Real-world applications often involve domain-specific and task-based performance objectives that are not captured by the standard machine learning losses, but are critical for decision making. A key challenge for direct integration of more meaningful domain and task-based evaluation criteria into an end-to-end gradient-based training process is the fact that often such performance objectives are not necessarily differentiable and may even require additional decision-making optimization processing. We propose the Task-Oriented Prediction Network (TOPNet), an end-to-end learning scheme that automatically integrates task-based evaluation criteria into the learning process via a learnable surrogate loss function, which directly guides the model towards the task-based goal. A major benefit of the proposed TOPNet learning scheme lies in its capability of automatically integrating non-differentiable evaluation criteria, which makes it particularly suitable for diversified and customized task-based evaluation criteria in real-world tasks. We validate the performance of TOPNet on two real-world financial prediction tasks, revenue surprise forecasting and credit risk modeling. The experimental results demonstrate that TOPNet significantly outperforms both traditional modeling with standard losses and modeling with hand-crafted heuristic differentiable surrogate losses.


Creating new 3D printed objects by recombining models found in hobbyist repositories has been referred to as "re-mixing". In this paper, we explore how to best support users in remixing a specific class of 3D printed objects, namely those that perform mechanical functions. In our survey, we found that makers remix such machines by manually extracting parts from one parent model and combine it with parts from a different parent model. This approach often puts axles made by one maker into bearings made by another maker or combines a gear by one maker with a gear by a different maker. This approach is problem-atic, however, as parts from different makers tend to fit poorly, which results in long series of tweaks and test-prints until all parts finally work together. We address this with our interactive system grafter. Grafter does two things. First, grafter largely automates the process of extracting and recombining mechanical elements from 3D printed machines. Second, it enforces a more efficient approach to reuse: it prevents users from extracting indi-vidual parts, but instead affords extracting groups of me-chanical elements that already work together, such as axles and their bearings or pairs of gears. We call this mecha-nism-based remixing. In a final user study, all models that participants had remixed using grafter could be 3D printed without further tweaking and worked immediately.


After the identification of nociceptin/orphanin FQ (N/OFQ) peptide (NOP) and its cognate receptor, the unique functional profiles of the N/OFQ-NOP receptor system have been uncovered. NOP receptors are distributed in the key regions that regulate pain and reward processing in the central nervous system. In non-human primates (NHPs), activation of the NOP receptor causes antinociception and anti-hypersensitivity via spinal and supraspinal effects. Moreover, activation of the NOP receptor attenuates dopaminergic transmission and potentiates mu-opioid peptide (MOP) receptor-mediated analgesia. Here, we highlight the functional profiles of bifunctional NOP and MOP receptor agonists based on their promising effects for the treatment of pain and drug abuse. Bifunctional NOP/MOP receptor "partial" agonists, such as AT-121, BU08028, and BU10038, exert potent analgesic effects without MOP receptor-related side effects such as abuse liability, respiratory depression, physical dependence, and itching in NHPs. These novel NOP/MOP receptor agonists reduce rewarding and the reinforcing effects of abused drugs. Furthermore, a mixed NOP/opioid receptor "full" agonist, cebranopadol, is undergoing several clinical trials, and the therapeutic advantage of the coactivation of NOP and MOP receptors has also been confirmed in humans. Therefore, this class of drugs that coactivate NOP and MOP receptors proposes a wide therapeutic range with fewer side effects, indicating a greater potential for the development of novel safer opioid analgesics.


Advances in technology have led to the creation of many nano-scale devices and carbon nanotubes are representative materials to construct these devices. Double-walled carbon nanotubes with the inner tube oscillating can be used as gigahertz oscillators and form the basis of possible nano-electronic devices. Such gigahertz oscillating devices made from carbon nanotubes might be instrumental in the micro-computer industry, which is predominantly based on electron transport phenomena. There are many experiments and molecular dynamics simulations which show that a wave is generated on the outer cylinder by the oscillation of the carbon nanotubes and that the frequency of this wave is also in the gigahertz range. However, conventional applied mathematical modelling techniques are generally lacking. In order to analyse and model such devices, it is necessary to estimate accurately the resultant force distribution due to the inter-atomic interactions. Here, we find the van der Waals force using the Lennard-Jones potential to calculate the oscillation frequency using Newton's second law for double-walled carbon nanotubes of any length of the inner and the outer tubes, 2L1 and 2L2, respectively. These results are based on work by the present authors derived in (Baowan and Hill).


Objective To audit intravenous fluid prescribing for surgical patients against Birmingham Children's Hospital inhouse intravenous prescribing guidelines and national guidance.1 2 Method A retrospective analysis of patient drug charts and medical records (including electronic biochemical records) on two general surgical wards during a 5 day working week. The following details were recorded: consultant team, procedure undertaken, type of intravenous fluid prescribed, the rate prescribed, does it contain potassium and if so the concentration prescribed, weight of the patient and number of times patient was re-weighed, duration of intravenous fluid prescribed, frequency of monitoring for sodium and potassium levels while on intravenous fluids. The data was analysed using Microsoft Excel 2007. Results 25-patients were reviewed from 17 consultant teams from different specialities. More than half of the intravenous fluids prescribed were by a surgical team (56%). The average age of patients was 4 years and 4 months (range: 3 weeks to 16 years) and 60% of the patients were female. The average weight was 16.25 kg (range: 3.56 kg–53 kg). In terms of monitoring for sodium and potassium levels, about 35% of patients were not monitored. In terms of the rate prescribed, 44% of patients were prescribed an incorrect rate with no reason why the rate was prescribed. All patients were initially weighed on admission but none of the patients were re-weighed daily while on intravenous fluids. 19 (75%) of patients assessed for appropriate intravenous fluid prescribing did not comply with local and national guidance and failed to meet the standards for this audit. 92% of patient were prescribed incorrect fluid type postoperatively in relation to local guidance,1 however 100% of patients complied to national standards2 for peri-operative fluid choice and 28% of patients with a low sodium episode had no changes to their intravenous fluid type prescribed. Conclusion Inconsistencies in prescribing were identified in all consultant teams. These mainly included the choice of fluid, the rate prescribed, lack of monitoring and lack of weight monitoring in all cases. This raises the risk of injury to the patient from hospital-acquired hyponatraemia. Training needs to be improved within all consultant teams prescribing intravenous fluids to improve current trends and to adhere to local and national guidance, in order to reduce this potential risk.2


Background: Homocysteine is suspected to increase the risk of diabetes mellitus (DM)
complications and is associated with CV disease. While dyslipidemia and DM are risk factors
for death due to CV disease, studies on relationship between homocysteine and glycemic control
were inconsistent. Objective: To analyze the difference of Hcy level and lipid profile on nonDM
(Group I), DM with CV (II) and without CV (III). Methods: This crosssectional study was
conducted in Dr. Kariadi Hospital Semarang from April to October 2016. Samples were
recruited consecutively, of which group I consists of 26 persons, group II (30) and III (30). All
of the samples aged 30-75 years old, with long DM duration of more than 5 years. Fasting and
2 hours PP blood glucose, lipid profile was analyzed with auto analyzer, while Hcy was analyzed
with ELISA. Data were analyzed using independent t test. Significance is expressed at p <0.05.
Results: A significant difference on Hcy level was found between group I and III (p=0.000), but
not between group I and II or II and III. No significant difference was observed on total
cholesterol (TC) and LDLC in all groups. Significant differences were found on HDLC level
between group I and II (p=0.009); II and III (p=0.000); I and III (p=0.033). Triglyceride level on
group I was significantly different compared to group II and III (p=0.030 and 0.013
respectively), but was not significantly different compared to group II and III. Conclusion:
The highest Hcy level, the lowest HDL-C and the highest triglyceride level were found in DM
patients with cardiovascular complication.
Keywords: DM, Homocysteine, Lipid Profile, CHD


This study identifies a novel cross-talk paradigm between the type I insulin-like growth factor receptor (IGF1R) and epidermal growth factor receptor (EGFR) in colon cancer cells. IGF1R activation by ligand exposure in growth factor-deprived cells induces Akt activation in the FET, CBS, and GEO colon cancer cell lines. Investigation of IGF1R-mediated signaling pathways using small interfering RNA approaches indicated that, as expected, phosphatidylinositol 3'-kinase (PI3K) was activated by IGF1R. Mitogen-activated protein kinase (MAPK) activity as reflected by phospho-extracellular signal-regulated kinase (ERK) induction was not significantly activated until later times following release of these cells from growth factor deprivation stress. The appearance of phospho-ERK was proximal to EGFR activation. Treatment of cells with the PI3K inhibitor LY294002 before release from stress resulted in a concentration-dependent loss of EGFR activation, whereas treatment with the MAPK inhibitor PD98059 did not block EGFR activation, indicating that EGFR activation was downstream of the IGF1R/PI3K pathway. PD98059 inhibition of MAPK was associated with a concentration-dependent reduction in EGFR-mediated phospho-ERK. EGFR inhibitor blocked induction of phospho-ERK, showing that MAPK activity was a consequence of EGFR-mediated signaling. On the other hand, a small-molecule IGF1R inhibitor, PQIP, blocked Akt phosphorylation. The divergent signaling functions of IGF1R and EGFR suggested the potential for synergism by a combination of therapy directed at the two receptors. Combination treatment with PQIP and EGFR inhibitor Tarceva resulted in synergistic effects as indicated by combination index analysis in all three cell lines tested.


The aim of this research was to develop a tool to identify and assess the qualities of cancer-related loneliness in adult cancer survivors who have completed treatment. In addition to reporting the development of the tool, we explicate the process of using the findings of a qualitative analysis to generate questionnaire items, as currently little guidance exists on this topic. The findings of our qualitative research exploring the experience of loneliness in adult cancer survivors who had completed treatment, together with the findings of our concept analysis of loneliness, were used to develop an assessment tool for cancer-related loneliness following treatment completion. Cognitive testing was undertaken to assess fidelity of comprehension and feasibility in administration. The Cancer-Related Loneliness Assessment Tool is a 10-item self-report questionnaire capturing the essential elements of cancer-related loneliness following treatment completion. Experts believed the questionnaire to be face-valid and usable in clinical practice, and preliminary cognitive testing indicated that the items generate the information intended and individuals have little trouble completing the tool. Following further development work, the tool could be employed to identify cancer-related loneliness following treatment completion. It could also aid with the development/adaptation and evaluation of person-centred interventions to address such loneliness.


Three-dimensional numerical simulations of nonNewtonian fluid flows are a challenging problem due to the particularities of the involved differential equations leading to a high computational effort in obtaining numerical solutions, which in many relevant situations becomes infeasible. Several models has been developed along the years to simulate the behavior of non-Newtonian fluids together with many different numerical methods. In this work we use a one-dimensional hierarchical approach to a proposed generalized third-grade fluid with shear-dependent viscoelastic effects model. This approach is based on the Cosserat theory related to fluid dynamics and we consider the particular case of flow through a straight and rigid tube with constant circular cross-section. With this approach, we manage to obtain results for the wall shear stress and mean pressure gradient of a real three-dimensional flow by reducing the exact three-dimensional system to an ordinary differential equation. This one-dimensional system is obtained by integrating the linear momentum equation over the constant cross-section of the tube, taking a velocity field approximation provided by the Cosserat theory. From this reduced system, we obtain the unsteady equations for the wall shear stress and mean pressure gradient depending on the volume flow rate, Womersley number, viscoelastic coefficients and the flow index over a finite section of the tube geometry. Attention is focused on some numerical simulations for constant and non-constant mean pressure gradient using a Runge-Kutta method.


The values of "Responsibility, Respect, Relationality and Reciprocity (the 4Rs)" in Indigenous research methodologies inform the core principles of Indigenous kinship systems. This is most often understood as the interconnectedness to land, relatives, animals, and spirits. Despite ongoing systems of oppression, Indigenous kinship values have not only survived but continue to demand a rightful a place within our education, health, justice, and welfare systems. Through critical self-reflective praxis, I explore how the values of "Responsibility, Respect, Relationality and Reciprocity" that guide Indigenous research methodologies (IRM) can disrupt Western based psychotherapies and counselling practices that too often reproduce harm onto Indigenous peoples. The 4Rs upheld in IRM strengthen kinship by centring the values that promote the beauty and intelligence of Indigenous knowledge systems and generations of knowledge holders.


BACKGROUND
 The prevalence of gestational diabetes mellitus (GDM) is increasing worldwide. A healthy diet and stable blood glucose levels during pregnancy can prevent adverse health outcomes for the mother and the newborn child. Mobile health may be a useful supplement to prenatal care, providing women with targeted dietary information concerning GDM.

 OBJECTIVE
 We analyzed secondary data from a two-arm, multicentered, nonblinded randomized controlled trial to determine if a smartphone app with targeted dietary information and blood glucose monitoring had an effect on the dietary behavior of women with GDM.

 METHODS
 Women with a 2-hour oral glucose tolerance test level of ≥9 mmol/L were individually randomized to either the intervention group receiving the Pregnant+ app and usual care or the control group receiving usual care only. Eligible women were enrolled from 5 diabetes outpatient clinics in the Oslo region, Norway, between October 2015 and April 2017. The Pregnant+ app promoted 10 GDM-specific dietary recommendations. A healthy dietary score for Pregnant+ (HDS-P+) was constructed from a 41-item food frequency questionnaire and used to assess the intervention effect on the dietary behavior completed at trial entry and at around gestation week 36. Dietary changes from baseline to week 36 were examined by a paired sample two-tailed t test. Between-group dietary differences after the intervention were estimated with analysis of covariance, with adjustment for baseline diet.

 RESULTS
 A total of 238 women participated: 115 were allocated to the intervention group and 123 to the control group. Of the 238 women, 193 (81.1%) completed the food frequency questionnaire both at baseline and around gestational week 36. All the participants showed improvements in their HDS-P+ from baseline. However, the Pregnant+ app did not have a significant effect on their HDS-P+. The control group reported a higher weekly frequency of choosing fish meals (P=.05). No other significant differences were found between the intervention and control groups. There were no significant demographic baseline differences between the groups, except that more women in the intervention group had a non-Norwegian language as their first language (61 vs 46; P=.02).

 CONCLUSIONS
 Our findings do not support the supplementation of face-to-face follow-up of women with GDM with a smartphone app in the presence of high-standard usual care, as the Pregnant+ app did not have a beneficial effect on pregnant women's diet.

 CLINICALTRIAL
 ClinicalTrials.gov NCT02588729; https://clinicaltrials.gov/ct2/show/NCT02588729


Introduction and objectives As part of the care of Ataxia Telangiectasia Patients, a baseline swallow profile is obtained using a videofluoroscopy. It was observed that penetration or aspiration of oral intake did not appear to have a direct link to chest infections in these patients. The authors conducted a pilot study, analysing retrospective data to explore this observation further. Methods All variant AT patients who attended a multi-disciplinary (MDT) annual review appointment between 01/2013–11/2015 and underwent a videofluoroscopy were included. The patient was ranked on the Penetration Aspiration Score (PAS) from the videofluoroscopy. Retrospective data of the frequency of chest infections requiring treatment with antibiotics in the last 12 months was collected from the annual assessment reports in the medical notes. Initially, 37 patients were included, this was reduced to 30 as 7 videofluoroscopies were not sufficient for calculating the swallow trigger delay. Data was analysed using excel and xlstat (standard descriptive tests and Spearman's) to evaluate any correlation between aspiration or penetration and number of chest infections. Results With a confidence interval of 95%, there was a negative correlation of rs 0.079 (p-value < 0.0001) indicating a very weak correlation. The number of chest infections data was significantly skewed at a result of 2.643. This may be due to the small sample size. Conclusions This data suggests there is no correlation between aspiration or penetration and the chest infections experienced by AT Patients. However, this was a small sample due to the rarity of the genetic disorder. A larger sample either through increased length of time that the data is collected or an international study could help provide greater insights into the correlation between aspiration or penetration of oral intake and the number of chest infections experienced. Reference Rosenbek JC, Robbins JA, Roeker EB et al. A penetration-aspiration scale. Dysphagia 1996;11(2):93–98. Abstract P262 Figure 1 Aspiration penetration and number of chest infestions


The current thesis focuses on three detailed experimental QTAIM charge density studies on small molecules based on high resolution X-ray diffraction experiments. Each of the three studies required the application of different analytical methods.

The first of the studies (chapter 3) deals with the experimentally challenging piano stool complex tris(ammine)cyclopentadienyl sodium. The anticipated highly ionic character of the metal–cyclopentadienyl interaction was confirmed by means of the integrated atomic charges and the atomic Source Function contributions in a QTAIM analysis. An out-of-plane bending of the cyclopentadienyl hydrogen atoms, apparently violating traditional theoretical predictions, was experimentally observed. More sophisticated theoretical calculations taking the lattice environment into account were carried out by our cooperation partner Diego Andrada from the Mata workgroup. The calculations exactly reproduced the experimentally observed bending angle. The out-of-plane-bending was explained by the charge reorganization and accumulation on top of the Cp ring, caused by strong intermolecular N–H∙∙∙π interactions with adjacent ammonia molecules. These in-termolecular interactions were visualised by a state-of-the-art Hirshfeld surface analysis and traced by the recently published NCI (non-covalent interactions) method and the Source Function. The results confirm the excellent quality of the acquired data and the appropriateness of the refined model despite a 50:50 disorder in one out of three ammonia groups. Those experimental data might even serve for benchmarking in the development of new, more resilient theoretical methods.
It was demonstrated that the sodium/cyclopentadienyl as well as the N–H∙∙∙π interactions have a strongly polarising effect on the partially delocalised valence density of the cyclopentadienyl anion. This is visible in plots of the deformation density as well as of the Laplacian distribution. It can be postulated that the strength of the polarising effect of the cation and the ammonia protons compete on similar levels.

The second charge density study elucidates the bis(2-benzothiazolyl)phosphane, a sec-ondary phosphane in an unusual tautomeric form. Embarking on the primary goal to characterize the ambiguous character of the P–C bonds (chapter 4), the investigations turned out to have account for the even more general issue of conjugation and heteroaromaticity. The Source Function as a tool for the quantification of delocalisation was evaluated, and the first results on the fuzzy set of heteroaromaticity were presented.
Several complementary measures for aromaticity confirmed the aromaticity of the five- and six-membered rings. They were applied in cooperation with specialists from the Institute of Physical Chemistry (R. A. Mata and J. Dieterich) and from the University of Oslo (H. Fliegl).
It was shown that the interpretation of valence shell charge concentrations as VSEPR-concept lone pairs and the deduction of hybridisation states of third-row elements from these features of the charge density map are accepted in the experimental charge density community. The physical appropriateness of this interpretation was questioned and disproved in this thesis, which is in accordance with other opinions.
Weak intermolecular C–H∙∙∙S and C–H∙∙∙P interactions in the crystal packing of bis-(2-benzothiazolyl)-phosphane were identified as attractive interactions by means of the NCI descriptor. The existence of the corresponding intermolecular bond paths underlines this conclusion.

The experimental charge density study on N-benzyl-2-(hydroxymethyl)benzamide had the aim to provide a rationale for the inert behaviour of this compound towards hydridic reduction agents (chapter 5).
A QTAIM analysis of the benzamide 3 was carried out, confirming the long known electron delocalisation in the bonds of the C(=O)–N amide group by their topological bond orders. No double bond character could be found in the C(amide)–phenyl bond and thus a stabilising conjugation of the amide group to the phenyl ring can be ruled out. A variety of relatively strong intermolecular interactions was characterised, among them two C–H∙∙∙O interactions.
The analysis of the electrostatic potential around the molecule revealed that an envelope of negative potential together with a steric shielding of the positive potential regions by the ortho hydrogen atom of the phenyl ring prevents the reaction of the carboxy carbon atom with hydridic reduction agents.

The last two chapters of this thesis (chapters 6 and 7) deal with some sources of errors in modern single crystal X-ray diffraction experiments:
The problems and the observed irregularities in the data sets from a synchrotron source were shown in chapter 6. Different strategies for data acquisition and data procession were evaluated. A discussion of possible errors was provided and future investigations were suggested.
A hitherto largely neglected flaw in the design of modern focusing optics was subject of chapter 7: the low-energy contamination of the used radiation by total reflection of bremsstrahlung from the target of the X-ray source.
The chapter provided evidence based on data statistics suggesting that the effect of the contamination should not be neglected in the future. A simple filter insert for the beam path of a diffractometer was designed that enables the filtering of the contamination.
Two multipole refinements against datasets of tris(ammine)cyclopentadienyl sodium with and without contamination were compared. While a bond path between the sodium atom and the cyclopentadienyl moiety was observed when the model from the non-contaminated data was analysed, this path was absent in the result from the refinement against contaminated data, which highlighted the importance of accurately measured data.

The current thesis provides several links and cues to possible future projects. Charge density studies are generally considered to be mature, but it became clear that some of the used methods in the analysis of the results require further development. A lot more studies on the delocalisation in heteroaromatic systems using the Source Function and the delocalisation index as the measures for delocalisation are needed.
More investigations are needed to enable the efficient exploitation of the enormous potential of the beamline 15 ID-B at the Advanced Photon Source. The source of the observed error remains unresolved yet, but the range of potential errors has been narrowed down so that the combined efforts of the German (Stalke) and the Danish group (Iversen) will eventually lead to success.
The influence of the low energy contamination in multilayer focused X-ray beams will have to be further investigated. The future will show whether the effect should best be tackled by hardware (filter foils) or by software that remains to be developed.


Recent development of network technology realizes multi-tier server systems, where several tiers perform functionally different processing requested by clients. It is an important issue to allocate resources of the systems to clients dynamically based on their current requests. On the other hand, Q-RAM has been proposed for resource allocation in real-time systems. In the server systems, it is important that execution results of all applications requested by clients are the same QoS(quality of service) level. In this paper, we extend Q-RAM to multi-tier server systems and propose a method for optimal resource allocation with fairness of the QoS levels of clients' requests. We also consider an assignment problem of physical machines to be sleep in each tier sothat the energy consumption is minimized.


Monodisperse mesoporous zirconium titanium oxide microspheres with varying compositions (Zr content from 0 to 100%), high surface areas (up to 413 m2/g) and well‐interconnected mesopores are synthesized via a combined sol–gel self‐assembly and solvothermal process. Surface areas, pore diameters, crystallinity and mesostructures of the products are controlled by changing the composition of the microspheres. The resulting mesoporous microspheres are tested as adsorbents to remove Cr (VI) anions from solution and the binary oxides show very high adsorption capacities (>25.40 mg/g, that is 0.49 mmol/g) in contrast to previously reported oxides (4.25 mg/g for TiO2, 4.47 mg/g for α‐Fe2O3, 5.8 mg/g for CeO2). The maximum adsorption capacities of the mesoporous microspheres of varying compositions correlate with the amount of surface hydroxyl groups on the materials. A maximum adsorption capacity of 29.46 mg/g (0.57 mmol/g) is achieved on the microspheres containing 30% Zr due to abundant active hydroxyl groups for heavy metal ion adsorption. Owing to their integrated features (including variable compositions, high specific surface area, tunable pore size and monodisperse grain size) as well as specific acid‐base surface properties, such mesoporous zirconium titanium oxide microspheres are also expected to have potential either as catalysts or catalyst supports for industrial applications.


Fluidelastic instability is generally regarded as the most severe type of flow excitation mechanism. When this mechanism prevails, it could cause serious damage to tube arrays in a very short period of time. This mechanism is characterized by a critical flow velocity beyond which the tubes undergo unstable oscillations. Recently, a number of experimental investigations showed that it is possible to have instability in the streamwise direction; previously, it was believed that fluidelastic instability was only a concern in the direction transverse to the flow.The purpose of this study is to characterize the flow in the channels surrounding a vibrating tube in a normal triangular bundle with P/d = 1.5. The tube is oscillating in the streamwise direction with a constant amplitude. Numerical simulations were conducted by solving the unsteady Reynolds Averaged Navier-Stokes equations (uRANS) cast in Arbitrary Lagrangian-Eulerian (ALE) form. The unsteady flow perturbation is estimated along the flow channel. The pressure perturbation is used to compute the streamwise unsteady force coefficients in the context of Chen's model. The perturbation phase and decay are extracted and utilized in the framework of the Lever & Weaver model to study the stability of tube bundles due to tube motion in the streamwise direction.Copyright © 2015 by ASME


Objective To evaluate for potential predictors of intraoperative conversion from robotic sacrocolpopexy (RSC) to open abdominal sacrocolpopexy. Patients and Methods We identified 83 consecutive patients from 2002-2012 with symptomatic high-grade post-hysterectomy vaginal vault prolapse that underwent RSC. Multiple clinical variables including patient age, comorbidities (body-mass index [BMI], hypertension, diabetes mellitus, tobacco use), prior intra-abdominal surgery and year of surgery were evaluated for potential association with conversion. Results Overall, 14/83 cases (17%) required conversion to an open sacrocolpopexy. Patients requiring conversion were found to have a significantly higher BMI compared to those who did not (median 30.2kg/m2 versus 25.8kg/m2; p=0.003). Other medical and surgical factors evaluated were similar between the cohorts. When stratified by increasing BMI, conversion remained associated with an increased BMI. That is, conversion occurred in 3.8% (1/26) of patients with BMI ≤25 kg/m2, 14.7% (5/34) with BMI 25-29.9 kg/m2 and 34.7% (8/23) with BMI ≥30 kg/m2 (p=0.004). When evaluated as a continuous variable, BMI was also associated with a significantly increased risk of conversion to an open procedure (OR 1.18, p=0.004). Conclusions Higher BMI was the only clinical factor associated with a significantly increased risk of intra-operative conversion during robotic sacrocolpopexy. Recognition of this may aid in pre-operative counseling and surgical patient selection.


A total of 267 cases of male subfertility seen during a three year period beginning April 1980 were studied. The results of treatment for the various groups were analyzed. Good improvement of semen analysis results were obtained for varicocele ligation but pregnancy rates had not yet been studied in detail because of the short span of follow-up. Vaso-vasotomy results had been excellent.


Abstract. A simple 1-D energy budget model (SIMO) for the prediction of the vertical temperature profiles in small, monomictic lakes forced by a reduced number of input meteorological variables is proposed. The model estimates the net heat flux and thermal diffusion using only routinely measured hourly mean meteorological variables (namely, the air temperature, relative humidity, atmospheric pressure, wind speed, and precipitation), hourly mean ultraviolet B radiation (UVB), and climatological monthly mean cloudiness data. Except for the initial vertical temperature profile, the model does not use any lake-specific variables. The model performance was evaluated against lake temperatures measured continuously during an observational campaign in two lakes belonging to the Plitvice Lakes, Croatia (Lake 1 and Lake 12). Temperatures were measured at 15 and 16 depths ranging from 0.2 to 27 in Lake 1 (maximum depth of 37.4 m) and 0.2 to 43 m in Lake 12 (maximum depth of 46 m). A sensitivity analysis of the simulation length was performed for simulation lengths from 1 to 30 days. The model performed reasonably well and it was able to satisfactorily reproduce the vertical temperature profile at the hourly scale, the deepening of the thermocline with time, and the annual variation in the vertical temperature profile. A yearlong simulation initiated with an approximately constant vertical profile of the lake temperature (≈ 4 °C) was able to reproduce the onset of stratification and convective overturn. However, the thermocline depth was underestimated while the epilimnion temperatures were overestimated. Nevertheless, the values of the model performance measures obtained for a yearlong simulation were comparable with those reported for other more complex models. Thus, the presented model can be used for the assessment of the onset and duration of lake stratification periods when water temperature data are unavailable, which can be useful for various lake studies performed in other scientific fields, such as biology, geochemistry, and sedimentology.


In this paper, we propose a feedback based cooperative transmission (FBCT) scheme for multiuser multichannel communication systems. We focus on uplink channels and consider a user, say user 1, who has a weak uplink channel. Another user (who is possibly located somewhere between the base station and user 1), say user 2, can be a relay for cooperative transmission. Using the feedback information of a positive acknowledgment (ACK) or negative acknowledgment (NACK) signaling from the base station, the signal from user 1 can be re-relayed by the relay (i.e., user 2) or re-transmitted by the source (i.e., user 1) in the proposed FBCT scheme. The resulting FBCT scheme can be seen as a hybrid of cooperative transmission and automatic repeat request (ARQ) protocol. We show that a mixed strategy of re-relay and re-transmission of the proposed FBCT scheme can perform better than a pure strategy of re-relay or re-transmission.


The European Trial on Reduction of Cardiac Events with Perindopril in Stable Coronary Artery Disease (EUROPA) involved 12,218 patients with stable coronary artery disease. Patients in this trial were randomized to the angiotensin‐converting enzyme inhibitor perindopril (8 mg/d) or placebo in addition to optimized conventional therapy and followed for an average of 4 years. Perindopril reduced the primary end points of cardiovascular disease, myocardial infarction, and cardiac arrest by 20% (p=0.0003). Moreover, the angiotensin‐converting enzyme inhibitor reduced the rate of fatal and nonfatal myocardial infarction by 24% (p=0.001). The results from EUROPA complement those observed in the Heart Outcomes and Prevention Evaluation (HOPE) study and provide further support for the concept of angiotensin‐converting enzyme inhibitors conferring cardiovascular protection as a class effect.


There are many data sets based on the population of discovered cartels and it is from this data that average cartel duration and the annual probability of cartel death are estimated. It is recognized, however, that these estimates could be biased because the population of discovered cartels may not be a representative sample of the population of cartels. This paper constructs a simple birth-death-discovery process to theoretically investigate what it is we can learn about cartels from data on discovered cartels.


The main purpose of this study was to analyze the impact on Mental Health and Motivation levels of university students because of nCOV-19. This study analyzed the perception of students' mental health and Motivation level due to nCOV-19. The population comprised 25000 students of the University of Education Multan, Baha Uddin Zakariya University Multan, and MNS University of Agriculture Multan. They selected a sample of 250 students through the cluster and stratified sampling technique. A survey was conducted for the quantitative components of the study amongst students using a self-made questionnaire based on the factors of mental health and motivation level. Three factors of mental health are stress, anxiety, and depression. The researcher distributed and administered the questionnaires himself. The study reviewed relevant literature regarding nCOV-19, character and higher educational institutions, and other factors influencing these variables. The received information was broken down using illustrative and inferential measurements. Descriptive statistics included mean, median, mode, and standard deviation. The results show that students receive a high level of data collected about the motivational level of students. Both anxiety and depression at a low level, and stress at moderate level amongst university students during the nCOV-19 Pandemic. Inferential statistics included t-test, Pearson correlation, and linear regression. The commonness of stress and depression in females is greater than males with a minimum margin, which shows females face a slightly higher level of stress and depression than males. But the commonness of anxiety in females is greater than males with a moderate margin, which shows females face a higher level of anxiety than males. Pearson coefficient correlation indicates a negative low degree of correlation between the impact of motivational levels and students' academic achievement.


Technology for actively supporting groups of collaborating users is being applied to many kinds of cooperative work activities. The following topics are addressed: (1) the authors' definition of groupware, (2) a conceptual framework in which to examine research issues, and (3) high-level groupware research issues within this framework. One potentially fertile area of application for such technologies is the problem of software process management. Software process means one of the teamwork, cooperation, coordination, and communication activities that occur within and across groups and organizations of persons throughout the life of software projects, including processes that occur under the broad categories of proposal writing, software engineering, development, and maintenance. This application domain contains a number of research issues and technology problems in such areas as communication, distribution, concurrence control, and human-computer interface design. The research areas needed for groupware to facilitate software processes are described. >


Abstract This study examines determinants of leftist violence at the municipal level in Colombia from 2000 through 2010. A multilevel GLMM model with a negative binomial distribution is used to take advantage of the information available at the municipal and department level. Surprisingly, inequality was not a significant covariate of violence, and agricultural GDP tended to reduce, instead of increase, guerrilla violence. The main risk factors identified include physical characteristics such as rugged topography and prior violence, but also factors that are candidates for policy action, such as unemployment, incorporation of the poor into public services, repression, and the energy and mining sector. These findings suggest interventions to decrease risks of guerrilla violence beyond merely strengthening the state. While repression tends to escalate violence, targeted policies to provide health benefits to those currently underserved, and securing mining and oil operations can effectively reduce the risk of violence.


Gavin Kennedy has carefully shown that the "Invisible Hand" myth, that greedy and selfish private optimizing behavior leads to a social macro optimum that benefits all, had nothing to do with Adam Smith's use of the invisible hand metaphor in The Wealth of Nations. Kennedy also showed that this myth, although correctly rejected by Paul Samuelson, was ascribed to Smith by Paul Samuelson in all of the editions of his Economics text book starting in 1948. Samuelson most likely picked up this myth from either Jacob Viner, when he took Viner's course, and/or fellow student George Stigler.


This paper will examine the relation between artists and their communities from the particular perspective of the Research Quality Framework proposed by DEST for assessing the quality and impact of research in Australia. The recent Federal Government discussion paper on the proposed RQF sends the clear warning that the link between university-based artists and their communities is to become a most contested relationship. The Framework for Measuring Research Impact (Table 3) presented in the paper explicitly and exclusively endorses performative knowledge with commercialization as its primary measure of impact. Even the points listed to exemplify knowledge relationships outside the university and engagement with the community focus solely on industry cooperation, consultancy and economic activities. Of the suitable measures for assessment of Research Impact Outputs, suggested in the paper (Table 2), only three relate directly to art and design. Included as one of these is "audience/attendances at exhibitions/performances" - raising the spectre of visual and performing arts assessment reduced to the mentality of bums on seats. Most disturbing of all, for studio-based researchers, the impact of their investigations on visual culture is explicitly excluded. Research does not impact on culture, quoting the paper: "In a broader sense, research impact refers to social, environmental or economic impacts." I will argue in this paper for a radical reassessment of the strategy, spearheaded by ACUADS over the last decade, that has attempted to equate research in the visual arts with humanities and science research. The limited success in demonstrating equivalence between creative arts outputs and the established framework of publications and bibliometric measures favoured by science and humanities has been determined by peer review of quality and varying degrees of goodwill by research committees in individual universities, if not in DEST itself. With the establishment of the RQF in 2006 more rigorous, competitive and rigid attitudes to measurement of research quality and impact will be legislated and the current expedient masquerade of dressing artists and designers in academic gowns will be exposed. If the visual and performing arts are to gain their rightful share of research support funding they must be seen as distinctively different to science and the humanities in their mode of operational research, outputs and community impacts. In particular their cultural sphere of influence must be acknowledged. The knowledge embedded in arts practice must be articulated on its own terms if the amorphous, emotive and critical forms of understanding presented in creative outputs are to be recognized. To contribute to this process, my paper will highlight specific instances of practice-based endeavour that represent quality cultural production and consumption.


This essay reads Sylvia Wynter's "Black Metamorphosis" as a text that both examines and embodies maroonage, significantly, in various ways and on various levels. It takes off from Aimé Césaire's underacknowledged imperative, "Marronnons-nous," recognizing and demonstrating the import of Césaire's work for Wynter's own work over time. The argument is that "Black Metamorphosis" makes a contribution to the study of maroonage narrowly construed, while also transcending the ironically narrow conception of maroonage as a bound empirical reference. The manuscript speaks of "species of maroonage" and represents one such species itself as an epic political project of African/diasporic resistance anchored all across the Americas.


The effects of regularity in spatial inferences with and without landmarks on spatial learning Kayoko Ohtsu Graduate School of Education, Waseda University Yoshihiro Ouchi Teikyo-Gakuen Junior College Abstract: Spatial inferences during wayfindign could be closely related to spatial learning. We examined the effects of regularity in the inferences on learning of relative locations through wayfinding in the context of available information about an environment. In the experiment using a real maze, participants visited multiple targets in one of four conditions by a combination of two factors: an updating mode (regular or irregular) and an environmental information (with or without global landmarks). The results suggest that although the global landmarks facilitate the learning regardless of the updating modes, the difference in the regularity produces opposite effects depending on the landmark conditions. While the irregular updating, which involves multidirectional self-to-object updating, has a facilitation effect when the landmark information is available, it impedes the learning without the landmarks. The regular updating, which would allow a relatively easier wayfinding strategy facilitates the learning only in the latter condition.


This work discusses the development and calibration of the x-ray reflective and diffractive elements for the Soft X-ray Materials Science (SXR) beamline of the Linac Coherent Light Source (LCLS) free-electron laser (FEL), designed for operation in the 500 to 2000 eV region. The surface topography of three Si mirror substrates and two Si diffraction grating substrates was examined by atomic force microscopy (AFM) and optical profilometry. The figure of the mirror substrates was also verified via surface slope measurements with a long trace profiler. A boron carbide (B4C) coating especially optimized for the LCLS FEL conditions was deposited on all SXR mirrors and gratings. Coating thickness uniformity of 0.14 nm root mean square (rms) across clear apertures extending to 205 mm length was demonstrated for all elements, as required to preserve the coherent wavefront of the LCLS source. The reflective performance of the mirrors and the diffraction efficiency of the gratings were calibrated at beamline 6.3.2 at the Advanced Light Source synchrotron. To verify the integrity of the nanometer-scale grating structure, the grating topography was examined by AFM before and after coating. This is to our knowledge the first time B4C-coated diffraction gratings are demonstrated for operation in the soft x-ray region.


Creative pattern cutting really pushes the boundaries of design. It is a luxury that breaks all traditional rules. The whole process, however, is costly, in both the use of cloth and the time it takes to produce a pattern. This article examines creative cutting from final year fashion students. It celebrates the students' individual philosophies towards creative cut and examines how the industry promotes pattern cutting to students as a viable career option. The role of the pattern cutter can have as much glamorous allure as the role of the designer, although it is at a lower key. Its allure comes from creative satisfaction and integrity. The article also discusses the realistic and commercial cost implications in the production of creatively cut garments and suggests pragmatic ways to maintain this luxurious creativity with cost effectiveness.


In recent years, "employability" has become an increasingly central concept in higher education, in no small part since it constitutes an important aspect of the Bologna Process. The project "Teachers' employability" is a project carried out on behalf of the Faculty of Teacher Education at Umeå University – one of the major providers of teacher education in Sweden – and is a part of a broader university effort to evaluate and increase employability. The aim of the project is to examine the situation of the university's teacher students after graduation, as well as to find out how the former students and their employers view their education. The study is based on the longitudinal individual database ASTRID, questionnaires and interviews. This paper reports findings from the project, focusing on 1) employment situation, income development and mobility patterns of recent alumni (class of 2000) and 2) primary employers' (school leaders) view of the quality and usefulness of the present teacher education curriculum. While employability is generally high, there are significant differences in career paths and income development, depending on for instance type of degree and place of residence. The interviews with school leaders reveal that although the present curriculum is perceived to have certain general limitations, it is viewed as more suited for pre-school rather than comprehensive school and gymnasium teacher education.


Ribbons are long narrow strips possessing three distinct material length scales (thickness, width, and length) which allow them to produce unique shapes unobtainable by wires or filaments. For example when a ribbon has half a twist and is bent into a circle it produces a M\"obius strip. Significant effort has gone into determining the structural shapes of ribbons but less is know about their behavior in viscous fluids. In this paper we determine, asymptotically, the leading-order hydrodynamic behavior of a slender ribbon in Stokes flows. The derivation, reminiscent of slender-body theory for filaments, assumes that the length of the ribbon is much larger than its width, which itself is much larger than its thickness. The final result is an integral equation for the force density on a mathematical ruled surface, termed the ribbon plane, located inside the ribbon. A numerical implementation of our derivation shows good agreement with the known hydrodynamics of long flat ellipsoids, and successfully captures the swimming behavior of artificial microscopic swimmers recently explored experimentally. We also study the asymptotic behavior of a ribbon bent into a helix, that of a twisted ellipsoid, and we investigate how accurately the hydrodynamics of a ribbon can be effectively captured by that of a slender filament. Our asymptotic results provide the fundamental framework necessary to predict the behavior of slender ribbons at low Reynolds numbers in a variety of biological and engineering problems.


Xanomeline is a unique agonist of muscarinic receptors that possesses functional selectivity at the M1 and M4 receptor subtypes. It also exhibits wash-resistant binding to and activation of the receptor. In the present work we investigated the consequences of this type of binding of xanomeline on the binding characteristics and function of the M1 muscarinic receptor. Pretreatment of CHO cells that stably express the M1 receptor for 1 hr with increasing concentrations of xanomeline followed by washing and waiting for an additional 23 hr in control culture media transformed xanomeline-induced inhibition of [3H]NMS binding from monophasic to biphasic. The high-affinity xanomeline binding site exhibited three orders of magnitude higher affinity than in the case of xanomeline added directly to the binding assay medium containing control cells. These effects were associated with a marked decrease in maximal radioligand binding and attenuation of agonist-induced increase in PI hydrolysis and were qualitatively similar to those caused by continuous incubation of cells with xanomeline for 24 hr. Attenuation of agonist-induced PI hydrolysis by persistently-bound xanomeline developed with a time course that parallels the return of receptor activation by prebound xanomeline towards basal levels. Additional data indicated that blockade of the receptor orthosteric site or the use of a non-functional receptor mutant reversed the long-term effects of xanomeline, but not its persistent binding at an allosteric site. Furthermore, the long-term effects of xanomeline on the receptor are mainly due to receptor down-regulation rather than internalization.


Abstract Reduced chick survival has been implicated in declines of greater sage-grouse (Centrocercus urophasianus) populations. Because monitoring survival of unmarked sage-grouse chicks is difficult, radiotelemetry may be an effective technique to estimate survival rates, identify causes of mortality, and collect ecological data. Previous studies have used subcutaneous implants to attach radiotransmitters to hatchlings of several species of birds with precocial young. Previous researchers who used subcutaneous implants in free-ranging populations removed chicks from the capture location and implanted transmitters at an alternate site. Because logistics precluded removing newly hatched greater sage-grouse chicks from the field, we evaluated a method for implanting transmitters at capture locations. We captured 288 chicks from 52 broods and monitored 286 radiomarked chicks daily for 28 days following capture during May and June 2001–2002. Two (<1%) chicks died during surgery and we did not radiomark them. At the end of the monitoring period, 26 chicks were alive and 212 were dead. Most (98%, 207/212) radiomarked chick mortality occurred ≤21 days posthatch and predation (82%, 174/212) was the primary cause of death. Necropsies of 22 radiomarked chicks did not indicate inflammation or infection from implants, and they were not implicated in the death of any chicks. Fate of 48 chicks was unknown because of transmitter loss (n = 16), radio failure (n = 29), and brood mixing (n = 3). Overall, the 28-day chick survival rate was 0.220 (SE = 0.028). We found that mortalities related to the implant procedure and transmitter loss were similar to rates reported by previous researchers who removed chicks from capture sites and implanted transmitters at an alternate location. Subcutaneous implants may be a useful method for attaching transmitters to newly hatched sage-grouse chicks to estimate survival rates, identify causes of mortality, and collect ecological data.


Force (and power)-velocity characteristics were determined at different stimulation frequencies in th situ rat muscle with nerve stimulation at 36 degrees C. In isometric contractions (duration, 150 ms), maximal force is generated at approximately 120 Hz. In contrast, in the high velocity (250 mm s-1) shortening contractions, frequencies of approximately 400 Hz were needed to obtain maximal dynamic force, while 120 Hz elicited only approximately 26% of the maximum. At the highest velocity measured, power production was significantly different (P < 0.05) among frequencies of 80, 120, 200 and 400 Hz, suggesting that maximal shortening velocity should be assessed using very high stimulation frequencies. However, the results further indicate that lower frequencies may be adequate in exercise studies that investigate fatigue and changes in power output during series of repetitive contractions.


In this study, we report a large family cluster consisting of 29 genetically related patients hospitalized with coronavirus disease‐2019 (COVID‐19). We sought to determine the clinical characteristics relevant to the clinical course of COVID‐19 by comparing the family cluster to unrelated patients with SARS‐CoV‐2 infection so that the presence of potential determinants of disease severity, other than traditional risk factors previously reported, could be investigated. Twenty‐nine patient files were investigated in group 1 and group 2 was created with 52 consecutive patients with COVID‐19 having age and gender compatibility. The virus was detected for diagnosis. The clinical, laboratory and imaging features of all patients were retrospectively screened. Disease course was assessed using records regarding outcome from patient files retrospectively. Groups were compared with respect to baseline characteristics, disease severity on presentation, and disease course. There was no difference between the two groups in terms of comorbidity and smoking history. In terms of inhospital treatment, use differed not significantly between two groups. We found that all 29 patients in the group 1 had severe pneumonia, 18 patients had severe pneumonia. Hospitalization rates, length of hospital stay, and transferred to intensive care unit were found to be statistically significantly higher in the group 1. In the present study, COVID‐19 cases in the large family cluster were shown to have more severe disease and worse clinical course compared with consecutive patients with COVID‐19 presenting to the same time. We believe further studies into potential genetic mechanisms of host susceptibility to COVID‐19 should include such family clusters.


Infusing factual knowledge into pre-trained models is fundamental for many knowledge-intensive tasks. In this paper, we proposed Mixture-of-Partitions (MoP), an infusion approach that can handle a very large knowledge graph (KG) by partitioning it into smaller sub-graphs and infusing their specific knowledge into various BERT models using lightweight adapters. To leverage the overall factual knowledge for a target task, these sub-graph adapters are further fine-tuned along with the underlying BERT through a mixture layer. We evaluate our MoP with three biomedical BERTs (SciBERT, BioBERT, PubmedBERT) on six downstream tasks (inc. NLI, QA, Classification), and the results show that our MoP consistently enhances the underlying BERTs in task performance, and achieves new SOTA performances on five evaluated datasets.


Ti, SiC and their composite materials have been widely used as high temperature structural material. The knowledge of interfacial stability between SiC and Ti is vital in high temperature applications. In this study, SiC/Ti diffusion couples were prepared to investigate the interfacial reactions between SiC and Ti at 1273 K. Phase forming sequence, microstructure and thermal stability of SiC/Ti interface were studied. It was indicated that after annealed at 1273 K for 10 days, 4 reaction layers were formed at the SiC/Ti interface. The diffusion path between SiC and Ti is SiC/Ti3SiC2/Ti5Si3/Ti5Si3+TiC/Ti3Si/Ti. As the annealing time prolong, the thicknesses of these reaction layers increased.


Abstract Over the past few years, volume interpretation software has made great usability achievements related in part to a continually advancing hardware sector. These applications showcase abilities to mine large quantities of data, mapping quickly with good accuracy, working with multi-attribute data and displaying all this information clearly. The value of volume interpretation software is clearly demonstrated on good quality data but rarely do we see examples when the quality of the data is less than desirable, such as subsalt environments in the Gulf of Mexico. Although interpreters are unable to leverage all the benefits of volume interpretation software, this is not a time to shy away from the software, rather it needs to be embraced. When the data quality is low, with limited frequency content, peak frequencies in the 11 to 13 Hz range, low signal to noise due to complex geometries, an interpreter has to use every bit of good data available to interpret salt related features and sediment interactions. By interactively animating through data and changing view angles, interpreters can effectively distinguish good signal from noise, identify residual multiples that were not eliminated in preprocessing, and gain insight into structural evolution of salt and related salt-sediment interactions. In addition, the ability to load multiple data volumes into memory enables interactive use of different types of data that aids the interpretation process, such as near, mid, or far stack data, sediment velocity flood, and velocity model to name a few. Volume interpretation and visualization is not new to the geoscience community, gaining exposure in the mid to late 1990s. One could argue that rapid growth of usage was inhibited more by the limitations and expense associated with hardware than the applications themselves. With the rollout of a more stable Linux environment and cheaper and more powerful hardware, 3-D volume interpretation and visualization software is becoming integrated into the common interpretation workflow. Working in team environments or at solitary workstations, interpreters use this software to scan large quantities of data, work with multiple data volumes, identify hydrocarbon indicators, study stratigraphic relationships and potential traps, and analyze complex structural environments. Interpreters, limited only by their imagination, have formulated workflows optimizing the interpretation process, coining phrases such as Parallel Interpretation (De La Pena et al., 2003) to describe workflows permitting quick and full evaluation of large datasets. Software venders consistently showcase their software, focusing on ease of use, efficiency, speed, and cycle time reduction. There is no question that with good data quality these applications are efficient and effective interpretation tools, utilizing capabilities such as seeding amplitudes, rapid automated horizon interpretations, and effective fault interpretations algorithms. What is never showcased is the application's effectiveness when good data quality is not longer available, such as the subsalt environment, where the signal to noise ratio is low, and frequency content is limited to 10 to 15 Hz with complex geometries. In this environment, automated horizon interpretation algorithms break down, and direct hydrocarbon indicators are no longer relevant. An interpreter than asks, "Are 3-D volume interpretation applications effective in such challenging environments, where many of its showcased capabilities are ineffective?" Although rarely discussed, the answer is yes, particularly because there is more to interpretation that automated picking. There is a need to comprehend the data and in order to comprehend the data, we need the most effective tools to see the data. This is where strengths of volume interpretation software come into play and make it a necessary tool for interpretation in data-poor areas. These strengths include data animation and manipulation. Another strength is the ability to quickly and simultaneously work with multiple data sets. One way volume interpretation software is effective in data challenging areas is its ability to smoothly animate data. Cognitive psychologists have found that dynamic visual stimuli, such as moving objects, attract attention (Pinto, 2006). In addition, the visual system uses mechanisms to integrate patterns along a trajectory for recognition (Nishida, 2004). Objects in motion are easier to identify and recognize. Nature works in the opposite way where animals use camouflage and remain motionless to hide from predators. The way objects move is also important for recognition. For example, dots that may appear random become familiar when organized into a pattern of motion that we recognized. Extending this practice to data challenging areas such as the subsalt environment in the Gulf of Mexico, and using volume interpretation software to animate the data, interpreters begin to distinguish noise from signal, artifacts from true geologic events, and identifying residual multiples. By analyzing the changing characteristics of the data during animation, geologic events become separated from noise trains and uncollapsed migrations that have different patterns of motion. Such characteristics would not be recognized using traditional interpretation software viewing every 10th or 20th line/trace, and geologic events hidden by the low signal may not be seen. Some companies have applied this theory to proprietary applications incorporating motion to enhance recognition and interpretation. Volume manipulation, interactively changing the viewing perspective, is another attribute of volume interpretation. Traditional interpretation software provides one perspective view, that being perpendicular to the screen. Remember the days of paper interpretation? It was not an uncommon sight to see geoscientists with their heads on the table, looking down a seismic section, changing their perspective view of the data to see if any subtle events appear. Monitors, particularly because of their size, make this very difficult to reproduce (have you ever seen a geoscientist looking down the length of a monitor?). Volume interpretation software puts this ability back into the hands of interpreters. Because these application take advantage of three dimensions, the way data are viewed is limited only by the interpreter. Data can be positioned in any orientation that may be advantageous for interpretation. This includes looking down the length of the data, tilting the data up or down, zooming in and out, and any combination of the above in order to capture maximum information. The prestack depth model building process is a workflow that is aided by volume interpretation software's capabilities, where salt model accuracy is the key to successful depth reprocessing projects. Animation and volume manipulations play a vital role in salt interpretation. Viewing salt morphologies in motion and changing the viewing angles helps interpreters work though more complex geometries, ensuring a more accurate salt model. Base of salt interpretation is the most challenging portion of the pre-stack depth migration workflow and the most pivotal. Even with an accurate top salt interpretation, the base of salt is not always an easily interpretable surface after the salt flood. Automated auto picking may work in isolated areas, but it is the animation and volume manipulation that aids interpreters. Animating though the data helps separate noise and residual multiples from signal by analyzing their movements. While in motion subtle events become more obvious, making base salt reflections easier to identify. Working with multiple data sets also assists base salt interpretation. Sequencing between different data such as full stack, mid stack and, if available, gathers, helps the interpreter identify potential base salt events, increasing confidence in the overall salt model. Working good quality data with high peak spectral frequencies is a luxury many interpreters do not have, especially in the deep-water Gulf of Mexico. Contrary to conventional wisdom, this is not a time to dismiss volume interpretation software's interpretation effectiveness. Although automated picking is limited, other characteristics makes the software an instrumental tool. Used in conjunction with traditional interpretation packages, abilities such as animation, volume manipulation, as well as working with multiple data sets enables the interpreter to use the limited data to the fullest extent, gleaning all available information.


Diminished bioavailability of nitric oxide (NO), the gaseous signaling molecule involved in the regulation of numerous vital biological functions, contributes to the development and progression of multiple age- and lifestyle-related diseases. While l-arginine is the precursor for the synthesis of NO by endothelial-nitric oxide synthase (eNOS), oral l-arginine supplementation is largely ineffective at increasing NO synthesis and/or bioavailability for a variety of reasons. l-citrulline, found in high concentrations in watermelon, is a neutral alpha-amino acid formed by enzymes in the mitochondria that also serves as a substrate for recycling l-arginine. Unlike l-arginine, l-citrulline is not quantitatively extracted from the gastrointestinal tract (i.e., enterocytes) or liver and its supplementation is therefore more effective at increasing l-arginine levels and NO synthesis. Supplementation with l-citrulline has shown promise as a blood pressure lowering intervention (both resting and stress-induced) in adults with pre-/hypertension, with pre-clinical (animal) evidence for atherogenic-endothelial protection. Preliminary evidence is also available for l-citrulline-induced benefits to muscle and metabolic health (via vascular and non-vascular pathways) in susceptible/older populations. In this review, we examine the impact of supplementing this important urea cycle intermediate on cardiovascular and metabolic health outcomes and identify future directions for investigating its therapeutic impact on cardiometabolic health.


Mineralizer is a key factor in the hydrothermal crystallization of most metal oxide materials. However, the effect of mineralizer on crystal facet growth is not well understood. Herein, YbFeO3 is taken as a model compound to determine the effect of mineralizer on its shape evolution during a mild hydrothermal crystallization process. By adjusting the concentration and ratio of NaOH and KOH, the shapes of YbFeO3 crystals showed two different facet formation routes: NaOH stabilizes {110} and {002} facets, while KOH stabilizes {101} facets. The percentage of each family of crystal facets could be tailored by changing the concentrations of mineralizer and NH4+. The shape formation mechanism of YbFeO3 was analyzed based on Bravais–Friedel–Donnay–Harker theory, in addition to their facet structures and interactions between crystal facets and Na+, K+ and NH4+. This study will not only improve understanding of the role of mineralizers in oxide crystallization, but also provide a crystal facet controllable method for the hydrothermal synthesis of oxide materials with potential anisotropy applications.


It is the policy of Kansas State University Agricultural Experiment Station and Cooperative Extension Service that all persons shall have equal opportunity and access to its educational programs, services, activities, and materials without regard to race, color, religion, national origin, sex, age, or disability. Kansas State University is an equal opportunity organization. These materials may be available in alternative formats.


Following the 2008 financial crisis, the United States' economy went into one of the most severe recessions since the Great Depression. In an attempt to stimulate the economy, the Federal Reserve lowered the federal funds rate to near zero in 2008. The unemployment decrease is not as large or fast as many had hoped, spurring much debate on whether business confidence may play a role in the federal funds rate's inability to affect the unemployment rate. It was hypothesized that high levels of economic policy uncertainty and low levels of business confidence negatively affect the unemployment rate. Using a regression analysis, results indicate that a negative contemporaneous relation exists between the federal funds rate and unemployment. Given the long term positive relationship between the federal funds rate and unemployment, lowering the federal funds rate should have brought down the unemployment rate, but that hasn't happened. The persistently high unemployment exists because the low level of business confidence is deterring businesses from hiring in the face of economic policy uncertainty despite the incentive of a low interest rate's incentive to do so.


Breast cancer is a leading cause of female mortality and despite advancements in diagnostics and personalized therapeutics, metastatic disease largely remains incurable due to drug resistance. Fortunately, identification of mechanisms of therapeutic resistance have rapidly transformed our understanding of cancer evasion and is enabling targeted treatment regimens. When the druggable estrogen receptor (ER, ESR1), expressed in two-thirds of all breast cancer, is exposed to endocrine therapy, there is risk of somatic mutation development in approximately 30% of cases and subsequent treatment resistance. A more recently discovered mechanism of ER mediated endocrine resistance is the expression of ER fusion proteins. ER fusions, which retain the protein's DNA binding domain, harbor ESR1 exons 1-6 fused to an in-frame gene partner resulting in loss of the 3' ER ligand binding domain (LBD). In this report we demonstrate that in no-special type (NST) and invasive lobular carcinoma (ILC) cell line models, ER fusion proteins exhibit robust hyperactivation of canonical ER signaling pathways independent of the ligand estradiol or anti-endocrine therapies such as Fulvestrant and Tamoxifen. We employ cell line models stably overexpressing ER fusion proteins with concurrent endogenous ER knockdown to minimize the influence of endogenous wildtype ER. Cell lines exhibited shared transcriptomic enrichment in pathways known to be drivers of metastatic disease, notably the MYC pathway. The heterogeneous 3' fusion partners, particularly transcription factors SOX9 and YAP1, evoked varying degrees of transcriptomic and cistromic activity that translated into unique phenotypic readouts. Herein we report that cell line activity is subtype-, fusion-, and assay-specific suggesting that the loss of the LBD, the 3' fusion partner, and the cellular landscape all influence fusion activity. Therefore, it will be critical to generate additional data on frequency of the ER fusions, in the context of the clinicopathological features of the tumor. Significance ER fusion proteins exhibit diverse mechanisms of endocrine resistance in breast cancer cell lines representing the no special type (NST) and invasive lobular cancer (ILC) subtypes. Our emphasize upon both the shared and unique cellular adaptations imparted by ER fusions offers the foundation for further translational research and clinical decision making.


As a state long noted for its potentially destabilizing ethnic heterogeneity, China has been extremely mindful of the northwestern region of Xinjiang, which is often viewed as one beset by what the Chinese have termed the "three evils" of separatism, fundamentalism, and terrorism. However, this mindfulness extends far beyond domestic policy alone. Indeed, China role in Central Asia is inextricably tied to its desire to strengthen its political control over, economic links with, and security posture in the adjacent Xinjiang region. The principal mechanism for achieving these intertwining aims is the Shanghai Cooperation Organization (SCO). Founded on June 15, 2001 by Russia, China, and the Central Asian republics of Kazakhstan, Kyrgyzstan, Tajikistan, and Uzbekistan, the SCO calls for closer political and economic cooperation and coordinated action among the member states to fight the "three evils," whether in Xinjiang or in the neighboring states themselves. In fact, at its inaugural meeting the SCO decided that China may be allowed to intervene militarily in Central Asia to combat terrorist threats at the request of regional governments. The organization's purpose was strengthened at the SCO's latest annual meeting on June 7,2002, in St. Petersburg as the presidents of the organization's member states legally created an SCO Anti-Terrorism Center. At the same time, the grouping is of great interest to China, not only to reinforce its hold over Xinjiang, but also to curb the rising influence of the United States in the region, in tandem with Russia if possible. The 2,060-mile border between China and the three Central Asian republics of Kazakhstan, Kyrgyzstan, and Tajikistan is in many places mountainous and difficult to patrol. Since China's major concern for the region is to ensure its peace and stability as a means of guaranteeing the security of its own restive western frontier, the Chinese leadership considers the presence of US military bases in Kazakhstan and Kyrgyzstan an attempt by Washington to bolster its own influence in Central Asia at the expense of China, Russia, and Iran. The US presence in Central Asia after the terrorist attacks of September 11, 2001, and the subsequent war on Afghanistan threaten China's defense of Xinjiang and challenge Beijing's nascent but conspicuous political, economic, and strategic roles in neighboring Central Asia. The SCO and Domestic Stability China spearheaded the establishment of the SCO largely as part of a security strategy to prevent Uighur separatists from using Central Asian states as a base for separatist activities in Xinjiang. The joint fight by SCO states against terrorism and threats to national sovereignty has won China assurances from Muslim Central Asian states that they will not provide assistance to their religious and ethnic brethren engaged in militant separatist activities in Xinjiang. Indeed, Islam is a salient characteristic of Xinjiang's eight-million strong Turkic-speaking Uighur ethnic group, which constitutes around 45 percent of the region's population. Thus, Beijing's commitment to regional security through the SCO to fight separatism and terrorism is based not only on its fear of violent Islamic rebellion in Central Asia affecting the Uighurs, but also its concern for being branded an anti-Muslim country by Central Asian republics or Middle Eastern states if it suppresses major uprisings in Xinjiang. This concern is valid, for Central Asia is host to a Uighur diaspora of about 500,000 individuals, with 200,000 of them in Kazakhstan alone. According to a statement released by the People's Republic of China (PRC) State Council Information Office on January 21, 2002, Uighur separatists were responsible for 200 terrorist incidents in Xinjiang from 1990 to 2001, killing 162 people and injuring more than 440 in their agitation for an independent state of "Eastern Turkestan" or "Uighuristan," their preferred names for Xinjiang. …


satisfactory according to modern standards. As an example of technical excellence I would mention the extremely fine changes which often accompany pneumoconiosis due to the more inert forms of dust. The resultant markings on a really good skiagram are considerably less than 1 mm. thick and afford proof that miliary tubercle should be recognized at a very early stage. I suppose the truth is that the supreme importance of the time factor is still not fully appreciated, especially among those whose aim appears to be the production of perfect studies in black-and-white rather than in a translucent grey, which is rich in -diagnostic detail for those who have eyes to see. Like Dr. Bannen, I am disturbed by the statement, " It is clear that x-ray examination cannot be relied upon for the early diagnosis of miliary tuberculosis," not only because I do not believe it, but because I have an instinctive dislike of so dogmatic a statement in medical matters.-I am, etc.,


Sometimes the problem of being unhappy raised when the children and their parents didn't have the same perceptions and indicators of child's happiness. The purpose of this study was to identify indicators of child happiness from the perspectives of the children and their mothers and to find out the link of the two perspectives. This research conducted in two phases. The purpose of Phase 1 was to find the definition and indicators of child's happiness from parents' and children's perspectives. Fifteen children (8-11 years old) and their mother were involved in FGD. The second phase was aimed to find out the link of the two. The child's happiness questionnaire was used to collect data on children's happiness from the children and their mother point of view. The participants were 112 primary school children (8-10 years old) in Yogyakarta and their mothers. Data were analyzed using ANOVA and t-test. In the first phase of the study was found both children and their mother perceive happiness as positive emotions but there were differences in its indicators. The second phase of the study indicated that there were significant differences on abstract child happiness indicators between mother and child (t=11.26, p=0.05; children's M=47.5; mothers' M=54.1). No differences in concrete indicators (t=10.01, p=0.06). There were significant differences in abstract indicators in terms of age group (F=6.37, p=0.01).


In humans, hypohydration attenuates sweat secretion and attenuates whole‐body heat loss, probably to mitigate further fluid losses and thereby support blood pressure regulation. Recently, however, we demonstrated that the hypohydration‐mediated reduction in net whole‐body heat exchange (evaporative heat loss – dry heat gain) was blunted in middle‐aged compared to younger men during moderate exercise in dry heat; albeit, the underpinning mechanisms could not be determined. Here we evaluated the hypothesis that those findings stemmed from a diminished influence of extracellular hyperosmolality on net whole‐body heat exchange in middle‐aged‐to‐older compared to young men. Consistent with that hypothesis, extracellular hyperosmolality induced by an intravenous infusion of hypertonic saline (3% NaCl) reduced net heat exchange and augmented rectal temperature to a greater extent in the young compared to middle‐aged‐to‐older men. Thus, age‐related differences in the influence of hypohydration on thermoregulatory function appear to be due to blunted sensitivity to hyperosmolality with ageing.


The open science movement, although not new to social science broadly, has gained momentum recently within communication science. In response, journals in our field have begun encouraging open science practices, from data and materials sharing to submitting preregistered research reports. However, this momentum has also led to some confusion over what is and is not considered open science and what the value of open sciences practices is. In this editorial we lay out an "onion model" of open science that describes increasing levels of transparency and suggests how open science practices can be understood less as a revolutionary concept but more as a logical extension of some of the historical pillars of scientific norms. Through this model, we provide tangible steps for how scholars may begin thinking about how to introduce open science practices into their current and future empirical efforts.


This study proposes that international joint ventures (IJVs) are terminated either when the initial purposes of the formation of the IJV have been achieved (intended termination), or when unanticipated contingencies that emerge in the external, internal, or inter-partner conditions after the establishment of the IJV impede the continuation of its operation (unintended termination). Our study examines the factors that affect intended and unintended termination and the longevity of IJVs. The findings show that approximately 90 percent of all IJV terminations are unintended and 10 percent intended, and that the frequency of intended termination and unintended termination varies noticeably depending on the initial purposes of formation. This suggests that the termination of IJVs is significantly contingent on their formation. The findings also show that the longevity of IJVs varies according to the initial purposes of formation, the initial conditions under which the IJV is formed, and the types of unanticipated contingencies that it encounters. The key theoretical issues and practical implications of the distinction between the intended and unintended termination of IJVs are also discussed. Copyright © 2007 John Wiley & Sons, Ltd.


We propose and analyze a novel theoretical and algorithmic framework for structured prediction. While so far the term has referred to discrete output spaces, here we consider more general settings, such as manifolds or spaces of probability measures. We define structured prediction as a problem where the output space lacks a vectorial structure. We identify and study a large class of loss functions that implicitly defines a suitable geometry on the problem. The latter is the key to develop an algorithmic framework amenable to a sharp statistical analysis and yielding efficient computations. When dealing with output spaces with infinite cardinality, a suitable implicit formulation of the estimator is shown to be crucial.


A smart grid will require, to greater or lesser degrees, advanced tools for planning and operation, broadly accepted communications platforms, smart sensors and controls, and real-time pricing. The smart grid has been described as something of an ecosystem with constantly communication, proactive, and virtually self-aware. The use of smart grid has a lot of economical and environmental advantages; however it has a downside of instability and unpredictability introduced by distributed generation (DG) from renewable energy into the public electric systems. Variable energies such as solar and wind power have a lack of stability and to avoid short-term fluctuations in power supplied to the grid, a local storage subsystem could be used to provide higher quality and stability in the fed energy. Energy storage systems (ESSs) would be a facilitator of smart grid deployment and a "small amount" of storage would have a "great impact" on the future power grid. The smart grid, with its various superior communications and control features, would make it possible to integrate the potential application of widely dispersed battery storage systems as well other ESSs. This work deals with a detailed updated review on available ESSs applications in future smart power grids. It also highlights latest projects carried out on different ESSs throughout all around the world.


-Height and age structures and recent height growth rates of white pine (Pinus strobus) and red maple (Acer rubrum) advance regeneration were examined in an even-aged bigtooth aspen ecosystem to determine if height growth inhibition in the understory is characteristic of these systems, as is suggested in general for even-aged forests. We hypothesized that the overstory was inhibiting height growth of understory stems and that the degree of inhibition would vary with overstory basal area and the relative contribution to total basal area of species differing in light-attenuating ability. The study was conducted in a mature bigtooth aspen forest on a dry-mesic site in which little density-independent mortality in the overstory had yet occurred. Correlations between age and height of advance regeneration on replicate plots were significant in 14 of 16 cases, but were highly variable and, on average, not very high. Correlations were stronger for white pine, indicating more consistent height growth than for red maple. However, red maple advance regeneration had greater mean height growth rates than white pine. Height distributions of advance regeneration, distributions of relative height increment over 5 yr, and mean 5-yr relative height increment were unrelated to plot-level measures of total overstory basal area and relative basal area of bigtooth aspen. These results indicate that height growth of advance regeneration was occurring in this forest, but height growth rates varied among individuals and species. The degree of inhibition in height growth was unrelated to plot-level measures of total overstory competition, as reflected in basal area. Further, variation in height growth rate was unrelated to the relative contribution to total basal area of canopy species differing in light-attenuating ability. The results of this study indicate that large overstory gaps are not required to promote establishment and height growth of advance regeneration in all even-aged aspen forests and that controls other than overstory structure may lead to variation in height growth rates of advance regeneration.


Sectors or industries characterized by limited or no use of technology to innovate are called lowtechnology (LT) sectors. They are usually dominated by small firms. Identifying a dearth of academicand practitioner work, this paper helps explain how institutions within a small-firm sector and interactions of these firms with institutions influence the occurrence or non-occurrence of LT innovation. Marble sector firms primarily located in north-west Pakistan have been selected for this purpose. Advocating the need for critical realism that has been an often ignored paradigm in management research, this paper offers a unique perspective on the paradigm's fundamental tenets which are events, objects, mechanisms and causal powers through an extensive and robustqualitative analysis using case study methodology. Findings reveal strong normative and cognitive institutions but weak regulative institutions with varying levels of consistencies or otherwise in terms of small firms' interactions with these institutions. Interestingly, cognitive institutions emerge as the main barrier to LT innovation which is a key contribution of this paper along with a hard tofind critical realist perspective.
Keywords: Low-technology innovation, LT innovation, institutions, interactions, critical realism


: Intrahepatic cholelithiasis is commonly associated with suppurative cholangitis and occurs equally in males and females. Patients usually present with a history of recurrent symptoms and a differential diagnosis which includes viral hepatitis, pancreatitis, myocardial infarction and perforated ulcer. Cholangiography including stereocholangiography is essential for localizing intrahepatic stones and ductal strictures. The guiding operative principle is to drain all infected bile distal to ducts obstructed with stones or stricture. This may also necessitate a bilioenterostomy with or without partial hepatic resection. Although these procedures are formidable in an acutely ill patient, a more simple but inappropriate choledocholithotomy and t-tube drainage done proximal to an obstructed intrahepatic duct will be ineffective and may result in continued sepsis and death.


Euler deconvolution is, as Pat Millegan describes it in a 2005 TLE article, "leading the pack" amongst automated interpretation techniques. The strength of the method rests primarily on its sound theoretical framework, namely the assumption that the measured potential field is homogeneous. On the other hand, a well documented weakness is the ambiguity introduced because the structural index must be input. We feel, then, it is worthwhile investigating a related approach that also begins by assuming homogeneity, but follows with a solution strategy that computes depths by some means other than solving Euler's equations. Importantly, this solution strategy bypasses the need for a priori knowledge of source geometry (structural index).


Women are increasingly being recognised internationally as essential actors in successful water supply management. Despite this, women are nevertheless still being excluded from water management activities which have proved to frequently result in water project failure. This has great consequences for water supply and water distribution capacity and efficiency. Women"s exclusion often stems from traditional and deeply rooted gender differences where women, compared to men, are not given the same rights and opportunities. Therefore, in particular focuses in this study are cultural barriers and socio-economic obstacles and challenges that may hinder female participation. Although Ghana is considered to have rich water resources, the production, distribution and use of water is not efficient, sufficient, or sustainable. This impedes the country"s socio-economic development. Most affected are women and children as they are often directly linked to the water source through their role as water collectors. In relation to this, the study investigates the importance of women"s participation in water management within the Republic of Ghana. Furthermore, the study examines the efficiency and adequacy of measures and actions implemented to improve female participation in water supply management. For data collection, a case study approach was adopted including an in-depth literature review, interviews with essential actors in Ghana and document analysis of Ghana"s National Water Policy and National Gender and Children Policy. Interviews and documents were analysed with a content analysis and a comparative analysis approach. The study found that women in Ghana, despite acknowledging their important role in Ghanaian water "society", experience great limitations in their participation in water management. Traditional norms and practices constitute a major obstacle together with a strongly male-dominated society that often prevents women from participating in the public sphere. The study indicates that there is a need to reform the legal system and the procedures of enforcement to encourage female participation in the water management. Furthermore, the Government of Ghana ought to improve financial, human, and material support within its agencies and associates to facilitate and enable female involvement. Moreover, there is a great need to improve women"s rights to, and attendance in, education. Additionally, raising the awareness of gender and women"s issues in general is crucial in order to initiate changes of traditional norms and practices and consequently improve their participation in the water management. By reforming Ghanaian women"s situation, their role and status will be strengthened, not only within water management, but as well in the wider society.


This article focuses on two interrelated themes that structure and fracture much of Sallust's monograph: time and morality. Driven by a strong narrative voice, vivid representations of its characters' speeches, and an innovative historiographical structure, the Bellum Catilinae imagines moral progress and decline from often-contradictory perspectives, with its narrative riven by the same asymmetry and variation that characterizes the author's Latin. Here, by considering several elements of Sallust's Preface and subsequent narrative of the conspiracy, I argue that Sallust challenges his readers' expectations about temporal structures and ultimately creates an atmosphere akin to that of a temporal civil war, where the moral value of memory loses its mooring and time's movement threatens to become meaningless. No longer, in other words, does the memory of earlier events prompt the performance of similarly virtuous actions in the present, and no longer can Rome's path be imagined to proceed upwards from the valorous deeds of its current citizens. Divided into two main sections, the paper considers first how Sallust offers a tentative hope for Rome's future in his Preface and early depictions of Catiline's conspiracy and then how those glimpses of optimism are utterly undone as the narrative proceeds. In Sallust's descriptions of Rome's origins, his own reasons for writings, and Catiline's impact on the Romans, he portrays both the conspiracy and his own record of it as the kind of forces that could prompt Rome to return to its earlier glory. In the second half of the paper, I claim that this possibility is destroyed in Sallust's construction of the speeches of Catiline, Caesar, and Cato. Each of these figures exploits the rhetorical power inherent in examples from the past, but they do so in strikingly different ways and for strikingly different reasons. The juxtaposition of their speeches shows the essentially malleable nature of memory, both in terms of its moral impact and its relationship to past events.


The boundary-value problem of diffraction from shallow metal gratings with finite conductivity is solved numerically by using an integral equation method. The electromagnetic field in the material is described by means of a series expansion of evanescent waves. As suggested by Hessel and Oliner, grating anomalies can be divided into two types: a Rayleigh type and a resonance type. The Rayleigh-type anomaly characterized by its appearance just at the Rayleigh wavelength λR occurs for both polarizations, but its appearance has some differences, depending on polarization. In the case of E∥ polarization, the grazing mode is suppressed, while in case of H∥ polarization, it is not. The resonance-type anomaly can be observed only for H∥ polarization as a strong peak or a dip at the longer-wavelength side of λR. It can be explained as the result of the resonance excitation of one surface mode which corresponds to a surface plasmon, and its marked features are the extra absorption of light and the relative phase shift of the diffracted field, which are not observed in Rayleigh-type anomalies.


The present study investigated the subcellular localization of inducible nitric oxide synthase (iNOS) during mouse oocyte meiotic maturation and fertilization using confocal microscopy, and further studied the roles of iNOS-derived NO in oocyte maturation by using an iNOS-specific inhibitor aminoguanidine (AG) and iNOS antibody microinjection. In germinal vesicle-stage oocytes, iNOS immunoreactivity was mainly localized in the germinal vesicle. Shortly after germinal vesicle breakdown, the iNOS immunoreactivity accumulated around the condensed chromosomes. At metaphase I and metaphase II, with the organization of chromosomes to the equatorial plate, iNOS immunoreactivity was concentrated around the aligned chromosomes, putatively the position of the metaphase spindle. The accumulation of iNOS immunoreactivity could not be detected at anaphase I and anaphase II. However, at telophase I and telophase II, the staining of iNOS was concentrated in the region between the separating chromosomes/chromatids. Furthermore, the staining of iNOS also accumulated in the male and female pronuclei in fertilized eggs. Germinal vesicle breakdown and the first polar body emission of the oocytes were significantly blocked by the iNOS-specific inhibitor AG in a dose-dependent manner. The germinal vesicle breakdown in oocytes injected with iNOS antibody was also inhibited. We found that the phosphorylation of mitogen-activated protein kinase in oocytes after germinal vesicle breakdown was inhibited by AG treatment. The control oocytes extruded a normal first polar body, while the AG-treated oocytes exhibited an elongated protrusion or no elongated protrusion. The results of confocal microscopy showed that the AG-treated oocytes were arrested at anaphase I-telophase I. Our results suggest that the iNOS-derived NO pathway plays important roles in mouse oocyte meiotic maturation, especially in germinal vesicle breakdown and the anaphase-telophase transition.