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Abstract: Antagonism of the kappa opioid receptor (KOR) has been reported to have anti-depressant-like properties. The dynorphin/KOR system is a crucial neurochemical substrate underlying the pathologies of addictive diseases, affective disorders and other disease states. However, the molecular underpinnings and neuroanatomical localization of the dysregulation of this system have not yet been fully elucidated. Utilizing the Porsolt Forced Swim Test (FST), an acute stressor commonly used as in rodent models measuring antidepressant efficacy, male Sprague–Dawley rats were subject to forced swimming for 15min, treated 1h with vehicle or norbinaltorphimine (nor-BNI) (5 or 10mg/kg), and then 1day later subject to FST for 5min. In accordance with previous findings, nor-BNI dose dependently increased climbing time and reduced immobility. In comparison to control animals not exposed to FST, we observed a significant elevation in prodynorphin (pDyn) mRNA levels following FST using real-time optical polymerase chain reaction (PCR) in the caudate putamen but not in the nucleus accumbens, hypothalamus, amygdala, frontal cortex, or hippocampus. nor-BNI treatment did not affect pDyn mRNA levels in comparison to animals that received vehicle. The corresponding brain regions from the opposite hemisphere were analyzed for underlying chromatin modifications of the prodynorphin gene promoter region using chromatin immunoprecipitation with antibodies against specifically methylated histones H3K27Me2, H3K27Me3, H3K4Me2, and H3K4Me3, as well as CREB-1 and MeCP2. Significant alterations in proteins bound to DNA in the Cre-3, Cre-4, and Sp1 regions of the prodynorphin promoter were found in the caudate putamen of the FST saline-treated animals compared to control animals, with no changes observed in the hippocampus. Epigenetic changes resulting in elevated dynorphin levels specifically in the caudate putamen may in part underlie the enduring effects of stress. [Copyright &y& Elsevier]

Abstract: Background and Aim: In patients with type 2 diabetes mellitus, the relationship between lowering glycated hemoglobin (HbA1c) and macrovascular complications is not clear and therefore lowering the level of HbA1c is controversial. Methods and Results: We searched for all randomized controlled trials comparing the effects of intensive and standard glycemic control on vascular events in patients with type 2 diabetes mellitus. The primary endpoint was combined macrovascular complications, including cardiac events, stroke and peripheral vascular disease. Fixed and random effect models were used to analyze the results. Eight studies were included according to selection criteria. The results showed no benefits of intensive glycemic control on macrovascular and microvascular complications (P >0.1), but a higher rate of severe hypoglycemia (P <0.00001) in the intensive control group when the target HbA1c level was <7.0%. When the target HbA1c level was lowered to 7.0–7.9%, intensive glycemic control showed benefits on the reduction of microvascular events (P <0.05) without increasing the risk of severe hypoglycemia (P =0.74), but no influence on macrovascular complications (P >0.1). Conclusion: The results of this analysis suggest that a target HbA1c level of 7.0–7.9% may be a better glycemic control target than that of <7.0% in patients with established type 2 diabetes mellitus. [Copyright &y& Elsevier]

Abstract: Titanium alloy Ti–6Al–4V and nickel-based superalloy Inconel 718 have been widely employed in modern manufacturing. The published literature on high speed machining (HSM) of the two materials often involves different machining set-up, which makes it difficult to directly apply the research findings from one material to the other to select the most appropriate tool geometry and cutting conditions. A comparative experimental study of HSM of Ti–6Al–4V and Inconel 718 is conducted in this paper using the same machining set-up. The scope of this study is limited in high speed finish machining, where the tool edge geometry plays a significant role. The experimental set-up and the methods of measuring the cutting forces and the tool edge radius are introduced. A total of 40 orthogonal high speed tube-cutting tests were performed, involving five levels of cutting speeds and four levels of feed rates. Based on extensive experimental data, the similarities and differences between HSM of Ti–6Al–4V and Inconel 718 are quantitatively compared and qualitatively explained in terms of four quantities: (1) the cutting force F c , (2) the thrust force F t , (3) the resultant force R, and (4) the force ratio F c /F t . A total of 12 empirical regression relationships are obtained. [Copyright &y& Elsevier]

Abstract: The effects of tool edge geometry in machining have received much attention in recent years due to a variety of emerging machining techniques, such as finish hard turning and micro-machining. In these techniques, the uncut chip thickness is often on the same order of magnitude as tool edge dimension. This paper presents and analyses the results of our recent experimental and theoretical study on the effects of tool edge geometry in machining. Both chamfered and honed tools are investigated covering a wide range of cutting speed and feed rate conditions. The three aluminum alloys 7075-T6, 6061-T6, and 2024-T351 are selected as work materials for particular research purposes. The cutting force, the thrust force, the ratio of the cutting force to the thrust force, and the chip thickness are measured. The similarities and differences in machining with a chamfered tool and with a honed tool are compared. A new slip-line model of chip formation for machining with a chamfered tool is proposed. Good agreement has been reached between the predicted and experimental results. The effects of different aluminum alloys and cutting speeds on the cutting forces, especially on the thrust force, are also studied. [Copyright &y& Elsevier]

Abstract: Extensive investigations on built-up edge (BUE) formation in machining have been conducted in the past. However, very little effort has been made to quantitatively predict the size of the BUE and its effect on chip flow and cutting forces under different machining conditions. This prediction is important because it is the key to predicting the fluctuation of cutting forces and provides better rationale for explaining various machining phenomena associated with BUE formation. A new slip-line model for machining with BUE formation and its associated hodograph are proposed in this paper. Consisting of four slip-line sub-regions, the new slip-line model meets both the stress equilibrium and velocity requirements of material flow. The new model simultaneously predicts the length and height of the BUE, cutting and thrust forces, chip up-curl radius, chip thickness, and tool–chip contact length. Dewhurst and Collins''s matrix technique for numerically solving the slip-line problem is employed in the mathematical formulation of the model, with non-unique solutions being obtained. It is demonstrated that one of the four slip-line angles included in the new model directly governs the size and surface shape of the BUE. Compared with the well-known Lee and Shaffer''s model, the new model predicts a much longer BUE covering a larger portion of the tool rake face. A small tool rake angle tends to generate a large BUE. The predicted trends of the variation of relevant machining parameters are consistent with experimental observations. [Copyright &y& Elsevier]

The forces, chip thickness, and natural tool–chip contact length in machining with a double-rake-angled tool are predicted in Part II of the present study. It is revealed that in comparison with a single-rake-angled tool, a double-rake-angled tool increases the forces, especially the thrust force. However, the increase in chip thickness and tool–chip contact length is not significant under the input conditions specified in the present study. The effect of seven input variables of the proposed model is quantitatively investigated. The predicted variations of forces, chip thickness, and natural tool–chip contact length are in good agreement with theoretical and experimental results obtained by other researchers. The interrelationships among the resultant force, the chip thickness, and the natural tool–chip contact length are established, which provides a new and promising method to estimate the tool–chip contact length by employing the resultant force. It is demonstrated that the model can also be extended to study the problem of machining with a groove-type chip breaker tool. [Copyright &y& Elsevier]

Given the growing number of applications of groove-type chip breaker tools in modern machining, it is becoming increasingly important to study the tool–chip contact on the tool secondary rake face. This type of tool–chip contact significantly changes not only the state of stresses in the plastic deformation region, but also changes the distribution of forces and temperatures over the tool rake face. A new slip-line model accounting for the tool–chip contact on the tool secondary rake face is proposed in this paper. The model also takes into account chip curl and incorporates seven slip-line models developed for machining during the last six decades as special cases. Dewhurst and Collins''s matrix technique for numerically solving slip-line problems and Powell''s algorithm of nonlinear optimization are employed in the mathematical formulation of the model. The inputs of the model include (a) the tool primary rake angle γ1, (b) the tool secondary rake angle γ2, (c) the tool land length h, (d) the undeformed chip thickness t1, (e) the ratio of hydrostatic pressure PA to the material shear flow stress k, (f) the ratio of frictional shear stress τ1 on the tool primary rake face to the material shear flow stress k, and (g) the ratio of frictional shear stress τ2 on the tool secondary rake face to the material shear flow stress k. The outputs of the model include (a) the cutting force Fc/kt1w and the thrust force Ft/kt1w, (b) the chip up-curl radius Ru, (c) the chip thickness t2, and (d) the natural tool–chip contact length ln. [Copyright &y& Elsevier]

This paper presents analytical predictions and experimental validation of a recently developed universal slip-line model for machining with restricted contact cut-away tools. Three important machining parameters, i.e. the cutting force ratio, chip thickness, and chip back-flow angle, are predicted on the basis of: (1) the universal slip-line model; (2) a maximum value principle for determining the state of stresses in the plastic region in restricted contact machining; (3) Dewhurst and Collins’ matrix technique for numerically solving slip-line problems; and (4) Powell’s algorithm for non-linear optimizations. All predictions are based on purely theoretical calculations with no experimental/empirical data as input. The extensive comparisons between theory and experiments show a reasonable agreement. Major new research findings from this study include: (1) the applicable ranges of an extreme friction slip-line model and of Johnson’s and Usui and Hoshi’s slip-line models; and (2) the general rule of the variation of tool–chip friction conditions. Tool–chip contact in machining with restricted contact cut-away tools is categorized into three broad cases. A theoretical method is also presented in the paper to distinguish different tool–chip contact cases in practical machining situations. [Copyright &y& Elsevier]

In this work, we examined the microstructure evolution, as well as the micromechanical and magnetic properties of FeCoNiAlSi high-entropy alloys (HEAs) under high pressure solidification (HPS). According to the results, FeCoNiAlSi alloy solidified at 0.1 MPa (atmospheric pressure) contains three kinds of phases: grain boundary (GB)phases, peritectic phases, and primary phases. As the solidification pressure increases to 7 GPa, the volume fraction of GB phases and peritectic phases decreases, while the volume fraction of primary phase increases by 82.8%. In addition, the Fe of the primary phase increases by 63.6 %, which enhances the ferromagnetism and exchange coupling properties of the alloy. Furthermore, HPS also reduces the magneto-crystal anisotropy of the GB phases and the pinning effect of boundaries on domain movement. Additionally, with the increasing solidification pressure, the FeCoNiAlSi HEAs shows stronger ferromagnetic. When solidified at 7Gpa, a reduction of 51.5 % in intrinsic coercivity(H MC) was observed, as was an increase of 106 % in magnetic polarization strength (Js). As well, HPS significantly increased the high temperature magnetic properties of FeCoNiAlSi alloy as well as the microhardness(i.e. from 8.25 GPa to 10.15 GPa). According to these results, HPS is an effective method for developing new functional applications for FeCoNiAlSi HEAs. • The Js (HMC)of the FeCoNiAlSi HEAs increased (decreased) by 106% (51.5%) after HPS at 7Gpa, The Tc are also improved. • The pinning effect of boundary on magnetic domain movement were reduced after HPS and exchange coupling was enhanced. • The volume fraction of primary phase and the content of Fe in primary phase increased when solidified under 7GPa. • The promoted solution strengthening after HPS significantly improved the microhardness (i.e. from 8.25GPa to 10.15GPa). [ABSTRACT FROM AUTHOR]

A comprehensive study has been conducted on the effects of high-pressure solidification (HPS) on the evolution of microstructures, micromechanical properties, and magnetic properties of FeCoNiSi alloys. As solidification pressure increases(up to 7GPa), FeCoNiSi alloy's columnar grain changes into an equiaxed grain, and the grain size and Ni-rich precipitates are significantly refined. Furthermore, HPS facilitates the conversion of in-coherent matrix/precipitates interface of alloy solidified under atmospheric pressure into semi-coherent, which reduces the pinning effect of phase boundaries on the motion of the magnetic domains and enhances the exchange coupling between matrix and precipitates. As FeCoNiSi alloy solidifying under 7GPa, the maximum magnetic permeability (μ m) is significantly increased (from 52,600 to 113,000), the inherent coercivity is decreased by 29.5%, and the saturation magnetic polarization(Js) is increased by 21%. In addition, the high temperature magnetic properties of FeCoNiSi alloys are improved by HPS. Furthermore, HPS produces compressive stress in both the precipitates and matrix, which significantly improved the modulus of precipitates and matrix (i.e. from 171GPa to 215 GPa in matrix),as well as microhardness (i.e. from 5.46 GPa to 10.65 GPa in matrix). Based on the results of these studies, HPS is capable to improve the comprehensive properties of magnetic alloys significantly. • The J s and μ max (H MC) of FeCoNiSi alloy are increased (decreased) by 21% and 114% (29.5%) after solidified under 7GPa. • HPS produces compressive stress in the precipitates and matrix and significantly improved the modulus and microhardness. • HPS refine the microstructure of FeCoNSi alloy and result in the semi-coherent interface. • The semi-coherent interface enhances the exchange coupling effect between precipitates and matrix. [ABSTRACT FROM AUTHOR]

Abstract: Exposure to arsenic through domestic burning arsenic-containing coal causes various tumors in a population of Guizhou, China. The glycophorin A (GPA) assay is a human mutation assay detecting somatic variation in erythrocytes expressing the MN blood type, and was used to assess genotoxicity of arsenic-exposed patients. Peripheral blood was collected from 18 adult healthy subjects and 40 arsenic-exposed patients in heparin-treated tubes. Erythrocytes were isolated, fixed in formalin and immuno-labeled with fluorescent antibodies against GPA, followed by flow cytometry analysis. Arsenic exposure increased the variant frequency (expressed as the number of variant red cells per 106 erythrocytes): NN, 3.7 in healthy subjects versus 21.2 in arsenic-exposed patients; Nφ, 12.6 versus 33.1; MM, 13.1 versus 110; and Mφ, 5.2 versus 20.3. The total GPA variant frequency was increased about five-fold (34.7 in healthy subjects versus 185 in arsenosis patients). Furthermore, the variant frequency was significantly higher in skin tumor-bearing patients: NN, 19.4 in arsenic-exposed non-tumor patients versus 31.5 in tumor-bearing patients; Nφ, 29.5 versus 54.5; MM, 102 versus 159; Mφ, 15.9 versus 45.1. Total GPA variant frequency in arsenic-exposed patients bearing skin tumors was significantly increased compared to patients without skin tumors (167 versus 290). The relationship between arsenic exposure history and GPA variant frequency was less evident. These data demonstrate that arsenic exposure is associated with mutations at the GPA locus, an effect exaggerated in patients bearing arsenic-induced skin tumors. The variant frequency of GPA could be a useful biomarker for arsenic exposure and arsenic carcinogenesis. [Copyright &y& Elsevier]