GREGORY BONFIGLIO is the Founder and Managing Partner of Proteus, LLC – an investment and advisory firm focused solely on Regenerative Medicine. Formed in 2006, Proteus provides fund management and consulting services to the regenerative medicine industry. Proteus works with cell and gene therapy companies across all stages of development from early stage entities to large public companies, as well as governmental organizations pursuing RM initiatives. Mr Bonfiglio serves on the Board of Healios KK, one of the largest publicly traded RM companies in Japan. He is on the Investment Committee of the Centre for Commercialization of Regenerative Medicine (RM Translation Center in Toronto, Canada). He is on the Advisory Board of BioBridge Global (RM Translation Center in San Antonio, Texas). He is on the ISSCR Finance Committee. Mr Bonfiglio was an early investor in the RM field, and he continues to be actively involved in the space. He has over 35 years' experience working with technology companies. He received his BA in Mathematics (magna cum laude) from Michigan State University in 1975, and his JD (magna cum laude) from the University of Michigan Law School in 1981.


Extant analytic methods for evaluating two-center electron repulsion integrals in a Slater-type orbital (STO) basis using ellipsoidal coordinates and the Neumann expansion of 1/r12 have problems of numerical stability that are analyzed in detail using computer-assisted algebraic techniques. Some of these problems can be eliminated by use of procedures known in this field 40 years ago but seemingly forgotten now. Others can be removed by use of a formulation suitable for small values of the STO screening parameter. A recent attempt at such a formulation is corrected and extended in a way permitting its practical use. The main functions encountered in the integrations over the ellipsoidal coordinate of the range 1 … ∞ are Bessel functions or generalizations thereof, as pointed out here for the first time. This fact is used to motivate the derivation of recurrence relations additional to those previously known. Novel techniques were devised for using these recurrence relations, thereby providing new ways of calculating the quantities that enter the ellipsoidal expansion. The convergence rate of this expansion and the numerical characteristics of several computational strategies are reported in enough detail to identify the ranges where various schemes can be used. This information shows that recent discussions of the "convergence characteristics of [the] ellipsoidal coordinate expansion" are in fact not that, but are instead discussions of an inability to make accurate calculations of the individual terms of the expansion. It is also seen that the parameter range suitable for use of Kotani's well-known recursive scheme is more limited than seems generally believed. The procedures discussed in this work are capable of yielding accurate two-center electron repulsion integrals by the ellipsoidal expansion method for all reasonable STO screening parameters, and have been implemented in illustrative public-domain computer programs. © 2002 Wiley Periodicals, Inc. Int J Quantum Chem, 2002


Natural language generation of coherent long texts like paragraphs or longer documents is a challenging problem for recurrent networks models. In this paper, we explore an important step toward this generation task: training an LSTM (Longshort term memory) auto-encoder to preserve and reconstruct multi-sentence paragraphs. We introduce an LSTM model that hierarchically builds an embedding for a paragraph from embeddings for sentences and words, then decodes this embedding to reconstruct the original paragraph. We evaluate the reconstructed paragraph using standard metrics like ROUGE and Entity Grid, showing that neural models are able to encode texts in a way that preserve syntactic, semantic, and discourse coherence. While only a first step toward generating coherent text units from neural models, our work has the potential to significantly impact natural language generation and summarization1.


Pyrolysis experiments were conducted in a tubular furnace from room temperature to 600 °C at 5 °C /min, and kept for 15 min. The light tar was then derived from the liquid products of pyrolysis by n-hexane supersonic extraction. Gas chromatography–mass spectrometry was employed to analyze the light tars from cotton stalk (CS) pyrolysis, Shenmu coal (SM) pyrolysis, and co-pyrolysis of CS/SM. Microcrystalline cellulose (MCC) was selected as a model compound, and the light tar from co-pyrolysis tar of MCC/SM was investigated for comparison. The results indicated that CS improved the yields and quality of phenols and benzenes in co-pyrolysis tar and that MCC had excellent performance in the formation of mononuclear aromatics during the co-pyrolysis of MCC/SM. Based on the pyrolytic behavior of CS and SM, the mechanisms of aromatic formation were further determined. It was shown that the free radicals that cracked from CS accelerated the formation of aromatics. The alkyl and mononuclear aromatic radicals of CS pyrolysis combined with the radicals from the SM aromatic structure, which then converted to benzenes and phenols. Finally, the most favorable reaction routes of mononuclear aromatics formation were proposed.


In this paper we present a strategy and a set of algorithms for developing qualitative positioning services that provide a qualitative location optimised for the environment where they are to be deployed. We argue that for many contextaware applications this may be more appropriate than more common quantitative location systems, where the positioning API may make unrealistic demands on the underlying measurement service, and unrealistic promises to the application. We show how a symbolic location system can be learnt from training data in an unsupervised manner. We present experimental results using 802.11 and GSM signal strength levels and wireless beacon data.


C. difficile is a spore-forming anaerobic bacterium which causes infection of the large intestine with high mortality rates. The C. difficile infection is difficult to prevent and treat, as the pathogen is resistant to many antimicrobial agents. Prolonged use of β-lactam antibiotics for treatment of various infectious diseases triggers the infection, as these drugs suppress the abundance of protective gut bacteria, allowing the resistant C. difficile bacteria to multiply. While resistance of C. difficile to β-lactam antibiotics plays the major role in the development of the disease, the mechanism of resistance is unknown. The significance of our research is in the discovery in C. difficile of β-lactamases, enzymes that destroy β-lactam antibiotics. These findings ultimately can help to combat deadly C. difficile infections. ABSTRACT Clostridium difficile is the causative agent of the deadly C. difficile infection. Resistance of the pathogen to β-lactam antibiotics plays a major role in the development of the disease, but the mechanism of resistance is currently unknown. We discovered that C. difficile encodes class D β-lactamases, i.e., CDDs, which are intrinsic to this species. We studied two CDD enzymes, CDD-1 and CDD-2, and showed that they display broad-spectrum, high catalytic efficiency against various β-lactam antibiotics, including penicillins and expanded-spectrum cephalosporins. We demonstrated that the cdd genes are poorly expressed under the control of their own promoters and contribute only partially to the observed resistance to β-lactams. However, when the cdd1 gene was expressed under the control of efficient promoters in the antibiotic-sensitive Clostridium cochlearium strain, it produced high-level resistance to β-lactams. Taken together, the results determined in this work demonstrate the existence in C. difficile of intrinsic class D β-lactamases which constitute a reservoir of highly potent enzymes capable of conferring broad-spectrum, clinically relevant levels of resistance to β-lactam antibiotics. This discovery is a significant contribution to elucidation of the mechanism(s) of resistance of the clinically important pathogen C. difficile to β-lactam antibiotics. IMPORTANCE C. difficile is a spore-forming anaerobic bacterium which causes infection of the large intestine with high mortality rates. The C. difficile infection is difficult to prevent and treat, as the pathogen is resistant to many antimicrobial agents. Prolonged use of β-lactam antibiotics for treatment of various infectious diseases triggers the infection, as these drugs suppress the abundance of protective gut bacteria, allowing the resistant C. difficile bacteria to multiply. While resistance of C. difficile to β-lactam antibiotics plays the major role in the development of the disease, the mechanism of resistance is unknown. The significance of our research is in the discovery in C. difficile of β-lactamases, enzymes that destroy β-lactam antibiotics. These findings ultimately can help to combat deadly C. difficile infections.


Background Recent guidelines for the treatment of irritable bowel syndrome (IBS) emphasize the need for research to facilitate home-based self-management for these patients in primary care. The aim of the current study was to test the efficacy of a manualized cognitive behavioural therapy (CBT)-based self-management programme for IBS in a pilot randomized controlled trial (RCT). Method Sixty-four primary-care patients meeting Rome criteria for IBS were randomized into either self-management plus treatment as usual (TAU) (n=31) or a TAU control condition (n=33). The self-management condition included a structured 7-week manualized programme that was self-administered in conjunction with a 1-hour face-to-face therapy session and two 1-hour telephone sessions. The primary outcome measures were the Subject's Global Assessment (SGA) of Relief and the Irritable Bowel Syndrome Severity Scoring System (IBS-SSS) assessed at baseline, end of treatment (2 months), and 3 and 6 months post-treatment. Results Analysis was by intention-to-treat. Twenty-three (76.7%) of the self-management group rated themselves as experiencing symptom relief across all three time periods compared to seven (21.2%) of the TAU controls [odds ratio (OR) 12.2, 95% confidence interval (CI) 3.72–40.1]. At 8 months, 25 (83%) of the self-management group showed a clinically significant change on the IBS-SSS compared to 16 (49%) of the control group (OR 5.3, 95% CI 1.64–17.26). Conclusions This study provides preliminary evidence that CBT-based self-management in the form of a structured manual and minimal therapist contact is an effective and acceptable form of treatment for primary-care IBS patients.


Synthetic Biology is the latest attempt in experimental biology to reach the long lasting goal of mastering processes of life by engineering them. This emergent discipline results from the novel convergence of biology and concept and tools from other fields such as computing and engineering sciences. It relies on rational design of bioparts, modules, or organisms, as opposed to the tinkering methods provided so far by the even most sophisticated biotechnologies. Such an approach could have major consequences, for both applied and fundamental research. But this appealing narrative may obscure important epistemological issues, some of them being rooted in old misconceptions or shortcomings in biology. By focusing mainly on the mechanistic dimension of living beings, Synthetic Biology partially recycle ancient debates and could miss the opportunity to provide an integrative account of what makes life actually specific in the natural world. A first insight into a critical reassessment of some of the goals, the lexicon, and the theoretical foundations of Synthetic Biology is proposed, as other natural dimensions of the biological world are highlighted. Taken as a whole, these considerations challenge several core concepts of the discipline, but may help to redefine some of its strategies and overcome some major hurdles.


In this paper we present how the design of a power converter can be effectively improved by means of EMI phenomena simulation. We will consider the design of a converter intended as battery charger for telecommunication facilities. First of all, the phenomena involved in the generation of electromagnetic interference are reviewed. Then the main ideas used to obtain the EMI simulation model are outlined. A model of the power converter in the frequency-domain is obtained and validated through experimental measurements. Finally, this model is used to improve the design of the converter from the EMI point of view, resulting in a reduction of space, weight and cost of the filtering devices.


The m4 subtype of muscarinic acetylcholine receptor regulates many physiological processes and is a novel therapeutic target for neurologic and psychiatric disorders. However, little is known about m4 regulation because of the lack of pharmacologically selective ligands. A crucial component of G protein-coupled receptor regulation is intracellular trafficking. We thus used subtype-specific antibodies and quantitative immunocytochemistry to characterize the intracellular trafficking of m4. We show that following carbachol stimulation, m4 co-localizes with transferrin, and the selective marker of early endosomes, EEA1. In addition, m4 intracellular localization depends on Rab5 activity. The dominant negative Rab5S34N inhibits m4 endocytosis initially following carbachol stimulation, and reduces the size of m4 containing vesicles. The constitutively active Rab5Q79L enhances m4 intracellular distribution, even in unstimulated cells. Rab5Q79L also produces strikingly enlarged vacuoles, which by electron microscopy contain internal vesicles, suggesting that they are multivesicular bodies. m4 localizes both to the perimeter and interior of these vacuoles. In contrast, transferrin localizes only to the vacuole perimeter, demonstrating divergence of m4 trafficking from the pathway followed by constitutively endocytosed transferrin. We thus suggest a novel model by which multivesicular bodies sort G protein-coupled receptors from a transferrin-positive recycling pathway to a nonrecycling, possibly degradative pathway.


A stimulated Brillouin scattering sensor system with a reflector at the end of the test fiber is proposed and analyzed. The merits for BOTDR and BOTDA are combined in the proposed configuration. A reflector for the pump and prove lights are used at the end of the test fiber. A signal processing method to increase the performance is introduced.


The Veterans Health Administration (VHA) provides care to over 8 million Veterans and operates over 1,700 sites of care across 21 regional networks in the United States. Health care providers within VHA report large seasonal variation in the demand for services, especially in the southern United States because of arrival of "snowbirds" during the winter. Because resource allocation activities are primarily carried out through an annual budgeting process, the seasonal load imposed by "traveling Veterans"-Veterans that seek care at VHA sites outside of their home network-make providing high-quality services more challenging. This work constitutes the first major effort within VHA to understand the impact of traveling Veterans. We discovered strong seasonal fluctuations in demand at a clinic located in the southeastern United States and developed a seasonal autoregressive integrated moving average model to help the clinic forecast demand for its services with significantly less error than historical averaging. Monte Carlo simulation of the clinic revealed that physicians are overutilized, suggesting the need to re-evaluate how the clinic is currently staffed. More broadly, this study demonstrates how operations management methods can assist operational decision making at other clinics and medical centers both within and outside VHA.


An intelligent detection platform was developed through molecular logic gate operation based on CRISPR-Cas12a and signal amplification circuits using two kinds of pesticides [acetamiprid (ACE) and atrazine (ATR)] as inputs. The pesticide-aptamer bindings activate the signal amplification process to produce numerous double-stranded DNA, which can be identified by CRISPR-Cas12a. Under the optimal assay conditions, the sensor exhibits excellent analytical performance, with the detection limits for ACE and ATR of 2.5 and 0.2 pM, respectively. The practicality of the platform was verified by testing pesticide concentrations in food samples. Several molecular logic gates (OR, AND, XOR, and INHIBIT) were constructed using "0" and "1" to encode the target pesticides and the fluorescence readout. The logic detection platform with simple operation, high sensitivity, and multiple logic functions is promising to become a powerful sensing system for the intelligent assay of different pesticides in food samples.


The increased use of construction materials and waste, particularly waste from new construction and the destruction of worn-out fabric has caused a slew of issues. The most important of which are the problems of environmental pollution caused by the non-disposal or unprincipled and non-technical disposal of these materials. This paper reviews construction material caused by demolition from a global perspective. A comprehensive literature analysis on the subject has been done to guarantee that the most relevant studies have been taken into account. This type of review makes the selection criteria for the publications clear, allowing for an evaluation of the research conducted and its replication or expansion.


Disclosed is a baby seat bed. The present invention provides a baby seat bed integrally manufactured by compression molding of a resilient material, including a wall part and a support part, wherein the wall part is formed to surround the edges so as to prevent the baby from moving outside, and the support part consists of a head support part shaped concave for supporting the head of the baby, a neck support part projected round for supporting the neck of the baby below the head support part, and a back support part for supporting the back of the baby below the neck support part.


The eastern Mediterranean is susceptible to biological invasions because of its placement between the Atlantic, Pontic and Erythrean regions, busy maritime traffic, and lagoons and bays that are crowded with fish and shellfish farms. However, the greatest influx of invaders resulted from the opening of the Suez Canal in 1869, which allowed entry of Indo-Pacific and Erythrean biota. Exotic macrophytes, invertebrates and fish are found in most coastal habitats in the eastern Mediterranean. Some invaders have outcompeted or replaced native species locally, some are considered pests or cause nuisance, whereas other invaders are of commercial value. However, at variance with other invaded seas, the invasion into the eastern Mediterranean has increased the region's biodiversity. The rate of marine biotic invasions has increased in recent decades; collectively they have significant ecological and economic impacts in the eastern Mediterranean. Ssome Erythrean invaders have already spread as far west as Malta and Sicily , and if global warming was to affect the Mediterranean sea-water temperature, then tropical invasive species would gain a distinct advantage over the


A GP was suspended for 4 months in 2005 from the medical register after a Fitness to Practise panel found him guilty of serious professional misconduct. A female patient had consulted him with bowel problems. He proceeded to examine her back and in bending her right knee, placed his hand directly into her vulval area.1

Cases of sexual misconduct are on the increase. The General Medical Council (GMC) in December 2001 issued guidance on intimate examinations, recommending a chaperone is present during examination of the breasts, genitalia, and rectum.2 This case highlights the requisite for these guidelines to be challenged and the situations in which chaperones are required to be redefined. It is likely and possible, either advertently or inadvertently, that patients are sexually harassed by their doctor even during an examination of the torso.

### How do you define a chaperone?

In medical practice there is no exact definition of a chaperone. The English word was first recorded in the 15th century and originally meant 'hood for a hawk.' It later came to mean 'a woman who protects a young single woman.' The French verb 'chaperonner' means 'to cover with a hood' and therefore the word came to have the sense 'protector.'

### GMC guidelines

Physicians have long been advised to have a chaperone present during specific parts of the physical examination. The GMC in 2001 produced guidelines for doctors performing intimate examinations. Intimate examinations include examination of breasts, genitalia or rectum. It is recommended that doctors offer a chaperone or invite the patient (in advance if possible), to have a friend or relative present.2 The GMC pointed out that in the case of Clifford Ayling, a GP alleged to have assaulted former patients, a chaperone must be a third party of the same sex as the patient and with nothing to gain by interpreting the …


In this study, we explore the origin of lower crustal seismicity and the factors controlling rift propagation using seismological data recorded within the youngest part of the East African Rift System, the North Tanzanian Divergence (NTD). Most earthquakes below Lake Manyara occur at depth ranging between 20 and 40 km and have a swarm‐like distribution. Focal mechanisms of 26 events indicate a combination of strike‐slip and normal faulting involving Archaean basement structures and forming a relay zone. The derived local stress regime is transtensive and the minimum principal stress is oriented N110°E. Crustal seismic tomography reveals low‐velocity anomalies below the rifted basins in the NTD, interpreted as localized thermomechanical perturbations promoting fluid release and subsequent seismicity in the lower crust. SKS splitting analysis in the NTD indicates seismic anisotropy beneath 17 stations most likely due to aligned magma lenses and/or dikes beneath the rift and to the lithospheric fabrics. Our results favor a strain pattern intermediate between purely mechanical and purely magmatic. We suggest that melt products arising from a large asthenospheric thermal anomaly enhance lithospheric weakening and facilitate faulting and creeping on critically oriented inherited structures of the Precambrian lower crust. Although the crust is unlikely weakened at a point comparable to other parts of the East African Rift System, this deep‐seated thermomechanical process is efficient enough to allow slow rift propagation within the eastern Tanzanian cratonic edge.


The main goal of this project was to develop some sort of a diverter for pipestransporting waste in a vacuum system. This unit was supposed to be both cheap andeasy to serve/exchange worn out parts. With a limited space to install the pipeexchanger, the challenge was to keep it as compact as possible without constructingbends with to small radius or to sharp angles as this would wear out the system a lotfaster than planned. The system was also supposed to be able to handle clothes andscrubs from hospitals. Having too much sharp edges or angles would tear the clothesapart. We were also limited to the building plan. The diverting unit had an inlet thatwas required to be aligned with a hole in the wall that was currently being molded tofollow the already thought out flow. The two outlets also had to align with the rest ofthe piping system, to make sure that the containers on the loading bay did notbecome offset from the original position. This would cause problems with the spacefor the trucks that retrieve them in the building.The result from this thesis is a solution that is adaptable for different situations, and indifferent scales. This is really beneficial as the company has two different sizedsystems and will be able to use the same module for all of their constructions. It doesnot matter whether the construction is mounted horizontally or vertically.Throughout the designing process there were aspects about costs, simplicity and lastbut not least function that was taken into account. There are a lot of things that isdependent of these three mayor aspects. As for design, a more esthetic design, makesit more costly to produce. And having unnecessary weight in the construction affectsboth the simplicity as in it gets harder to mount into place and serve, as well as anunnecessary cost. Keeping it simple was also required as we had to keep it compact.


Incorporation of a range of higher concentrations of CuSO 4 _ 5H 2 O in MS medium significantly enhanced direct shoot bud induction and proliferation from cultured leaf and nodal explants taken from mature plants of Stevia rebaudiana Bertoni . Shoot bud induction medium was supplemented with BAP (2.2 µ M) and NAA (2.8 µ M). When the concentration of CuSO 4 _ 5H 2 O in the induction medium was raised to 0.5 µ M (five times the MS level, i.e. 0.1 µ M) there was significant increase in percentage response along with increase in shoot bud number per explant. The shoots were healthy, well developed with dark green broader leaves. There was remarkable increase in total biomass at increased (0.5 µ M) copper level in the medium. During proliferation stage also presence of high copper levels in the medium favoured increase in shoots bud number per explant.


Five cases (four females, one male) of ketoconazole-related liver damage are presented, two of whom died. All patients received ketoconazole (400 mg/day) for various mycoses. In the four women the first signs of hepatotoxicity appeared after four weeks of therapy. One fatal case developed massive necrosis with fulminant liver failure and the other, submassive necrosis. In four cases cholestasis was a prominent finding. Biochemical evidence of biliary stasis may persist for several months, as occurred in the three surviving patients of our series. The two fatal cases continued receiving the drug in spite of its adverse effects. Consequently, repeated evaluation is recommended to detect early signs of liver environment.


With an ever increasing need for the reduction of carbon and nitrogen based emissions, gas turbine technology has evolved over the years. Lean burning (i.e. high air to fuel ratio) has proven to be an effective method in reducing the nitrous oxide emissions. However, these flames are susceptible to combustion oscillations that could lead to excessive heat transfer, oscillatory thermal and mechanical stresses and flame blow-off or flashback. The addition of hydrogen fuel to turbulent flames has been studied in the past and been reported to have reduced combustion oscillations and nitrous oxide formation, however, there are studies in literature that show combustion oscillations triggered by the addition of hydrogen. This project aimed to further investigate the effects of local hydrogen addition on the dynamics of turbulent lean premixed flames in a model gas turbine combustor. The flames were subjected to controlled reactant mass flow oscillations (created by acoustic speakers) that led to flame surface roll-up, thus causing heat release perturbations (i.e. combustion oscillations). Under these conditions hydrogen fuel was locally added into the flow to study the effects on the response of the flame. A secondary objective was to develop a laser technique for imaging the laser induced fluorescence of atomic hydrogen in turbulent flames. While earlier studies had only focused on laminar flames, this project concentrated on imaging large sections of turbulent premixed flames which were subjected to acoustic forcing. The results showed that the local addition of hydrogen reduced the heat release oscillations of the flame under certain operating conditions. The change in the response of the flame was due to the alteration of the flame surface area. While there were benefits of reducing heat release oscillations, the addition of hydrogen to the flame had a negative impact on the nitrous oxide exhaust emissions.


Scientific Meeting of the Faculty of Accident and Emergency Medicine, Royal College of Physicians, London, 3–4 December 1999 Prize Session, 3 December 1999 A descriptive study of a chest pain observation unit in a UK hospital S W GOODACRE, F P MORRIS, K ANGELINI, J A ARNOLD Accident and Emergency Department, Northern General Hospital, Herries Road, SheYeld S5 7AU Background—The chest pain observation unit (CPOU) has been developed in the United States as a safe and cost eVective alternative to hospital admission for patients attending with chest pain. We aimed to reproduce a CPOU protocol in a United Kingdom hospital, describe its function, and evaluate its safety. Method—A protocol consisting of 4 to 6 hours continuous ST monitoring and serial electrocardiograms (ECGs), CK-MB (mass), and troponin T measurement and, when appropriate, exercise stress testing was made available for patients attending A&E with chest pain who were at low risk of myocardial infarction. Criteria for admission or discharge were drawn up and applied. All patients were followed up— those admitted by case note review, and those discharged by clinical assessment, ECG, and troponin T measurement at 72 hours after discharge. Results—To date 200 patients have been assessed according to the protocol. Mean age was 53 years, 60% were male, and 22% were known to have ischaemic heart disease; 35 (18%) were admitted and 165 (83%) discharged. Reasons for admission were positive enzyme tests for 12 patients (34%), serial ECG changes for eight (23%), positive or inconclusive stress tests for 11 (31%), and other reasons for four (11%). A final diagnosis of myocardial infarction was made in seven (3.5%). 90% of the discharged patients attended for follow up. No evidence of missed pathology was found at 72 hour follow up. Conclusion—The US model of the chest pain observation unit can be safely reproduced in the UK. Studies are now required to determine its eVectiveness and cost eVectiveness compared with routine UK practice. In vitro evaluation of the eVect of haemodilution with crystalloid and colloid solutions on coagulation profile measured by Sonoclot analysis E V BRAZIL, T J COATS Academic Unit, Accident and Emergency Department, Royal London NHS Trust, Whitechapel, London E1 1BB Introduction—The "Sonoclot analyser" is a device used to measure the quality of a developing blood clot. It measures the changing resistance to movement imposed by a developing clot on a small probe vibrating at an ultrasonic frequency in a coagulating blood sample. Two commonly used measurements derived from Sonoclot analysis are the rate of fibrin formation from fibrinogen (rate) and the time to reach maximum resistance (peak). This device has not previously been used to investigate the eVect of haemodilution on


Background:  Although metformin is widely used in the management of type 2 diabetes, its mechanism(s) of action is not fully known, and there have been remarkably few reports on short‐term effects of the drug. Here, we examined early effects on glucose and lipid metabolism, and on certain adipose tissue and inflammatory markers during treatment for 28 days.


At 26 h after inoculation of rats with Diplococcus pneumoniae, the serum concentrations of 10 and 20 individual amino acids were lower than corresponding values observed in pair-fed controls. In contrast, only 2 of 20 serum amino acids were similarly decreased in rats inoculated with Salmonella typhimurium. Despite these serum differences, a greater accumulation of labeled non-metabolizable amino acids occurred in the livers of rats infected with S. typhimurium. These data suggested a greater increase in the flux of amino acids from muscle to liver in the rats infected with S. typhimurium as compared to those infected with D. pneumoniae. A similar increase in serum protein synthesis was observed in rats infected with D. pneumoniae or S. typhimurium. However, with the latter infection, a larger percentage of the amino acids appeared to be utilized as a source of energy in addition to their role as precursors of proteins.


This thesis describes the coincident prediction and observation of thermo-acoustic instabilities in a turbulent, swirl-stabilized research combustor using a stability model constructed from validated reduced-order component models. The component models included the acoustic response to flame heat release rate at various locations in the combustor, the turbulent diffusion of uneven fuel-air mixing, and the flame's response to perturbations in both inlet velocity and equivalence ratio. These elements are closed in a system-level model to reflect their natural dynamic coupling and assessed with linear stability criteria. The results include the empirical validation of each of the component models and limited validation of the total closed-loop model with a lean premixed gaseous fuel combustor not dissimilar to an industrial burner. The degree of agreement between the predictions and the measurements encourages the conclusion that the reduced-order technique described herein not only includes the relevant physics, but has characterized them with sufficient acuracy to be the basis for design techniques for the passive avoidance of thermo-acoustic instabilities.


Traditional CSCW systems generally use point-to-point architecture for mutual communication. Peer-to-peer (P2P) architecture requires all the participants to contribute their individual resources in a collaborative group. In this paper, we propose a real-time collaborative editing system based on P2P network architecture. This architecture provides a reliable and efficient communication environment for collaborative editing. Each collaborator participates in the routing of other clients' requests, and contributes bandwidth to relay data-streams. Another advantage is to reallocate the network resources among the whole collaborative group, thus facilitate the mutual awareness and optimize the collaborative effect.


Regina septemvittata (Queen snake) is a semi-aquatic snake occurring throughout central and eastern North America that exhibits extreme dietary specialization, feeding almost exclusively on freshly molted crayfishes. Though it is known R. septemvittata forage on crayfishes, little is understood about prey preferences at the species and genus level. Because different crayfish species have varying life history patterns, and molting frequency is allied to life history attributes, it is not clear whether there is a preference based on crayfish species or prey availability based on molt state. To determine if R. septemvittata has preferences for species, we surveyed four streams in the northern panhandle of West Virginia for R. septemvittata and completed seasonal life history studies on crayfish species occurring in those streams from March through October 2018. Over the collecting season 101 Queen snakes were captured. From these, we recovered 24 prey samples that were subsequently identified using either polymerase chain reaction (PCR) or visual identification. Monthly crayfish sampling was used to determine molting frequency of the two available prey species in the study streams: Cambarus carinirostris and Faxonius obscurus. Preliminary results seem to indicate that freshly molted crayfish availability dictates foraging behavior in R. septemvittata, and a lack of specialization at the taxonomic level occurs in this species.


Hepatitis B virus (HBV) infection is a serious global health problem. Globally more than 2 (Two) billion people are infected with Hepatitis B virus and about 400 million people are chronic carriers who are at risk of death from liver cirrhosis and liver cancer that kill more than one million people globally each year. Prevalence of HBV infection in Bangladesh is 2.3 to 9.7% and approximately 10 million people are harboring the virus as carrier. HBV infection is increasing at an alarming rate in Bangladesh due to lack of health education, poverty, illiteracy and lack of hepatitis B vaccination. This cross sectional study was carried out in the Department of Clinical Pathology, in collaboration with Department of Hepatology and Department of Pathology, Bangabandhu Sheikh Mujib Medical University (BSMMU), Dhaka, Bangladesh from September 2013 to August 2014 to assess the role of Red cell distribution width to platelet ratio (RPR) as a non invasive marker in predicting hepatic fibrosis in chronic hepatitis B patients. Total 40 patients with chronic hepatitis B virus infection who fulfilled the criteria of chronic hepatitis B were included in this study. In this study, majority of the patients belonged to 20-29 years, most of the patients were male and HBeAg negative .Histopathology was gold standard to identify the stages of hepatic fibrosis. We also measured RDW and Platelet count by automated haematology analyzer when platelet count was rechecked manually; RDW to platelet ratio was calculated to see the correlation between RPR with different stages of hepatic fibrosis. In chronic hepatitis B patients a positive and significant correlation was found between RPR and stages of hepatic fibrosis and Spearman's correlation coefficient for RPR was 0.749 which was positive and highly significant (p<0.001). Sensitivity, specificity, positive predictive value, negative predictive value and accuracy of RDW to Platelet ratio (RPR) was 62.86%, 80%, 95.65%, 23.53% and 65% respectively. To assess the diagnostic performance of RPR we also used receiver-operating curve (ROC). The area under ROC was 0.889 for identification of hepatic fibrosis. This data revealed that RPR is strongly associated with stages of hepatic fibrosis in chronic hepatitis B patients. As such RPR may be a useful diagnostic tool for assessing the hepatic fibrosis in chronic hepatitis B patients.


This thesis is an exploration of leadership dimensions of academic organisational processes. It consists of four case studies, each presenting a leadership challenge. These studies of specific situations offer great opportunities to investigate the variety of leading that the academy contains. There is focus, not so much on the task but on the process in which the challenges are positioned, how they are understood and approached, and what action ensues. The cases also inform on individual circumstances as well as group and organizational situations, and there is an additional focus on personal and organizational developmental processes.Qualitative research methods have been used throughout the studies, for the purpose of reflection and understanding, rather than verifiable facts. The closeness of the case study to real-life situations and its almost infinite wealth of details provides the opportunity to develop nuanced view and theory of leadership in the academy. Thematic and narrative analyses, applied in these studies, give access to knowledge about sense-making and coping in the different leadership challenges. They also make it possible to sort out differences that matter in ideas and approaches to leadership embedded in the processes of these challenges.The findings from the four cases studies of this thesis show that (1) reflections on art and architecture may be conducive for stimulating innovative inclusive ways of conducting leadership development, (2) there are four different "rooms of leadership" at the university, which are all based on varying institutional logics, (3) formal leaders interpret and act in line with a particular sequence of episodes when dealing with destructive research leaders in their organization, and (4) there is a variety of types of disharmony influencing creativity in a long lasting research environment, and these can be managed with different strategies.Altogether, these studies show that the process dimensions of the four leadership challenges contain various notions and practices of leading that in situations of stress reach a state of tension or conflict with one another. These tensions are in the thesis understood as organisational paradoxes, or polarities, i.e. problems that cannot be solved but can be lived and led. The findings also suggest that a both/and approach, and the psychoanalytic concept of holding can be helpful in an understanding of leading towards constructive outcomes of these leadership challenges. (Less)


This paper introduces a new segmentwise technique which consolidates multiple principles for nonrigid structure from motion (NRSfM) into a single energy-based framework. The energy functional of our Consolidating Monocular Dynamic Reconstruction (CMDR) approach is optimised by non-linear least squares and includes terms allowing to define the deformation model and additional constraints simultaneously in the metric and trajectory spaces. The proposed method achieves high accuracy on several tested sequences while providing robustness and scalability due to the spatial scene segmentation and the new lifted spatial Laplacian term. CMDR is flexible and easy to implement, thanks to the unified optimisation framework. It allows for scenario-specific extensions and can be used for rapid prototyping of new NRSfM methods.


Purpose: Evaluation and selection of efficient suppliers is one of the key issues in supply chain management which depends on wide range of qualitative and quantitative criteria. The aim of this research is to develop a mathematical model for evaluating and selecting efficient suppliers when faced with supply and demand uncertainties. Design/methodology/approach: In this research Grey Relational Analysis (GRA) and Data Envelopment Analysis (DEA) are used to evaluate and select efficient suppliers under uncertainties. Furthermore, a novel ranking method is introduced for the units that their efficiencies are obtained in the form of interval grey numbers. Findings: The study indicates that the proposed model in addition to providing satisfactory and acceptable results avoids time-consuming computations and consequently reduces the solution time. To name another advantage of the proposed model, we can point out that it enables us to make decision based on different levels of risk. Originality/value: The paper presents a mathematical model for evaluating and selecting efficient suppliers in a stochastic environment so that companies can use in order to make better decisions.


Quantile regression allows for broad (conditional) characterizations of a response distribution beyond conditional means and is of increasing interest in economic and financial applications. Because quantile regression estimators have complex limiting distributions, several bootstrap methods for the independent data setting have been proposed, many of which involve smoothing steps to improve bootstrap approximations. Currently, no similar advances in smoothed bootstraps exist for quantile regression with dependent data. To this end, we establish a smooth tapered block bootstrap procedure for approximating the distribution of quantile regression estimators for time series. This bootstrap involves two rounds of smoothing in resampling: individual observations are resampled via kernel smoothing techniques and resampled data blocks are smoothed by tapering. The smooth bootstrap results in performance improvements over previous unsmoothed versions of the block bootstrap as well as normal approximations based on Powell's kernel variance estimator, which are common in application. Our theoretical results correct errors in proofs for earlier and simpler versions of the (unsmoothed) moving blocks bootstrap for quantile regression and broaden the validity of block bootstraps for this problem under weak conditions. We illustrate the smooth bootstrap through numerical studies and examples. . 05 and 0 . 05 for the sizes n = 50, 100 and 200. This demonstrates the potential usefulness of the SETBB method in QR-based forecasting problems in addition to quantile parameter estimation.


A tunable chromatic dispersion and dispersion slope compensator is proposed that has a single lattice-form filter configuration. Wavelength dependence is intentionally added to its tunable couplers, which produces dispersion slope compensation in addition to the dispersion compensation. Dispersion tunability of +/- 500 ps/nm and a slope of -4.9 ps/nm(2) over 40 GHz are successfully demonstrated, thus meeting the requirement for 40 Gbits/s differential quadrature phase shift keying transmission with an 80 km long nonzero dispersion-shifted fiber.


Pseudotumor cerebri (PTC) or Idiopathic Intracranial Hypertension (IIH) is a well-known syndrome in the pediatric population. PTC/IIH is less common in children than in adults, has distinct clinical manifestations and different characteristics in the prepubertal versus the pubertal age groups. Secondary risk factors are relatively common. As in adults, the pathophysiological basis of PTC/IIH is as yet undefined.


PURPOSE
To study oculomotor disorders after transpalpebral bony orbital decompression (TPBOD) for dysthyroid orbitopathy. Pathophysiology, risk factors, preventive and therapeutic care were examined.

MATERIAL AND METHODS
Forty-four patients were included in this retrospective study (76 orbits). Thirteen patients underwent surgery for severe orbital inflammation or optic neuropathy and 31 for cosmetic rehabilitation. 21 previously had orbital radiotherapy. Class IV of NOSPECS classification, primary position of gaze, diplopia and Lancaster coordimetry were studied comparatively pre and postoperatively.

RESULTS
Diplopia appeared in 23.6% of the cases without deviation before surgery (tropia or phoria-tropia). Predictive factors were age and amblyopia whereas amount of retrodisplacement of the globe and radiotherapy were not. Lack of oculomotor restriction did not prevent from diplopia but may decrease its incidence. Unilateral decompression is more likely to create a vertical disorder. Pathophysiology is discussed.

CONCLUSION
Oculomotor disorders can be explained by several mechanisms. Some of them can be prevented. Each patient should be aware of the risk of diplopia.


Based on the observation of 929 patients who had to be subjected to tonsillectomy within a period of twelve months, the authors concluded that the vast majority of post operative haemorrhages occurred during the beginning of a good weather period (clearing from the west), not quite so often during a "Föhn"-period (warm winds from the south). This contrasts somewhat with the observations of other authors who found a connection between haemorrhages and the beginning of a period of bad weather (close and stuffy, increasing humidity, high clouds). The dependence of postoperative haemorrhages on meteorological influences would perhaps give a reason for the hitherto medically unexplainable 40 per cent bleedings. Based on these observations it would be desirable for the meteorologic stations (or the media) to inform the doctors and hospitals about the weather phases.


Many approaches to trajectory generation for nonlinear systems approximate the feasible set using polytopes. This approximation can be very poor even for simple differentially flat systems. For a large class of flat systems arising in aerospace applications, the feasible flat output set is defined in terms of rational function inequalities. We use this observation and a well-known result from robust control to derive a linear fractional representation (LFR) of the feasible set. It is possible to obtain good convex sufficient conditions for trajectory generation from the LFR as similar problems have been tackled in p-analysis related work. In this paper, we develop a sufficient bilinear problem from the LFR. The global optimization algorithm of Floudas and Visweswaran (1990) can be used to check feasibility though not in polynomial time. We present an example to illustrate the difficulties with polytopic approximations and the advantages of the proposed LFR approach.


Abstract. Ireland has significantly increased its climate mitigation ambition, with a recent government commitment to reduce greenhouse-gases by an average of 7 % per year in the period to 2030 and a "net-zero" target for 2050, underpinned by a series of five-year carbon budgets. Energy systems optimisation modelling (ESOM) is a widely-used tool to inform pathways to address long-term energy challenges. This article describes a new ESOM developed to inform Ireland's energy system decarbonisation challenge. The TIMES-Ireland Model (TIM) is an optimisation model of the Irish energy system, which calculates the cost-optimal fuel and technology mix to meet future energy service demands in the transport, buildings, industry and agriculture sectors, while respecting constraints in greenhouse-gas emissions, primary energy resources and feasible deployment rates. TIM is developed to take into account Ireland's unique energy system context, including a very high potential for offshore wind energy and the challenge of integrating this on a relatively isolated grid, a very ambitious decarbonisation target in the period to 2030, the policy need to inform five-year carbon budgets to meet policy targets, and the challenge of decarbonising heat in the context of low building stock thermal efficiency and high reliance on fossil fuels. To that end, model features of note include "future proofing" with flexible temporal and spatial definitions, with a possible hourly time resolution, unit commitment and capacity expansion features in power sector, residential and passenger transport underpinned by detailed bottom-up sectoral models, cross-model harmonisation and soft-linking with demand and macro models. The paper also outlines a priority list of future model developments to better meet the challenge of deeply decarbonising energy supply and demand, taking into account equity, cost-effectiveness and technical feasibility. To support transparency and openness in decision-making, TIM is available to download under a Creative Commons licence.


Spatial criticism is an attempt to study environmental literature to demonstrate re-lationships between physical spaces and identity. Place attachment is a concept of environmental psychology that deals with the emotional bonds between individuals and the environment in which they feel secure. It is through the concepts of place identity and sense of place that scholars bring to the fore the concept of place attachment. Extending this thinking, the present paper seeks to propose place attachment and fear of disruption in attachment as the main reason for Jack Gladney's fear of death. The protagonist of Don DeLillo's White Noise (1985) has developed a strong sense of place, identity and belonging to the space of town, supermarket, and his house. Jack's obsession with the cyberspace of TV and its psychic data is also ex-amined in this paper. The aim of this paper is thus to study the formulation of the sense of place in Gladney. His place attachment and the fear of disruption are also studied at the crossroad of spatial criticism and trauma theory. The paper concludes by demonstrating how the fear of displacement causes haunting fear and anxiety in Jack Gladney.


Previous research of the effect of winter on wellbeing has yielded contradictory findings. While there is evidence that the lack of sunlight in wintertime can lead to seasonal depression and negative emotions, many individuals are able to thrive during the winter. What might determine whether the darkness of winter leads to poor psychological outcomes? To investigate whether or not mindset contributes to wintertime wellbeing, we assessed wintertime mindset via a Wintertime Mindset Scale measuring attitudes towards winter. A survey of 238 respondents from southern Norway, northern Norway, and the Arctic island of Svalbard identified correlations between positive wintertime mindset and measures of wellbeing, including life satisfaction and positive emotions. Latitude and wintertime mindset were also correlated, with more northern residents, who experience significantly more darkness and somewhat colder temperatures during the winter, holding more positive wintertime mindsets, and wintertime mindset statistically mediating the relationship between location and wellbeing. These results suggest that mindset is a previously overlooked factor of seasonal wellbeing, especially in places where the winter darkness is more extreme. Implications of these findings and suggestions for further research are discussed.


Ampelopsis grossedentata (AG) is an ancient medicinal plant that is mainly distributed and used in southwest China. It exerts therapeutic effects, such as antioxidant, anti-diabetic, and anti-inflammatory activities, reductions in blood pressure and cholesterol and hepatoprotective effects. Researchers in China recently reported the anti-obesity effects of AG extract in diet-induced obese mice and rats. To verify these findings, we herein investigated the effects of AG extract and its principal compound, ampelopsin, in high-fat diet (HFD)- and alcohol diet-fed mice, olive oil-loaded mice, and differentiated 3T3-L1 cells. The results obtained showed that AG extract and ampelopsin significantly suppressed increases in the weights of body, livers and abdominal fat and also up-regulated the expression of carnitine palmitoyltransferase 1A in HFD-fed mice. In olive oil-loaded mice, AG extract and ampelopsin significantly attenuated increases in serum triglyceride (TG) levels. In differentiated 3T3-L1 cells, AG extract and ampelopsin promoted TG decomposition, which appeared to be attributed to the expression of hormone-sensitive lipase. In alcohol diet-fed mice, AG extract and ampelopsin reduced serum levels of ethanol, glutamic oxaloacetic transaminase (GOT), and glutamic pyruvic transaminase (GPT) and liver TG. An examination of metabolic enzyme expression patterns revealed that AG extract and ampelopsin mainly enhanced the expression of aldehyde dehydrogenase and suppressed that of cytochrome P450, family 2, subfamily e1. In conclusion, AG extract and ampelopsin suppressed diet-induced intestinal fat accumulation and reduced the risk of fatty liver associated with HFD and alcohol consumption.


Majority of the existing text classification algorithms are based on the "bag of words" (BOW) approach, in which the documents are represented as weighted occurrence frequencies of individual terms. However, semantic relations between terms are ignored in this representation. There are several studies which address this problem by integrating background knowledge such as WordNet, ODP or Wikipedia as a semantic source. However, vast majority of these studies are applied to English texts and to the date there are no similar studies on classification of Turkish documents. We empirically analyze the effect of using Turkish Wikipedia (Vikipedi) as a semantic resource in classification of Turkish documents. Our results demonstrate that performance of classification algorithms can be improved by exploiting Vikipedi concepts. Additionally, we show that Vikipedi concepts have surprisingly large coverage in our datasets which mostly consist of Turkish newspaper articles.


This paper presents a simulation program for computation of field coupling to multiconductor transmission line cable bundles above a perfectly conducting ground plane. The approach is based on an extended transmission line theory which considers shielded multiconductor transmission lines as well as the influence caused by bends. For validation the results of a single transmission line with a bend above a ground plane are compared with results provided by a simulation program based on the method of moments. Simulation results for a practical line arrangement with bends as well as the coupling to a shielded multiconductor transmission line are discussed.


Background Localized disease manifestations including inflammatory subglottic stenosis in GPA have been associated with a refractory disease course in case series and small cohorts [1, 2]. Objectives To identify and characterize GPA patients with inflammatory subglottic stenosis (SST) and/or tracheobronchitis (TB) retrospectively within our monocentric cohort of 1184 GPA patients followed from January 1990 to August 2011 with respect to disease stage, disease manifestations, course of disease, treatment (including interventional procedures) and outcome. Methods All patients who fulfilled the American College of Rheumatology criteria or the Chapel Hill Consensus Conference Definition (n=70) or the EMEA algorithm for GPA (n=20) [3] or had localised GPA [2] and developed SST and/or TB were included. Patients were assessed in 4-6 monthly intervals by a standardized interdisciplinary setting [2] with respect to SST and/or TB (including ENT opinion and/or bronchoscopy and/or high-resolution CT), all other clinical manifestations, disease stages and activity, ANCA-status, duration and intensity of immunosuppressive treatment, interventional procedures, treatment effect, relapse rate, chronic organ damage and side effects of treatment. Results 1184 GPA patients were seen during the follow-up period, 90 of whom (7.6%; 94.4% ANCA positive, 62.2% female) developed SST and/or TB and had a follow-up of >6 months (median follow-up: 56 months, range: 6-262 months). 33 (36.7%) patients were under immunosuppression when SST/TB occurred; 58 (64.4%) received cyclophosphamide and glucocorticoids for remission induction (47.2% for SST/TB, 52.8% for other disease manifestations), 18 (20%) medium-potent immunosuppression. 78 (86.7%) achieved response/remission, 12 (13.3%) were refractory. Interventional procedures during remission induction were required in 30 patients (33.3%) including tracheostomas in 12 patients. 40 patients (44.4%) developed chronic SST and 19 (21.1%) developed chronic bronchial stenosis, 35 (38.9%) of whom required interventional procedures for scarring. 29 patients (32.2%) had 1-4 relapses. Conclusions ST/TB is a less common disease manifestation (7.6%) which was treated successfully by immunosuppression in the majority of cases (86.7%) but frequently recurred. SST/TB is associated with a high burden of disease and damage (44.4% chronic SST, 21.1% chronic bronchial stenosis) requiring interventional procedures in 35 patients (38.9%) to secure airways during active disease or to treat scarring processes during remission. References Langford CA, Sneller MC, Hallahan CW, Hoffman GS, Kammerer WA, Talar-Williams CW et al. Clinical features and therapeutic management of subglottic stenosis in patients with Wegener's granulomatosis. Arthritis Rheum 1996; 39: 1754-1760. Holle JU, Gross WL, Holl-Ulrich K, Ambrosch P, Noelle B, Both M et al. Prospective long-term follow-up of patients with localized Wegener's granulomatosis: does it occur as persistent disease stage? Ann Rheum Dis 2010; 69: 1934-1039. Watts R, Lane S, Hanslik T, Hauser T, Hellmich B, Koldingsnes W et al. Development and validation of a consensus methodology for the classification of the ANCA-associated vasculitides and polyarteritis nodosa for epidemiological studies. Ann Rheum Dis 2007; 66: 222-227. Disclosure of Interest None Declared


The September 11, 2001 terrorist attack birth the idea of biometric measures, when the traditional methods of identification were concluded to be prone to leakage of personal information, identity theft, fraud, etc., and there are great security risks in identity recognition. Biometrics is a device used to identify and reliably confirm a person's individuality using the physiological or behavioral characteristics. This term paper examined some of the gray areas surrounding biometric technology and informs the public about the growing number of ethical concerns associated with the use. The idea came up as a result of the rising popularity of biometric systems and their application in mainstream society which led to many ethical concerns, where biometric sensors and scanners are being implemented with no consideration for unintended negative consequences. A systematic review of related literatures was adopted and used to examine the relevant ethical issues. The identified ethical issues paved way for the recommendation of 7 points guidelines, which when adopted will alleviate the fear associated with biometric technology.


Seed for invasive cardiology was sown in early part of nineties. Cardiac catheterization was actually pioneered by Werner Forssmann in 1929. However, credit for therapeutic interventional cardiology should go to US vascular radiologist, Charles Theodore Dotter for performing first peripheral arterial angioplasty [PTA] in 1964. Subsequently, a German cardiologist by name Andreas Gruentzig adapted the technique in 1974 to suit coronary artery disease and performed the first human coronary balloon angioplasty to treat blockage in coronary artery in 1977.


Interleukin-2 (IL-2), a product of activated T-cells, is now being used in a number of protocols for cancer immunotherapy. In one stem cell transplantation protocol for breast cancer, IL-2 is used together with interferon-gamma (IFN-gamma) and cyclosporine to stimulate a graft-versus-tumor response and improve the likelihood of a prolonged remission. We present the case of a patient who developed peripheral eosinophilia, perihilar infiltrates, and hypoxemia after autologous stem cell transplantation and the use of recombinant IL-2 and IFN-gamma. Histologic analysis of transbronchial lung biopsies demonstrated a few eosinophils within the bronchial submucosa. Immunostaining using antibodies directed against eosinophil major basic protein (MBP), however, revealed massive extracellular deposition of this toxic granule protein throughout the lung parenchyma. IL-2 therapy is well known to induce a peripheral eosinophilia and to be associated with the capillary leak syndrome characterized by weight gain, edema, and oliguria. The findings noted in this case report suggest that the eosinophil activation that accompanies immunologic therapy with IL-2 can result in direct toxicity to the lung and a localized vascular leak syndrome. This syndrome should be considered in the differential diagnosis of pulmonary infiltrates that occur acutely after bone marrow transplantation with cytokine augmentation.


Objective: To evaluate the outcome of presurgical nasoalveolar molding (PNAM) therapy in the treatment of patients with nonsyndromic unilateral cleft and palate (UCLP). Design: A prospective study with blinded measurements. Patients: Twelve patients with UCLP treated from 1997 to 2003. Interventions: The starting age for PNAM therapy was 26 days and the average length of the therapy was 110 days. Main Outcome Measures: Measurements of intraoral and extraoral casts were made, and statistical analyses were used to compare the differences between pre- and posttherapy measurements. Results: After PNAM therapy, there was a statistically significant decrease in both intersegment alveolar cleft distance and columellar deviation (p < .05). There was also a statistically significant increase in cleft nostril height, maxillary width, and columellar width (p < .05). Moreover, although there was no statistically significant reduction of the affected nostril width, it demonstrated on average 1.7-mm reduction after PNAM therapy. The length of the time the patient utilized the appliance and postmolding nostril height were found to have a statistically significant positive correlation (p < .05). Conclusions: PNAM therapy decreases intersegment alveolar cleft distance while permitting an increase in posterior maxillary arch width. It also increases nasal symmetry by decreasing columellar deviation, increasing nostril height on the affected side, maintaining bialar width of nose, increasing columellar width, and creating more symmetrical nostril heights and widths. The improvement of the height of the cleft nostril was correlated with the time the appliance was applied.


Commissive speech  acts  in  discourse  dialogue  with  the  candidates  for  mayor  of Pariaman -IJP- sympathizers aimed at explaining the form of speech act commissive and contextual explanation. Commissive speech act is used in dialogue with sympathizers in the form of speech promise and offer something. But the speakers did not use the speech act commissive dengna form of oath. Commissive speech acts speech acts are used only with the form of promises and offers, while the speech act with a form of oath was not found. In utter promises and offers something of speakers seem to be careful in communicating with supporters. This is done so that the speaker hearer does not feel offended or deceived by the utterances of speakers. Because the purpose of a dialogue with the speakers of sympathizers to steal sympathetic and settled on the speakers as the prospective head region. In addition to speech acts speech acts commissive also found another use of a speaker and hearer in the dialogue that is assertive speech act with the report form, mentions, and shows as well as expressive speech acts in the form of criticism.


Appropriate for undergraduate-level courses in Introduction to Engineering Experimentation found in departments of Mechanical, Aeronautical, Civil, and Electrical Engineering. Wheeler and Ganji introduce many topics that engineers need to master in order to plan, design and document a successful experiment or measurement system. The text offers thorough discussions of topics often ignored or merely touched upon by other texts, including modern computerized data acquisition systems, electrical output measuring devices, and in-depth coverage of experimental uncertainty analysis.


Objective To determine the efficacy of narrowband ultraviolet B therapy (NBUVB) with needling in patients of vitiligo. Methods A total of 100 cases were included in this study. In each patient a patch of 15 to 5 cm diameter skin area was selected as a target lesion for the study. Needling was done on the whole patch with a disposable insulin syringe, from the pigmented margins or the islands in the vitiliginous patch. After the procedure, the whole patch was subjected to NBUVB. The repigmentation was assessed according to 5-grades scale. Results Out of 100 patients of vitiligo, 45% males and 55 % females, treated with NBUVB with needling, 58% patients showed grade 4 response i.e. 75% or more repigmentation. Conclusion Narrowband UVB with needling is an effective, useful and well-tolerated therapy for treatment of vitiligo.


We constructed a new apparatus, built upon a trap-based slow positron beam, for the production of a collimated, energy-tunable positronium beam under ultra-high vacuum conditions employing the photodetachment of positronium negative ions. A slow positron generator consisting of a 22Na radioisotope (20 mCi) combined with a buffer-gas positron trap is employed to generate high-quality, nano-second positron bursts with a repetition rate of 1 Hz-1 kHz. The positron bursts are focused onto an efficient positron-to-positronium negative ion converter, a Na-coated W thin film in a transmission geometry, using a magnetic lens system. The ions emitted from the opposite surface of the film are electrostatically accelerated to a given energy and photodetached by a pulsed infrared laser to form a mono-energetic positronium beam with kinetic energies of 0.2 keV-3.3 keV. The achieved detection rate of Ps atoms is 23 cps at the energy of 3.3 keV with a signal-to-background ratio as high as 300. The energy spread of the beam was evaluated by comparing the result of the time-of-flight measurements and particle-tracking simulations. With the use of a collimator of 1 mm diameter, a coherent beam with an angular divergence of less than 0.3° is obtained. The obtained Ps beam, having a much higher quality than those reported hitherto, will open up a new field of experimental investigations, such as Ps interacting with a variety of materials and fundamental studies on Ps spectroscopy.


Abstract The implementation of Lean Six Sigma in the public sector has grown considerably in recent years and may be accentuated in times of global economic crisis. Even so, general aspects that can guide managers for its implementation in the public sector were not found in the related scientific literature. This paper proposes management guidelines for LSS implementation in public service organizations aiming to support the continuous improvement regarding their processes and results. The guidelines originated from LSS principles under management perspective and literature review on both LSS and public sector using the grounded theory method, being refined afterwards by experts in public management and LSS. This paper can encourage public managers to start a low-cost improvement process in the organizations and support the LSS continuity. Concerning the scientific contribution, this proposal provides a more comprehensive perspective on LSS implementation in the public sector raising persistent management challenges and being a starting point for new research on LSS guidelines directed to specific services within the public sector.


Purpose

The performance of earthmoving operations, in terms of emissions, production and cost, is dependent on many variables and has been the study of a number of publications. Such publications look at typical operation design and management, without establishing what the penalties or bonuses might be for non-standard, but still observed, practices. To fill this gap in knowledge, this paper examines alternative loading policies of zero waiting-time loading, fractional loading and double-sided loading, and compares the performance of these with standard single-sided loading.

Design/methodology/approach

Original recursive relationships, that are amenable to Monte Carlo simulation, are derived. Case study data are used to illustrate the emissions, production and cost penalties or bonuses.

Findings

Double-sided loading contributes the least impact to the environment and is the most cost effective. Zero waiting-time loading performs the worst in terms of environmental impact and cost. Minimizing truck waiting times through using fractional loading is generally not an attractive policy because it leads to an increase in unit emissions and unit costs. The consequences of adopting fractional loading are detailed. Optimum unit emissions and optimum unit cost are coincident with respect to fleet size for single- and double-sided loading policies. That is, by minimizing unit cost, as in traditional practice, then least impact on the environment is obtained. Not minimizing unit cost will lead to unnecessary emissions.

Practical implications

The results of this paper will be of interest to those designing and managing earthmoving operations.

Originality/value

All modeling and results presented in the paper do not exist elsewhere in the literature.


Virtual enterprises (VEs) are the most promising structure for future enterprises. The cooperative environment of VEs is investigated in this paper. The cooperation in a VE is a process and the depth of the cooperation and the information transparency change in different phases of the cooperation. A tri-layered cooperative structure pattern is discussed with a tri-layered cooperative process model which includes the conceptual cooperation model, the detailed cooperation model, and the executive cooperation model. Analysis of the tri-layered process modeling provides a foundation for the cooperation environment.


Background: The parasitoid wasp Trichogramma dendrolimi can successfully enter diapause at the prepupal stage. Thus, diapause is an efficient preservation method during the mass production of T. dendrolimi . Previous studies on diapause have focused largely on ecological characteristics, so the molecular mechanism of diapause in T. dendrolimi is mostly unknown. In this study, we compared transcriptomes of diapause and non-diapause T. dendrolimi to identify key genes and pathways involved in the development of diapause. Results: Transcriptome sequencing was performed using different samples, including diapause prepupae, pupae after diapause, normal prepupae, and pupae. Initially, it yielded a total of 87,022 unigenes with an average length of 1,604 bp. By removing redundant sequences and those without significant BLAST hits, a non-redundant dataset was generated, containing 7,593 sequences with an average length of 3,351 bp. Among them, 5,702 genes were differentially expressed. The result of Gene Ontology (GO) enrichment analysis revealed that regulation of transcription, DNA-templated, oxidation-reduction process, and signal transduction were significantly affected. Ten genes were selected for validation using a quantitative real-time PCR (qPCR). The changes showed the same trend between the qPCR and RNA-Seq results. Based on our data, several genes were identified to be involved in diapause, including ribosomal proteins, zinc finger proteins, homeobox proteins, forkhead box proteins, UDP-glucuronosyltransferase , Glutathione-S-transferase , p53 , DNA damage-regulated gene 1 ( pdrg1 ), and genes related to lipid metabolism were also included. Conclusions: In this study, we generated a great amount of transcriptome data from T. dendrolimi , providing a resource for gene function research. The diapause-related genes that we identified establish a valuable basis for future studies on the molecular mechanisms of diapause, not only for T. dendrolimi , but for other species as well.


The purpose of this study was to establish the career maturity and career decision making status of secondary school students in Kisumu Municipality and to determine the relationship between career maturity and career indecision of secondary school students in Kisumu Municipality, Kenya. A sample of 370 secondary school students from year one to year four were surveyed on career maturity and career indecision. The current study found that students from public schools are more career mature and have lower career indecision than their counter parts from private schools, receiving career counseling significantly increases one's level of career maturity and females scored significantly higher on career indecision. Career maturity was found to be a significant predictor of career indecision. Based on the results, the researcher came to the conclusion that the type of school a student attends and career counseling has significant influence on their career maturity and decision making status. As career maturity increases, students' level of career indecision decreases. Secondary school students should be provided with adequate career information encouraged to explore various careers and consult widely so as to improve their levels of career maturity.


The paper presents the results of SWOT-analysis of social competence of foreign students to define strengths and weaknesses of students, opportunities and threats to environment which influence the process of social competence formation. Vocational education aims at professional development and personal formation; the student acquires certain knowledge, skills, and competences that allow to participate in activities of social and working life. Higher educational establishments face the task of helping foreign students to become socially competent, i.e. to master a high level of social competence. Formation of social competence of students was studied by many Ukrainian and foreign scientists, but the social competence of foreign students has not been researched and there have been no attempts to analyse the initial data (internal and external) that influence its formation. Before choosing the means for the formation and development of social competence, it is necessary to assess its initial level, the potential of foreign students, also external environmental factors that affect this process. For this purpose, SWOT-analysis can be conducted. The SWOT-analysis method was primarily used in political and corporate management for strategic planning; for pedagogical purpose it helps to get the general knowledge about the current state, development of the situation, and then for creation of a model of behavioural strategies in the educational process. At the first stage of the analysis, information is collected about the internal factors (advantages and disadvantages) of the investigated object and about the external factors (favourable and threatening) that affect its activities. The collected data are analysed according to the following vectors: strengthening of internal advantages by external opportunities; elimination of external threats due to internal advantages; overcoming internal disadvantages due to external opportunities; promoting the elimination of internal weaknesses. To reveal the strengths and weaknesses and to identify environmental factors that influence the formation of social competence of foreign students, a survey was conducted in Dnipro State Agrarian and Economic University and Alfred Nobel University (Dnipro) among foreign students and teachers who work with them. From the SWOT-analysis it is seen that the motivation of foreign students, the willingness to be engaged in extracurricular activities are the drivers of the process of forming social competence; foreign students are tolerant to other cultures, they are ready to improve their communication with others. The maximum attention teachers should pay to the issues of social and emotional intelligence, communication skills; and also the students should be acquainted with the social roles of the new environment. Regarding external factors of influence, the issues of pedagogical support of foreign students and lack of their involvement in extracurricular activities need to be corrected. Also, mixed groups can be the opportunity to improve the situation with involving foreign students into extracurricular activities. Highly qualified teachers and general humanization of the educational process are the factors to be relied upon in forming social competence of foreign students. On the basis of the given research the pedagogical conditions for the formation of social competence of foreign students can be formulated and the methods for successful educational process are chosen.


Over the past several years the NRC has developed a generic cost methodology for the quantification of cost/economic impacts associated with a wide range of new or revised regulatory requirements. This methodology has been developed to aid the NRC in preparing Regulatory Impact Analyses (RIAs). These generic costing methods can be useful in quantifying impacts both to industry and to the NRC. The FORECAST program was developed to facilitate the use of the generic costing methodology. This PC program integrates the major cost considerations that may be required because of a regulatory change. FORECAST automates much of the calculations typically needed in an RIA and thus reduces the time and labor required to perform these analysis. More importantly, its integrated and consistent treatment of the different cost elements should help assure comprehensiveness, uniformity, and accuracy in the preparation of needed cost estimates.


Abstract:Transition of care from a child-centered care environment to an adult-centered care environment for pediatric patients with diabetes is needed to ensure continued diabetes care. The transition process should start early and be tailored to the developmental stage of the patient. The typical challenges of adolescence and young adulthood including pubertal changes, parent-child conflict and the potential for high-risk behavior complicate the transition process. Methods of transfer of care are variable and less than optimal. Ongoing study and continued efforts are needed to improve the transition process so that young patients with diabetes receive high quality uninterrupted care.


Abstract This study was aimed at assessing the attitude of health care professionals in Jeddah city toward prenatal diagnosis (PND) and termination of pregnancy (TOP). A cross-sectional study was conducted, and the participants completed a self-administered questionnaire. Approximately 82% of participants showed a consistent trend of accepting PND when appropriate, and 47.5% of the respondents were in favor of TOP if the fetus had a severe disease. Compared with men (69.3%), a significantly greater number of women (88%) accepted to have PND. The most acceptable prenatal diagnostic tests in the study were invasive techniques as most of the participants thought that noninvasive tests were nonspecific.


The study examined the impact of capital budget expenditure implementation on economic growth in Nigeria. Specifically the study assessed the impact of implementation of capital expenditure on administration, economic services, socio-community services on the growth of Nigerian economy. Secondary data used in the study were collated from Central Bank of Nigeria (CBN) statistical bulletins, and analyzed with the use of Augmented Dickey-Fuller unit root test, co-integration test and error correction model (ECM) analysis. The long run normalized estimation reported coefficient values of -387,2292, 69.05, 184.17 for capital expenditure on administration, economic services and socio-community services respectively, while the short run parsimonious ECM estimation reported coefficient estimates and probability value of 27.20(p=0.11), -27.82(p=0.001), -17.23(p=0.49) respectively. Thus, it was concluded that capital expenditure implementation is germane in maintaining and sustaining economic growth in Nigeria. Hence, it was recommended that government should ensure adequate implementation of capital expenditure in the country especially in areas of economic and socio-community services and also overhaul ministries, government agencies and parastatals to curb and curtail loopholes impeding effective and efficient implementation of capital budget in the country.


ABSTRACT Introduction: Fungal infection burden related to Mucorales has been on the rise with significant associated morbidity and mortality. The major obstacle in the management has been lack of a non-invasive rapid and a reliable diagnostic test. Developing a culture-independent biomarker for the early diagnosis of mucormycosis is a major unmet need in modern mycology. Several approaches have been developed, such as immunohistochemistry (IHC) that can confirm the histopathologic diagnosis of the invasive mold infection, polymerase chain reaction (PCR) on formalin-fixed paraffin-embedded (FFPE) or fresh tissue, body fluids such as bronchoalveolar fluid (BAL), and detection directly from serum/blood. Serologic tests, matrix assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF/MS), metabolomics and metagenomic shotgun sequencing are other evolving technologies. Area covered: In this review paper, we report the current status of the molecular diagnostics in the diagnosis of mucormycosis: serologic tests, IHC, PCR, protein-based with MALDI-TOF, metabolomics and metagenomic sequencing. Expert commentary: This review will conclude with an expert commentary on the potential uses/challenges of the currently available tests and the future of molecular diagnostics for mucormycosis.


Within the oil and gas industry there is an emerging trend to estimate expenses for pipelines and system components using a Life Cycle Cost (LCC) basis. This paper describes a new sizing model for swing check valves that can assist in significantly reducing the LCC of the valve. The incremental fuel cost of the compressor arising from pressure loss across the valve is the largest component of the valve`s LCC. The valve`s pressure loss can be minimized by correct valve sizing ensuring full valve opening under normal flow conditions. This new sizing program, applied to an NPS 20 natural gas pipeline, can result in cost savings in the order of two times the capital cost of a swing check valve when compared to traditional sizing methods. The pressure loss across the valve is primarily determined by the opening angle of the valve disc during steady state operation. A steady state valve model was developed and formed the basis for a sizing program for swing check valves. The sizing program assists in optimizing the valve for specified operating conditions. Within margins, the valve opening characteristic can be optimized by adjusting the valve sizing parameters such as valve size, disc weight, countermore » balance mass and position for a specified set of operating conditions. The LCC of a swing check valve can be further reduced by up to 45% through optimization of the valve design. The sizing program was used in a parametric study to assess the areas relevant in the design optimization of the valve. To further reduce the LCC of swing check valves, research should focus on improving the internal flow profile of the valve, reducing disc weight and eliminating the need for counter balance weights through improving low friction seal design.« less


Patients with end-stage renal disease (ESRD) who receive hemodialysis have high rates of psychosocial distress and nonadherence to diet prescription. The purpose of this study was to examine the quantitative research evidence about the effect of depressive symptoms on dietary adherence. A systematic search of the literature using MEDLINE, CINAHL, PubMed, and PsycINFO databases was performed for quantitative research studies. Forty-four studies met inclusion criteria and were included in this review. Nearly all studies supported an association between depressive symptoms and dietary adherence in patients with ESRD. Depressive symptoms were associated with dietary nonadherence in patients with ESRD.


Racial and ethnic groups are severely underrepresented in clinical trials in the United States. This Nevada based study addresses the Nevada Comprehensive Cancer Control Plan to increase the number and diversity of clinical trial participants in Nevada. We provide preliminary findings on Latino and Native Americans current views toward cancer and cancer trials and the influences that affect decisions about seeking cancer treatment or cancer prevention as part of a cancer trial. We are excerpting the findings from a larger study where 5 racial/ethnic groups were part of this study. We will provide comparative data for two groups from focus group (FG) research and a population based randomized survey (N=1,388) conducted spring and summer of 2008 in Las Vegas, Nevada. We provide these two groups views and findings. Conclusions: We found in the two FGs, ethnic variation on issues about trust in the research process, about participation in clinical trials and what constitutes an 'incentive' to participate in a clinical trial. We also found similar beliefs about cancer and the cancer trials process within and between each of the focus groups. Preliminary survey data indicates that there is a strong need for educational programs in underserved populations, especially among Latinos and Native Americans. Likewise, educational program efforts about cancer and the cancer trials process need to be delivered with sensitivity to cultural beliefs and historical relationships between racial/ethnic groups and the medical establishment. Clinical trials educational programs should be tailored to unique ethnic groups so that knowledge of cancer and the cancer trials process can be most clearly understood.


Brassicaceae is an important family in the plant kingdom. The Simple Sequence Repeats (SSRs) play a vital role in the study of Brassicaceae. By using 13 known sequenced Brassicaceae species with bioinformatics and comparative genomics methods, a total of 1,786,619 SSR loci and 1,919,464 pair of primers have been developed. The results show that the SSRs are widely distributed in the Brassicaceae species' genomes, 1 3 bases duplication have a high ratio among these genomes and gene sequences, AT/TA repeats units have a high numbers in all of the 2 base duplication. In addition, 435,414 specific SSR primers could be used to analyze the correlation between the species of Brassicaceae. 11 pairs of universal primers' developed shows that there exist some consistent base fragments and could be amplified across different species. In this study, we constructed the world's first SSR molecular marker database platform (BSSRD, Brassicaceae Simple Sequence Repeats Database http://biodb.sdau.edu.cn/BSSRD) which will play an important role in the construction of genetic map, gene mapping and genetic breeding of Brassicaceae.


PURPOSE
To evaluate the effect of keratinized tissue width (KTW) on periodontal regenerative surgery for the treatment of intrabony defects.

METHODS
The clinical data of 14 patients (44 intrabony defect sites) treated with periodontal regenerative surgery were retrospectively analyzed at baseline and 2-year of follow-up. Forty four sites were divided into KTW2 mm group and KTW≤2 mm group according to KTW at baseline. Periodontal clinical indicators of the 2 groups were analyzed by SPSS 25.0 software package.

RESULTS
At 2-year post-treatment, probing depth (PD) and clinical attachment loss (CAL) in the 2 groups were decreased significantly compared with those at baseline(P<0.05). There was no significant difference in ΔPD, but ΔCAL in KTW2 mm group was significantly greater than that in KTW≤2 mm group.

CONCLUSIONS
Periodontal regenerative surgery for the treatment of intrabony defects can effectively reduce periodontal pocket inflammation, decrease periodontal pocket depth and increase the level of attachment. When the width of the keratinized gingiva is insufficient(KTW≤2 mm), the regeneration of the attachment level obtained by surgery is limited, and the efficacy of regenerative surgery is poor.


The principle of hemodialysis (HD) was first described over a century ago while the first human HD treatment was performed in 1923 with collodion tubes. Since that time, a variety of different hemodialyzer configurations and membranes have been used. The purpose of this article is to provide a historical review of these various configurations and membranes. The rotating drum, coil, parallel flow, and hollow fiber artificial kidneys are discussed. Emphasis is placed on the factors that have influenced the shaping of the contemporary HD market.


Like many other important evolutionary transitions, our knowledge of the origin of vertebrates is limited to windows of exceptional preservation of soft‐bodied fossils. Unfortunately, these fossils are rare and have been subjected to complex taphonomic filters including decay, collapse and distortion. To maximize our ability to utilize these crucial fossils to reconstruct the timing and sequence of evolutionary events, we are in the need of a robust taphonomic framework with in which to interpret them. Here, we report the results of a series of experiments designed to examine patterns of transformation and loss during decay of important anatomical characters of chordates and primitive vertebrates (ammocoete, adult lamprey, hagfish, juvenile chondrichthyans and a non‐vertebrate chordate, Branchiostoma). Complex and repeated patterns of transformation during decay are identified and figured for informative character complexes including eyes, feeding apparatus, skull and brain, muscles, branchial apparatus, axial structures, viscera, heart and fins. The resulting data regarding character decay and relative loss serve as a guide to recognition and interpretation of the anatomy of non‐biomineralized fossil vertebrates. The methods and techniques outlined are eminently applicable to other soft‐bodied groups and present a new way to interpret the exceptionally preserved fossil record.


Adding autonomic capabilities to network management systems provides great promise in delivering high QoS while lowering operation and maintenance cost. In this paper, we present a model-based approach to adding autonomic capabilities to a fault management system for cellular networks. We propose the use of modeling techniques to specify software failures and their dispositions at the model level for the target system. This facilitates the deployment of a control loop for adding autonomic capabilities into the system architecture, which include self-monitoring, self-healing, and self-adjusting. Our case study on the intelligent network fault management system illustrates the proposed approach by adding and deploying these autonomic capabilities derived from self-model specifications, to mitigate the risk of specified failures and maintain the level of healthiness of the system, dynamically and effectively.


Resonance Raman (RR) scattering from intact pea phytochrome was observed in resonance with the blue band at ambient temperature. The relative populations of the red-light-absorbing form (Pr) and far-red-light-absorbing form (Pfr) under laser illumination were estimated from the absorption spectra. The most prominent RR band of Pr obtained by 364-nm excitation under 740-nm pumping exhibited a frequency shift between H2O and D2O solutions, but that of Pfr obtained by 407-nm excitation under 633-nm pumping did not, indicating a distinct difference in a protonation state of their chromophores. Since the protonation level of a whole molecule of intact phytochrome remains unchanged between Pr and Pfr, this observation indicates migration of a proton from the chromophore of Pr to the protein moiety of Pfr. As model compounds, octaethylbiliverdin (OEBV-h3), its deuterated and 15N derivatives, and their protonated forms were also studied with both RR and 1H and 15N NMR spectroscopies. The RR spectrum of the protonated form, for which the protonation site was determined to be C-ring pyrrole nitrogen by NMR, displayed a deuteration shift corresponding to that of Pr, suggesting a similar protonated structure for the pyrrolic rings of Pr. The RR spectral difference between OEBV-h3 and OEBV-d3 and that between H2O and D2O solutions of Pfr suggested that the N-H protons of the A-, B-, and D-rings of intact phytochrome are replaced with deuterons in D2O. A role of the 7-kDa segment of phytochrome is discussed on the basis of RR spectral differences between the intact and large phytochromes.


In the many essays in this volume, we can only indicate those which seem especially significant. The book begins with an autobiographical sketch and concludes with Buber's response to the comments and criticisms contained in the intervening essays. Gabriel Marcel offers a searching treatment of 'I and Thou,' Charles Hartshorne is fittingly chosen to discuss Martin Buber's metaphysics, von Balthasar considers the relation of Buber to Christianity, Jean Wahl evaluates Buber's existentialist stance, and W. Kaufmann assesses Buber's religious significance. James Mullenberg's treatment of Buber's interpretation of the Bible is valuable for its analysis of the methodology, and for its conclusion that Buber's views are, in many ways, receiving striking confirmation.


Neutrophil extracellular traps (NETs) were described more than one decade ago, but recently, the interest in these structures has increased due to their involvement in cancer progression, cancer-related thrombosis, and development of metastasis. This protumoral role of NETs strengthens their potential as new prognostic markers of cancer.


A flexible 0.4-mm-dia pH probe potentially suitable for physiological use has been developed. It is based on the concept of utilizing two single plastic fiber optic strands to illuminate and remotely sense the color change of a dye indicator contained within an acutely implanted sealed cellulosic hollow fiber permeable to hydrogen ions. A supporting electronic module provides tungsten filament illumination, light sensing with a photodiode/operational amplifier, analog and digital circuitry to provide appropriate signal averaging and processing, and a mechanical assembly to enable the optical density measurements to be made both at 560 nm and, for normalization purposes, in the red. Over the physiological pH range from 7.0 to 7.4, the fiber optic probe agrees with a standard glass pH electrode to within 0.01 pH units in buffer solutions, to within 0.017 pH units in heparinized dog blood in vitro, and it has performed successfully while implanted in the jugular vein of a sheep.


Therapeutic options for prostate cancer are limited and treatment responses to currently existing therapies are often unsatisfactory. Thus, there is an urgent need for novel agents to target advanced and metastatic prostate cancer cells. We have recently carried out a chemical-biological high-throughput screening of 4,910 known drugs and drug-like molecules in four prostate cancer cell models and two non-tumorigenic prostate epithelial cell lines to identify prostate cancer cell growth selective inhibitors. Only four compounds, antibiotic ionophore monensin, aldehyde dehydrogenase (ALDH) inhibitor disulfiram, histone deacetylase inhibitor trichostatin A and fungicide thiram inhibited selectively cancer cell growth at nanomolar concentrations. The mechanistic studies indicated that monensin inhibited prostate cancer cell growth by inducing oxidative stress and apoptosis. In addition, monensin reduced androgen receptor signaling, showed a synergistic anti-proliferative effect with anti-androgens as well as reduced the levels of MYC and ERG oncogenes and reduced the activity of ALDH in prostate cancer cells. Moreover, antioxidant vitamin C rescued the monensin induced growth inhibition, indicating that oxidative stress plays a key role in the antineoplastic effect of monensin in cultured prostate cancer cells. Our previous Connectivity Map results indicated that monensin has agonistic effects to NF-κB inactivator and oxidative stress inducer niclosamide. Here, we show that monensin indeed reduced the activity of NF-κB pathway. NF-κB maintains cellular antioxidant defence capacity and its inhibition induces oxidative stress as well as reduces tumorigenesis, metastasis and cancer stem cell potential. Cancer stem cells have a controlled redox balance system including high ALDH and CD44 expression which protect cancer stem cells from oxidative stress. Our results confirmed that monensin reduced the cancer stem cell markers in prostate cancer cells. Moreover, monensin induced epithelial cell differentiation shown as well as reduced motility in cultured prostate cancer cells, suggesting that monensin inhibits prostate tumorigenesis by multiple ways. Furthermore, the steroid profiling indicated that monensin increases the levels of oxidative stress inducing steroids and reduces androgen precursors in cultured prostate cancer cells. In conclusion, our results suggest that impairing the redox control, which has a crucial role in cancer cells enabling survival under high intracellular ROS, is a potent way to target prostate cancer cells and potentially also prostate cancer stem cells. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the AACR-NCI-EORTC International Conference: Molecular Targets and Cancer Therapeutics; 2011 Nov 12-16; San Francisco, CA. Philadelphia (PA): AACR; Mol Cancer Ther 2011;10(11 Suppl):Abstract nr A62.