OBJECTIVE
To compare the efficacy of laparoscopic appendectomy (LA) and open appendectomy (OA) in the treatment of acute appendicitis.

DESIGN
A prospective randomized trial.

SETTING
A university teaching hospital.

PATIENTS
Eighty-one patients with a diagnosis of acute appendicitis were prospectively randomized to undergo either LA or OA. The two groups were matched for age and sex.

INTERVENTIONS
LA or OA.

MAIN OUTCOME MEASURES
Number of days in hospital and time to full recovery.

RESULTS
The mean hospital stay for LA was 3.23 days compared with 3.03 days for OA (p < 0.001). The mean number of narcotic injections required for patients in the LA group was 4.05 compared with 5.58 for patients in the OA group (p < 0.001). The mean time to complete recovery for patients in the LA group was 9.0 days compared with 16.2 days for patients in the OA group (p < 0.001). The mean operative time for LA was 73.8 minutes compared with 45.0 minutes for OA (p < 0.001). Three patients in the LA group had intra-abdominal abscesses (p > 0.25). No significant difference in wound infection rates was demonstrated (p > 0.05). Similarly, pain scores at 7 and 28 days showed no significant difference (p > 0.05).

CONCLUSIONS
With LA significantly fewer narcotic injections are required and there is a more rapid return to normal activities. LA takes longer to perform and was associated with three intra-abdominal abscesses. In cases of simple acute appendicitis the hospital stay for LA is significantly shorter.


To predict the response of plant pathogens to climate warming, data are needed on current thermal adaptation, the pathogen's evolutionary potential, and the link between them. We conducted a common garden experiment using isolates of the fungal pathogen Rhynchosporium commune from nine barley populations representing climatically diverse locations. Clonal replicates of 126 genetically distinct isolates were assessed for their growth rate at 12°C, 18°C, and 22°C. Populations originating from climates with higher monthly temperature variation had higher growth rate at all three temperatures compared with populations from climates with less temperature fluctuation. Population differentiation in growth rate (QST) was significantly higher at 22°C than population differentiation for neutral microsatellite loci (GST), consistent with local adaptation for growth at higher temperatures. At 18°C, we found evidence for stabilizing selection for growth rate as QST was significantly lower than GST. Heritability of growth rate under the three temperatures was substantial in all populations (0.58–0.76). Genetic variation was lower in populations with higher growth rate at the three temperatures and evolvability increased under heat stress in seven of nine populations. Our findings imply that the distribution of this pathogen is unlikely to be genetically limited under climate warming, due to its high genetic variation and plasticity for thermal tolerance.


Cyclin-dependent kinase inhibitor p16INK4a is implicated in replicative senescence, cell immortalization, and tumor generation. However, the mechanism regulating its overexpression in senescent cells is unknown. We used the enhanced green fluorescent protein reporter system to scan regulatory elements in the upstream region of p16INK4a. The results of 5′-deletion studies indicated that the transcription regulatory elements contributing to overexpression of p16INK4a in senescent cells were located in the region of the p16INK4a promoter from −622 to −280 bp. According to the results of in vitro DNase I footprinting, EMSA, and Southwestern blotting, we found a novel negative regulatory element, the INK4a transcription silence element (ITSE), at −491 to −485 bp of the p16INK4a promoter. A 24-kDa protein that was highly expressed in young cells may inhibit the expression of p16INK4a by interacting with the ITSE. The activity of the p16INK4a promoter increased significantly in young cells when the ITSE was deleted. The GC-rich region of the p16INK4a promoter from −466 to −451 was a positive transcription regulatory element. Deletion of this region showed 91.4% loss of p16INK4a promoter activity in senescent cells, and the promoter activity decreased by 41.2% in young cells comparably.


The widespread environmental presence and commercial use of nanoparticles have raised significant health concerns as a result of many in vitro and in vivo assays indicating toxicity of a wide range of nanoparticle species. Many of these assays have identified the ability of nanoparticles to damage cell membranes. These interactions can be studied in detail using artificial lipid bilayers, which can provide insight into the nature of the particle-membrane interaction through variation of membrane and solution properties not possible with cell-based assays. However, the scope of these studies can be limited because of the low throughput characteristic of lipid bilayer platforms. We have recently described an easy to use, parallel lipid bilayer platform which we have used to electrically investigate the activity of 60 nm diameter amine and carboxyl modified polystyrene nanoparticles (NH2-NP and COOH-NP) with over 1000 lipid bilayers while varying lipid composition, bilayer charge, ionic strength, pH, voltage, serum, particle concentration, and particle charge. Our results confirm recent studies finding activity of NH2-NP but not COOH-NP. Detailed analysis shows that NH2-NP formed pores 0.3-2.3 nm in radius, dependent on bilayer and solution composition. These interactions appear to be electrostatic, as they are regulated by NH2-NP surface charge, solution ionic strength, and bilayer charge. The ability to rapidly measure a large number of nanoparticle and membrane parameters indicates strong potential of this bilayer array platform for additional nanoparticle bilayer studies.


Abstract Objectives Evidence for a genetic influence on psychological treatment outcome so far has been inconsistent, likely due to the focus on candidate genes and the heterogeneity of the disorders treated. Using polygenic risk scores (PRS) in homogenous patient samples may increase the chance of detecting genetic influences. Methods A sample of 342 phobic patients treated either for clinically relevant dental fear (n = 189) or other (mixed) phobic fears (n = 153) underwent highly standardised exposure-based CBT. A brief five-session format was used to treat dental fear, whereas longer multi-session treatments were used with the mixed-fear cohort. PRS were calculated based on large genetic studies of Neuroticism, Educational Attainment (EA), Intelligence, and four psychopathology domains. We compared PRS of post-treatment and follow-up remitters and non-remitters and regressed PRS on fear reduction percentages. Results In the dental fear cohort, EA PRS were associated with treatment outcomes, i.e. drop-out, short- and long-term remission state, fear reduction, and attendance of subsequent dental appointments. In the mixed fear treatment cohort, no gene effects were observable. Conclusions Results indicate the importance of EA-related traits for outcomes following brief, but not long, standardised exposure-based CBT. Such use of PRS may help inform selection and tailoring of treatments.


In a previous paper we considered the function χ(r) ≡ (1/N) Σk eik·r, where the sum runs over the first Brillouin zone of a crystal, and its expansion into series of Cubic Harmonics Kj:χ(r)=∑j=0∞gj(r)×Ki(θ,φ). Houston's method was used in order to find the radial functions gj(r) for several values of j, for χ(r) given for the simple cubic and the face‐centered cubic lattices. In this paper, the same considerations are applied to χ(r) given for the body‐centered lattice. gj(r), with j = 0, 2, 3, are calculated in the region of small r which is assumed as 0 ≤ r ≤ 2a, where a is the lattice constant. In most of the problems of solid‐state physics, where the function χ(r) occurs, it is satisfactory to know its values only for small r, usually not larger than 2a. The function g0(r) is calculated using 3‐, 6‐, and 9‐term expansion formulas, g2(r) and g3(r) using only 3‐ and 6‐term formulas. Comparing gj(r) obtained from the formulas with different number of terms it is established that, for r in the region 〈0, ...


Backgrounds: In Chronic Obstructive Pulmonary Disease (COPD) a multi factorial effort limitation becomes pro- gressively relevant as the disease progresses in the consecutive stages. It is measured by both six minutes walking test (6MWT) and maximal cardiopulmonary incremental test (CPET). Aim: It is important to assess in each stage of dis-ease the metabolic load during 6MWT referring to the outcome of CPET and to ascertain whether there is a significant rela- tionship between the measures obtained by CPET and 6MWT. Methods: Four group of fifteen patients affected by COPD in stage I to IV underwent 6MWT and maximal CPET in the same day and results were compared to a group of healthy people. Airflow obstruction was measured by whole body plethysmography, blood gases by gas analysis, maxi- mal oxygen consumption and metabolic parameters by ergometer, lactic acid levels by analyzer. Results: Maximal oxygen consumption (V'O2max) and 6MWT are progressively impaired and related (V'O2max = 1.25 ? 0.26, 1.152 ? 0.4, 1.03 ? 0.44, .85 ? 0.2 l/m; 6MWD = 452 ? 84, 446 ? 82, 381 ? 165, 200 ? 100 respectively in GOLD I to IV stage). Oxygen consumption (V'O2) during 6MWT becomes stable after 3 - 4 minutes and reached at the end of the test close to those measured at de-compensated metabolic acidosis anaerobic threshold (TDMA) (85 ± 0.4 l/m vs. 9 ? 0.4 l/m) in stage I to III, while in COPD there is no difference between V'O2max and V'O2 during 6MWT (0.85 ? 0.2 vs. 0.8 ? 0.23 l/m). 6MWT is more suitable to determine oxygen desaturation than CPET (dSaO2 ?4 ± 2% vs. ?2 ± 1%). 6MWD, the workload performed in 6MWT and V'O2max are significantly related. Conclusion: 6MWT looks as a suitable sub maximal test related CPET. Metabolic requirements under 6MWT are close to TDMA and are obtained in a suitable, self paced, usual exercise, close to everyday experience and thus related to activity daily levels. As the disease worsens the differences between V'O2 during 6MWT and V'O2max wane.


The luteinizing hormone (LH) receptor plays an important role in fertility and certain cancers. The endogenous ligands human chorionic gonadotropin (hCG) and LH bind to the large N terminal domain of the receptor. We recently reported on the first radiolabeled low molecular weight (LMW) agonist for this receptor, [(3)H]Org 43553, which was now used to screen for new LMW ligands. We identified a terphenyl derivative that inhibited [(3)H]Org 43553 binding to the receptor, which led us to synthesize a number of derivatives. The most potent compound of this terphenyl series, 24 (LUF5771), was able to increase the dissociation rate of [(3)H]Org 43553 by 3.3-fold (at 10 muM). In a functional assay, the presence of 24 resulted in a 2- to 3-fold lower potency of both Org 43553 and LH. Thus, the compounds presented in this paper are the first LMW ligands that allosterically inhibit the LH receptor.


Background: Coronavirus disease-2019 (COVID-19) is a public health problem where the world's 3.3 billion global workforces are at risk of losing their livelihoods. The present study sought to determine the knowledge, and practices of community health care workers (HCWs) toward COVID-19 in the Regional Director of Health Services in Galle District, Sri Lanka. Methods: A descriptive cross-sectional study was conducted with the objective of knowledge, and practices among healthcare workers at the Regional Director of Health Services in Galle district, Sri Lanka, during August 2020. A selfadministered questionnaire was used as the study instrument. The sample consisted of 20 -Medical Officers of Health,18 Additional Medical Officers of Health, 14-Senior Public Health Inspectors, and 101Public Health Inspectors, who are directly involved in the management of the COVID-19 pandemic. Knowledge and practices towards COVID-19 were assessed by using a pre-tested questionnaire. A cut-off of 60% was used to determine sufficient knowledge (≥60%), and good practice (≥60%). All analyses were performed using SPSS version 21, chi-square and binary logistic regression were performed for the significance of the data. Results: Of the 153 healthcare workers, approached, 118(77%) responded. A majority of the participant were male (76.7%, n=90). Overall, 83.1%(n=98) had a sufficient level of knowledge, and 87.3%(n=103) had high to moderate level preventive practices toward COVID-19. Univariate and multivariate analysis showed: Female health care workers had high knowledge level than male health care workers (OR=6.86, 95% CI:1.07-235.6; p=0.05) and junior health care workers had good preventive practices than senior workers (OR: 3.63; 95%CI: 1.01-120.3; p=0.05). Conclusion: Continued professional education on Covid-19 is advised among healthcare workers in Sri Lanka to improve knowledge, hence averting negative attitudes and promoting positive preventive and therapeutic practices.


In mammalian cells, many secretory proteins are targeted to the endoplasmic reticulum co-translationally, by the signal recognition particle (SRP) and its receptor. In Escherichia coli, the targeting of secretory proteins to the inner membrane can be accomplished post-translationally. Unexpectedly, despite this variance, E. coli contains essential genes encoding Ffh and FtsY with a significant similarity to proteins of the eukaryotic SRP machinery. In this study, we investigated the possibility that the prokaryotic SRP-like machinery is involved in biogenesis of membrane proteins in E. coli. The data presented here demonstrate that the SRP-receptor homologue, FtsY, is indeed essential for expression of integral membrane proteins in E. coli, indicating that, in the case of this group of proteins, FtsY and the mammalian SRP receptor have similar functions.


— Alternative fuel use in cement industry has seen a rise in the recent years in lieu of the growing concerns about the growing share of the industry in global green house emissions which stand at 8% of overall carbon dioxide emissions worldwide. Prominent amongst the reasons for this high emission is the use of conventional coal in providing heat requisite for processing in the cement industry. The use of alternative fuel, however, has started a positive downward trend in the emissions of the industry. The use of alternative fuel, most prevalent among which is Refuse Derived Fuel (RDF), has a twofold advantage: economic fuel for cement production, and a venue for disposing off the solid waste in the landfills around big cities. This experiment of alternative fuels use in cement industry is largely without any impact assessment on the economy and ecology of the cement manufacturing. Obviously the technical assessment has been performed by the industries themselves in terms of energy contents, the larger impact of these fuels on economy and environment is still unknown or not published. This research undertook the technical analysis of these alternative fuels used in three cement industries in Pakistan comprised of characteristics like calorific value, Sulphur and chlorine contents, carbon emissions accruing from the use of the these fuels. In addition the economics associated with the use of these fuels were also investigated through comparison with economy of the conventional fuels.


Generalised anhidrosis (GA) shows a uniform clinical picture whether the pathogenesis involves intrinsic abnormalities of sweat glands or postganglionic sympathetic cholinergic nerve dysfunction. We describe two patients who presented intolerance to heat and anhidrosis. In the first patient, symptoms started at 33 years of age, and were associated with absent tendon reflexes and a mydriatic right pupil unreactive to light. The other patient had been unable to sweat since birth. GA was diagnosed on the basis of clinical findings and thermoregulatory tests. Microneurography and morphological analysis of the skin and its innervation disclosed a different lesion site underlying GA in the two patients, and distinguished between a postganglionic autonomic nerve fibre lesion and sweat gland dysfunction.


Abstract Myogenic fibrosis of the flexor tendons in a 23-year-old patient was caused by intense drug abuse. He was presented in the clinic with spastic flexor tendon contracture of his right hand. The patient was treated by tendon elongation with a satisfactory result. The treatment of flexor tendon contracture in those cases is very difficult and needs to be done in a complex way.


A new modification of specific estrogen-binding protein (SEBP) assay in the liver was used to measure the content of this protein at different stages of ontogenesis in male and female rats after administration of testosterone propionate (TP). It was shown that liver capability to form SEBP could be initially programmed by androgens. The crucial period of the SEBP-determining action of androgens in females is not restricted, since potential capability of androgens of primary induction of SEBP may be realized both neonatally and in the course of pubertation. The emergence of SEBP in the liver of males may be the result of natural pre(neo)natal androgenization. Androgens do not play any decisive role in the control of the level of induced SEBP, inasmuch the content of SEBP in the liver of non-pubertal and pubertal males does not appreciably change after TP administration but grows with pubescence. SEBP is capable of long-term existence in the absence of androgens. The presence of the ovaries produces an inhibitory effect on the level of androgen-induced SEBP and the time of its existence after TP discontinuation. Hypophysectomy does not provoke SEBP emergence in pubertal intact and ovariectomized females but prevents its induction with androgens. Adrenal- and thyroectomy produce no influence on the SEBP-programming effect of TP or promote its spontaneous appearance in the same groups of female rats.


The spermatogenesis, spermatozoon differentiation and fine structure of Acanthobothrium filicolle benedenii Loennberg, 1889 and Onchobothrium uncinatum (Rud., 1819) were studied by means of light and electron microscopy. Spermatogenesis in both species is of the rosette type. During sperm differentiation, the five following stages have been distinguished: (1) formation of arching membranes and differentiation zone; (2) nuclear elongation; (3) formation of two flagella with a median cytoplasmic process; (4) flagellar rotation; (5) fusion of two flagella with the median cytoplasmic process induced by the migration of nucleus into the latter. The mature spermatozoa of both species are threadlike structures about 250 mum long. They consist of two axonemes of the platyhelminth type (9+1 pattern), elongated nucleus and cortical microtubules embedded in a cytoplasmic matrix containing numerus beta-glycogen particles. The body which appears on cross-sections as crest, lateral with respect to the axoneme, is present in both species. Such a body is reported for the first time in Cestode spermatozoa. There is no mitochondrion in the two Onchobothriidae sperms studied.


Purpose: In an eye with geographic atrophy (GA) secondary to age-related macular degeneration, we correlated ex vivo histologic features with findings recorded in vivo using optical coherence tomography (OCT), near-infrared reflectance imaging, and fundus autofluorescence. Methods: In the left eye of an 86-year-old white woman, in vivo near-infrared reflectance and eye-tracked OCT B-scans at each of 6 clinic visits and a baseline fundus autofluorescence image were correlated with high-resolution histologic images of the preserved donor eye. Results: Clinical imaging showed a small parafoveal multilobular area of GA, subfoveal soft drusen, refractile drusen, hyperreflective lines near the Bruch membrane, subretinal drusenoid deposit (reticular pseudodrusen), and absence of hyperautofluorescent foci at the GA margin. By histology, soft drusen end-stages included avascular fibrosis with highly reflective cholesterol crystals. These accounted for hyperreflective lines near the Bruch membrane in OCT and plaques in near-infrared reflectance imaging. Subretinal drusenoid deposit was thick, continuous, extracellular, extensive outside the fovea, and associated with distinctive retinal pigment epithelium dysmorphia and photoreceptor degeneration. A hyporeflective wedge corresponded to ordered Henle fibers without cellular infiltration. The external limiting membrane descent, which delimits GA, was best visualized in high-quality OCT B-scans. Retinal pigment epithelium and photoreceptor changes at the external limiting membrane descent were consistent with our recent histologic survey of donor eyes. Conclusion: This case informs on the extent, topography, and lifecycle of extracellular deposits. High-quality OCT scans are required to reveal all tissue features relevant to age-related macular degeneration progression to GA, especially the external limiting membrane descent. Histologically validated signatures of structural OCT B-scans can serve as references for other imaging modalities.


This study explored the feasibility and clinical value of susceptibility weighted imaging (SWI) in depicting fetal vertebral growth and related anomalies. The results showed that vertebral development in fetuses on SWI was remarkably linearly correlated with gestational ages. In addition, SWI demonstrated superior image quality and higher diagnostic accuracy compared to conventional Half-Fourier acquisition single-shot turbo spin-echo (HASTE) or true fast imaging with steady-state precession (TrueFISP) sequences. In conclusion, SWI is a reliable choice when imaging fetal vertebrae and vertebral anomalies.


Narratives come out to arrange the human experience altered by the disruption in its canonical status. In this sense, a disease like cancer can be considered an exceptional experience that requires the narrative to mean it. This study investigated the construction of meanings about the disease and death in the narratives of children with cancer in different stages of treatment. Thus, six sessions of play were performed with each child. Data analysis showed that children in longer treatment tend to conclude their narratives with the death of the characters and the children under shorter treatment time present narratives related both to physical discomfort to which the treatment leads to and impairments that the disease cause in their lives. The results indicate the need for greater attention on how children talk about the disease and the subsequent possibility of death during the course of cancer treatment, so that we can be aware of the diversity of treatment moments, understanding that they configure different subjective relationships about children's health problem and death.


We develop and extend a theoretical framework to analyze the impacts of changes in temperature and alkalinity on the ocean‐atmosphere carbon partitioning. When investigating the impact of temperature, we assume that there is no change in the global ocean alkalinity. This idealized situation is probably most relevant on intermediate timescales of hundreds to thousands of years. Our results show that atmospheric pCO2 depends approximately exponentially on the average ocean temperature, since the chemical equilibria involved have an exponential (Arrhenius‐type) dependence. The dependence of pCO2 on alkalinity is more complicated, and our theory suggests several regimes. The current ocean‐atmosphere system appears to have an exponential dependence of pCO2 on global mean ocean alkalinity, but at slightly higher alkalinities, the dependence becomes a power law. We perform experiments with a numerical physical‐biogeochemical model to test the validity of our analytical theory in a more complex, ocean‐like system: in general, the numerical results support the analytical inferences.


While hippocampal and cortical mechanisms of memory consolidation have long been studied, their interaction is poorly understood. We sought to investigate potential interactions with respect to trace dominance, strengthening, and interference associated with postencoding novelty or sleep. A learning procedure was scheduled in a watermaze that placed the impact of novelty and sleep in opposition. Distinct behavioural manipulations—context preexposure or interference during memory retrieval—differentially affected trace dominance and trace survival, respectively. Analysis of immediate early gene expression revealed parallel up-regulation in the hippocampus and cortex, sustained in the hippocampus in association with novelty but in the cortex in association with sleep. These findings shed light on dynamically interacting mechanisms mediating the stabilization of hippocampal and neocortical memory traces. Hippocampal memory traces followed by novelty were more dominant by default but liable to interference, whereas sleep engaged a lasting stabilization of cortical traces and consequent trace dominance after preexposure.


Objectives The purpose of this study was to make clear the descriptive epidemiology and the relationship between the room temperature of living room, bedroom, dressing room, and outdoor during winter, based on the climate areas in Japan.Methods This study targeted 3,781 people, survey for 5 years from 2014, based on the Smart Wellness Housing (SWH) project, which was carried out nationwide with the support of the Ministry of Land, Infrastructure, Transport and Tourism. During winter, we recorded the outdoor temperature and living room, bedroom, and dressing room temperatures at 1 m above the floor and near the floor for two weeks. Covariance structure analyses were used to clarify the relationship between room temperature and outdoor temperature based on six climate areas in Japan. The analyses were performed using SPSS22.0 and AMOS22.0 for Windows.Results The temperature near the floor inside the house was lower than the room temperature at 1 m above the floor, and both the room and near the floor temperature in the morning tended to be the lowest. The temperature disparity between the dressing room and living room was the largest. Based on climate areas, the room temperature in the Area 2 was the highest, while the room temperature in the Area 4 was the lowest. The outdoor temperature was more closely associated with the room temperature near the floor than the room temperature at 1 m above the floor, especially in the southern Areas, except Area 7.Conclusion The temperature near the floor inside the house was lower than room temperature at 1 m above the floor. The temperature disparity between dressing room and living room was the largest. The room temperature and near the floor temperature were lowest in the energy-saving Area 4. The outdoor temperature was more closely associated with the room temperature near the floor than the room temperature at 1 m above the floor, especially in the southern Areas, except Area 7.


South Africa is the largest CO2 emitter on the African continent. These emissions stem from a heavy reliance on coal as the primary energy fuel and contributor toward socio-economic development. The South African government has targeted reducing CO2 emissions by more than half in the next 10 years. To meet climate change mitigation scenarios, while alleviating continued emissions, South Africa will look to technologies such as carbon capture, utilisation and storage. Initial assessments of South Africa's potential for CO2 storage have focused on deep saline aquifers within volcano-sedimentary sequences along the near and offshore regions. Sustaining the Just Transition will, however, require additional storage capacity. In this study, we make an initial assessment of possible CO2 storage in basaltic sequences of the Ventersdorp Supergroup. Geological and mineralogical information was ascertained from borehole data. The geological information suggests that the subsurface extent of the Ventersdorp Supergroup is at least 80 000 km2 larger than previously mapped, extending beneath major point-source CO2 emitters and active coalfields. Furthermore, petrographic analyses suggest pore space of up to ca 15% with minimal alteration, and preservation of mafic silicate minerals that would enable reactive carbonation of injected CO2. Notable metasomatic and hydrothermal alteration is confined to significant contact horizons, such as the lowermost Ventersdorp Contact Reef. These results suggest that basaltic sequences may exponentially increase South Africa's CO2 sequestration storage capacity and may have a significant impact on the country's Just Transition.


Background: Most non-syndromic congenital heart defects (CHD) are caused by a complex interaction between maternal lifestyle factors, environmental exposures, and maternal and fetal genetic variants. Maternal periconceptional intake of folic acid containing vitamin supplements is reported to decrease the risk of CHD. The 677C→T and 1298A→C polymorphisms in the methylenetetrahydrofolate reductase (MTHFR) gene decrease enzyme activity. Objective: To examine the relation between CHD and maternal and fetal MTHFR polymorphisms Methods: 375 nuclear families were studied. The transmission/disequilibrium test was used to test for transmission distortion in complete triads. A log-linear approach was used to test for associations between CHD and maternal and offspring polymorphisms, and to estimate independently the contributions of maternal and fetal variants to relative risks. Haplotype frequencies were estimated and a haplotype transmission disequilibrium test carried out. Results: The 1298C allele was transmitted less often than expected (p = 0.0013). There was no distortion in the transmission of the 677T allele, neither was there evidence of a parent of origin effect in the transmission of either of the single nucleotide polymorphisms. The 677C–1298C haplotype was also transmitted less often than expected (p = 0.0020). The relative risk associated with inheriting one copy of the 1298C allele was 0.64 (95% confidence interval, 0.48 to 0.87) and the that associated with inheriting two copies of the 1298C allele, 0.38 (0.21 to 0.70). Conclusions: The apparent protective effect of the MTHFR 1298C allele against CHD could have several explanations and further study is needed.


Ensuring that wireless sensor networks (WSNs) are robust to failures requires that the physical network topology will offer alternative routes to the sinks. This requires sensor network deployments to be planned with an objective of ensuring some measure of robustness in the topology, so that when failures occur that routing protocols can continue to offer reliable delivery. Our contribution is a solution that enables fault-tolerant WSN deployment planning by judicious use of a minimum number of additional relay nodes. A WSN is robust if at least one route to a sink is available for each remaining sensor node after the failure of up to k-1 nodes. In this paper, we define the problem for increasing WSN reliability by deploying a number of additional relay nodes to ensure that each sensor node in the initial design has k node-disjoint paths to the sinks. We present GRASP-ARP, a centralised offline algorithm to be run during the initial topology design to solve this problem. We have implemented this algorithm and demonstrated in simulation that it improves the efficiency of relay node placement for k node-disjoint paths compared to the most closely related published algorithms.


The article deals with the issues of determining the sustainable socio-economic development of the region. Various points of view of domestic and foreign scientists and researchers to the study of sustainable development of the socio-economic development of the region are analyzed. Based on the analysis of modern literature, the definitions are clarified and methods for assessing the dynamics of sustainable development of the socio-economic development of the region in modern conditions are supplemented. When writing the article, the authors took state programs as a basis, including the Concept for the transition of the Republic of Kazakhstan to a "green economy", etc.


We investigate some properties of string theory on Kaluza-Klein Melvin background. We discuss what happens when closed string tachyons in the theory condense, by using a linear sigma model of the Kaluza-Klein Melvin background. e-mail address : email@example.com


Single-pass connected components analysis (CCA) algorithms suffer from a time overhead to resolve labels at the end of each image row. This work demonstrates how this overhead can be eliminated by replacing the conventional raster scan by a zig-zag scan. This enables chains of labels to be correctly resolved while processing the next image row. The effect is faster processing in the worst case with no end of row overheads. CCA hardware architectures using the novel algorithm proposed in this paper are, therefore, able to process images at higher throughput than other state-of-the-art methods while reducing the hardware requirements. The latency introduced by the conversion from raster scan to zig-zag scan is compensated for by a new method of detecting object completion, which enables the feature vector for completed connected components to be output at the earliest possible opportunity.


Cognitive psychologists have long hypothesized that experiences are encoded in a temporal context that changes gradually over time. When an episodic memory is retrieved, the state of context is recovered—a jump back in time. We recorded from single units in the MTL of epilepsy patients performing an item recognition task. The population vector changed gradually over minutes during presentation of the list. When a probe from the list was recollected, the population vector reset to the neighborhood of the original presentation of that probe during study—a neural "jump back in time". Probes that were not recollected did not cause a jump back in time. These results constitute the first direct evidence that recollection of an episodic memory in humans is associated with recovery of a gradually-changing state of temporal context—a neural "jump-back-in-time" that parallels the act of remembering.


We propose and study a simple stochastic model for the dynamics of a limit order book, in which arrivals of market order, limit orders and order cancellations are described in terms of a Markovian queueing system. Through its analytical tractability, the model allows to obtain analytical expressions for various quantities of interest such as the distribution of the duration between price changes, the distribution and autocorrelation of price changes, and the probability of an upward move in the price, conditional on the state of the order book. We study the diffusion limit of the price process and express the volatility of price changes in terms of parameters describing the arrival rates of buy and sell orders and cancelations. These analytical results provide some insight into the relation between order flow and price dynamics in order-driven markets.


Abstract Allomembers A and B, re-defined herein, are the uppermost components of the Dunvegan Formation, and are of ?late Middle to early Late Cenomanian age. They record the final drowning of the huge Dunvegan delta complex that occupied the western margin of the Cretaceous foreland basin in Alberta and British Columbia. During deposition of allomembers A and B, the delta-front back-stepped north-westward by about 220 km relative to allomember C, on a timescale estimated at 105–440 k.y. Allomembers A and B are now divided into three sequences A1–A3 and B1–B3, bounded by marine transgressive surfaces; each sequence is estimated to span approximately 18–72 k.y. Sequences shoal upward and represent wave-influenced delta, prodelta, and coastal plain environments. Sequence B3 is incised by an extensive system of narrow (much less than 1 km) sandstone-filled paleo-valleys, up to 16 m deep. Although sequences rarely exceed 10 m thick, they are mappable for hundreds of km and appear to be primarily of allogenic (?eustatic) origin. Sequences were probably deposited in water no more than approximately 15 m deep and each records at least several metres of relative sea-level fall. Eustatic changes on a vertical scale of several metres, over a few tens of thousands of years are potentially attributable to thermal expansion/contraction of seawater, water storage on land, and glacio-eustasy. All three mechanisms may have contributed to the observed sea-level changes, and were probably driven by orbitally-modulated climate cycles. A regional isopach map of allomember C shows negligible updip (westward) thickening, suggesting that contemporaneous thrust loading of the basin margin was minimal. In contrast, allomembers A and B collectively show dramatic thickening to the west, suggestive of renewed loading in that direction. Although all sequences in allomembers A and B thicken westward, this trend is most prominent in sequences B3 to A3, suggesting that the rate of tilting accelerated over time. The transgressive limit of the shoreline mapped for successive sequences shows about 20 km of backstep per sequence, with the principal transgressive direction being towards the NW. This is oblique to the pattern of flexural subsidence inferred from isopach mapping and suggests that the depositional surface (coastal plain and prodelta) was inclined down to the SE, despite maximum tectonic subsidence being down to the west. This implies that the rate of sediment supply exceeded that of subsidence, and that depositional systems were able to maintain a slope inclined from NW to SE. The overall transgression recorded by allomembers A and B appears to have been strongly influenced by an accelerating rate of flexural subsidence, and, probably by slow eustatic rise during the Greenhorn transgression. However, this trend was modulated by higher-rate eustatic oscillations of at least several metres that caused corresponding shoreline excursions of several tens of kilometres within an overall transgressive regime.


Background Autoimmunity in Rheumatoid arthritis (RA) patients is characterized by a spectrum of anti-modified protein antibodies (AMPA) directed against post-translationally modified (PTM) proteins. The best-known AMPA in RA are anti-citrullinated protein antibodies (ACPA). Much less is known about the occurrence and aetiology of other AMPA responses in RA such as autoantibodies directed to malondialdehyde-acetaldehyde (MAA) adducts, acetylated antigens, and carbamylated proteins. Anti-carbamylated protein (anti-CarP) autoantibodies recognize carbamylated proteins containing a homocitrulline, a PTM structurally similar to citrulline. With the presence of various AMPA responses in RA, PTM proteins have been implicated in the breach of autoreactive B-cell tolerance leading to the formation of these autoantibodies. At present it is unkown how AMPA are generated and how autoreactive B-cell responses against PTM proteins are induced. Objectives To investigate how PTM proteins, more specifically carbamylated proteins, could contribute to a breach of B-cell tolerance. Methods Serum reactivity towards five different carbamylated proteins was determined for 160 RA-patients and 40 healthy individuals. Anti-CarP antibody cross-reactivity was studied by inhibition experiments. Mass spectrometry was performed to identify carbamylated self-proteins in human rheumatic and osteoarthritic joint tissue. Mice were immunized with carbamylated- or non-modified foreign (OVA) and self-antigens (mouse Albumin). Sera of immunized mice and monoclonal antibodies were analyzed for antigen reactivity. Results We show that anti-CarP antibodies in RA are highly cross-reactive towards multiple carbamylated proteins, including modified self- as well as modified non-self proteins. Immunization with carbamylated foreign proteins (Ca-OVA) induced a strong anti-CarP response against both carbamylated foreign- and self-proteins. Similar to murine serum anti-CarP antibodies, murine monoclonal anti-CarP antibodies were highly specific and cross-reactive to multiple carbamylated (auto)antigens. Although citrulline greatly resembles homocitrulline residues in structure, murine anti-CarP antibodies differ in antigen recognition profile from ACPA as they are able to discriminate between citrullinated and homocitrullinated forms of the same protein. Interestingly, we were able to identify carbamylated-albumin, in RA synovial tissue, indicating that albumin is present in carbamylated form locally in the inflamed joint. Conclusions Self-reactive AMPA-responses can be induced by exposure to foreign proteins containing PTM. Our findings show that autoreactive B-cell responses against PTM self proteins can be induced by exposure to PTM foreign proteins and provide new insights on the breach of autoreactive B-cell tolerance by foreign proteins. Disclosure of Interest None declared


In every year, Indonesia has some problems related to inflation.The general
accounting accepting principles is historical method, this concept does not recognize
inflation as influencing change during transaction period due to Stable Monetery Unit.
These facts reveal into relevance of corporate financial statements. To find the resistence of
the company in facing crisis and competition conditions which are difficult to predict,
further more the additional report from the general price level accounting (GPLA) is
required. This concept assessment the actual value of rupiah of the products or services
exchanged known as purchasing power. The purpose of this research is to analyze the
fairness of financial statements based on GPLA method. Description content and table
analysis is applied by theoritical comparison. The conclusion of this paper indicates that
the financial statement of PT HM Sampoerna has presented fairly by GPLA method.


We have developed a hybrid wind tunnel, where 2D measurement-integrated (MI) simulation, which utilizes actual data acquired from real air flow behind a square cylinder, plays an important role in improving the accuracy of the numerical analysis. The wind tunnel requires an accompanying visual analysis tool with which we can effectively peer into the relationships between the actual and simulated flow fields. In this paper, we attempt to exploit an augmented reality display to that end. The basic idea is to superimpose the computationally-visualized MI simulated pressure field onto the actual flow velocity structure physically-visualized with oil misttraced streaklines instantaneously. Spatial registration of these two visual sources is rather straight-forward since the fixed cylinder of the wind tunnel is easily identified, whereas visualizing the MI simulated pressure field can be characterized with a sophisticated scheme based on differential topology. Considering the fact that vortex centers are located at local minima in the pressure field, and each minimum is surrounded by a derived topological feature called ridge cycle, we can colorize the field adaptively and keep track of Karman vortex streets robustly, regardless of drastic change in the Reynolds number of the flow field.


This paper deals with multiobjective integer programming problems by considering fuzzy goals of the decision maker for objective functions. After determining the fuzzy goals of the decision maker, if the decision maker specifies the reference membership values, the corresponding Pareto optimal solution can be obtained by solving the augmented minimax problem which becomes an integer programming problem. For solving the problem, decoding algorithms for 0-1 programming problems are revised and ringed double strings are also introduced. Then an interactive fuzzy satisficing method is presented together with an illustrative numerical example.


Mutations in ribosomal protein (RP) genes can result in the loss of erythrocyte progenitor cells and cause severe anemia. This is seen in patients with Diamond-Blackfan anemia (DBA), a pure red cell aplasia and bone marrow failure syndrome that is almost exclusively linked to RP gene haploinsufficiency. While the mechanisms underlying the cytopenia phenotype of patients with these mutations are not completely understood, it is believed that stabilization of the p53 tumor suppressor protein may induce apoptosis in the progenitor cells. In stark contrast, tumor cells from zebrafish with RP gene haploinsufficiency are unable to stabilize p53 even when exposed to acute DNA damage despite transcribing wild type p53 normally. In this work we demonstrate that p53 has a limited role in eliciting the anemia phenotype of zebrafish models of DBA. In fact, we find that RP-deficient embryos exhibit the same normal p53 transcription, absence of p53 protein, and impaired p53 response to DNA damage as RP haploinsufficient tumor cells. Recently we reported that RP mutations suppress activity of the AKT pathway, and we show here that this suppression results in proteasomal degradation of p53. By re-activating the AKT pathway or by inhibiting GSK-3, a downstream modifier that normally represses AKT signaling, we are able to restore the stabilization of p53. Our work indicates that the anemia phenotype of zebrafish models of DBA is dependent on factors other than p53, and may hold clinical significance for both DBA and the increasing number of cancers revealing spontaneous mutations in RP genes.


We report observation of a new non dissipative and non local Josephson current, carried by quartets, each made of four entangled electrons originating from a pair of Cooper pairs. This super-current is a result of a new kind of Andreev bound states, formed between three biased superconducting terminals deposited on a semiconducting nanowire. Sensitive cross-correlation measurements of current fluctuations, accompanied by non-local conductance measurements, proves the non local nature of the supercurrent and points to its origin. In addition, a rich sub-gap structure, resulting from non local multiple Andreev reflections, was observed. An extensive and detailed theoretical study is intertwined with the experimental results.


Abstract:This article examines the pedagogical response of English and writing faculty to a controversy that took place at their liberal arts college. Findings from faculty interviews highlight a number of ways that instructors might engage local controversies, in keeping with their curricular goals and commitments to pedagogical transparency.


With echocardiography images collected by a transthoracic transducer, can be used to evaluate the mitral valve problems. Incorrect surgical of mitral valves failure will cause death and the surgical repair can be improved by knowing the correlations between backflow and the rigidity of mitral valve. In this study, a nearly method for identifying the mitral valve rigidity from two-dimensional (2D) images of echocardiography is presented. This method employs the grid independent technique. Systolic and diastolic stages of mitral valve condition were investigated by 10 patients with MVP. The results show linear correlation between degeneration of the valves and volume of backflow. The findings are the prediction of the behavior of the mitral valves and blood flow which can assist the medical practitioners in their decision on the patients' treatments


During diseases of the pancreas not only extrasecretory but also intrasecretory disorders are observed. The disturbances are dependent on excessive or insufficient releasing of hormones which are physiologically secreted by the pancreas. The most common endocrine disorder, which develops in pancreatic diseases, is insufficient insulin production which leads to carbohydrates balance disorders. The occurrence of endocrine pancreatic tumors (insulinoma, gastrinoma) is visibly less common--2-10% of neoplasmy of the organ. In group of endocrine tumors of the pancreas are also observed some changes which are able to release the vase-active intestinal peptide (VIP-oma), glucagon tumors, carcinoid released serotonine and somatostatinoma. More over, low-differentiated endocrine carcinomas of the pancreas consist about 1% of all pancreatic tumors and 2-3% of the all endocrine tumors.


Author(s): Deltoro, Damian Jorge | Advisor(s): Smith, Douglas E | Abstract: In this dissertation we take advantage of the real-time manipulating, high force generating, and small displacement measuring abilities of dual-trap optical tweezers to investigate properties and mechanisms of motor enzymes that act on DNA, including the DNA translocation motor of bacteriophage lambda and the proposed ATP-driven annealing helicase HARP. Through a combined approach of genetic mutagenesis, biochemical analysis, and single-molecule analysis we reveal potential functional roles of the residues residing in the ATP phosphate binding motif (Walker A) of phage lambda's large terminase subunit. Direct DNA packaging measurements of phages with mutated residues within this motif reveal a range of impaired translocation phenotypes. Analysis of the slipping and pausing exhibited by mutant enzymes suggests that residues A78, R79, and V80 mediate coupling between ATP binding/hydrolysis and DNA binding/translocation while implicating residues A78, R79, V80, and G81 in proper ATP alignment for hydrolysis. The combined findings of each analysis also implicate residue R79 in ADP release and triggering ATP hydrolysis. In other studies, initial investigation into the mechanism of termination of DNA packaging in phage lambda provides evidence against a velocity-monitoring model. A higher resolution optical tweezers system was designed and constructed and a new and improved calibration method was developed and applied to initial high-resolution measurements of DNA translocation. The use of environmental and measurement noise reduction techniques and improved optical alignment procedures have yielded tweezers with approximately nanometer spatial resolution. The calibration technique, which optimizes fits of the worm-like chain model to DNA force-extension curves, yields calibration with at least a 7-fold improvement in accuracy over our prior method. The use of these tools in measuring lambda packaging yield preliminary evidence for discrete translocation steps. Lastly, tweezer measurements of HARP interactions with forked DNA provide supporting evidence that HARP is a forked-DNA binding protein that resists DNA unzipping and is not an unwinding helicase. In addition preliminary measurements suggest that this protein forcibly reanneals DNA, prevents reannealing, resists high forces, slows reannealing in an ATP dependent manner, and is recruited to bind to forked DNA with replication protein A coated single-stranded DNA.


In a recent study, Sanders and Hoffman (2002, hereafter SH) found that only about half of the cold-front segments appearing on surface maps of the National Centers for Environmental Prediction (NCEP) from December 1999 through February 2000 were associated, even loosely, with a moderately strong surface baroclinic zone. In an earlier study (Sanders and Kessler 1999), some extreme examples had been identified in which an abrupt nocturnal temperature rise was analyzed as the passage of a cold front. These features are clearly not the type of structure described by Bjerknes (1918). To enlarge the sample of comparisons between analyzed fronts and baroclinic zones reported by SH, a comparison was made for the period between 7 February and 29 March 2002. The fronts were again taken from analyses prepared by the Hydrometeorological Prediction Center (HPC) of NCEP. The maps of surface potential temperature were prepared at the Department of Atmospheric Science, The University of Arizona, and were manually analyzed without knowledge of the concurrent frontal analysis. As in SH, the times were 0000 and 1200 UTC and the area of analysis was the same. The analysis consisted of isotherms at intervals of 8°C. Areas of moderate or intense gradient, representing an 8°C contrast of potential temperate over distances of no more than 220 or 110 km, respectively, were marked. These distances represent values of the gradient close to those used by SH. Edges of frontal segments occurred where the analyzed notation changed, generally at centers of low pressure, or where indicated in the analyses, or at the edge of the analyzed area. Warm fronts, cold fronts, and stationary fronts were separately considered. A small number of occluded segments occurred but were considered as extended portions of cold or warm fronts, depending on whether the air following the frontal wind shift was colder or warmer than the air ahead. Whereas SH considered each segment as associated or not associated with a baroclinic zone, in this study the total length of each segment was measured, as was the length associated with a baroclinic zone. Association was considered to occur if the analyzed front lay within 220 km of the warm edge of a zone, or was within it. Where the orientations of the front and of the zone differed by nearly 90°, the two were considered associated if the air on the cold side of the front was significantly colder than the air on the warm side, but not otherwise. The length and proportions of frontal segments associated with baroclinic zones are presented in Table 1. In the table the fractional length of segments associated with baroclinic zones was around one-half for both times and for all frontal types. Cold frontal segments were not less associated, as in the study by SH (seen in their Table 3). The lengths of stationary and cold fronts is understated because in many instances the segment was terminated when it reached the limits of the area of analysis of potential temperature, usually over the ocean. If the temperature analysis had extended over the oceanic regions, the association would have likely been weaker because of the lack of prominent contrasts in these regions. Warm fronts were fewer and shorter than other types, representing in many cases stubs ahead of an analyzed cold front with less than compelling indications. In the earlier study a decision was made whether the segment as a whole was or was not associated with a baroclinic zone. The present study may be less subjective. In an attempt to mimic the procedure used in the earlier study, we determined whether each individual frontal segment was or was not associated with a baroclinic zone over at least 50% of its length. The proportions of each frontal type meeting this criterion were 0.53, 0.43, and 0.45 for stationary, cold, and warm segments, respectively. In both studies it is apparent that many analyzed fronts are not assoCorresponding author address: Dr. Frederick Sanders, 9 Flint Street, Marblehead, MA 01945-3716. E-mail: email@example.com AUGUST 2005 F O R E C A S T E R S ' F O R U M 647


-^ In a bright new century bent on releasing markets from the shackles that have hitherto prevented them from delivering bright new centuries, schools are set to become traders in Information Communications Technology (ICT) skills, dealers in multiple intelligences, retailers of social mobility, vendors of social and economic advantage and, at no extra cost, designers of personal marketability. Schools are set to be banded and branded as good or bad producers of technowise citizens. Is this the sort of bright newness we want? Do we really want a system more interested in costs, benefits, and productivity outcomes than in developing the human potential and creativity needed to solve the problems that our current way of life manages to proliferate at such an alarming rate? If we want schooling to encourage young people to care, then current 'reforms' must do more than tailor education to meet the needs of the national/ global economy and to fashion techno-wise, producer/consumers. If we want education to make a difference, then we have to figure out how it might: stimulate our ability to imagine social alternatives; demonstrate that 'now' is only one of many other ways of being in the world; prompt greater dissatisfaction with our recently commodified existence; offer alternatives which build on differences; show that accepted commonplaces of 'human nature' can be re-designed to make cooperation as appealing as rivalry or apathy; and nurture care and concern about social inequality.


The design and experimental performance of a wide-band K-band parametric amplifier (paramp) for the experimental domestic satellite communication earth station are described. An optimum idler frequency for a minimum noise temperature is derived taking into account the varactor diode skin effect. Wide-band paramps with a double-tuned signal circuit are discussed and it is shown that triple-tuned gain characteristics are realizable with this configuration. Finally, an 18-GHz paramp is described, which can be operated from room- to liquid-helium (LHe) temperature, only requiring adjustment of pumping power and bias voltage and using lithium ferrite circulators. Triple-tuned gain characteristics with a bandwidth of 1300 MHz at a gain of 10 dB are obtained using a miniature pill prong packaged varactor.


In this paper, I explore the local cultural space and community engagement, and the meaning making process of everyday lives of fictional characters through the signs, or the objects. Using a case of Rohinton Mistry's (2002) novel Family Matters, I look into the cultural representation and community engagement derived from cultural and material interpretation of various objects that highlight arbitrary nodes of signifier and signified-the linguistic meaning making process. The family is a central semiotic construct of the novel; thus, all meaning derives from the patriarch of that family: Nariman, the main fictional character. This essay also analyzes the text through diachronic tour winding through how words, symbols, and contradictions open up new decoding of cultural variance. The phenomenon of collective strength, glorification of Persian culture, and decoders' longing to their roots are aligned with people's messages, context, code, and discourse. Amid the growing debate on media (film, television, still images, advertisement and other works of art), I intend to examine how the social production and structuration of meaning come into play in this novel.


The growing global interest in biodiversity conservation and the role of forestland sustainability in climate change mitigation has led to the emergence of a new specific field of global environmental governance that we called 'forest diplomacy'. With the largest tropical forest area after the Amazon, Congo Basin countries (CBc) constitute a major negotiation bloc within global forest-related governance arenas. Despite this position, CBc seem embedded in a failure trap with respect to their participation in forest diplomacy arenas. This paper examines the major causes of the recurrent failures of CBc within forest diplomacy. A qualitative empirical approach (including key informant interviews, groups discussion, participant observation, and policy document review) was used. From a conceptual and theoretical perspective, this research combines global and political sociology approaches including environmentality and blame avoidance works. The main finding reveals that the recurrent failures of CBc in forest diplomacy are partly due to the lack of strategic and bureaucratic autonomy of CBc that strongly depend on financial, technical, and knowledge resources from Western cooperation agencies or consultancy firms. Our discussion highlights that this dependency is maintained by most of the key actor groups involved in forest diplomacy related to CBc, as they exploit these failures to serve their private interests while avoiding the blame of not reducing deforestation and biodiversity loss in the Congo Basin.


Digital pathology has entered a new era with the availability of whole slide scanners that create the high-resolution images of full biopsy slides. Consequently, the uncertainty regarding the correspondence between the image areas and the diagnostic labels assigned by pathologists at the slide level, and the need for identifying regions that belong to multiple classes with different clinical significances have emerged as two new challenges. However, generalizability of the state-of-the-art algorithms, whose accuracies were reported on carefully selected regions of interest (ROIs) for the binary benign versus cancer classification, to these multi-class learning and localization problems is currently unknown. This paper presents our potential solutions to these challenges by exploiting the viewing records of pathologists and their slide-level annotations in weakly supervised learning scenarios. First, we extract candidate ROIs from the logs of pathologists' image screenings based on different behaviors, such as zooming, panning, and fixation. Then, we model each slide with a bag of instances represented by the candidate ROIs and a set of class labels extracted from the pathology forms. Finally, we use four different multi-instance multi-label learning algorithms for both slide-level and ROI-level predictions of diagnostic categories in whole slide breast histopathology images. Slide-level evaluation using 5-class and 14-class settings showed average precision values up to 81% and 69%, respectively, under different weakly labeled learning scenarios. ROI-level predictions showed that the classifier could successfully perform multi-class localization and classification within whole slide images that were selected to include the full range of challenging diagnostic categories.


The human leukemia cell lines HL-60, KG-1, KLM-2, ML-3, THP-1, and U-937 were treated with the phorbol ester 12-O-tetradecanoylphorbol 13-acetate (TPA). TPA partially or completely inhibited the proliferative activity of the cell cultures. The number of cells with the ability to reduce nitroblue tetrazolium increased in the TPA-treated cell lines HL-60, ML-3, THP-1, and U-937, whereas the cell lines KG-1 and KLM-2 remained nitroblue tetrazolium negative. Except for KG-1 and KLM-2, all TPA-treated cell lines showed varying degrees of strong adherence to plastic surface. The carboxylic esterase, acid phosphatase, hexosaminidase, and lactate dehydrogenase isoenzyme profiles from these cell lines were analyzed by isoelectric focusing on horizontal polyacrylamide gels. The new or stronger expression of an esterase isoenzyme which is specific for monocytes-macrophages was induced in HL-60, ML-3, THP-1, and U-937 but not in KG-1 or KLM-2. The new expression of the tartrate-resistant acid phosphatase isoenzyme was induced in ML-3, THP-1, and U-937. The number of esterase and acid phosphatase isoenzymes and the staining intensity of isoenzymes characteristic for myeloid cells were increased by TPA in all cell lines. The loss of the hexosaminidase I isoenzyme which is a marker of immature hematopoietic cells was noted in KG-1, ML-3, THP-1, and U-937. TPA triggered an increase in number and staining intensity of the lactate dehydrogenase isoenzymes in all cell lines. Some isoenzymatic changes (e.g., monocyte-specific esterase, tartrate-resistant acid phosphatase, hexosaminidase I) appear to correlate with TPA-induced differentiation while other alterations in the isoenzyme patterns do not (e.g., lactate dehydrogenase, other esterase and acid phosphatase isoenzymes). Differentiation of nonmonocytoid cells appears, at the isoenzyme level, to be quite different from that of the monocytoid cell lines.


Five mutations in the ligand-binding domain (LBD) of the human androgen receptor (hAR) found in patients with varying degrees of androgen insensitivity syndrome (AIS) were investigated for their effects on receptor dynamics. These were Arg(871)Gly (mild), Ser(814)Asn (partial), Glu(772)Ala (partial), Val(866)Met (complete), and Arg(774)Cys (complete). Previous analysis showed that the mutant receptors exhibited near-normal kinetics, except Arg(774)Cys, which had severely reduced androgen binding, and Val(866)Met, which showed increased equilibrium dissociation constant (K(d)) and elevated dissociation rate (k) values. Ser(814)Asn exhibited ligand-selective k values, i.e. increased for dihydrotestosterone and mibolerone, but normal for methyltrenolene. Using mammalian two-hybrid assays, hAR amino/carboxyl (N/C)-terminal interactions of the mutant receptors were analyzed in the presence and absence of the hAR coactivator transcription intermediary factor 2 (TIF2). The mutations conferred decreased hAR N/C-terminal interaction, i.e. mild (approximately 1.5-fold), partial (2-fold), and complete (10-fold), that mirrored the degree of AIS. All mutant LBDs showed a 2- to 3-fold increase in N/C-terminal interactions when TIF2 was cotransfected, although of a magnitude still less than that of wild-type LBD with TIF2. The ligand-selective properties of the Ser(814)Asn mutant were also clearly reflected by the N/C-terminal interactions. Thus, measurement of N/C-terminal interactions may assist in the molecular analysis of mutant hARs associated with AIS.


Automatic text summarization involves reducing a text document or a larger corpus of multiple documents to a short set of sentences or paragraphs that convey the main meaning of the text. In this paper, we discuss about multi-document summarization that differs from the single one in which the issues of compression, speed, redundancy and passage selection are critical in the formation of useful summaries. Since the number and variety of online medical news make them difficult for experts in the medical field to read all of the medical news, an automatic multi-document summarization can be useful for easy study of information on the web. Hence we propose a new approach based on machine learning meta-learner algorithm called AdaBoost that is used for summarization. We treat a document as a set of sentences, and the learning algorithm must learn to classify as positive or negative examples of sentences based on the score of the sentences. For this learning task, we apply AdaBoost meta-learning algorithm where a C4.5 decision tree has been chosen as the base learner. In our experiment, we use 450 pieces of news that are downloaded from different medical websites. Then we compare our results with some existing approaches.


Traditional scientific methods of visualising sound data have focused on techniques that attempt to capture distinct elements of the audio signal, such as volume and length. However, existing methods such as spectrograms and waveform analysis are limited in their expression of the characteristics associated with complex sounds such as bird song. This research explores strategies to visualise sound in an aesthetically engaging manner. It uses sound data from native New Zealand birds as a design tool for creating an audio-visual design system. The distinct focus on timing and pitch within these songs makes the data suitable for visual comparison. The design techniques explored throughout this research project attempt to express the unique characteristics of a variety of New Zealand bird songs and calls. It investigates how artistic audio-visual methods can be integrated with scientific techniques so that the auditory data can be made more accessible to non-specialists.
More specifically, this research aims to take advantage of the natural phonaesthetic connections people make between sonic and visual elements. The final output of this research consists of a generative design system that uses auditory data to create visualisations of New Zealand bird song. These visualisations have a mathematical basis, as well as being audio-visual artworks in themselves.


During photosynthesis of higher plants, absorbed light energy is converted into chemical energy that, in part, is accumulated in the form of transitory starch within chloroplasts. In the following night, transitory starch is mobilized to sustain the heterotrophic metabolism of the plant. β-amylases are glucan hydrolases that cleave α-1,4-glycosidic bonds of starch and release maltose units from the non-reducing end of the polysaccharide chain. In Arabidopsis, nocturnal degradation of transitory starch involves mainly β-amylase-3 (BAM3). A second β-amylase isoform, β-amylase-1 (BAM1), is involved in diurnal starch degradation in guard cells, a process that sustains stomata opening. However, BAM1 also contributes to diurnal starch turnover in mesophyll cells under osmotic stress. With the aim of dissecting the role of β-amylases in osmotic stress responses in Arabidopsis, mutant plants lacking either BAM1 or BAM3 were subject to a mild (150mM mannitol) and prolonged (up to one week) osmotic stress. We show here that leaves of osmotically-stressed bam1 plants accumulated more starch and fewer soluble sugars than both wild-type and bam3 plants during the day. Moreover, bam1 mutants were impaired in proline accumulation and suffered from stronger lipid peroxidation, compared with both wild-type and bam3 plants. Taken together, these data strongly suggest that carbon skeletons deriving from BAM1 diurnal degradation of transitory starch support the biosynthesis of proline required to face the osmotic stress. We propose the transitory-starch/proline interplay as an interesting trait to be tackled by breeding technologies aimingto improve drought tolerance in relevant crops.


At the present time there are more than 100.000 people over 85 and this progression will continue in the future. At the same time there is a motion of cares the context of the expense provokes the scarce development of the social and domiciliary attention services. In this contexture the influence of those person who take care of the elder people, as much at home as during the episode of hospital admission, can be decisive in the loss of and cognitive capacity of the elder person. Our aim is to analyze the influence of various people who work as the main caregiver at home and during the hospital admission in the functional and cognitive of the elder person. To reach the investigation results that have been proposed in this work a "quasi" experimental design of repeated measures. Among the results, the influence of the people who act as the main caregivers worth an especial mention, during the elder hospitalization, watching that those people accompanied by their couples and children suffer a softer functional loss, meanwhile their hospitalization. This difference means a great reveal as it makes manifest through the computation of the size of the effect that give us a value for the "d" of Cohen of 0`984. We stand out the novelty of including the type of the main caregiver person at the hospital as one of the factors of back dependence at home and a change of residence after the hospitalization.


Impulsive projective synchronization in 1 + N coupled chaotic systems are investigated with the drive–response dynamical network (DRDN) model. Based on impulsive stability theory, some simple but less conservative criteria are achieved for projective synchronization in DRDNs. Furthermore, impulsive pinning scheme is also adopted to direct the scaling factor onto the desired value. Numerical simulations on generalized chaotic unified system are illustrated to verify the theoretical results.


Purpose Cardiovascular disease risk factors have been associated with androgen-deprivation therapy (ADT) in white and Hispanic populations. It is therefore relevant to determine if there exists a relationship between these parameters in the African population. Patients and Methods The design of the study was cross sectional. Prostate-specific antigen concentration, waist circumference, body mass index (BMI), lipid profile, glucose level, and insulin level were determined in 153 patients with prostate cancer and 80 controls. The patients with prostate cancer were divided into subgroups of treatment-naïve patients and those receiving ADT. Results Mean total cholesterol (P = .010), LDL cholesterol (P = .021), BMI (P = .001), and waist circumference (P = .029) values were significantly higher in patients treated with ADT when compared with treatment-naïve patients. In patients treated with ADT for up to 1 year, only mean BMI was significantly higher than in treatment-naïve patients, whereas those treated with ADT for more than 1 year had significantly higher mean BMI, waist circumference, total cholesterol, and LDL cholesterol values when compared with treatment-naïve patients. There were no significant differences in insulin or glucose levels. Those undergoing hormone manipulation after orchiectomy had fewer cardiovascular risk factors compared with those undergoing hormone manipulation alone. Conclusion This study shows that ADT results in elevated total cholesterol, LDL cholesterol, BMI, and waist circumference values, all of which are risk factors of cardiovascular disease. Screening for cardiovascular risk factors should be included in treatment plans for patients with prostate cancer.


Abstract. The author has shown that modern technologies do not always meet the expectations of farmers, and this may adversely affect the pace of innovation. It has been confirmed that the developers of agricultural equipment do not clearly understand the context of the use of products and identified the need to use a multi-factor approach: therefore, partners possessing specific knowledge in different areas should join efforts in project activities at all stages of innovation. (Research purpose) To prove that a user-centered design and a multi-factor approach in the development of agricultural machinery increase their efficiency and accelerate the introduction of innovations. (Materials and methods) It is shown that Finnish research and development projects of agricultural machinery design involve numerous participants and end users. For example, the seven-metre-wide combi drill 'Junkkari W700' was designed by the Finnish manufacturer Junkkari Oy in close cooperation with end-users and researchers. As a result of the innovation process several benefits have been realized. The drill is easy to operate and service. The users appreciate the straight-forward construction and moderate cost of the drill as compared to competing pneumatic drills. The need for hydraulics is minimized and the row spacing and coulter design has been optimized so that economical tractors with moderate drawbar power can be used. The ISOBUS-based control electronics was designed to be fitted either in the existing tractor or, if ISOBUS is missing, with an optional cable-set and terminal. That enables the users to easily integrate the drill in existing machine chains, having either modern or older tractors, without extra tractor investments. Much attention was put on quality, e.g. individual feeders for every coulter give accurate dosage of seed and fertilizer. The prototyping together with end-users and researchers enabled Junkkari to speed up the innovation process. (Results and discussion) Several benefits proved to have been realized. First of all, the drill is easy to operate and service. The users appreciate the straight-forward construction and moderate cost of the drill as compared to competing pneumatic drills. The need for hydraulics is minimized and the row spacing and coulter design has been optimized so that economical tractors with moderate drawbar power can be used. The ISOBUS-based control electronics as well as an optional cable-set and terminal were designed to be fitted either in the existing tractor. That enables the users to easily integrate the drill in existing machine types, having either modern or older tractors, without extra tractor investments. The design quality was approved, e.g. individual feeders for every coulter give accurate metering of seeds and fertilizers. (Conclusions) The author proves that user-centered design and multi-factor approach methodologies have benefits both for the users and manufacturers. Swift innovation process saves resources and minimizes the need for excess iterations in the innovation process.


A study of the history of Scotland between 1700 and 1900. It is part of a series which offers an insight into Scotland's past and a general overview of the country's history. These books aim to develop historical skills and provide suggestions for further research. The volume: seeks to integrate social, economic, political and cultural developments to give a balanced view of Scottish history; places events in context through comparison with contemporary developments outside Scotland; helps readers to understand the past through the analysis of historical evidence; and uses timelines to give an overview of the period.


An assessment of a non-invasive technique for measurement of stroke distance was made using a portable Doppler ultrasound machine. The aim was to determine the measurement error of repeated stroke distance measurements (within-observer variability) and to assess measurement agreement between two operators (between-observer variability). The measurement error (within-observer variability) for both operators was similar at approximately 2 cm. However, the measurements of the two operators (between-observer variability) did not agree well. Using the mean (SD) of three readings by each operator, the mean difference between the operators was −0.21 cm (1.96) giving a 95% confidence interval for the differences of −4.0 to +3.6 cm. There were significant positive and negative correlations between stroke distance and a variety of variables (age, height, weight, heart rate), but the relations were weak. The results indicate that the Doppler ultrasound technique for measurement of stroke distance would best be used to study trend changes in an individual patient, or subject, by a single operator.


This paper will first describe the optoelectronic generation and detection of freely-propagating fsec pulses of THz electromagnetic radiation, and then applications of the optoelectronic THz beam system to THz time-domain spectroscopy (TDS) will be presented. Via optoelectronic excitation, a transient point source of THz radiation is generated at the focus of a dielectric collimating lens, followed by an additional paraboloidal focusing and collimating mirror. This source produces well collimated beams of fsec pulses of THz radiation. Matched to an identical receiver, the resulting system has extremely high collection efficiency (1). With a demonstrated signal-to-noise ratio of 1000, a time resolution of less than 150 fsec and a frequency range from 0.2 THz to more than 5 THz, the performance of this optoelectronic THz system is limited by the intrinsic response time of the semiconductor (2).


Although housing can be a powerful channel of monetary policy transmission this channel can be weakened by social customs and financial liberalization as well as accompanying innovation that create alternatives to bank mortgages controlled by a central bank. This paper utilizes some unique questions in the 1999 and 2002 Cyprus Surveys of Consumer Finances, as well as data from the 1998 and 2001 US Surveys of Consumer Finances, in order to study the role of social customs (in the form of parental housing gifts) and financial liberalization for the incidence of homeownership rates, mortgage debt and borrowing constraints. Unlike existing studies of financially developed countries, the data from the Cyprus Surveys suggest that only a very small proportion of Cypriot households are credit constrained and that a number of important economic characteristics of the household are irrelevant for homeownership and for the use of mortgages. Our findings suggest that the presence of such customs may interfere with the monetary transmission mechanism by limiting the sensitivity of housing investment to changes in credit market conditions. Financial liberalization leading to innovation could work in the opposite direction if it leads to increased household participation in formal loans controlled by the central bank.


Herbal medicine is widely used as alternative and complementary health practice. At recent years, the use of herbal medicine is increased in psychiatric practise. In this review it was mentioned in which conditions the herbal medicine were used, the adverse effects of herbals, the interactions between other drugs and the essential points were emphasized that the clinicians should keep in mind.


Before a variety is released for adoption by farmers in a region it is subject to comparative field testing. An economic issue is how extensive and prolonged should be this field testing within the region; over how many locations, years and with what number of plot replications should testing occur? This paper addresses this issue for the main broadacre crops grown in Western Australia and shows through sensitivity analysis how robust are the findings for each crop type. Findings are contrasted with those already published for southern New South Wales.


First, the issue of data handling –large datasets and low number of samples compared to variableswas considered by the definition of a workflow of data preprocessing and processing, including the creation of a study template, the rigorous selection of good chromatographic quality features, and the multiplication of statistic techniques to be combined before test validation. In practice, 94 injections were made over 4 weeks, consisting of 70 study samples along with 16 QC samples and 8 reinjections due to QC system rejection. The chromatogram template included 524 verified features that were then reduced to less than two hundreds after selection of the ones having an analytical variation under 30%, based on the QC samples. This resulted in the finding of robust biomarkers that positively discriminated between the different phenotypes of inflammation, including high and low inflammation, remission, and healthy statutes.


Unraveling the association between microbiome and plant phenotype can illustrate the effect of microbiome on host and then guide the agriculture management. Adequate identification of species and appropriate choice of models are two challenges in microbiome data analysis. Computational models of microbiome data could help in association analysis between the microbiome and plant host. The deep learning methods have been widely used to learn the microbiome data due to their powerful strength of handling the complex, sparse, noisy, and high-dimensional data. Here, we review the analytic strategies in the microbiome data analysis and describe the applications of deep learning models for plant–microbiome correlation studies. We also introduce the application cases of different models in plant–microbiome correlation analysis and discuss how to adapt the models on the critical steps in data processing. From the aspect of data processing manner, model structure, and operating principle, most deep learning models are suitable for the plant microbiome data analysis. The ability of feature representation and pattern recognition is the advantage of deep learning methods in modeling and interpretation for association analysis. Based on published computational experiments, the convolutional neural network and graph neural networks could be recommended for plant microbiome analysis.


This paper deals with the problem of measuring business cycles: short, medium or long-term, with both theoretical and empirical discussions on the regularity of fluctuations versus asymmetries in their measurement phases. For this, the employed approach is based on the combination of deviations on the level of trends (alternative filters) with the algorithm of Harding & Pagan (2002). At the same time, there are considered the effective rates of economic growth by Markovian chains in order to identify non-linear regimes of expansion and economic contraction. Finally, quantifications on the natural rate of growth for Bolivia are offered under a sustained expansion regime from 1950 to 2015. The results suggest that the way of measuring the business cycle denotes alternative inferences in average duration and due to asymmetries.


Flexible responses of lipid metabolism to changes in cultivation conditions characteristic of oleaginous microalgae of the genus Nannochloropsis render them a promising source of triacylglycerols for biodiesel (under nutrient-deprivation and high-light stress) and eicosapentaenoic acid (EPA; C20:5, n-3) (under nutrient sufficient conditions). We investigated the responses of fatty acid and pigment profile in the euryhaline Nannochloropsis oceanica CCALA 804 to the combined stresses of high light (HL), salinity (0, 27, and 40 g/L NaCl) and nitrogen deprivation. The growth in nitrogen-replete medium under HL triggered a rapid acclimation of the microalgae to the HL stress in a salinity-dependent manner associated with a moderate decrease of EPA proportion of total FA. Nitrogen starvation (i) slowed the biomass accumulation, (ii) enhanced the production of reserve lipids at the expense of chloroplast lipids, and (iii) triggered photoprotective responses of pigment apparatus in N. oceanica. Regardless of cultivation conditions, the stress-induced changes in pigments and fatty acid profile were highly coordinated. Nitrogen-starvation promoted total FA accumulation on the background of a marked decline in EPA and light-harvesting Car as well as up-regulation of violaxanthin cycle with concomitant rise in non-photochemical quenching. Zero-NaCl conditions appeared to be beneficial for biomass and EPA accumulation and alleviated, especially under nitrogen starvation, the effects of salinity stresses (the decline in biomass accumulation rate, content of light-harvesting carotenoids and EPA, and photosynthetic efficiency). Strategies of N. oceanica acclimation to stresses of different nature and their possible implications for the biotechnology of this species are discussed.


Background We used the results of a contact behavior survey in conjunction with droplet pattern measurement to investigate the indoor population transmission dynamics of respiratory infections. Methods A total of 404 questionnaires on all contact behaviors were distributed to junior high school students. Droplet number concentration and size distribution generated by coughing and talking were measured by droplet experimentation. A deterministic susceptible–exposed–infected–recovery (SEIR) model was used to simulate the indoor transmission dynamics of influenza infection among schoolchildren. Results Results indicated that the average contact rates ranged from 9.44 to 11.18 person−1 day−1 for grades 7 to 9. We showed that total median droplet number concentrations were 9.01 × 107 and 8.23 × 107 droplets per cubic meter for coughing and talking, respectively. Population dynamic simulations indicated that the size-dependent median number of droplets per person resulted in a maximum of 8 and 10 infected persons on day 4, respectively, for talking and coughing activities. Conclusions Human contact behavior and airborne droplet characteristics may substantially change predicted indoor population transmission dynamics of influenza infection.


We use an experiment to examine whether the way in which climate change is framed affects individuals' beliefs about its importance as a policy issue. We employ frames that emphasize national security, human rights, and environmental importance about the consequences of climate change. We find no evidence that issue frames have an overall effect on opinions about the importance of climate change policy. We do find some evidence that the effect of issue frames varies across ideological and partisan groups. Most notably, issue frames can lead Republicans and those on the political right to view climate change policy as less important. We conclude by discussing our findings relative to extant literature and considering the implications of our findings for those who seek to address the issue of climate change.


This paper was delivered as part of a one-day painting symposium, titled: British Abstract Painting in the Eighties, which took place in the Herbert Art Gallery & Museum, Coventry, on Friday 14th September 2018. The speakers were: Maggie Ayliffe, Rebecca Fortnum, Susan Liggett, Christopher McHugh, Tom Palin, Zino Pece, Daniel Sturgis, David Sweet, and the Key Note, David Ryan. The symposium was co-hosted by the Visual Arts Group (Coventry University) and the Herbert Museum & Art Gallery, and focussed on developments in British abstract painting in the 1980s. The presentations considered the legacies of abstraction, and what it is possible or credible to pursue within painting. My paper addresses the functionality of abstract painting in respect of the phenomenon of pareidolia, against the backdrop of a pluralisation of practices brought about, in part, by responses to Geenbergian formalism and the advent of Conceptual Art. Of particular note is the importance and retention of likeness as a perceptual framework within which to approach abstract painting's meaning, the particularities of spectatorship, and the experiential possibilities of picturing more generally.


The paper focusses on a control design that aims to achieve a low hump sensitivity function for dual stage servo systems in hard disk drives. Two microactuator models are studied, a MEMS (microelectromechanical system) actuator and a PZT (piezoelectric) actuator. A nearly flat sensitivity function is accomplished in the continuous-time domain for the dual-stage servo loop using the H∞-loop shaping method and an LMI (linear matrix inequality) approach. The implementation result for the parallel dual-stage system with a PZT-actuated suspension demonstrates the effectiveness of the proposed design and the hump of the sensitivity function is shown to be lower than 3 dB.


National security protection emerges as an indispensable factor for the development of personality, society, and state amid the increasing complexity of international migration processes. The article touches upon the peculiarities of ethnic and social relations between migrants and members of the host country providing insight into the novel category of "migration security".


The present field study was an archival study that used an adapted version of the Parents as Reading Tutors program utilizing cross-age tutors instead of parents. The study was conducted by a school psychologist employed by the Hays Unified School District. Participants in the study included 40 second grade students enrolled in a five week summer school session. Twenty of these participants were randomly assigned to the treatment group and 20 to the control group. However, only 22 students were included in the study at the end of the tutoring sessions after subject drop out. Students were administered pre- and post-test curriculum-based measurement probes at the beginning and at the conclusion of the study. Actual tutoring sessions consisted of students reading orally from age appropriate reading books of their choice. Students were excluded from the study if they did not participate in either pre- or post-testing, or d1d not participate in at least one-half of the reading tutoring sessions. After participant drop out, eleven of these subjects remained in the reading tutoring group, and 11 remained in the control group. Informed consent of the participants was obtained by a letter written to each student's parents upon enrollment into the summer school program. The study was conducted during the five-week time span that summer school was in session. Gains in reading fluency rate were measured by pre-and post-test curriculum-based measurement reading scores. This study attempted to demonstrate that a tutoring program in reading improves student's oral reading fluency scores. Results indicated no significant difference between the treatment and control groups on improvement in reading fluency rates, or between the number of days the students received peer tutoring and the subsequent gains in reading fluency rate.


This paper presents a new approach to TCP congestion control. The new scheme includes two parts: (I) the smooth-start algorithm, which replaces the slow-start algorithm at the start of a TCP connection or after a retransmission timeout, and (2) the dynamic recovery algorithm, which replaces the fast recovery algorithm to recover packet losses when a TCP connection is congested. Both algorithms require modifications only to the sender side of the TCP implementation. Simulation is used to evaluate the performance of the algorithms. The simulation experiments are conducted using the ns simulator to facilitate comparisons with Tahoe, Reno, New-Reno, SACK, and FACK TCP. The simulation results show that the new scheme performs at least as well as SACK and FACK TCP, which in turn consistently outperform TCP Tahoe and Reno. Furthermore, the implementation of the new scheme is simpler than that of SACK and FACK.


Dissemination of Leishmania within the host is related to parasites undergoing unchecked proliferation. We therefore studied the effects of oxidant generating systems on promastigote multiplication by (i) direct determinations of organism proliferation and (ii) the incorporation of [3H]uracil into promastigote nucleoprotein. These two parameters correlated closely as measures of organism replication as demonstrated by parallel suppression of them by the protein synthesis inhibitors puromycin and cycloheximide and the nucleic acid synthesis inhibitors actinomycin D and mitomycin C. Promastigotes showed dose-related susceptibility to reagent and generated hydrogen peroxide (H2O2) as reflected in quantitatively similar decreases in multiplication and [3H]uracil incorporation. These effects were specific for H2O2 as catalase abrogated the dimunition in multiplication. The generation of superoxide anion by acetaldehyde-xanthine oxidase (10 mU/ml) did not alter promastigote replication or nucleoprotein synthesis. These results indicate that Leishmania donovani promastigotes are damaged by H2O2 and that the incorporation of [3H]uracil into promastigote nucleoprotein may be useful for studying the interaction of this parasite with host effector cells.


In polycystic kidney disease (PKD), the rate of cyst formation and disease progression is highly variable. The lack of predictability in disease progression may be due to additional environmental factors or pathophysiological processes called "third hits." Diabetes is a growing epidemic, and recent studies suggest that PKD patients may be at an increased risk for this disease. We sought to determine if hyperglycemia enhances the initiation and rate of cystogenesis. Tamoxifen was administered to adult Ift88 conditional floxed allele mice to induce cilia loss in the presence of Cre. Subsequent administration of streptozotocin resulted in equivalent hyperglycemia in cilia(+) and cilia(-) mice. Hyperglycemia with loss of cilia increased the rate of cyst formation and cell proliferation. Structural and functional alterations in the kidney, including focal glomerular foot process effacement, interstitial inflammation, formation of primitive renal tubules, polyuria, and increased proteinuria, were also observed in hyperglycemic cilia(-) mice. Gene array analysis indicated enhanced Wnt and epithelial-to-mesenchymal transition signaling in the kidney of hyperglycemic cilia(-) mice. These data show that hyperglycemia, in the absence of cilia, results in renal structural and functional damage and accelerates cystogenesis, suggesting that diabetes is a risk factor in the progression of PKD.


Graphene field-effect transistor (GFET) biosensors exhibit high sensitivity due to a large surface-to-volume ratio and the high sensitivity of the Fermi level to the presence of charged biomolecules near the surface. For most reported GFET biosensors, bulky external reference electrodes are used which prevent their full-scale chip integration and contribute to higher costs per test. In this study, GFET arrays with on-chip integrated liquid electrodes were employed for COVID-19 detection and functionalized with either antibody or aptamer to selectively bind the spike proteins of SARS-CoV-2. In the case of the aptamer-functionalized GFET (aptasensor, Apt-GFET), the limit-of-detection (LOD) achieved was about 103 particles per mL for virus-like particles (VLPs) in clinical transport medium, outperforming the Ab-GFET biosensor counterpart. In addition, the aptasensor achieved a LOD of 160 aM for COVID-19 neutralizing antibodies in serum. The sensors were found to be highly selective, fast (sample-to-result within minutes), and stable (low device-to-device signal variation; relative standard deviations below 0.5%). A home-built portable readout electronic unit was employed for simultaneous real-time measurements of 12 GFETs per chip. Our successful demonstration of a portable GFET biosensing platform has high potential for infectious disease detection and other health-care applications.


RATIONALE FOR THE STUDY
The aims of the study, conducted as a student research project in the 2004-5 session, were to develop an interactive, online computer-aided learning (CAL) package on the topic of small-animal husbandry; to validate the resource as a suitable lecture replacement for first-year veterinary students; and to raise awareness of current guidelines and legislation relating to small-animal housing among local catteries and kennels and in the wider community.

METHODOLOGY
Quantitative feedback was collected from student and teaching staff using paper-based questionnaires. Qualitative feedback was gathered from open questionnaire responses and through focus-group discussions with students. Student examination marks were compared for 2004 and 2005, allowing a comparison of student performance before and after the replacement of the traditional lecture with the CAL package. Ethical approval for the study was granted by the faculty's Ethics Committee.

RESULTS AND CONCLUSIONS
The CAL package on small-animal housing was well received by teaching staff and students; student performance in examinations improved after the introduction of the CAL program, suggesting that it provides a suitable alternative to didactic teaching. The creation and distribution of the CAL package on CD-ROM and its availability via the Internet are intended to contribute to small-animal welfare education in local catteries and kennels and further afield. The package sets a precedent for the development of more Internet-based, student-authored CAL packages in the future, providing additional resources for independent learning.