Unique Gap Structure and Symmetry of the Charge Density Wave in Single-Layer VSe_{2}.

Single layers of transition metal dichalcogenides (TMDCs) are excellent candidates for electronic applications beyond the graphene platform; many of them exhibit novel properties including charge density waves (CDWs) and magnetic ordering. CDWs in these single layers are generally a planar projection of the corresponding bulk CDWs because of the quasi-two-dimensional nature of TMDCs; a different CDW symmetry is unexpected. We report herein the successful creation of pristine single-layer VSe_{2}, which shows a (sqrt[7]×sqrt[3]) CDW in contrast to the (4×4) CDW for the layers in bulk VSe_{2}. Angle-resolved photoemission spectroscopy from the single layer shows a sizable (sqrt[7]×sqrt[3]) CDW gap of ∼100 meV at the zone boundary, a 220 K CDW transition temperature twice the bulk value, and no ferromagnetic exchange splitting as predicted by theory. This robust CDW with an exotic broken symmetry as the ground state is explained via a first-principles analysis. The results illustrate a unique CDW phenomenon in the two-dimensional limit.

Gastrointestinal Stromal Tumors: A Review.

The understanding of aberrant molecular pathways that result in gastrointestinal stromal tumors (GISTs) and the rapid development of molecular therapies that target these pathways represent one of the great milestones in translational oncology. The story of GIST is unique in that targeted molecular therapy was successfully applied in clinical therapeutics, with dramatic results redefining the management of these traditionally chemotherapy-resistant tumors. We briefly review the molecular biology and clinical presentation of GIST and then discuss the adjuvant and neoadjuvant use of tyrosine kinase inhibitors in early-stage GIST and their use in metastatic disease. Newer therapeutic advances in the rapidly changing field of GIST management are also discussed.

A Case Report on Varenicline Induced Delirium in an Alcohol and Nicotine Dependent Patient.

Varenicline is a smoking cessation agent. Varenicline acts as a partial agonist of α4ß2 neuronal nicotinic acetylcholine receptor and prevents nicotine binding to the same. It also causes dopamine (DA) stimulation that decreases craving and symptoms of dependence. A 40-year-old male diagnosed with alcohol and nicotine dependence syndrome was treated with 1 mg of varenicline for 3 days. Patient developed episodes of transient delirium within 15-30 min after administration of varenicline. Patient was disoriented and did not respond relevantly. Patient would have disorientation and would respond irrelevantly and was unable to recall the event completely. There were no features suggestive of seizures. The episodes resolved after the medication was stopped. Varenicline, with its partial agonistic effect on nicotinergic receptors, stimulates the release of multiple neurotransmitters including DA. DA dysregulation is probably responsible for the development of neuropsychiatric adverse reactions due to varenicline. This is the first case report to the best of our knowledge reporting varenicline induced dilirium. In this case, the adverse event was found in an alcohol and nicotine dependent patient undergoing treatment. It is essential to monitor uncommon adverse effects as this can cause significant morbidity.

Large single crystal growth, transport property, and spectroscopic characterizations of three-dimensional Dirac semimetal Cd3As2.

The three dimensional (3D) Dirac semimetal is a new quantum state of matter that has attracted much attention recently in physics and material science. Here, we report on the growth of large plate-like single crystals of Cd3As2 in two major orientations by a self-selecting vapor growth (SSVG) method, and the optimum growth conditions have been experimentally determined. The crystalline imperfections and electrical properties of the crystals were examined with transmission electron microscopy (TEM), scanning tunneling microscopy (STM), and transport property measurements. This SSVG method makes it possible to control the as-grown crystal compositions with excess Cd or As leading to mobilities near 5-10(5) cm(2)V(-1)s(-1). Zn-doping can effectively reduce the carrier density to reach the maximum residual resistivity ratio (RRRρ300K/ρ5K) of 7.6. A vacuum-cleaved single crystal has been investigated using angle-resolved photoemission spectroscopy (ARPES) to reveal a single Dirac cone near the center of the surface Brillouin zone with a binding energy of approximately 200 meV.

Visualizing Landau levels of Dirac electrons in a one-dimensional potential.

Using scanning tunneling spectroscopy, we study a 3D topological insulator Bi(2)Te(3) with a periodic structural deformation (buckling). The buckled surface allows us to measure the response of Dirac electrons in a magnetic field to the presence of a well-defined potential variation. We find that while the n=0 Landau level exhibits a 12 meV energy shift across the buckled structure at 7 T, the amplitude of this shift changes with the Landau level index. Modeling these effects reveals that the Landau level behavior encodes information on the spatial extent of their wave functions. Our findings have important implications for transport and magnetoresistance measurements in Dirac materials with engineered potential landscapes.

Effect of Smilax zeylanica roots and rhizomes in paracetamol induced hepatotoxicity.

CONTEXT: Smilax zeylanica L.(Smilacaceae) is a climbing shrub with woody prickly stems. OBJECTIVE: This study evaluated the hepatoprotective effect of S. zeylanica against paracetamol induced hepatotoxicity in Wistar rats. MATERIALS AND METHODS: The protective effects of the methanol extract (200 and 400 mg/kg) of root and rhizome of S. zeylanica were studied on paracetamol induced (1 g/kg) hepatic damage in Wistar rats by estimating the serum levels of AST, ALT, alkaline phosphatase (ALP), total proteins, total bilirubin and albumin. Sections of liver were observed for histopathological changes in liver architecture. RESULTS: Rats were protected from the hepatotoxic action of paracetamol as evidenced by the significant reduction in the elevated serum levels of ALT (P<0.001), AST (P< 0.01, P< 0.001), ALP (P<0.05, P< 0.001), total bilirubin (P< 0.05) and an increased level of total protein (P< 0.05) and albumin (P< 0.05, P<0.01) with a significant reduction in liver weight (P<0.001), when compared with the paracetamol control. Silymarin (100 mg/kg) was used as the standard. DISCUSSION AND CONCLUSION: The biochemical observations were supplemented by the histopathological studies on the liver sections of different groups. The methanol extract of S. zeylanica was found to alter the damage caused to hepatocytes by paracetamol and prevent the leakage of vital serum markers, which confirmed the hepatoprotective effect of this plant.

Ripple-modulated electronic structure of a 3D topological insulator.

Three-dimensional topological insulators host linearly dispersing states with unique properties and a strong potential for applications. An important ingredient in realizing some of the more exotic states in topological insulators is the ability to manipulate local electronic properties. Direct analogy to the Dirac material graphene suggests that a possible avenue for controlling local properties is via a controlled structural deformation such as the formation of ripples. However, the influence of such ripples on topological insulators is yet to be explored. Here we use scanning tunnelling microscopy to determine the effects of one-dimensional buckling on the electronic properties of Bi(2)Te(3.) By tracking spatial variations of the interference patterns generated by the Dirac electrons we show that buckling imposes a periodic potential, which locally modulates the surface-state dispersion. This suggests that forming one- and two-dimensional ripples is a viable method for creating nanoscale potential landscapes that can be used to control the properties of Dirac electrons in topological insulators.

Rationally designed aberrant kinase-targeted endogenous protein nanomedicine against oncogene mutated/amplified refractory chronic myeloid leukemia.

Deregulated protein kinases play a very critical role in tumorigenesis, metastasis, and drug resistance of cancer. Although molecularly targeted small molecule kinase inhibitors (SMI) are effective against many types of cancer, point mutations in the kinase domain impart drug resistance, a major challenge in the clinic. A classic example is chronic myeloid leukemia (CML) caused by BCR-ABL fusion protein, wherein a BCR-ABL kinase inhibitor, imatinib (IM), was highly successful in the early chronic phase of the disease, but failed in the advanced stages due to amplification of oncogene or point mutations in the drug-binding site of kinase domain. Here, by identifying critical molecular pathways responsible for the drug-resistance in refractory CML patient samples and a model cell line, we have rationally designed an endogenous protein nanomedicine targeted to both cell surface receptors and aberrantly activated secondary kinase in the oncogenic network. Molecular diagnosis revealed that, in addition to point mutations and amplification of oncogenic BCR-ABL kinase, relapsed/refractory patients exhibited significant activation of STAT5 signaling with correlative overexpression of transferrin receptors (TfR) on the cell membrane. Accordingly, we have developed a human serum albumin (HSA) based nanomedicine, loaded with STAT5 inhibitor (sorafenib), and surface conjugated the same with holo-transferrin (Tf) ligands for TfR specific delivery. This dual-targeted "transferrin conjugated albumin bound sorafenib" nanomedicine (Tf-nAlb-Soraf), prepared using aqueous nanoprecipitation method, displayed uniform spherical morphology with average size of ∼150 nm and drug encapsulation efficiency of ∼74%. TfR specific uptake and enhanced antileukemic activity of the nanomedicine was found maximum in the most drug resistant patient sample having the highest level of STAT5 and TfR expression, thereby confirming the accuracy of our rational design and potential of dual-targeting approach. The nanomedicine induced downregulation of key survival pathways such as pSTAT5 and antiapoptotic protein MCL-1 was demonstrated using immunoblotting. This study reveals that, by implementing molecular diagnosis, personalized nanomedicines can be rationally designed and nanoengineered by imparting therapeutic functionality to endogenous proteins to overcome clinically important challenges like molecular drug resistance.

Protective effects of Capparis sepiaria root extracts against acetaminophen-induced hepatotoxicity in Wistar rats.

Capparis sepiaria L. known as Himsra is an important drug in Ayurveda. In this study extracts of the root of C. sepiaria were evaluated for their hepatoprotective potential on acetaminophen-induced hepatotoxicity in albino Wistar rats. The extent of hepatoprotection was evaluated by estimating the serum levels of hepatic transaminases (SGPT and SGOT), alkaline phosphatase (ALP), total protein (TP), and bilirubin (total and direct). Aqueous and ethanol extracts of C. sepiaria significantly reduced the increased liver weight as well as serum levels of SGPT, SGOT, ALP, and bilirubin, and normalized the reduced serum protein levels in the treated rats. These observations were supported by the results of histopathology studies as well. The extracts were also subjected to preliminary organic analysis and chromatographic studies including HPTLC finger print studies. The results indicate that the roots of C. sepiaria show significant hepatoprotective effect on acetaminophen-induced hepatotoxicity, thus substantiating its use as a potential hepatoprotective drug.

Vibrational spectroscopic studies and computational calculations of 5-chloro-2-(3-chlorophenylcarbamoyl)phenylacetate.

The FT-IR and FT-Raman spectra of 5-chloro-2-(3-chlorophenylcarbamoyl)phenylacetate were studied. The vibrational wave numbers and corresponding vibrational assignments were examined theoretically using the Gaussian 03 set of quantum chemistry codes and the normal modes are assigned by Potential Energy Distribution calculations. The synthesis, elemental analysis and NMR values are presented. The red shift of the NH stretching wave number in the infrared spectrum from the computed wave number indicates the weakening of the NH bond resulting in proton transfer to the neighboring oxygen atom. The first hyperpolarizability, infrared intensities and Raman activities are reported. The calculated first hyperpolarizability is comparable with the reported values of similar derivatives and is an attractive object for future studies of nonlinear optics. The geometrical parameters of the title compound are in agreement with that of similar reported derivatives.

Formulation and characterization of ketoprofen liquisolid compacts by Box-Behnken design.

INTRODUCTION: Liquisolid technique is used in delivery of lipophilic and poorly water soluble drugs through oral route. It involves dissolving water insoluble drugs in nonvolatile solvents and converting into acceptably flowing and compressible powders. The objective of the present work was to enhance the dissolution rate of ketoprofen using microcrystalline cellulose as carrier, aerosil 200 as coating material, and polyethylene glycol as nonvolatile water miscible liquid vehicle. MATERIALS AND METHODS: The drug concentration was kept constant in all formulations at 40% w/w. Optimization was carried out using Box-Behnken design by selecting liquid load factor, amount of coating material, and amount of magnesium oxide as independent variables; cumulative percentage drug release and angle of repose were considered as dependent variables. RESULTS: The Fourier transform infrared (FTIR) and differential scanning calorimetry (DSC) studies revealed that there was no possible interaction between drug and tablet excipients. Prepared ketoprofen liquisolid tablets were evaluated for hardness, weight variation, friability, in-vitro disintegration time, drug content uniformity, and in-vitro dissolution studies. The optimized formulation yielded the response values, which were very close to the predicted values. The accelerated stability studies conducted showed that liquisolid tablets were not affected by ageing and there were no appreciable changes in the drug content.

Combining scanning tunneling microscopy and synchrotron radiation for high-resolution imaging and spectroscopy with chemical, electronic, and magnetic contrast.

The combination of high-brilliance synchrotron radiation with scanning tunneling microscopy opens the path to high-resolution imaging with chemical, electronic, and magnetic contrast. Here, the design and experimental results of an in-situ synchrotron enhanced x-ray scanning tunneling microscope (SXSTM) system are presented. The system is designed to allow monochromatic synchrotron radiation to enter the chamber, illuminating the sample with x-ray radiation, while an insulator-coated tip (metallic tip apex open for tunneling, electron collection) is scanned over the surface. A unique feature of the SXSTM is the STM mount assembly, designed with a two free-flex pivot, providing an angular degree of freedom for the alignment of the tip and sample with respect to the incoming x-ray beam. The system designed successfully demonstrates the ability to resolve atomic-scale corrugations. In addition, experiments with synchrotron x-ray radiation validate the SXSTM system as an accurate analysis technique for the study of local magnetic and chemical properties on sample surfaces. The SXSTM system's capabilities have the potential to broaden and deepen the general understanding of surface phenomena by adding elemental contrast to the high-resolution of STM.

The efficacy and safety of panitumumab administered concomitantly with FOLFIRI or Irinotecan in second-line therapy for metastatic colorectal cancer: the secondary analysis from STEPP (Skin Toxicity Evaluation Protocol With Panitumumab) by KRAS status.

BACKGROUND: Panitumumab, a fully human monoclonal antibody targeting the epidermal growth factor receptor (EGFR), is used as monotherapy for chemorefractory metastatic colorectal cancer (mCRC) in patients with wild-type (WT) KRAS tumors. Although skin toxicities are the most common adverse events associated with EGFR inhibitors, the differences in efficacy and safety between pre-emptive and reactive skin treatment according to KRAS tumor status has not been reported. PATIENTS AND METHODS: Eligible patients had mCRC with disease progression or unacceptable toxicity with first-line treatment containing fluoropyrimidine and oxaliplatin-based chemotherapy ± bevacizumab. Patients were randomized 1:1 to pre-emptive or reactive skin treatment (after skin toxicity developed). Patients received either panitumumab 6 mg/kg + FOLFIRI every 2 weeks or panitumumab 9 mg/kg + irinotecan every 3 weeks. Key study endpoints included overall response rate (ORR), overall survival, progression-free survival (PFS), and safety according to KRAS tumor status. RESULTS: Eighty-seven (92%) of 95 enrolled patients had evaluable KRAS tumor status: 49 (56%) patients with WT and 38 (44%) patients with mutant (MT) KRAS tumors, respectively. The ORR was 16% and 8% for patients with WT and MT KRAS tumors, respectively. Median PFS was 5.5 and 3.3 months for patients with WT and MT KRAS tumors, respectively. The most commonly observed adverse events by KRAS tumor status included dermatitis acneiform and pruritus. CONCLUSION: Panitumumab in combination with irinotecan-based chemotherapy has an acceptable toxicity profile in second-line therapy for mCRC. Numerical differences trending in favor of the patients with WT KRAS tumors were observed for most efficacy endpoints.

Direct observation of broken time-reversal symmetry on the surface of a magnetically doped topological insulator.

We study interference patterns of a magnetically doped topological insulator Bi(2-x)Fe(x)Te(3+d) by using Fourier transform scanning tunneling spectroscopy and observe several new scattering channels. A comparison with angle-resolved photoemission spectroscopy allows us to unambiguously ascertain the momentum-space origin of distinct dispersing channels along high-symmetry directions and identify those originating from time-reversal symmetry breaking. Our analysis also reveals that the surface state survives far above the energy where angle-resolved photoemission spectroscopy finds the onset of continuum bulk bands.

Skin toxicity evaluation protocol with panitumumab (STEPP), a phase II, open-label, randomized trial evaluating the impact of a pre-Emptive Skin treatment regimen on skin toxicities and quality of life in patients with metastatic colorectal cancer.

PURPOSE: Panitumumab, a fully human monoclonal antibody targeting the epidermal growth factor receptor (EGFR), is approved in the United States and Europe for the treatment of refractory metastatic colorectal cancer (mCRC). Skin toxicities are the most common adverse events with EGFR inhibitors. This is the first study designed to examine differences between pre-emptive and reactive skin treatment for specific skin toxicities in patients with mCRC for any EGFR inhibitor. PATIENTS AND METHODS: Patients receiving panitumumab-containing therapy were randomly assigned 1:1 to pre-emptive or reactive treatment (after skin toxicity developed). Pre-emptive treatment included use of skin moisturizers, sunscreen, topical steroid, and doxycycline. The primary end point of the study was the incidence of protocol-specified >or= grade 2 skin toxicities during the 6-week skin treatment period. Quality of life (QOL) was assessed with the Dermatology Life Quality Index (DLQI). RESULTS: Of 95 enrolled patients, 48 received pre-emptive treatment, and 47 received reactive treatment. The incidence of protocol-specified >or= grade 2 skin toxicities during the 6-week skin treatment period was 29% and 62% for the pre-emptive and reactive groups, respectively. Mean DLQI score change from baseline to week 3 was 1.3 points and 4.2 points in the pre-emptive and reactive groups, respectively. CONCLUSION: The pre-emptive skin treatment regimen was well tolerated. The incidence of specific >or= grade 2 skin toxicities during the 6-week skin treatment period was reduced by more than 50% in the pre-emptive group compared with the reactive group. Patients in the pre-emptive group reported less QOL impairment than patients in the reactive group.

Sustained ophthalmic delivery of ofloxacin from an ion-activated in situ gelling system.

The poor bioavailability and therapeutic response exhibited by conventional ophthalmic solutions due to rapid pre-corneal elimination of the drug may be overcome by the use of in situ gel forming systems that are instilled as drops into the eye and then undergo a sol-gel transition in the cul-de-sac. The present work describes the formulation and evaluation of an ophthalmic delivery system of an antibacterial agent ofloxacin, based on the concept of ion-activated in situ gelation. Sodium alginate was used as the gelling agent in combination with HPC (Hydroxy Propyl Cellulose) that acted as a viscosity-enhancing agent. In vitro release studies indicated that the alginate/HPC solution retained the drug better than the alginate or HPC solutions alone. The formulations were therapeutically efficacious, sterile, stable and provided sustained release of the drug over a period of time. These results demonstrate that the developed system is an alternative to conventional ophthalmic drops, patient compliance, industrially oriented and economical.

FT-IR, FT-Raman and DFT calculations of 4-chloro-2-(3,4-dichlorophenylcarbamoyl)phenyl acetate.

FT-IR and FT-Raman spectra of 4-chloro-2-(3,4-dichlorophenylcarbamoyl)phenyl acetate were recorded and analyzed. Synthesis and elemental analysis are also reported. The vibrational wavenumbers of the compound have been computed on the basis of density functional theory using B3LYP/6-31G* basis set. The predicted infrared intensities and Raman activities are reported.

Antibacterial Activity of Leaves of Cadaba trifoliata (Roxb.) Wt. & Arn.

Antibacterial activity of aqueous and ethanol leaf extracts of Cadaba trifoliata was evaluated by cup plate method against bacterial strains such as Staphylococcus aureus, Bacillus subtilis, Acinetobacter, Enterobacter aerogenes, Erwinia and Escherichia coli. The ethanol extract of the leaves demonstrated a high degree of activity against all the tested bacterial strains except Erwinia and Acinetobacter, whereas the aqueous extract of the leaves showed moderate activity against E. coli, B. subtilis and Staph. aureus and Enterobacter aerogenes.

Coexistence of competing orders with two energy gaps in real and momentum space in the high temperature superconductor Bi_{2}Sr_{2-x}La_{x}CuO_{6+delta}.

Through a combined scanning tunneling microscopy and angle-resolved photoemission spectroscopy study, we report the observation of two distinct gaps (a small and a large gap) that coexist both in real space and in the antinodal region of momentum space, below the superconducting transition temperature (T_{c}) of Bi_{2}Sr_{2-x}La_{x}CuO_{6+delta}. We show that the small gap is associated with superconductivity. The large-gap persists above T_{c}, and seems linked to observed charge ordering. We find a strong correlation between the large and small gaps suggesting that they are affected by similar physical processes.

Fingerprinting of Plumbagin in lic>Drosera burmannii Vahl using High Performance Thin Layer Chromatography.

HPTLC fingerprinting profile of the alcohol and aqueous extracts of Drosera burmannii is described. Seven components have been detected in the alcohol extract. Further, plumbagin, an useful antifertility agent, was also detected by comparison with the reference standard. The aqueous extract revealed two spots with no spot corresponding to plumbagin.