Search

The programmed synthesis of sequence-defined biomaterials whose monomer backbones diverge from those of canonical α-amino acids represents the next frontier in protein and biomaterial evolution. Such next-generation molecules provide otherwise nonexistent opportunities to develop improved biologic therapies, bioremediation tools, and biodegradable plastic-like materials. One monomer family of particular interest for biomaterials includes β-hydroxy acids. Many natural products contain isolated β-hydroxy acid monomers, and polymers of β-hydroxy acids (β-esters) are found in polyhydroxyalkanoate (PHA) polyesters under development as bioplastics and drug encapsulation/delivery systems. Here we report that β2-hydroxy acids possessing both (R) and (S) absolute configuration are substrates for pyrrolysyl-tRNA synthetase (PylRS) enzymes in vitroand that (S)-β2-hydroxy acids are substrates in cellulo. Using the orthogonal MaPylRS/MatRNAPylsynthetase/tRNA pair, in conjunction with wild-type E. coliribosomes and EF-Tu, we report the cellular synthesis of model proteins containing two (S)-β2-hydroxy acid residues at internal positions. Metadynamics simulations provide a rationale for the observed preference for the (S)-β2-hydroxy acid and provide mechanistic insights that inform future engineering efforts. As far as we know, this finding represents the first example of an orthogonal synthetase that acylates tRNA with a β2-hydroxy acid substrate and the first example of a protein hetero-oligomer containing multiple expanded-backbone monomers produced in cellulo.

As genetic code expansion advances beyond l-α-amino acids to backbone modifications and new polymerization chemistries, delineating what substrates the ribosome can accommodate remains a challenge. The Escherichia coliribosome tolerates non-l-α-amino acids in vitro, but few structural insights that explain how are available, and the boundary conditions for efficient bond formation are so far unknown. Here we determine a high-resolution cryogenic electron microscopy structure of the E. coliribosome containing α-amino acid monomers and use metadynamics simulations to define energy surface minima and understand incorporation efficiencies. Reactive monomers across diverse structural classes favour a conformational space where the aminoacyl-tRNA nucleophile is <4 Å from the peptidyl-tRNA carbonyl with a Bürgi–Dunitz angle of 76–115°. Monomers with free energy minima that fall outside this conformational space do not react efficiently. This insight should accelerate the in vivo and in vitro ribosomal synthesis of sequence-defined, non-peptide heterooligomers.

Background: The high-density lipoprotein (HDL) cholesterol level is a strong predictor of cardiovascular events in epidemiologic studies. Until recently, it has been less extensively studied as a therapeutic target. Objective: To assess the angiographic and clinical effects of a pharmacologic strategy to increase HDL cholesterol levels. Design: Randomized, double-blind, placebo-controlled trial conducted from 1993 to 1996. Setting: Outpatient specialty clinic of a large U.S. military medical center. Participants: 143 military retirees younger than 76 years of age with low HDL cholesterol levels and angiographically evident coronary disease. Intervention: Gemfibrozil, niacin, and cholestyramine or corresponding placebos, with aggressive dietary and lifestyle intervention at baseline. Measurements: Change from baseline to 30 months and a composite measure of clinical events that included hospitalization for angina, myocardial infarction, transient ischemic attack and stroke, death, and cardiovascular procedures. Results: At baseline, mean ([+ or -]SD) lipid values were as follows: total cholesterol, 5.1 [+ or -] 0.8 mmol/L (196 [+ or -] 31 mg/dL); low-density lipoprotein (LDL) cholesterol, 3.3 [+ or -] 0.7 mmol/L (128 [+ or -] 27 mg/dL); and HDL cholesterol, 0.9 [+ or -] 0.2 mmol/L (34 [+ or -] 6 mg/dL). Compared with placebo, the pharmacologically treated group experienced a 20% (95% CI, 14.8% to 24.3%) decrease in total cholesterol level, a 36% (CI, 28.4% to 43.5%) increase in HDL cholesterol level, a 26% (CI, 19.1% to 33.7%) decrease in LDL cholesterol level, and a 50% (CI, 40.5% to 59.2%) reduction in triglyceride levels. Focal coronary stenosis increased by 1.4% in the placebo group but decreased by 0.8% in the drug group (difference, -2.2 percentage points [CI, -4.2 to -0.1 percentage points]). A composite cardiovascular event end point was reached in 26% of patients in the placebo group and 13% of those in the drug group (difference, 13.7 percentage points [CI, 0.9 to 26.5 percentage points]). Side effects, particularly flushing and gastrointestinal in-tolerance, were more common in the drug group but rarely led to withdrawal from the study. Limitations: The study was small and used a composite clinical outcome. Whether improvements in angiographic findings were due to reductions in LDL cholesterol or increases in HDL cholesterol was not established. Flushing may have led to inadvertent unblinding in patients who were randomly assigned to active study drugs. Conclusions: A combination regimen aimed at increasing HDL cholesterol levels improves cholesterol profiles, helps prevent angiographic progression of coronary stenosis, and may prevent cardiovascular events in some people who exercise regularly and eat low-fat diets.

La dermatoscopia es una técnica no invasiva que ha demostrado mejorar la precisión diagnóstica en el carcinoma basocelular (CBC). Desde la descripción inicial llevada a cabo por Menzies et al., basada fundamentalmente en hallazgos asociados a la presencia de pigmento, se ha generado una importante cantidad de bibliografía útil en la práctica clínica diaria. De una forma práctica, podemos clasificar las estructuras dermatoscópicas asociadas al diagnóstico de CBC en estructuras pigmentadas, vasculares y no pigmentadas/no vasculares. Una de las aplicaciones más recientes de la dermatoscopia en el CBC trata de pronosticar el subtipo histológico mediante el examen dermatoscópico y permite fundamentalmente diferenciar entre el CBC superficial y no superficial. Sin embargo, la dermatoscopia también nos permite sospechar variantes agresivas con mayor riesgo de recurrencia. La exploración dermatoscópica exhaustiva en el seguimiento de pacientes con daño actínico o historia de múltiples CBC posibilita la detección de lesiones muy incipientes, con repercusiones terapéuticas y pronósticas importantes.

Abstract: In this study, titanium dioxide (TiO2) nanocolloid was synthesized through sol–gel method, and nonlinear optical properties were studied using z-scan method. The refractive index and other nonlinear optical properties of the nanomaterials were measured using z-scan technique. Also, a Fabry–Perot interferometer was utilized to explore the changes of output intensity from the colloid by using of optical bistability setup. The radiated power to the resonator was elevated till 20 mW for laser beam with the same spot size. Hysteretic loops have been observed due to optical bistability of the TiO2nano-composites and results were perfectly fitted with theoretical curves. Experiments were repeated for Au and Ag nanocolloid and also the mixture of the TiO2and metal nanocolloids. Meaningful amplification in nonlinear refractive index, absorption coefficient, and bistable response of the mixture occur due to plasmon resonance of metal nanoparticles.

Experience in the use of apremilast in clinical practice complements the information available from pivotal clinical trials.

The development of medications to treat cocaine use disorders has thus far defied success, leaving this patient population without pharmacotherapeutic options. As the dopamine transporter (DAT) plays a prominent role in the reinforcing effects of cocaine that can lead to addiction, atypical DAT inhibitors have been developed that prevent cocaine from binding to DAT, but they themselves are not cocaine-like. Herein, a series of novel DAT inhibitors were synthesized, and based on its pharmacological profile, the lead compound 10awas evaluated in phase I metabolic stability studies in mouse liver microsomes and compared to cocaine in locomotor activity and drug discrimination paradigms in mice. A molecular dynamic simulation study supported the hypothesis that atypical DAT inhibitors have similar binding poses at DAT in a conformation that differs from that of cocaine. Such differences may ultimately contribute to their unique behavioral profiles and potential for development as cocaine use disorder therapeutics.

Medication-assisted treatments are unavailable to patients with cocaine use disorders. Efforts to develop potential pharmacotherapies have led to the identification of a promising lead molecule, JJC8-091, that demonstrates a novel binding mode at the dopamine transporter (DAT). Here, JJC8-091 and a structural analogue, JJC8-088, were extensively and comparatively assessed to elucidate neurochemical correlates to their divergent behavioral profiles. Despite sharing significant structural similarity, JJC8-088 was more cocaine-like, increasing extracellular DA concentrations in the nucleus accumbens shell (NAS) efficaciously and more potently than JJC8-091. In contrast, JJC8-091 was not self-administered and was effective in blocking cocaine-induced reinstatement to drug seeking. Electrophysiology experiments confirmed that JJC8-091 was more effective than JJC8-088 at inhibiting cocaine-mediated enhancement of DA neurotransmission. Further, when VTA DA neurons in DAT-cre mice were optically stimulated, JJC8-088 produced a significant leftward shift in the stimulation-response curve, similar to cocaine, while JJC8-091 shifted the curve downward, suggesting attenuation of DA-mediated brain reward. Computational models predicted that JJC8-088 binds in an outward facing conformation of DAT, similar to cocaine. Conversely, JJC8-091 steers DAT towards a more occluded conformation. Collectively, these data reveal the underlying molecular mechanism at DAT that may be leveraged to rationally optimize leads for the treatment of cocaine use disorders, with JJC8-091 representing a compelling candidate for development.

Neurotransmitter:sodium symporters (NSS) terminate neurotransmission through Na+-driven reuptake of cognate neurotransmitters. Crystallographically, whereas both substrates and inhibitors have been found to bind in the central binding (S1) site of NSS, inhibitors were found to bind to a second binding (S2) site in the extracellular vestibule (EV) of transporters for leucine (LeuT) and serotonin. On the basis of computational and experimental studies, we proposed that substrates bind to the S2 site of LeuT as well and that substrate binding to the S2 site is essential for Na+-coupled symport. Recent binding experiments show that substrate (l-Trp) binding in the S2 site of MhsT, another bacterial NSS, is also central to the allosteric transport mechanism. Here, we used extensive molecular dynamics simulations combined with Markov state model analysis to investigate the interaction of l-Trp with the EV of MhsT and identified potential binding poses of l-Trp as well as induced conformational changes in the EV. Our computational findings were validated by experimental mutagenesis studies and shed light on the ligand binding characteristics of the EV of NSS, which may facilitate development of allosteric ligands targeting NSS.

The microstructure and mechanical properties of extruded Mg-Zn alloy containing Y element were investigated in temperature range of 300–450 °C and strain rate range of 0.001–1 s−1through hot compression tests. Processing maps were used to indicate optimum conditions and instability zones for hot deformation of alloys. For Mg-Zn and Mg-Zn-Y alloys, peak stress, temperature and strain rate were related by hyperbolic sine function, and activation energies were obtained to be 177 and 236 kJ/mol, respectively. Flow curves showed that the addition of Y element led to increase in peak stress and decrease in peak strain, and indicated that DRX started at lower strains in Mg-Zn-Y alloy than in Mg-Zn alloy. The stability domains of Mg-Zn-Y alloy were indicated in two domains as 1) 300 °C, 0.001 s−1; 350 °C, 0.01–0.1 s−1and 400 °C, 0.01 s−1and 2) 450 °C, 0.01–0.1 s−1. Microstructural observations showed that DRX was the main restoration mechanism for alloys, and fully dynamic recrystallization of Mg-Zn-Y alloy was observed at 450 °C. The instability domain in Mg-Zn-Y alloy was located significantly at high strain rates. In addition, the instability zone width of Mg-Zn and Mg-Zn-Y alloys increased with increasing strain, and cracks, twins and severe deformation were considered in these regions.

Several letters to the editor are presented in response to articles in previous issues including one on a battle in the North Korean town of Unsan in the November 13, 1950 issue, an article on the universe in the November 20, 1950 issue, and "Man or Dog?" in the November 20, 1950 issue.

Methotrexate (MTX) is the most frequently used conventional systemic drug in the treatment of psoriasis. Despite over 50years of experience in this setting, certain aspects of the use of this drug in clinical practice are still little standardized and poorly understood. For this reason, a group of 15 experts took part in a consensus development conference to achieve consensus on a series of recommendations on the use of MTX in psoriasis. The guidelines, which were developed on the basis of a systematic review of the literature, were validated by 2 rounds of voting and categorized by level of evidence and grade of recommendation. Before MTX can be used to treat moderate to severe psoriasis, the patient must be evaluated to assess the suitability of the treatment, including consideration of vaccination status and screening for tuberculosis and pregnancy. The recommended starting dose for a patient with no risk factors is 10 to 20mg/wk, the therapeutic dose for most patients is 15mg/wk, and the maximum dose is 20mg/wk. Most patients who respond to treatment will show improvement within 8weeks. Parenteral administration of MTX is desirable when there is a risk of erroroneous dosing, nonadherence, gastrointestinal intolerance, or inadequate response to the therapeutic dose taken orally. Noninvasive methods are preferred for monitoring hepatotoxicity. MTX is a good treatment option for patients with a history of cancer, but is not recommended in patients with chronic hepatitisB infection or individuals who are seropositive for human immunodeficiency virus.

Metotrexato (MTX) es el fármaco sistémico convencional más empleado en el tratamiento de la psoriasis. A pesar de que la experiencia en su uso se remonta a más de 50años, todavía existen aspectos en el manejo clínico poco estandarizados o conocidos. Bajo esta premisa, un grupo de 15 expertos participó en una conferencia de consenso en la que, a partir de una revisión sistemática y 2 rondas de validación previas, se validaron recomendaciones categorizadas por nivel de evidencia y grado de recomendación sobre el uso de MTX en la psoriasis.

Los fármacos biológicos han mostrado un excelente perfil en el tratamiento de la psoriasis moderada-grave. Sin embargo, existen situaciones de la práctica clínica habitual que se pueden beneficiar de combinaciones con los diferentes fármacos sistémicos, asi como de la fototerapia, permitiendo mejorar la eficacia, disminuir toxicidades o reducir los costes de tratar la enfermedad psoriásica. Hasta ahora la experiencia publicada de estas combinaciones es escasa pero los resultados son en muchos casos satisfactorios. En esta revisión se repasan las experiencias publicadas más relevantes con respecto a la combinación del fármaco biológico con más experiencia en este campo, etanercept, con metotrexato, acitretina, ciclosporina y fototerapia con ultravioleta B de banda estrecha. La experiencia procedente de la literatura puede ayudar a la hora de tomar decisiones importantes en el manejo de fármacos biológicos y sistémicos en la psoriasis moderada-grave.

Biologic drugs have provided excellent results in the treatment of moderate to severe psoriasis. Nevertheless, in routine clinical practice, combinations of biologic drugs with phototherapy or systemic drugs can increase efficacy, diminish toxicity, and reduce the cost of treatment. Published experience with these combinations is scarce, although the results are often satisfactory. This review examines the most relevant published experience in the combination of the most studied drug in this field—etanercept—with methotrexate, acitretin, ciclosporin, and narrowband UV-B phototherapy. Findings reported in the literature can help when taking major decisions on the management of biologic and systemic drugs in moderate to severe psoriasis.

As new antiangiogenic therapies have been introduced and added to the therapeutic arsenal against various types of cancer, previously unknown adverse effects have been detected. These effects negatively impact patients’ quality of life and can even make it necessary to suspend treatment. Adverse skin reactions occur in 90% of patients treated with angiogenesis inhibitors. In some cases, a correlation has been observed between the severity of reactions and treatment efficacy and tumor response. It is therefore extremely important that dermatologists be able to recognize and manage these reactions. Moreover, in order to avoid the unjustified withdrawal of potentially life-extending treatments, dermatologists must be able to differentiate between non-life-threatening reactions and life-threatening reactions that necessitate the suspension of treatment. In this review article, we analyze the main cutaneous adverse effects of the most common antiangiogenic agents.

Biologic therapy has represented a major advance in the treatment of moderate to severe psoriasis but its use depends upon the characteristics of the patient and the criteria applied by the dermatologist. The aim of this survey was to determine the criteria employed by dermatologists in the decision to use these drugs.

Silica coated multi-wall carbon nanotubes (MWCNTs), silica@MWCNTs and nanocomposites were synthesized by a sol-gel method. By using the synthesized nanocomposites and also CNTs as templates, silica nanotubes (silica-NTs) were prepared. The optical properties of fabricated nanocomposites and nanotubes were characterized by back-scattering micro Raman, UV/Vis/NIR and FT-IR spectra, which show the presence of CNTs structure in the nanocomposites. UV/Vis/NIR and FT-IR spectra also show the presence of silica compounds. The recorded spectra from UV/Vis/NIR and FT-IR also confirm the presence of silica compounds in the nanotubes. The results of FE-SEM imaging data indicate that the synthesized samples are MWCNTs coated uniformly by silica molecules, which act as the template to synthesize silica-NTs.

Calcium channel blockers are clinically useful vasodilators, used widely in the treatment of hypertension. These agents are reported to preserve or improve renal function in patients with essential hypertensive renal disease or diabetic renal disease. Among the classes of calcium channel blockers, dihydropyridine derivatives are widely used because of their potent vasodilating activity and weak cardiodepressant action. Mebudipine and dibudipine are two new 1,4-dihydropyridine calcium channel blockers that recently have been synthesized. In previous research mebudipine and dibudipine showed considerable relaxant effects on vascular and ileal smooth muscle cells. In this study we investigated the effects of these new drugs on vascular flow of isolated kidney of diabetic rat and compare their potencies to amlodipine. It is concluded that mebudipine and dibudipine (1–10 μM) are at least as potent as amlodipine in inhibiting PE-induced perfusion pressure in isolated kidney of diabetic rats. These new dihydropyridines improve kidney perfusion of diabetic rat in the setting of PE infusion. Similarly, amlodipine.

:Various treatment options are available for use in moderate-to-severe psoriasis and election is dependent upon the clinical criteria applied by the attending physician. We undertook a survey among dermatologists to assess the treatment of moderate-to-severe psoriasis currently used in clinical practice in Spain.

Skin diseases account for a high proportion of presenting complaints in primary health care. In Spain, the growing demand for consultations and the resulting longer waiting lists make it necessary to establish criteria for appropriate referrals to a specialist. This study aimed to investigate the characteristics of referrals from primary care centers to dermatology specialists as well as the correlation between the presenting complaint and the final dermatologic diagnosis.

In recent years there has been an increase in the size of the immigrant population consulting dermatology services in Spain. The aim of this study was to describe the epidemiological characteristics of this sector of the population in the health care area served by Miguel Servet Hospital in Saragossa, Spain.

In this work, soot free non-thermal plasma reforming was experimentally investigated. Experiments were conducted for gas temperatures up to 200°C, gas flow rate from 0.1 to 2 LPM and percentage mixture of oxygen to fuel gases (Propane-nitrogen) from 0 to 30%. The flow stabilized corona discharge device under pulsed corona operations will be discussed. The results show that; (1) up to 40% of propane was converted to hydrogen, ethylene, methane, propylene and ethane etc.; (2) the hydrogen selectivity is near 50% of reformed gas; (3) soot free condition can be achieved with more then 3% of oxygen in the fuel gases at 200°C. The fundamental discharge characteristics of the discharge devices and soot formation characteristics will be discussed in detail.

Solid waste disposal has become a major concern since there are a limited number of landfill disposal sites. In the past, incineration of solid wastes was considered a solution to the landfill site limitation since solid waste volume can be reduced to 1/6 by conversion to incinerator ash, and heat and electricity recovery from the incineration processes can be attained. The landfill of fly and bottom ashes has been considered a potential environmental hazard due to leaching of heavy metals from the ashes after landfill, hence recycling them as construction material is beneficial not only economically but also is less impacting on the environment in long term. In this work, two different thermal plasma processes for ash volume reduction (approximately 60 to 70% of the volume of incinerator ashes) based on the plasma torch and submerged three-phase arc processes were compared based on the treatment of ash from the same incineration source. Detailed solid product detoxicity characteristics for each process will be presented and compared.

Childhood acute lymphoblastic leukaemia is treated by combination chemotherapy with a number of drugs, almost always including the enzyme l-asparaginase (ASNase). Although the initial remission rate is quite high, relapse and associated drug resistance remain a problem. In vitro studies have demonstrated an adaptive increase in asparagine synthetase (AS) expression in ASNase-resistant cells, which is believed to permit ASNase-resistant human leukaemia cells to survive in vivo. The present results, obtained with ASNase-sensitive and -resistant human MOLT-4 leukaemia cell lines, illustrate that several other adaptive processes occur to provide sufficient amounts of the AS substrates, aspartate and glutamine, required to support this increased enzymic activity. In both cell populations, aspartate is derived almost exclusively from intracellular sources, whereas the necessary glutamine arises from both intracellular and extracellular sources. Transport of glutamine into ASNase-resistant cells is significantly enhanced compared with the parental cells, whereas amino acid efflux (e.g. asparagine) is reduced. Most of the adaptive change for the amino acid transporters, Systems A, ASC and L, is rapidly (12h) reversed following ASNase removal. The enzymic activity of glutamine synthetase is also enhanced in ASNase-resistant cells by a post-transcriptional mechanism. The results demonstrate that there are several sites of metabolic adaptation in ASNase-treated leukaemia cells that serve to promote the replenishment of both glutamine and asparagine.

Childhood acute lymphoblastic leukaemia (ALL) is treated by combination chemotherapy with a number of drugs, always including the enzyme l-asparaginase (ASNase). Although the initial remission rate is quite high, relapse and associated drug resistance are a significant problem. In vitro studies have demonstrated increased asparagine synthetase (AS) expression in ASNase-resistant cells, which has led to the hypothesis that elevated AS activity permits drug-resistant survival. The data presented show that not only is elevated AS expression a property of ASNase-resistant MOLT-4 human leukaemia cells, but that short-term (12h) treatment of the cells with ASNase causes a relatively rapid induction of AS expression. The results also document that the elevated expression of AS in ASNase-resistant cells is not fully reversible, even 6 weeks after ASNase removal from the culture medium. Furthermore, ASNase resistance, assessed as both drug-insensitive cell growth rates and decreased drug-induced apoptosis, parallels this irreversible AS expression. Mimicking the elevated AS activity in ASNase-resistant cells by overexpression of the human AS protein by stable retroviral transformation of parental MOLT4 cells is sufficient to induce the ASNase-resistance phenotype. These data document that ASNase resistance in ALL cells is a consequence of elevated AS expression and that although other drug-induced metabolic changes occur, they are secondary to the increased asparagine biosynthetic rate.

Photorefractive two-beam coupling and energy transfer in BaTiO3are studied at multiple wavelengths using He-Cd, He-Ne, and diode lasers. The photorefractive signal beam gain is measured as a function of the pump beam intensity, beam ratio intensity, spatial frequency of the grating, and angle between the grating vector and caxis of the crystal. The exponential gain coefficient is calculated from signal beam gain, and its dependence on the same parameters is studied. The dependence of the signal beam gain and exponential gain coefficient on spatial frequency are also evaluated theoretically and found to be in good agreement with the experimental data. Also, the signal beam gain is studied as a function of wavelength, and a very high value is obtained at 441.6 nm. Figure-of-merit parameters such as the maximum change in the refractive index, the space charge field at saturation, the trap density of the charge carriers, and the photorefractive sensitivity of the crystal are calculated from the experimental data. Since the absorption in BaTiO3varies strongly with wavelength, its influence has been included in the calculations of the figure-of-merit parameters. The results are discussed in the light of the present understanding of photorefractive phenomena in crystals. © 2000 Society of Photo-Optical Instrumentation Engineers.

It is controversial whether altered levels of TCR/CD3-associated signalling molecules play a role in the T-cell dysfunction of cancer patients. In multiple myeloma (MM), peripheral blood T (PBT) lymphocytes are functionally impaired by prolonged exposure to tumour cells, and so we investigated the organization of the TCR/CD3-associated signal transduction machinery. The aim of this study was two-fold: first, to investigate the levels of CD3ζ, p56lck, p59fyn, ZAP-70, protein kinase C-α (PKC-α) and phospholipase C-γ (PLC-γ) in MM PBT cells; second, to determine whether levels of expression were correlated with clinical or prognostic factors. Forty-four MM patients were studied and 25 age-matched normal donors served as controls. On average, PKC-α was the only significantly decreased (P<0.001) signalling molecule, whereas levels of CD3ζ, p56lck, p59fyn, PLC-γ and ZAP-70 were not statistically different. However, there was wide variation between individual patients, and levels for each single protein also varied. A 75% or greater decrease in protein expression was observed, ranging from 8% (p59fyn) to 68% (PCK-α) of MM patients. When patients were grouped according to the cut-off values of prognostic factors such as the serum levels of C reactive protein (CRP), β2-microglobulin (β2M), neopterin (NPT) and the labelling index (LI%) of bone marrow (BM) plasma cells, the only difference observed was the lower PKC-α expression in patients with high serum NPT values. None of the T-cell signalling molecule levels was affected by the duration of tumour exposure, calculated on the number of years and/or months that had elapsed since diagnosis, or by disease status. In conclusion, there was a significant decrease of PCK-α in MM T cells; however, neither this decrease nor the heterogenous levels of the other T-cell signalling molecules were clearly correlated with prognosis, duration of tumour exposure, and disease status.

Recent studies on eosinophilic fasciitis have lead to this investigation of eosinophilia in progressive systemic sclerosis and localized scleroderma.

A real-time visual approach for the calibration of phase step in image plane holography using BaTiO3crystal as a recording medium is reported. In this method, the diffuse object is illuminated symmetrically with two collimated beams and a pump beam is added at the crystal plane. Each illuminating beam generates an individual interferogram at the observation plane when the object is subjected to load. A phase shift to one of the illuminating beams results in the complete disappearance of the fringes due to phase reversal between the individual interferograms, and at 2 phase change, the fringe pattern is restored. After calibration, a single-beam illumination configuration is used for phase measurement. We present the theory of the method and experimental results for a centrally loaded diaphragm rigidly clamped along the periphery. © 1998 Society of Photo-Optical Instrumentation Engineers.

Despite its versatility and effectiveness in numerous studies, the vaccinia/HeLa cell expression model may not be optimal for the study of all transport proteins. To evaluate an alternative expression model for amino acid transport Systems ASC and XAG−, the mRNA content and transport activity encoded by human hippocampal ASCT1 cDNA and rat hippocampal EAAC1 cDNA, respectively, were measured in pDR2-cDNA-transfected human embryonic kidney 293 cells made competent by stable transfection with the Epstein–Barr neutral antigen-1 (EBNA-1) cDNA (293c18 cells) to evaluate the EBNA-1/293c18 expression system. The results show that (i) the EBNA-1/293c18 expression system results in a larger increase over background of Systems ASCT1 (6.4×) and EAAC1 (39×) transport activity than does the vaccinia/HeLa expression system (2.6× and 22×, respectively); (ii) transfection and hygromycin B selection for the pDR2 vector do not affect the endogenous transport velocities of Systems ASC, X−AG, or A; and (iii) the endogenous transport velocities of Systems ASC and XAG−in 293c18 cells were not affected by the expression of exogenous EAAC1 or ASCT1. We conclude that the EBNA-1/293c18 cell expression model represents a useful transient expression regimen to characterize mammalian amino acid transport proteins, especially for transporters that may exhibit relatively low activity in transient expression systems lacking a selection mechanism.

We tested the hypothesis that the constitutive glucose transporter (GLUT 1) in 3T3-L 1 adipocytes belongs to the family of glucose-regulated proteins which are transcriptionally regulated by glucose deprivation. Using cDNA probes for both GRP78 (BiP) and GLUT1, we show that the level of GRP78 mRNA increased by 15-fold within 24 h of glucose deprivation with little change in GLUT1 mRNA. The elevated GRP78 mRNA in turn led to a time-dependent increase in GRP78 protein. While glucose deprivation did not alter the expression of the normal glycoform of GLUT 1, a lower molecular weight glycoform accumulated with extended deprivation. Mannose and fructose, but not galactose, prevented the induction of GRP78 and accumulation of the abnormal GLUT1. Because GRP78 acts as a chaperone in other cell systems, we also sought evidence to support this activity in 3T3-L1 adipocytes. Using the technique of co-immunoprecipitation, we demonstrate that GRP78 bound several proteins unique to the glucose-deprived state. No deprivation-specific proteins could be detected in association with GLUT 1. These data lead us to conclude that GLUTl does not display characteristics of the glucose-regulated proteins, at least in 3T3-L1 adipocytes, a widely used model for differentiation, hormone action, and nutrient control. However, the mechanisms for activating traditional members of this family appear intact.

Dermoscopy is a noninvasive technique that has been demonstrated to improve diagnostic accuracy in basal cell carcinoma (BCC). The first dermoscopic model for the diagnosis of BCC, based mainly on the identification of pigmented structures, was described by Menzies and colleagues, and since then dermoscopy has generated an abundance of literature useful to routine clinical practice. From a practical perspective, dermoscopic structures associated with BCC can be classified as pigmented, vascular, or nonpigmented/nonvascular. One of the most recent applications of dermoscopy in BCC is as an aid to predicting histologic subtype and essentially differentiating between superficial and nonsuperficial BCC. It can also, however, help raise suspicion of more aggressive variants with a higher risk of recurrence. A thorough dermoscopic examination during follow-up of patients with actinic damage or a history of multiple BCCs can facilitate the detection of very incipient lesions and significantly impact treatment and prognosis.

Wu: Concert Pharmaceuticals, Inc.: Employment, Equity Ownership. Aslanian:Concert Pharmaceuticals, Inc.: Employment, Equity Ownership. Liu:Concert Pharmaceuticals, Inc.: Employment, Equity Ownership. Hogan:Concert Pharmaceuticals, Inc.: Employment, Equity Ownership. Tung:Concert Pharmaceuticals, Inc.: Employment, Equity Ownership, Membership on an entity's Board of Directors or advisory committees.

The article presents an obituary for Paul Weimann, a member of the Photographic Society of America (PSA).

Analyzes the financial report of the International Exhibition of Photography. Net profit of the exhibition; Entree fee of the exhibition; Reason for the high entrance fee of the 18th Ridgewood Camera Club International.

Discusses photography competitions and the things that a judge looks for in evaluating a photograph. Expectations of competitors from the judge; Basis and criteria for judging photographic works; Mechanical functions that competitors should consider.

ChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 100 leading journals. To access a ChemInform Abstract of an article which was published elsewhere, please select a “Full Text” option. The original article is trackable via the “References” option.