Chronic myeloid leukemia (CML) is a blood cancer originated by expression of BCR-ABL, a constitutively activated kinase product of the chromosomal translocation t(9;22), in hematopoietic stem cells (HSC). Although tyrosine kinase inhibitors (TKI) can efficiently induce molecular remission in CML patients, drug discontinuation often leads to relapse caused by reactivation of leukemic stem cells (LSC) spared from TKI therapy via BCR-ABL-independent mechanisms of self-renewal and survival. Thus, there is a need for alternative drugs for relapse patients to prevent expansion of BCR-ABL-positive LSC during discontinuation of chemotherapy or emergence of chemoresistance. We found that somatic deletion of the reprogramming factor Kruppel-like factor 4 (KLF4) in BCR-ABL(p210)-induced CML severely impaired disease maintenance. This inability to sustain CML in the absence of KLF4 was caused by a progressive attrition of LSCs in bone marrow and the spleen and impaired ability of LSCs to recapitulate leukemia in secondary recipients. Analyses of global gene expression and genome-wide binding of KLF4 revealed that the dual-specificity tyrosine-(Y)-phosphorylation regulated kinase 2 (DYRK2) is repressed by KLF4 in CML LSCs. Immunoblots revealed elevated levels of DYRK2 protein that were associated with a reduction of c-Myc protein and increased levels of p53 (S46) phosphorylation and PARP cleavage in KLF4-deficient LSCs purified from the bone marrow of CML mice. Genomic silencing of KLF4 in the murine CML cell line 32D-BCR-ABL resulted in increased levels of DYRK2 and phosphorylated c-Myc (S62) leading to diminished levels of c-Myc protein, which was reverted by treatment with a proteasome inhibitor, suggesting that KLF4 prevents c-Myc degradation triggered by DYRK2-mediated priming phosphorylation. Consistent with an inhibitory role in leukemia, DYRK2 levels are significantly reduced both in CD34+CD38+ and CD34+CD38− cells from CML patients compared to normal stem/progenitor cells. Aiming at pharmacological activation of DYRK2 to abrogate self-renewal and survival of CML cells, we treated CML cells with vitamin K3 that inhibits Siah2, an ubiquitin E3 ligase involved in Dyrk2 proteolysis. Vitamin K3, and not Vitamin K1 and K2, induces dose-dependent cytotoxicity in a panel of human-derived CML cell lines by stabilizing Dyrk2 protein and consequently promoting c-Myc degradation. Interestingly, combination of vitamin K3 with Imatinib exhibit additive effect inducing cytotoxicity in CML cells. Collectively, the identification of Dyrk2 as a critical mediator of LSC downfall is a novel paradigm poised to support the development of LSC-specific therapy to induce treatment-free remission in conjunction with Imitinib in CML patients.

Disclosures No relevant conflicts of interest to declare.


Abstract #6046 Purpose: The recent ACO/CAP guidelines revised the cut-point for HER2 expression by immunohistochemistry (IHC) from 10% up to 30%. Recently we showed that heterogeneity of expression is a function of the assessed biomarker and, for HER2, >80% area of expression was most prognostic and predictive. Here we test this hypothesis in CALGB 9840, a prospective cooperative group clinical trial of Paclitaxel (P) and Trastuzumab (T).
 Experimental Design: Tissue from 274 cases selected from cases with available slides from the TH arm were first scored by pathologists as 0-3+, but then again scored to assess percentage of tissue staining with prospectively chosen cut points of >10%, >30% or >80%. Response was assessed by modified RECIST criteria, including complete and partial response. Stable disease and progressive disease were considered non-response.
 Results: Amongst the 176 cases treated with P+T there were 90 (52%) responses (PR+CR), 3 cases were unevaluable for response. In the subset of cases treated with T, there was inconsistent differences in the >10% vs the >30% categories but the >80% category was uniformly statistically significantly predictive of response. Receiver Operator Characteristic (ROC) curves constructed to assess prediction of response showed areas under the curves (AUC) of 0.59 for IHC and 0.60 for FISH suggesting both are failed tests for defining an optimal cut-point. However, selecting only the cases scored as 3+ shows an AUC of 0.72 and the optimal cut-point is for the test is at 95% positive 3+ HER2 staining. This modification of the cut-point would have denied T to 6 of the 49 patients who responded to therapy in the 3+ group. However, there were also 41 (of 86) patients in the 0,1+ and 2+ groups that responded to therapy, raising the possibility that the response in those 6 patients may have been unrelated to T therapy.
 Conclusions: When using clinical outcome to assess the value of the current tests for prediction of response to T, ROC curves suggest that both the old and new HER2 tests fail at defining an optimal cut-point. However, using only strongly positive cases (3+), an acceptable test can be achieved which is maximized at 95% area of expression. This cut-point, while statistically rigorous, is limited by the fact that the patients were treated with both P and T. This result suggests a similar analysis is warranted on a larger cohort of T treated patients, perhaps in the adjuvant or neoadjuvant setting. The availability of other options for HER2 amplified cases (ie lapatinib) and the increased use of T in the adjuvant setting warrant optimization of tests for the best possible patient selection. Citation Information: Cancer Res 2009;69(2 Suppl):Abstract nr 6046.


Diffuse large B-cell lymphoma (DLBCL) is a common, aggressive cancer of notorious genotypic and phenotypic heterogeneity. A major challenge is predicting response to drug treatment that has typically been done using genomic tools alone with little success. A novel method that incorporates phenotypic profiling for predicting the effectiveness of therapy for individual patients is desperately needed. BioDynamic Imaging (BDI) is a technique for measuring time-dependent fluctuations in back-scattered light through living tumor tissues to identify critical changes in intracellular dynamics that are associated with phenotypic response to drugs. In this study, BDI and RNA sequencing (RNA-seq) data were collected on tumor samples from dogs with naturally occurring DLBCL, an animal model of increasingly recognized relevance to the human disease. BDI and RNA-seq data were combined to identify correlations between gene co-expression modules and linear combinations of biomarkers to provide biological mechanistic interpretations of BDI biomarkers. Using regularized multivariate logistic regression, we combined RNA-seq and BDI data to develop a novel machine learning model to accurately predict the clinical response of canine DLBCL to combination chemotherapy (i.e. CHOP). Our model incorporates data on the expression of 4 genes and 3 BDI-derived phenotypic biomarkers, capturing changes in transcription, microtubule related processes, and apoptosis. These results suggest that multi-scale genomic and phenotypic data integration can identify patients that respond to a given treatment a priori in a disease that has been difficult to treat. Our work provides an important framework for future development of strategies and treatments in precision cancer medicine. Key Points Combined intracellular Doppler spectra and RNA-seq classify DLBCL samples as sensitive or resistance to CHOP chemotherapy Key dynamic features were identified that can be used to classify dogs with naturally-occurring DLBCL as CHOP-sensitive or -resistant


Twelve wetlands occurring in four different ecozones in Uttar Pradesh (UP), India, were selected for studying the winter composition and dynamics of avian populations. Wetland information was collected from office records of the UP Forest department. Bird populations were estimated by transect method and block-in-flock-in-sector method for woodland and aquatic birds, respectively. Across the twelve selected wetlands a total of 486,182 individuals belonging to 161 species of birds on 15,592 ha were recorded during the winter of 2010-11. The data were analyzed to assess the relationship between wetland characteristics and avian populations. Aquatic vegetation, surrounding vegetation, water availability and climate were found as important factors related to avian populations. January was found to be the peak of bird assemblage, while winter times before and after January were the waxing and waning period, respectively. Species richness and species diversity of aquatic birds varied between 18-58 and 1.90-3.20, respectively, and of all bird species between 23-109, and 1.73-3.81, respectively. The density of aquatic birds ranged between 17-384 ha -1 . The most common migratory birds in wetlands were Northern Pintail, Common Teal and Greylag Goose. Common resident birds included Asian Openbill, Darter, Little Egret, Common Coot, Little Cormorant, Grey Heron, Purple Heron, Indian Pond Heron, Common Moorhen, Purple Swamphen, Cattle Egret, Indian Sarus Crane and White-throated Kingfisher. For improved conservation of aquatic avian fauna, management prescriptions are suggested for wetlands under current management which could also be extended to other wetlands, whereas conservation of avian fauna to be the emphasis.


Although Turkey's agricultural sector is important in terms of national economy, it faces some important structural problems such as decrease in human capital in the agricultural sector. In order to solve these problems, within the "National Agricultural Project", a policy instrument named "Support for Young Farmers Projects" (YFPS) was added to the support in 2016. The aim of this study was to evaluate the criteria used in the selection of the beneficiaries of young farmers' support within the scope of YFPS in Turkey. A survey was prepared to determine what features young farmers benefiting from project support have and the extent to which the selection criteria served the purposes of the support program. The survey was conducted in the TR 71 Region, which is at the center of Turkey, in June-August, 2017. A total of 248 young farmers (139 supported, and 109 non-selected farmers for support) were interviewed. The methodology used in this study was the Categorical Regression. The results showed that the applicants who benefited more from YFPS were in the following order: Female> married> those aged 18-30> people from rural areas with a population of 1,000 or less> those with education in agricultural production> the disabled / martyr's relatives / ghazi, and those from enterprises with an annual income of TL 10,000 or less. YFPS has breathed new life into agriculture by encouraging youths in rural areas, but this support has to be aimed at creating economically sustainable and viable enterprises.


The programming and run-time environment used for the authors' multicomputer visualization software are described. The particular approach to using multicomputers for scientific visualization provides a uniform interface to system and communications facilities and promotes modularity and code reuse. No breakthrough technology is involved; rather, a collection of methods that have been developed by others has been optimized for visual computing applications and unified into a system that is simple to use and easy to port to new hardware. The C language is used. Initial experience with the system has been good.<<ETX>>


We address the advantages and disadvantages of maintaining the mandatory use of masks in health centers and nursing homes in the current epidemiological situation in Spain and after the declaration of the World Health Organization on May 5, 2023 of the end of COVID-19 as public health emergency. We advocate for prudence and flexibility, respecting the individual decision to wear a mask and emphasizing the need for its use when symptoms suggestive of a respiratory infection appear, in situations of special vulnerability (such as immunosuppression), or when caring for patients with those infections. At present, given the observed low risk of severe COVID-19 and the low transmission of other respiratory infections, we believe that it is disproportionate to maintain the mandatory use of masks in a general way in health centers and nursing homes. However, this could change depending on the results of epidemiological surveillance and it would be necessary to reconsider returning to the obligation in periods with a high incidence of respiratory infections.


The theory of nonreactive atom--diatom collisions in the presence of multiple electronic surfaces is developed in both space-fixed and body-fixed coordinate frames. The formalism is applied to the scattering of fluorine atoms by para- and ortho-hydrogen molecules. Coupled-channel computations of integral cross sections for fine structure and rotational transitions are carried out in the rigid rotor approximation using ab initio self-consistent-field potential energy surfaces and are facilitated by the use of a diabatic representation of the molecular channel states. The magnitudes of the cross sections at a specific translational energy are found in general to decrease with increasing energy defect. For F(/sup 2/P/sub 1/2/)+p-H/sub 2/ the cross section for a near resonant electronic-to-rotational energy transfer process dominates other inelastic transitions by at least an order of magnitude.


With the Increase in line lengths, power transmitted introduced a number of new problems in relation to protection. New methods have become necessary to handle such problem. Firstly important to see these lines are not unnecessarily disconnected, at the same time shorter operating times for protective relays are demanded on faulted section sections to preserve stability. Moreover, extreme variations of fault current are often encountered with long lines necessitating the protective relays to take this aspect. Two major types of transmission line protection been developed extensively to meet requirements are distance and carrier current systems. Pilot wire system of protection is not applicable to long and overhead transmission lines because of high cost of pilots and unreliability. Transmission line demo panel is designed to demonstrate fault clearing process on transmission line using distance (impedance) relay. The principle of operation of these relays depends on fault current and power factor under fault conditions. As a matter of fact such relays are designed to operate according to impedance of line up to fault point or ratio of voltage to current under fault condition. As fault impedance is proportional to distance of line from location of relay to fault point, relay indicates distance over which fault has occurred.


The integration of distributed energy resources for the production of electrical energy is related to the evolution of future power distribution networks in order to achieve: flexibility (meeting final user's requirements); accessibility (allowing access to local generation and particularly to renewables); reliability (ensuring the highest possible security and power quality levels); economy (allowing an adequate management of energy in an efficient and competitive way).In this framework, the paper presents some results of a joint research project involving five Italian universities. The focus is on the proposition and development of the main functionalities implemented into a centralized Distribution Management System (DMS) for the operation and control of the energy resources connected to distribution networks (generation, storage and loads) and of the network itself (automation systems, protection, etc.). Architecture, hierarchical structure and relevant functions for the control, operation and management of the active distribution network, are illustrated.


Fosfomycin is an antibacterial substance of low molecular weight and negligible binding to plasma proteins exhibiting in-vitro activity against most pathogens involved in bacterial meningitis including pneumococci. Due to these properties the drug has been recommended for therapy of central nervous system (CNS) infections. For this reason, fosfomycin at doses of 10, 40, 80 and 160 mg/kg/h iv, was investigated in the rabbit model of pneumococcal meningitis. Bacterial counts in cerebrospinal fluid (CSF) before, and 2, 5 and 8 h after initiation of therapy were quantitated by plating on blood agar. Fosfomycin concentrations in serum and CSF were determined by the agar well diffusion method. The MIC and MBC of fosfomycin for the Streptococcus pneumoniae type 3 strain used was 4 and 32 mg/L, respectively. The MIC of ceftriaxone was 0.016 mg/L. In vitro, both drugs showed an additive effect (fractional inhibitory concentration index = 0.75). In vivo at each dose tested, fosfomycin was less active than ceftriaxone (means +/- S.D.): delta log cfu/mL/h at 10 mg/kg/h + 0.130 +/- 0.062 (n = 2), at 40 mg/kg/h -0.217 +/- 0.185 (n = 3), at 80 mg/kg/h -0.270 +/- 0.121 (n = 3), at 160 mg/kg/h -0.331 +/- 0.118 (n = 3) vs -0.647 +/- 0.193 at 10 mg/kg/h ceftriaxone (n = 3). CSF penetration of fosfomycin as estimated by the CSF-to-serum concentration ratio at 8 h was 0.55 +/- 0.22 (n = 11). For bactericidal activity CSF concentrations of at least ten times the MIC were necessary. Coadministration of both drugs (1 mg/kg/h ceftriaxone + 40 mg/kg/h fosfomycin) tended to be more active than either drug alone (in-vivo drug interaction = 1.3). In conclusion, fosfomycin at very high doses reduced bacterial counts in CSF. However, fosfomycin CSF concentrations usually observed in patients with meningitis receiving fosfomycin were not bactericidal in this model. At all doses tested the bactericidal rate was lower than that of ceftriaxone. Fosfomycin is therefore unsuitable as a single agent, but may be used as a reserve antibiotic in combination with a newer cephalosporin for pneumococcal meningitis unresponsive to conventional therapy.


Dielectric, impedance, modulus and conductivity studies were performed over temperature 35 °C–600 °C and frequency 45 Hz–5 MHz range on the Lead Potassium Lithium Niobate (Pb 4.0 K 1.0 Li 1.0 Nb 10 O 30 , PKLN) ceramics. These studies established the conduction ion motion and polarization mechanism in the material. The dispersive dielectric loss at high temperature reveals the ionic conductivity. From frequency variation of e l response the pre-factor A(T) and critical exponent n(T) are evaluated, and are used in Jonscher's dielectric dispersion relation for e ' to fit with the experimental data. Complex impedance plots showed a non – Debye type relaxation, are used to evaluate the grain and grain boundary conduction and relaxation activation energies. DC and ac conduction activation energies are estimated from Arrhenius plots. Occupancy of Li + for C-sites gave a completely filled structure and enhanced the phase transition temperature to 520 °C compared to PKN. This is supported by the conduction activation energy in ferro region is more than the para region. Also, the dc conductivity characterized from bulk resistance and M ll peak frequency. Polaron hoping mechanism at room temperature has been confirmed via the linear variation of the plot log ( σ ac – σ dc ) as a function of log ω 2 . Stretched exponential parameter, β (0 β 1) has been evaluated from impedance plots, interpreted as a result of correlated motions between the Li +  ions and distribution of dielectric relaxation. Compared the results from different techniques, and discussed the conduction mechanism in the material.


Antenna selection is a simple but effective technique to enhance the performance of a spatial multiplexing multiple-input-multiple-output (MIMO) system. The selection criterion depends on the detector used at the receiver. For the maximum-likelihood detector, the criterion is to maximize the free distance. However, an exhaustive search is required to derive the distance, and the computational complexity can be prohibitively high. To avoid the exhaustive search, a lower bound of the free distance derived with the singular value decomposition (SVD) was then developed. This bound only involves the smallest singular value of the channel matrix, and its maximization can easily be conducted. An alternative lower bound of the free distance with the QR decomposition (QRD) was also derived in the literature. In this paper, we first propose a QRD-based selection method maximizing the lower bound. With some matrix properties, we theoretically prove that the lower bound yielded by the QRD is tighter than that by the SVD. We then propose a basis transformation method so that the lower bound yielded by the QRD can further be tightened. As a result, the QRD-based selection method can achieve near optimum performance. Finally, we extend the use of the proposed methods to other applications, such as receive antenna selection, joint transmit/receive antenna selection, and antenna selection in MIMO relay systems. Simulations show that the proposed selection methods can significantly outperform existing methods.


Novel static hybrid instabilities in smectic C liquid (SmC) crystal films are described. The Frederiks transition, well known for nematic liquid crystals, also takes place in smectic C layers, but here it is spatially periodic and coupled to undulations of the smectic layer. The Helfrich-Hurault undulational instability, typical for smectic A liquid crystals, occurs in SmC liquid crystals too, but the wave vector of the undulation of the layers is oblique to the applied external field. In addition, this modified Helfrich-Hurault instability not only involves layer undulations, but also contains deformations of the director field, which are typical for the Frederiks transition. The coupled deformations depend on all three coordinate axes, thus characterizing 3-dimensional patterns. There are parameter ranges, where both types of static instabilities, which differ by the spatial wave number, compete with each other near codimension-2 bifurcations.


Membranous cytoplasmic bodies (MCBs) were observed both in the intermediate cells of the stria vascularis and in the fibrocytes of the spiral ligament in normal cats. The MCBs in the intermediate cells were round or ovoid, ranged from 1 to 5 μm in diameter, and consisted of 2 to 40 or more layers disposed concentrically about a core. The core was composed of not only cytoplasm but also of mitochondria in various stages of disintegration, empty vacuoles, and many kinds of dense bodies similar to lysosomes. The MCBs in the fibrocytes were similar to those in the intermediate cells, but they were a little smaller in diameter and consisted of fewer than 10 layers. Both in the intermediate cells and in the fibrocytes, MCBs seem to have a phagocytic function.


Because of differences in their foraging patterns, different herbivores are likely to have different effects on plant fitness. We compared the effects of two contrasting patterns of leaf damage on the growth and reproduction of the wild gourd Cucurbita pepo ssp. texana. Plants were assigned to one of four damage treatments: (1) concentrated (15% damage on every third leaf); (2) dispersed (5% on each leaf); (3) high intensity (15% on each leaf); and (4) control (undamaged). We measured the growth rate of the main vegetative axis of the plants, internode length, the proportions of staminate and pistillate nodes, the proportions of staminate and pistillate buds that reached anthesis, the proportion of pistillate flowers that produced fruit, pollen production and pollen grain size, fruit production, fruit size, number of seeds per fruit, and seed size. Only one trait was significantly affected by the spatial pattern of damage: pollen production per flower increased under the concentrated but not the dispersed damage treatment. Fruit production showed a marginal decrease in the dispersed but not in the concentrated treatment. Very few traits were affected by foliar damage, regardless of the spatial pattern of distribution, suggesting that these plants have a high tolerance to simulated herbivory.


A reversible solid oxide fuel cell (RSOFC) system, consisting of a RSOFC stack, heat store, and electrical inverters to convert DC to AC power, is shown by computer modeling to have the potential to efficiently store electrical energy. This paper describes the modeling of a single RSOFC, based on a proposed cell geometry, empirical data on the resistivities of the components, and calculation of activation and diffusion polarization resistances from electrochemical theory. Data from ac impedance spectroscopy measurements on symmetrical cells are used to model RSOFC impedance. A RSOFC stack is modeled by electrically linking the individual cells inside a pressurized vessel. A phase change heat store is added to improve energy storage efficiency. The model is implemented in MATLAB®/Simulink®. Two competing inverter control schemes are compared, trading off DC bus ripple against AC power quality. It is found that selection of appropriate DC bus capacitance is important in certain scenarios, with potential system cost implications. It is shown that the system can store electrical energy at an efficiency of 64% over a single discharge–charge cycle, i.e., hydrogen to electricity and heat to hydrogen.


Layered Pnictides are proven to be a great reservoir for superconductors in the past and ternary zirconium pnictide chalcogenides of ZrXY-type (X = P, As; Y = S, Se) might be a platform for new superconductors. The superconducting properties of carefully grown (chemical transport reaction) single crystals of ZrP1.54S0.46 with a transition temperature of Tc = 3.5 K are investigated. This compound (PbFCl structure type) contains square planar nets: One of the nets is completely occupied (no vacancies) by P, the other one characterized by a random distribution of P and S (full occupation: no vacancies). Besides zero-field-cooling (zfc), field-cooling (fc), and remanent moment (rem) measurements, especially magnetization and ac susceptibility measurements are performed. A nearly ideal type-II behavior with a Ginzburg-Landau parameter = 24 is found. The magnetization curves between Bc1 and Bc2 for increasing field are in excellent agreement with theoretical calculations performed by E. H. Brandt based on the Ginzburg-Landau theory. The decreasing branches of the magnetization curves are asymmetric about the field axis indicating weak pinning and also large diamagnetic behavior. © 2016 The Authors. Published by Elsevier B.V. Peer-review under responsibility of the ISS 2015 Program Committee.


Naturally occurring potassium micas with a range of composition have been examined employing the analytical techniques of far infrared (IR) spectroscopy, X-ray powder diffraction (XRD), and major oxide and F analysis. Structure parameters predicted by geometric models, including torsional mode interlayer frequency (v,), d value (doo,), and b celL parameter are compared with those determined from structural refinement of potassium micas of similar composition. Differences are likely the result of assumptions inherent in the geometric models, including the frequency of the interlayer mode as a proxy for the K inner-O bond distance and the constancy ofthe combined octahedral-tetrahedral sheet thickness. Study of the IR, XRD, and chemical parameters shows the following relationships: (l) Solid solution of OH and F in trioctahedral structures significantly affects torsional vibrational modes, with increasing frequency correlating with increasing F. (2) Heating-induced dehydroxylation ofdioctahedral species and heating-induced oxidation ofFe2* trioctahedral species provide strong evidence that OH-orientation controls the frequency of the interlayer torsional mode. (3) Multivariate statistical analysis of potassium-mica intralayer sheet composition and the frequency of the interlayer torsional mode reveals a strong correlation between the vibrational frequency of the K interlayer torsional mode and octahedral sheet composition. The following preliminary formula is presented, assuming22 O equivalents per unit formula: z' (cm-') :79.6 + 0.96Mg'z* - 4.23Fe2* + 7.6lA13* * 9.09Fe3* - 4.65Li* + 2.20F . The frequency of the interlayer torsional mode directly reflects the tetrahedral sheet environment. This relationship therefore supports previous suggestions, based on XRD data alone, that the sheet dimensions and distortions of phyllosilicates are controlled largely by the composition of the octahedral layer. (4) Multiple-mode behavior provides evidence for the presence of compositionally different octahedral cation sites within a given structure. However, absorption spectra alone do not provide information about ordering of the octahedral environments.


Activin, a member of the TGFβ family inhibits cell growth in various target tissues. Activin interacts with a complex of two receptors that upon activation phosphorylate specific intracellular mediators, the Smad proteins. The activated Smads interact with diverse DNA binding proteins and co-activators of transcription in a cell-specific manner, thus leading to various activin biological effects. In this study, we investigated the role and mechanism of action of activin in the human breast cancer T47D cells. We found that activin treatment of T47D cells leads to a dramatic decrease in cell growth. Thus activin appears as a potent cell growth inhibitor of these breast cancer cells. We show that activin induces the Smad pathway in these cells but also activates the p38-mitogen-activated protein kinase pathway, further leading to phosphorylation of the transcription factor ATF2. Finally, specific inhibitors of the p38 kinase (SB202190, SB203580, and PD169316) but not an inactive analogue (SB202474) or the MEK-1 inhibitor PD98059 completely abolish the activin-mediated cell growth inhibition of T47D cells. Together, these results define a new role for activin in human breast cancer T47D cells and highlight a new pathway utilized by this growth factor in the mediation of its biological effects in cell growth arrest.


Originally developed mainly for solar energy utilization, the Ormat Closed Cycle Vapor Turbines were first applied to fossil-fuel on-site power generation in remote locations because of their inherent high reliability and low maintenance characteristics. Latterly, conditions changed and the technology has been reapplied to its original use: e.g. solar ponds, waste heat recovery and moderate temperature geothermal sources. This paper presents the results of actual field experience of operating some 3,500 turbogenerators in various applications.Copyright © 1985 by ASME


Human serum (pH 7.0) was incubated for 30 min at 0°C with ovalbumin-IgG anti-ovalbumin complexes in the presence of 50 µg/ml soybean trypsin inhibitor. After centrifugation and three washes at 0°C in a buffer containing 5 mM CaCl2 and 40 µg/ml STI (pH 7.0), C1̄r and C1̄s were resolubilized. From the C1̄s esterase activity and the SDS-polyacrylamide gel electrophoresis pattern, extracted C1̄r and C1̄s were found to be 75% activted. Complete activation was obtained by incubation for 30 min at 30°C before extraction.
 Extraction of C1q, C1r and C1s in the presence of calcium. At pH 7.5, C1̄r and C1̄s were both readily extracted by increasing relative salt concentrations above 0.15. In contrast, C1q extraction started at RSC = 0.30 and increased more slowly.
 C1̄r extraction paralleled C1̄s extraction as a function of pH, with a minimum at pH 7.0 and maxima at extreme pH values.


Inhibitors of cAMP phosphodiestereses (PDEs) promoted an increase in intracellular [cAMP]c and an influx of Ca, in both MMQ pituitary cells and αPancreatic cells. The specific targets for PDEs and the domains of PDEs are still unknown. Pituitary MMQ cells were used as a model to test modulation of calcium influx through the L-type calcium channel with PDE inhibitors. cAMP analogs were used to determine cAMP molecular targets. 8-cpt-cAMP initiated an Epac mediated pathway and had strong effects on calcium influx in the cell; suggesting, a relatively strong cAMP target. Experiments of α-Pancreatic cells were done in 2mM glucose and 8mM glucose to stimulate hypoglycemia and resting states respectively. Ca induced Ca release (CICR) was observed when αMSH was applied with the three PDE inhibitors. When αMSH was applied without a PDE inhibitor there was no increase in [cAMP]c, suggesting a micro domain. Extracellular solutions of 2mM glucose with PDE inhibitors such as Milironone, there was influx through N-type and L-type channels and then steady CICR. Rolipram decreased the amount of [Ca]c influx compared to the control, suggesting an inhibitory effect. PDE locations within the cell dictate the level of [cAMP]c increase and the influx of [Ca]c.


Abstract The fundamental interactions between naturally occurring pigments in light-harvesting systems are responsible for the high efficiency of the photosynthetic apparatus. We describe the role of carotenoids (Cars) in light-harvesting systems, including our work elucidating the mechanism of energy transfer from the optically dark Car singlet excited state (S1) to chlorophyll (Chl) and calculations on the electronic structure of Cars by means of time-dependent density functional theory (TDDFT). We highlight new studies on the charge-transfer state of the Car, peridinin (Per), which enhances the light-harvesting efficiency of the Car by increasing the electronic coupling to Chl. The role of another Car, zeaxanthin (Zea), is discussed with respect to its role in the mechanism of the feedback deexcitation quenching in green plants, a vital regulation process under light conditions which exceed photosynthetic capacity. Lastly, we provide insight on how the 96 Chls in Photosystem I are optimized to generate a pigment-protein complex which utilizes solar energy with near unit efficiency.


Weight gain is a serious health concern. People with mental illnesses are at increased risk of weight gain. The primary treatment is lifestyle changes such as increasing physical activity and dietary changes. This qualitative study explored the experience of people with schizophrenia who participated in a healthy lifestyle program. Four themes were identified. The findings indicate that benefits of the program were more than physical health improvements and included regular access to a health professional, gaining social relationships, and a sense of belonging. Future recommendations include retaining a group structure in lifestyle interventions to facilitate these additional benefits.


Nowadays there is an increasing need to facilitate the knowledge and research tool sharing and realize effective high-level collaboration among members of the same Virtual Organization. E-Science Gateways are t he primary solutions dedicated to support such needs. With EScience Gateways researchers can use grid infrastru ct re to run shared, well-tested applications customized to their own research field. In this paper the development lifec ycle of an e-Science Gateway is described, role definitions of a generic gridification process is provided and the general s teps of the application porting process are also identified. In the second part of the paper a developed external module of PGrade Grid Portal called Application Specific Module is introduced, which extends the portal's functionality set. This Application Specific Module allows developers to convert a gene ric PGRADE grid portal into a domain specific e-Science Gateway. At the end of the paper two case studies a re detailed, to show the development and usage possibi lities of the Application Specific Module.


To meet the future demand for highly educated labour, the "College Enrolment Expansion" policy was implemented in China at the end of the 20th century. But after a few years, new college graduates found it hard to get skilled jobs and some of them were unemployed. Many college graduates had to do unskilled work, living in groups, settling on fringes of cities—they are called "Ants". Unlike some scholars who blame the "Ants" problem on market frictions or barriers, this thesis indicates the core reason is that the capability of these graduates was not recognized by employers because they could not match skilled job requirements. Lack of qualified lecturers and resources, and course programs that were out of touch with work requirements led to a quality decline in teaching as colleges expanded, so students could not learn enough skills before graduation. The thesis develops a concept of market recognition to study this phenomenon. Market recognition is the degree of recognition of some group of persons as perceived by employers in the labour market. It is a competitive concept. When persons try to find jobs, they always face competition. Market recognition is a reflection of workers' capabilities in the employers' view and determines the chance for persons to win in the competition for job vacancies. For example, a primary-educated worker cannot get a technician job when competing with a higher-educated worker because his capability is not recognized by the employer when comparing with the higher-educated worker. Many new college graduates' lack of success in finding skilled jobs was due to their failure in competing with other experienced college-educated persons. We develop a labour market module as an extension of the computable general equilibrium (CGE) model to depict this process in history. In the module, workers are classified by six occupation types and three education levels; different types of labour compete with each other when seeking jobs; labour flows between occupations through a dynamic job vacancy chain, in which job vacancies emerge and then are filled by winners in job competition in each time; market recognition will determine who is the winner. We develop a very detailed baseline to replicate the history that the worsening situation for college graduates to find skilled jobs. In this baseline, structural changes in China's GDP components, employment, sectoral output, consumption, imports and exports are captured as well as many macro indicators and price indices. It means our model has traced the features of China's economic growth, which provides an accurate background for labour market transition. Inside the labour market, we inform the model of occupational and educational wage gap changes, numbers of unemployment, numbers of new school graduates and yearly "Ants" entry. Under these constraints, our labour market module draws a potential labour transition matrix for each year, in which labour flows between occupations in each education level are captured as well as changes of the market recognition of new college graduates. In the baseline of history replication, our model reveals a strong positive demand shift for college-educated labour in China since 1998, which is mainly caused by new technology requirements and the rapid expansion of highly-educated-intensive sectors. The baseline also captures the rapid increasing demand for college-educated labour, accompanied by a high unemployment rate of college graduates in these years. Taking account of historical wage adjustment and demand shifts, the baseline clearly reveals that the market recognition of college graduates experienced a continuous decline during college expansion, which explains the increasing number of "Ants" and high college graduate unemployment rates. On one side, new college graduates thought they had college degrees and deserved skilled jobs; on the other side, employers did not recognize capabilities of these graduates and would not provide them skilled jobs. As a result, more and more new college graduates had to do unskilled jobs or became unemployed. For example, the labour transition matrix tells that over 50% of new college graduates could get technician jobs and the unemployment rate of college graduates was below 8% in 1997; while in 2011, only 11% of college graduates became technicians directly and the corresponding unemployment rate was 12%. The plan of college expansion is to increase labour supply of the highly educated to meet the future demand for skilled workers, but the decline of the market recognition of college graduates made it inefficient. "Ants" are considered as a loss in effective highly educated labour supply, and a counterfactual simulation is designed to assess its effect and the corresponding cost to China's economy. In the simulation, the market recognition of college graduates is assumed to decline less than what happened in history. The result indicates the unemployment rate of college graduates would drop sharply due to this reduced decline; the equivalent losses in effective highly educated labour supply are approximately five million persons to 2011; and the corresponding cost to the level of China's annual GDP is above 0.3%.


The inducible nitric oxide synthase (iNOS) has been suggested to play an important role in the pathogenesis of asthma by contributing to eosinophilia and the ensuing oxidative damage after allergen exposure. IL-5 was shown to induce iNOS expression and that a reduction in iNOS expression reduces airway recruitment of eosinophils in response to allergen exposure. We recently showed that PARP-1 also plays a critical role in the pathogenesis of the disease by promoting eosinophil recruitment by participating in the cascade leading to IL-5 production. Here, we investigated the interrelationship between PARP-1 and iNOS in inducing eosinophilia. Our results show that iNOS gene deletion reduces eosinophil recruitment but to lesser degree as compared to PARP-1 gene deletion, suggesting a partial role for this protein in airway inflammation. PARP-1 gene deletion severely reduced iNOS expression in the airways of ovalbumin (allergen)-challenged mice and consequent nitration of target proteins and this phenomenon was closely associated with an impairment of p65 NF-κB nuclear translocation and phosphorylation of its inhibitor, I-κBα. IL-5-intranasal administration restored the eosinophilia in ovalbumin-challenged PARP-1−/− mice but did not reverse iNOS expression, suggesting that iNOS may be dispensable for eosinophil recruitment after IL-5 production. Altogether, our results further support the role of PARP-1 in the process of eosinophil recruitment during allergen-induced lung inflammation and provide evidence for a potential specific relationship between PARP-1 and iNOS.
 Support: NIH-HL072889 and 1P20RR18766 to HB.


This paper has described the radar absorbing materials characterization and radar cross section measurements, in the frequency range of 8 to 12 GHz, using a very simple setup. Simple targets like sphere, cylinder, flat plate, and dihedral corner were characterized by measuring the backscattered radiation patterns when these targets were illuminated by monostatic microwave radiation. Measurements were carried out inside an anechoic chamber (9x5x4m 3 ). Typical radar cross section patterns were obtained in different aspect angles, by rotating the targets around their vertical axes. The measured values and the theoretical previsions for each metallic target showed that the used setup guarantees a good precision of the obtained data. By recovering one of the targets, a cylinder, with a specific radar absorbing material developed at Materials Division of the Brazilian Aeronautics and Space Institute, it was possible to compare the obtained patterns and to discuss the influence of radar absorbing materials on the observed radar cross section reduction patterns. The used methodology showed to be useful for attending aeronautical and telecommunication applications.


In the past decade, to help maintain political stability and promote economic growth, South Korea has committed substantial resources to commercialized sports, including golf. A major source of support for building golf courses has come from government leaders and economic and social incentives as well. In the past 4 years the government has given permission to build 135 new golf courses. The official government discourse about the new golf courses is that they are being built in the interest of "sport for all." But the golf courses overwhelmingly require membership, which is extremely expensive. Despite the enormous power and resources of the dominant groups in Korea, there are elements of opposition. The golf boom has been severely criticized because it removes large amounts of land from agricultural and industrial productivity, contaminates farm land, and pollutes water. It also represents the worst aspects of the social imbalance of wealth.


The SERS is enhanced when KCl is added to silver colloid and cation molecule. The hypothesis supposed that Cl- bridged between nano-silver and molecule, as a result the molecule adsorbing on nano-silver surface is promoted and the SERS is therefore enhanced. The CN- and NH3 can be better adsorbed when they are added separately to the nano-silver particles, Cl- and anion molecule. The SERS reduces when CN- and NH3 are added separately to Cl-, anion molecule and silver colloid. The result is that the CN- and NH3 are so strong that they have replaced Cl- and anion molecules. Therefore the SERS reduces. This has proved the bridge role of Cl-.


Recent findings have challenged the current view of Plasmodium falciparum (P falciparum) blood-stage biology by demonstrating the cytoadhesion of early ring-stage-infected erythrocytes (rIEs) to host endothelial cells and placental syncytiotrophoblasts. The adhesion of rIEs was observed only in parasites that bind to the placenta via chondroitin sulfate A (CSA). In this work, a panel of mouse monoclonal antibodies (mAbs) that specifically inhibit cytoadhesion of rIEs but not of mature IEs was generated The previously described ring surface protein 2 (RSP-2), a 42-kDa protein, was identified as the target of the ring-stage-specific mAbs. Time course surface fluorescence experiments revealed a short overlap (approximately 4 hours) of expression between RSP-2 and P falciparum erythrocyte membrane protein 1 (PfEMP1). Their consecutive expression enables IEs to adhere to endothelial cells during the entire blood-stage cycle. During this study, a new phenotype was detected in parasite cultures, the adhesion of normal erythrocytes (nEs) to endothelial cells. All adherent nEs were coated with RSP-2. Immunolocalization studies show that RSP-2 is a rhoptry-derived protein that is discharged onto the erythrocyte membrane during contact with merozoites. Our results identify RSP-2 as a key molecule in sequestration of young blood-stage forms and nEs to endothelial cells.


We report the analysis results of far-ultraviolet (FUV) observations, made for a broad region around α Vir (Spica) including the interaction zone of Loop I and the Local Bubble. The whole region was optically thin and a general correlation was seen between the FUV continuum intensity and the dust extinction, except in the neighborhood of the bright central star, indicating the dust scattering nature of the FUV continuum. We performed Monte Carlo radiative transfer simulations to obtain the optical parameters related to the dust scattering as well as to the geometrical structure of the region. The albedo and asymmetry factor were found to be 0.38 ± 0.06 and 0.46 ± 0.06, respectively, in good agreement with the Milky Way dust grain models. The distance to and the thickness of the interaction zone were estimated to be 70 pc and 40 pc, respectively. The diffuse FUV continuum in the northern region above Spica was mostly the result of scattering of the starlight from Spica, while that in the southern region was mainly due to the background stars. The C iv λλ1548, 1551 emission was found throughout the whole region, in contrast to the Si ii* λ1532 emission which was bright only within the H ii region. This indicates that the C iv line arises mostly at the shell boundaries of the bubbles, with a larger portion likely from the Loop I than from the Local Bubble side, whereas the Si ii* line is from the photoionized Spica Nebula.


A pivotal question in Automatic Speech Recognition (ASR) is the robustness of the trained models. In this study, we investigate the combination of two methods commonly applied to increase the robustness of ASR systems. On the one hand, inspired by auditory experiments and signal processing considerations, multi-band band processing has been used for decades to improve the noise robustness of speech recognition. On the other hand, dropout is a commonly used regularization technique to prevent overfitting by keeping the model from becoming over-reliant on a small set of neurons. We hypothesize that the careful combination of the two approaches would lead to increased robustness, by preventing the resulting model to over-rely on any given band. To verify our hypothesis, we investigate various approaches for the combination of the two methods using the Aurora-4 corpus. The results obtained corroborate our initial assumption, and show that the proper combination of the two techniques leads to increased robustness, and to significantly lower word error rates (WERs). Furthermore, we find that the accuracy scores attained here compare favourably to those reported recently on the clean training scenario of the Aurora-4 corpus.


This Note argues that the OVDP's value depends on the taxpayer's exposure to willful FBAR penalties. This Note also provides a guide to willfulness in FBAR violations. The OVDP is a program that the IRS adopted as part of its recent crackdown on taxpayers with undisclosed offshore bank accounts. The OVDP provides taxpayers with amnesty from willful FBAR penalties. On the other hand, entering the OVDP can be an expensive and protracted ordeal. For taxpayers with a high risk of facing willful FBAR violations, the OVDP is a good deal. For other taxpayers, the OVDP is an unnecessary ride. Deciding whether or not to enter the program is difficult because there is a dearth of guidance regarding what makes an FBAR violation willful. There are very few criminal FBAR cases and there are only two civil FBAR cases. This Note examines judicial guidance on willfulness in other contexts and extrapolates principles of willfulness that apply to FBAR violations. Using these principles, this Note examines the FBAR cases to identify current judicial thinking on FBAR willfulness. This exercise indicates that there is currently a strong inclination to find that FBAR violations are willful. This makes entering the OVDP more compelling and a better deal for taxpayers than it may seem.


The double revolving fiber positioning technology is one of the key technologies for the success of the Large Sky Area Multi-Object Fiber Spectroscopic Telescope (LAMOST). The accuracy of fiber positioning will directly affect the observation efficiency of LAMOST. To achieve higher fiber positioning accuracy, the original open-loop controlled fiber positioning system urgently needs to be upgraded into a closed-loop control system. The fiber detection is the most important part of the closed-loop controlled fiber positioning system. The back-illuminated detection method is usually used to detect the fiber position by directly detecting the light spot generated at the fiber end in the multi-fiber spectral surveys. In this paper, we introduce a new method to measure the fiber position based on the image of the front-illuminated LAMOST focal plane. The front-illuminated image does not require lighting devices inside the spectrograph, and it could reduce the instability and light pollution in the spectrograph end. Our method measures the fiber position by fitting the profile of the fiber pinhole with a 2D Gaussian function. A series of tests show that the relative position measurement precision of the front-illuminated method is about 0.″12, and the method could have the same accuracy as the back-illuminated method once the system bias is calibrated by a simple radial correction function. The required fiber positioning accuracy of LAMOST is 0.″4, and the new method satisfies the requirement of LAMOST fiber detection accuracy and could be used in the closed-loop fiber control system.


Macrophages are heterogeneous leukocytes regulated in a tissue- and disease-specific context. While in vitro macrophage models have been used to study diseases empirically, a systematic analysis of the transcriptome thereof is lacking. Here, we acquired gene expression data from eight commonly-used in vitro macrophage models to perform a meta-analysis. Specifically, we obtained gene expression data from unstimulated macrophages (M0) and macrophages stimulated with lipopolysaccharides (LPS) for 2–4 h (M-LPSearly), LPS for 24 h (M-LPSlate), LPS and interferon-γ (M-LPS+IFNγ), IFNγ (M-IFNγ), interleukin-4 (M-IL4), interleukin-10 (M-IL10), and dexamethasone (M-dex). Our meta-analysis identified consistently differentially expressed genes that have been implicated in inflammatory and metabolic processes. In addition, we built macIDR, a robust classifier capable of distinguishing macrophage activation states with high accuracy (>0.95). We classified in vivo macrophages with macIDR to define their tissue- and disease-specific characteristics. We demonstrate that alveolar macrophages display high resemblance to IL10 activation, but show a drop in IFNγ signature in chronic obstructive pulmonary disease patients. Adipose tissue-derived macrophages were classified as unstimulated macrophages, but acquired LPS-activation features in diabetic-obese patients. Rheumatoid arthritis synovial macrophages exhibit characteristics of IL10- or IFNγ-stimulation. Altogether, we defined consensus transcriptional profiles for the eight in vitro macrophage activation states, built a classification model, and demonstrated the utility of the latter for in vivo macrophages.


Social media have been adopted by many businesses. Many companies are using social media tools such as Facebook and Twitter to provide various services and interact with customers. As a result, a large amount of user-generated content is freely available on social media sites. To increase competitive advantage and effectively assess the competitive environment of businesses, companies need to monitor and analyze not only the customer-generated content on their own social media sites, but also the textual information on their competitors' social media sites. In an effort to help companies understand how to perform a social media competitive analysis and transform social media data into knowledge for decision makers and e-marketers, this paper describes an in-depth case study which applies text mining to analyse unstructured text content on Facebook and Twitter sites of the three largest pizza chains: Pizza Hut, Domino's Pizza and Papa John's Pizza. The results reveal the value of social media competitive analysis and the power of text mining as an effective technique to extract business value from the vast amount of available social media data. Recommendations are also provided to help companies develop their social media competitive analysis strategy.


This research examines the influence of job satisfaction and three dimensions of organizational commitment (i.e., affective, continuance, and normative) on the intention to leave, job search activity, performance, and leadership effectiveness of executives. Job satisfaction and the commitment dimensions were hypothesized to negatively predict the retention-related variables. Results generally supported the hypotheses. Job satisfaction had the strongest relationship, but both affective and continuance commitment showed an incremental effect even in the presence of job satisfaction. We also hypothesized that job satisfaction and affective commitment would positively and continuance commitment would negatively associate with general performance and leadership. As predicted, job satisfaction associated positively with performance, though not with leadership. Continuance commitment negatively associated with both performance and leadership.


A technique for the time-variant analysis of quadratic phase coupling (QPC) in heart rate data is introduced and tested in 6 human neonates during quiet sleep. The set up of the approach is based up on the assumption that QPCs in the heart rate variability (HRV) are related to amplitude modulation effects. The application of the biamplitude deals with the detection of the coupling pattern and the bicoherence is used for the statistical quantification of coupling. By means of the results of bispectral analysis the time-variant processing has been adapted. The frequency-selective complex demodulation of the HRV leads to the envelope of the respiratory sinus arrhythmia (RSA), this has been used as one input for a time-variant coherence analysis. The other input is the low-pass filtered 10-second-rhythm of the HRV. A time-continuous quantification of the QPC, caused by amplitude modulation (10-second-rhythm modulates the RSA), is possible using this approach. According to our observed results in neonatal HRV both a phase co-ordination between the 10-second-rhythm and RSA as well as a non-linear coupling (amplitude modulation) between these HRV components can be seen.


Removal efficiency of phenol from aqueous solutions was determined using Pseudomonas putida (NCIM 2102). Experiments were made as a function of pH (4 - 9), temperature (28 - 36oC), and agitation speed (100 - 200 rpm). Optimization of these three process parameters for phenol degradation was studied. Statistically designed experiments using response surface methodology was used to get more information about the significant effects and the interactions between these three parameters. A 23 full-factorial central composite design was employed for experimental design and for analysis of the results. A second order polynomial regression model, has been developed using the experimental data. It was found that the degrading potential of P.putida (NCIM 2102) was strongly affected by the variations in pH, temperature and agitation speed. The experimental values were in good agreement with the predicted values and the correlation coefficient was found to be 0.9871. The optimum process conditions for maximizing phenol degradation were recognized as follows: pH (7.49), temperature (29.99oC), and agitation speed (138.89) rpm.


Even though global trade has fluctuated over the years, it has also rapidly increased. However, the structure and pattern of trade vary significantly by-products and regions. Undoubtedly, trade has come with both benefits and daunting challenges to countries involved, especially in African nations, where primary and intermediate merchandise formed a substantial share of exports. Because advanced and newly industrialized econo- mies have better technology and know-how, manufacturing industries, access to finance, and market than Africa, they have a greater market proportion in the world trade. Arguably, African countries have been left in the cold as they struggle to compete with advanced economies. As presented in this chapter, Africa has been struggling to be rel- evant in the world market. However, its global share of merchandise trade has reduced over the decades. This is partly because the continent has concentrated on the exportation of few primary commodities (i.e., mineral fuels, iron ores, gold, cocoa beans) with volatile prices and demand in the global markets. The frequent global oil crunch other raw prod- ucts are a wake-up call for a rapid industrialization and diversification for competitiveness in Africa. The World Trade Organization (WTO) has to ensure that defensive trade remedies should not be the next frontier of protectionism. Finally, for trade, growth, and development to be stimulated, African countries should urgently open their markets to expand intra-African trade.


The genus Cavia occurs in South America, mainly in grasslands. We collected blood samples from 97 individuals in six field populations and analyzed them with RAPD molecular markers. One wild type (C. anolaimae) was differentiated from the domestic form (C. porcellus), in agreement with other authors who used morphological, osteological and karyotipic results. Genetic diversity was considerable in both species, but higher in C. porcellus. The levels of genetic heterogeneity were also higher among the populations of C. porcellus (F(ST) = 0.254) than among the populations of C. anolaimae (F(ST) = 0.118). These significant levels of genetic heterogeneity, and the low levels of gene flow, were consistent with a complex domestication process for Cavia porcellus.


General Comment: Title of the manuscript: "The paradox of assessing greenhouse gases from soils for nature based solutions" addresses an important topic and will help to improve our understanding of the greenhouse gas fluxes from the soils. Manual chamber techniques are currently widely used for measuring the three GHG fluxes from soils, since they allow parallel deployment of multiple treatments and lands. However, it requires a lot of care and post-field lab analyses thus limiting temporal representations due to its labourintensive nature. Since soil N2O and CH4 exhibit sporadic peaks due to their time resolution, a significant problem may arise here; however, CO2 may not be a big concern since it tends to be highly autocorrelated. The availability of automatic chamber sampling thus improves this time resolution concern but they are quite pricey.


After 2007 year the world economy entered not only a financial crisis, but also structural changes in the international division of labor. The crisis affected different sectors and trading partners, which influences their position in the global economy. While world trade has returned to a dynamic growth path since 2011, the global economy has undergone qualitative change due to the decline in exchange of well-developed countries and growth in trade of New Industrial Countries (NIC). The emerging trends of trade after the crisis is worth examining, for at least two reasons: firstly, because, through the crisis, they verify the theories of international trade, while at the same time giving a response — the thesis of which theories correspond to modern reality. Secondly, they shed light on the shaping of the future division of labor in the global economy and the new balance between sectors and partners. After 2007, international exchange was growing by increasing the demand for technologically advanced products, on diversity, and on services. The increase of NIC in global trade points to the importance of competitiveness factors, diffusion of knowledge and development of Global Value Chains. The EU and the USA are seeing the steady progress of NIC, especially when it comes to exchanging office and telecommunications equipment, chemicals, computers, construction and travel services, but they are of marginal importance when it comes to charges for intellectual property rights.


This report documents the first case of biliary coccidiosis in the ferret. Multiple life stages of a coccidian parasite, including meronts, gametocytes, and oocysts were present in the epithelium of hepatic bile ducts and the gallbladder. Based on morphologic characteristics, the organisms were identified as Eimeria sp., most likely E. furonis.


Microsomal fractions were prepared from canine and bovine airway smooth muscle (ASM) by differential and gradient centrifugations. Surface membrane vesicles were characterized by binding assays and incorporated into planar lipid bilayers. Single-channel activities were recorded in symmetric or asymmetric K+ buffer systems and studied under voltage and Ca2+ clamp conditions. A large-conductance K(+)-selective channel (greater than 220 pS in 150 mM K+) displaying a high Ca2+, low Ba2+, and charybdotoxin (CTX) sensitivity was identified. Time analysis of single-channel recordings revealed a complex kinetic behavior compatible with the previous schemes proposed for Ca(2+)-activated K+ channels in a variety of biological surface membranes. We now report that the open probability of the channel at low Ca2+ concentration is enhanced on in vitro phosphorylation, which is mediated via an adenosine 3',5'-cyclic monophosphate-dependent protein kinase. In addition to this characterization at the molecular level, a second series of pharmacological experiments were designed to assess the putative role of this channel in ASM strips. Our results show that 50 nM CTX, a specific inhibitor of the large conducting Ca(2+)-dependent K+ channel, prevents norepinephrine transient relaxation on carbamylcholine-precontracted ASM strips. It was also shown that CTX reversed the steady-state relaxation induced by vasoactive intestinal peptide and partially antagonized further relaxation induced by cumulative doses of this potent bronchodilatator. Thus it is proposed that the Ca(2+)-activated K+ channels have a physiological role because they are indirectly activated on stimulation of various membrane receptors via intracellular mechanisms.


In this paper, we present a non-coherent energy detection scheme for spatial modulation (SM) systems. In particular, the use of SM is motivated by its low-complexity implementation in comparison to multiple-input multiple-output (MIMO) systems, achieved through the activation of a single antenna during transmission. Moreover, energy detection-based communications restrict the channel state information to the magnitude of the fading gains. This consideration makes the design applicable for low-cost low-powered devices since phase estimation and its associated circuitry are avoided. We derive an energy detection metric for a multi-antenna receiver based on the maximum-likelihood (ML) criterion. By considering a biased pulse amplitude modulation, we develop an analytical framework for the SM symbol error rate at high signal-to-noise ratios. Numerical results show that the diversity order is proportional to half the number of receive antennas; this result stems from having partial receiver channel knowledge. In addition, we compare the performance of the proposed scheme with that of the coherent ML receiver and show that the SM energy detector outperforms its coherent counterpart in certain scenarios, particularly when utilizing non-negative constellations. Ultimately, we implement an SM testbed using software-defined radio devices and provide experimental error rate measurements that validate our theoretical contribution.


Computer methods are described for trend-surface analysis of D'Arcy Thompson transformation grids, illustrated by data on skulls and jaws of hominoids.

In comparing two diagrams the following steps are required. First, corresponding points on each diagram are marked, and their co-ordinates are recorded. Second, the diagrams are scaled and fitted to give the best possible fit; this gives measures of size and shape difference. Third, the displacements of each point relative to its partner on the other diagram are subjected to trend-surface analysis. The displacements are analysed in terms of linear, quadratic, cubic and higher order trends. Fourth, the differences based on the trends alone can now be estimated.

The results on the illustrative examples are discussed, together with the difficulties in applying such methods. The nature of taxonomic (phenetic) affinity is also discussed, with suggestionsfor measuring different components of this concept.

The techniques show promise for a wide variety of taxonomic and morphological applications.


This paper presents MCP, a novel distributed and reactive transport protocol for data center networks (DCNs) to achieve minimal per-packet delay while providing guaranteed transmission rates to meet flow deadlines. To design MCP, we first formulate a stochastic packet delay minimization problem with constraints on deadline completion and network stability. By solving this problem, we derive an optimal congestion window update function which establishes the theoretical foundation for MCP. To be incrementally deployable with existing switch hardware, MCP leverages functionality available on commodity switch, i.e., ECN, to approximate the optimal window update function. Our preliminary results show that MCP holds great promise in terms of deadline miss rate and goodput.


The vertical-cavity surface-emitting laser (VCSEL) is a low cost light source with inherent high speed capabilities. These properties, along with low power consumption and a circular output beam, have made the VCSEL a well established component in digital communication networks, particularly in short reach optical data transmission where links consisting of GaAs-based 850nm VCSELs and multimode fiber have become the standard solution. Development of higher speed VCSELs is therefore crucial to meet the market's need for higher speed digital communication services in the near future. The scope of this work has been to extend the possible data transmission rate for 850nm VCSELs beyond the 10 Gbit/s bit-rate limit of today's commercially available devices. By tailoring the device design for high speed performance, we have demonstrated that 10 Gbit/s is far from the endpoint of 850nm VCSEL technology. Thermal conductivity is improved through the use of binary compounds in the bottom mirror and parasitics are kept at a minimum by incorporating a large diameter double layered oxide aperture in the design. It is shown that significant improvements of the high speed performance can be obtained by replacing the traditional GaAs quantum wells (QWs) with strained InGaAs QWs in the active region. The best overall performance in the VCSELs developed and fabricated for this work is demonstrated for a device with 9 μm diameter double oxide aperture and strained InGaAs QWs, with a threshold current of 0.6 mA, a maximum output power exceeding 9mW, a thermal resistance of 1.9 C/mW and a differential resistance of 80 Ohm. This type of component has a parasitically limited 3dB bandwidth exceeding 20 GHz and is shown to be capable of error-free transmission (BER<10^-12) under direct modulation at a record-high bit-rate of 32 Gbit/s over 50m of OM3 fiber at room temperature, and at 25 Gbit/s over 100m of OM3 fiber at 85 C. These results are obtained with the VCSEL biased at current densities in the range 11-14 kA/cm2, which is in the range of the 10 kA/cm2 industry benchmark for reliability.


Coordination of respiratory pump and valve muscle activity is essential for normal 55 breathing. A hallmark respiratory responses to hypercapnia and hypoxia is the emergence of 56 active exhalation, characterized by abdominal muscle pumping during the late one-third of 57 expiration (late-E phase). Late-E abdominal activity during hypercapnia has been attributed to 58 the activation of expiratory neurons located within the parafacial respiratory group (pFRG). 59 However, the mechanisms that control emergence of active exhalation, and its silencing in restful 60 breathing, are not completely understood. We hypothesized that inputs from the Kölliker-Fuse 61 nucleus (KF) control the emergence of late-E activity during hypercapnia. Previously, we 62 reported that reversible inhibition of the KF reduced post-inspiratory (post-I) motor output to 63 laryngeal adductor muscles and brought forward the onset of hypercapnia-induced late-E 64 abdominal activity. Herein, we explored the contribution of the KF for late-E abdominal 65 recruitment during hypercapnia by pharmacologically disinhibiting the KF in in situ decerebrate 66 arterially-perfused rat preparations. These data were combined with previous results and 67 incorporated into a computational model of the respiratory central pattern generator. Disinhibition of the KF through local parenchymal microinjections of gabazine (GABA A receptor antagonist) prolonged vagal post-I activity and inhibited late-E abdominal output during 70 hypercapnia. In silico , we reproduced this behavior and predicted a mechanism where the KF 71 provides excitatory drive to post-I inhibitory neurons, which, in turn, inhibit late-E neurons of the pFRG. Although the exact mechanism proposed by the model requires testing, our data confirm that the KF modulates the formation of late-E abdominal activity during hypercapnia.


ABSTRACT Background: Community mobility (CM) is considered a part of community reintegration that enhances Quality of Life (QoL). Achieving an appropriate gait speed is essential in attaining an independent outdoor ambulation and satisfactory CM. Objective: The aim of this study was to identify whether gait speed is a predictor of CM and QoL in patients with stroke following a multimodal rehabilitation program (MRP). Methods: This was a baseline control trial with 6-months follow-up in an outpatient rehabilitation setting at a university hospital. Twenty-six stroke survivors completed the MRP (24 sessions, 2 days/wk, 1 hr/session). The MRP consisted of aerobic exercise, task-oriented exercises, balance exercises and stretching. Participants also performed an ambulation program at home. Outcome variables were: walking speed (10-m walking test) and QoL (physical and psychosocial domains of Euroquol and Sickness Impact Profile). Results: At the end of the intervention, comfortable and fast walking speed increased by an average of 0.16 (SD 0.21) (*p < .05) and 0.40 (SD 0.51) (**p < .001) m/s, respectively. After the intervention, all participants achieved independent outdoor ambulation with an increase of 34.14 of walking minutes/day in the community and a decrease of sitting time of 95.45 minutes/day. Regarding QoL there were increased mean scores on the physical and psychosocial dimensions of Euroquol and the Sickness Impact Profile, respectively (**p < .001). Conclusions: The results suggest that improved walking speed after the MRP is associated with CM and higher scores in QoL. These findings support the need to implement rehabilitation programs to promote increased speed.


Four (2+1)-dimensional nonlinear evolution equations, generated by the Jaulent-Miodek hierarchy, are investigated by the bifurcation method of planar dynamical systems. The bifurcation regions in different subsets of the parameters space are obtained. According to the different phase portraits in different regions, we obtain kink (antikink) wave solutions, solitary wave solutions, and periodic wave solutions for the third of these models by dynamical system method. Furthermore, the explicit exact expressions of these bounded traveling waves are obtained. All these wave solutions obtained are characterized by distinct physical structures.


SUMMARY In order to investigate risk factors for the acquisition of trachoma, and to study the effect of continued exposure to ocular chlamydial infection on the severity of inflammatory trachoma and its cicatricial sequelae, a longitudinal study was conducted in a Gambian village. Over a 20-month period, the incidence of active (inflammatory) trachoma was significantly higher among those sharing a bedroom with an active case (64/561, 11·4%) than among those who were not exposed in this way (37/658, 5·6%) (relative risk 1·97, 95% confidence interval 1·33–2.90). There was a positive trend in the odds ratio for severe to moderate inflammatory disease versus mild disease as the number of active cases in the bedroom increased, but this failed to achieve statistical significance (P = 0·0506). Individuals with inflammatory trachoma of moderate or severe intensity at one survey were significantly more likely than others to have moderate or severe inflammatory changes at a previous or subsequent survey (odds ratio 14·9, 95% confidence interval 3·9–68·0), implying that host factors may be more important determinants of severity than the frequency of exposure to reinfection.


P opular media depictions of AI often involve apocalyptic visions of killer robots, humans mined for resources, or the elimination of the human race altogether. Even the rosier visions of an AI-driven world imagine most traditional human efforts and behaviors replaced with machines. Our collective imaginations of AI are often focused on this "singularity"—an irreversible point when technology overtakes humanity.


It is shown that besides well-known Lie algebra structures, the so(3) tensor operators have also a natural superalgebra structure. This property is used to relate the existence of the nontrivial zero {2 2 2|3/2 3/2 3/2} = 0 to the vanishing of some structure constants of the superalgebra gl(2/2) built from the spin-3/2 tensor operators.


The main purpose of establishing an information system is to facilitate human work easier. In this study, the Point of Sales (POS) information system is a system that regulates the flow and also the sale and purchase reports or transactions as well as incoming goods from the production process. The latest goal is that the system can provide valid reports, both transaction reports and goods reports. Therefore the author develops a system that has been running at PT. MAAN GHODAQO SHIDDIQ LESTARI which still uses a Microsoft Excel based on the system. Where the system is still using manual methods in processing transaction data and incoming goods. In the development of this application, the author uses the UML modelling language (Unified Modeling Language). While in the implementation stage the author uses the PHP programming language for servers and warehouse administrators and uses Basic4android programming language for sales. The result of the development of the system is an integrated POS information system, in that integration is expected to be able to regulate sales transactions and also incoming goods from the production process.

Keywords: point of sales, unified modelling language, PHP, basic4android


Those that create, promote and disseminate jazz are experiencing a period of radical change. The dwindling interest from the major labels in releasing jazz has led to a mushrooming of both traditionally imagined and virtual independent jazz labels, often musician-led by individuals or collectives. Despite the 'democratised' potentials of digital dissemination made possible through third party vendors and streaming services such as iTunes and Spotify, modest or non-existent advertising budgets and lack of coherent marketing strategies often result in independent releases being drowned in the noise of an overcrowded marketplace. Financial returns from limited sales are also modest. The commercial underpinning that in previous times afforded the jazz musician both potential apprenticeship and metier has become fractured through increasing scarcity of record company and private/public funding. Against this black backdrop, musicians have engaged in new ways of disseminating their work. DIY strategies, such as free download netlabels or interactive app-albums, have become increasingly commonplace. Fresh approaches — the need for which are highlighted in this article with reference to the European jazz scene — indicate how musicians are networking informally, often with little or no institutional support. This paper highlights to what extent market realignments have prompted individual and collective creative responses to current difficulties associated with the promotion of jazz music.


Abstract : The U.S. Army Engineer Research and Development Center, Construction Engineering Research Laboratory (ERDC-CERL) has been conducting investigations to help develop and evaluate engineered polymer composite railroad ties since 1993. Recent efforts, through funding and support from the Railway Administration, center around track safety issues relative to the use of these new products in mainline heavy-axle-load track. Performance criteria have been developed and published in Chapter 30 of the American Railway Engineering and Maintenance-of-Way Associations (AREMA) Manual for Railway Engineering. One item not completely resolved in this engineering guidance is the test method procedure to measure the bending strength and modulus of elasticity (stiffness) of the composite ties. The objective of this investigation is to compare variations in bending strength test methods currently being used to measure strength and modulus values for engineered polymer composite railroad ties.


There is a substantial body of evidence to support the positive impact of bystander-initiated cardiopulmonary resuscitation (CPR) on the outcome of victims of cardiac arrest. 1-3 Furthermore, there would seem to be little question that the medical community supports American Heart Association (AHA) and American Red Cross training programs for citizen-initiated CPR. A recent survey of cardiologists, internists, and family practitioners substantiates overwhelming support for such programs. 4 Since the development of the original standards in 1974 by the National Academy of Sciences-National Research Council and the AHA, 5 investigators have concerned themselves with the question of skill attainment and retention. Particular interest has focused on the degree of skill deterioration during various intervals of time. In all studies, a deterioration of CPR psychomotor skills was observed at either 12, 6, or 3 months. 6-11 These studies, which encompass almost a decade of research, are not easily compared because of


Weblogs can be used as a tool for learning support, providing additional features that are lacking in many Learning Management Systems (LMSs). This research aims to demonstrate that weblogs can enhance the learning experience by allowing students to reflect on their learning, and by allowing students to easily collaborate with their tutors and with one another. Laurillard's conversational framework is used a basis for describing how weblogs should be incorporated into the existing learning environment. In an initial study, students set up weblogs and created a weblog post each week over a 10-week period. Analysis of this study has begun, and preliminary results show that the use of weblogs with RSS (Rich Site Summary) helps to reduce tutor workload in comparison to the use of a Learning Management System, and helps to increase student involvement in learning.


Laparoscopy was performed on twenty-seven hospital inpatients presenting with acute lower abdominal pain. Nineteen of the twenty-seven were admitted with a provisional diagnosis of appendicitis. Following laparoscopy, nine patients underwent appendicectomy, and a further three underwent laparotomy. Fifteen patients had a laparoscopy as the sole procedure, and all were discharged from hospital without need for further surgery. Of those patients in the operative group, five had their proposed incisions modified as the result of the laparoscopic findings. The only complications attributable to laparoscopy was one small wound haematoma.


In order to assist decision makers in considering different approaches to improving mathematics and reading performance of elementary school children, a cost-effectiveness study was undertaken of computer-assisted instruction (CAI) and three other interven tions. In general, peer tutoring is found to be more cost-effective than CAI, and both are more cost-effective than reducing class size or increasing the length of the school day. A discussion of the cost-effectiveness methodology and its application to educational interventions is stressed .


Abstract The purpose of this study was to improve teacher's instruction to comparative, analytic method about the excellent teachers and general teachers of Korean subject through Flanders' Interaction System.The objects for analysis were field excellent instructions which were known as the best lectures from the instruction contest in Busan city, and the normal lectures by school curriculum which were video recorded and openly released on the web. This study was limited the use of same grade, subject and period. The analytic method used the software of AF(Advanced Flanders) based on the frame of Flanders' language Interaction System. Results showed as follows: (a) The excellent teachers used more interactions with the praise and encouragement than general teachers. (b) The excellent teachers induced students asked questions and answers with voluntary. These results could provide effective self-checking tools for enhance their instruction. Key word : Language Interaction, Flanders, excellent teacher Corresponding author : 051-629-5510, firstname.lastname@example.com


An instance of nerve abscesses developing in a patient with lepromatous leprosy is reported. The pathogenesis of nerve abscess in lepromatous leprosy is briefly discussed. It appears that such abscesses may develop (i) from an ENL lesion in the nerve during ENL reaction, (ii) because of exacerbation of existing lepromatous lesion, (iii) arise as an "exacerbation nodule", (iv) due to quiet necrosis in a lepromatous granuloma, or (v) it may be iatrogenic.


Abstract: The study of coleopteran assemblages associated with the canopies of tropical forests can help to expand the knowledge about species diversity and the ecological patterns related to the distribution of this diversity in tropical environments, including wetlands such as the Brazilian Pantanal. In this scenario, the present study examined the effect of temporal variation on the abundance, richness and distribution of the Coleoptera assemblage associated with canopies of Callisthene fasciculata (Spr.) Mart. (Vochysiaceae) throughout the dry and high-water seasonal periods in the Northern Pantanal of Mato Grosso, Brazil. Twelve specimens of C. fasciculata were sampled between 2010 and 2011, six per seasonal period, by thermal fogging with insecticide. A total of 1,663 coleopterans were collected, consisting of 1,572 adults and 91 larvae. The adults are distributed into 38 families and 251 species or morphospecies. Chrysomelidae, Curculionidae, Nitidulidae and Tenebrionidae predominated in terms of abundance and richness. Family distribution, abundance, species richness and trophic guilds varied between the dry and high-water periods, demonstrating a relationship with the phenological conditions of C. fasciculata in addition to seasonality effect. In conclusion, the seasonality imposed by the hydrological regime and its influence on the phenology of C. fasciculata affect the structure of the coleopteran assemblage associated with the canopy of this monodominant vegetation formation in the Pantanal of Mato Grosso.


The minimum concave cost network flow problem (MCCNFP) has many applications in areas such as telecommunication network design, facility location, production and inventory planning, and traffic scheduling and control. However, it is a well known NP-hard problem, and all existing search based exact algorithms are not practical for networks with even moderate numbers of vertices. Therefore, the research community also focuses on approximation algorithms to tackle the problems in practice. In this paper, we present an improved local search algorithm for the minimum concave cost network flow problem based on multi-cycle reduction. The original cycle reduction local search algorithm as proposed by Gallo and Sodini considers only negative cost single cycles; however, we find that such cycle reduction is not complete. We show that negative cost multi-cycles may exist in a network with concave edge costs that has no negative cost cycles, and an existing flow can be reduced to an adjacent neighboring flow with lower cost by redirecting flows along these negative multi-cycles. In this paper, we present an improved local search algorithm based on multi-cycle reduction.We evaluate our proposed algorithm in networks with a simple concave edge cost in different topologies and sizes. The experimental results show that the original cycle reduction algorithms can improve the quality of solutions obtained from a simple minimum cost augmentation approximation heuristic (LDF), and that a multi-cycle Type of Report: Other Department of Computer Science & Engineering Washington University in St. Louis Campus Box 1045 St. Louis, MO 63130 ph: (314) 935-6160 Improved Local Search Algorithm with Multi-Cycle Reduction for Minimum Concave Cost Network Flow Problems Ruibiao Qiu and Jon Turner WUCSE-2004-74 December 9, 2004 Department of Computer Science and Engineering Campus Box 1045 Washington University One Brookings Drive St. Louis, MO 63130-4899, USA Abstract The minimum concave cost network flow problem (MCCNFP) has many applications in areas such as telecommunication network design, facility location, production and inventory planning, and traffic scheduling and control. However, it is a well known NP-hard problem, and all existing search based exact algorithms are not practical for networks with even moderate numbers of vertices. Therefore, the research community also focuses on approximation algorithms to tackle the problems in practice. In this paper, we present an improved local search algorithm for the minimum concave cost network flow problem based on multi-cycle reduction. The original cycle reduction local search algorithm as proposed by Gallo and Sodini considers only negative cost single cycles; however, we find that such cycle reduction is not complete. We show that negative cost multi-cycles may exist in a network with concave edge costs that has no negative cost cycles, and an existing flow can be reduced to an adjacent neighboring flow with lower cost by redirecting flows along these negative multi-cycles. In this paper, we present an improved local search algorithm based on multi-cycle reduction. We evaluate our proposed algorithm in networks with a simple concave edge cost in different topologies and sizes. The experimental results show that the original cycle reduction algorithms can improve the quality of solutions obtained from a simple minimum cost augmentation approximation heuristic (LDF), and that a multi-cycle reduction yields more improvements; however, it reaches a point of diminished returns when we attempt to reduce more than bicycles.The minimum concave cost network flow problem (MCCNFP) has many applications in areas such as telecommunication network design, facility location, production and inventory planning, and traffic scheduling and control. However, it is a well known NP-hard problem, and all existing search based exact algorithms are not practical for networks with even moderate numbers of vertices. Therefore, the research community also focuses on approximation algorithms to tackle the problems in practice. In this paper, we present an improved local search algorithm for the minimum concave cost network flow problem based on multi-cycle reduction. The original cycle reduction local search algorithm as proposed by Gallo and Sodini considers only negative cost single cycles; however, we find that such cycle reduction is not complete. We show that negative cost multi-cycles may exist in a network with concave edge costs that has no negative cost cycles, and an existing flow can be reduced to an adjacent neighboring flow with lower cost by redirecting flows along these negative multi-cycles. In this paper, we present an improved local search algorithm based on multi-cycle reduction. We evaluate our proposed algorithm in networks with a simple concave edge cost in different topologies and sizes. The experimental results show that the original cycle reduction algorithms can improve the quality of solutions obtained from a simple minimum cost augmentation approximation heuristic (LDF), and that a multi-cycle reduction yields more improvements; however, it reaches a point of diminished returns when we attempt to reduce more than bicycles. Improved Local Search Algorithm with Multi-Cycle Reduction for Minimum Concave Cost Network Flow Problems Ruibiao Qiu Jonathan S. Turner {ruibiao,email@example.com Applied Research Laboratory Department of Computer Science and Engineering Washington University St. Louis, MO 63130, USA


Encrypted protocols, such as Secure Socket Layer (SSL), are becoming more prevalent because of the growing use of e-commerce, anonymity services, and secure authentication. Likewise, traffic analysis is becoming more common because it is often the only way to analyze these protocols. Although there are many valid uses for traffic analysis (such as network policy enforcement and intrusion detection), it can also be used to maliciously compromise the secrecy or privacy of a user. While the payload can be strongly protected by encryption, analysis of traffic patterns can yield information about the type and nature of traffic. In this paper we use simulation and analytic models to examine the impact on user experience of a scheme that masks the behavior of real traffic by embedding it in synthetic, encrypted, cover traffic. Through simulation and an analytic model we investigate the effects on the user experience using disparate and similar traffic models. This point provides a novel context where we observe the synergy of simulation and analytic modeling. We show that a detailed simulation model of network traffic characteristics can be used to estimate the parameters of an analytic model of tunneling. We see that the accuracy of the model's predictions is directly dependent on the accuracy of parameters we obtain from the simulation. However, the simulation model does not need to have any concept of tunneling. Using simulation and analytic modeling together, we obtain an analysis whose whole is greater than the sum of its parts.


The objective of this article is to analyse the establishment of consumer law and the effects this has had in Colombia and other Latin American countries as well as in the European Union.The main principles of consumer protection such as social justice, economic freedom and solidarity, consecrated in the Colombian Constitution of 1991, have gradually developed into solid legislation but have been seriously affected by the reality of dominant economic interests. With reference to European Union Law, this article is a comparative study of consumer law in order to demonstrate how the legislator should determine the conditions which constitute the consumer profile.


ABSTRACT The dynamics of viral infections have been investigated extensively, often with a combination of experimental and mathematical approaches. Mathematical descriptions of virus spread through cell populations are well established in the literature and have yielded important insights, yet the formulation of certain fundamental aspects of virus dynamics models remains uncertain and untested. Here, we investigate the process of infection and, in particular, the effect of varying the target cell population size on the number of productively infected cells generated. Using an in vitro single-round HIV-1 infection system, we find that the established modeling framework cannot accurately fit the data. If the model is fit to data with the lowest number of cells and is used to predict data generated with larger cell populations, the model significantly overestimates the number of productively infected cells generated. Interestingly, this deviation becomes stronger under experimental conditions that promote mixing of cells and viruses. The reason for the deviation is that the standard model makes certain oversimplifying assumptions about the fate of viruses that fail to find a cell in their immediate proximity. We derive from stochastic processes a different model that assumes simultaneous access of the virus to multiple target cells. In this scenario, if no cell is available to the virus at its location, it has a chance to interact with other cells, a process that can be promoted by mixing of the populations. This model can accurately fit the experimental data and suggests a new interpretation of mass action in virus dynamics models. IMPORTANCE Understanding the principles of virus growth through cell populations is of fundamental importance to virology. It helps us make informed decisions about intervention strategies aimed at preventing virus growth, such as drug treatment or vaccination approaches, e.g., in HIV infection, yet considerable uncertainty remains in this respect. An important variable in this context is the number of susceptible cells available for virus replication. How does the number of susceptible cells influence the growth potential of the virus? Besides the importance of such information for clinical responses, a thorough understanding of this is also important for the prediction of virus levels in patients and the estimation of crucial patient parameters through the use of mathematical models. This paper investigates the relationship between target cell availability and the virus growth potential with a combination of experimental and mathematical approaches and provides significant new insights.


Introduction The emerging role of non-albicans Candida species (NACS) as causal agents of mild to life-threatening mycoses is increasingly being appreciated. Some NACS are known for intrinsic resistance or reduced susceptibility to some antifungal drugs. To inform therapeutic options and management of candidiasis, we embarked on Candida species surveillance in Southwest Nigeria. Method We obtained retrospective yeast isolates from urogenital samples of patients in a tertiary hospital in south western Nigeria. Among 47 isolates identified phenotypically, we encountered a yeast which failed to produce pseudohyphae in human serum but was morphologically similar to Candida albicans. We characterized this yeast by sequencing the internal transcribed spacer (ITS1-5.8S-ITS2) region of the ribosomal DNA. Results A BLAST search and sequence homology identified the yeast as Candida (Diutina) mesorugosa, with a strong bootstrap. Conclusion Candida mesorugosa, a rarely isolated yeast from clinical samples worldwide, should be considered among potentially relevant NACS in Nigerian clinics. To the best our knowledge, this is the first report of Candida mesorugosa from a patient sample in Nigeria. This finding confirms the need for more specific methods, such as DNA sequencing, for extensive surveillance of NACS. Key words: Candida mesorugosa, Candida rugosa complex, Non-albicans Candida species surveillance, ribosomal DNA sequencing, NACS