Ratios of T-cell immune-effectors with tumour associated macrophages and PD-1/PD-L1 axis immune-checkpoint molecules, as prognosticators in diffuse large B cell lymphoma: A population-based study

Background Risk-stratification of diffuse large B-cell lymphoma (DLBCL) requires identification of patients with disease that is not cured despite initial R-CHOP. Although the prognostic importance of the tumour microenvironment (TME) is established, the optimal strategy to quantify it is unknown. Methods The relationship between immune-effector and inhibitory (checkpoint) genes was assessed by NanoString™ in 252 paraffin-embedded DLBCL tissues. A model to quantify net anti-tumoural immunity as an outcome predictor was tested in 158 R-CHOP treated patients, and validated in tissue/blood from two independent R-CHOP treated cohorts of 233 and 140 patients respectively. Findings T and NK-cell immune-effector molecule expression correlated with tumour associated macrophage and PD-1/PD-L1 axis markers consistent with malignant B-cells triggering a dynamic checkpoint response to adapt to and evade immune-surveillance. A tree-based survival model was performed to test if immune-effector to checkpoint ratios were prognostic. The CD4*CD8:(CD163/CD68)*PD-L1 ratio was better able to stratify overall survival than any single or combination of immune markers, distinguishing groups with disparate 4-year survivals (92% versus 47%). The immune ratio was independent of and added to the revised international prognostic index (R-IPI) and cell-of-origin (COO). Tissue findings were validated in 233 DLBCL R-CHOP treated patients. Furthermore, within the blood of 140 R-CHOP treated patients immune-effector:checkpoint ratios were associated with differential interim-PET/CT+ve/-ve expression.

EIT as a tool to observe dual wavelength operation of a semiconductor laser

We propose a simplified technique for dual wavelength operation of an extended cavity semiconductor laser, and its characterization using electromagnetically induced transparency (EIT). In this laser cavity scheme light beam is made converging before it incidences on the cavity grating. The converging angle of the beam creates two longitudinal oscillating modes of resonating cavity. Frequency separation between the longitudinal modes are measured with the help of beat frequency generation in a photodiode and creating pair of EIT spectra in Rb vapor. The pair of EIT dips that are generated due to dual wavelength of this laser (that is used as control laser) can be used to estimate frequency difference between the generated wavelengths. Width of EIT spectra can be used to estimate line width of individual wavelength components.

Enhanced catharanthine and vindoline production in suspension cultures of Catharanthus roseus by ultraviolet-B light

Suspension cultures of Catharanthus roseus were used to evaluate ultraviolet-B (UV-B) treatment as an abiotic elicitor of secondary metabolites. A dispersed cell suspension culture from C. roseus leaves in late exponential phase and stationary phase were irradiated with UV-B for 5 min. The stationary phase cultures were more responsive to UV-B irradiation than late exponential phase cultures. Catharanthine and vindoline increased 3-fold and 12-fold, respectively, on treatment with a 5-min UV-B irradiation.

Two-dimensional tin disulfide nanosheets for enhanced sodium storage

Sodium-ion batteries (SIBs) are considered as complementary alternatives to lithium-ion batteries for grid energy storage due to the abundance of sodium. However, low capacity, poor rate capability, and cycling stability of existing anodes significantly hinder the practical applications of SIBs. Herein, ultrathin two-dimensional SnS2 nanosheets (3-4 nm in thickness) are synthesized via a facile refluxing process toward enhanced sodium storage. The SnS2 nanosheets exhibit a high apparent diffusion coefficient of Na+ and fast sodiation/desodiation reaction kinetics. In half-cells, the nanosheets deliver a high reversible capacity of 733 mAh g-1 at 0.1 A g-1, which still remains up to 435 mAh g-1 at 2 A g-1. The cell has a high capacity retention of 647 mA h g-1 during the 50th cycle at 0.1 A g-1, which is by far the best for SnS2, suggesting that nanosheet morphology is beneficial to improve cycling stability in addition to rate capability. The SnS2 nanosheets also show encouraging performance in a full cell with a Na3V2(PO4)3 cathode. In addition, the sodium storage mechanism is investigated by ex situ XRD coupled with high-resolution TEM. The high specific capacity, good rate capability, and cycling durability suggest that SnS2 nanosheets have great potential working as anodes for high-performance SIBs. © 2015 American Chemical Society.

An optimal weighted-average congestion based pricing scheme for enhanced QoS

Pricing is an effective tool to control congestion and achieve quality of service (QoS) provisioning for multiple differentiated levels of service. In this paper, we consider the problem of pricing for congestion control in the case of a network of nodes under a single service class and multiple queues, and present a multi-layered pricing scheme. We propose an algorithm for finding the optimal state dependent price levels for individual queues, at each node. The pricing policy used depends on a weighted average queue length at each node. This helps in reducing frequent price variations and is in the spirit of the random early detection (RED) mechanism used in TCP/IP networks. We observe in our numerical results a considerable improvement in performance using our scheme over that of a recently proposed related scheme in terms of both throughput and delay performance. In particular, our approach exhibits a throughput improvement in the range of 34 to 69 percent in all cases studied (over all routes) over the above scheme.

High-strength bulk Al-based bimodal ultrafine eutectic composite with enhanced plasticity

An in situ bulk ultrafine bimodal eutectic Al-Cu-Si composite was synthesized by solidification. This heterostructured composite with microstructural length scale hierarchy in the eutectic microstructure, which combines an ultrafine-scale binary cellular eutectic (alpha-Al + Al2Cu) and a nanometer-sized anomalous ternary eutectic (alpha-Al + Al2Cu + Si), exhibits high fracture strength (1.1 +/- 0.1 GPa) and large compressive plastic strain (11 +/- 2%) at room temperature. The improved compressive plasticity of the bimodal-nanoeutectic composite originates from homogeneous and uniform distribution of inhomogeneous plastic deformation (localized shear bands), together with strong interaction between shear bands in the spatially heterogeneous structure.

The effects of entacapone on cardiorespiratory, autonomic, and clinical responses in L-dopa-treated patients with Parkinson's disease

Rest tremor, rigidity, and slowness of movements-considered to be mainly due to markedly reduced levels of dopamine (DA) in the basal ganglia-are characteristic motor symptoms of Parkinson's disease (PD). Although there is yet no cure for this illness, several drugs can alleviate the motor symptoms. Among these symptomatic therapies, L-dopa is the most effective. As a precursor to DA, it is able to replace the loss of DA in the basal ganglia. In the long run L-dopa has, however, disadvantages. Motor response complications, such as shortening of the duration of drug effect ("wearing-off"), develop in many patients. In addition, extensive peripheral metabolism of L-dopa by aromatic amino acid decarboxylase and catechol-O-methyltransferase (COMT) results in its short half-life, low bioavailability, and reduced efficacy. Entacapone, a nitrocatechol-structured compound, is a highly selective, reversible, and orally active inhibitor of COMT. It increases the bioavailability of L-dopa by reducing its peripheral elimination rate. Entacapone extends the duration of clinical response to each L-dopa dose in PD patients with wearing-off fluctuations. COMT is important in the metabolism of catecholamines. Its inhibition could, therefore, theoretically lead to adverse cardiovascular reactions, especially in circumstances of enhanced sympathetic activity (physical exercise). PD patients may be particularly vulnerable to such effects due to high prevalence of cardiovascular autonomic dysfunction, and the common use of monoamine oxidase B inhibitor selegiline, another drug with effects on catecholamine metabolism. Both entacapone and selegiline enhance L-dopa's clinical effect. Their co-administration may therefore lead to pharmacodynamic interactions, either beneficial (improved L-dopa efficacy) or harmful (increased dyskinesia). We investigated the effects of repeated dosing (3-5 daily doses for 1-2 weeks) of entacapone 200 mg administered either with or without selegiline (10 mg once daily), on several safety and efficacy parameters in 39 L-dopa-treated patients with mild to moderate PD in three double-blind placebo-controlled, crossover studies. In the first two, the cardiovascular, clinical, and biochemical responses were assessed repeatedly for 6 hours after drug intake, first with L-dopa only (control), and then after a 2 weeks on study drugs (entacapone vs. entacapone plus selegiline in one; entacapone vs. selegiline vs. entacapone plus selegiline in the other). The third study included cardiovascular reflex and spiroergometric exercise testing, first after overnight L-dopa withdrawal (control), and then after 1 week on entacapone plus selegiline as adjuncts to L-dopa. Ambulatory ECG was recorded in two of the studies. Blood pressure, heart rate, ECG, cardiovascular autonomic function, cardiorespiratory exercise responses, and the resting/exercise levels of circulating catecholamines remained unaffected by entacapone, irrespective of selegiline. Entacapone significantly enhanced both L-dopa bioavailability and its clinical response, the latter being more pronounced with the co-administration of selegiline. Dyskinesias were also increased during simultaneous use of both entacapone and selegiline as L-dopa adjuncts. Entacapone had no effect on either work capacity or work efficiency. The drug was well tolerated, both with and without selegiline. Conclusions: the use of entacapone-either alone or combined with selegiline-seems to be hemodynamically safe in L-dopa-treated PD patients, also during maximal physical effort. This is in line with the safety experience from larger phase III studies. Entacapone had no effect on cardiovascular autonomic function. Concomitant administration of entacapone and selegiline may enhance L-dopa's clinical efficacy but may also lead to increased dyskinesia.

Polysaccharopeptide enhanced the anti-cancer effect of gammatocotrienol through activation of AMPK

Prostate cancer (PCa) frequently relapses after hormone ablation therapy. Unfortunately, once progressed to the castration resistant stage, the disease is regarded as incurable as prostate tumours are highly resistant to conventional chemotherapy. Therefore, an effective treatment strategy is urgently needed for improving the treatment outcome of the patients.

Kinetics of photocatalytic reduction of NO by CO with Pd2+-Ion-Substituted Nano-TiO2

The objective of the present study is to develop the reaction mechanism and kinetics of photoreduction of NO by CO. For this purpose, the reactions were conducted in the presence of Pd-ion-substituted nano-TiO2, Ti1-xPdxO2-delta, which was synthesized via a solution combustion method. The photocatalytic activity was investigated with unsubstituted TiO2, 1% Pd/TiO2(imp), and Ti1-xPdxO2-delta (where x = 0.05-0.3). No appreciable NO conversion was observed over unsubstituted TiO2, although, despite competitive adsorption of NO and CO on the Pd2+ sites, there was a significant reduction of NO over Ti1-xPdxO2-delta. The kinetic model showed that the enhanced catalytic activity is due to the NO photodissociation at the oxide-ion vacancy.

Enhanced adsorption capacity of activated alumina by impregnation with alum for removal of As(V) from water

Alum-impregnated activated alumina (AIAA) was investigated in the present work as an adsorbent for the removal of As(V) from water by batch mode. Adsorption study at different pH values shows that the efficiency of AIAA is much higher than as such activated alumina and is suitable for treatment of drinking water. The adsorption isotherm experiments indicated that the uptake of As(V) increased with increasing As(V) concentration from 1 to 25 mg/l and followed Langmuir-type adsorption isotherm. Speciation diagram shows that in the pH range of 2.8–11.5, arsenate predominantly exists as H2AsO4− and HAsO42− species and hence it is presumed that these are the major species being adsorbed on the surface of AIAA. Intraparticle diffusion and kinetic studies revealed that adsorption of As(V) was due to physical adsorption as well as through intraparticle diffusion. Effect of interfering ions revealed that As(V) sorption is strongly influenced by the presence of phosphate ion. The presence of arsenic on AIAA is depicted from zeta potential measurement, scanning electron microscopy (SEM) and energy-dispersive analysis of X-ray (EDAX) mapping study. Alum-impregnated activated alumina successfully removed As(V) to below 40 ppb (within the permissible limit set by WHO) from water, when the initial concentration of As(V) is 10 mg/l.

Enhanced dielectric response of ZrO2 upon Ti doping and introduction of O vacancies

We determine the electronic properties and dielectric response of zirconia (ZrO2) with oxygen vacancies (O vacancies) and Ti doping using first-principles density functional theory calculations based on pseudopotentials and a plane wave basis. We find significantly enhanced static dielectric response in zirconia with Ti doping and introduction of oxygen vacancies. Softening of phonon modes are responsible for the enhanced dielectric response of doped samples compared to pure zirconia.

Link route pricing for enhanced QoS

Pricing is an effective tool to control congestion and achieve quality of service (QoS) provisioning for multiple differentiated levels of service. In this paper, we consider the problem of pricing for congestion control in the case of a network of nodes under multiple service classes. Our work draws upon [1] and [2] in various ways. We use the Tirupati pricing scheme in conjunction with the stochastic approximation based adaptive pricing methodology for queue control (proposed in [1]) for minimizing network congestion. However, unlike the methodology of [1] where pricing for entire routes is directly considered, we consider prices for individual link-service grade tuples. Further, we adapt the methodology proposed in [21 for a single-node scenario to the case of a network of nodes, for evaluating performance in terms of price, revenue rate and disutility. We obtain considerable performance improvements using our approach over that in [1]. In particular, our approach exhibits a throughput improvement in the range of 54 to 80 percent in all cases studied (over all routes) while exhibiting a lower packet delay in the range of 26 to 38 percent over the scheme in [1].

Leveraging Partially Enhanced Scan for Improved Observability in Delay Fault Testing

Enhanced Scan design can significantly improve the fault coverage for two pattern delay tests at the cost of exorbitantly high area overhead. The redundant flip-flops introduced in the scan chains have traditionally only been used to launch the two-pattern delay test inputs, not to capture tests results. This paper presents a new, much lower cost partial Enhanced Scan methodology with both improved controllability and observability. Facilitating observation of some hard to observe internal nodes by capturing their response in the already available and underutilized redundant flip-flops improves delay fault coverage with minimal or almost negligible cost. Experimental results on ISCAS'89 benchmark circuits show significant improvement in TDF fault coverage for this new partial enhance scan methodology.

X-ray scattering and diffraction enhanced imaging studies of in vitro breast tissues

This thesis is a study of the x-ray scattering properties of tissues and tumours of the breast. Clinical radiography is based on the absorption of the x-rays when passing right through the human body and gives information about the densities of the tissues. Besides being absorbed, x-rays may change their direction within the tissues due to elastic scattering or even to refraction. The phenomenon of scattering is a nuisance to radiography in general, and to mammography in particular, because it reduces the quality of the images. However, scattered x-rays bear very useful information about the structure of the tissues at the supra-molecular level. Some pathologies, like breast cancer, produce alterations to the structures of the tissues, being especially evident in collagen-rich tissues. On the other hand, the change of direction due to refraction of the x-rays on the tissue boundaries can be mapped. The diffraction enhanced imaging (DEI) technique uses a perfect crystal to convert the angular deviations of the x-rays into intensity variations, which can be recorded as images. This technique is of especial interest in the cases were the densities of the tissues are very similar (like in mammography) and the absorption images do not offer enough contrast. This thesis explores the structural differences existing in healthy and pathological collagen in breast tissue samples by the small-angle x-ray scattering (SAXS) technique and compares these differences with the morphological information found in the DEI images and the histo-pathology of the same samples. Several breast tissue samples were studied by SAXS technique in the European Synchrotron Radiation Facility (ESRF) in Grenoble, France. Scattering patterns of the different tissues of the breast were acquired and compared with the histology of the samples. The scattering signals from adipose tissue (fat), connective tissue (collagen) and necrotic tissue were identified. Moreover, a clear distinction could be done between the scattering signals from healthy collagen and from collagen from an invasive tumour. Scattering from collagen is very characteristic. It includes several scattering peaks and scattering features that carry information about the size and the spacing of the collagen fibrils in the tissues. It was found that the collagen fibrils in invaded tumours were thinner and had a d-spacing length 0,7% longer that fibrils from healthy tumours. The scattering signals from the breast tissues were compared with the histology by building colour-coded maps across the samples. They were also imaged with the DEI technique. There was a total agreement between the scattering maps, the morphological features seen in the images and the information of the histo- pathological examination. The thesis demonstrates that the x-ray scattering signal can be used to characterize tissues and that it carries important information about the pathological state of the breast tissues, thus showing the potential of the SAXS technique as a possible diagnostic tool for breast cancer.

Enhanced Tetrahedral Ordering of Water Molecules in Minor Grooves of DNA: Relative Role of DNA Rigidity, Nanoconfinement, and Surface Specific Interactions

Confinement and Surface specific interactions call induce Structures otherwise unstable at that temperature and pressure. Here we Study the groove specific water dynamics ill the nucleic acid sequences, poly-AT and poly-GC, in long B-DNA duplex chains by large scale atomistic molecular dynamics simulations, accompanied by thermodynamic analysis. While water dynamics in the major groove remains insensitive to the sequence differences, exactly the opposite is true for the minor groove water. Much slower water dynamics observed in the minor grooves (especially in the AT minor) call be attributed to all enhanced tetrahedral ordering (< t(h)>) of water. The largest value of < t(h)> in the AT minor groove is related to the spine of hydration found in X-ray Structure. The calculated configurational entropy (S-C) of the water molecules is found to be correlated with the self-diffusion coefficient of water in different region via Adam-Gibbs relation D = A exp(-B/TSC), and also with < t(h)>.