The phenological and physiological responses of arctic tundra plant species are key to predicting their survival in a warmer climate. One of the consequences of a warmer climate in the Arctic will be a longer growing season. We examined the effects of lengthened growing season and soil warming on the widely distributed forb, Polygonum bistorta L. Three treatments were established near Toolik Lake, Alaska in 1995 and 1996: extended season, extended season with soil warming, and an unmanipulated control. The season was extended by removing the snow load in the spring and keeping the treatments free of snow in the autumn. The spring snow removal extended the snow‐free period over that of controls by 8 d in 1995 and 24 d in 1996. As a result, the number of accumulated soil thaw days and consequently the depth of soil thaw increased on the treatment plots. Polygonum bistorta responded to the treatments by becoming active earlier and senescing earlier, resulting in a growth period of similar duration to that of the controls. Leaf size and leaf number were unaffected by the treatments, as were leaf photosynthetic assimilation rates and nutrient concentrations. The results indicate that internal constraints limit the response of this species to lengthened growing season, suggesting that it is a determinant or periodic species. With climate warming, this periodic growth will put P. bistorta at a competitive disadvantage relative to plants that can respond to lengthened growing season.


Recent economic policy debates have centered on increasing and quantifying the value chain, and the objective of this research is to characterize the value chain of vitiviniculture in Baja California according to organizational subsystems, including management, marketing, quality, productivity and environment. This study presents a comparative analysis between the capabilities of the vitiviniculture industry and sectors within which it participates. The analysis shows that the primary issues are related to sectors that have weak productive infrastructure, marketing problems, product shortages and few local suppliers, and additional problems include insufficient funding, water shortages and high taxes. Moreover, investments in human capital are required to train human resources.


This paper presents a literature review on the use of depth for hand tracking and gesture recognition. The survey examines 37 papers describing depth-based gesture recognition systems in terms of (1) the hand localization and gesture classification methods developed and used, (2) the applications where gesture recognition has been tested, and (3) the effects of the low-cost Kinect and OpenNI software libraries on gesture recognition research. The survey is organized around a novel model of the hand gesture recognition process. In the reviewed literature, 13 methods were found for hand localization and 11 were found for gesture classification. 24 of the papers included real-world applications to test a gesture recognition system, but only 8 application categories were found (and three applications accounted for 18 of the papers). The papers that use the Kinect and the OpenNI libraries for hand tracking tend to focus more on applications than on localization and classification methods, and show that the OpenNI hand tracking method is good enough for the applications tested thus far. However, the limitations of the Kinect and other depth sensors for gesture recognition have yet to be tested in challenging applications and environments.


The distributed and continuous representations used by neural networks are at odds with representations employed in linguistics, which are typically symbolic. Vector quantization has been proposed as a way to induce discrete neural representations that are closer in nature to their linguistic counterparts. However, it is not clear which metrics are the best-suited to analyze such discrete representations. We compare the merits of four commonly used metrics in the context of weakly supervised models of spoken language. We compare the results they show when applied to two different models, while systematically studying the effect of the placement and size of the discretization layer. We find that different evaluation regimes can give inconsistent results. While we can attribute them to the properties of the different metrics in most cases, one point of concern remains: the use of minimal pairs of phoneme triples as stimuli disadvantages larger discrete unit inventories, unlike metrics applied to complete utterances. Furthermore, while in general vector quantization induces representations that correlate with units posited in linguistics, the strength of this correlation is only moderate.


Abstract Most conventional optimization approaches are deterministic and based on the derivative information of a problem's function. On the other hand, nature-inspired and evolution-based algorithms have a stochastic method for finding the optimal solution. They have become a more popular design and optimization tool, with a continually growing development of novel algorithms and new applications. Flexibility, easy implementation, and the capability to avoid local optima are significant advantages of these algorithms. In this study, shapes, and shape perturbation limits of a bracket part, which is used in aviation, have been set using the hypermorph tool. The objective function of the optimization problem is minimizing the volume, and the constraint is maximum von Mises stress on the structure. The grey wolf optimizer (GWO) and the moth-flame Optimizer (MFO) have been selected as nature-inspired evolution-based optimizers.


In this work, friction loss investigations and comparisons of three different four-cylinder engines for passenger car applications are presented, using a recently developed combined approach. By merging extensive experimental with reliable and predictive journal bearing simulation results, a sub-assembly-resolved friction loss analysis of the piston group, crankshaft journal bearings and valve train is conducted for all three engines. The engines have been chosen individually based on their specific power output and crank train geometry. The measurement program covers a wide range of corresponding engine operation points (identical speed, load and thermal boundary conditions). In addition, the investigations are carried out for different engine media supply temperatures ranging from 70 ∘ C to 110 ∘ C for a comprehensive consideration of the friction losses at reduced lubricant viscosity. For reasons of comparability, all investigations conducted in this work have been carried out using the same modern SAE 5W30 lubricant. This is done to exclude influences from different lubricant properties which may have significant effects on the tribological behaviour of the engines' sub-assemblies. While the diesel engine showed a friction reduction potential over the entire engine operation range when increasing the engine media supply temperatures, the gasoline engines showed a different behaviour. For the gasoline engines, disadvantages arise especially at low engine speeds. By using the developed combined approach, it was possible to assign mixed lubrication regimes at the valve train systems and at the piston groups.


This paper describes a very flexible, high-speed current-mode winner-take-all network (WTA) for use in artificial neural systems. Since the WTA is based on a network of identical current switching cells requiring only adjacent transistor matching, it is particularly suited to use in large systems. In addition, since the network is based on a tree structure, very little space is occupied by interconnect, thus ensuring a very compact layout. This WTA has current (matching score) inputs and provides a buffered, binary encoded voltage output. >


We construct a theoretical model to study the orbital Kondo effect in a parallel double quantum dot (DQD). Recently, pseudospin-resolved transport spectroscopy of the orbital Kondo effect in a DQD has been experimentally reported. The experiment revealed that when interdot tunneling is ignored, two and one Kondo peaks exist in the conductance-bias curve for pseudospin-non-resolved and pseudospin-resolved cases, respectively. Our theoretical studies reproduce this experimental result. We also investigate the case of all lead voltages being non-equal (the complete pseudospin-resolved case) and found that there are at most four Kondo peaks in the curve of the conductance versus the pseudospin splitting energy. When interdot tunneling is introduced, some new Kondo peaks and dips can emerge. Furthermore, the pseudospin transport and the pseudospin flipping current are also studied in the DQD system. Since the pseudospin transport is much easier to control and measure than the real spin transport, it can be used to study the physical phenomenon related to the spin transport.


Aims & Objectives: Sickle cell anemia is a chronic hemolytic disease presented by special clinical course attributed to ischemic changes resulting from vascular occlusion by masses of sickle cells. In-vitro studies with piracetam indicate that it has potential for inhibition and reversal of the process of sickling of erythrocytes so it has been reported to be an effective drug for the treatment of patients with SCA. The aim of this prospective study was to evaluate and compare the effect of different doses of Piracetam on clinical status and laboratory investigations of sickle cell anemia patients.
Materials and methods: The study was carried out on 30 sickle cell anemia patients (14 females), aged ranged from 5 to 16 years old and their weights ranged from 18kg to 33kg; from hematology clinic at Beni Suef University Hospital. Patients were divided into three equal groups. Group A received 80mg/kg/day piracetam, group B received 160mg/kg/day piracetam and group C represents the control group which did not receive Piracetam. Patients were treated and followed for 6 month. They were represented to full history taking, clinical examination, laboratory investigations and determination of frequency of packed red cells transfusion, crises and hospitalization on admission and every month for six months.
Results: There was an improvement in general health of children after therapy and pallor, decrease in the elevated serum ferritin level, decrease in frequency of crises and hospitalization, decrease in the frequency of transfusion, increase in packed red cells transfusion intervals and increase in hemoglobin level. The increase in Reticulocyte count% was in all groups, more in control group, but still with no significant difference between the three groups.
Conclusion: Dose of 160mg/kg/day of Piracetam showed more improvement than dose 80mg/kg/day in pallor and laboratory findings except Reticulocyte count% and more effective in reduction of frequency of transfusion, crises and hospitalisation.


In this chapter, we present a state-of-the-art of topic about thermal transport and the thermoelectric property of nanoscale materials. We firstly review the fundamental physical phenomena for thermal transport in nanoscale materials, including carbon nanotubes, silicon nanowires, graphene and monolayer MoS2. Various impacts on thermal conductivity of these nanomaterials are discussed. Then, we provide a review on the current status of research on the thermoelectric property of semiconducting nanowires, including silicon nanowire, silicon-germanium nanowire and ZnO nanowire. We also discuss envisioned applications of nanostructures in the area of heat dissipation to phononic devices.


OBJECTIVE
To establish fluorescence microscopy combined with HPLC method for rapid detection the distribution and content of resveratrol tissues in different growth stages of Polygonum cuspidatum.

METHODS
Used sequential experiment to design conditions of frozen and observe of the section by fluorescence microscopy; Resveratrol was extracted by ultrasonic-assisted extraction and its content was detected by HPLC.

RESULTS
The results showed that frozen condition for concentration of gum Arabic was from 20% (dipping time was 5 - 6 h) to 40% (2 - 5 min), the freezer temperature was -5 degrees C, and the thickness was 15 microm. Resveratrol in polygonum cuspidatum was mainly accumulated in the organs, tissues and cells of fiber and cellulose, its content in rhizomes declined as the following sequence: spinal cord > xylem > phloem > periderm; Its content declined in organ as the following sequence: buds > rhizomes > ground stem > leaves; The content of resveratrol in root increased with age.

CONCLUSION
The results of fluorescence microscopic observation is in accordance with the HPLC results, indicating that the method is simple, fast and reliable, and provides a fast and reliable detection method for the determination of optimum harvesting period of Polygonum cuspidatum and acquisition of quality.


Surface electromyography (sEMG) is a pivotal approach in clinical and basic neurophysiology, allowing us to extract the summed activity of motor units in a given muscle. Due to the bipolar nature of the motor unit action potential, the sEMG is a non-linear representation of their underlying motor unit activity and therefore affected by signal cancellation. It is not clear how this cancellation influences evoked responses in sEMG. The aim of our study was to characterise how representative an evoked sEMG response was to the firing behaviour of the underlying motor pool. To do this, we first simulated a population of motor units (and their action potentials) that responded to a stimulus with a change in firing probability. Their activity was summed then rectified to generate a simulated sEMG signal or was rectified and then summed, to generate a sEMG signal with no cancellation. By comparing the two responses to that of the underlying pool we would then compare for discrepancies. We repeated this process but by using the responses of tibialis anterior motor units to weak tibial nerve stimulation. We find that both for the simulated and experimental data the response measured through the sEMG is almost always an underestimate of the evoked response in the underlying motor pool. This is the case for both inhibitory and excitatory evoked responses. The magnitude of the inaccuracy depends on the size of the evoked response, but it cannot be accounted solely by signal cancellation, suggesting other factors may also contribute.


ABSTRACT
 Insects that arrive in new regions can be hosts for a variety of unseen metazoans, including microscopic nematodes, which are carried phoretically as dauer juveniles or as internal/ external parasites in various stages. This includes insects that arrived by natural means, were purposefully introduced for biological control before strict APHIS/PPQ provisions, were inadvertently introduced as hitchhikers or stowaways, or were brought in as part of the pet trade or for food. In some cases, the host associations are so specific that they may pose little threat, but in other cases where host specificity is relatively wide and/or host transfer opportunities exist, the nematode associates can expand, colonize and establish associations with native insects causing various downstream environmental effects. Because nematodes are mostly microscopic, the consequences of such introductions are usually not considered in the pet trade or as an added consequence as introduced or invasive insects arrive in the state and establish themselves. These arrival scenarios are discussed with real-world examples, including one with damage potential for Florida and the southeastern U.S., i.e. the red ring nematode that is associated with palm weevils.


Resource endowment ought to be source of blessing and a platform for sustainable national development. This scenario has been true of resource rich countries. Generally, the disposition of states to the utilization of available resources can be responsible for the possibility or otherwise of achieving national development that will inevitably lead to the guaranteeing of national security. This justifies the assertion that the state plays a key role in the management of the national economy. Critical to this assertion is the notion of the centrality of the state by virtue of the resources available at her disposal to enforce rules and compel obedience. - Instead of making efforts to improve the quality of life of Nigerians, Nigeria government has deployed the military might to harass, alienate, intimidate, and oppress her citizens. The current spates of insecurity have been argued to be a fall out of the inherent contradictions of security, development, and prosperity.


In the industrial age of today. non-destructive evaluation of materials, components. and assemblies has become increasing) important. and plays a crucial role, be it in space. power, oil, automobile, or steel sector. As the consequences of component failure are more serious than ever, the integrity of component has to be evaluated and assessed at even* stage of its production. Presence of harmful defects, tensile residual stress, and unwanted microstructure affects the integrity of any component. Hence, assessment of defects, and evaluation of residual stress and microstructure are very essential. Man' nondestructive testing and evaluation techniques are being used for detection and characterization of defects, evaluation of residual stress, and assessment of microstructure. The' provide it tool by which integrity evaluation, and assurance activities for components can he carried out. In this paper, an attempt has been made to present the basic concepts of non¬destructive evaluation. The principles of different non-destructive test techniques have been discussed, and the application of these techniques for evaluation of castings has been highlighted.


This paper presents investigations into the development of PD-type Fuzzy Logic Control with different polarities input shaping for anti-sway control of a gantry crane system. A nonlinear overhead gantry crane system is considered and the dynamic model of the system is derived using the Euler-Lagrange formulation. To study the effectiveness of the controllers, initially a PD-type Fuzzy Logic Control is developed for cart position control of gantry crane. This is then extended to incorporate input shaper control schemes for anti-sway control of the system. The positive and modified specified negative amplitude (SNA) input shapers with the derivative effects respectively are designed based on the properties of the system. Simulation results of the response of the system with the controllers are presented in time and frequency domains. The performances of the control schemes are examined in terms of level of input tracking capability, swing angle reduction, time response specifications and robustness to parameters uncertainty in comparison to the PDtype Fuzzy Logic control. Finally, a comparative assessment of the amplitude polarities of the input shapers to the system performance is presented and discussed.


In this paper, the 120 keV Ar+-ion-irradiation-induced phase transformation from the Al62Cu25.5Fe12.5 icosahedral quasicrystal (IQC) to B2(CsCl)-based phases has been studied by means of transmission electron microscopy. The dose dependence of the Ar+ ion irradiation effect and the subsequent in-situ heating and cooling behaviours after irradiation have been investigated. The experimental results show that the r+-irradiation-enhanced diffusion can accelerate the transformation from the Al62Cu25.5Fe12.5 IQC to a B2-type or B2-based phase at room temperature and that this B2 or B2-based phase transforms reversely to the IQC when the Ar+ dose is equal to or lower than 1014 Ar+ cm-2 and the temperature is increased to about 1000 K.


Near-surface soil temperatures are important because they have implications for climate change and agricultural productivity worldwide. Nonetheless, historic records of soil temperature are much less common than records of air temperature or precipitation. Those that exist do not indicate a predominant global trend in soil temperature over the last century, but suggest regional and seasonal differences that include both cooling and warming. In this paper, we compared the annual date at which near-surface soil temperatures in Kansas reached each of seven thresholds (five degree increments between 40 and 70° F) for each of two decades (the 1990s and 2000s) in order to see if soil temperatures warmed earlier in the year in one decade than in the other. Of the 13 stations tested, only Colby warmed more quickly in the 2000s than in the 1990s for all seven thresholds, and no station warmed more quickly in the 1990s across all thresholds. Typically lower thresholds that occur in the winter were reached earlier in the 1990s than in the 2000s, while higher temperature thresholds that occur in the spring were reached earlier in the 2000s than in the 1990s. These results generally reflect changes in temperature and precipitation during these two decades. Despite the relatively short duration of the data, these findings for Kansas show some similarities to those from studies in other parts of North America and the world. Most notably, areas with warming soil temperatures are often in areas with cooler climates.


A novel taxonomic model for structuring and accessing large heterogeneous information bases is presented. The model is designed to simplify both classification and access by computer-illiterate people. It defines simple and intuitive operations to access large information bases at the conceptual level and at different levels of abstraction, in a totally assisted way, through a simple, yet effective visual interface. The model can also be used to summarize result sets computed by other query methods, such as information retrieval, shape retrieval, etc., and to provide user maps for complex hypermedia networks. The experience gained by applying this model to commercial applications is reported.


We report on two teenage girls presenting following significant paracetamol overdoses (>28 g paracetamol). Both presented within 4 h of the overdose and both were treated with N-acetylcysteine, in accordance with the National Poisons Information Service protocol. Within 8 h of presentation both had developed significant hypokalaemia with serum potassium concentrations <3.0 mmol/L and were treated with intravenous potassium chloride. Potassium concentrations returned to within reference limits (>3.5 mmol/L) after commencing potassium chloride supplementation. An audit of potassium concentrations in 254 patients presenting with significant paracetamol overdose (paracetamol >0.5 mmol/L) admitted through four A&E departments in the West of Scotland showed a significant decline in mean serum potassium from 3.9 mmol/L on admission to 3.6 mmol/L (P = <0.001) over the next 36 h. The mechanism for this hypokalaemia in these two individuals is unclear, however regular monitoring of potassium is advocated in such patients during their initial treatment.


High-efficiency monolithic SiGe balanced frequency doublers have been developed for Ku- and Ka-band applications. A novel miniature second harmonic reflector is presented, and the impact of the parasitic inductor from emitter to ground is also explored to optimize the conversion efficiency of the doubler. The Ku-band design presents an output power of 5-6 dBm from 15.4-18 GHz for an input power of 1.5 dBm. DC power consumption is 28 mW and the corresponding power-added efficiency (PAE) is 9.2%. The Ka-band design demonstrates an output power of 10.5 dBm at 36 GHz for an input power of 6 dBm while consuming 114 mW of dc power, which results in a PAE of 6.4%. It also shows high spectral purity operation with the fundamental suppression of 35 dB. To our knowledge, these are the best results for active doublers using any technology


Supplemental Digital Content is available in the text. Background. International travel for transplantation remains a global issue as countries continue to struggle in establishing self-sufficiency. In the United States, the United Network for Organ Sharing (UNOS) requires citizenship classification at time of waitlisting to remain transparent and understand to whom our organs are allocated. This study provides an assessment of patients who travel internationally for liver transplantation and their outcomes using the current citizenship classification used by UNOS. Methods. Adult liver UNOS data from 2003 to 2019 were used. Patients were identified as citizens, noncitizen, nonresidents (NCNR), or noncitizen residents (NC-R) according to citizenship status. Descriptive statistics compared demographics among the waitlisted patients and demographics and donor characteristics among transplant recipients. A competing risks model was used to examine waitlist outcomes. The Kaplan-Meier method and Cox proportional hazards were used for posttransplant outcomes. Results. There were significant demographic differences according to citizenship group among waitlisted (n = 125 652) and transplanted (n = 71 536) patients. Compared with US citizens, NCNR was associated with a 9% increase in transplant (subdistribution hazard ratio [SHR], 1.09; 95% confidence interval [CI], 1.00-1.18; P = 0.04), and NC-R was associated with a 24% decrease in transplant (SHR, 0.76; 95% CI, 0.72-0.79; P < 0.0001) and a 23% increase in death or removal for being too sick (SHR, 1.23; 95% CI, 1.14-1.33; P < 0.0001). US citizens had significantly inferior graft and patient survival (P < 0.001). Conclusions. Though the purpose of the citizenship classification system is transparency, the results of this study highlight significant disparities in the access to and outcomes following liver transplantation according to citizenship status.


Most personal (egocentric) network studies describe networks using measures that are not structural, opting instead for attribute-based analyses that summarize the relationships of the respondent to network members. Those researchers that have used structural measures have done so on networks of less than 10 members who represent the network core. Although much has been learned by focusing on attribute-based analyses of personal network data, the application of structural analyses that are traditionally used on whole (sociocentric) network data may prove fruitful. The utility of this approach becomes apparent when the sample of network members elicited is relatively large. Forty six respondents freelisted 60 network members and evaluated tie strength between all 1,770 unique pairs of members. Graph-based measures of cohesion and subgroups revealed variability in the personal network structure. Non-hierarchical clustering generated subgroups which were subsequently verified by respondents as meaningful. Further analysis of the correlation between subgroup types and overlap between subgroups demonstrates how the analysis of each network can be summarized across subjects. Four case studies are presented to illustrate the richness of the data and the value of contrasting individual matrix results to the norm as defined by all 45 subjects.


The overall power conversion efficiency of organic Rankine cycle (ORC) systems is highly sensitive to the isentropic efficiency of expansion machines. No expansion machine type is universally ideal as every machine has its own advantages and disadvantages and is suitable for a comparatively narrow range of operations of the highest efficiency. Therefore, an optimum selection of an expansion machine type is important for a financially viable ORC implementation. This chapter presents the mode of operation, technical feasibility, and challenges in the application of turbo-expanders (radial inflow, radial outflow, and axial machines) and volumetric expansion machines (scroll, screw, piston, and vane) for use in ORC systems. It can be concluded that different machines are suitable for a different range of power output in commercial applications. In general, volumetric machines are suitable for 50 kWe and below but turbomachines are more suitable for power outputs higher than 50 kWe.


Patients with advanced, recurrent or metastatic cancer have poor prognosis despite treatment advancements. Vesicular stomatitis virus (VSV)-GP (BI 1831169) is a chimeric VSV with its neurotropic glycoprotein G replaced by the non-neurotropic glycoprotein (GP) of the lymphocytic choriomeningitis virus. This live, recombinant oncolytic virus has demonstrated preclinical efficacy as a viral-based immunotherapy due to its interferon-dependent tumor specificity, potent oncolysis and stimulation of antitumor immune activity. Co-administration of the immune checkpoint inhibitor, ezabenlimab (BI 754091), alongside VSV-GP may synergistically enhance antitumor immune activity. Here, we describe the rationale and design of the first-in-human, phase I, dose-escalation study of VSV-GP alone and in combination with the immune checkpoint inhibitor ezabenlimab in patients with advanced, metastatic or relapsed and refractory solid tumors (NCT05155332).


The risk of gastrointestinal (GI) events induced by nonoperative therapies in patients with neuroendocrine tumors (NETs) is unclear. Nonoperative therapies include somatostatin analogs, molecular targeted agents, cytotoxic chemotherapy, interferon-α, and peptide receptor radionuclide therapy. We undertook an up-to-date meta-analysis to determine the incidence and relative risks (RRs) of GI events in NET patients treated with these therapies. MEDLINE, EMBASE, the Cochrane Central Register of Controlled Trials, and ClinicalTrials.gov were searched to identify relevant trials. Eligible trials were selected according to the PRISMA statement. Summary incidence, RR, and 95% CIs were calculated using random- and fixed-effects models. We included 2,890 patients from 17 randomized controlled trials in this meta-analysis. The experimental treatments led to increased incidence and risks of GI events compared to the control treatments (P<0.05). Diarrhea was the most common GI event. The experimental treatments were associated with increased risks of high-grade nausea (RR 2.36; 95% CI 1.05–5.25; P<0.01) and vomiting (RR 1.89; 95% CI 1.04–3.44; P<0.05). In regard to specific therapy regimens, everolimus led to increased risks of diarrhea (RR 2.97; 95% CI 1.83–4.83; P<0.05), vomiting (RR 2.19; 95% CI 1.38–3.48; P<0.05), and anorexia (RR 3.20; 95% CI 1.69–6.06; P<0.05), whereas VEGFR inhibitors led to increased risk of diarrhea (RR 2.12; 95% CI 1.39–3.25; P<0.05). Additionally, GI NETs led to higher risk of GI events than pancreatic NETs. Thus, nonoperative therapies are associated with increased risks of GI events in NET patients, and rigorous management is warranted to minimize the adverse impact on treatment outcomes and to improve quality of life.


This paper describes a study which assesses a software prototype designed as part of the POSTURE project. POSTURE (Pressure Offloading Support Technologies for Ulcer REduction) comprises the design and development of a prototype system to help patients suffering from Diabetic Foot Ulcer (DFU) self-manage their treatment. The system is designed to take input from commercial wellness sensors and other sensors specially crafted for tracking aspects of foot ulcer progress. The sensor data is fed into a data-backed decision support tool which interacts with users via an intelligent agent, using a chatbot style interface, underpinned by computational argumentation-based dialogue. A recent Patient and Public Involvement (PPI) study was conducted in which DFU patients were presented with the prototype system design and offered opinions about the utility of the system from their unique perspectives. The preliminary results of this study are presented here.


Background:
 Monocytes and neutrophilic granulocytes are critical for innate immunity, through recognition and phagocytosis of pathogens, and mediation of acute inflammation through secretion of pro-inflammatory cytokines. Furthermore, monocytes constitute an important link between innate and adaptive immunity through antigen presentation to lymphocytes. Patients with chronic lymphocytic leukemia (CLL) have an increased risk of infection, despite often displaying normal neutrophil and monocyte counts. CLL-cells depend on interactions with the immune microenvironment (IME) for proliferation and survival, while inducing changes in surrounding immune cells. However, changes in myeloid cell function in patients with CLL remain sparsely documented. Since the btk-inhibitor ibrutinib impairs B-cell receptor signaling and disrupts CLL-IME interactions (Niemann et al, CCR, 2016), we investigated the impact of ibrutinib and venetoclax on monocyte- and neutrophil phenotype and function in CLL patients.
 Methods:
 Nine patients treated with ibrutinib 420 mg daily for 8 weeks followed by addition of venetoclax with an initial 5-week ramp up period were included. Blood samples were taken at baseline, after 8 weeks ibrutinib monotherapy, and after another 8 weeks of ibrutinib and venetoclax combination therapy. Immune phenotype was assessed in whole blood by an 8-tube, 10 color flow cytometry panel with custom designed lyophilized antibodies (Duraclone). Immune function was characterized using TruCulture, a whole blood-ligand stimulation assay applying the toll like receptor (TLR) ligands heat killed candida albicans (TLR 2,4,6), lipopolysaccharide (LPS; TLR4), resiquimod (single-stranded RNA-virus analog, TLR7,8), and Poly:IC (double-stranded RNA-virus analog, TLR3), after which the cytokine response was measured. Informed consent from patients and approval from the ethics committee was obtained.
 Results:
 Monocyte and neutrophil counts, as wells as distribution of mature and immature neutrophils, were within normal range at baseline (n=9) and remained unchanged throughout treatment. At baseline, expression of HLA-DR on monocytes was suppressed, but increased significantly upon combination treatment with ibrutinib and venetoclax (p=0.04). HLA-DR expression on neutrophils was high at baseline, remained unchanged upon ibrutinib treatment (n=8), but declined after addition of venetoclax (n=7) (p<0.01). LPS-stimulated TNF-α and IL-6 production was suppressed at baseline, IL-6 levels increased significantly upon ibrutinib monotherapy, and levels of both TNF-α and IL-6 almost normalized upon addition of venetoclax to ibrutinib (p=0.02 for TNF-α, p=0.009 for IL-6).
 Conclusion:
 Here we show for the first time that myeloid leukocytes in CLL patients exhibit an altered HLA-DR expression at baseline, which is paralleled by an impaired cytokine response to LPS stimulation. Following treatment with ibrutinib and venetoclax, HLA-DR expression increased on monocytes and decreased on neutrophils, both representing normalization. In parallel, LPS-induced TNF-α and IL-6 production improved, likely reflecting an improved monocytic function, as monocytes respond strongly to whole-blood LPS-stimulation. Increased monocyte HLA-DR expression has previously been linked to improved cytokine response (Belge et al, J Immunol, 2002). The contribution of neutrophils to the improved cytokine response is unclear, since the function of HLA-DR expressing neutrophils in CLL is largely unknown. We propose a model where ibrutinib and venetoclax eradicate CLL-cells, disrupt tumor-IME interactions, and maybe directly impact microenvironmental cell signaling, thereby restoring neutrophil and monocyte function and improving immune function. Further investigation of myeloid function in CLL at baseline and upon different treatment regimens is warranted to guide personalized treatment based on modulation of infection-risk.

 Svanberg: Novo Nordisk Foundation: Research Funding; Abbvie: Other: Travel grant. Kater:Genentech: Research Funding; Roche: Other: Travel funding, Research Funding; AbbVie: Consultancy, Honoraria, Research Funding. Niemann:Acerta: Consultancy, Research Funding; Roche: Other: Travel grant; Astra Zeneca: Consultancy, Research Funding; Novo Nordisk Foundation: Research Funding; CSL Behring: Consultancy; Janssen: Consultancy, Other: Travel grant, Research Funding; Gilead: Other: Travel grant; Sunesis: Consultancy; Abbvie: Consultancy, Other: Travel grant, Research Funding.


This essay examines the work of four recent Jewish-American poets of successive generations (respectively, George Oppen, Armand Schwerner, Michael Heller, and Norman Finkelstein). In documenting and elucidating their interrelationships, the essay argues simultaneously for the central, and fundamental, role literacy plays in the formation of the self and in the structure of Jewish identity, and in doing so the essay reveals a core ideological value and even an essentialized aesthetic the four poets share. The essay rests on a basic assumption developed by Walter Ong and other theorists of literacy—that writing, in creating the self and thus self-awareness, also gives rise to alienation. Such alienation can be seen to be if not synonymous with exile then at least intimately involved with it, and so, in reading these four poets, the Jewish Diaspora is given full exploration, and is related back to a considered Jewish sense of exile from the Divinity.


Detailed mean flow measurements were obtained at stations up to thirty chordlengths downstream in an airfoil trailing vortex using a yawhead pressure probe in the Virginia Tech Six-Foot Subsonic Tunnel. Mass injection at the wingtip was shown to hasten the vortex decay. A theoretical method has been developed to show the effect of wing circulation distribution on the structure of the outer portion of the vortex and excellent agreement with the experimental data is demonstrated. Experimental results indicate a much slower decay and higher tangential velocities than previously expected.


Abstract Many tire performances are associated with the tire design, among which maneuverability and tire durability become major ones to be considered. The former performance is determined by the tension‐value distribution along the sidewall carcass, and the latter by the peak strain energy density in the belt edge region. These two mechanical quantities are closely related to the sidewall carcass contour, so that the above‐mentioned two performances could be improved by sidewall contour optimization. Unfortunately, however, this kind of multi‐objective optimization requires interactive methods, for which the designer's decision‐making is involved, owing to the existence of multi‐peaks. In this study, we basically apply the satisficing trade‐off method (STOM), but we intend to systemize it more by introducing aspiration‐level indicators that control the entire optimization process. Through numerical experiment, we confirm that the proposed refined STOM leads systematically and efficiently to a nearly opt...


A case of prolonged corneal edema developed after xenon arc retinal photocoagulation. Heat absorption by the anterior segment is thought to be the main cause of endothelial damage and consequent stromal edema. Iris overlap by the light beam, high intensity energy, and cataract seem to be favorable conditions for aqueous and corneal overheating. The contact lens used during photocoagulation may have aggravated heat retention by insulating the cornea from its normally cooler environs. Caution is warranted when several of the factors favoring heat absorption by the anterior segment are present.


Due to the repetitive and lengthy nature, automatic content-based summarization is essential to extract a more compact and interesting representation of sport video. State-of-the art approaches have confirmed that high-level semantic in sport video can be detected based on the occurrences of specific audio and visual features (also known as cinematic). However, most of them still rely heavily on manual investigation to construct the algorithms for highlight detection. Thus, the primary aim of this paper is to demonstrate how the statistics of cinematic features within play-break sequences can be used to less-subjectively construct highlight classification rules. To verify the effectiveness of our algorithms, we will present some experimental results using six AFL (Australian Football League) matches from different broadcasters. At this stage, we have successfully classified each play-break sequence into: goal, behind, mark, tackle, and non-highlight. These events are chosen since they are commonly used for broadcasted AFL highlights. The proposed algorithms have also been tested successfully with soccer video.


Improvements have been made to the fracture-flow model being used in the total-system performance assessment of a potential high-level radioactive waste repository at Yucca Mountain, Nevada. The ``weeps model`` now includes (1) weeps of varied sizes, (2) flow-pattern fluctuations caused by climate change, and (3) flow-pattern perturbations caused by repository heat generation. Comparison with the original weeps model indicates that allowing weeps of varied sizes substantially reduces the number of weeps and the number of containers contacted by weeps. However, flow-pattern perturbations caused by either climate change or repository heat generation greatly increases the number of containers contacted by weeps. In preliminary total-system calculations, using a phenomenological container-failure and radionuclide-release model, the weeps model predicts that radionuclide releases from a high-level radioactive waste repository at Yucca Mountain will be below the EPA standard specified in 40 CFR 191, but that the maximum radiation dose to an individual could be significant. Specific data from the site are required to determine the validity of the weep-flow mechanism and to better determine the parameters to which the dose calculation is sensitive.


Purpose - What are the reasons for writing this paper? The purpose of this paper is to make the case for liberty, and free enterprise, against the criticisms of this system. Specifically, the present essay is an attempt to criticize the case for inheritance taxation. This is made by many, but the author focuses on James Buchanan's contribution to this support for socialism. The author does so because James Buchanan is widely known as a champion of capitalism and free markets, and he is nothing of the sort, at least in this one case. Design/methodology/approach - The approach used in this paper is to quote widely from the adherents of inheritance taxes, and then to show the flaws in the cases they offer in support of this system. Findings - The finding is that none of the arguments offered on behalf of inheritance taxation have been shown to be valid. There are flaws in all of them. This, of course, does not imply no such arguments can be shown to be successful; only that the ones herein cited do not justify this market interference. Social implications - Why do entrepreneurs engage in entrepreneurship? For a whole host of reasons, surely; these might in the extreme be as different as there are different entrepreneurs. But one motivation, certainly an important one, likely to be felt by most entrepreneurs, is to leave a bequest upon demise, so that one's heirs and loved ones may share in the fruits of one's entrepreneurial activities. Thus, taxes on inheritances, let alone those approaching the 100 percent level, must be anathema to at least most if not all entrepreneurial activities. The present paper makes the case against such attacks on wealth, bequests, inheritances. Originality/value - To the best of the author's knowledge, although there are of course defenses of bequests, and critiques of Buchanan on other matters, there are no criticisms of this Nobel prize winning economist on this particular issue.


Although hundreds of GWAS-implicated loci have been reported for adult obesity-related traits, less is known about the genetics specific for early-onset obesity, and with only a few studies conducted in non-European populations to date. Searching for additional genetic variants associated with childhood obesity, we performed a trans-ancestral meta-analysis of thirty studies consisting of up to 13,005 cases (≥95th percentile of BMI achieved 2-18 years old) and 15,599 controls (consistently <50th percentile of BMI) of European, African, North/South American and East Asian ancestry. Suggestive loci were taken forward for replication in a sample of 1,888 cases and 4,689 controls from seven cohorts of European and North/South American ancestry. In addition to observing eighteen previously implicated BMI or obesity loci, for both early and late onset, we uncovered one completely novel locus in this trans-ancestral analysis (nearest gene: METTL15). The variant was nominally associated in only the European subgroup analysis but had a consistent direction of effect in other ethnicities. We then utilized trans-ancestral Bayesian analysis to narrow down the location of the probable causal variant at each genome-wide significant signal. Of all the fine-mapped loci, we were able to narrow down the causative variant at four known loci to fewer than ten SNPs (FAIM2, GNPDA2, MC4R and SEC16B loci). In conclusion, an ethnically diverse setting has enabled us to both identify an additional pediatric obesity locus and further fine-map existing loci.


The research of pastures influenced by Carpathian sheep milk farming as a typical archetype was conducted in study areas of the mountain even subalpine landscape in the forest zone of the Western Carpathians in the Slovak Republic. We have chosen 28 areas that have been effected by mountain sheep farming since the  period of the  Wallachian colonization. The  research works were under way from 1998 to 2016. The  pastures of observation were from 615 to 1 421 meters above sea level (m a.s.l.) in the areas of 1 398 ha in total that was of various exposition and inclination, from flat surface to steep hillsides with 28° slope. The studied pastures ranged from the species‐rich to species‐poor, from Festuca‐Agrostis grasslands through Nardo‐Agrostion tenuis alliance to Nardion. The number of plant species (from 18 to 48, average 33 at 1 m2) shows a rather varied composition of grasslands. There were only two study sites with higher dominance of Festuca rubra (51 % and 64 %) recorded. The quality of grassland depends on the floristic composition (cover in %) and forage value of the particular species. Evaluation of the grassland quality (EGQ) reached the average value 57.5 in the scale from 0 to 100. Value varied from least valuable grasslands with 40.1 points in two study plots to valuable grasslands with 69.4 points. Relations between selected environmental factors were analysed by means of redundancy analysis (RDA). Among the significant factors of environment, the impact on data set variability was the strongest by altitude (18.1 %), then by total precipitation in the vegetation period (5.6 %) and grassland quality EGQ (5.2 %).


Mark Twain once remarked that the reports of his death were greatly exaggerated. So too, the death of virology.

In certain quarters, it is now fashionable to declare the passing of virology. "Viruses are retro," a faculty colleague once told me, deadly serious.

We have heard this before. In 1967, the U.S. Surgeon General allegedly proclaimed, "The time has come to close the book on infectious disease. We have basically wiped out infection in the United States" (1). This was before the arrival of AIDS and severe acute respiratory syndrome (SARS) and the discovery of hepatitis C virus, before the fear of an avian flu pandemic and bioterrorism.

Virology was once held in high esteem. In the first half of the 20th century, plant viruses held center stage. Studies of mosaic disease of tobacco revealed the existence of a new class of infectious agents smaller than bacteria, and tobacco mosaic virus taught us that viruses could be crystallized, disassembled, and reassembled into an infectious form: "life" could be studied with chemical approaches (2, 3). In the 1950s and 1960s, viruses that infect bacteria played a central role in the biological sciences. They formed the basis of the Hershey-Chase experiment, the first widely accepted evidence that DNA is the genetic material (4). Bacteriophage also led to the discovery of mRNA and the triplet nature of the genetic code and played a leading role in the birth of molecular biology (5). The 1970s and 1980s were a golden age for animal virology. The small genomes of many animal viruses and the ease of introducing them into cells made them the model organisms of choice to study eukaryotic cells. mRNA splicing, transcriptional enhancers, oncogenes, tumor suppressor proteins, antiapoptotic proteins, cellular trafficking signals and pathways, major histocompatibility complex (MHC) restriction, and much fundamental …


The purpose of the present work is the reconstruction of motorcycle lateral dynamics. The main idea is to estimate pertinent states and unknown inputs (rider action) with respect to nonlinear outputs due to motion transformation frames (inertial sensors are away from the local frame). To overcome this issue, we propose a new Unknown Input Observers with variable output matrix. In this paper, we take into account the ground truth measurements provided in the body-fixed frame, parametric uncertainties as well as sensors noise. This step leads to a nonlinear parameter-dependent output equation with unmeasured premise variables in the observer design. The observer synthesis is specified in term of convergence and stability study by considering a quadratic Lyapunov function associated with the Input To State Stability (ISS) property. Sufficient conditions are agreed in terms of Linear Matrix Inequalities (LMIs). Finally, the performances, usefulness and robustness of the proposed approach are assessed throughout an electric Scooter under urban riding scenario.


The fire spalling of concrete is a complex phenomenon, which can affect the integrity of the structures during a fire. This thermal instability is associated with a complex coupled chemo-thermo-hydro-mechanical mechanism and it can be influenced by many factors, related to material (e.g. per- meability, porosity and water content), geometry (e.g. shape and size) and environmental parameters (e.g. mechanical load and heating rate). Concrete made with recycled concrete aggregates presents higher porosity, higher water content and different interfaces between aggregates and mortar. All these aspects can lead to a different behaviour under fire exposure, including the spalling risk of these sustainable concretes. The main objective of this paper is to analyse the influence of the use of recycled concrete aggregates on the spalling risk of concrete. In this paper, concrete prisms with different replacement rates of recycled coarse aggregates (0 up to 100%) were exposed to a standard fire curve (ISO 834-1) with a constant uniaxial compression load. After heating, samples surfaces were evaluated by means of digital photogrammetry. Results showed that concrete with RCA is sensitive to explosive spalling. All replacement rates presented higher degree of spalling than concrete made with natural aggregates.


A scientist from the Bernard Nocht Institute for Tropical Medicine in Hamburg who was quarantined for a week because of a possible infection with the Ebola fever virus has left the isolation ward of Hamburg University Hospital. She has been transferred to a normal ward, because she had no clinical signs of infection, and neither the virus nor any antibodies against the virus were found in her blood.

This positive development may be due to the use of an experimental vaccine given to the scientist that has never previously been used in humans. The vaccine virus was …


The aim of this thesis was to investigate the postnatal development of inhibitory signalling in spinal pain pathways by the inhibitory transmitters GABA and glycine. Immunohistochemical studies and western blot analysis have shown that two key molecules, the scaffolding protein gephyrin and the potassium cation co-transporter KCC2, are postnatally upregulated in the rat superficial dorsal horn. Low levels of gephyrin limit postsynaptic clustering of GABAa and glycine receptors reducing the efficiency of synaptic inhibition, whereas the relative paucity of the cation-chloride co-transporter KCC2 in the neonatal period reduces the cell's ability to actively extrude chloride, producing a reversal of the electrochemical gradient. The upregulation of KCC2 was accelerated in vivo by peripheral inflammation and in cultured neurons by potassium induced depolarisation, while spike blockade with TTX produced the opposite effect. Gephyrin expression on the other hand, was not activity dependent. The functional consequences of these low levels of KCC2 in the neonatal period upon GABA and glycine signalling were tested using intrathecal injections of GABA and glycine antagonists. In adults these antagonists are known to produce sensitisation of mechanical withdrawal thresholds but in neonates they had the opposite effect, causing reduced sensitivity. Correspondingly, GABA and glycine, whilst having no effect in adult rats produced sensitisation in neonatal rat pups. This difference was abolished on spinalisation, demonstrating the importance of supra spinal connections in controlling segmental inhibition. Benzodiazepines, are GABA agonists commonly used in neonatal intensive care. In order to test whether the results of this thesis have practical implications for clinical care, a questionnaire survey of neonatologists was carried out. Myoclonus and seizures were reported following the use of midazolam in young patients suggesting that low levels of KCC2 may also be a feature of the human neonatal CNS.


Stress fractures of the medial malleolus are rare injuries associated with substantial morbidity. These debilitating fractures represent a diagnostic challenge, as they are often mistaken for ligamentous or syndesmotic injuries. The proper management of medial malleolar stress fractures is also unclear, however there is a substantial body of literature describing the need for open reduction and internal fixation using cancellous screws in elite athletes. We report a case of a 20-year-old Division I football player sustaining a medial malleolar stress fracture that was successfully treated nonoperatively with no time missed from games. Case B.H., a 20-year-old Division I Football tight end was attempting to block another player when he sustained a forced hyper-dorsiflexion injury to his right ankle. He could not sprint for the remainder of practice and any attempt to push off was also painful. On clinical exam, he demonstrated 5/5 strength and full range of motion with pain at full passive dorsiflexion. He did not demonstrate a joint effusion and was negative for talar tilt, anterior drawer, and squeeze tests. Radiographs taken the next morning were negative, however one month later he was seen by team physicians for persistent anterior ankle pain during running activities and during squats in the weight room. Repeat right ankle radiographs were significant for a subtle linear lucency of the medial distal tibia, and MRI demonstrated diffuse marrow edema extending through the medial tibial plafond with a partial tear of the tibiocalcaneal component of the deltoid ligament. CT scans confirmed a fracture of the anterior cortex of the medial distal tibia. The athlete was restricted to a walking boot for all activities of daily living and practices were modified to limit impact loading and sprinting. He was placed on a bone stimulator for four weeks and received rehabilitation including strengthening, proprioceptive work, and lower extremity stretching. He began to improve over the next several weeks and was able to participate fully on game-days throughout his injury. He was followed with serial radiographs. At the end of the season, (8 weeks s/p injury) he was placed in a fiberglass cast and non-weightbearing on crutches. Twelve days later the cast was removed and he was then placed in a walking boot. Follow-up CT scan at this time revealed progressive healing. As he was asymptomatic, he was weaned from the walking boot and is now participating fully in spring football.


Genistein is an isoflavone naturally present in numerous staple food crops, such as soybeans and chickpeas. This study utilized the Gallus gallus intraamniotic administration procedure to assess genistein administration effects on trace mineral status, brush border membrane (BBM) functionality, intestinal morphology, and intestinal microbiome in vivo. Eggs were divided into five groups with 1 mL injection of the following treatments: no-injection, DI H2O, 5% inulin, and 1.25% and 2.5% genistein (n = 8 per group). Upon hatch, blood, cecum, small intestine, and liver were collected for assessment of hemoglobin, intestinal microflora alterations, intestinal morphometric assessment, and mRNA gene expression of relevant iron and zinc transporter proteins, respectively. This study demonstrated that intraamniotic administration of 2.5% genistein increased villus surface area, number of acidic goblet cells, and hemoglobin. Additionally, genistein exposure downregulated duodenal cytochrome B (DcytB) and upregulated hepcidin expression. Further, genistein exposure positively altered the composition and function of the intestinal microbiota. Our results suggest a physiological role for genistein administration in improving mineral status, favorably altering BBM functionality and development, positively modulating the intestinal microbiome, as well as improving physiological status.


A new state of CuO, labelled Y2Σ+, predicted by ab initio calculations, has been observed in an infrared transition with the X2Πi ground state at 7800 cm-1 (λ = 1.3 μm). Significant population of the new Y state was achieved via collisional transfer from the A2Σ state, itself populated by c.w. dye-laser pumping. From ab initio calculations, it is shown that the Y2Σ+ and X2Πi states from an unique perturber pair interacting on oxygen centered 2pσ-2pπ orbitals. In the frame of this interpretation, the theoretical magnitude of the X2Π1/2 Λ-type splitting deduced from the ab initio wavefunctions is in good agreement with the spectroscopic value. It fixes a positive sign for the corresponding p parameter and determines definitively the electronic parities of all the 2Σ levels of CuO.


In order to investigate a breakdown phenomenon occurring after current interruption, we measured currents on the order of milliamperes to amperes after current interruption. The pre-breakdown current changed depending on the elapsed time from current zero. The post arc current (PAC) rose again around the peak of the transient recovery voltage (TRV), when the breakdown occurred at the peak of the TRV. On the other hand, precursor pulsed currents were observed before breakdown from time to time, which occurred several milliseconds after current zero. The pulsed currents were on the order of milliamperes, and their time widths were on the order of $0.1\ \boldsymbol{\mu}\mathbf{s}$. The current waveform after current interruption varied according to the elapsed time from current zero. This shows that the factors involved in breakdown varied according to the elapsed time from current zero.


Bilingualism is a widespread phenomenon, yet its economic effects are under researched. Typically studies find that bilingual workers are disadvantaged. Governments often protect minority languages through official promotion of bilingualism, with potential economic consequences. This paper addresses the impact of bilingualism on earnings, using the example of Wales. Results show a positive raw differential of 8 to 10 per cent depending on definition of linguistic proficiency. This differential persists in earnings function estimates, which control for human capital and demographic characteristics as well as local area effects. The potential endogeneity of language choice and earnings is addressed through the use of appropriate instrumental variables. Results suggest that bilingualism may be exogenous to the determination of earnings.


Introduction: Edentulousness falls in a special category among the various conditions of dental origin. A simple estimation of the partial edentulous condition is a rough indication of the prevalence of dental diseases and success or failure of dental care. Methodology: In this study a cross sectional survey was carried out among 1000 patients of rural population in JKK Nataraja Dental College, Komarapalayam, Namakkal District, Tamilnadu, India. The aim of this study was to evaluate the epidemiological features of partial edentulous condition in the age group of 30-60 years in a rural Population based on the Kennedy classification. A pre tested questionnaire was Used in this study. Result: Chi-square test was conducted and results were obtained and P value <0.05 was considered stastically significant. Conclusion: The study revealed Kennedy Class III partially edentulous condition was more common than other conditions. There is significant correlation between lack of awareness,education and socio-economic status in relation to loss of teeth among population.


When using built-in self-test (BIST) for testing VLSI circuits the circuit response to an input test sequence, which may consist of thousands to millions of bits, is compacted into a signature which consists of only tens of bits. Usually a linear feedback shift register (LFSR) is used for response compaction via polynomial division. The compacting function is a many-to-one function and as a result some erroneous responses may be mapped to the same signature as the good response. This is known as aliasing. In this paper we deal with the selection of a feedback polynomial for the compacting LFSR, such that an erroneous response resulting from any modeled fault is mapped to a signature that is different from that for the good response. Such LFSRs are called zero-aliasing LFSRs. Only zero-aliasing LFSRs with primitive or irreducible feedback polynomials are considered due to their suitability for BIST test pattern generation. >


Treatment of Malignant Tertian Malaria SIR,-The case of malignant tertian malaria recorded by Drs. W. L. Anderson and D. B. Bradshaw (April 24, p. 508) is of interest inasmuch as the man was apparently cured by quinine. The patient in the case recorded by Shute and myself in the Lancet (1942, 2, 365) had, in point of fact, been taking regular doses of quinine, which suppressed the severe malarial symptoms without curing the disease, and it was not until quinine was discontinued that the diagnosis of malaria was possible. In the case reported by Anderson and Bradshaw the small doses of qulinine did not prevent the diagnosis of malignant tertian malaria being made, but it did suppress the severe clinical symptoms, and had quinine been stopped there is little doubt that these symptoms would have been much more severe. An important finding was the large number of gametocytes (crescents) present in the peripheral blood. This is evidence that the patient had been suffering from malaria for some considerable time, and that the quinine had failed to destroy the asexual parasites, because, had this been so, gametocytes could not have been so numerous. Mepacrine (atebrin) would have probably benefited the patient more than did the longcontinued daily doses of quinine. As regards the mepacrine treatment, when a severe case of malignant tertian is admitted to hospital it is the practice at Horton to treat tjhe patient as follows: on the 1st day 0.6 g.; on the 2nd day 0.3 g.; on the 3rd and 4th days none; on the 5th, 6th, 7th, and 8th days 0.3 g. The reason for giving ,a reasonably large dose on the 1st day is that the parasites are subjected to drastic treatment, which will destroy most of the developing forms, either in the peripheral or internal circulation, particularly in the capillaries of the brain. The dose of 0.3 g. on the 2nd day will kill off most of the survivors of the previous day's treatment. The two-days rest followed by 0.3 g. for a further period of four days invariably cures the attack and possibly the disease as well. Finally, a few small doses of plasmoquin 0.02 g. twice weekly for two or three weeks would have destroyed the sexual parasites (crescents) and so rendered the patient uninfective to anopheles mosquitoes.-I am, etc., Epsom. J. ELLIOT MURRAY, M.D.


Producing hydroxy fatty acids (HFAs) in transgenic crops represents a promising strategy to meet our demands for specialized plant oils with industrial applications. The expression of Ricinus communis (castor) OLEATE 12-HYDROXYLASE (RcFAH12) in Arabidopsis has resulted in only limited accumulation of HFA in seeds, which likely results from inefficient transfer of HFAs from their site of synthesis (phosphatidylcholine; PC) to triacylglycerol (TAG), especially at the sn-1/3 positions of TAG. Phospholipase As (PLAs) may be directly involved in the liberation of HFAs from PC, but the functions of their over-expression in HFA accumulation and distribution at TAG in transgenic plants have not been well-studied. In this study, the functions of lecithin:cholesterol acyltransferase-like PLAs (LCAT-PLAs) in HFA biosynthesis were characterized. LCAT-PLAs were shown to exhibit homology to LCAT and mammalian lysosomal PLA2 , and to contain a conserved and functional Ser/His/Asp catalytic triad. In-vitro assays revealed that LCAT-PLAs from HFA-accumulating plant species Physaria fendleri (PfLCAT-PLA) and castor (RcLCAT-PLA) could cleave acyl chains at both the sn-1 and sn-2 positions of PC, and displayed substrate selectivity towards sn-2-ricinoleoyl-PC over sn-2-oleoyl-PC. Furthermore,co-expression of RcFAH12 with PfLCAT-PLA or RcLCAT-PLA, but not Arabidopsis AtLCAT-PLA, resulted in increased HFA occupation at the sn-1/3 positions of TAG as well as small but insignificant increases in HFA levels in Arabidopsis seeds compared to RcFAH12 expression alone. Therefore, PfLCAT-PLA and RcLCAT-PLA may contribute to HFA turnover on PC, and represent potential candidates for engineering unusual fatty acid production in crops.


Background Palliative Care is an approach that seeks to improve the quality of life for patients and their families, for those facing a terminal illness. Palliative Care is being increasingly perceived as a discipline and becoming an integral part of the health and social systems. Preventive measures and requirement planning are important elements in the Palliative Treatment mission. Advance Care Planning (ACP) is prevailing as more and more of an international concept. ACP derived from procedural, repetitive end-of-life conversations, whose results have influenced preventive measures and current treatment plans. The focus is on the observance and adherence to the individual needs of patients. Aim The study evaluated a discussion guide (dialogue guide), which can be used as a tool for ACP. Methods The Delphi study was conducted with two rounds of questioning. A draft of the discussion guide was presented to an anonymous group and was reviewed for content, relevance, and validity. Results The dialogue guide, which was received in the Delphi-process, has been evaluated as an appropriate tool for ACP in Palliative Care. Discussion The relevance of the Guide has been confirmed. Use of this guide is dependent on the current situation, the knowledge and experience of the user, but also by the institutional conditions. Conclusion The developed dialogue guide can be used as a discussion guide for ACP in Palliative Care. A discussion on the use and practicality in patient care must follow.


Cometary nuclei consist mostly of dust and water ice, but the internal structure of a comet nucleus is essentially unknown. Bulk properties such as mass, volume (size and shape), and particularly the density, must be known for constraining its internal structure. The radio science experiment RSI on the Rosetta spacecraft derived the mass and the gravity field of comet 67P/Churyumov-Gerasimenko at distances varying between 100 km and 10 km, and together with the current best estimates of the volume by the OSIRIS camera, the bulk density of the nucleus. A model of the internal structure is derived from the information of two shape models by comparing observed and theoretical gravity coefficients. The comet nucleus appears to be a body of low mass, low density and high porosity with approximately four times more dust than ice by mass and 1.5 times more dust than ice by volume.


To provide an exposé of digital-age library and information science (LIS) education for an African agenda, this paper adopts an emergent qualitative research design by drawing on the literature on LIS education in Africa. It also draws on data gleaned from a survey of heads of schools of LIS in South Africa, and from content analyses of LIS school websites in South Africa and selected parts of the continent. The paper locates its narrative within Abbott's chaos of disciplines theory and concludes that the LIS discipline's "interstitial nature," its "fractal distinctions in time," and the resulting chaos of disciplines should not be seen as a crisis for LIS education in Africa and globally, but as an opportunity for a paradigm shift to broaden the LIS disciplinary domain and to stake an intellectual claim on this extended domain—and so contribute to the growth and development of LIS services in Africa within the context of an African development agenda.


This guide looks at privacy in the digital age. It provides research tips as well as tools and strategies to protect your privacy and personal information.


The technological aspects of modification of epoxy oligomer DER – 331 to provide improvement of thermophysical characteristics of composite materials and protective coatings based on them are presented. Cold-cured triethylenetetramine TETA hardener was used to crosslink the epoxy binder (q = 10 parts by weight per 100 parts by weight of DER-331 epoxy resin). Thermogravimetric (TGA) and differential thermal (DTA) analysis was performed to study modified composites under the influence of elevated temperatures. A mathematical calculation of the values of the activation energy of thermal destruction to determine the resistance to destruction of chemical bonds under the influence of temperature factor.


Multidisciplinary teams are needed to address the needs of patients

With the support of the World Health Organization and the blessing of the Pope, the 1997 charter for people with Parkinson's disease declared that patients have the right to consult a doctor with a special interest in Parkinson's disease (box).1 This demand was reinforced at the launch of the global declaration on Parkinson's disease in Mumbai, India, last month at a symposium of a working group originally formed by WHO. Yet where can this reasonable demand be met at present? Not in India, and perhaps not in most other places in the world—developing or developed. A doctor with a special interest usually means a neurologist (but it could be a geriatrician or a general practitioner), and given the shortage of neurologists in most countries including the United Kingdom this demand is unlikely to be met till the shortage is addressed.2 w1 w2 Moreover, neurologists on their own are perhaps not suited to look after people with Parkinson's disease, and these patients need to be looked after by multidisciplinary teams, keeping in mind the needs of patients as identified by patients and doctors. This charter could easily be applicable to other chronic neurological disorders too.

Although the number of incident cases of Parkinson's disease is relatively small (20 per 100 000 per year) the prevalence of the disorder …


The study of photoionized environments is fundamental to many astrophysical problems. Up to the present most photoionization codes have numerically solved the equations of radiative transfer by making the extreme simplifying assumption of spherical symmetry. Unfortunately very few real astronomical nebulae satisfy this requirement. To remedy these shortcomings, a self-consistent, three-dimensional radiative transfer code has been developed using Monte Carlo techniques. The code, MOCASSIN, is designed to build realistic models of photoionized nebulae having arbitrary geometry and density distributions, with both the stellar and diffuse radiation fields treated self-consistently. In addition, the code is capable of treating one or more exciting stars located at non-central locations. The gaseous region is approximated by a cuboidal Cartesian grid composed of numerous cells. The physical conditions within each grid cell are determined by solving the thermal equilibrium and ionization balance equations. This requires a knowledge of the local primary and secondary radiation fields, which are calculated self-consistently by locally simulating the individual processes of ionization and recombination. The structure and the computational methods used in the MOCASSIN code are described in this paper. MOCASSIN has been benchmarked against established one-dimensional spherically symmetric codes for a number of standard cases, as defined by the Lexington/Meudon photoionization workshops: at Meudon in 1985 and at Lexington in 1995 and 2000. The results obtained for the benchmark cases are satisfactory and are presented in this paper. A performance analysis has also been carried out and is discussed here.


Progression of cardiovascular disease is often caused by a deficiency of magnesium in the human body. Magnesium belongs to the necessary vital macronutrients providing many physiological and pathological reactions and is involved in the constructive, energy, electrolyte metabolism. Correction of magnesium deficiency is realized using magnesium-containing drugs, for example magnesium orotate, having pleiotropic effects due to independent metabolic activity of orotic acid.


Palm oil is among the first commodity in Malaysia. The production of palm oil can be increased by implementing smart agriculture technology. To produce a good quality of palm oil, good soil quality is vital. Lack of soil information can make it hard for the farmer to maintain the nutritious of the oil palm tree. Thus, a real-time palm oil soil monitoring system has been developed for Palm Oil Soil Monitoring in a Smart Agriculture. The system measured the pH, moisture and tilt of palm oil soil. These parameters were essential to determine the palm oil soil status of alkalinity, tilt and moisture. These sensors are connected to Arduino microcontroller, which captures, processes and analyses the data. The captured data will be sent via the WiFi connectivity to the cloud database for the record. Based on the data analysis, the quality of the soil will be determined for further action by the farmer. The results showed that the system had successfully processed, transmitted, displayed and concluded the soil's status. As a result, real-time reading will be displayed in the graphical graph using ThingSpeak.


Let be a Riesz algebra with an extended norm such that is complete. Also, let be another extended norm in weaker than such that whenever (a) and in , then ; (b) and in , then . Let and be two nonnegative real numbers. Assume that a map satisfies and for all . In this paper, we prove that there exists a unique derivation such that , (). Moreover, for all .


Background. We aimed to present the immediate and long term effect of percutaneous balloon compression (PBC) for idiopathic trigeminal neuralgia (ITN). Methods. ITN patients who underwent PBC for the first time in the past seven years were enrolled. Base line data and immediate postoperative outcomes were collected by reviewing the medical records and long term results. Kaplan-Meier curve, life-table analysis proportional-hazards analysis were utilized to assess the long term results and the likelihood of tic recurrence. Results. 12,797 patients were enrolled. Immediate after the PBC procedure, complete and partial pain relief were achieved in 95.6% and 1.1% patients respectively, with no relief in 1.7 % patients; the common side effects on the affected side of face included the sense loss in 98.9% patients, with 3.8% of them experienced sense loss combined abnormal sense; masseter weakness in 90.6%, herpes eruption in 51.4%, corneal reflex weakness or loss in 12.7% patients. The fewer perioperative complications covered diplopia in 139 patients (1.1%), partial hearing loss in 190 patients (1.5%), vascular complications in 5 patients (0.05%), brainstem hematoma in one patient (0.01%), ischemic stroke in two patients (0.02%), intracranial hemorrhage in 11 patents (0.09%), and intracranial infection in one patient (0.01%) patients. Of three deaths happened in the perioperative period, two died of intracranial hemorrhage, and the other one died of intracranial infection. 5794 (49.2%) patients, who were followed than one year after the procedure, were included in the follow-up study, with the median follow-up period of 7.2 years. Complete and partial pain relief were obtained in 82.9% and 6.8% patients respectively, while the pain recurrence occurred in 8.5% patients. Side effects included sense loss without abnormal sense in 54.3%, with acceptable abnormal sense in 6.0%, and with severe abnormal sense in 2.0% patients. Masseter weakness was reported by 7.5% patients. 96.4% patients were satisfied with the procedure. Conclusion. Our study shows PBC is a safe, simple and effective procedure, with both immediate and long-term success rates, acceptable side effects and fewer deadly complications, should be considered as one of the best choice for the treatment of ITN patients.


This case study explores building design competencies and a design-driven organizational culture within an American healthcare non-profit. With a staff are primarily from the healthcare space, as well as some in banking and sales, we look at how the staff has adapted to working within a design-driven organization. By applying iterative design methods and embracing innovation and uncertainty we observe how the organization's founder has helped guide team members through a process of discomfort and vulnerability within an experimentally-driven and human-centered organization.Using interviews with employees and the founder at various points in new employee on-boarding processes we chart a transformational arc over six months. The learnings to share include both the universal and the particular: what are the core competencies to develop in all organizational members, and what are the specific and different ways competencies can take form. From building explicitly shared languages to facilitated sensemaking this case study offers an opportunity to share new and developing practices for embedding design-driven innovation and management practices in new fields and contexts.


Reasearch and technology developments in the field of spintronics have grown tremendously in the past 10-15 years and already have had a major impact on the data storage industry.The future looks even brighter, as many new spintronic discoveries have been recently made that promise an even bigger impact in the future.This article summarizes the past accomplishments, describes some of the major discoveries that will have a lasting impact on the field, and discusses some of the technologies that may revolutionize data storage in the next decade.


Oxidation of lipoproteins is believed to play a key role in atherogenesis. In this study, influence of two fat vehicles, corn oil (unsaturated) or beef tallow (saturated), on cholesterol induced effects in terms of a) plasma lipoprotein peroxidation and b) aortic accumulation of cholesterol, cholesterol oxide and malonaldehyde was investigated in weanling rabbits. Although the increase in plasma cholesterol induced by cholesterol feeding was similar in both the groups Cu2+ ion induced peroxidation of lipoprotein cholesterol to oxysterols was significantly higher in corn oil group. This difference persisted even at 5 weeks after switching to chow diet. Aortic content of cholesterol and cholesterol oxides was also significantly higher in corn oil group at the end of chow diet period. Aortic accumulation of malonaldehyde (detected by immunocytochemistry) appeared to be greater in corn oil group at the end of the study. These results suggest that fatty acid composition of a given diet during exposure to high dietary cholesterol can influence cholesterol peroxidation to oxysterols and its accumulation in aorta.


We review the concept of uncertainty for thermophysical properties and its critical impact for engineering applications in the core courses of chemical engineering education. To facilitate the translation of developments to engineering education, we employ NIST Web Thermo Tables to furnish properties data with their associated expanded uncertainties. We present four pertinent examples for the engineering classroom and an application to research, which illustrate the practical combination of the concept of uncertainty with online data resources


Solar energy applications being developed to assist in limiting the extent of climate change through low-carbon technologies, rely on the natural environment that may be sensitive to changes in the climate, resulting from rising carbon emissions. Climate models are essential to predict the future of solar irradiance fields needed for long range planning of solar energy use. Despite the wide use of numerial models on precipitation and agriculture, their applications on measuring the effect of changing climate on renewable energy resources and weather parameters that contribute to building comforts are very sparse. In this study, the nature of seasonal and interannual variability of solar radiation is investigated alongside global solar radiation climatologies. The International Centre for Theoretical Physics regional climate model (ICTP-RegCM3) driven by European Centre/Hamburg 5 general circulation model (ECHAM5-GCM) and based majorly on the fundamental principles of Newton's second law, the conservation of mass, the equation of state and the first law of thermodynamics was generated for Nigeria under an enhanced atmospheric CO2 level for the period 1981 to 2100. The model was validated using 11-year solar radiation and mean atmospheric temperature data from two observatories (Nigerian Meteorological Agency (NIMET) and the National Aeronautic and Space Administration (NASA)). Data were analysed using descriptive statistics and Fisher test (p<0.01). The model performed reasonably well when compared with the observed data. The best simulations for seasonal cycle of global solar radiation was obtained over the North having σ' = 1.45, R = 0.84 and σ' = 0.97, R = 0.98 whereas the worst simulations occur over the South with σ' = 0.93, R = 0.62 and σ' = 0.85 and R = 0.87 for the NIMET and NASA respectively. RegCM3 was also found to indicate a fair prediction of the interannual variability of solar radiation and mean air temperature over the climatic zones. Correlations for the solar radiation range from (NIMET) and (NASA) reflecting that the simulated interannual variability over the South and North climatic zones fairly agree with the observed, but more consistent with that observed in the Middle-belt zone . The simulated seasonal global solar radiation bias for the RegCM3 with NIMET and NASA observed datasets in the control period (1981–2010) are of similar magnitudes and showed a mixture of persistent positive and negative biases ranging between –10 and 30%. The seasonal potential future changes in period 1 (2011–2040), showed a reduction in the range of 0 (North) to 3.27% (South) whereas more reduction in global solar radiation is observed in period 2 (2041–2070), having general decrease ranging from 0.11 (Middlebelt) to 3.39% (South). Potential changes in period 3 (2071–2100), is generally characterized with mixed increase and decrease in global solar radiation across the country than the previous two periods. The model has predicted well, the potential effect of changing climate on solar radiation over Nigeria. It was also observed that the finer the resolution in grid spacing, the better the model in representing the observed data.


Enset is an ideal crop for climate smart, sustainable agriculture, especially in low-input, fragile environments. Its main strengths are: prolonged canopy cover, recycling of nutrients, drought resistance, stable dry matter allocation, large storage capacity of starch, high harvest index, easy vegetative reproduction, and its ability to prevent soil erosion. Enset also has high radiation use efficiency and is tolerant against repetitive removal of leaves and repetitive transplanting. The plant and crop architecture of enset are special and deserve to be investigated in more detail by architectural models, such as functional-structural plant models (FSPMs). Through such FSPMs we can investigate the consequences of (trans) planting and gap filling practices on crop performance. Similarly, FSPMs can be used to assess the effects of repetitive leaf pruning. Moreover, these models should be used for 3D modelling of rainfall interception and water transfer by individual leaves and the entire canopy, enabling the study of water storage in the plant, drought tolerance, water use efficiency and protection against erosion. The influence of leaf tearing and tattering on performance of individual leaves is also relevant. Effects on photosynthesis and transpiration can be either positive or negative at the level of the individual leaves. Upscaling these effects to plant and crop performance is essential. Finally, it is likely that current crop stands are infected by viruses. Quantifying the yield reduction by such infections and the relation between virus titre and crop performance can help to assess the need for virus-free planting material. Keywords/phrases: Functional-structural plant modelling, Leaf pruning, Sustainability, Transplanting, Virus infections


Triple negative breast cancer (TNBC) is the most aggressive breast cancer subtype with the worst prognosis and few effective therapies. Here, we undertook a screen of epigenetic chemical probes to systematically uncover the epigenetic regulators critical for TNBC growth. We identified MS023, an inhibitor of type I protein arginine methyltransferases (PRMTs), as having anti-tumor growth activity in TNBC in vitro and in vivo. Pathway analysis of TNBC cell lines indicates that the activation of interferon responses pre- and post-MS023 treatment is a functional biomarker and determinant of response; and these observations extend to a panel of patient-derived organoids. Inhibition of type I PRMT triggers an interferon response through the antiviral defense pathway with the induction of double-stranded RNA (dsRNA). The observed dsRNA accumulation is derived, at least in part, from inverted-repeat Alus (IR-Alus), many of which are expressed from retained introns induced by MS023, which inhibits arginine methylation of RNA-binding proteins and alters mRNA splicing machinery. Together, our results represent a shift in understanding the anti-tumor mechanism of type I PRMT inhibitors and provide a novel rationale and biomarker approach for the clinical development of type I PRMT inhibitors.


Feminism is a powerful conceptual tool for critiquing traditional sociological research, but notions of conducting 'feminist research' may contain some unchallenged assumptions about who should be researched and which methodologies are used. Two key concepts within feminist research - empowerment of women and the equality of the research relationship - are interrogated in the light of research conducted on a population of women unsympathetic to feminism and constructions of gender. This research suggests that whilst there is a need to conduct gender-sensitive work, too orthodox a definition of feminist research may inhibit rather than facilitate research which could lead to helpful insights for women. A better strategy might be to site the conflict in epistemology, rather than methodology, and to define feminist research in terms of values which it might uphold rather than techniques it might use. Doing feminist research on unsympathetic populations can lead to conflicts between the researcher and participant's construction of the meaning of gendered experience. Researchers can justify their accounts with reference to feminist 'successor sciences' which have been postulated as an alternative to traditional positivistic rationalism. In the context of this study both feminist standpoint theory and feminist postmodernism are considered as useful justifications for the decisions taken in the research.


Animals depend on other species to live, with monophagy being an extreme mode. Monophagous animals depend on their diet not only for nutritients but also for developmental and reproductive controls. Thus, dietary components may be useful in culturing tissues from monophagous animals. We hypothesized that a dedifferentiated tissue from the monophagous silkworm, Bombyx mori, would re-differentiate when cultured in a medium containing an extract of mulberry (Morus alba) leaves, the only food of B. mori. Over 40 fat-body transcriptomes were sequenced, and we concluded that it is possible to establish in vivo-like silkworm tissue cultures using their diet.


The authors report a case of Majocchi's granuloma and onychomycosis in a liver transplant recipient caused by a Trichophyton spp., phenotypically consistent with Trichophyton rubrum var. raubitschekii. A 48-year-old female patient who had undergone liver transplantation nine months earlier, presented with red papules and nodular lesions on her back, buttock and thigh of two months duration. She also had onychomycosis of toe nails for a few years, which worsened post transplant. Two fungal isolates were derived from her infected toe nails and nodular tissue. Physical, pathological and mycological examination, including KOH preparation, fungal culture and DNA sequencing of the internal transcribed spacer(ITS) of rRNA were performed. The clinical diagnosis was Majocchi's granuloma and onychomycosis caused by the Trichophyton rubrum var. raubitschekii. This is the first case report of this organism from China.


A case of fungal keratitis was diagnosed in a young female who had been wearing daily disposable soft contact lenses for 2 Years. No risk factor was demonstrated and specific treatment was effective. This case emphasizes that patients must be aware of the importance of hygiene as daily disposable contact lenses must be discarded daily.


We investigate the spin Hall magnetoresistance (SMR) in all-antiferromagnetic heterostructures α-Fe2O3/Cr2O3 with Pt contacts. When the temperature is ultralow (< 50 K), the spin current generated in the Pt layer cannot be transmitted through Cr2O3 (t = 4 nm), and the SMR is near zero. Meanwhile, when the temperature is higher than the spin fluctuation temperature T
 F (≈ 50 K) of Cr2O3 and lower than its Néel temperature T
 N (≈ 300 K), the spin current goes through the Cr2O3 layer and is reflected at the α-Fe2O3/Cr2O3 interface; an antiferromagnetic (negative) SMR is observed. As temperature increases higher than T
 N, paramagnetic (positive) SMR mainly arises from the spin current reflection at the Cr2O3/Pt interface. The transition temperatures from negative to positive SMR are enhanced with increasing Cr2O3 layer thickness, accompanied by the absence of SMR signals when t = 10 nm. Such a tunable SMR builds a bridge between spin transport and structures. It also enriches antiferromagnetic spintronics.


During the anisotropic growth from globular to wormlike micelles, the basic interactions among distinct parts of the surfactant monomer, its counterion, and additives are fundamental to tune molecular self-assembly. We investigate the addition of sodium salicylate (NaSal) to hexadecyltrimethylammonium chloride and bromide (CTAC and CTAB), 1-hexadecylpyridinium chloride and bromide (CPyCl and CPyBr), and benzyldimethylhexadecylammonium chloride (BDMC), which have the same hydrophobic tail. Their potential to enhance viscoelasticity by anisotropic micellar growth upon salt addition was compared in terms of (i) the influence of the headgroup structure, and (ii) the influence of surfactant counterion type. Employing proton nuclear magnetic resonance ((1)H NMR), we focused on the molecular conformation of surfactant monomers in the core and polar shell regions of the micelles and their interactions with increasing concentration of NaSal. The viscoelastic response was investigated by rotational and oscillatory rheology. We show that micellar growth rates can be tuned by varying the flexibility and size of the surfactant headgroup as well as the dissociation degree of the surfactant counterion, which directly influences the strength of headgroup-counterion pairing. As a consequence, the morphological transitions depend directly on charge neutralization by electrostatic screening. For example, the amount of salt necessary to start the rodlike-to-wormlike micelle growth depends directly on the number of dissociated counterions in the polar shell.


Today inRussiathere is no system of indicators, characterizing the level of research intensity of domestic industry through the assessment of the sustainability of the scientific production in the national economy of the country. The sake of development innovation economy of country it is necessary valuation scientifically – technology and productive potential, about at modernization and instruction personnel spend means smaller than building and forming a new specialist.


BACKGROUND
The aim of this study is to use modeling methods to estimate the antiviral activity of natural molecules extracted from Ginkgo biloba for the treatment of variola which is a zoonotic disease posing a growing threat to human survival. The recent spread of variola in nonendemic countries and the possibility of its use as a bioterrorism weapon have made it a global threat once again. Therefore, the search for new antiviral therapies with reduced side effects is necessary.

METHODS
In this study, we examined the interactions between polyphenolic compounds from Ginkgo biloba, a plant known for its antiviral activity, and two enzymes involved in variola treatment, VarTMPK and HssTMPK, using molecular docking.

RESULTS
The obtained docking scores showed that among the 152 selected polyphenolic compounds; many ligands had high inhibitory potential according to the energy affinity. By considering Lipinski's rules, we found that Liquiritin and Olivil molecules are the best candidates to be developed into drugs that inhibit VarTMPK because of their high obtained scores compared to reference ligands, and zero violations of Lipinski's rules. We also found that ginkgolic acids have good affinities with HssTMPK and acceptable physicochemical properties to be developed into drugs administered orally.

CONCLUSION
Based on the obtained scores and Lipinski's rules, Liquiritin, Olivil, and ginkgolic acids molecules showed interesting results for both studied enzymes, indicating the existence of promising and moderate activity of these polyphenols for the treatment of variola and for possible multi-targeting. Liquiritin has been shown to exhibit anti-inflammatory effects on various inflammation- related diseases such as skin injury, hepatic inflammatory injury, and rheumatoid arthritis. Olivil has been shown to have antioxidant activity. Olivil derivatives have also been studied for their potential use as anticancer agents. Ginkgolic acids have been shown to have antimicrobial and antifungal properties. However, ginkgolic acids are also known to cause allergic reactions in some people. Therefore, future studies should consider these results and explore the potential of these compounds as antiviral agents. Further experimental studies in-vitro and in-vivo are required to validate and scale up these findings.


Background and objective: The parkinson variant of multiple system atrophy (MSA-P) and progressive supranuclear palsy (PSP) present with atypical parkinsonism, which may be misdiagnosed as PD, particularly in early disease stages. It was previously shown that diffusion-weighted MRI (DWI) is a sensitive tool to discriminate MSA-P from PD based on increased apparent diffusion coefficients (ADCs) in the putamen. In this study DWI was evaluated in 10 patients with PSP compared with 13 patients with PD and 12 with MSA-P. Methods: Disease was diagnosed according to established diagnostic criteria and groups were matched for age, disease duration, and Hoehn and Yahr "off" stage. Regional ADCs (rADCs) were determined in different brain regions including basal ganglia, gray matter, white matter, substantia nigra, and pons. Results: In patients with PSP compared with those with PD, rADCs were significantly increased in putamen, globus pallidus, and caudate nucleus. Stepwise logistic regression analysis followed by receiver operating characteristics analysis identified an optimal cut-off value for putaminal rADC, discriminating PSP and PD with a sensitivity of 90% and a positive predictive value of 100%. DWI failed to discriminate PSP and MSA-P. Conclusions: These results show that DWI detects basal ganglia abnormalities in PSP patients within few years of disease onset, discriminating patients with PSP from those with PD, but not from those with MSA-P.