable improvement (p<0.05) in comparison to the plain drug which reached around 32% (Fig. 1). The dissolution enhancement ratio was polymer type and concentration-dependent. Adding Tween 80 to the SD did not show further dissolution enhancement but reduced the required amount of the polymer to get the same dissolution enhancement. The DSC and FT-IR studies indicated that using SD resulted in transformation of drug from crystalline to amorphous form.

CONCLUSIONS

This study indicated that SDs prepared by using both polymers i.e. PEG 3350 and PEG 6000 improved the in-vitro solubility and dissolution of ESM remarkably which may result in improving the drug bioavailability in vivo.

Acknowledgments

This work is a part of MSc thesis of O.M. Ali at the Faculty of Pharmacy, Aleppo University, Syria.

REFERENCES

[1] Ruilope L, Jager B: Eprosartan for the treatment of hypertension. Expert Opin Pharmacother 2003; 4(1):107-14

[2] Tenero D, Martin D, Wilson B, Jushchyshyn J, Boike S, Lundberg, D, et al. Pharmacokinetics of intravenously and orally administered Eprosartan in healthy males: absolute bioavailability and effect of food. Biopharm Drug Dispos 1998; 19(6): 351- 6.

ARB: Phase II window of opportunity study of short-term preoperative treatment with enzalutamide in ER-positive and triple-negative breast cancer

The androgen receptor (AR) is expressed in 60-80% of breast cancers (BC) across all molecular phenotypes, with a higher incidence in oestrogen receptor positive (ER+) BC compared to ER negative tumours. In ER+ disease, AR-expression has been linked to endocrine resistance which might be reversed with combined treatment targeting ER and AR. In triple negative BCs (TNBC), preclinical and clinical investigations have described a subset of patients that express the AR and are sensitive to androgen blockade, providing a novel therapeutic target. Enzalutamide, a potent 2nd generation anti-androgen, has demonstrated substantial preclinical and clinical anti-tumour activity in AR+ breast cancer. Short-term preoperative window of opportunity studies are a validated strategy for novel treatments to provide proof-of-concept and define the most appropriate patient population by directly assessing treatment effects in tumour tissue before and after treatment. The ARB study aims to assess the anti-tumour effects of enzalutamide in early ER+ breast cancer and TNBC, to identify the optimal target population for further studies and to directly explore the biologic effects of enzalutamide on BC and stromal cells. Methods: ARB is an international, investigator sponsored WOO phase II study in women with newly diagnosed primary ER+ BC or AR+ TNBC of ≥ 1cm. The study has two cohorts. In the ER+ cohort, postmenopausal patients will be randomised 2:1 to receive either enzalutamide (160mg OD) plus exemestane (50mg OD) or exemestane (25mg OD). In the TNBC cohort, AR+ will receive single agent treatment with enzalutamide (160mg OD). Study treatment is planned for 15–29 days, followed by surgery or neo-adjuvant therapy. Tissue and blood samples are collected before treatment and on the last day of study treatment. The primary endpoint is inhibition of tumour-cell proliferation, as measured by change in Ki67 expression, determined centrally by 2 investigators. Secondary endpoints include induction of apoptosis (Caspase3), circulating hormone levels and safety. ARB aims to recruit ≈235 patients from ≈40 sites in the UK, Germany, Spain and USA. The study is open to recruitment.

Threat Analysis of BlackEnergy Malware for Synchrophasor based Real-time Control and Monitoring in Smart Grid

The BlackEnergy malware targeting critical infrastructures has a long history. It evolved over time from a simple DDoS platform to a quite sophisticated plug-in based malware. The plug-in architecture has a persistent malware core with easily installable attack specific modules for DDoS, spamming, info-stealing, remote access, boot-sector formatting etc. BlackEnergy has been involved in several high profile cyber physical attacks including the recent Ukraine power grid attack in December 2015. This paper investigates the evolution of BlackEnergy and its cyber attack capabilities. It presents a basic cyber attack model used by BlackEnergy for targeting industrial control systems. In particular, the paper analyzes cyber threats of BlackEnergy for synchrophasor based systems which are used for real-time control and monitoring functionalities in smart grid. Several BlackEnergy based attack scenarios have been investigated by exploiting the vulnerabilities in two widely used synchrophasor communication standards: (i) IEEE C37.118 and (ii) IEC 61850-90-5. Specifically, the paper addresses reconnaissance, DDoS, man-in-the-middle and replay/reflection attacks on IEEE C37.118 and IEC 61850-90-5. Further, the paper also investigates protection strategies for detection and prevention of BlackEnergy based cyber physical attacks.

Towards a Resilience Metric Framework for Cyber-Physical Systems

Resilience is widely accepted as a desirable system property for cyber-physical systems. However, there are no metrics that can be used to measure the resilience of cyber-physical systems (CPS) while the multi-dimensional nature of performance in these systems is considered. In this work, we present first results towards a resilience metric framework. The key contributions of this framework are threefold: First, it allows to evaluate resilience with respect to different performance indicators that are of interest. Second, complexities that are relevant to the performance indicators of interest, can be intentionally abstracted. Third and final, it supports the identification of reasons for good or bad resilience to improve system design.