Quantum Wires and Waveguides Formed in Graphene by Strain.

Confinement of electrons in graphene to make devices has proven to be a challenging task. Electrostatic methods fail because of Klein tunneling, while etching into nanoribbons requires extreme control of edge terminations, and bottom-up approaches are limited in size to a few nanometers. Fortunately, its mechanical flexibility raises the possibility of using strain to alter graphene's properties and create novel straintronic devices. Here, we report transport studies of nanowires created by linearly-shaped strained regions resulting from individual folds formed by layer transfer onto hexagonal boron nitride. Conductance measurements across the folds reveal Coulomb blockade signatures, indicating confined charges within these structures, which act as quantum dots. Along folds, we observe sharp features in traverse resistivity measurements, attributed to an amplification of the dot conductance modulations by a resistance bridge incorporating the device. Our data indicates ballistic transport up to ∼1 µm along the folds. Calculations using the Dirac model including strain are consistent with measured bound state energies and predict the existence of valley-polarized currents. Our results show that graphene folds can act as straintronic quantum wires.

A low-cost paper-based platform for fast and reliable screening of cellular interactions with materials.

A paper-based platform was developed and tested for studies on basic cell culture, material biocompatibility, and activity of pharmaceuticals in order to provide a reliable, robust and low-cost cell study platform. It is based upon a paper or paperboard support, with a nanostructured latex coating to provide an enhanced cell growth and sufficient barrier properties. Wetting is limited to regions of interest using a flexographically printed hydrophobic polydimethylsiloxane layer with circular non-print areas. The nanostructured coating can be substituted for another coating of interest, or the regions of interest functionalized with a material to be studied. The platform is fully up-scalable, being produced with roll-to-roll rod coating, flexographic and inkjet printing methods. Results show that the platform efficiency is comparable to multi-well plates in colorimetric assays in three separate studies: a cell culture study, a biocompatibility study, and a drug screening study. The color intensity is quantified by using a common office scanner or an imaging device and the data is analyzed by a custom computer software without the need for expensive screening or analysis equipment.

Influence of sample characteristics on quantification of carbamazepine hydrate formation by X-ray powder diffraction and Raman spectroscopy.

This study aimed to assess the suitability of two widely utilized solid state characterization techniques namely powder X-ray diffraction (XRPD) and Raman spectroscopy, in polymorph detection and quantification for carbamazepine anhydrate and dihydrate mixtures. The influences of particle size, particle morphology, mixing, and in particular, surface bias on quantitation were investigated. Binary mixtures of carbamazepine anhydrate (form III) and dihydrate were prepared and analyzed using both XRPD and Raman spectroscopy in combination with partial least squares analysis. It was found that in principle both XRPD and Raman spectroscopy could be used to build calibration models for quantitative analysis, and a satisfactory correlation between the two techniques could be achieved. However, Raman spectroscopy appeared to be a more reliable quantification method because problems such as different particle size, morphology, and special distribution of the two solid state forms of the drug seemed to have no significant influence on Raman scattering in this study. The robust nature of Raman analysis greatly facilitates the whole quantification process from the preparation of calibration models to the quantification of in situ CBZ-DH conversion.

Visualizing the conversion of carbamazepine in aqueous suspension with and without the presence of excipients: a single crystal study using SEM and Raman microscopy.

Visual observations of the hydration process of single carbamazepine (CBZ) crystals in water and in various excipient solutions [(1% w/v) - hydroxypropyl cellulose (HPC), poly(vinyl pyrrolidone) (PVP), sodium carboxymethylcellulose (CMC) at pH 7.5 and 3.0, and polyethylene glycol (PEG)] using scanning electron microscopy (SEM) are reported in this paper. Raman microscopy was used to confirm the chemical structures of the unconverted CBZ and the CBZ dihydrate (DH) needles. It was found that defect structures were a more important driving force than the nature of crystal faces for the initiation of the hydration, but face differences became obvious after 6 h immersion. The biggest crystal face grown from methanol, (100), was the slowest one to be covered with DH needles. A comparison of the molecular arrangements along the three crystal faces [(100), (010) and (001)] was carried out using crystal structure visualization software, and fewer polar groups exposed on the (100) face than on the (001) and (010) faces were found, explaining the comparatively weak interaction of the (100) face with water during hydration. Furthermore, investigation of the influence of excipients on the hydration of CBZ showed that both HPC and PVP strongly inhibited conversion, and no conversion of CBZ to DH was found after 18 h immersion in water. PEG and CMC (pH 7.5) were less potent inhibitors than HPC and PVP, and DH needles were observed on all the faces except the (100) face after 18 h immersion. No conversion was detected for the crystal immersed in CMC solution at pH 3.0. This is likely to be caused by the decreased polarity of CMC in water at pH 3.0 (pKa,cmc = 4.3), and thus a higher surface adsorption of CMC to the CBZ crystals in dispersion. The influence of excipients on the conversion of CBZ observed in this study agreed well with our previous quantitative studies using Raman spectroscopy. In this study, visual observation using electron microscopy has been demonstrated to be a unique and powerful tool to improve our understanding of polymorphic conversions of CBZ in aqueous suspension.

Fano resonances in hexagonal zigzag graphene rings under external magnetic flux.

We study transport properties of hexagonal zigzag graphene quantum rings connected to semi-infinite nanoribbons. Open two-fold symmetric structures support localized states that can be traced back to those existing in the isolated six-fold symmetric rings. Using a tight-binding Hamiltonian within the Green's function formalism, we show that an external magnetic field promotes these localized states to Fano resonances with robust signatures in transport. Local density of states and current distributions of the resonant states are calculated as a function of the magnetic flux intensity. For structures on corrugated substrates we analyze the effect of strain by including an out-of-plane centro-symmetric deformation in the model. We show that small strains shift the resonance positions without further modifications, while high strains introduce new ones.

Liver injury is associated with mortality in sickle cell disease.

BACKGROUND: Increased life expectancy in sickle cell disease (SCD) has resulted in greater recognition of the consequences of repeated intravascular vaso-occlusion and chronic haemolysis to multiple organ systems. AIM: To report the long-term consequences of liver dysfunction in SCD. METHODS: A cohort of SCD patients was prospectively evaluated at the National Institutes of Health (NIH) Clinical Center. The association of mortality with liver enzymes, parameters of liver synthetic function and iron overload was evaluated using Cox regression. RESULTS: Exactly, 247 SCD patients were followed up for 30 months of whom 22 (9%) died. After controlling for predictors, increased direct bilirubin (DB), ferritin, alkaline phosphatase and decreased albumin were independently associated with mortality. In a multivariable model, only high DB and ferritin remained significant. Ferritin correlated with hepatic iron content and total blood transfusions but not haemolysis markers. Forty patients underwent liver biopsies and 11 (28%) had fibrosis. Twelve of 26 patients (48%) had portal hypertension by hepatic venous pressure gradient (HVPG) measurements. All patients with advanced liver fibrosis had iron overload; however, most patients (69%) with iron overload were without significant hepatic fibrosis. Ferritin did not correlate with left ventricular dysfunction by echocardiography. DB correlated with bile acid levels suggesting liver pathology. Platelet count and soluble CD14 correlated with HVPG indicating portal hypertension. CONCLUSIONS: Ferritin and direct bilirubin are independently associated with mortality in sickle cell disease. Ferritin likely relates to transfusional iron overload, while direct bilirubin suggests impairment of hepatic function, possibly impairing patients' ability to tolerate systemic insults.

Membrane-protein phosphorylation in the Bacillus subtilis cell cycle.

Sphingosine, an inhibitor of Ca(2+)-dependent protein kinases in eukaryotic cells, inhibited initiation of DNA replication in Bacillus subtilis at a concentration of 10 microM, without inhibiting elongation. The tumor promoter 12-tetradecanoyl 13-phorbol acetate, (TPA), an activator of protein kinase C in eukaryotic cells, partially counteracted the inhibition of initiation by sphingosine. Phosphorylation of polypeptides was observed in vivo at initiation of DNA replication in B. subtilis. Sphingosine, TPA, and vancomycin affected this protein phosphorylation.

Expression of chromosomally inserted bacillus thuringiensis israelensis toxin genes in bacillus sphaericus

Bacillus thuringiensis israelensis delta-endotoxin genes were inserted into transposon Tn917 in plasmid pTV51Ts and cloned into the chromosome of Bacillus sphaericus 2362. Many of the transformants reacted with antibody to the 135-, 128-, 65-, and 28-kDa B.t.israelensis toxin proteins and were approximately 10 times more toxic to A. aegypti larvae than the untransformed host. Some of the transformants differed physiologically and morphologically from the wild-type B. sphaericus. The toxicity of the transformed phenotype was maintained through many transfers in the absence of selective pressure. Copyright 1998 Academic Press.

Differential diagnosis of jaw pain in the elderly.

While many diseases are marked by pain in the mandible or maxilla, a number of these conditions appear to be more prevalent in people 65 years and older. People in this age group often have a number of medical problems and take a variety of medications, so clear-cut diagnosis of jaw pain can be difficult. Memory deficits or concomitant somatic complaints can further complicate the diagnosis. This article presents a differential for jaw pain in the elderly and reports on a pertinent case.

The use of bispectral analysis to monitor outpatient sedation.

The bispectral (BIS) index has been used to interpret partial EEG recordings to predict the level of sedation and loss of consciousness in patients undergoing general anesthesia. The author has evaluated BIS technology in determining the level of sedation in patients undergoing outpatient deep sedation. These experiences are outlined in this review article. Initially, the correlation of the BIS index with traditional subjective patient evaluation using the Observer's Assessment of Alertness and Sedation (OAA/S) scale was performed in 25 subjects. In a second study, the recovery profile of 39 patients where the BIS was used to monitor sedation was compared with a control group where the monitor was not used. A strong positive relationship between the BIS and OAA/S readings was found in the initial subjects. From the recovery study, it appears that use of the BIS monitor may help titrate the level of sedation so that less drugs are used to maintain the desired level of sedation. A trend to earlier return of motor function in BIS-monitored patients was also demonstrated. BIS technology offers an objective, ordinal means of assessing the depth of sedation. This can be invaluable in comparing studies of techniques. The BIS index provides additional information to standard monitoring techniques that helps guide the administration of sedative-hypnotic agents. The trend to earlier return of motor function in BIS-monitored patients warrants further investigation.

Additional clinical observations utilizing bispectral analysis.

Additional observations were made in the use of the bispectral (BIS) index with the use of ketamine and in performing general anesthesia without the use of local anesthesia in nonintubated patients. Twenty-five subjects undergoing extraction procedures in an outpatient setting were analyzed using bispectral analysis with ketamine and midazolam. Despite repeated injections of midazolam during the procedure, only transient decreases of the BIS occurred to the 80s, with a low value of 77 in all but 1 patient where ketamine was used. In comparison, values in the 50-70 range are typically seen immediately after the administration of sedative doses of midazolam, propofol, or methohexital. In the second study, once propofol anesthesia was initiated, BIS readings in the 30s were commonly seen in patients during their procedure. The lowest BIS level observed was 18. Bispectral analysis was useful to trend the present anesthetic state and adjust the dose of propofol accordingly. In no case was laryngospasm or total airway obstruction observed. In 1 case, partial airway obstruction secondary to retro-positioning of the tongue occurred with a subsequent decrease in oxygen saturation to 89%. This was rectified by repositioning the patient to alleviate the obstruction. Consistent with previous studies utilizing ketamine, BIS values are consistently higher when compared with other hypnotic agents. With the subsequent injection of midazolam, the BIS level did not decrease to anticipated levels. In the final study reviewed, when local anesthesia was not used during general anesthesia, bispectral analysis was a useful adjunct in helping maintain a steady state of general anesthesia in nonintubated patients undergoing third molar extractions. Bispectral analysis offers additional information on the depth of the hypnotic state and is useful in helping control the depth of anesthesia. A limitation of the index includes the inability to titrate the level of sedation induced by hypnotic agents such as midazolam when ketamine is concomitantly administered.

Real-time image-based investigation of spheronization and drying phenomena using different pellet formulations.

Extrusion-spheronization (ES) is a frequently used agglomeration process in the pharmaceutical industry to manufacture spherical solid units or pellets with a narrow size and shape distribution. In this study, photometric stereo imaging was applied in real-time during the final steps of the ES process, being spheronization and drying. In addition to the pellet size distribution of undispersed (wet) samples, the imaging technique captures visual information on pellet shape and surface brightness. Pellet samples were taken at 20 time points during spheronization and were imaged at-line (during spheronization) and off-line (after spheronization). Particle size distributions and visual image information were both used to characterise the spheronization behaviour of different formulations. Next, particle size distributions and surface brightness values calculated from the at-line obtained images during fluid bed drying of pellets were analysed. The particle size distribution and brightness value changes occurring during pellet drying were explained both by the reduction in residual moisture content and drug solid-state transition. Due to the rapidness of the technique with regard to sample preparation, sample measurement and the acquisition of results in combination with the possibility to measure undispersed (wet) samples, valuable information on spheronization and drying characteristics of different formulations was obtained in real-time.

Cell wall synthesis and initiation of deoxyribonucleic acid replication in Bacillus subtilis.

We have observed a connection between cell wall synthesis and the initiation of chromosome replication in Bacillus subtilis. Initiation of chromosome replication was prevented in synchronous cultures in the presence of the cell wall synthesis inhibitor vancomycin. When vancomycin was added to the cultures after initiation of chromosome replication, one round of replication was completed but no reinitiation occurred. Similar results were obtained when cell wall synthesis was inhibited by ristocetin, cycloserine, cloxacillin, or cephaloridine. When sucrose was added to the medium, initiation of deoxyribonucleic acid replication occurred in the presence of vancomycin, to an extent which allowed replication of no more than approximately one-half of the deoxyribonucleic acid of the culture. The same was found in cultures of spheroplasts of B. subtilis. However, initiation of chromosome replication in spheroplasts was completely insensitive to cloxacillin.

Changes in sporulation potential during the growth cycle of Bacillus subtilis.

The sporulation potential of Bacillus subtilis as a function of position in the cell cycle was determined by transferring cells from growth medium to sporulation medium at various times during growth. Growth was induced by incubating heat-activated spores in rich medium or by diluting stationary phase vegetative cultures with fresh growth medium. The results supported earlier observations that sporulation potential is cell cycle dependent. The rise in sporulation potential was studied by exposing cultures to the inhibitors of cell wall and protein synthesis, vancomycin and chloramphenicol. The delay in the appearance of the peak of sporulation potential caused by these inhibitors compared with the reported lack of effect of nalidixic acid, indicates that the appearance of sporulation potential requires synthesis of a macromolecular component other than deoxyribonucleic acid. The effect of nalidixic acid in preventing the decline of the sporulation potential was compared with the effect of high temperature on a mutant temperature sensitive for the initiation of DNA replication. It was found that prevention of chromosome completion with nalidixic acid maintained a high sporulation potential, whereas prevention of chromosome re-initiation in the temperature sensitive mutant did not affect the decline in sporulation potential as the cells enter stationary phase.

Membrane binding and release of Bacillus subtilis DNA as a function of the cell cycle.

The presence of origin-region DNA in preparations containing bacterial cell wall and cytoplasmic membrane is well established, but little is known about the relationship between this association and events of the cell cycle. We have observed, during renewed growth of stationary-phase cultures of Bacillus subtilis, an association of DNA, including newly synthesized regions, with a specific region of the plasma membrane. Attachment was transitory, occurring once per replication cycle, and was prevented by inhibitors of cell wall synthesis.