Background: Dry eye disease is a multifactorial chronic disorder of the ocular surface, which leads to symptoms of discomfort and distress. Dry eye disease is a global health concern and is one of the most frequent ocular diseases encountered in an ophthalmology clinic. The estimated prevalence of dry eye disease in the literature ranged from 7.4% to 93.2%. Saudi Arabia's population, especially in the eastern province, is at great risk of developing dry eye disease, however, there is hardly any nationwide study that assesses the prevalence of dry eye disease among the general population and its risk factors. Aim: The aim is to estimate the prevalence of dry eye disease and determine its risk factors among the general population of Saudi Arabia. Methods: This study was a cross-sectional study conducted on the general population of Saudi Arabia between September 2022 and November 2022. A convenient sampling technique was deployed for participant recruitment, where a self-administered questionnaire was created and dispersed to the general population all over the country with an invitation to participate in the study. Dry eye disease prevalence was assessed using Ocular Surface Disease Index survey. The Chi-square test was used to test for factors associated with the prevalence of dry eye disease, and undiagnosed dry eye disease. Multivariate logistic regression was also used to determine risk factors for dry eye disease. Results: A total of 1,381 participants were included in this study. The prevalence of dry eye disease among the general population of Saudi Arabia was observed to be (17.5%). Among the participants (11%) had mild dry eye disease, (4.7%) had moderate dry eye disease, and (1.7%) had a severe dry eye disease. Among those observed to have a dry eye disease, (58.09%) were not previously diagnosed. The following factors were observed to be significantly associated with having dry eye disease, being female, having thyroid disease, having systemic lupus erythematosus/rheumatoid arthritis, using antidepressants, using antihistamine/decongestants, using electronic devices for a prolonged time, using contact lenses, having a history of eye surgery, history of conjunctival/eyelid infection, and history corneal abrasions/erosions/ulceration. Conclusion: This study revealed that the prevalence of dry eye disease among the general population of Saudi Arabia is notably lower than what was observed in other local studies and similar to what was found in some global studies. Adjusted binary multivariate logistic regression revealed that the risk factors were only: being female, using antidepressants, using antihistamines/decongestants, and prolonged use of electronic devices.


We calculate the critical exponent of nonlinear Schrödinger (NLS) equations with anisotropic negative fourth-order dispersion using an anisotropic Gagliardo–Nirenberg inequality. We also prove global existence, and in some cases uniqueness, for subcritical solutions and for critical solutions with small L2 norm, without making use of Strichartz-type estimates for the linear operator. At exponents equal to or above critical, the blowup profile is anisotropic. Our results imply, in particular, that negative fourth-order temporal dispersion arrests spatio-temporal collapse in Kerr media with anomalous time-dispersion in one transverse dimension but not in two transverse dimensions. We also show that a small negative anisotropic fourth-order dispersion stabilizes the (otherwise unstable) waveguide solutions of the two-dimensional critical NLS.


While the morphology of the various formed elements of the blood is now on a fairly scientific basis, there remains considerable lack of knowledge in regard to the origin and function of these cells. It is a matter of common agreement that the red cells are formed in the bone-marrow in adults and in the liver and spleen in embryos, while the origin of platelets is still in doubt. The polymorphonuclear leukocytes come originally from bone-marrow; the lymphocytes are derived from lymph glands and from tissue, and the large mononuclears have either the same origin as lymphocytes, or develop from endothelial cells lining blood or lymph vessels. Not all the functions of these cells have been elucidated, although the evidence indicates that the red cells are concerned chiefly in tissue respiration, or the carriage of oxygen to the tissues; while the blood platelets are apparently involved in the phenomena of


In this paper, the characterizations of cellular mechanics of W303 yeast cells have been conducted using nanoneedles inside environmental-SEM (ESEM). This enhanced ESEM system comprises of a standard ESEM instrument as a nano imaging tool, a cooling stage as a cellular biology's humidity controller and 7 D.O.F. linear actuators as nanomanipulator/effector. Four types of nanoneedles have been used in the experiments, i.e. silicon (Si) nanoneedle, titanium (Ti) coated Si nanoneedle and tungsten (W) nanoneedles. The former two nanoneedles are fabricated using 2 N/m spring constant's cantilevers. While the latter nanoneedles are fabricated using 0.09 N/m and 2 N/m spring constant's cantilevers (W0.09 and W2 nanoneedles). All types of the nanoneedles, i.e. Si, Ti-Si, W0.09 and W2 nanoneedles are able to be used for single cells' local stiffness characterizations. This ability can be used in future fast disease detection where the disease cells may shows different cell mechanics properties compare to the normal cell. In addition to this, the Si-Ti and W2 nanoneedles have shown an ability to penetrate the cell without cell bursting. This ability is important in the future single cell surgery where the cell damage can be eliminated as much as possible.


It is a common goal in biophysics to understand protein structural properties
and their relationship to protein function. I investigated protein structural
properties using three coarse graining methods: a rigidity analysis method First, a
geometric simulation method Froda and normal mode analysis as implemented in
Elnemo to identify the protein directions of motion. Furthermore, I also compared
the results between the coarse graining methods with the results from molecular
dynamics and from experiments that I carried out. The results from the rigidity
analysis across a set of protein families presented in chapter 3 highlighted two different
patterns of protein rigidity loss, i.e. "sudden" and "gradual". It was found
that theses characteristic patterns were in line with the rigidity distribution of glassy
networks. The simulations of protein motion by merging flexibility, rigidity and normal
mode analyses presented in chapter 4 were able to identify large conformational
changes of proteins using minimal computational resources. I investigated the use
of RMSD as a measure to characterise protein motion and showed that, despite it
is a good measure to identify structural differences when comparing the same protein,
the use of extensive RMSD better captures the extend of motion of a protein
structure. The in-depth investigation of yeast PDI mobility presented in chapter
5 confirmed former experimental results that predicted a large conformational
change for this enzyme. Furthermore, the results predicted: a characteristic rigidity
distribution for yeast PDI, a minimum and a maximum active site distance and a
relationship between the energy cutoff, i.e. the number of hydrogen bonds part of the
network of bonds, and protein mobility. The results obtained were tested against
molecular dynamics simulations in chapter 6. The MD simulation also showed a
large conformational change for yeast PDI but with a slightly different minimum
and maximum inter-cysteine distance. Furthermore, MD was able to reveal new
data, i.e. the most likely inter-cysteine distance. In order to test the accuracy of the
coarse graining and MD simulations I carried out cross-linking experiments to test
the minimum inter-cysteine distance predictions. The results presented in chapter
7 show that human PDI minimum distance is below 12A whereas the yeast PDI
minimum distance must be above 12A as no cross-linking structures where found
with the available (12A long) cross-linkers.


According to the high fault rate and the great difficulty of diagnosis for the automobile engine, an automobile engine faults detection system was designed. Because the vibration signal of the engine could reflect the faults types to a great extent, a fault detection method was proposed based on the extraction of the vibration signal correlation dimension. The collected vibration signal which was from different type of automobile engines was processed and analyzed. The correlation dimension was extracted and an improved correlation algorithm was proposed in the system, the computational accuracy was improved, and the standard deviation of the improved algorithm lowers about 50% in comparison with the traditional algorithm, the classification performance is raised variously, the excellent detection performance was showed in the system. The detection result shows that the correlation dimension feature extraction method that this paper proposed can detect and diagnose different types of automobile engine faults such as start subsystem fault, ignition subsystem fault, fuel supply subsystem, etc. The detection conclusion was stable and the simulation result has much great application performance.


Major bottlenecks in the expansion of human β-cell mass are limited proliferation, loss of β-cell phenotype, and increased apoptosis. In our previous studies, activation of Wnt and mTOR signaling significantly enhanced human β-cell proliferation. However, isolated human islets displayed insulin signaling pathway resistance, due in part to chronic activation of mTOR/S6K1 signaling that results in negative feedback of the insulin signaling pathway and a loss of Akt phosphorylation and insulin content. We evaluated the effects of a new generation insulin sensitizer, MSDC-0160, on restoring insulin/IGF-1 sensitivity and insulin content in human β-cells. This novel TZD has low affinity for binding and activation of PPARγ and has insulin-sensitizing effects in mouse models of diabetes and ability to lower glucose in Phase 2 clinical trials. MSDC-0160 treatment of human islets increased AMPK activity and reduced mTOR activity. This was associated with the restoration of IGF-1-induced phosphorylation of Akt, GSK-3, and increased protein expression of Pdx1. Furthermore, MSDC-0160 in combination with IGF-1 and 8 mM glucose increased β-cell specific gene expression of insulin, pdx1, nkx6.1, and nkx2.2, and maintained insulin content without altering glucose-stimulated insulin secretion. Human islets were unable to simultaneously promote DNA synthesis and maintain the β-cell phenotype. Lithium-induced GSK-3 inhibition that promotes DNA synthesis blocked the ability of MSDC-0160 to maintain the β-cell phenotype. Conversely, MSDC-0160 prevented an increase in DNA synthesis by blocking β-catenin nuclear translocation. Due to the counteracting pathways involved in these processes, we employed a sequential ex vivo strategy to first induce human islet DNA synthesis, followed by MSDC-0160 to promote the β-cell phenotype and insulin content. This new generation PPARγ sparing insulin sensitizer may provide an initial tool for relieving inherent human islet insulin signaling pathway resistance that is necessary to preserve the β-cell phenotype during β-cell expansion for the treatment of diabetes.


AI image generators such as DALL-E 2 are deep learning models that enable users to generate digital images based on natural language text prompts. The impressive and often surprising results leave many people puzzled: is this art, and if so, who created the art: the human or the AI? These are not just theoretical questions; they have practical ethical and legal implications, for example when raising authorship and copyright issues. This essay offers two conceptual points of entrance that may help to understand what is going on here. First it briefly discusses the question whether this this art and who or what is the artist based on aesthetics, philosophy of art, and thinking about creativity and computing. Then it asks the question regarding human-technology relations. It shows that existing notions such as instrument, extension, and (quasi) other are insufficient to conceptualize the use of this technology, and proposes instead to understand what happens as processes and performances, in which artistic subjects, objects, and roles emerge. It is concluded that based on most standard criteria in aesthetics, AI image generation can in principle create art, and that the process can be seen as poietic performances involving humans and non-humans potentially leading to the emergence of new artistic (quasi)subjects and roles in the process.


We have developed an in vivo model of human chronic myeloid leukemia (CML). A peripheral blood (PB) sample of Philadelphia (Ph) chromosome-positive CML cells in lymphoid blast crisis was transplanted intravenously (IV) into sublethally irradiated severe combined immunodeficient (SCID) mice, and this resulted in engraftment with systemic proliferation. Growth of leukemia was monitored by PB cell morphology and by flow cytometric analysis of murine PB cells labelled with an anti-human leukocyte antigen (HLA) monoclonal antibody. Human cells were first detected in the PB at 4 weeks and comprised a mean of 57% of the total nucleated cells in the PB of these mice by 15 weeks. The Ph chromosome was retained and the population has been successfully passaged. BCR/ABL fusion gene expression was detected in a subsequent passage. Experiments are underway to use this in vivo model to assess the antileukemic activity of BCR/ABL antisense oligonucleotides.


There is an increase in the prevalence of neurological diseases and the burden they impose. Therefore, identifying the frequency of symptoms and the functional alterations is of paramount importance to develop an adequate treatment plan. A cross-sectional study was carried out to pinpoint the main symptoms and functional alterations in neurological patients at a rehabilitation center in Colombia. The five most frequent symptoms and functional alterations identified were: walking disorders (65.5%), communication disorders (36.98%), memory and emotional alterations (38%), pain (29.45%), and alterations in activities of daily living (24.3%). Fifty percent of the patients who reported pain, 30% of those who complained of insomnia, and 80% of those who mentioned constipation did not receive treatment during the first consultation. Some of the identified symptoms are not characteristics that define the disease, and are not always the subject of intervention. The results of this study can contribute to recognition of the burden of the symptoms of neurological diseases, by making health professionals more aware of the importance of palliative care for patients with non-oncological progressive diseases.


One of the central problems in computational biology is to identify the protein function in an automated and high-throughput fashion. A key step in this process is to predict subcellular compartment the protein belongs to, since the protein localization closely correlates with its function. A wide variety of methods for protein subcellular localization has been proposed over recent years. They fall into two categories, sequence-based and database-based. The first one is to extract useful features from amino acid sequences and strives to discover the principles behind protein localization process. The second one is more apt to conduct data mining from existing public annotation databases. This paper focuses on the sequence-based approach and exploits the discriminative ability contained in amino acid sequences for protein subcellular localization. By using support vector machines (SVMs) as predictors, we conducted comparisons among amino acid composition approach, amino acid tuple approach, voting scheme, and a new characteristic representation of proteins proposed in this paper. Our experiments are carried out on 7579 eukaryotic protein sequences from 12 subcellular locations. The highest accuracy, 82.8% across 5-fold cross validation, is obtained by voting scheme using five predictors. This is the best performance achieved on this dataset using sequence-based approach. Our experiments demonstrate that there are considerable potentials on improving prediction accuracy by exploiting protein sequences, which have not been fully utilized so far, and more explorations are still needed in this direction


Leukemic cells, like many other cancer cells, are often deficient in DNA repair capacity. PARP inhibitors have demonstrated synthetic lethality in cancer cells with defective DNA repair. E7449 is an orally bioavailable, potent, small molecule inhibitor of poly(ADP-ribose) polymerase (PARP)1 and PARP2. In this study we describe the therapeutic potential of the PARP inhibitor E7449 in acute myeloid leukemia (AML). E7449 inhibited proliferation of leukemia cells in a long term in vitro growth inhibition assay in a panel of leukemic cell lines. The MV-4-11 AML cell line was identified as particularly sensitive to E7449 PARP inhibition, and induction of apoptosis was observed in these cells. An in vivo survival model of acute myeloid leukemia (AML) was established in NSG mice using MV-4-11-luc2/AcGFP human AML cells. Daily dosing of E7449 at 100 mg/kg resulted in statistically significant anticancer activity in this model. Reduced disease burden as measured by luciferase signal was observed. This decrease in leukemic load also translated into a statistically significant survival benefit in E7449 treated mice. In AML cells, high P-glycoprotein (P-gp) expression is often observed, particularly in older patients, and this often leads to resistance to typical therapies. E7449 anti-proliferative activity was assessed in paired murine leukemia cells with basal (P388/S) and overexpressed P-gp protein (P388/VMDRC.04). E7449 effectively inhibited growth of the high P-gp expressing cells as well as the parent P388/S cells, with no significant difference in the presence or absence of verapamil, in contrast to data obtained for the P-gp substrate doxorubicin. These data demonstrate that E7449 is not a substrate for P-gp transport. Importantly, E7449 also significantly inhibited proliferation of primary patient AML cells ex vivo. In addition, E7449 proved highly potent at inhibiting colony formation in the majority of primary patient AML specimens assessed in long term (14 day) clonogenic survival assays. Studies to discern the mechanism underlying sensitivity to E7449 in AML cells are underway. Conclusion: In this study, E7449 possessed potent anti-cancer activity against AML cell lines and primary patient AML cells in vitro and ex vivo, it was not a substrate for P-gp transport, and it reduced disease burden and increased survival in an AML in vivo model. These data support the assessment of E7449 as a therapy for AML in the clinic. Citation Format: Sharon McGonigle, Zhihong Chen, Jiayi Wu, Donna Kolber-Simonds, Shannon McGrath, Karen TenDyke, Zichun Wang, Kenichi Nomoto. E7449, a potent inhibitor of PARP 1 and 2, is active in acute myeloid leukemia. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 3323. doi:10.1158/1538-7445.AM2013-3323


This paper investigates the wealth effects of private equity (PE) investor purchases of shares in German quoted companies. It is the first study to analyze these effects for the German market which is particularly interesting due to its distinct characteristics with regard to the ownership structure of publicly listed companies and the protection of minority shareholders. We find that PE investors generate positive wealth effects for target shareholders of 5.90% around the event day (t = -1 to t = 0). In addition, we find that the wealth effects of PE investor involvement in Germany are positively related to the target's tax liabilities and degree of undervaluation and negatively related to the target's leverage and the shareholding of the second largest ownership block. The latter effect can be interpreted as a supplementary monitoring effect of the management or a monitoring effect of the largest shareholder through which private benefits of control are reduced.


The aim of treatment of hypertension as of other diseases is to relieve symptoms and to improve prognosis. Most of the symptoms of hypertension are due to the associated cardiovascular complications, and these also have a decisive effect on prognosis. The effectiveness of treatment for hypertension depends on the extent of reduction of blood pressure, and there is good evidence that consistently lowering the blood pressure may lead to improvement in many symptoms such as headache, paroxysmal nocturnal dyspnoea, and angina of effort, and to a decrease in mortality. However, all methods of treatment have some disadvantages. Most drugs have some side effects, which range in severity from mild nuisance effects to major complications. Moreover, many drugs are capable ofinducing falls of blood pressure so large that transient or permanent tissue ischaemia may develop, especially in patients with severe vascular disease. For these reasons in the past most of us have considered that not all hypertensive patients should be given active treatment and that only those with either symptoms or an obviously poor prognosis should be treated. This has been necessary because of the need to try to improve symptoms and prognosis without the substitution of severe or disabling side effects. Perhaps the most striking improvement in the effectiveness of drug treatment of hypertension in the last decade has resulted from increased awareness on the part ofphysicians ofthe value of combinations of drugs. While many still remain suspicious of drug combinations, this is probably because the successful use of multiple therapeutic agents needs to be soundly based on an understanding of the mechanism of drug actions.


The murine breast cancer cells (4T1) grown both in female BALB/c mice and in culture were treated with anastrozole (50 $\mu$ g/mL), tamoxifen citrate (5 $\mu$ g/mL), and the combination of the two drugs in order to determine treatment efficacies, toxic potential, and the mechanism of cell death. The in vivo treatments were evaluated by monitoring tumor growth, development, and life span. The in vitro effects were measured through cell growth kinetics, cell proliferation, mitochondrial membrane potential disruption assay, and light and scanning electron microscopy. All drug treatments extended the mean life span of the 4T1-inoculated tumor-bearing mice; however, only tamoxifen and combination treatments statistically increased the life span when compared to untreated mice. Although the most drug inhibitory effect on cell multiplication was observed in the combination treatment, both anastrozole and tamoxifen individually inhibited cell proliferation significantly at most time periods in this mouse breast cancer cell line. The mitochondrial membrane potential disruption assay demonstrated significant increase in the percent of cells undergoing apoptosis in all treatment groups. However, the combination treatment was the most effective in inducing cell death via apoptosis. Light and scanning electron microscopy of the treated cells revealed characteristics such as rounding, clumping, and shrinkage of the cells as well as formation of cell surface blebbing and apoptotic bodies suggestive of cell death via apoptotic pathway.


The WiBro is a wireless Internet system toward next generation system designed to be able to provide a variety of information and multimedia contents services through high speed wireless Internet access via various user terminals. In this paper, we introduce the WiBro system and present designed logical structure of WiBro Access Terminal for the system. We propose a stable execution model preventing system failure generated by the inconsistency of the data manipulation. The model has the characteristic of eliminating the data inconsistency with accomplishing by using the delayed tasklet concept. Analytic model shows minimizing the service time for tasklet make the system stable against system failure.


Studied were the acute toxicity (albino mice and rats, chicken broilers), species specific tolerance (lambs, sheep, goats, pigs, calves, chicks, chickens), and subchronic toxicity (albino rats, pigs, pulets) of tiabendazole Pharmachim (TP). It was found that LD50 of TP at the oral application to albino mice, weighing 18-20 g was 2.7 g (2.14 divided by 3.40) per kg for albino rats weighing 120-200 g it proved technically undeterminable. For broilers at one month it was 4.0 g (2.54 divided by 6.28) per kg. LD50 of TP of the firm Merck Sharp and Dome for albino mice was 2.9 g (2.28 divided by 3.68), and for broilers -- 5.0 g (4.31 divided by 5.8) per kg. The lethal dose for lambs was 400 mg/kg, for sheep -- 800 mg/kg, for goats -- 500 mg/kg, and for calves -- 500 mg/kg. When treated with amounts of 450 and 850 mg/kg pigs vomited. The same was true of drugs when offered the preparation at the rate of 300 mg/Kg chicks and chickens tolerated amounts of 500 mg/kg. TP was well tolerated by pigs, rats, and pullets when given with the feed for 30 days in 0.1 per cent conc.; in 0.4% conc. (pigs), 0.5% (albino rats), 0.3% (pullets), and 1% (albino rats and pullets) led to the arrest of growth and rise of transaminases and urea in the blood serum (rats and pigs) and the adverse effect of the red blood picture (rats, pigs, and pullets). Histologically, there were vascular troubles and granular degeneration that predominated in the kidneys, and were more slightly expressed in the remaining parenchymal organs.


The article considers the concept of legal liability and shows how pragmatist legal thinkers (1) reshaped it in the light of their philosophical externalism and (2) developed an economic analysis of it that is certainly stimulating but raises some serious concerns. The main characters of this story are Oliver Holmes for the classical pragmatist reshaping of the concept, and Learned Hand and Richard Posner for the more recent economic analysis of it. The paper suggests that, despite those concerns, that pragmatist reshaping was, and still is, welcome.


The number of patients with hypertension in Gianyar Regency tent to increase in recent years. Hypertension is the first among the tenth rank from the most common diseases, with 23% cases according to the priority scale. Hypertension treatment and management include prevention, early diagnosis, diagnosis with therapy, and screening to detect early hypertension disease. This screening includes elderly >40 years old who come to Public Health Centre in September 2021. The screening uses a questionnaire to uphold the diagnosis of hypertension disease by using a digital tensimeter as the gold standard. Based on World Health Organisation in 2018, which said it would be confirmed as hypertension if systolic ≥140 mmHg or diastolic ≥90 mmHg. 86% of 255 respondents were diagnosed with hypertension, that's 40% were >65 years old, 75% were female, and 31% worked as housewives. The screening tool with a question list of dizziness has a sensitivity value of 99%, a specificity value of 73% with a Positive Predictive Value (PPV), and each value of Negative Predictive Value (NPV) is 96% and 89%, respectively. Headache contains a sensitivity value of 90%, a specificity of 100%, with PPV value of 100% and NPV value of 61%. The combination of symptoms of dizziness and headache has a sensitivity value of 76%, and a specificity value of 82%, with PPV of 96% and NPV of 36%. Clinical symptoms are considered an early diagnosis of hypertension. If people who experience complaints of dizziness, headaches, or a combination of the two should immediately check their blood pressure as early as possible.


Pulsed electron-beam deposition (PED) is a recently developed pulsed energy ablation/deposition technique with distinct advantages for its cost effectiveness, nature of the electron-material interactions, and large-scale production. By the proper control of the ablation/deposition parameters, one can produce high purity quantum dots and thin films in situ in vacuum chamber. Further, PED can also be used for unique material syntheses by introducing reactive gases in the chamber. However, little systematic work has been done to demonstrate PED's potential applications except for few on film and nanoparticle fabrications. Particular efforts are made here to study the spatial variations of the deposited materials.


Objective The European Increlex® Growth Forum Database Registry monitors the effectiveness and safety of recombinant human insulin-like growth factor-1 (rhIGF1; mecasermin, Increlex®) therapy in patients with severe primary IGF1 deficiency (SPIGFD). We present data from patients with and without a reported genetic diagnosis of Laron syndrome (LS). Design Ongoing, open-label, observational registry (NCT00903110). Methods Children and adolescents receiving rhIGF1 therapy from 10 European countries were enrolled in 2008–2017 (n = 242). The treatment-naïve/prepubertal (NPP) cohort (n = 138) was divided into subgroups based on reported genetic diagnosis of LS (n = 21) or non-LS (n = 117). Multivariate analysis of the NPP-non-LS subgroup was conducted to identify factors predictive of growth response (first-year-height standard deviation score (SDS) gain ≥ 0.3). Assessments included change in height and weight over 5 years and adverse events (AEs). Results Height SDS gain from baseline was greater in the NPP-LS than the NPP-non-LS subgroup after 1 years' treatment (P < 0.05). In the NPP-non-LS subgroup, 56% were responders; young age at baseline was a positive independent predictive factor (P < 0.001). NPP-non-LS-responders and the NPP-LS subgroup had a similar mean age (6.07 years vs 7.00 years) at baseline and height SDS gain in year 1 (0.64 vs 0.70), although NPP-non-LS-responders were taller (P < 0.001) at baseline. BMI SDS changes did not differ across subgroups. Treatment-emergent AEs were experienced by 65.3% of patients; hypoglycaemia was most common. Conclusions In most NPP children with SPIGFD, with or without LS, rhIGF1 therapy promotes linear growth. The safety profile was consistent with previous studies.


Optical coherence tomography (OCT) is considered a key research tool to monitor neurodegenerative processes in CNS disorders. This is particularly applicable to multiple sclerosis (MS), in which retinal changes (peripapillary retinal nerve fiber layer and ganglion cell–inner plexiform layer [GCIPL] thicknesses) tend to reflect MRI markers of CNS damage and atrophy, especially in eyes not affected by previous optic neuritis.1


The aim of this study is to examine the perceptions of preschool teachers on gender roles and classroom practices in a comparative manner. Qualitative research method was used in this study. The participants of the study are preschool teachers working in Turkey and Turkish Republic of Northern Cyprus. In this study, convenience sampling method was used. The study group comprised 21 preschool teachers volunteering to participate and provided written consent. The data were collected through an interview schedule that comprised 9 semi structured questions. The results obtained from teachers in Turkey and Turkish Republic of Northern Cyprus showed teachers showed gender stereotypical behaviors in their classrooms in both countries. According to the teacher perceptions, women are passive, fragile and emotional while men are independent and powerful. It can be concluded that teachers in both countries have practices aimed to prevent the development of gender prejudices in children.


Two sepharose-bound 1-deoxynojirimycin N-alkyl derivatives, N-(9-carboxynonyl)- and N-(11-carboxyundecyl)-deoxynojirimycin, were used for the affinity purification of acid beta-glucosidase (beta-Glc) from normal and type-1 Ashkenazi Jewish Gaucher disease (AJGD) sources. The capacities of these nondegradable inhibitor supports were 0.5 and 0.75 mg of normal beta-Glc/ml of settled gel, respectively. The purified normal enzyme (14-18% yield) had a specific activity of 1.6 X 10(6) nmol/h/mg protein and was homogeneous as evidenced by a single protein species of Mr = 67,000 on sodium dodecylsulfate-polyacrylamide gel electrophoresis and reverse phase high-performance liquid chromatography (HPLC). Microsequencing demonstrated a single N terminus, and the sequence of the first 22 N-terminal amino acids was colinear with that predicted from the beta-Glc cDNA. Amino acid composition analyses of beta-Glc revealed a high content (35%) of hydrophobic amino acids. The N-decyl-deoxynojirimycin support facilitated the purification of the residual enzyme from type-1 AJGD spleen to about 7,500-fold in four steps with a yield of about 11%. These new affinity supports provided improved stability, capacity and/or specificity compared to other affinity or HPLC methods for purifying this lysosomal glycosidase.


Background A promising strategy to create stimuli-responsive gene delivery systems is to exploit the redox gradient between the oxidizing extracellular milieu and the reducing cytoplasm in order to disassemble DNA/cationic lipid complexes (lipoplexes). On these premises, we previously described the synthesis of SS14 redox-sensitive gemini surfactant for gene delivery. Although others have attributed the beneficial effects of intracellular reducing environment to reduced glutathione (GSH), these observations cannot rule out the possible implication of the redox milieu in its whole on transfection efficiency of bioreducible transfectants leaving the determinants of DNA release largely undefined. Methodology/Principal Findings With the aim of addressing this issue, SS14 was here formulated into binary and ternary 100 nm-extruded liposomes and the effects of the helper lipid composition and of the SS14/helper lipids molar ratio on chemical-physical and structural parameters defining transfection effectiveness were investigated. Among all formulations tested, DOPC/DOPE/SS14 at 25∶50∶25 molar ratio was the most effective in transfection studies owing to the presence of dioleoyl chains and phosphatidylethanolamine head groups in co-lipids. The increase in SS14 content up to 50% along DOPC/DOPE/SS14 liposome series yielded enhanced transfection, up to 2.7-fold higher than that of the benchmark Lipofectamine 2000, without altering cytotoxicity of the corresponding lipoplexes at charge ratio 5. Secondly, we specifically investigated the redox-dependent mechanisms of gene delivery into cells through tailored protocols of transfection in GSH-depleted and repleted vs. increased oxidative stress conditions. Importantly, GSH specifically induced DNA release in batch and in vitro. Conclusions/Significance The presence of helper lipids carrying unsaturated dioleoyl chains and phosphatidylethanolamine head groups significantly improved transfection efficiencies of DOPC/DOPE/SS14 lipoplexes. Most importantly, this study shows that intracellular GSH levels linearly correlated with transfection efficiency while oxidative stress levels did not, highlighting for the first time the pivotal role of GSH rather than oxidative stress in its whole in transfection of bioreducible vectors.


Reliable feature correspondence between frames is a critical step in visual odometry (VO) and visual simultaneous localization and mapping (V-SLAM) algorithms. In comparison with existing VO and V-SLAM algorithms, semi-direct visual odometry (SVO) has two main advantages that lead to state-of-the-art frame rate camera motion estimation: direct pixel correspondence and efficient implementation of probabilistic mapping method. This paper improves the SVO mapping by initializing the mean and the variance of the depth at a feature location according to the depth prediction from a single-image depth prediction network. By significantly reducing the depth uncertainty of the initialized map point (i.e., small variance centred about the depth prediction), the benefits are twofold: reliable feature correspondence between views and fast convergence to the true depth in order to create new map points. We evaluate our method with two outdoor datasets: KITTI dataset and Oxford Robotcar dataset. The experimental results indicate that improved SVO mapping results in increased robustness and camera tracking accuracy. The implementation of this work is available at https: //github.com/yan99033/CNN-SVO


We report a case of chromophobe renal cell carcinoma in a 39-year-old woman. The squash cytological specimen showed tumor cell clusters composed of large-sized polygonal cells with a low nucleocytoplasmic ratio. The cytoplasm was characteristically cloudy and reticular or eosinophilic granular. Occasionally, a perinuclear halo was visible. The nuclei were spherical and contained small nucleoli. The unique clinicopathological and molecular biological characteristics of chromophobe renal cell carcinoma make cytology a very useful tool for its correct diagnosis.


Patient and public involvement (PPI) has emerged as a key consideration for organisations delivering health research and has spawned a burgeoning literature in the health and social sciences. The literature makes clear that PPI in health research encompasses a heterogeneous set of practices with levels of participation and involvement ranging from relatively minimal contributions to research processes to actively driving the research agenda. In this article, we draw on the work of Jurgen Habermas to explore the ways in which PPI was accomplished in a cancer research setting in England. Drawing on ethnographic data with PPI participants and professional researchers, we describe the ways in which the life-world experiences of PPI participants were shaped by the health research system. We argue that PPI in this setting is less about exploring differences with regard to a plurality of expertise and more about simply watching or supporting the professional researchers at work.


At the end of the nineties the munition for the TOW weapon system in use at The Netherlands army, has to be replaced. The Life of Type of The Tow carrier ends in 2005. The long range anti armour study is to gain insight into the possibilities and limitations for the Netherlands army to deploy future (time period 1995-2000) weapon systems in the long range anti armour battle. The first study results are expected at the end of 1989. The study is sponsored by the Netherlands army and is carried out by the three National Defense Research Organization Laboratories: The Physics and Electronics Laboracory TNO, the Prins Maurits Laboratory TNO and the Institute for Perception TNO. The study considers two categories of candidate weapon systetms namely line of sight and non line of sight weapon systems. The Operations Research effort within this study is mainly focussed on analyzing and comparing the effectiveness of the different weapon systems options. Therefore wargaming, terrain analysis and combat simulation techniques are used. In the paper these techniques will be presented and some results will be shown.


Background: By complexing poly (ADP-ribose) (PAR) in reaction to breaked strand, PAR polymerase1 (PARP1) acts as the key enzyme participated in DNA repair. However, recent studies suggest that unrepaired DNA breaks results in persistent PARP1 activation, which leads to a progressively reduce in hexokinase1 (HK1) activity and cell death. So the molecular mechanism of PARP1 remains elusive. Methods: 212 colorectal cancer (CRC) patients who had the operation at our hospital were recruited. Used immunohistochemistry to evaluate PARP1 expression. Survival analysis was calculated based on PARP1 expression.Results: Compared with matching adjacent noncancerous tissue, in CRC tissue, PARP1 expression was remarkably higher, which was correlated with the degree of differentiation, TNM stage, depth of invasion, distant metastasis, and 5-year survival. Furthermore, after constructing CRC cell lines stably expressing low or high PARP1, we found that PARP1 overexpression promoted proliferation, and proved PARP1 interacted with XRCC2 in CRC cells by immunoprecipitation (IP) analysis.Conclusions: PARP1 was upregulated in CRC cells and promoted its proliferation of colorectal cancer cells. Furthermore, PARP1 expression status was significantly related to some clinicopathological features and 5-year survival.


Revision arthroplasty for femoral stem breakage can be challenging. We report a new method for the removal of the distal stem segment performed in 6 cases between 2004 and 2008. After extracting the proximal part of the femoral component, the femoral canal was opened at the knee joint and a modified intramedullary nail was used to dislodge the distal stem under fluoroscopic control. In five cases the surgery was uneventful. In one case femoral perforation occurred due to the contour of the cement mantle at the tip of the stem. In the postoperative period all patients progessed well. Removal of a broken stem using our method has limited indications, and it is not recommended in septic cases or when the cement mantle at the tip of the stem has an oblique contour. It also requires opening of the knee joint, but the technique is simple, saves surgical time and in selected cases it does not weaken the femur.


Diana Evans is a writer from mixed origins. Her multiracial family has provided her with the basic framework to write 26a. This research tackles issues of non-belonging and sense of restoration in the novel, which the characters feel after being dislocated and pushed to live in different locations or with different people. The notions of belongingness and diaspora have received considerable attention from literary and social scholars as different diasporic writers start to bring out their experiences and articulate their worldviews. The issues of cultural diversity, belonging and diaspora are found in Evans' novel 26a. In this novel, the sense of home and feeling of belonging overwhelm the narrative as protagonists start to mix with more than one culture. According to their various origins. This study sheds light on the cultural diversity of the novel 26a and its impact on the identity and sense of belonging of the characters.


The greatest threat to the OFDM system is the loss of orthogonality between subcarriers due to the carrier frequency offset (CFO) which results in significant performance degradation. In addition to this last problem was the effect of propagation over multipath fading channel. Hence, both the channel and the CFO need to be estimated and corrected at the receiver for subsequent symbol detection. A new joint semi-blind CFO and channel estimation methods for OFDM systems based on maximum-likelihood (ML) is investigated in this paper. The proposed algorithm is based on virtual subcarriers (VSCs) and on a new design of pilot patterns in OFDM blocks. The simulation results are given to verify the validity of the proposed methods.


Loss of cognitive function in the aging population, particular those with Alzheimer disease, presents unique challenges to health practitioners. For the dental practitioner these include management of periodontal diseases, caries, and other dental conditions in this special population. It is well established in the cognitively impaired patient that a lack of adherence to dental hygiene routines and professional care leads to increases in the prevalence and severity of these dental conditions, leading to increased loss of teeth. More recent evidence has indicated a possible role of the microbiota of dental plaque associated with periodontal diseases in the development and progression of Alzheimer disease, thereby supporting a two-way interaction of these two diseases. New therapies are needed to address the potential upstream events that may precede overt signs of Alzheimer disease. One of these approaches would be to target these various bacterial, viral, and other microbial pathogens associated with periodontal disease that can translocate into the bloodstream and then to distal sites, such as the brain. Such microbial translocation would lead to local inflammation and buildup of the hallmark signs of Alzheimer disease, including amyloid beta deposits, tau fragmentation and tangles, breakdown of host protective molecules, such as the apolipoproteins, and neuron toxicity. In this review, evidence for the biological basis of the role of the periodontal disease microflora on the initiation and progression of Alzheimer disease will be presented with a focus on the potential role of the keystone pathogen Porphyromonas gingivalis with its family of gingipain enzymes. The various mechanisms for which P. gingivalis gingipains may contribute to the initiation and progression of Alzheimer disease are presented. Small-molecule inhibitors of these gingipains and their effects on reducing biological markers of Alzheimer disease may have beneficial effects for the initiation and progression of loss of cognitive function in Alzheimer disease. In addition to these targeted therapies for specific periodontal pathogens, considerations for the dental practitioner in applying more general approaches to reducing the periodontal plaque microflora in the management of the cognitively impaired patient are discussed for this special population.


In this study, a wavelength-shift-based colorimetric sensing approach for the peroxide number of milk powder using CsPbBr3 perovskite nanocrystals (CsPbBr3 NCs) has been developed. Through the fat extraction, REDOX reactions and halogen exchange, as well as the optimized experimental conditions, a colorimetric sensing method was established to determine the peroxide number of milk powder samples. The integrated process of milk powder fat extraction and the REDOX process greatly shortened the determination time. This colorimetric method has a good linear correlation in the range of the peroxide number from 0.02 to 1.96 mmol/kg, and the detection limit was found to be 3 μmol/kg. This study further deepens the application prospect of wavelength-shift-based colorimetric sensing using CsPbBr3 NCs.


Background Systematic reviews examining associations of depressive disorder with coronary heart disease and stroke produce mixed results. Failure to consider reverse causation and dose–response patterns may have caused inconsistencies in evidence. Design This prospective cohort study on depressive disorder, coronary heart disease, and stroke analysed reverse causation and dose–response effects using four 5-year and three 10-year observation cycles (total follow up 24 years) based on multiple repeat measures of exposure. Methods Participants in the Whitehall II study (n = 10,036, 31,395 person-observations, age at start 44.4 years) provided up to six repeat measures of depressive symptoms via the 30-item General Health Questionnaire (GHQ-30) and one measure via Center for Epidemiologic Studies Depression Scale (CES-D). The cohort was followed up for major coronary events (coronary death/nonfatal myocardial infarction) and stroke (stroke death/morbidity) through the national mortality register Hospital Episode Statistics, ECG-screening, medical records, and self-report questionnaires. Results GHQ-30 caseness predicted stroke over 0–5 years (age-, sex- and ethnicity-adjusted HR 1.60, 95% CI 1.1–2.3) but not over 5–10 years (HR 0.94, 95% CI 0.6–1.4). Using the last 5-year observation cycle, cumulative GHQ-30 caseness was associated with incident coronary heart disease in a dose–response manner (1–2 times a case: HR 1.12, 95% CI 0.7–1.7; 3–4 times: HR 2.06, 95% CI 1.2–3.7), and CES-D caseness predicted coronary heart disease (HR 1.81, 95% CI 1.1–3.1). Conclusions There was evidence of a dose–response effect of depressive symptoms on risk of coronary heart disease. In contrast, prospective associations of depressive symptoms with stroke appeared to arise wholly or partly through reverse causation.


On Dec. 15, 2000, Congress approved the use of single-stock futures. This essay analyzes some of the policy issues related to that approval. In particular, I discuss (1) the benefits and costs of margin rules applicable to single-stock futures, (2) the amendments to the securities laws to cover single-stock futures in areas such as insider trading and market manipulation, and (3) some potential benefits associated with the use of single-stock futures to avoid restrictions on shorting stock (e.g., the elimination of so-called "parent-subsidiary" anomalies, as when 3Com was worth less than Palm even though 3Com owned 95 percent of Palm's stock).


Although cancer genomes often contain complex genomic rearrangements, its impact on tumorigenesis is still unclear, especially when they are involved in non-coding regions. Understanding 3D genome architecture is crucial for uncovering the impacts of genomic rearrangements. Here, we present InfoHiC, a method for predicting 3D genome folding and cancer Hi-C from complex genomic rearrangements. InfoHiC provides distinct interaction views of multiple contigs from the cancer Hi-C matrix. We then validated cancer Hi-C prediction using breast cancer cell line data and found contig-specific interaction changes. Moreover, we applied InfoHiC to patients with breast cancer and identified neo topologically associating domains and super-enhancer hijacking events associated with oncogenic overexpression and poor survival outcomes. Finally, we applied InfoHiC to pediatric patients with medulloblastoma, and found genomic rearrangements in non-coding regions that caused super-enhancer hijacking events of medulloblastoma driver genes (GFI1, GFI1B, and PRDM6). In summary, InfoHiC can predict genome folding changes in cancer genomes and may reveal therapeutic targets by uncovering the functional impacts of non-coding genomic rearrangements.


Severe Congenital Neutropenia (SCN) is characterized as a deficiency of mature neutrophils, which leads to recurrent bacterial and fungal infections. Mutations in the Ela2 gene predominate in SCN, but Ela2 mutation in mice does not recapitulate SCN. The Growth factor independent-1 (Gfi1) transcriptional repressor regulates Ela2. The N382S mutation in Gfi1 is associated with human SCN. Unlike Ela2, genetic deletion of Gfi1 results in murine neutropenia. Here we show that the human-SCN-associated Gfi1N382S mutant blocks murine granulopoiesis in a Csf1 dependent manner. Gfi1 functions as a rate-limiting granulopoietic molecular switch, and the DNA-binding-defective Gfi1N382S mutant acts as a dominant negative to block granulopoiesis by selectively derepressing a subset of Gfi1 target genes. One gene repressed by Gfi1 and derepressed by Gfi1N382S is the macrophage colony stimulating factor (Csf1). Chromatin immunoprecipitation and electrophoretic mobility shift analyses demonstrate direct binding of Gfi1 to the Csf1 promoter. Importantly, both antibody absorption of Csf1 and genetic deletion of Csf1 prevent the Gfi1N382S-mediated block to granulopoiesis. These data represent the first identified Gfi1 target gene to be critically required for SCN-like phenotypes engendered by Gfi1N382S, and suggest new potential treatment avenues for Gfi1-mutant SCN patients.


Plasma concentrations of LH, FSH, progesterone and total oestrogens were determined (by radioimmunoassay) throughout late pregnancy and lactation in samples taken by cardiac catheter from 10 Camborough hybrid sows. At 2-3 weeks post partum, 5 were housed individually with their litters (Group I) and 5 grouped with their litters, a boar being introduced 1 day later (Group II). Plasma progesterone fell 1-2 days per partum and oestrogens at parturition, each remaining low in early lactation. Plasma LH was undetectable in most samples in this period, but FSH fell slightly during parturition, showing signs of resurgence from Day 10 post partum. Group I sows remained in lactational anoestrus until weaning. In Group II there was increased plasma LH activity, and all Group II sows displayed oestrus during lactation. Only one farrowed to service at the lactational oestrus; of the remainder, oestrus in one was clearly anovulatory, and in two others was incomplete or atypical judged by plasma progesterone concentrations. The data suggest that whilst oestrus can be induced by appropriate lactation management, poor conception rates to service at this oestrus may be due to the absence or impairment of ovulation.


Purpose : Human umbilical vein endothelial cells(HUVECs) play an important role in regulating blood flow by releasing vasoactive substances. It has been reported that endothelial impairment and dysfunction might be a primary cause of placental vascular disease, which is manifested clinically as preeclampsia in mother and intrauterine growth restriction in fetus. Furthermore, the frequency of apoptotic changes is increased in umbilical and placental tissues from growth-restricted pregnancies. However, the various mechanisms of umbilical endothelial cell apoptosis have not been broadly proposed. We investigate the effects of amiloride derivatives on apoptotic death of HUVECs and identify their ionic mechanism. Methods : HUVECs were purchased from Clonetics, and cultured on endothelial cell growth medium. MTT assay and flow cytometry were used for assessing cytotoxic effect and confirming the apoptosis. Changes in intracellular ion concentrations were measured with specific fluorescent dyes and fluorescence imaging analysis system. Results : Amiloride derivatives elicited cytotoxic effects on HUVECs with dose-dependent manners and the rank order of potency is HMA(IC50 11.2 μM), MIA>EIPA>>amiloride. HMA-induced cytotoxicity is dependent on extraand intracellular pH, that is, increase extraand intracellular pH augmented the cytotoxic effects of HMA. HMA dose-dependently reduced intracellular major ions, such as K + and Cl . Interestingly, the depletion of intracellular ions induced by HMA was also significantly enhanced at alkaline extracellular pH. Conclusion : Amiloride derivatives induce apoptosis of HUVECs with dose and pH dependent manners. They reduce intracellular K + and Cl concentration, which is also extracellular pH dependent. (J Korean Pediatr Soc 2003;46:56-66)


We study the effects of a positive export shock on labor allocation between the informal, microenterprise sector and the formal firm sector in a low-income country. The United States-Vietnam Bilateral Trade Agreement led to large reductions in US tariffs on Vietnamese exports. We find that the share of manufacturing workers in Vietnam in the formal sector increased by 5 percentage points in response to the US tariff reductions. The reallocation was greater for workers in more internationally integrated provinces and for younger cohorts. We estimate the gap in labor productivity within manufacturing across the informal and formal sectors. This gap and the aggregate labor productivity gain from the export-induced reallocation of workers across the two sectors are reduced when we account for worker heterogeneity, measurement error, and differences in labor intensity of production. (JEL F16, J24, O14, O17, O19, P23, P33)


A method for the determination of short time changes of Q factor and resonance of a cavity has been developed. The method is based on the observation of the change in reflection coefficient. As long as the cavity is coupled undercritically there always exist two frequencies at which no change of the reflection coefficient occurs. The measurement of these frequencies is sufficient for evaluating the changed values of the unloaded Q and the resonant frequency assuming no change of the external Q during perturbation. This assumption can be made in most cases of application. If there also exists a perturbation of the external Q, the value of the changed reflection coefficient must be measured at any additional freqnency preferably at the resonant frequency of the unperturbed cavity. Experimental results demonstrate the applicability of this method.


The evolution of genes is usually studied and reconstructed at the sequence level, that is, by comparing and aligning their genomic, transcript or protein sequences. However, including the exon–intron structure of genes in the analysis can provide further and useful information, for example to draw reliable phylogenetic relationships left unsolved by traditional sequence-based evolutionary studies, or to shed further light on patterns of intron gain and loss. In spite of this, no tool especially devised for this task is currently available. In this work we present Exalign, an algorithm designed to retrieve, compare and search for the exon-intron structure of existing gene annotations, that has been implemented in a software tool freely accessible through a web interface as well as available for download. We present different applications of our method, from the reconstruction of the evolutionary history of homologous gene families to the detection of as of today unknown cases of intron loss in human and rodents, and, remarkably, two never reported intron gain events in human and mouse. The web interface for accessing Exalign is available at http://www.pesolelab.it/exalign/ or http://www.beacon.unimi.it/exalign/


A method for setting the offset of a time stamp, in which the offset value that is added to the time stamp is automatically controlled according to a transmission window value in a packetizing system for a high speed serial bus, and an apparatus therefor are provided. An apparatus for transmitting a packet in a packetizing system for a high speed serial bus includes an adder 213 for generating a time stamp value by adding a cycle time value which is a data segmentation size to an offset value 214 in consideration of data delay time and/or the amount of jitter, a memory 218 for storing the input data according to the time stamp in units of packets, a window generator 220 for estimating the time stamp value generated by the adder 213 and determining a transmission time range, and a controller 216 for adding the time stamp generated by the adder to the data in units of packets, which are stored in the memory 218, outputting the data in units of packets, to which the time stamp is added, and controlling the offset value when overflow generated by read and write timing errors is detected in the memory.


Abstract. Neutral gas atmosphere bends and delays propagation of microwave signals in satellite-based navigation. Weather prediction models can be used to estimate these effects by providing three-dimensional refraction fields to ray-trace the signal delays. In this study, a global numerical weather prediction model (Open Integrated Forecasting System (OpenIFS) licensed for Academic use by the European Centre for Medium-Range Weather Forecast) is used to generate the refraction fields. The ray-traced slant delays are supplied as such – in contrast to mapping – for an orbit solver (GROOPS (Gravity Recovery Object Oriented Programming System) software toolkit of Graz University of Technology) which applies the raw observation method. Here we show that such a close coupling is possible without need for major additional modifications in the solver codes. The main finding here is that the adopted approach provides a very good a priori model for the atmospheric effects on navigation signals. We suspect that removal of the intermediate mapping step allows us to take advantage of the local refraction field asymmetries in the GNSS signal processing. Moreover, the direct coupling helps in identifying deficiencies in the slant delay computation because the modeling errors are not convoluted in the mapping procedures. These conclusions appear robust, despite the relatively small data set of raw code and phase observations covering the core network of 66 ground-based stations of the International GNSS Service over 1-month periods in December 2016 and June 2017. More generally, the new configuration enhances our control of geodetic and meteorological aspects of the orbit problem. This is pleasant because we can, for instance, regulate at will the weather model output frequency and increase coverage of spatiotemporal aspects of weather variations. The direct coupling of a weather model in precise GNSS orbit determination presented in this paper provides a unique framework for benefiting even more widely than previously the apparent synergies in space geodesy and meteorology.


OBJECTIVE
To evaluate the efficacy of a vapocoolant spray to provide local anaesthesia for calves during ear tagging and ear notching.

STUDY DESIGN
Randomized study.

ANIMALS
Twenty Black Angus calves aged 4-16 weeks old.

METHODS
Temperature validation studies using thermocouples and a temperature data logger were conducted on dead and live tissue to determine optimal spray distance and duration to achieve tissue anaesthesia (<10 °C). A behavioural trial was conducted to assess efficacy for ear tagging and ear notching. Calves (n = 20) were randomly assigned to the vapocoolant spray (VS) or the water spray (WS) group. A 3 second spray was administered from 10 cm to both sides of the ear immediately prior to ear tagging and ear notching. A numerical rating scale (NRS) was used to score behavioural response to each procedure, with responses categorized from 0 (no response) to 3 (severe).

RESULTS
Temperature and tissue validation studies indicated that a vapocoolant spray reduced dead and live tissue temperature to below nociceptive threshold levels (10 °C) for 10-16 seconds. Univariate analysis indicated that ear notching was more painful than ear tagging [odds ratio (OR) = 19.2, 95% confidence interval (CI): 5.34-68.99, p < 0.001]. When adjusted for the multivariate model, there was a significant effect of treatment, with WS calves showing higher pain response scores than VS calves (OR = 4.08, 95% CI: 1.34-12.42, p = 0.011). Ear notching resulted in greater pain response scores than ear tagging (OR = 23.19, 95% CI: 6.18-87.05, p < 0.001).

CONCLUSIONS
and clinical relevance Vapocoolant spray induced local anaesthesia and significantly reduced the pain response to ear tagging and ear notching in calves. Ear notching is more painful than ear tagging. Cryoanaesthesia is an effective option for reducing the perioperative pain associated with these simple husbandry procedures.


Using deep learning architectures, disease detection from medical images such as brain images, chest X-rays, and cytology images is used in many areas. With the use of deep learning architectures in the faster detection of diseases, the possibility of starting treatment early increases. Benign and malignant cell clusters are formed from body cavity effusions. Diagnosis is made by visual inspection of images of centrifuged body fluid effusions deposits. Bad cells are usually abundant in body cavity fluids. Here, separating malignant cells from the proliferation of mesothelial cells or inflammatory cells is the problematic part. In this case, a classifier can be used to distinguish benign mesothelial or inflammatory cells from malignant carcinoma cells. In this study, using Convolutional Neural Network (CNN) based models, the detection of benign and malignant cells from cytology images consisting of fluids in the body cavity will be an aid to pathologists by detecting early and accurately. The dataset contains 693 images with two classes of 256x192 benign and malignant cells. These images are trained using AlexNet, ResNet50, DarkNet53, GoogleNet, MobileNetv2, and EfficientNetb0 architectures. As a result of the test phase, the highest classification accuracy was obtained in the DarkNet53 architecture with 98.56%.


Thirty partial coding DNA sequences (CDSs) of the spike gene of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) were obtained from nasopharyngeal swab samples collected in March to July 2021 in Dhaka, Bangladesh, during the second wave of the coronavirus disease 2019 (COVID-19) pandemic, using Sanger sequencing technology. Sequence analysis showed the presence of multiple WHO-designated variants of concern (VOCs), including Alpha, Beta, Gamma, and Delta, with predominant circulation of Delta variants during that period. ABSTRACT Thirty partial coding DNA sequences (CDSs) of the spike gene of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) were obtained from nasopharyngeal swab samples collected in March to July 2021 in Dhaka, Bangladesh, during the second wave of the coronavirus disease 2019 (COVID-19) pandemic, using Sanger sequencing technology. Sequence analysis showed the presence of multiple WHO-designated variants of concern (VOCs), including Alpha, Beta, Gamma, and Delta, with predominant circulation of Delta variants during that period.


Parapneumonic effusions or empyemas are frequently seen in patients with lower respiratory tract infections. The condition is associated with significant morbidity and mortality. Since Gram stains and bacterial cultures are usually negative, treatment focuses on empiric antibiotic treatment and chest tube drainage. The role of intrapleural fibrinolytics is still a matter of debate. Medical thoracoscopy is a simple and effective therapeutic alternative associated with better outcome and fewer complications than conservative treatment. Furthermore, it can be performed in analgo-sedation in a bronchoscopy suite. Video-assisted thoracic surgery carries the advantage of providing optimal visibility of the pleural cavity, thus allowing better debridement. Thoracotomy is the treatment of choice when thoracoscopic cleaning is not satisfactory.


This chapter looks at a study carried out among 80 small and medium sized enterprises (SMEs) in two Canadian cities, Montreal and Winnipeg, based on a survey and case studies, which show the importance of innovation among Canadian SMEs. These innovations in turn create new demands for skill development, both through formal training and in informal activities. The outcomes of the study show two significant trends. First, an uneven development of learning activities among SMEs is related not only to the size of firms, but also to their orientation towards innovation and shared productivity measures. Second, because they do not have enough internal resources and flexibility to drive productivity growth through learning and training by themselves, SMEs need some form of group based mechanisms to solve this structural problem. However, it is noted that participation of unskilled employees in both formal and informal learning remains an important challenge for the great majority of SMEs.


Distance learning is acquiring a role that becomes more and more important with the huge diffusion of the Internet and related technologies. This paper proposes a novel heuristic intelligent distance learning platform based on information technology and cloud computing. The proposed platform that are committed to accessibility assure that course designers understand the program's commitment to accessibility, have access to guidelines and resources. Experimental results show that the proposed platform can effectively improve the system throughput and reduce the execution time.


The purpose of a mineral comminution circuit with a ball mill running in closed-loop with a hydrocyclone classification battery is to feed the downstream process with the target pulp particle size. Maintaining the optimal particle size in the flotation feed can significantly improve plant cash flow. In particular, reducing the amount of coarse material is often a major challenge. Existing instrumentation to provide on-line particle size measurement is considered standard equipment in most modern concentrator plants. However, its very low availability, in spite of high maintenance requirements, and its relatively slow update rate have made it difficult to use the information for real-time automatic control of the grind and classification circuit to achieve the target particle size for the flotation feed. This paper introduces two novel and robust technologies developed by CiDRA Minerals Processing that address this challenge by providing high reliability and very low maintenance systems for online measurement of coarse material in the overflow of individual hydrocyclones. The first system is noninvasive and measures pebbles and rocks greater than 6mm. The second system is a wetted sensor design with no moving parts and provides a real-time trend of the desired target grind size parameter, such as P80 or %+150 um. Both systems have simple robust designs and measure in the primary overflow stream of the individual hydrocyclone. They do not require sampling and associated sample transfer piping circuits that are prone to plugging, thus avoiding high maintenance requirements. The second system will be described in detail along with its implementation in a robust control scheme in a major copper concentrator in North America. Plant data will be shown that demonstrate that the very high availability, achieved with very low maintenance, has enabled improved process control, such maintaining throughput and ball mill target power while reducing grind size.


Central nervous system biogenic amine metabolism was studied in 35 children suffering from autism, atypical development, epilespy, and movement disorders. After oral administration of probenecid, a membrane blocking compound, a cerebrospinal fluid (CSF) sample was obtained for assay of homovanillic acid (HVA), 5-hydroxyindoleacetic acid (5HIAA), and probenecid. The concentrations of HVA and 5HIAA in the CSF are thought to reflect the rate of formation in the brain of their parent amines, dopamine and serotonin, respectively. There are statistically significant differences in CSF HVA and 5HIAA levels between the psychotic and epileptic children. The HVA and 5HIAA are significantly correlated with each other. Each of these acid metabolites covaries with the CSF levels of probenecid and interpretation of the significance of CSF HVA and 5HIAA requires simultaneous measurement of probenecid concentration.


Mitogen-activated protein kinases (MAPK) allow a cell to respond to external signals to grow, divide or undergo apoptosis. One example is the c-Jun N-terminal kinase 2 (JNK2). This protein is unique in that it can autophosphorylate, or phosphorylate itself. It was found that these proteins tend to form aggregates of four, or tetramers, when inactive and remain as single units, or monomers, when active. In glioblastoma and lung carcinoma cells, JNK2s are reported to be constitutively, or always, active. This study aimed to investigate a selection of JNK2 mutations determine which of these mutations can alter JNK2 activity and oligomerization state. Results from size-exclusion chromatography and light scattering analysis (SEC-LS) suggested that while the wild type JNK2 exists as a mixture of monomers and tetramers, the activation loop chimera mutant (C177G/N179S) exists only as monomers. Additionally, phosphorylation assay analysis showed increased autophosphorylation activity of the activation loop chimera mutant compared to the wild type. These results suggest that the activation loop may be involved in the mechanism of JNK2 regulation. Elucidation of MAPK regulation mechanisms may allow more effective cancer therapy screening and increase overall understanding of tumor growth mechanisms.


The effects of habitual physical activity on physical fitness parameters and serum cholesterol profile were studied in middle-aged male workers. The subjects were 3376 middle-aged men (age: 30-59 yrs) who worked at two enterprises in HIROSHIMA Prefecture. As for physical fitness parameters, grip strength, vertical jump, side step, and step test scores were measured. Atherogenic index was calculated as (total Chol-HDL Chol)/(HDL Chol). Because daily physical activity mainly consists of physical activities during leisure time and working time, by using a questionnaire, physical activity during leisure time was assessed and categorized by frequency into three categories: 'frequently', 'sometimes', and 'seldom': and physical activity during work was categorized as 'high' or 'low' according to the average walking time per day during work. The effect of these physical activities on physical fitness parameters and serum cholesterol profile was evaluated by analysis of covariance (PC-SAS: GLM procedure) adjusting for several confounding factors such as age, body mass index, type of job, smoking and drinking habits. The main results are summarized as follows: 1) Physical activity during leisure time was positively related to vertical jump, side step, and step test score, independent of physical activity during working time, and 2) physical activity during leisure time was negatively associated to LDL-C and AI in the group with 'low' physical activity during work. These results show that in middle-aged male workers, even moderate or light physical activity during leisure time has some beneficial health promoting effects through changes in physical fitness and serum cholesterol profile.


Dr Simon Baynham examines a number of anti-colonial struggles and post-independence military conflicts and coups against the backdrop of the imperial withdrawal. By way of a preface to this series, he discusses some socio-economic and political similarities and differences between African countries. His next article will focus on the political, economic and security implications of recent geopolitical developments on the continent of Africa. In many aspects, Africa's enormous landmass of 30 million square kilometres - some 22 percent of the globe's total - is an area that defies rigorous descriptionption. Except for a slender isthmus of territory linking it to Asia Minor, the continent is completely surrounded by sea. Indeed, 33 of its mainland states have ocean contiguities.2 A century ago, Africa supported a population estimated at 100 million. Today that figure has reached 500 million, double the number for 1960 and growing at 3 per cent each year.


In most developed countries worldwide, the number of patients with chronic heart failure is growing, with 1–3% of the adult population suffering from this syndrome, rising to about 10% in the very elderly. Because the incidence of heart failure increases with age, its prevalence will greatly increase as our population ages. In the near future a large part of the western population will suffer from heart failure and society will be faced with the financial consequences. Heart failure is consuming about 1.5–2.5% of the health care budget, with approximately 70% of this being spent on hospitalisation.1 On average one in five patients is readmitted within 12 months, making heart failure one of the most common causes of hospitalisation in people over 65 years of age. In a recent international study comparing three states in the USA and three European countries, it was found that among a number of diagnoses, including diabetes, stroke, or hip fracture, the diagnoses of congestive heart failure and chronic obstructive pulmonary disease have the highest hospital readmission rates.2

Not only are readmission rates of heart failure patients higher compared to chronic medical conditions, but also the quality of life of these patients seems to be highly affected. Compared with the healthy general population, heart failure patients show a global reduction in quality of life in several domains (physical functioning, role functioning, and social functioning), reflecting the severe impact of congestive heart failure on daily life, even though some patients are in an ambulatory setting.3

Heart failure reduces quality of life more than any other chronic medical condition (for example, diabetes, arthritis, or chronic lung disease) and patients with multiple conditions have greater decrements in functioning and wellbeing than those with only one condition.3 This decrease in quality of life is not directly …


Introduction: Most of the diseases come up or get worsened with the results of staggering health condition of its survivors. It was happened in case of Covid pandemic too. It definitely had a deleterious impact on human health and economy. This certainly hint towards the need to implement a health promotion strategy during the period of convalescence. Convalescence is the period of recuperation of health after a serious illness or injury or weakness. The care given during this period are meant to improve immunity, body strength and vitality in a systematic manner by providing gradual nourishment and also to prevent further occurrence of the disease. Materials And Methods: A comprehensive literature search related to convalescent care and description related to basic principles of Ayurveda using all available Ayurvedic compendium, research papers, editorials and review papers from various databases were thoroughly screened, compiled, analyzed and presented in a systematic manner. Results And Discussion: Health is depended up on Bala. Convalescent care in Ayurveda comprises the practices that enhance Bala and Vyadhikshamatva and improve the quality of life after an illness/weakness, gradually bringing back to normalcy. In Ayurveda, the intention of convalescent care is to bring back Dhatusamya which was deranged by a disease or due to intense treatment Bheshajakshapita. Such a care is essential during some physiological conditions like Garbha kaala and Soothika kaala also.


A 3D computational fluid dynamics model of the human carotid bifurcation has been created to explore plaque excavation and plaque rupture. The model considers different degrees of atherosclerotic stenosis, the form of which is determined using computerised tomography scans of a patient with moderate plaque stenosis. The results suggest that 70% stenosis will diminish blood flow to the brain from 245 ml/min to 71 ml/min. Pressure in the 50% stenosis model is increased by only 3.3%, while pressure in the 70% and 80% stenosis models are increased by 8.8% and 15.4%, respectively. Starting at 30% stenosis, each increase of 10% stenosis increases the peak wall shear stress value by a factor of two. Severely elevated magnitudes in the product of the pressure and the wall shear stress gradient were found on the upstream face of the stenosis. In specific cases, these peaks can be correlated to excavation points observed clinically.


This article first describes the Japanese professional development practice of lesson study and its articulation within the Japanese educational system. Next, insights gained from an empirical study that explored the feasibility of lesson study in a U.S. setting are discussed. More specifically, challenges to lesson study practice are highlighted, with particular attention paid to the difficulties faced by American teachers in trying to adopt the research focus that is inherent in lesson study. The article concludes with reflections about what the study of lesson study can teach us about efforts to improve teaching, which, like lesson study, center on having teachers examine their practice or that of others.


Modeling Creativity (doctoral dissertation, 2013) explores how creativity can be represented using computational approaches. Our aim is to construct computer models that exhibit creativity in an artistic context, that is, that are capable of generating or evaluating an artwork (visual or linguistic), an interesting new idea, a subjective opinion. The research was conducted in 2008-2012 at the Computational Linguistics Research Group (CLiPS, University of Antwerp) under the supervision of Prof. Walter Daelemans. Prior research was also conducted at the Experimental Media Research Group (EMRG, St. Lucas University College of Art & Design Antwerp) under the supervision of Lucas Nijs.
Modeling Creativity examines creativity in a number of different perspectives: from its origins in nature, which is essentially blind, to humans and machines, and from generating creative ideas to evaluating and learning their novelty and usefulness. We will use a hands-on approach with case studies and examples in the Python programming language.


This work is done for improving the current international standard cross section of nuclear reaction. The features of covariance propagation in R-matrix model fitting for 7Li, 11B and 16O systems are researched systematically with Code RAC, and the results about propagation of non-diagonal elements of covariance matrix are presented. It is found that in R-matrix model fitting, short-energy-range parameters result in relatively smaller covariance propagation coefficient (CPC), medium and long-energy-range parameters produce relatively larger CPC. Especially the medium-energy-range component of systematic error plays very important role in propagation of covariance. In the evaluation procedure of nuclear data both long-energy-range component (LERC) and medium-energy-range component (MERC) of systematic error should be considered in experimental data-base file. Furthermore, these conclusions are suitable for the similar model fitting in other science fields.


Follow the six steps in this series to learn how to calculate your expenses and determine your financial goals. With this information, you can compare your expenses against your income to find out how to best budget your money. Fill out these worksheets to build your own spending plan. This revised publication collects all six steps of the Building a Spending Plan series in one document. Written by Nayda I. Torres, Josephine Turner, and Brenda C. Williams, and published by the UF Department of Family, Youth and Community Sciences, July 2012.


Regional sequence stratigraphic analysis revealed the presence of Paleocene(?)-Lower Eocene lowstand turbiditic deposits in Maracaibo Basin. The emplacements of the Lara nappes on the north during late Paleocene triggered the development of a foredeep in the northeastern part of the Maracaibo Basin. During the ensuing lowstand stage, siliciclastic sediments poured into the foredeep principally from the southwest, and secondarily from the Merida and Banbacoas highs; olistoliths and argillaceous sediments could have come from the north. These sediments were deposited as lowstand prograding wedge (slopefan complex) and submarine fan lobes in a belt trending northwest-southeast beyond the eastern shore of the present day Lake Maracaibo. The slope-fan complex consists of stacked progradational clinoforms with toesets of shingled turbidites. The exploratory potential of the slope-fan complex is still under study. Basinward the slope-fan facies grades into a thick, mappable and convex submarine fan lobe (Basin Floor Fan) overlying Paleocene strata. Farther eastward of this subsurface turbidite complex, extensive outcrops of coeval turbidites of the Trujillo-Rancheria formations occur in the Serrania de Trujillo. The subsurface shelf-fed turbidite complex, as yet untested, may be of considerable economic interest as the potential fan lobe trap overlies the rich La Luna Eocene kitchen. Oil generation wasmore » relatively early (Middle Eocene) in this part of the basin. Early hydrocarbon generation and migration along vertical/subvertical faults would have filled the trap and preserved the porosity from destructive diagenesis. If hydrocarbons are present, this area may well become the new exploration frontier of the Maracaibo Basin.« less


Autobiographical descriptions and clinician observations suggest that some individuals with autism, particularly females, 'camouflage' their social communication difficulties, which may require considerable cognitive effort and lead to increased stress, anxiety and depression. Using data from 60 age- and IQ-matched men and women with autism (without intellectual disability), we operationalized camouflaging in adults with autism for the first time as the quantitative discrepancy between the person's 'external' behavioural presentation in social–interpersonal contexts (measured by the Autism Diagnostic Observation Schedule) and the person's 'internal' status (dispositional traits measured by the Autism Spectrum Quotient and social cognitive capability measured by the 'Reading the Mind in the Eyes' Test). We found that the operationalized camouflaging measure was not significantly correlated with age or IQ. On average, women with autism had higher camouflaging scores than men with autism (Cohen's d = 0.98), with substantial variability in both groups. Greater camouflaging was associated with more depressive symptoms in men and better signal-detection sensitivity in women with autism. The neuroanatomical association with camouflaging score was largely sex/gender-dependent and significant only in women: from reverse inference, the most correlated cognitive terms were about emotion and memory. The underlying constructs, measurement, mechanisms, consequences and heterogeneity of camouflaging in autism warrant further investigation.


2, 2, 4 Abstract: Power electronics is an area that concerns the applications of electronic principle into situations where the power level is controlled than signal level. Semiconductor power switches such as thyristors, GTOs, MOSEFTS, etc. works on the principal of power electronics. The industrial applications demands the inventions in converter, Pulse width modulation techniques, control and estimations, DSP, ASICs, etc. which also needs contribution of power control operations. This paper provides brief summary of power control device i.e. thyristor working in different modes of operations. Applications of thyristor using different modes to control the speed of motor are also summarized at glance.


____________________________________ Introduction __________________________ Acknowledgments ____________________ General geologic setting ___________________________ Volcanic and sedimentary rocks ___________ Basaltic assemblage ______________ Andesitic assemblage ________________ Plutonic rocks _____________________________ Dioritic batholiths ________________ Granodiorite gneiss ___________ Late-orogenic or postorogenic plutons _______ Layered gabbro and associated rocks __ Granodiorite to granite intrusions ____ Najd fault system ______________________ Previous geochronologic studies ____________________ Analytical techniques _____________________ Results of rubidium-strontium analyses __________ Basaltic assemblage _________________________ Page


The Central Asian Orogenic Belt (CAOB) is the most significant accretionary orogenic belt since the Phanerozoic and the most ideal site for studying continental growth evolution processes. A 460‐km‐long high‐resolution crustal‐scale seismic reflection study was conducted across the eastern CAOB in North‐Central China to constrain the closure mode and location of the Paleo‐Asian Ocean, that is, the previous ocean of the CAOB. The resultant seismic reflection profile revealed opposite‐dipping reflectors in the northern and southern parts of the profile, which converge at the profile center to form an inverted U‐shaped reflector pattern near the crust–mantle transition zone beneath the Solonker Suture. The dipping reflectors represent bidirectional fossil subduction zones sloping to the north and south, and the convergence reflector pattern represents the ocean closure location. Integration of these results with available geological data facilitated model construction whereby Paleo‐Asian Ocean closure was accomplished by divergent subduction of the Paleo‐Asian oceanic plate, with northward subduction beneath the southern margin of the Mongolian Block and southward subduction beneath the northern margin of the North China Craton. The oceanic lithosphere contracted and deformed, yielding the observed inverted U‐shaped reflector pattern, representing Paleo‐Asian Ocean closure. This subsurface location lies beneath the Solonker Suture surface exposure, suggesting that this suture marks the ocean closure location, rather than the previously proposed Hegenshan–Heihe Suture to the north or Xar Moron Suture to the south. Our study suggests that divergently dipping subduction and associated accretion and magmatism may constitute the primary continental growth mode for accretionary‐type orogens.


A study was carried out to define the level of health knowledge and education of 756 healthy people and 189 patients with active tuberculosis. The study revealed an insufficient awareness of both the healthy subjects and patients in such aspects, as nature of tuberculosis infection, ways of its transmission, preventive measures, early detection of the disease and its curing opportunities. Systematic discussions with the persons interviewed and individual contacts with the patients allowed one to increase their knowledge of tuberculosis, influenced their discipline and made them active aids to the attending doctors.


Background: Heart rate variability is the most important noninvasive tool to quantify cardiac autonomic function. Aim: To compare the "frequency domain" parameters of "heart rate variability" in male and female subjects. Study Design: Cross-sectional study. Methodology: Present study was carried out at Islamic International Medical College and Yusra medical and dental college from June 2014 to December 2018. Four hundred subjects from both the genders between 20-40 years of age were included in the study after filling written informed consent. Ten minutes ECG of the subject was taken using power lab and explored for heart rate variability observing the protocols of "Task Force of European Society of Cardiology and the North American Society of Pacing Electrophysiology Frequency domain indices of heart rate variability obtained using "fast Fourier transform" .and were compared among male female groups. Results: Male subjects have considerably low high frequency in absolute unit and normalized unit (p≤ 0.05)and high low frequency in normalized unit and absolute unit (p ≤ 0.05 and .001 respectively)and low to high frequency ratio when compared with females(p ≤0.001). Conclusion: We concluded that assessment of Heart rate variability is an important measure of autonomic nervous system. Males exhibit reduced HRV parameters as compared to females showing that female have good vagal control than males. Keywords: Heart Rate Variability, Frequency Domain Methods, Low Frequency, High Frequency and Low Frequency


Following Bernard Lonergan's lead, a systematic-theological account of the human world in relation to God will have a trinitarian "shape," inasmuch as finite, contingent realities participate in the divine relations that constitute the three who are God. While Robert Doran has proposed an excellent beginning of such an account, the author argues that this proposal can be improved, and that as there are three really distinct relations in God, so too there are three ways in which humanity can be, and is being, taken into God's own being.


Focal adhesion kinase (FAK) is a non‐tyrosine kinase that localizes to focal adhesion plaques. It is activated in response to intergin binding to cellular ligands and when phosphorylated inhibits anoikis allowing for anchorage independent cell growth. Recent studies have shown increased FAK expression and phosphorylation status in many types of invasive and aggressive human tumors strongly suggesting FAK is a possible target for anticancer chemotherapy. Literature, in house HTS and de novo studies identified 2, 4‐diaminopyrimidines as potent FAK inhibitors. Early SAR efforts quickly determined that smaller substituents, particularly CF3, were optimal in the C5 position. Parallel medicinal chemistry strategies were executed for the C2 and C4 positions. These studies suggested that substituted aryl and fused heteroaryl groups at the C2 position in conjunction with substituted phenyl and heterocycles at the C4 position imparted optimum activity and metabolic stability. Inhibitor‐FAK co‐crystal structures were utilized to guide in the SAR strategy around the 2, 4‐diaminopyrimidine template which afforded several lead compounds. The team9s effort culminated in the advancement of PF‐562,271 as a potent and reversible inhibitor of FAK (kinase IC50 of 2 nM and cell IC50 of 5 nM) that is > 100x selective against a long list of non‐target kinases. In summary, detailed SAR studies were executed on the 2, 4‐diaminopyrimidine templates that produced potent inhibitors of FAK with improved ADME properties, and identified a novel and potent series of FAK inhibitors that are selective against most other kinases and have shown activity in clinical trials. This poster will present design, synthesis, challenging chemistry, optimization, and complete inhibitor chemical structures of lead analogs. Citation Information: Mol Cancer Ther 2009;8(12 Suppl):A86.


Among the many virtues of Christopher Decker's edition of the FitzGerald Rubaiyat is its patient elucidation, not only of the various circumstances surrounding the text's multiple versions, but of what we can infer about the translator's equally various attitude toward his work. (1) Enthusiastic, torpid, apologetic, cavalier, across two decades and more between the first edition of 1859 and the final one of 1879 the anonymous agent who once signed himself in correspondence "Fitz-Omar" remains hard to read with assurance--by reason partly of a diffidence that was specific to the man's character, partly of ambivalences that haunt the translator's art generally. (2) But amid this history of many shifts and much effacement, across the variorum Rubaiyat there emerges an unswerving commitment that goes far toward explaining the work's extraordinary appeal. I mean FitzGerald's commitment to interpreting Omar Khayyam's quatrains not mystically but--in a term of FitzGerald's that becomes intriguingly complex--literally. The apparatus to each version he authorized sets at defiance all "Pretence at divine Allegory" (1859, p. 6), all trafficking "in Allegory and Abstraction" (1868, p. 35), all "Spiritual" decoction of what "is simply the Juice of the Grape" (1872, p. 67). Keeping faith with his Persian original meant, for FitzGerald, scouting any and all "Mysticism" that might distract from Omar's manifest aim, which his Victorian translator deeply embraced too. That aim was "to soothe the Soul through the Senses into Acquiescence with Things as he saw them" (1868, p. 31). "No doubt," averred the preface of 1868, "many of these Quatrains seem unaccountable unless mystically interpreted; but many more as unaccountable unless literally" (p. 35). FitzGerald's literalist affirmation so often took a feisty form because it was embroiled from the start in a polemic against Omar Khayyam's allegorizers. They were a tribe who had been around a long time--medieval Christianity had nothing on medieval Islam when it came to wresting heretic texts into hermeneutic line--and had voluble representatives still during the nineteenth century, and even in Europe. Well before 1859 FitzGerald was politely differing with his young tutor in Persian studies, Edward Cowell, about how to take some of Omar's bitter pills, and then in 1868 he stepped into the public ring to square off against J. B. Nicolas, a French exponent to whom the poems were dark Sufi conceits disclosing an orthodox message after all. FitzGerald survived this challenge handily, but the question that lay behind it has gone on to survive him. It flared up again just a generation ago, when no less an antagonist than the poet Robert Graves placed before the public a defense and illustration of Omar's hidden and mystical meaning. The Original Rubaiyyat of Omar Khayaam: A New Translation with Critical Commentaries is a title whose every adjective bristles with polemic--and whose aggressively repossessive orthography prepares us to learn that counterattacks were soon mounted in polemical turn by harder-headed sons of Fitz. The latter have long since carried the day against the allegorically credulous Graves and his ignorant or unscrupulous informant, the Sufi mystagogue votary Omar Ali-Shah. (3) I am spectacularly ill equipped to pronounce on the merits of this or any other matter pertaining to the astronomer algebrist with a nine-hundred-years-old name. But I can propose that his Victorian popularizer's firm commitment to taking old Omar at his word--taking him "literally," which is to say, in part, linguistically--had, as its cardinal literary consequence, a mode of poetic presentation to which the Rubaiyat has owed the breadth and longevity of its circulation among an anglophone public as "the most popular verse translation into English ever made" (Decker, p. xiv). For in FitzGerald's freely translating hands the this-worldly, bodily thematics of the poem found consistent correlates in its poetics. …


A method is presented for solving the problem of fitting decay-type experimental data by sums of exponentials. Both the exponents and the coefficients of the exponentials are considered as unknowns. The novel idea presented here is to consider the sum of exponentials as a solution of an integral equation. A step-by-step procedure is given for the solution of the problem in the least-squares sense. An advantage of the proposed method is that the data need not be equidistant.


This working paper is based on very recent PhD research with people ('staff' and 'managers') living through an organisational 'zombie apocalypse'. It draws on psychoanalytic theory and practice, social and cultural theory and some limited aspects of academic/organisational literature. The case centres on the experiences of eight individuals (all female) who have been living with extreme organisational turbulence and uncertainty for several months. Four of these had been with the organisation for over ten years, the others for between four and seven years. While two of these individuals had recently moved on, the other six were facing the end in their current organisational 'home'.
Based on a psychoanalytically-informed approach, the case reflects how this external, organisational, collapse is 'played out' internally. I have used a 'Working Note' approach (Miller, 1995), enabling a strong sense of connection with the experiences of the research participants as well as allowing for an on-going dialogue, where emerging working hypotheses have been tested during the research process.


In the title molecule, C13H15Cl2NO, the cyclohexane ring adopts a chair conformation. The aromatic ring plane is oriented with respect to the N/O/C plane at a dihedral angle of 51.88 (7)°. In the crystal structure, intermolecular N—H⋯O hydrogen bonds link the molecules into infinite chains along the [010] direction.