Uneven Reduction Research Articles

Optimization of tolerability and efficacy of the novel dual amylin and calcitonin receptor agonist KBP-089 through dose escalation and combination with a GLP-1 analog.

Amylin and GLP-1 agonism induce a well-known anorexic effect at dose initiation, which is managed by dose escalation. In this study we investigated how to optimize tolerability while maintaining efficacy of a novel, highly potent dual amylin and calcitonin receptor agonist (DACRA), KBP-089. Furthermore, we tested the GLP-1 add-on potential of KBP-089 in high-fat diet (HFD)-fed rats. KBP-089 potently activated both the amylin and calcitonin receptors in vitro and demonstrated a prolonged receptor activation as well as a potent reduction of acute food intake. HFD rats dosed every day or every second day obtained equal weight loss at study end, albeit with an uneven reduction in both food intake and body weight in rats dosed every second day. In a 4-fold dose escalation, KBP-089 induced a transient reduction in food intake at every escalation step, with reducing magnitude over time, and the following treatment with 2.5, 10, and 40 µg/kg resulted in an ~15% vehicle-corrected weight loss, a corresponding reduction in adipose tissue (AT), and, in all treatment groups, improved oral glucose tolerance (P < 0.01). Twofold and linear escalations suppressed body weight evenly with no significant reduction in food intake at either escalation step. KBP-089 (1.25 µg/kg) and liraglutide (50 µg/kg) reduced 24-h food intake by 29% and 37% compared with vehicle, respectively; however, when they were combined, 24-h food intake was reduced by 87%. Chronically, KBP-089 (1.25 µg/kg) and liraglutide (50 µg/kg) lowered body weight 8% and 2% in HFD rats, respectively, whereas the combination resulted in a 12% body weight reduction. Moreover, the combination improved glucose tolerance (P < 0.05). In conclusion, DACRAs act complementarily with GLP-1 on food intake and body weight. Furthermore, on escalation, KBP-089 was well tolerated and induced and sustained a significant weight loss and a reduction in AT in lean and HFD rats, underscoring the potential of KBP-089 as an anti-obesity agent.

Uneven reductions in high school students' alcohol use from 2007 to 2012 by age, sex, and socioeconomic strata

ABSTRACTBackground: Many Western countries have reported declines in adolescent alcohol use. This study examined changes in adolescent alcohol use in New Zealand between 2007 and 2012 and explored variations across sociodemographic strata. Methods: Data from 2 nationally representative, cross-sectional high school surveys conducted in 2007 (n = 7709) and 2012 (n = 7266) were examined. Changes in the prevalence of drinking in the past 4 weeks were examined among the total sample, as well as the frequency of drinking in the past 4 weeks and typical drinking-occasion quantity among drinkers. Only students residing in urban areas were included. Variation in changes was investigated across 4 demographic groups characterized by age (<16 years, ≥16 years) and sex. Interactions with household- and neighborhood-level socioeconomic position (SEP) identified any differential changes between socioeconomic strata. Results: From 2007 to 2012, significantly fewer students consumed alcohol in the past 4 weeks. Interaction analyses demonstrated that, among young females (<16 years), declines were significantly greater among those of high household SEP when compared with those of low household SEP. Among drinkers, reductions in the frequency of drinking were found among all demographic groups and SEP strata. Interaction analyses revealed that only young males (<16 years) showed significantly reduced typical drinking-occasion quantities. Among young females, significant interactions revealed a shift towards increasing typical drinking-occasion quantities among those of low household and neighborhood SEP, whereas their more advantaged counterparts showed no significant change over time. Conclusions: Fewer drinking occasions characterized the major declines in adolescent drinking between 2007 and 2012. Whereas young males showed reductions in the typical quantity consumed, young females of low household and neighborhood SEP progressed towards higher typical quantities. To address the uneven distribution of alcohol-related harm and improve the targeting of harm reduction initiatives, it remains imperative to examine changes in both the overall shift and shape of the distribution curve.

Computational study of gas dynamic influence on the flow in lattice of airfoils

A computational study of flow in lattices of airfoils of compressor of gas turbine engines with gas-dynamic effect on the aerodynamic traces behind outbound edges of input directing device was conducted. Summarized results of computational study in the form of dependency of levels of unevenness of flow from the intensity of gas-dynamic effect on the flow in a wide range of Reynolds numbers at fixed Mach numbers, the distances from the outbound edges and options for placement of slits for blowing additional air mass were presented. Using the results of computational study and comparative analysis with the results of some well-known experimental studies the data about the aerodynamic structure of the aerodynamic traces behind the axial compressor stator elements with the gas-dynamic effect on it were received and the efficiency of the gas-dynamic effect on the aerodynamic traces to improve the parameters and characteristics of the compressor elements of gas turbine engines was determined. Established that gas-dynamic effect on the flow in lattices of aerodynamic profiles is characterized by uneven flow reduction to minimum values of in a range of intensity values of blowing more air mass in the boundary layer. For Mach numbers of 0.15 – 0.45 at low, compared to the profile chord, distance from the original edge are actually centered on the axis of the trace. With increase of subsonic speeds and higher values of Reynolds numbers the opposite effect is observed – level unevenness of the flow begins to increase

Dynamic of girl students’ psycho-physiological indicators in process of their study at pedagogical higher educational establishment

Purpose: to study dynamic of psycho-physiological indicators of pedagogic higher educational establishments’ girl students. Material: in the research 510 girl students participated. We assessed: responsive abilities, static and dynamic balance, orientation in space, quickness of operational thinking, volume of rote memorization, distribution of attention, accuracy level, quickness and re-switching of attention, accuracy of fulfillment of task. Results: we have found weakening of accuracy of movement’s amplitude and pre-set value of force reproduction; reduction of indicators of response to vertically falling object, static and dynamic balance. We also registered improvement of indicators of nervous processes’ dynamic and ability to constructive praxis. Conclusions: uneven reduction of most of psycho-physiological indicators negatively reflects in girl students’ motor fitness level and professional abilities.

Influence of Anterior Cruciate Ligament Tear on Thigh Muscle Strength and Hamstring-to-Quadriceps Ratio: A Meta-Analysis.

Theoretical compensation after anterior cruciate ligament (ACL) tear could cause quadriceps weakness and hamstring activation, preventing anterior tibial subluxation and affecting the expected hamstring-to-quadriceps ratio. Although quadriceps weakness often occurs after ACL tears, it remains unclear whether hamstring strength and hamstring-to-quadriceps ratio increase in ACL deficient knees. This meta-analysis compared the isokinetic muscle strength of quadriceps and hamstring muscles, and the hamstring-to-quadriceps ratio, of the injured and injured limbs of patients with ACL tears. This meta-analysis included all studies comparing isokinetic thigh muscle strengths and hamstring-to-quadriceps ratio in the injured and uninjured legs of patients with ACL tear, without or before surgery. Thirteen studies were included in the meta-analysis. Quadriceps and hamstring strengths were 22.3 N∙m (95% CI: 15.2 to 29.3 N∙m; P<0.001) and 7.4 N∙m (95% CI: 4.3 to 10.5 N∙m; P<0.001) lower, respectively, on the injured than on the uninjured side. The mean hamstring-to-quadriceps ratio was 4% greater in ACL deficient than in uninjured limbs (95% CI: 1.7% to 6.3%; P<0.001). Conclusively, Decreases were observed in both the quadriceps and hamstring muscles of patients with ACL tear, with the decrease in quadriceps strength being 3-fold greater. These uneven reductions slightly increase the hamstring-to-quadriceps ratio in ACL deficient knees.

From Ex-Quota to In-Quota: An Analysis of Guidance Counsellorss Perceptions of the Impact of 2012 Budgetary Cutbacks on Their Care Work Across Different School Types.

Baker’s equality discourse (2004, 2009) and Lynch’s affective care dialogue (2002, 2007, 2009) informed this study on the impact of budgetary cutbacks on guidance in Irish schools, which found that uneven guidance reductions, primarily between fee-charging schools and schools in the Free Education Scheme (FES), resulted in an unequal distribution of care and a negative student care experience. From its inception in the 1970s, guidance in Irish schools had a holistic, equality agenda, and it is discussed as one means of reducing the impacts o f many inequalities in schools. While guidance in all schools helps students make choices in their lives, the thesis showed that it operated differently in fee-charging schools and FES schools, with greater demands from students for help with personal decisionmaking and counselling in FES schools and by contrast a greater emphasis on educational decision-making and career decision-making in fee-charging schools. Factors such as social class, familial habitus, parent-power, cultural, social and economic capitals, and institutional habitus were shown to influence young people and their parents’ decision-making, and in turn the guidance provided in schools. Care was not distributed equally across all school types. The study demonstrated that students in FES schools experienced compromised care, due to a large reduction in counselling appointments. With a reported rise in student mental health issues, the demand for counselling in FES schools increased, but as these schools prioritised career guidance, counselling was neglected, the quality of the service suffered and it became a reactionary crisis-intervention service, mirroring the trivialisation and neglect of the affective in education (Lynch, 2009). Managing greater care demands with less time resources also increased guidance counsellors’ stress. The change from an ex-quota to an in-quota guidance allocation thus had an unequal impact across schools and a negative impact on the quality and distribution of student care in some school types.

A Technique to Guide and Measure the Reduction of a Processed Mandibular Complete Denture for Resilient Soft Liner

A resilient soft liner (RSL) has been used in processed complete dentures but controlling its thickness has always been a challenge because of uneven reduction of the denture’s intaglio surface. Use of a thermoplastic vacuum-formed template and an endodontic K-file, as guides, for the reduction of a processed mandibular complete denture to receive RSL is described in the present report. A processed mandibular complete denture is prepared by reducing its borders and drilling holes in its surface. A thermoplastic sheet adapted to the intaglio surface and an endodontic K-file with rubber stop adjusted to the desired dimension are used as guides to the reduction procedure and allows intermittent measuring of the reduced areas. This technique helps in reducing the processed denture’s intaglio surface in a controlled manner thus maintaining the strength of the denture base and effectiveness of soft liner. It also makes the application of resilient soft liner a cost and time effective maneuver

Improving thermal model prediction through statistical analysis of irradiation and post-irradiation data from AGR experiments

As part of the High Temperature Reactors (HTR) R&D program, a series of irradiation tests, designated as Advanced Gas-cooled Reactor (AGR), have been defined to support development and qualification of fuel design, fabrication process, and fuel performance under normal operation and accident conditions. The AGR tests employ fuel compacts placed in a graphite cylinder shrouded by a steel capsule and instrumented with thermocouples (TC) embedded in graphite blocks enabling temperature control. While not possible to obtain by direct measurements in the tests, crucial fuel conditions (e.g., temperature, neutron fast fluence, and burnup) are calculated using core physics and thermal modeling codes. This paper is focused on AGR test fuel temperature predicted by the ABAQUS code's finite element-based thermal models. The work follows up on a previous study, in which several statistical analysis methods were adapted, implemented in the NGNP Data Management and Analysis System (NDMAS), and applied for qualification of AGR-1 thermocouple data. Abnormal trends in measured data revealed by the statistical analysis are traced to either measuring instrument deterioration or physical mechanisms in capsules that may have shifted the system thermal response. The main thrust of this work is to exploit the variety of data obtained in irradiation and post-irradiation examination (PIE) for assessment of modeling assumptions. As an example, the uneven reduction of the control gas gap in Capsule 5 found in the capsule metrology measurements in PIE helps identify mechanisms other than TC drift causing the decrease in TC readings. This suggests a more physics-based modification of the thermal model that leads to a better fit with experimental data, thus reducing model uncertainty and increasing confidence in the calculated fuel temperatures of the AGR-1 test.

Influence of repeated freeze-thaw on dynamic modulus and damping ratio properties of silty sand

Under repeated freezing and thawing in deep seasonal frozen regions, the stability and strength of the soil are imposed in the form of large uneven settlement, instability and strength reduction, which affect the normal operation of railway lines. This study is to obtain the influencing rules of freeze-thaw on the dynamic properties(dynamic strain, confining pressure and compactness) of silty sand. Based on an amount of inner tests, the dynamic modulus and damping ratio properties of silty soil subjected to repeated freeze-thaw cycles were deeply researched and analyzed. The results are as follows: At the same dynamic strain, the relationship of dynamic stress and freeze-thaw cycles presents negative correlation, and the relationship of dynamic stress, confining pressure and compactness present positive correlation. The dynamic modulus double decreases while the damping ratio double increases with incremental increase in dynamic strain. The dynamic modulus sharply decreases while the damping ratio increases with incremental increase in freeze-thaw cycles, and then the changes level off after six freeze-thaw cycles. The dynamic modulus increases while the damping ratio decreases as the confining pressure and compactness increase at the same strain level.

Mediterranean agriculture under climate change: adaptive capacity, adaptation, and ethics

In the coming decades, the Mediterranean region is expected to experience various climate impacts with negative consequences on agricultural systems and which will cause uneven reductions in agricultural production. By and large, the impacts of climate change on Mediterranean agriculture will be heavier for southern areas of the region. This unbalanced distribution of negative impacts underscores the significance and role of ethics in such a context of analysis. Consequently, the aim of this article is to justify and develop an ethical approach to agricultural adaptation in the Mediterranean and to derive the consequent implications for adaptation policy in the region. In particular, we define an index of adaptive capacity for the agricultural systems of the Mediterranean region on whose basis it is possible to group its different sub-regions, and we provide an overview of the suitable adaptation actions and policies for the sub-regions identified. We then vindicate and put forward an ethical approach to agricultural adaptation, highlighting the implications for the Mediterranean region and the limitations of such an ethical framework. Finally, we emphasize the broader potential of ethics for agricultural adaptation policy.

An application of the parametrization of all multi-period repetitive controllers for reduction of rotational unevenness in motors

Multi-period repetitive controllers were proposed by Gotou et al., in order to improve the disturbance attenuation characteristic of modified repetitive control systems. Rec ently, the parametrization of all stabilizing multi-perio d repetitive controllers was obtained. Since the parametrization of all stabilizing multi-period repetitive controllers was obta ined, we can express previous studies of multi-period repetitive co ntrollers in a uniform manner. In addition, a multi-period r epetitive controller can be designed systematically. However, an application of control system using the parametrization of all stabilizing multi-period repetitive controllers has not examined yet. In this paper, we show the effectiveness of the control system using the parametrization of all stabilizing multi-period repet itive controllers for reduction of rotational unevenness i n motors.

The fractions of short- and long-range connections in the visual cortex

When analyzing synaptic connectivity in a brain tissue slice, it is difficult to discern between synapses made by local neurons and those arising from long-range axonal projections. We analyzed a data set of excitatory neurons and inhibitory basket cells reconstructed from cat primary visual cortex in an attempt to provide a quantitative answer to the question: What fraction of cortical synapses is local, and what fraction is mediated by long-range projections? We found an unexpectedly high proportion of nonlocal synapses. For example, 92% of excitatory synapses near the axis of a 200-microm-diameter iso-orientation column come from neurons located outside the column, and this fraction remains high--76%--even for an 800-micromocular dominance column. The long-range nature of connectivity has dramatic implications for experiments in cortical tissue slices. Our estimate indicates that in a 300-microm-thick section cut perpendicularly to the cortical surface, the number of viable excitatory synapses is reduced to about 10%, and the number of synapses made by inhibitory basket cell axons is reduced to 38%. This uneven reduction in the numbers of excitatory and inhibitory synapses changes the excitation-inhibition balance by a factor of 3.8 toward inhibition, and may result in cortical tissue that is less excitable than in vivo. We found that electrophysiological studies conducted in tissue sections may significantly underestimate the extent of cortical connectivity; for example, for some projections, the reported probabilities of finding connected nearby neuron pairs in slices could understate the in vivo probabilities by a factor of 3.

Anisotropic Diffusion Of Fluorescently Labeled Atp In Cardiomyocytes Determined By Raster Image Correlation Spectroscopy

A series of experimental data point to the existence of profound diffusion restrictions of ADP/ATP in rat cardiomyocytes. To be able to analyze and estimate the role of intracellular diffusion restrictions on bioenergetics, the intracellular diffusion coefficients of metabolites have to be determined. The aim of this work was to develop a practical method for determining diffusion coefficients in anisotropic medium and to estimate the overall diffusion coefficients of fluorescently labeled ATP in rat cardiomyocytes. For that, we have extended raster image correlation spectroscopy (RICS) protocols. The extension of RICS that allowed us to study diffusion in anisotropic media is based on the fact that RICS relates spatial and temporal information in the analysis. By modifying the direction of the laser scan, we altered the relationship between spatial and temporal fluctuations. This allowed us to relate autocorrelation functions with direction of the scan thus discriminating between diffusion coefficients in different directions. Using this extended protocol, we estimated diffusion coefficients of ATP labeled with the fluorescent conjugate Alexa Fluor 647 (Alexa-ATP). In the analysis, we assumed that the diffusion tensor can be described by two values: diffusion coefficient along the myofibril and across it. The average diffusion coefficients found for Alexa-ATP were as follows: 83+/−14microm2/s in longitudinal and 52+/−16microm2/s in transversal directions (n=8, mean+/−SD). Those values are ∼2 (longitudinal) and ∼3.5 (transversal) times smaller than the diffusion coefficient value estimated for surrounding solution. Such uneven reduction of average diffusion coefficient leads to anisotropic diffusion in the rat cardiomyocytes. While the source for such anisotropy is uncertain, we speculate that it may be induced by ordered pattern of intracellular structures in rat cardiomyocytes.

Anisotropic diffusion of fluorescently labeled ATP in rat cardiomyocytes determined by raster image correlation spectroscopy

A series of experimental data points to the existence of profound diffusion restrictions of ADP/ATP in rat cardiomyocytes. This assumption is required to explain the measurements of kinetics of respiration, sarcoplasmic reticulum loading with calcium, and kinetics of ATP-sensitive potassium channels. To be able to analyze and estimate the role of intracellular diffusion restrictions on bioenergetics, the intracellular diffusion coefficients of metabolites have to be determined. The aim of this work was to develop a practical method for determining diffusion coefficients in anisotropic medium and to estimate the overall diffusion coefficients of fluorescently labeled ATP in rat cardiomyocytes. For that, we have extended raster image correlation spectroscopy (RICS) protocols to be able to discriminate the anisotropy in the diffusion coefficient tensor. Using this extended protocol, we estimated diffusion coefficients of ATP labeled with the fluorescent conjugate Alexa Fluor 647 (Alexa-ATP). In the analysis, we assumed that the diffusion tensor can be described by two values: diffusion coefficient along the myofibril and that across it. The average diffusion coefficients found for Alexa-ATP were as follows: 83 ± 14 μm2/s in the longitudinal and 52 ± 16 μm2/s in the transverse directions (n = 8, mean ± SD). Those values are ∼2 (longitudinal) and ∼3.5 (transverse) times smaller than the diffusion coefficient value estimated for the surrounding solution. Such uneven reduction of average diffusion coefficient leads to anisotropic diffusion in rat cardiomyocytes. Although the source for such anisotropy is uncertain, we speculate that it may be induced by the ordered pattern of intracellular structures in rat cardiomyocytes.

Reduction of Unevenness in Occupant Injury Index on Passenger Side in Frontal Collision

Reduction of Unevenness in Occupant Injury Index on Passenger Side in Frontal Collision

Modelling a mixed system of air pollution fee and tradable permits for controlling nitrogen oxide: a case study of Taiwan*

A mixed‐integer non‐linear programming model that minimises the total regulatory costs of controlling nitrogen oxide is used to investigate how a newly proposed permit trading scheme in Taiwan, which incorporates the features of banking and a non‐one‐to‐one trading ratio, may affect firms’ emission reduction strategies and permit trading decisions. Compared to the previous regulation where only an air pollution fee is used, the new regulation that requires a reduction in emissions by 10 per cent from the emission level in the year 2000 for a 5 year period will increase the costs by 77 per cent, which is equivalent to US$9.87 million. The design of banking and the increasing returns to scale characteristic of pollution control among firms might lead to an uneven reduction in emissions in each year. Setting a lower reservation rate for banking would, however, help maintain a more stable environmental quality without a significant loss to the government in terms of air pollution fee revenue.

Bringing Time Back In: A Study on the Influence of Travel Time Variations and Facility Opening Hours on Individual Accessibility

Although recent studies of individual accessibility have used detailed representations of urban street networks, unrealistic measures of travel time based on assumptions about constant travel speeds through the network were often used. Utilizing constant travel times does not allow for daily congestion and assumes that the effects of congestion are uniform throughout the city and affect all people equally. This research measures individual space-time accessibility in order to show that the incorporation of locally specific travel times within a street network allows a significant increase in the ability to realistically evaluate individual accessibility within cities. The results show that the accessibility of individuals within cities is not homogenous, and neither does access to employment or shopping opportunities vary according to common expectations about urban form and human behavior. Instead, the role of distance in predicting accessibility variations within cities is quite limited. This article also shows that incorporating time into accessibility measures in the form of congestion and business hours leads to additional (and highly spatially uneven) reductions in accessibility, revealing that the temporal dimension is very important to accurately assessing individual accessibility.

Reduction of torque unevenness of DC micro motor

Reduction of torque unevenness of DC micro motor

Analysis of electromagnetic fields using the finite‐difference time‐domain method in a microwave oven loaded with high‐loss dielectric

AbstractThere are few examples for three‐dimensional electromagnetic analysis for a high‐loss dielectric water load which has one of the highest relative permittivities of 80.4 among food items placed in a microwave oven. In this paper, the three‐dimensional finite‐difference time‐domain (FD‐TD) method is used for the analysis of the electromagnetic field inside the water load. In the fundamental investigation using the high‐loss dielectric loaded rectangular waveguide, it is confirmed that the FD‐TD numerical results with Yee's cell pitch which is set at about one‐tenth the wavelength reduced within the dielectric, agree almost with the exact solution based on the transmission theory. After the confirmation of the validity, the electromagnetic field within a water load placed on a metal turntable is analyzed. The water load has a cylindrical shape with a diameter of 64 mm and a height of 80 mm. As a result, the reduction of heating unevenness by the turntable can be predicted visually and quantitatively. In this analysis, the steady‐state solution can be obtained after 300 iterations while the heating pattern is stabilized after 100 to 200 iterations.

The histology of laser thermo-chondro-plasty

Introduction: Giving a new shape to a cartilage graft has been a matter of continuous study. In 1991, our group managed to change the shape of human nasal septal samples using CO 2 irradiation. This procedure, which we call thermo-chondro-plasty, was achieved without the macroscopic carbonization or ablation of the tissue. Methods: To study the thermo-chondro-plasty effect of the CO 2 laser irradiation on human nasal septal cartilage, samples were irradiated in selected laser parameters and then examined with light and electron microscopy. Results and Conclusion: We believe that it was primarily the proteoglycan component of the matrix in which we induced the maximum alterations. The destruction of their water-binding ability led to an uneven reduction of the interlocked tensile stresses of the cartilage and resulted in its transformation.