Regulation of serum calcium in vertebrates is maintained by the actions of the parathyroid glands working in concert with vitamin D and critical target tissues that include the renal tubules, the small intestine, and bone cells. The parathyroid glands release parathyroid hormone (PTH) into the systemic circulation as is required in order to maintain the serum calcium concentration within a narrow physiologic range. Excessive secretion of PTH from one or more abnormal parathyroid glands however results in primary hyperparathyroidism (HPT), a metabolic disease typically associated with abnormally elevated serum calcium. Although HPT is typically a sporadic disease, it can represent a manifestation of an inherited syndrome. Many sporadic parathyroid tumors result from inactivating mutations in tumor suppressor genes that were first discovered by the analysis of genomic DNA from patients with HPT as part of an inherited syndrome. Somatic and inherited alterations in DNA encoding proto-oncogenes can also cause parathyroid neoplasia. Two promis-ing future approaches for the discovery of novel genes pertinent to parathyroid tumor development are the analysis of acquired genetic alterations in DNA isolated from parathyroid tumors and the investigation of familial HPT in kindreds lacking germline mutation in the known genes predisposing to HPT.


AIM AND OBJECTIVE
Small molecule targeted drugs can effectively reduce the toxicity and side effects of drugs, and improve the efficacy of drugs by their specific antitumor activity. Hence, the development of small molecular targeted drugs for cancer has important significance. This study was undertaken to design and synthesize novel phenazine-chromene hybrid molecules in order to optimize the structure and improve the efficacy of this kind of hybrids.

MATERIALS AND METHODS
O-diaminobenzene was used as starting material to synthesize twentyfour heterocyclic compounds designed as hybrid molecules of phenazine and 4H-chromene pharmacophores by facile methods. The structures of the compound were confirmed by 1H NMR, 13C NMR and HRMS. Furthermore, the synthesized compounds were evaluated for in vitro activity against four human cancer cell lines and two non-cancer cell lines by MTT test.

RESULTS
Some compounds showed strong cytotoxic activities against HepG2 and A549 cancer lines (IC50 = 5-10 µM). Comparing 2i with 2l, the introduction of hydrophilic groups on the phenazine core could not improve the antiproliferative activity significantly. Except 2d and 3c, compounds owning chlorine substituent on the 4H-chromene pharmacophore seemingly contribute to enhance the compounds' antiproliferative activity. Specially, compound 3c showed highest cytotoxicity against A549 cells with IC50 values of 3.3±0.4 µM. Furthermore, all compounds showed low or no cytotoxicity against HUVEC and L02 non-cancer cells in vitro.

CONCLUSION
Compound 3c may be used as potential lead molecule against A549 cancer cells.


is wise he will do so and thus increase his chances of a gold medal. Of the pre-clinical years it is not for me to speak. Possibly it is essential that for a month or two we can write a page on the morphology of the notochord of the amphioxus: I doubt it. If medical practice continues along its present lines and we are to keep faith with the public, it seems to me that every man who receives a licence to practise should on that same day be qualified to offer sound advice on the ailments native to his community and to treat the simpler of these, and that he should have confidence in his powers and knowledge of his limitations. If we cannot so train a man in six years, and at the same time retain the questing mind that Nature has endowed him with, then Heaven help us! It has become manifest in many quarters that the will for change is he x. Let us not confuse true conservatism with inertia.-I am, etc.,


Purpose of review To highlight the current body of knowledge regarding the role of nicotinic acetylcholine receptors (nAChRs) in lung cancer predisposition. Recent findings Smoking is a documented risk factor for cancer, especially for lung carcinomas. Nicotine and its derived carcinogenic nitrosamines contribute to lung cancer development and progression through the binding to nAChRs, which then activate proliferation, apoptosis, angiogenesis and tumour invasion. Recent genome-wide association studies have associated single nucleotide polymorphisms spanning the nAChR encoding genes cluster CHRNA3/A5/B4 with both nicotine dependence and lung cancer incidence and susceptibility. The α7 nAChR has also been implicated in the regulation of inflammation and immunity and, as a repressor of airway basal cell proliferation, α7 nAChR plays a role in the remodelling of the airway epithelium. Its decreased function may lead to squamous metaplasia and possibly the emergence of preneoplastic lesions. Summary nAChRs participate in the predisposition for preneoplastic lesions and the further emergence of lung carcinomas. More studies are needed to determine the influence of gene polymorphisms on nAChRs function and of nAChRs activation/desensitization on lung diseases, which represents a new stimulating approach in the understanding of lung tumorigenesis with potential clinical applications.


The model of holistic care is focused on psychosocial needs which are very important for self-esteem and the healing process. These needs are an important part of medical care, where the patient is treated as a biopsychosocial and spiritual whole. The aim of the study was to evaluate and compare the level of expected and provided nursing care; in meeting the psychosocial needs of patients from two surgery wards. The study was conducted among 468 patients, 320 from the surgery clinic of teaching hospital and 148 from the surgery ward of a local hospital. We used standarised questionnaire which evaluated the level of expected care and provided nursing care--in patients' opinions. Patients from the surgery clinic had higher expectations in aspect of care. The difference of mean score for "no need" was 7.4 (statistically significant U = -10,029, p < 0.0001). Mean scores for "no need" were 7.28 in the surgery clinic and 14.68 in the surgery ward. The highest demands were observed in the area of adaptation to hospital environment, possibility of psychosocial activities and correct relationships with the personel. In patients' opinions the worst level of meeting the needs was observed in aspect of cooperation with care and treatment process (ward) and psychosocial activity during hospital stay.


Prolonged unloading of skeletal muscle, a common outcome of events such as spaceflight, bed rest and hindlimb unloading, can result in extensive metabolic, structural and functional changes in muscle fibres. With advancement in investigations of cellular and molecular mechanisms, understanding of disuse muscle atrophy has significantly increased. However, substantial gaps exist in our understanding of the processes dictating muscle plasticity during unloading, which prevent us from developing effective interventions to combat muscle loss. This review aims to update the status of knowledge and underlying mechanisms leading to cellular and molecular changes in skeletal muscle during unloading. We have also discussed advances in the understanding of contractile dysfunction during spaceflights and in ground‐based models of muscle unloading. Additionally, we have elaborated on potential therapeutic interventions that show promising results in boosting muscle mass and strength during mechanical unloading. Finally, we have identified key gaps in our knowledge as well as possible research direction for the future.


. The aim of the study was to develop an algorithm for choosing a rational tactics for surgical treatment of patients with coxo-vertebral syndrome. Material and methods. The study included 175 patients with coxo-vertebral syndrome who underwent total hip arthroplasty from 2009 to 2016. The results of surgical treatment were studied at an average time of 9 months. (from 8 to 10 months) after surgery in 134 patients. Their average age was 54.4 ± 12.7 years. The patients were divided into the main group (74 patients) and the comparison group (60 patients). In the comparison group, standard approaches to hip arthroplasty were used, implying restoration of the anatomical center of rotation and the length of the lower limb. The study group used the developed algorithm for choosing the optimal surgical tactics. Clinical and functional data were assessed using the Harris and Oswestry scales. Radiographic assessment was performed on radiographs of the spine-pelvic complex in a standing position, functional radiographs, CT and MRI. The significance of differences in the groups was assessed using the Mann-Whitney U-test and the McNemar test. Results. The use of the developed surgical approaches made it possible to increase the proportion of patients with good clinical and functional results (the main group - 82.4%, the comparison group -26.7%) and to achieve higher indicators of the functioning of the hip joint and the quality of life of patients in the postoperative period. Excellent results on the Harris scale in the main group were obtained in 53.2% of patients, in the comparison group - in 9.7%. The proportion of patients with complaints of pain in the lumbar region, lameness and the need to use a cane, preserved after hip arthroplasty, was lower in the study group than in the comparison group.


Author(s): Carrillo, Vicente | Advisor(s): Gaspar de Alba, Alicia | Abstract: Across the US, Chicana/o and Latina/o murals have served as artistic landmarks commemorating Chicana/o and Latina/o culture, history and identity. These murals, however, are predominantly heteronormative representations of Chicana/o culture and history. What happens, therefore, when queer Latinx and Chicanx artists use muralism to express their intersectional identities? This project focuses on the digital queer mural, Por Vida, designed by Los Angeles based artist Paul Manuel, installed June 13, 2015 on 24th and Bryant Street in San Francisco's Mission District in celebration of Pride Month. Just days after its installation, the mural was defaced multiple times, three times spray-painted, the fourth time incinerated. After the defacements, community tensions rose among local and non-local Mission District residents. To this day, the identity of individual(s) behind the violent vandalism are still unknown. In this project, I explore what I identify as the "contested conversations" regarding Por Vida's defacements between local and non-local residents. From over 230 Instagram comments, I identify five different types of arguments within these online conversations which include, 1) Cultural Gatekeepers of "The Cholo" 2) Spatial Entitlement 3) Gentrification Activism 4) Pro-LGBTQ and 5) Latinx Pro-LGBTQ. Drawing from queer of color critique, spatial theory, whiteness studies, and women of color feminism, I explore these contested debates, along with the Mission District's cultural and spatial relationship to Por Vida's installation. Using this analytics lens, I highlight and challenge the pervasive forms of whiteness in mainstream LGBTQ representation that, I argue, ultimately erase queer of color identities or "brown" pride (Mui?½oz). Rainbow capitalism is a racial social project that informs spatial imaginations, producing territorial boundaries (cultural and spatial) that intentionally exclude queer of color bodies. I argue that the censorship of the Por Vida mural reinforces rainbow capitalism's project of erasure–a project reaffirming queerness as a social identity belonging only to that of white, wealthier queer subjects. Indeed, I aim to question the "gentrification argument," pointing to instead the white gay subject's universal or dominant socio-spatial relationship to queer of color bodies and claims to safe spaces such as "gayborhoods." Through a queer of color spatial critique, I discovered that the anti-gentrification sentiments from local Mission District residents, while they openly resist against the displacement of low-income families of color, also simultaneously observe Por Vida's representation of queer of color intimacy as a symptom of gentrification. Interviews revealed that these sentiments are rooted in homophobic and transphobic attitudes but also territorial entitlements that continuously marginalize queer and trans bodies of color. I argue that Por Vida's representation of queer Latinx intimacy is an active disruption to public space's heteronormative social values of respectability and domesticity, that also render visible the pervasive homophobic and transphobic attitudes still informing Latina/o communities even as they support anti-racist, anti-displacement activism.


Medical image analysis will be used to develop image retrieval system to provide access to image databases using extracted features. Content Based Image Retrieval (CBIR) is used for retrieving similar images from image databases. During the last few years, medical images are grown and used for medical image analysis. Here, we are proposed that medical image retrieval using two dimensional Principal Component Analysis (2DPCA). For extracting medical image features, 2DPCA has advantageous that evaluates accurate covariance matrix easily as much smaller and also requires less time for finding Eigen vectors. Medical image reconstruction is performed with increased values of 2DPCA and observed from results that reconstruction accuracy improves with increase of principal component values. Retrieval is performed for transformed image space by calculating the Euclidean Distance(ED) between 2DPCA values of unknown images with database images. Minimum distance classifier is used for retrieval, which is simple classifier. Simulation results are reported by considering different medical images and showed that simulation results provide increased retrieval accuracy. Further, Segmentation of retrieved medical images is obtained using k-means clustering algorithm.


A hierarchical neural network structure capable of learning the control of a robot's arm and gripper is introduced. Based on T. Kohonen's algorithm (1982) for the formation of topologically correct feature maps and on an extension of the algorithm for learning of output signals, a simulated robot arm system learns the task of grasping a cylinder. The network architecture is that of a 3-D cubic lattice in which is nested at each lattice node a 2-D square lattice. The robot learns without supervision to position its arm and to orient its gripper properly by observing its own trial movements. In a simulation, the error in positioning the manipulator after training was 0.3% of the robot's dimension, and the residual error in orienting the gripper was 3.8°. Due to cooperation between neighboring neurons during the training phase, fewer than two trial movements per neuron were sufficient to learn the required control tasks


Numerous biochemical activities are known for the selenoorganic drug ebselen [(2-phenyl-1,2-benzoisoselenazol-3-(2H)-one]. The initial interest focussed on its GSH peroxidase-like activity and its inhibitory activity on 5-lipoxygenase, however, further activities of the drug on oxidative burst of leukocytes, nitric oxide synthases, protein kinases and on leukocyte migration were recognized. Here we report that Ebselen differentially interacts in vivo with the production and action of systemically released cytokines in various hyperinflammation models in mice. Ebselen given orally to mice protected dose-dependently from Concanavalin A-induced, T-cell dependent inflammatory liver injury. The release of the proinflammatory cytokines Tumor Necosis Factor alpha and Interferon gamma was downregulated, while the production of the anti-inflammatory cytokine Interleukin 10 was increased. Similar results were found in galactosamine-sensitized mice in an inflammatory liver model using the superantigen staphylococcal enterotoxin B as a T-cell activator. Moreover, Ebselen inhibited the release of TNF alpha initiated by endotoxin in vivo in mice. In galactosamine-pretreated mice. Ebselen also attenuated liver injury induced by recombinant Tumor Necosis Factor alpha and initiated enhanced release of Interleukin 10. These findings expand the pharmacological knowledge on ebselen to hitherto unknown immunomodulatory properties which encourage to develop the drug for treatment of T-cell related autoimmune diseases.


BackgroundThe clinical manifestations of Alzheimer disease (AD) are related to brain network degeneration, while genetic differences may mediate network change patterns. A number of AD-susceptible loci have been reported using genome-wide association studies, however, how they modulate intracerebral volume and relationships to cognitive outcomes remains to be established. We hypothesized that different genotype groups may modulate large-scale brain networks independently or interact with apolipoprotein E4 (ApoE4) status to determine neurobehavior test scores.MethodsGray matter structural covariance networks were constructed in 324 patients with AD using T1 magnetic resonance imaging with independent component analysis (ICA). We assessed 15 genetic loci (rs9349407, rs3865444, rs670139, rs744373, rs3851179, rs11136000, rs3764650, rs610932, rs6887649, rs7849530, rs4866650, rs3765728, rs34011, rs6656401, rs597668) using the additive, recessive and dominant model on clinical outcomes. Statistical analysis was performed to explore the independent role of each locus, interactions with ApoE4 status, and relationships to brain ICA network integrity score. We used Cognitive Abilities Screening Instrument (CASI) total score or short-term memory (STM) subscore as the major outcome factors, adjusted for covariates of education, disease duration and age.ResultsClinically, the CD2AP G allele showed a protective role in CASI-total and CASI-STM scores independently or via interactions with non-ApoE4 status, while the CR1 A genotype group was associated with lower STM independently of ApoE4 status. Three loci showed synergic interactions with ApoE4: BIN 1 T allele and MS4A6A G allele with non-ApoE4 status, and FTMT G allele with ApoE4 status. The network integrity scores revealed 9 significant ICA networks (anterior and posterior hippocampus, right temporal, right or left thalamus, inferior cerebellum, medial cerebellum, default mode network, frontal attention network) that correlated with cognitive scores, in which only the ApoE4 and MS4A6A genotype group was independently related to the hippocampus network. Genetic loci of MS4A6A, BIN1, CD2AP, CD33, CLU, BIN1, P73, EXOC3L2, CR1 and MS4AE4 exerted network influence independently or via interactions with ApoE4 status.ConclusionsThis study suggests that AD-susceptible loci may exert clinical significance independently, through interactions with ApoE4 status or by modulating ICA networks to determine cognitive outcomes.


This work proposes a holistic method for highway traffic video classification based on vehicle crowd properties. The method classifies the traffic congestion into three classes: light, medium and heavy. This is done by usage of average crowd density and crowd speed. Firstly, the crowd density is estimated by background subtraction and the crowd speed is performed by pyramidal Kanade-Lucas-Tomasi (KLT) tracker algorithm. The features classification with neural networks show 94.50% of accuracy on experimental results from 254 highway traffic videos of UCSD data set.


Posidonia oceanica (L.) Delile is a flowering plant not algae. It lives according to water clarity in sandy bottom, at depths from 1 to 40 m of the Mediterranean. The lessepsian fish, Siganus luridus (Ruppell, 1828) are common herbivores in the eastern Mediterranean, where they adapted themselves to the new environment. This member of Siganidae have considerably modified their diet to adapt themselves to new plant and algal resources. It appears that in the Eastern Mediterranean of Turkey (Gazipasa) S. luridus seems to select P. oceanica as an major food and they gradually destroy P. oceanica meadows.


BACKGROUND
Although COVID-19 is primarily an acute respiratory infection, 5%-40% of patients develop late and prolonged symptoms with frequent neurological complaints, known as long COVID syndrome. The presentation of the disease suggests that COVID infection may cause functional and/or morphological central nervous system alterations, but studies published in the literature report contradictory findings.

PURPOSE
To investigate the chronic effects of COVID-19 on cerebral grey matter in a group of young patients without comorbidities, with mild course of COVID infection and no medical complaints at the time of examination.

STUDY TYPE
Prospective.

POPULATION
Thirty-eight young (age = 26.6 ± 5.0 years; male/female = 14/24), adult participants who recovered from mild COVID infection without a history of clinical long COVID and 37 healthy control subjects (age = 25.9 ± 2.8 years; male/female = 14/23).

FIELD STRENGTH/SEQUENCE
Three Tesla, 3D T1-weighted magnetization-prepared rapid gradient-echo, 2D T2-weighted turbo spin-echo.

ASSESSMENT
MRI-based morphometry and volumetry along with neuropsychological testing and self-assessed questionnaire.

STATISTICAL TESTS
Fisher's exact test, Mann-Whitney U-test, and multiple linear regression analyses were used to assess differences between COVID and healthy control groups. P < 0.05 was used as cutoff for significance.

RESULTS
In the COVID group, significantly lower bilateral mean cortical thickness (left/right-hemisphere: 2.51 ± 0.06 mm vs. 2.56 ± 0.07 mm, η2 p  = 0.102/2.50 ± 0.06 mm vs. 2.54 ± 0.07 mm, η2 p  = 0.101), lower subcortical gray matter (57881 ± 3998 mm3 vs. 60470 ± 5211 mm3 , η2 p  = 0.100) and lower right olfactory bulb volume (52.28 ± 13.55 mm3 vs. 60.98 ± 15.8 mm3 , η2 p  = 0.078) were found. In patients with moderate to severe anosmia, cortical thickness was significantly lower bilaterally, as compared to patients without olfactory function loss (left/right-hemisphere: 2.50 ± 0.06 mm vs. 2.56 ± 0.05 mm, η2  = 0.173/2.49 ± 0.06 mm vs. 2.55 ± 0.05 mm, η2  = 0.189). Using further exploratory analysis, significantly reduced cortical thickness was detected locally in the right lateral orbitofrontal cortex in the COVID group (2.53 ± 0.10 mm vs. 2.60 ± 0.09 mm, η2 p  = 0.112).

DATA CONCLUSION
Even without any subjective or objective neurological complaints at the time of the MR scan, subjects in the COVID group showed gray matter alterations in cortical thickness and subcortical gray matter volume.

LEVEL OF EVIDENCE
2 TECHNICAL EFFICACY: Stage 3.


Messier 101, also known as the Pinwheel galaxy, is a face-on spiral galaxy 21 million light-years away. Its small companion, NGC 5474, is a peculiar dwarf galaxy being distorted by the gravitational influence of the Pinwheel. This is a stacked image of 30x180 second exposures using an 11" RASA telescope and colour CMOS camera on the roof of the UofS Physics Building.  My collaborators were Brennan Rodgers (who helped with data collection and processing) and Emery Dlugan (helped with data collection). It was done "for fun," and so no supervisors were involved. However, the telescopes on the roof of the Physics Building are regularly used by students in Astronomy lab classes for research in photometry and spectroscopy.


The Cetacean fishing, mainly of whales, was an important activity in several maritime villages during the Ancien Regime, because this mammal produced supplies for the people. The most important whale product was its «sain» a kind of oil, together with the meat whale and its whiskers and its bones. In the Canary Islands there was in- terest in developing this activity in the second half of the 18th Century. This was more important after the Treaty of Utrecht, when the Spanish lost the fishing bank of Terra Nova. These enterprises were supported by the Enlightened who tried to find new sources of development for the people. However, like other initiatives at this time, it never be- came a reality. The result was sev- eral injured whales and a few young cetaceans but the profitabil- ity was always low.


Numerical calculations of the positions and widths for anticrossings in Rydberg Stark states are scarce, largely due to the results' sensitive dependence on the wavefunctions chosen. With wavefunctions derived from a kind of potential model as a basis, we calculate the positions and sizes for the anticrossings of potassium Rydberg states in a static electric field by means of diagonalization, and show that the results are in good agreement with available experimental data. The results show that this potential model can be used to deal with the problem of anticrossings, and the accuracy of the potential model is sensitively and numerically tested in the situation of external fields for the first time.


A number of murine models recapitulate many of the features of systemic lupus. Spontaneous models of lupus have provided the basis for genetic linkage studies to define loci that confer an increased risk of nephritis in susceptible mice. Functional relevance of genes within susceptibility loci have been verified through the use of transgenic mice bearing targeted deletions or overexpression of candidate genes. Critical gene targets are involved in the production of autoantigens, stimulation of B cells to produce autoantibodies, stimulation of T cells to provide B cell help and cytokine-mediated damage following tissue deposition of immune complexes. In this overview, features of the commonly employed models of human lupus nephritis are reviewed. Strategies to identify candidate genes involved in the initiation and progression of lupus nephritis in these models are discussed. Finally, key studies to validate target genes as pathophysiologically relevant mediators of lupus nephritis and studies to identify potential targets for therapeutic intervention are summarized.


Background and objective Continuous monitoring of cardiac output during liver transplantation is essential to evaluate the patient's haemodynamic tolerance to acute volume variations. The aim of this study was to compare the cardiac output values obtained with a transoesophageal echo‐Doppler and those obtained with a continuous thermodilution cardiac output pulmonary artery catheter. Methods Twenty adult patients were prospectively studied during a 5 min hepatic vascular exclusion test performed at the end of the dissection phase. Echo‐Doppler and continuous thermodilution cardiac output, mean arterial pressure and end‐tidal CO2 were measured before and at the end of the test. Results Before the test, echo‐Doppler cardiac output was 7.0 ± 2.7 L min−1 and thermodilution was 9.4 ± 3.1 L min−1, (R = 0.85, P < 0.001). The end test values were, respectively, 3.5 ± 2.7 and 7.8 ± 3.5 L min−1 (R = 0.23, P = 0.34). Bland and Altman analysis showed a bias of −2.2 before the test, which increased to −4.4 at the end of the test. Mean arterial pressure decreased from 85.5 ± 15 to 66.8 ± 16 mmHg, end‐tidal CO2 from 31.4 ± 2.3 to 23.8 ± 2.7 mmHg. Conclusion Echo‐Doppler cardiac output values are different from those measured by thermodilution cardiac output in these patients. Echo‐Doppler cardiac output monitoring seems to detect the output changes, which can occur during acute haemodynamic changes more rapidly than thermodilution cardiac output in the course of liver transplantation.


The purpose of this article is to show that interaction can be seen as a trigger to phonological appropriation. Our methodology will be qualitative, descriptive, analytic and experimental. A quick survey shows that many teachers still rely on discrimination exercises to favour phonological appropriation. A first experiment in a class at a secondary high school in Reunion Island, France, with a teacher trainee confirms this choice and reveals non-satisfactory phonological results in a final interaction test. This situation comes from a confusing theoretical scope which gives contradictory data on the exact role of input and output, separate form-focused and meaning-focused phonological learning, the unclear link between conscious and unconscious processes. Cognitive psychology has very much influenced communication functions, but conative and affective functions are ignored. Our scientific scope can open up thanks to intrinsic motivation through interaction, emotional intelligence, sensory-motricity and the link between conscious and unconscious processes. A new experiment is set up in the same class with practical assumptions including an interaction-oriented sequence, a bodily involvement and a more motivational learner-centred approach. Phonological activities are based on fun and interactive games. A final interaction test reveals much better phonological results. To address the topic, the article is arranged in the following way: the acknowledgement of a confusing situation, a real need to enlarge the theoretical scientific scope and a newly assessed second experience. This would tend to show, as a conclusion, that interaction could be seen as a real trigger to phonological appropriation.


DESTIN, FLA. – Methadone can be an effective treatment for chronic pain, but there are a number of concerns that must be considered when prescribing this opioid, according to Dr. Perry G. Fine. Among the benefits of the effective mu-opioid analgesic with N-methyl-D-aspartate receptor antagonist properties are its low cost, dosing formulation versatility, long duration of action, and favorable metabolic profile. However, it also has highly variable pharmacokinetics, a very long half-life compared with its analgesic duration of action, and nonlinear dose conversion. Prescribing this drug requires methadone-specific knowledge and vigilance on the part of the prescriber, as well as a highly responsible patient and/or caregiver who will monitor use and side effects, particularly during titration, according to Dr. Fine, professor of anesthesiology at the Pain Research Center, University of Utah, Salt Lake City. Potential problems with methadone include drugdrug interactions and cardiac toxicity. Sudden death, even at therapeutic levels, can occur. Drug-drug interactions can include adverse reactions in patients on monoamine-increasing drugs. Also, serum levels are increased by CYP3A4 and CYP2B6 inhibitors (such as certain antiretrovirals, clarithromycin, itraconazole, erythromycin, fluconazole, grapefruit juice, and more), and this has been associated with multiple overdose deaths, prompting a black-box warning advisory in 2006, Dr. Fine said. Potential cardiac toxicity is the newest concern; treatment has been shown in some patients to prolong the corrected QT (QTc) interval, and while prescribing guidelines do not yet reflect this, a baseline electrocardiogram is advisable, Dr. Fine said. According to current guidelines from the American Pain Society–American Academy of Pain Medicine, a reasonable starting dose in most opioid-naive patients is 2.5 mg every 8 hours. Dose increases can begin after a minimum of 10 days. Older patients, or those with renal or hepatic comorbidities, require less frequent dosing, and more cautious dose titration. Methadone treatment is not advisable for breakthrough pain because of its long half-life and variable pharmacokinetics ( J. Pain 2009;10:113-20). Titration, according to Dr. Fine, should include dose increases of 1-2.5 mg every 8 hours in frail, older patients or patients with a history of sleep apnea, and 2.55 mg every 8 hours in robust younger patients. Increases should be made every 5-7 days if needed. Advise patients or caregivers that: Adequate pain relief from methadone may not occur for several days or weeks. Methadone should be taken exactly as directed. Short-acting rescue medications can be used until sufficient baseline analgesia is achieved. Any signs of increased sedations, mental clouding, snoring, or periodic apnea should be called in (supply an emergency phone number). No alcohol, benzodiazepines, or other CNS depressants should be used – especially at night – unless specifically prescribed or approved by the physician who prescribed the methadone. Also, follow up every day during dose titration by a telephone call, through home nursing, or by an office visit, and perform an in-person evaluation weekly until dose stabilization and then monthly thereafter if there are no major ongoing changes in health status, Dr. Fine said. In-person evaluations should be performed every 3 months once the patient is fully stable, he added. Dr. Fine has served as an advisory board member for Ameritox, Covidien, King Pharmaceuticals (now Pfizer), Meda Pharmaceuticals, and Purdue Pharma. He is a consultant for Cephalon and Johnson & Johnson. ■ 18 ARTHRITIS J U LY 2 0 1 1 • R H E U M AT O L O G Y N E W S


The bowel is not always suitable for cystoplasty. The use of a vicryl mesh lined with a peritoneal flap was investigated as material for partial replacement of the bladder. The procedure was performed on 20 rats divided into two groups. A partial cystectomy was first performed, then a cystoplasty was done using either a free peritoneal flap (group 1) or a vicryl mesh combined with a peritoneal flap (group 2). The results were evaluated using intravenous pyelography, macroscopic examination and histological analysis within one month. In group 1 (7 cases), there was one urinary fistula. In group 2 (13 cases), no fistula was observed but stones occurred in three cases. The histological analysis revealed good reconstruction of urothelium in both groups. Partial resorption of vicryl was observed at one month with organization of neo-muscular fibers. The vicryl prosthesis was well accepted and, when covered by a peritoneal flap, provided a strong and water-tight material for bladder replacement. The vicryl mesh increased the risk of stone formation in the presence of urinary tract infection.


The global image of the United States severely deteriorated under the Bush administration and anti-Americanism, an individual attitude of fundamental distrust towards what America is and does, rose accordingly during the same period. Favorable views of the US started to improve in the world in 2008, but then the financial crisis hit in September 2008. Did the crisis reignite anti-American sentiments worldwide? The crisis had the potential for increasing negative sentiments towards the US because it feeds into several of the underlying classical sources of anti-Americanism and because foreign leaders may be tempted to blame the US and stoke anti-Americanism domestically in order to absolve themselves from the failings of their own policies. Yet we do not observe such a spike in anti-American sentiments worldwide, at least at the level of public opinion. Why? The paper argues that this potential anti-Americanism has been mitigated by several factors, including the election of Obama, the new face of globalization, and the perception of US decline. The paper also examines whether anti-Americanism can affect the policy responses to the crisis.


A solid-phase extraction procedure was developed for the isolation of acidic, neutral, and basic drugs from whole blood. A blood sample was sonicated, diluted with phosphate buffer, and the drugs were extracted on a mixed-mode bonded-phase silica column at pH 6.0. The extraction system was adjusted to pH 3.3 with acetic acid. After column drying, the drugs were selectively eluted from the column by two different eluates, which were collected separately. Acidic, neutral, and weakly basic drugs with lower pKa values (e.g., benzodiazepines) were present in the first acetone-chloroform (1:1) fraction. The other basic drugs were present in the second fraction (basic ethyl acetate). The drugs with pKa's close to the pH of the extraction system (pH 3.3) appeared in both fractions. The two fractions were evaporated until approximately 100 microL of solvent remained in the tube and were then analyzed on a gas chromatograph equipped with a wide-bore capillary column and flame ionization detector. The absolute recoveries of all tested drugs exceeded 81% at a concentration of 2 micrograms/mL.


Learning analytics means gathering a broad range of data, bringing the various sources together, and analyzing them. However, to draw educational insights from the results of the analyses, these results must be visualized and presented to the educators and learners. This task is often accomplished by using dashboards equipped with conventional and often simple visualizations such as bar charts or traffic lights. In this paper we want to introduce a method for utilizing the strengths of directed graphs, namely Hasse diagrams, and a competence-oriented approach of structuring knowledge and learning domains. After a brief theoretical introduction, this paper highlights and discusses potential advantages and gives an outlook to recent challenges for research.


Large-scale structures are of special interest of aerospace applications, especially the ones involving smart materials. This paper deals with an archetypal system with two degrees of freedom that resembles the use of SMA elements as vibration isolation systems on a sparse aperture satellite array. The system has SMA elements in two perpendicular directions connected to a mass. Each SMA element is connected to a base structure. Imperfections are represented by establishing a comparison between two different systems: ideal and perturbed configuration system. The perturbed configuration is characterized by a situation where all SMA elements are in a stress-free state. The thermomechanical behavior of SMA elements is described by a constitutive model with internal constrains. Numerical tests of this system are of concern showing its general dynamical behavior. Periodic and chaotic motions are investigated showing the complex behaviors of this kind of system. The effect of imperfection in system dynamics is also discussed. Keywords: shape memory alloys, smart structures, aerospace structures, nonlinear dynamics


Background: Psychiatric case registers have been acknowledged as a valuable source of data, a long time ago. However, a growing interest exists in data on service utilization by patients belonging to groups with a related diagnosis to enable adequate planning of health resources. Aims: The aims of the Andalusian Case Register for Schizophrenia are to determine the prevalence of schizophrenia of those cared for by the public network of mental health services and to describe their pattern of care. Methods: Cases included on the Register are those persons resident in South Granada area with a diagnosis of schizophrenia and related disorders. The agencies which sent the information to the Register are all the mental health facilities in the catchment area. Conclusions: The Register is a flexible instrument to use for epidemiological research and mental health care planning.


A field trial of antimicrobial therapy for cases of undifferentiated bovine respiratory disease (UBRD) in beef calves was conducted at four Ontario feedlots. The primary purpose of the trial was to evaluate the efficacy of three different antimicrobials (oxytetracycline, penicillin, and trimethoprim-sulfadoxine) in the treatment of UBRD occurring within the first 28 days postarrival.The response, relapse, and case fatality rates overall were 85.7%, 14.8%, and 1.4%, respectively, and were not significantly different among the three antimicrobials evaluated. Weight gains of calves treated with the different drugs were not statistically different over the feeding period. Calves that suffered a relapse posttreatment were first treated significantly earlier (p<0.001) in the postarrival period than those that did not relapse. Considered together, treated calves gained significantly less (p<0.05) over the first 28 days and throughout the entire feeding period than controls that were never sick. Cases of UBRD that responded to therapy and did not relapse had rates of gain that were not significantly different from the controls.


Online optimization problems arise in many resource allocation tasks, where the future demands for each resource and the associated utility functions change over time and are not known apriori, yet resources need to be allocated at every point in time despite the future uncertainty. In this paper, we consider online optimization problems with general concave utilities. We modify and extend an online optimization algorithm proposed by Devanur et al. for linear programming to this general setting. The model we use for the arrival of the utilities and demands is known as the random permutation model, where a fixed collection of utilities and demands are presented to the algorithm in random order. We prove that under this model the algorithm achieves a competitive ratio of $1-O(\epsilon)$ under a near-optimal assumption that the bid to budget ratio is $O (\frac{\epsilon^2}{\log({m}/{\epsilon})})$, where $m$ is the number of resources, while enjoying a significantly lower computational cost than the optimal algorithm proposed by Kesselheim et al. We draw a connection between the proposed algorithm and subgradient methods used in convex optimization. In addition, we present numerical experiments that demonstrate the performance and speed of this algorithm in comparison to existing algorithms.


Background: Gene expression data from pancreatic cancer, histologically normal tissue adjacent to the cancer and normal pancreas reveals that adjacent normal has already acquired a number of transcriptional alterations and is not, therefore, an appropriate baseline for comparison with cancers. (Gadaleta et al., 2011) The purpose of this study was to determine if this is also the case for breast cancer and, if so, to identify the differences in gene expression between adjacent normal and normal breast. Methods: RNA-Seq data from breast cancer and adjacent normal was downloaded from the TCGA (The Cancer Genome Atlas) data portal. The epithelia from 20 frozen tissue cores from healthy premenopausal donors to the Susan G. Komen for the the Cure® Tissue Bank at the IU Simon Cancer Center were microdissected and the RNA isolated. RNA-seqeuncing was carried out using the Life Technologies SOLiD Platform. RPKM gene expression values from TCGA and sequencing of the Komen normal tissues were merged, quantile normalized, and batch effect corrected. Normalization and differential gene expression was performed using Partek Genomics Suite. Results: Principal component analysis (PCA) reveals complete separation between adjacent normal and healthy normal breast tissue. Setting a maximum FDR (false discover rate) of 5%, 2239 genes are differentially expressed between adjacent normal and healthy normal. Ingenuity pathway analysis reveals that the Fos, Jun and TGFbeta pathways are active in the adjacent normal. Conclusions: Tissue adjacent to a primary breast cancer is not normal when using healthy breast tissue as a comparator. As RNA-Seq data is digital, it is possible to quantify the changes in gene expression starting from healthy normal to normal adjacent to tumor to tumor. Increasing and decreasing gene expression values provide clues to the fundamental molecular changes occurring in histologically normal appearing adjacent tissue. The differences in gene expression we have identified are some of the earliest changes in breast carcinogenesis and provide insight into the etiology of this disease and, potentially, its prevention. Citation Information: Cancer Res 2012;72(24 Suppl):Abstract nr P1-03-02.


The main objective of the study was to validate the use of canopy temperature depression (CTD) as a rapid early generation screening tool for drought tolerance in wheat breeding. CTD was measured at 3 drought sites in Romania (Valu lui Traian, Modelu, Drăgăneşti-Vlaşca) on F6. Measurements of chlorophyll content (CHL) on F6 individual plants showed significant correlations with yield. Since a reliable yield estimate requires a plot approximately three times bigger than that needed for an estimate of CTD and CHL, the use of these methods instead of yield estimates may be considerably more efficient. Using alone either CTD or CHL could not provide enough data for drought resistant selection on winter wheat lines. Alternatively, both yield and CTD and CHL could be combined in a selection index as a more powerful indicator of drought tolerance. During the analysed period of three years, the climatic conditions were very different from one year to another. Forty-five lines of winter wheat in two repetition have been used for experiments, conducted in 3 locations in south of Romania. The study shows that genotype with high CTD values are correlated with high CHL values, but has lower drought tolerance. The lines with lower CTD values and high CHL values represent genotypes with high yield on drought conditions.


Abstract Purposes: The main goal of the paper is to determine the significance of selected sources of strategic information, used by Polish farmers in decision making. In addition, an attempt was made to determine the factors impacting the evaluation of those sources among the traits of the farmer and his farm. Methodology: Data was gathered using the questionnaire method and analysed with standard tools of descriptive statistics. Findings: The farmers deemed personalised sources of strategic information the most important, especially agricultural advisers, input suppliers and buyers of agricultural products. From among institutional (non-personalised) sources, local government and the chamber of agriculture were significant. Business information agencies and survey companies are the least important sources for farmers. The characteristics of the surroundings of the farm - specifically, its geographic location and the size of settlement where it is located proved to have the widest impact on the evaluation of the sources included in the study. From among the organisational factors, only farm size has a significant impact. Research limitations/implications: The study was confined to a representative group of farmers in Poland. A closed list of sources of strategic information was used. Originality/value: The study results contribute to the knowledge on the functioning of Polish agriculture and may also be used in comparative studies, characterising this sector's diversity within Europe. They can in turn contribute to properly focusing on supporting the policy of balanced agriculture development in the EU.


Records of in-patient stays which may contain multiple entries for the same patient are linked. These provide a profile of all in-patient hospital contacts for the same patient and statistics from which prevalence measures can be estimated. The linkage procedure is designed to link Scottish Morbidity Records for patients of the Greater Glasgow Health Board. It is suited to in-patient records generated from a relatively small number of hospitals (25-30). The records are selected by diagnosis. A suite of computer programs automates the method, which was initially investigated manually. Two types of linkage are performed. Type 1 links on the unique identifiers of hospital group code and case reference number to link records from the same hospital or group of hospitals. Type 2 linkage is designed to link patient stays in different hospitals or groups and links records with identical surname and date of birth and then identical surname and full unit postcode. The accuracy and efficiency of the automated procedure was estimated by linking records for 6 diagnoses (lung cancer, ischaemic heart disease, cerebrovascular disease, infectious diseases, road traffic accidents and head injuries). The gross difference between the actual number of patients and the number after linkage was between 0.6 and 2.1%. The net difference was within 1% for all diagnoses except lung cancer with a difference of 1.3%. These results compare favourably with other linkage procedures.


Background We often teach and assess medical students performing the respiratory examination in a traditional way, rather than based on evidence. An essential component of the respiratory clinical examination is that it is precise. The reliability of the examination is a fundamental element of this precision. There needs to be agreement between physicians that a clinical sign can be elicited independently in the same patient when it is present. When learning about the respiratory examination, medical students should have knowledge of the reliability of the different elements. Aims To establish medical students' knowledge of the reliability of different elements of the respiratory examination. Methods A cross sectional questionnaire survey of clinical medical students (years 3–5) was undertaken. The questionnaire assessed the reliability of tactile vocal fremitus, tracheal position, auscultation of wheeze, whispering pectoriloquy, auscultation of crackles and chest expansion using a five point Likert scale. Demographic data were also collected. The results of the perceived reliability of different elements of the respiratory examination was compared with Cohen's κ coefficient values; a statistical measure of inter-observer reliability. Results Of 104 questionnaires completed, 33% were male, 36% attached to respiratory firm, 11% graduate entry. Crackles, wheeze and percussion note are all regarded as reliable to very reliable signs by students. Perceived reliability of whispering pectoriloquy decreased as students become more experienced (p=0.003). There was no relationship between perceived reliability and graduate entry, previous respiratory attachment or gender. Factor analysis identified that tactile vocal fremitus and whispering pectoriloquy were grouped together separately from the other respiratory signs. Linear regression showed good correlation between students answers and actual κ values of reliability (r=0.722). Conclusions Students have a good intuition of the reliability of elements of the respiratory examination. For example, as experience increases, they correctly perceive whispering pectoriloquy as a less reliable sign. Reliability of elements of the respiratory examination needs consideration when teaching and assessing students.


Spontaneous facial expressions differ from posed expressions in both which muscles are moved, and in the dynamics of the movement. Advances in the field of automatic facial expression measurement will require development and assessment on spontaneous behavior. Here we present preliminary results on a task of facial action detection in spontaneous facial expressions. We employ a user independent fully automatic system for real time recognition of facial actions from the Facial Action Coding System (FACS). The system automatically detects frontal faces in the video stream and coded each frame with respect to 20 Action units. The approach applies machine learning methods such as support vector machines and AdaBoost, to texture-based image representations. The output margin for the learned classifiers predicts action unit intensity. Frame-by-frame intensity measurements will enable investigations into fa cial expression dynamics which were previously intractable by human coding.


Jupiter's icy moon Europa has captivated and perplexed the scientific community since the discovery of its global liquid water ocean. Over the course of several missions to the Jovian system, high-resolution observations of Europa have determined that there are spreading zones where new crust is created, similar to the mid-ocean spreading tectonic process we observe on Earth. These features, known as bands, have symmetric hills and valleys, indicating brief events of activity where material from the interior is exuded through a central crack, and solidifies on both sides, creating two positive topography. Recently, Europan scientists have been questioning how these features affect the total ice volume of the moon. After all, if ice is being created at these features, then the total volume of ice on Europa would be increasing, unless there was some mechanism in place to balance this net positive change in volume. In this thesis, I begin with a hypothesis: maybe the volume of ice being created through band extension can be compensated by compressional features. To test this hypothesis, we map, measure, and calculate surface area and volume estimates for bands and ridges in four regions across a global mosaic of Europa using moderate resolution images from the Galileo spacecraft. From our results, we may be able to draw important constraints on the thickness of the outer ice shell, which has been highly debated among scientists for decades. Initial results of this study show that the surface area of ridges can compensate for 35-70% of band surface area, with percentages varying greatly by region. Volume ratios of ridges to bands were calculated for several plausible values of shell thickness, ranging from 100 m 50 km. It appears that in order to compensate for band spreading, the bands would need to propagate to depths of 200 m – 1 km. While these calculations are only indicative of a small percentage (4.62%) of the total surface area of Europa and therefore are not yet conclusive for understanding the surface expression of tectonic activity, they prompt further investigation on a more global scale.


In this study the effect of recombinant human follicle stimulating hormone (rFSH) on oestradiol production by human granulosa-lutein cells was examined in long-term culture, in the presence or absence of androgens. Cells were harvested at the time of follicular aspiration after ovarian hyperstimulation for in-vitro fertilization and cultured for 9 days. Granulosa cells were capable of secreting oestradiol spontaneously even without androgen and gonadotrophin support. Basal oestradiol secretion was relatively high and variable (421.3 +/- 159.3 pg/ml, mean +/- SEM, n = 13) on the first day and decreased gradually to 16.7 +/- 3.1 pg/ml on day 9. Addition of androgens (testosterone or androstenedione) to the incubation medium enhanced dose-dependently basal oestrogen production on days 5, 7 and 9. The androgen/oestrogen conversion rate remained constantly high during the culture, even without rFSH. After pre-incubation for 3 days, addition of rFSH resulted in a dose- and time-dependent increase in granulosa-lutein cell oestrogen production in the absence of exogenous androgens. Testosterone supplementation caused considerably higher basal oestradiol concentrations, however rFSH failed to further stimulate the oestrogen release from granulosa-lutein cells, suggesting that these cells cultured in vitro possess high aromatase activity even without rFSH support.


Three representative types of houses in Beijing were selected and, in each type, smoking and nonsmoking households were compared, IP, RP, and CO concentrations in the living room and kitchen were monitored during each season, and the level of COHb in the heads of the households were measured. The study showed that indoor air pollution was rather severe, especially during winter, when particulate concentrations markedly exceeded the standard and CO concentration was as high as 47 ppm. Indoor air pollution was closely related to the type of house, particularly to the mode of heating. In houses, of the same type, pollution improved greatly after central heating facilities were installed. Analysis of 30 elements revealed that pollution was typically caused by coal burning, aggravated by dusty wind, but high indoor Pb levels were probably due to the use of LPG for cooking. In our study the effect of cigarette smoking was sometimes masked by the severe indoor pollution.


The conformal flow of metrics has been used to successfully establish a special case of the Penrose inequality, which yields a lower bound for the total mass of a spacetime in terms of horizon area. Here we show how to adapt the conformal flow of metrics, so that it may be applied to the Penrose inequality for general initial data sets of the Einstein equations. The Penrose conjecture without the assumption of time symmetry is then reduced to solving a system of PDE with desirable properties.


Enrolled nurses are being wrongly informed by their employers that they have to convert to registered nurse status in order to meet the UKCC's post-registration education and practice (PREP) requirements, the Council heard last week.


RECENTLY published reports have described a predominantly right-sided valvular heart lesion associated with cancerous argentaffinoma of the bowel.* These patients had some skin disorder such as intermittent cutaneous vasomotor flushing and/or a peculiar type of mottled cyanosis. There is a tendency to consider this combination of lesions as a new clinical syndrome. Some of the skin manifestations can be explained by a hormonal secretion, 5-hydroxytryptamine, of the argentaffinoma tumor.10The relationship between the tumor and the heart lesion is obscure. More clinical studies are needed to evaluate this rather rare combination of diseases. This paper reports an additional case which has been extensively studied and includes references not mentioned in previous reports. REPORT OF CASE A 54-year-old white woman was well until November, 1953, when she developed edema of the lower extremities, exertional dyspnea, and sub- sternal pressure sensations. Orthopnea was not present. Shortly afterwards she had episodes of


The influence of the precursors on the promoting effect of ceria on Pd/Al2O3 catalyst, when ceria is coated over alumina was studied. The reaction of propane oxidation proceeded under different feed conditions and the surface active sites were characterized by X-ray photoelectron spectroscopy (XPS) and in situ diffuse reflectance spectroscopy (DRS). XPS and DRS results show that PdO/Pd0 interface are the active sites independent of the precursor, while the catalysts containing CeO2 showed formation of palladium species in the highest oxidation state, probably PdO2 (338 eV) after the oxidation of propane. Besides, the O/Al and O/Ce ratios evidenced the increase of oxygen storage in the presence of CeO2. In addition, the precursor acetylacetonate favors the oxygen storage in the lattice.


The premise that acute non-fatal viral infections of the central nervous system (CNS) predispose to the subsequent development of chronic immune-mediated neurologic disease was investigated. Adult C57Bl/6 mice inoculated peripherally with 10(4) PFU of the A774 strain of Semliki Forest virus (SFV) develop a transient encephalomyelitis and sporadic (less than 20%) mild symptoms of paralysis with demyelination in the cerebellum from which they recover. Such recovered mice were found to develop signs characteristic of experimental allergic encephalomyelitis (EAE) 2 to 8 wk after either immunization with myelin basic protein (MBP) or receipt of 1 to 2 X 10(7) lymph node cells from MBP-primed syngeneic donors. These two methods of disease induction were unsuccessful when applied to normal B6 mice or those previously inoculated with noninfectious SFV. These findings suggest the possibility that virus-induced damage to CNS tissue may facilitate subsequent priming or clonal expansion of pre-existing myelin-reactive lymphoid cells.


Cystic fibrosis (CF) is characterized by considerable oxidative stress. However, it is not known whether oxidative stress is an important feature early in this disease. We have investigated a group of infants and young children with CF to establish whether oxidants are produced in their airways. Bronchoalveolar lavage fluid (BALF) was assayed for myeloperoxidase as a measure of neutrophilic inflammation, and 3-chlorotyrosine as a biomarker of the potent oxidant hypochlorous acid, which is formed by myeloperoxidase. Protein carbonyls were also measured as a nonspecific indicator of reactive oxidant production. Myeloperoxidase and 3-chlorotyrosine levels in BALF from children with CF were 10- and fivefold higher, respectively, than in disease control subjects. There was a strong correlation between myeloperoxidase and 3-chlorotyrosine. Myeloperoxidase levels were fourfold higher in children with infections in their airways. Median protein carbonyls were elevated by only twofold compared with disease control subjects, but some children had extremely high levels of protein oxidation. We conclude that hypochlorous acid is produced early in CF and that it is a candidate for precipitating the fatal decline in lung function associated with this disease. Also, there must be other sourcesof oxidants because protein carbonyls were not related to either inflammation or infection.


As global concern increases regarding pollution does the demand to develop more
ecient and environmental friendlier propulsion system come in high focus. The main
systems for transportation have been dominated by the Otto and Diesel engine for a long
time, but both are trade-o in local and global emissions, i.e. NOX, soot, HC and CO
versus CO2. This has driven the evolution to concepts as homogeneous charge compres-
sion ignition, HCCI and later partially premixed combustion, PPC. Although HCCI has
been shown to have ultra-low engine-out emissions in soot and NOX, has it been proven
to be unreliable in terms of combustion control and lack in eciency at higher loads.
PPC on the other hand is proven to be a good contester in both elds. This takes us
to where we are now, where the PPC analyzing and testing phase is ongoing. PPC has
been run with diesel as fuel, but with only a 25% of the conventional diesel combustion
range, due to self-ignition 6. This problem has been solved by running high octane fuels
with high resistance to ignite. These have shown to reduce emissions in soot and NOx
as a result of longer air and fuel mixing period and high EGR values for a low combus-
tion temperature. Ethanol has been tested with good results in eciency, combustion
control and emissions. The growing market for renewable fuel in Sweden and globally 1
indicates that this fuel is worth our eort for further investigation.
This thesis attempts to characterize PPC with ethanol as fuel. It has been shown, based,
and conrmed, that earlier testing by Manente 3 with double injection, EGR=50% and
=1.5 are suitable for PPC operation. New results shows that an injection strategy with
a pilot injection around -35 CAD ATDC, -5 CAD ATDC for second injection and an
injection ratio around 52% give good eciency, low emissions and low acoustic noise at
12 bar IMEPg. In this operation does the second injection provide with control over
the combustion duration. Earlier it has been stated that start of combustion (SOC)
was triggered by second injection, but results show no connection. Trends show that a
combination of, inlet temperature, lambda, and start of rst injection are key factors,
as they all coincide in creating a fuel and air mixture which is igniting at its certain
temperature. One can divide the combustion sequence in two parts. The pilot injection
which provides with a sucient fuel and air mixture which kinetically ignites due to the
high temperature just before TDC, causing a high rate of heat release. Followed by the
second injection, which is partially kinetically ignited and partially stratied that burns
in a diusion ame.
Concerning combustion sensitivity to parameter variation, inlet temperature has shown
to be an important factor, as variation of 5-10 oC clearly aects combustion in all
aspects. With too high temperature, SOC and phasing are advanced resulting in loud
acoustic noise and high combustion temperature, with too low inlet temperature SOC
and phasing are retarded which also leads to high noise, as well as higher emissions with
decreasing combustion eciency. Small variations of rail pressure, EGR and lambda does
not aect combustion at the same proportion, but even so they are as important to be
combined properly to gain a sucient ignition delay and combustion temperature.


This paper discusses pollution of surface water in 18 European countries. For each an account is given of its physical character, population, industries, and present condition of water supplies; the legal, administrative, and technical means of controlling pollution are then described, and an outline is given of current research on the difficulties peculiar to each country. A general discussion of various aspects common to the European problem of water pollution follows; standards of quality are suggested; some difficulties likely to arise in the near future are indicated, and international collaboration, primarily by the exchange of information, is recommended to check or forestall these trends.


Abstract The kinematic behavior of hailstones falling in their natural environment near the surface was studied using stroboscopic photography in a mobile van. The experimental results permitted determination of the shape and dimensions, velocity, and in a few cases the rotation rate, of hailstones failing into the van. Hailstones were sampled in southeast Wyoming, southwest Nebraska and northeast Colorado. About 84% of the hailstones photographed were classified spheroidal, the remainder being roughly conical. Change in orientation of stones is observed in most photographs, though only ∼6% of the hailstones could be assigned a rotation rate. Velocity data were obtained for more than 600 hailstones in the diameter range 5-25 mm. It is shown that the vertical velocity component of hailstones near the surface (air density =9.93×10−4 g cm−3) can be predicted by the expression VT where De0.50 (±m s−1), Deis the equivalent volume diameter of a spherical hailstone in centimeters. Fall-speed and hailstone oblate...


A series of experiments was performed in turtles, rodents, lagomorphs, dogs, and monkeys to determine and correlate differential growth and healing of bones and teeth. Vital stains, radiopaque implants in conjunction with serial radiography, autoradiography, histology, and other methods were employed. Histologic differences and rate of endochondral (tibia, rib, base of skull, and mandibular condyle) and nasal cartilaginous septal growth were noted. Similarly, differences were observed in growth between five facial sutures and also for the same suture at different times. The nasal bone side of the frontonasal suture grew about twice as fast as the frontal bone side. In the turtle shell the midsagittal suture grew faster than a transverse suture. A variety of differences in rate of appositional (and resorptive) growth were noted at different sites of the mandible and nasal bone region. Generally, there was deposition of bone along the posterior border of the mandibular ramus and resorption of bone along the anterior border. Variations in the volume of the orbital contents influenced orbital growth. Bone was highly reactive, while enamel and dentin were nonreactive, to trauma.


The quest for appropriate diagnostic tools and therapies for IBS runs in parallel with the different pathogenic mechanisms investigated. One of these mechanisms is visceral hypersensitivity, resulting from a disturbed neuronal signalling at the peripheral and/or central levels. 2 Rolland-Fourcade et al show, in this issue of Gut, that intestinal epithelial cells (Caco-2 cells) release a trypsin-like activity at the basolateral side of the cells after stimulation with a classical inflammatory stimulus (lipopolysaccharide) or with a stress-related stimulus (epinephrine), and they identified it as trypsin-3. They confirmed the clinical relevance of trypsin-3 by proving its presence in colonic tissue from patients with IBS (all subgroups). Besides, trypsin-3 increased epithelial permeability in the Caco-2 monolayers and increased the excitability of mouse dorsal root ganglia neurons in vitro. Moreover, it induced Ca transients in human submucosal neurons in vitro and caused visceral hyperalgesia in response to colorectal distension in two rat models of visceral hypersensitivity. The novelty of this manuscript lies within the identification of a specific protease, namely trypsin-3 and its source, the intestinal epithelium, providing additional evidence for serine proteases and protease-activated receptors (PAR). The importance of visceral hypersensitivity as a key contributor to the generation of symptoms in patients with IBS and thus an interesting target in the therapeutic counselling was recently endorsed by Simrén et al. Mast cells and their mediators, including histamine and proteases, are generally accepted to play a role in visceral hypersensitivity with histamine1 receptor antagonists representing a good example from 'bench to bedside' research. 6 Proteases can exert their activity via PARs, with PAR1 and PAR4 activation showing anti-nociceptive and PAR2 activation showing pronociceptive effects. Protease inhibition has been suggested as a therapeutic option in both IBS and IBD since an increased trypsin-like activity and enhanced tryptase contents have been shown in tissues from patients with IBS. In preclinical studies, PAR2antagonists and (serine) protease inhibitors indeed have shown beneficial effects on inflammation, intestinal permeability and recently on visceral hypersensitivity (for reviews, see refs 2 7 8). One has to be aware that besides mast cells releasing different serine proteases, such as tryptase and chymase, and inflammatory cells, the pancreas and the microbiome encompass an important source of proteases. Based on the existing data, one might definitely conclude that proteases are interesting molecules both as diagnostic biomarkers and/or as therapeutic targets in IBS. However, some important issues need to be solved and studied in more detail. The first issue relates to the origin of the proteases, the interactions between different proteases and their pathogenic potential in IBS. Proteases are present in large amounts and in different compartments both in the GI lumen (from pancreatic or microbial origin) and the GI wall (classically assumed derived from mast cells and inflammatory cells). In Gut, an additional source and its mechanisms are postulated regarding a specific protease, trypsin-3, released by intestinal epithelial cells and able to influence visceral sensitivity and the intestinal barrier function as stated above. In general, we need to unravel in more detail whether specific proteases are ubiquitously present or rather cell-specific as suggested here for trypsin-3. Next, it will be interesting to unravel how the epithelium-specific trypsin-3 relates to or interacts with, for instance, the mast cell-derived tryptase as both are postulated as important mediators in visceral hypersensitivity. Regarding the role of the different sources, there is evidence that the increased faecal serine protease activity detected in diarrhoeapredominant patients with IBS is from human and most probably from pancreatic origin. This does however not exclude a role for microbial and other luminal sources of proteases. We generally assume that these luminal proteases derived from the microbiome, pancreas or even food substances will remain in the GI lumen without crossing the mucosal barrier. However, we do not know exactly what happens in circumstances of impaired barrier dysfunction—as evidenced in many GI diseases—taking into account that proteases themselves are able to alter the intestinal permeability. 8 A second important issue that needs attention is the mechanism of action of the proteases considering the presence and activity of endogenous protease inhibitors as well. Specific protease inhibitors are needed in order to develop safe drugs that do not interfere with all the physiological roles of the different proteases and endogenous protease inhibitors, but on the other hand it is plausible that a combination of proteases needs to be targeted in order to obtain a sustained effect as well. 7 9 Regarding the mechanism of action, a PAR2-mediated pathway has been suggested for several proteases. In their present study, Rolland-Fourcade et al seem to exclude the involvement of PAR1 and PAR4 as the main receptor targets of trypsin-3. However, we cannot exclude a role for different PAR receptors when other (serine) proteases are involved. Moreover, the signalling cascade needs to be investigated in more detail, such as the involvement of transient receptor potential (TRP) channels downstream of the PAR receptors. The TRP vanilloid receptors TRPV1 and TRPV4 as well as the TRP ankyrin receptor TRPA1 have been linked to PAR2 activation and TRP channels also seem to be crucial for histaminergic signaling related to visceral hypersensitivity. 6 Finally, the methodologies used to measure protease activities need further development. One has to be aware that the substrates used to determine the activity of trypsin in this and other papers are cleaved by trypsin and by tryptase, and thus this non-specificity of the substrates used only provides information on a more broad trypsin-like activity. Recently, activity-based probes have been developed that bind the activity site of two serine proteases in an activity-dependent manner, namely trypsinlike and elastin-like activities, with proven efficacy in vitro but not yet in vivo. In summary, the role of serine proteases in IBS becomes more and more intriguing with evidence for the presence of different Correspondence to Professor Dr Benedicte Y De Winter, Laboratory of Experimental Medicine and Pediatrics, Division of Gastroenterology, University of Antwerp, Universiteitsplein 1, Antwerp 2610, Belgium; firstname.lastname@example.com


This study describes attempts to establish a culture system for cells derived from tissues of the grass prawn Penaeus monodon. No cell growth was observed in cultures on fragment of gill, nerve, muscle, gut and hepatopancreas. However, an observable cell growth was obtained in the culture of gonad and heart cells. The best growth of gonad cells occurred in a culture system containing double strength (2X) Leibovitz's L-15 medium supplemented with 10% fetal calf serum (FCS), 30% muscle extract, 0.006g/ml NaCl and 10% lobster or grass prawn haemolymph. When the gonad cells were cultured in this medium for 7-10 days and incubated at 28-31°C, a confluent monolayer cell sheet was formed. The primary cell culture, predominantly of epithelioid cells, could be maintained for approximately two months at 28-31°c with a weekly change of medium. After the third consecutive subculture, the cells degenerated and dislodged from the flask surface.


Agriculture can be considered one of the most important economic sectors, which has allocated to itself a significant percentage of the employees. So pay attention to this part of the economy and great cortex of workers and also development and improvement of its current is unavoidable. However, agricultural development depends on the backing of the government and organizations involved, because low-income segments account for most agricultural workers. Low- interest financing is one way of empowering low-income segments and is meant to provide loans with small amounts and without collateral to these classes that person is obliged to repay them in the short-term. Hence, the promotional schedule for the appropriate use of credits to reduce poverty and agricultural development is inevitable. The purpose of this study is evaluation of the viewpoint of villagers in the Ab shirin region of Kashan city about the role of extension programs in agricultural development and poverty reduction through the provision of low-interest credit that is done using the descriptive - correlation. The statistical population of this study is about 1296 people in the rural area of Ab Shirin in Kashan city, that 144 of them were selected as sample by using Cochran formula. A self-designed questionnaire was used for data collection. The questionnaire's validity was applied with business experts Agricultural Extension and Education and Cronbach's alpha test was approved about 89 percent. Reliability of the research is obtained by using SPSS software. The results showed that willingness of farmers to use the funds provided by the Agricultural Bank is positive. Based on the results, there is a significant relationship between impacts of extension programs the proper use of the funds provided by the government to reduce poverty.


Accountability is an important security property of distributed systems. It assures that every action executed in the system can be traced back to some entity. Accountability is even more crucial for assuring the safety and security in grid computing systems. Grid computing systems provide a vast amount of computing resources such as computing power, data storage, and network bandwidth. However, to date no comprehensive approach to accountability exists for the increasingly complex grid environments, wherein the number of users and the types of resources are large, diverse, and heterogeneous. Our work addresses this inadequacy by developing a comprehensive accountability system driven by policies and supported by accountability agents. In this thesis, we first discuss the key elements of our accountability framework and types of accountability data obtained in two strategies. We introduce accountability policy that specifies which data to collect and when to collect them, and more importantly how to coordinate data collection among different administrative domains. We then show that the proposed strategies can be realized upon accountability policy by sharing it among accountability agents.
In order to guarantee full accountability without conflicts when the policy is shared, the enforced accountability policies should be adapted based on the different risk levels of jobs and the different significance levels of a node. The support of flexible policies helps protect grid computing systems against malicious jobs, by increasing the level of accountability. To enable support of adaptable accountability policies, we propose a profile-based policy selection mechanism. This mechanism uses profiles of each job and node and considers node's capability to determine the level of accountability policy for the job and the node. We show how this mechanism can adapt the accountability policies, while at the same time achieving at least a minimum level of accountability.
Accountability data collected by the accountability agents according to the flexible accountability policies provides a basis for analyzing resource usage and finding bottlenecks and detecting security breaches. Additionally, data concerning user activities and actions enables mechanisms for timely identifying malicious users of faulty nodes and helping administrators to take proper defensive actions. In this thesis, we show how accountability data can be used to detect distributed denial of service attacks performed by exploiting resources made available by grid systems to suspend mission-critical websites or the grid itself and then to protect systems from these attacks. We present two approaches for protecting against attacks targeting sites outside or inside the grid.
In the thesis, we also describe a fully operational implementation of our accountability system and report the results from extensive experimental evaluations of it. Our experiments, carried out using the Emulab [1] test-bed, demonstrate that the implemented system is efficient and scalable for grid systems consisting of large numbers of resources and users. In addition, our experiments show that our system efficiently detects the distributed denial of service attacks and is effective in protecting the normal jobs.


Merozoite surface antigen 1 (MSA1) is a promising candidate for vaccine development against malaria parasites. Here, we report the complete nucleotide sequence of the gene encoding the precursor to this major surface antigen of Plasmodium berghei strain ANKA using cDNA library screening and polymerase chain reaction techniques. A single open reading frame of 5,376 basepairs encoding a protein with a calculated molecular mass of 197 kD was defined. The protein contains a putative signal peptide of 19 amino acids, a membrane anchor sequence of 18 residues, and shows two epidermal growth factor-like domains rich in Cys residues at the C-terminus. There are four repeat sequences of oligopeptides in the molecule: tetrapeptide (Ser-Thr-Thr-Thr), tripeptide (Pro-Thr-Pro and Pro-Ala-Ala), and dipeptide (Ser-Gly). Furthermore, three nine-residue stretches of a motif (Ala-Ser-Asn-Pro-Gly-Ala-Ser-Ala-Ser) are located near each other. All of these repeat sequences are unexceptionally located in the variable regions when compared with other MSA1 molecules. The molecule displays 79% overall identity to the analogous antigen of P. yoelii yoelii strain YM, 70% to that of P. chabaudi chabaudi strain AS, and 38% to that of P. falciparum strain Wellcome.


Abstract The standard approach to the follow-up of lymphoma includes computed tomography (CT) every 6–12 months for the first 2 years and, then, as clinically indicated. Recent evidence suggests that most relapses are detected clinically, outside scheduled CT which, on the other hand, increases risk of second malignancies and cost. In early-stage lymphomas, involved site CT instead of full body CT may be a reasonable alternative to reduce radiation dose. We analyzed whether regular CT surveillance detects asymptomatic relapses in a single-center Uruguayan early stage non-Hodgkin lymphoma (NHL) population. We evaluated utility of full body CT halfway and at the end-of-treatment evaluation and calculated the radiation exposure. In our study, CT surveillance added nothing to clinical follow-up. Moreover, 44% of our patients received a cumulative effective dose that doubles the risk of malignancies. Involved-site CT scan would be enough to monitor response during treatment in early stage NHL.


This paper presents a summary of results from a study carried out in 1980 and 1981 on the hume highway at picton, New South Wales, both before and after the opening of a section of the south western freeway (f5) which effectively bypassed the town. The study comprised surveys of traffic flow, traffic composition, speed and noise measurements, together with opinion surveys. The results obtained from the surveys are compared with previous studies of the effects of bypasses, carried out by the Country Roads Board of Victoria and by the Transport and Road Research Laboratory in the United Kingdom. Results are also compared, where appropriate, with results from the 1979/80 commercial vehicle surveys in New South Wales, and the 1974/75 National Association of Australian State Road Authorities (NAASRA) economics of road vehicle limits study. A number of trends in the operations of commercial vehicles on the road system are indicated. The opening of the freeway resulted in substantial decreases in road traffic and in noise levels. Five models were used to predict 'before' and 'after' traffic noise, and particular models are recommended for use. An estimate of the value of the environmental benefits of the bypass is presented, together with results from opinion surveys (a).


The certificate is a central concept in grid security infrastructure authentication. The certificate guarantees the authenticity of the data, thus effectively authenticating the sender. In this paper, we propose a secure certificate authentication framework using counting process to interact trusty for grid users. We intend to apply this approach in secured performance on grids as well as in grid application for authenticating users, protecting attacks, and recovering failed systems. The main idea presented in this paper is to add counting process and matching method into RSA algorithm to apply in grid certificate authentication


Barabási and Albert [1] find that many large networks exhibit a scale-free power-law distribution of vertex degrees. We show that when vertex degrees of large networks follow a scale-free power-law distribution with the exponent γ ≥ 2, the number of degree-1 vertices, when nonzero, is of the same order as the network size N and that the average degree is of order less than log N. Furthermore, let nk be the number of degree-k vertices. In this paper we prove that n1 must be divisible by the least common multiple of kγ<inf>1</inf>, kγ<inf>2</inf>,…, kγ<inf>l</inf>, where 1 = k1 < k2 <…> kl is the degree sequence of the network. Then we construct a general model of networks of scale-free and obtain some detail properties on scale-free and small-world networks. Our method has the benefit of relying on conditions that are static and easily verified. They are verified by many experimental results of diverse real networks and have comprehensive applications to social, natural and synthetic systems.


A novel platinum complex PtC with a tri-armed uracil hydrogen-bonded (H-bonded) unit was synthesized via a modular synthetic approach and characterized by 1H, 13C NMR and MALDI-TOF mass spectroscopies. Two H-bonded tetrads, PtC–(TPAD1)3 and PtC–(TPAD2)3, based on a metal core PtC complexed with two generations of triarylamine dendrimers, TPAD1 and TPAD2 (with electron-donating nature), were successfully constructed with improved organic solubility via a classical H-bonded self-assembly approach. Supramolecular H-bonding in solution and solid state was elucidated by 1H NMR titrations, IR spectral studies and time resolved photoluminescence (TRPL) measurements. The electron/energy transfers, as well as the self-assemblies of supramolecular tetrads, were established by UV-Vis and PL titrations and AFM morphological studies. Furthermore, metal complex core PtC showed selective sensitivity towards Ag+ ions through fluorescence turn-off responses without any interference from other common metal ions. The 1 : 1 binding stoichiometry and complexation mechanism between the probe and Ag+ ion was established by 1H NMR titration. Moreover, PL reversibility of PtC + Ag+ could be achieved on addition of PMDTA.


Proceedings: AACR Annual Meeting 2014; April 5-9, 2014; San Diego, CA

Introduction: MiRNAs have been implicated in the development of some if not all cancer types and have been identified as attractive targets for therapy. However, systemic delivery of bare miRNAs faces its own set of limitations because of degradation by RNases and filtration and excretion by the kidneys. In this work we propose miRNAs as therapeutic agents. We have developed a novel system for miRNA delivery applicable for both local and systemic administration with the use of mesenchymal stem cell (MSC) microparticles (MPs).

Methodology: MSCs were isolated from the Wharton's jelly of human umbilical cords. The MSC cultures were subjected to serum deprivation, leading to the formation of MPs (secreted membrane vehicles <1μm) which were harvested and characterized by SEM, PCR, FACS and Fluorescence Microscopy. Breast (MDA-MB-231 & MCF-7), colon (RKO & HT-29) and ovarian adenocarcinoma (SKOV3) cell lines were then exposed to MPs. The response to treatment was evaluated by cell morphology, proliferation, migration, gene expression and apoptosis. Furthermore, the therapeutic potential of MPs was tested in vivo in xenograft tumor mouse models. Innovative imaging modalities such as in vivo flow cytometry and whole body fluorescence-bioluminescence were employed to dynamically investigate the biodistribution and homing kinetics of MPs in mice.

Results: In vitro experiments confirmed that MSC-derived MPs can be internalized by the various cancer cell lines and induce a biological effect as evidenced by membrane damage, cell shrinkage and blebbing in the recipient cell. Significantly, there was evidence that MPs induce apoptosis, inhibit cell proliferation and tumor growth attenuation in a dose/time-dependent manner. The pro-apoptotic and anti-migration effects of MPs in cancer cells were almost completely abrogated by RNase treatment before administration to cultures. In vivo studies demonstrated that we were able to monitor and quantify fluorescently labelled MPs in circulation and to detect and image the biodistribution and incorporation in cells and organs in healthy and tumor-bearing mice.

Conclusion: MSC-derived MPs containing miRNAs possess tumor inhibitory properties both in vitro and in vivo. Administration of MPs after RNase treatment induces the loss of anti-cancer properties suggesting a horizontal transfer of small RNAs from MPs to cancer cells. MPs formulated to contain specific miRNAs, could affect the action of genes associated with carcinogenesis, neovascularization, metastasis and other cancer characteristics, thus leading to therapeutic benefit.

Citation Format: Marianna Prokopi, Agamemnon Epenetos, Andreas Anayiotos, Costas Pitsillides, Konstantinos Kapnisis, Christina Kousparou. Therapeutic miRNAs targeted selectively to tumors by mesenchymal stem cell derived microparticles. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 1977. doi:10.1158/1538-7445.AM2014-1977


ABSTRACT Few recent studies have investigated food label practices in older adults. This cross-sectional study surveyed adults, 60 years and older in Delaware (n = 100, 82% female, 74% between 60 and 79 years, 49% Caucasian, 45% African Americans) to examine associations between food label knowledge, attitudes, and usage patterns. A 28-item questionnaire assessed knowledge, attitudes, usage, and demographic information. Bivariate analysis results showed food label knowledge was associated with education and monthly income. Those reporting a high school education or less incorrectly identified calorie (P < 0.05) and carbohydrate information (P < 0.03). Monthly income ≤$2000 was associated with incorrectly interpreting carbohydrate information (P < 0.03). Label usage was associated with being female (P < 0.001), having a high school education or less (P < 0.000), being 70 years or older (P < 0.05), and having a monthly income ≤$2000 (P < 0.001). Respondent's usage and perceived label comprehension was high; however less than half could correctly interpret label information. When shown samples of the US Food and Drug Administration's proposed new labels, subjects had a very favorable attitude toward the new changes. Increasing nutrition knowledge through education interventions appropriate for older adult consumers may improve comprehension of information on the food labels.


Skid mark and coefficient of friction are usually utilized to calculate the velocity and behavior of vehicles. For a critical case such as traffic accident reconstruction, however, the initial velocity of the car should be calculated precisely. In this study, the skid marks on dry asphalt pavement were measured, and the velocity at brake onset was precisely recovered. A passenger car with new tires and non-contact optical speedometer were set up for the tests. A new methodology to determine the more precise velocity for Non-ABS vehicle at braking onset were suggested.


Observations of fluxes and energy spectra of electrons (0.19-3.2MeV) and protons (0.64-35MeV) by OHZORA satellite are reported. The results obtained during March 14-June 22, 1984 are discussed in this paper. The maximum fluxes of electrons and protons are observed in the South Atlantic Anomaly and the auroral zones. Narrow peaks of counting rate in "the midlatitude zone" of L=1.6 are observed over the south Pacific Ocean and Mexico, and the pitch angle distribution of the particles shows that these particles are geomagnetically trapped. Temporarily intensive proton and He ion fluxes at the north polar cap region are observed, and their particle energy spectrum shows that solar flare particles are injected into the polar cap.


Lung cancer has been the leading cause of cancer death for both men and women worldwide. Non-small-cell lung cancer (NSCLC) displays an array of molecular abnormalities most commonly involving ALK and EGFR pathways. NSCLC with ALK rearrangements comprises close to 5% of cases. Several ALK inhibitors (ALKI) have been approved with activity in brain metastases. However, there have been limited comparative studies exploring their relative efficacies. This meta-analysis was conducted to compare the relative efficacy of ALKIs against ALKI-naïve ALK+ lung cancer brain metastases.

 A review of the medical literature was conducted using online databases. Inclusion criteria consisted of English language; diagnosis of ALKI-naïve ALK+ lung cancer trials with brain metastases; treatment with Crizotinib (CRZ), Alectinib (ALC), Brigatinib (BRG), and Ceritinib (CER); and comparative studies reporting brain metastases specific responses/events. A Bayesian and a frequentists network meta-analysis were conducted using netmeta package and the random-effects model.

 Eight studies comprising a total of 665 participants with ALKI-naive ALK+ lung cancer brain metastases were included. When compared pair-wise to CRZ, ALC (RR=0.49;95%CI:0.36–0.66), BRG (RR=0.39;95%CI:0.24–0.64), and CER (RR=0.36;95%CI:0.19–0.68) demonstrated significantly superior response rates in patients with untreated or previously treated lung cancer brain metastases. When the efficacy of each ALKI was compared to each other, BRG and CER were ranked the highest, followed by ALC and CRZ in decreasing order.

 This network meta-analysis is the first to compare and rank approved ALKIs used in treating metastatic ALK+ lung cancer. It indicates that BRG, CER, and ALC are better therapeutic options for patients with ALK-naive ALK+ lung cancer brain metastases when compared to CRZ.


One-carbon chemicals (C 1s) are potential building blocks as they are cheap, sustainable, and abiotic components. Methanol-derived formaldehyde can be another versatile building block for the production of 2-keto-4-hydroxyacid derivatives that can be used for amino acids, hydroxy carboxylic acids, and chiral aldehydes. To produce 2-keto-4-hydroxybutyrate from C 1s in an environment-friendly way, we characterized an aldolase from Pseudomonas aeruginosa PAO1 (PaADL), which showed much higher catalytic activity in condensing formaldehyde and pyruvate than the reported aldolases. By applying a structure-based rational approach, we found a variant (PaADLV121A/L241A) that exhibited better catalytic activities than the wild-type enzyme. Next, we constructed a one-pot cascade biocatalyst system by combining PaADL and a methanol dehydrogenase (MDH) and, for the first time, effectively produced 2-keto-4-hydroxybutyrate as the main product from pyruvate and methanol via an enzymatic reaction. This simple process applied here will help design a green process for the production of 2-keto-4-hydroxyacid derivatives.


ABSTRACT Advocacy non-governmental organisations (NGOs) play an important role in society by keeping in check the power of corporations and governments and uncovering rights violations. They differ from other NGOs in terms of their agenda, funding structure and the stakeholders they serve, and operate in a context characterised by increasing demands for transparency, accountability and responsible advocacy. This study examines how the accountability agenda of advocacy NGOs is shaped by the need to maintain independence, preserve values and keep reputation unsullied when faced with financial and legitimacy pressures. A netnography method is employed to analyse the discussions taking place in the NGOs' online community of practice to understand the implications of the accountability challenges faced by advocacy NGOs through the perceptions of NGO professionals. The study reveals that the accountability agenda of advocacy NGOs is determined by the interrelated threats of financial vulnerability, potential loss of independence, legitimacy challenges and the high level of public scrutiny. The findings highlight that imperfect accountability mechanisms (e.g. financial reporting and performance management systems) hinder the ability of advocacy NGOs to demonstrate their accountability. HIGHLIGHTS Advocacy NGOs face the highest level of accountability demands among non-profits. Financial vulnerability and independence threats are the main accountability drivers. Complexities in performance management hinder signalling NGOs accountability. Netnography permits to explore perceptions of advocacy NGOs' practitioners.


In this paper, we consider extractive summarization of Chinese broadcast news speech. A unified probabilistic generative framework that combined the sentence generative probability and the sentence prior probability for sentence ranking was proposed. Each sentence of a spoken document to be summarized was treated as a probabilistic generative model for predicting the document. Two different matching strategies, i.e., literal term matching and concept matching, were extensively investigated. We explored the use of the hidden Markov model (HMM) and relevance model (RM) for literal term matching, while the word topical mixture model (WTMM) for concept matching. On the other hand, the confidence scores, structural features, and a set of prosodic features were properly incorporated together using the whole sentence maximum entropy model (WSME) for the estimation of the sentence prior probability. The experiments were performed on the Chinese broadcast news collected in Taiwan. Very promising and encouraging results were initially obtained.


Spiking neural networks have shown great promise for the design of low-power sensory-processing and edgecomputing hardware platforms. However, implementing onchip learning algorithms on such architectures is still an open challenge, especially for multi-layer networks that rely on the back-propagation algorithm. In this paper, we present a spikebased learning method that approximates back-propagation using local weight update mechanisms and which is compatible with mixed-signal analog/digital neuromorphic circuits. We introduce a network architecture that enables synaptic weight update mechanisms to back-propagate error signals across layers and present a network that can be trained to distinguish between two spikebased patterns that have identical mean firing rates, but different spike-timings. This work represents a first step towards the design of ultra-low power mixed-signal neuromorphic processing systems with on-chip learning circuits that can be trained to recognize different spatio-temporal patterns of spiking activity (e.g. produced by event-based vision or auditory sensors).