Here, we report the development of a simple, small, fast heating, and portable, homemade, inert gas (Ar) atmospheric annealing setup. Instead of using a conventional heating element, a commercial soldering rod having an encapsulated fast heating heater is used here. The sample holder is made of a block of stainless steel. It takes 200 s to reach 700 °C, and 10 min to cool down. The probability of oxidation or surface contamination has been examined by means of x ray photoelectron spectroscopy of virgin Cu sample after annealing at 600 °C. In addition, we compare the annealing of a hydrogenated carbon nitride film (HCN(x)) in both a conventional vacuum and our newly developed ambient Ar atmosphere setup.

BMS-663068 is the phosphonooxymethyl prodrug of BMS-626529, a novel small-molecule attachment inhibitor that targets HIV-1 gp120 and prevents its binding to CD4+ T-cells. The activity of BMS-626529 is virus-dependent, due to heterogeneity within gp120. In order to better understand the anti-HIV-1 spectrum of BMS-626529 against HIV-1, in vitro activity against a wide variety of laboratory strains and clinical isolates was determined. BMS-626529 had half-maximal effective concentration (EC(50)) values < 10 nM against the vast majority of viral isolates; however, susceptibility varied by > 6 log(10), with half-maximal effective concentration values in the low pM range against the most susceptible viruses. In vitro antiviral activity of BMS-626529 was generally not associated with either tropism or subtype, with few exceptions. Measurement of the binding affinity of BMS-626529 for purified gp120 suggests that a contributory factor to its inhibitory potency may be a relatively long dissociative half-life. Finally, in two-drug combination studies, BMS-626529 demonstrated additive or synergistic interactions with antiretroviral drugs of different mechanistic classes. These results suggest that BMS-626529 should be active against the majority of HIV-1 viruses and support the continued clinical development of the compound.

Impairment of vision is a devastating complication of tuberculous meningitis which may occur as a result of increased intracranial pressure, compression over the visual pathways or vasculitis. We herein present occurrence of neuroretinitis in a 35-year-old lady presenting with low grade fever and headache for one month, and associated with diminution of vision from 3weeks. She was diagnosed as a case of definite tuberculous meningitis and initiated on anti-tuberculous treatment as per WHO guidelines with supplemental corticosteroids. Marked improvement in vision was observed and at 3months of follow-up the patient was asymptomatic. Direct ophthalmoscopy, visual field analysis, fluorescein angiography, optical coherence tomography and magnetic resonance imaging of the brain were done to document the ophthalmological findings. Neuroretinitis, being an unusual cause of visual impairment in tuberculous meningitis, must be considered in patients without any evidence of raised intracranial pressure or compression, and with normal fluorescein angiography. We suggest that neuroretinitis may be added to list of causes of visual impairment in patients with tuberculous meningitis.

In parallel magnetic resonance imaging (MRI), the problem is to reconstruct an image given the partial K-space scans from all the receiver coils. Depending on its position within the scanner, each coil has a different sensitivity profile. All existing parallel MRI techniques require estimation of certain parameters pertaining to the sensitivity profile, e.g., the sensitivity map needs to be estimated for the SENSE and SMASH and the interpolation weights need to be calibrated for GRAPPA and SPIRiT. The assumption is that the estimated parameters are applicable at the operational stage. This assumption does not always hold, consequently the reconstruction accuracies of existing parallel MRI methods may suffer. We propose a reconstruction method called Calibration-Less Multi-coil (CaLM) MRI. As the name suggests, our method does not require estimation of any parameters related to the sensitivity maps and hence does not require a calibration stage. CaLM MRI is an image domain method that produces a sensitivity encoded image for each coil. These images are finally combined by the sum-of-squares method to yield the final image. It is based on the theory of Compressed Sensing (CS). During reconstruction, the constraint that "all the coil images should appear similar" is introduced within the CS framework. This leads to a CS optimization problem that promotes group-sparsity. The results from our proposed method are comparable (at least for the data used in this work) with the best results that can be obtained from state-of-the-art methods.

INTRODUCTION The weave, fabric cover, areal density and ultraviolet (UV) absorbers are some of the factors which influence the ultraviolet protection factor (UPF) of cotton fabrics. It will be of interest to know whether fabric cover or fabric areal density is a better predictor of cotton fabric UPF. It will also be of interest to know whether the UV absorbers are equally effective for all kinds of cotton fabric. OBJECTIVES To understand the role of weave, fabric cover, areal density and UV absorbers on the UPF of cotton fabrics. To establish quantitative relationships between the fabric cover, areal density and UPF for cotton fabrics. METHODS Sixty-four woven fabrics were manufactured using different weaves, cotton yarn count and picks per centimetre values. Nonlinear regression models were developed to relate the fabric cover and areal density with the UPF. The role of UV absorbers at different levels of cover has been analysed. RESULTS In case of bleached cotton fabrics woven with 40 Ne warp yarn count, 40 ends per cm, different weft yarn count (20-40 Ne) and picks per centimetre (15-27), weave does not have a statistically significant effect on the UPF. Fabric areal density is a better predictor of UPF than the fabric cover. The UV absorbers are more effective when the fabric cover is high. CONCLUSIONS The developed equations relating fabric cover and UPF can be used as a primary guideline while selecting fabrics for UV protection.

Background: Cold plasma, a new treatment principle in dermatology based on ionic discharge delivering reactive molecular species and UV-light, exhibits strong antimicrobial efficacy in vitro and in vivo. Before implementing plasma as new medical treatment tool, its safety must be proven, as well as assessing skin tolerance and patient acceptance. Patients and Methods: We investigated the plasma effects of three different plasma sources (pulsed, non-pulsed atmospheric pressure plasma jet (APPJ) and a dielectric barrier discharge (DBD)) on the transepidermal water loss (TEWL) and skin moisture after treating the fingertips of four healthy male volunteers. Results: TEWL values were reduced by pulsed APPJ and DBD by about 20% but increased after non-pulsed APPJ by 5-20%. TEWL values normalized 30 min after all forms of plasma treatment. Skin moisture was increased immediately and 30 min after treatment with pulsed APPJ but was not affected by non-pulsed APPJ and DBD. Conclusions: All plasma treatments were well-tolerated and did not damage the skin barrier nor cause skin dryness. Cold plasma fulfils basic recommendations for safe use on human skin and as future option may serve as the first physical skin antiseptic.

BACKGROUND: Neoadjuvant chemotherapy (NACT) is being increasingly used for patients with large-size operable breast cancer. This phase 2 study of sequential NACT with gemcitabine and doxorubicin (Gem + Dox) followed by gemcitabine and cisplatin (Gem + Cis) was conducted in women with large or locally advanced breast cancer. The objectives were to evaluate the pathological complete response (pCR) rate, toxicity, pathological and genetic markers predicting response, the proportion of patients undergoing breast conservation surgery, progression-free survival (PFS) and overall survival (OS) after 5 years, and time to treatment failure (TtTF). In this manuscript, we report the long-term OS, PFS, and TtTF results. METHODS: Female patients aged at least 18 years with large T2 (at least 3 cm) or locally advanced (T3, T4, or N2) breast carcinoma were included. Treatment consisted of 4 cycles of Gem + Dox (gemcitabine 1,200 mg/m(2) on days 1 and 8 plus doxorubicin 60 mg/m(2) on day 1 of each 21-day cycle), followed by 4 cycles of Gem + Cis (gemcitabine 1,000 mg/m(2) on days 1 and 8 plus cisplatin 70 mg/m(2) on day 1 of each 21-day cycle), and then surgery. RESULTS: Sixty-five patients were enrolled. The pCR rate was 20%. The 5-year OS probability was 71%(95% CI 56-82%), and the 4-year PFS and TtTF probabilities were 63%(95% CI 48-74%) and 45%(95% CI 32-57%), respectively. CONCLUSIONS: NACT with Gem + Dox followed by Gem + Cis was efficacious in patients with operable breast cancer.

Reversible lysine acetylation and methylation regulate the function of a wide variety of proteins, including histones. Here we have synthesized azalysine-containing peptides in acetylated and unacetylated forms as chemical probes of the histone deacetylases (HDAC8, Sir2Tm, and SIRT1) and the histone demethylase, LSD1. We have shown that the acetyl-azalysine modification is a fairly efficient substrate for the sirtuins, but a weaker substrate for HDAC8, a classical HDAC. In addition to deacetylation by sirtuins, the acetyl-azalysine analog generates a novel ADP-ribose adduct that was characterized by mass spectrometry, western blot analysis, and nuclear magnetic resonance spectroscopy. This peptide-ADP-ribose adduct is proposed to correspond to a derailed reaction intermediate, providing unique evidence for the direct 2'-hydroxyl attack on the O-alkylimidate intermediate that is formed in the course of sirtuin catalyzed deacetylation. An unacetylated azalysine-containing H3 peptide proved to be a potent inhibitor of the LSD1 demethylase, forming an FAD adduct characteristic of previously reported related structures, providing a new chemical probe for mechanistic analysis.

Many heme proteins undergo covalent attachment of the heme group to a protein side chain. Such posttranslational modifications alter the thermodynamic and chemical properties of the holoprotein. Their importance in biological processes makes them attractive targets for mechanistic studies. We have proposed a reductively driven mechanism for the covalent heme attachment in the monomeric hemoglobins produced by the cyanobacteria Synechococcus sp. PCC 7002 and Synechocystis sp. PCC 6803 (GlbN)(Nothnagel et al. in J Biol Inorg Chem 16:539-552, 2011). These GlbNs coordinate the heme iron with two axial histidines, a feature that distinguishes them from most hemoglobins and conditions their redox properties. Here, we uncovered evidence for an electron exchange chain reaction leading to complete heme modification upon substoichiometric reduction of GlbN prepared in the ferric state. The GlbN electron self-exchange rate constants measured by NMR spectroscopy were on the order of 10(2)-10(3) M(-1) s(-1) and were consistent with the proposed autocatalytic process. NMR data on ferrous and ferric Synechococcus GlbN in solution indicated little dependence of the structure on the redox state of the iron or cross-link status of the heme group. This allowed the determination of lower bounds to the cross-exchange rate constants according to Marcus theory. The observations illustrate the ability of bishistidine hemoglobins to undergo facile interprotein electron transfer and the chemical relevance of such transfer for covalent heme attachment.

A long-standing question in the study of long-term memory is how a memory trace persists for years when the proteins that initiated the process turn over and disappear within days. Previously, we postulated that self-sustaining amyloidogenic oligomers of cytoplasmic polyadenylation element-binding protein (CPEB) provide a mechanism for the maintenance of activity-dependent synaptic changes and, thus, the persistence of memory. Here, we found that the Drosophila CPEB Orb2 forms amyloid-like oligomers, and oligomers are enriched in the synaptic membrane fraction. Of the two protein isoforms of Orb2, the amyloid-like oligomer formation is dependent on the Orb2A form. A point mutation in the prion-like domain of Orb2A, which reduced amyloid-like oligomerization of Orb2, did not interfere with learning or memory persisting up to 24 hr. However the mutant flies failed to stabilize memory beyond 48 hr. These results support the idea that amyloid-like oligomers of neuronal CPEB are critical for the persistence of long-term memory.