Geometric Challenges in Designing Parts for Machining using Wire-fed DED

Wire-fed DED using MIG welding systems allows for high deposition rates above 30lbs/hr, enabling much larger parts to be printed than would be possible on other DED systems. However, a drawback to this high deposition rate is a relatively low bead resolution on the printed part. Post-processing using machining is usually required on any mating surfaces printed using wire-fed DED. Problems such as residual stress in the build plate and printed part, underbuilding, and path interpolations can all lead to insufficient material deposition and deviation from the desired shape. These areas where the printed part varies from the model can leave defects on post-processed surfaces. This paper will cover common geometry issues that can arise from wire-fed DED and design changes that can be made to ensure that the printed design contains the required material to achieve the finished part.Mechanical Engineerin

Off-Diagonal Long-Range Order in Bose Liquids: Irrotational Flow and Quantization of Circulation

On the basis of gauge invariance, it is proven in an elementary and straightforward manner, but without invoking any {\it ad hoc} assumption, that the existence of off-diagonal long-range order in one-particle reduced density matrix in Bose liquids implies both the irrotational flow in a simply connected region and the quantization of circulation in a multiply connected region, the two fundamental properties of a Bose superfluid. The origin for both is the phase coherence of condensate wave-functions. Some relevant issues are also addressed.Comment: Revtex, 4 pages, no figure

Thickening of the pulmonary artery wall in acute intramural hematoma of the ascending aorta

BACKGROUND: The occurrence of pulmonary artery obstruction in the course of acute aortic dissection is an unusual complication. The mechanism implicated is the rupture of the outer layer of the aorta and the subsequent hemorrhage into the adventitia of the pulmonary artery that causes its wall thickening and, at times, produces extrinsic obstruction of the vessel. There are no reports of this complication in acute intramural hematoma. CASE PRESENTATION: An 87-year-old woman was admitted to the hospital in shock after having had severe chest pain followed by syncope. An urgent transesophageal echocardiogram revealed the presence of acute intramural hematoma, no evidence of aortic dissection, severe pericardial effusion with cardiac tamponade, and periaortic hematoma that involved the pulmonary artery generating circumferential wall thickening of its trunk and right branch with no evidence of flow obstruction. Urgent surgery was performed but the patient died in the operating room. The post mortem examination, in the operating room, confirmed that there was an extensive hematoma around the aorta and beneath the adventitial layer of the pulmonary artery, with no evidence of flow obstruction. CONCLUSION: This is the first time that this rare complication is reported in the scenario of acute intramural hematoma and with the transesophageal echocardiogram as the diagnostic tool

Cyp2c70 is responsible for the species difference in bile acid metabolism between mice and humans

Bile acids are synthesized from cholesterol in the liver and subjected to multiple metabolic biotransformations in hepatocytes, including oxidation by cytochromes P450 (CYPs) and conjugation with taurine, glycine, glucuronic acid, and sulfate. Mice and rats can hydroxylate chenodeoxycholic acid (CDCA) at the 6β-position to form α-muricholic acid (MCA) and ursodeoxycholic acid (UDCA) to form β-MCA. However, MCA is not formed in humans to any appreciable degree and the mechanism for this species difference is not known. Comparison of several Cyp-null mouse lines revealed that α-MCA and β-MCA were not detected in the liver samples from Cyp2c-cluster null (Cyp2c-null) mice. Global bile acid analysis further revealed the absence of MCAs and their conjugated derivatives, and high concentrations of CDCA and UDCA in Cyp2c-null mouse cecum and feces. Analysis of recombinant CYPs revealed that α-MCA and β-MCA were produced by oxidation of CDCA and UDCA by Cyp2c70, respectively. CYP2C9-humanized mice have similar bile acid metabolites as the Cyp2c-null mice, indicating that human CYP2C9 does not oxidize CDCA and UDCA, thus explaining the species differences in production of MCA. Because humans do not produce MCA, they lack tauro-β-MCA, a farnesoid X receptor antagonist in mouse that modulates obesity, insulin resistance, and hepatosteatosis

Pituitary Adenylate Cyclase-Activating Polypeptide Stimulates Glucose Production via the Hepatic Sympathetic Innervation in Rats

OBJECTIVE-The unraveling of the elaborate brain networks that control glucose metabolism presents one of the current challenges in diabetes research. Within the central nervous system, the hypothalamus is regarded as the key brain area to regulate energy homeostasis. The aim of the present study was to investigate the hypothalamic mechanism involved in the hyperglycemic effects of the neuropeptide pituitary adenylyl cyclase-activating polypeptide (PACAP). RESEARCH DESIGN AND METHODS-Endogenous glucose production (EGP) was determined during intracerebroventricular infusions of PACAP-38, vasoactive intestinal peptide (VIP), or their receptor agonists. The specificity of their receptors was examined by coinfusions of receptor antagonists. The possible neuronal pathway involved was investigated by 1) local injections in hypothalamic nuclei, 2) retrograde neuronal tracing from the thoracic spinal cord to hypothalamic preautonomic neurons together with Fos immunoreactivity, and 3) specific hepatic sympathetic or parasympathetic denervation to block the autonomic neuronal input to liver. LTS-Intracerebroventiicular infusion of PACAP-38 increased EGP to a similar extent as a VIP/PACAP-2 (VPAC2) receptor agonist, and intracerebroventricular administration of VIP had significantly less influence on EGP. The PACAP-38 induced increase of EGP was significantly suppressed by preinfusion of a VPAC2 but not a PAC1 receptor antagonist, as well as by hepatic sympathetic but not parasympathetic denervation. In the hypothalamus, Fos immunoreactivity induced by PACAP-38 was colocalized within autonomic neurons in paraventricular nuclei projecting to preganglionic sympathetic neurons in the spinal cord. Local infusion of PACAP-38 directly into the PVN induced a significant increase of EGP. CONCLUSIONS-This study demonstrates that PACAP-38 signaling via sympathetic preautonomic neurons located in the paraventricular nucleus is an important component in the hypothalamic control of hepatic glucose production. Diabetes 59: 1591-1600, 201

Elevated Serum Uric Acid Is Associated with High Circulating Inflammatory Cytokines in the Population-Based Colaus Study

BACKGROUND: The relation of serum uric acid (SUA) with systemic inflammation has been little explored in humans and results have been inconsistent. We analyzed the association between SUA and circulating levels of interleukin-6 (IL-6), interleukin-1beta (IL-1beta), tumor necrosis factor- alpha (TNF-alpha) and C-reactive protein (CRP). METHODS AND FINDINGS: This cross-sectional population-based study conducted in Lausanne, Switzerland, included 6085 participants aged 35 to 75 years. SUA was measured using uricase-PAP method. Plasma TNF-alpha, IL-1beta and IL-6 were measured by a multiplexed particle-based flow cytometric assay and hs-CRP by an immunometric assay. The median levels of SUA, IL-6, TNF-alpha, CRP and IL-1beta were 355 micromol/L, 1.46 pg/mL, 3.04 pg/mL, 1.2 mg/L and 0.34 pg/mL in men and 262 micromol/L, 1.21 pg/mL, 2.74 pg/mL, 1.3 mg/L and 0.45 pg/mL in women, respectively. SUA correlated positively with IL-6, TNF-alpha and CRP and negatively with IL-1beta (Spearman r: 0.04, 0.07, 0.20 and 0.05 in men, and 0.09, 0.13, 0.30 and 0.07 in women, respectively, P<0.05). In multivariable analyses, SUA was associated positively with CRP (beta coefficient +/- SE = 0.35+/-0.02, P<0.001), TNF-alpha (0.08+/-0.02, P<0.001) and IL-6 (0.10+/-0.03, P<0.001), and negatively with IL-1beta (-0.07+/-0.03, P = 0.027). Upon further adjustment for body mass index, these associations were substantially attenuated. CONCLUSIONS: SUA was associated positively with IL-6, CRP and TNF-alpha and negatively with IL-1beta, particularly in women. These results suggest that uric acid contributes to systemic inflammation in humans and are in line with experimental data showing that uric acid triggers sterile inflammation

Financial risk tolerance of Chinese American families

This chapter investigates the factors that affect financial risk tolerance of Chinese American households. Research on the economic well-being of Chinese American households is extremely limited. Few national datasets differentiate Chinese Americans from other race/ethnicity groups. For this study, a survey of Chinese American households residing in Midwestern states was conducted. The results showed that about 80.5 % of the sample households expressed a willingness to take at least some financial risks. Factors that have an impact on financial risk tolerance of Chinese American households included gender, non-financial assets, income, and investment time horizon. Chinese Americans represents a small but fast-growing population in the USA. More research should be done to better serve the financial needs of this group.Includes bibliographical references

A Novel Screening System for Claudin Binder Using Baculoviral Display

Recent progress in cell biology has provided new insight into the claudin (CL) family of integral membrane proteins, which contains more than 20 members, as a target for pharmaceutical therapy. Few ligands for CL have been identified because it is difficult to prepare CL in an intact form. In the present study, we developed a method to screen for CL binders by using the budded baculovirus (BV) display system. CL4-displaying BV interacted with a CL4 binder, the C-terminal fragment of Clostridium perfringens enterotoxin (C-CPE), but it did not interact with C-CPE that was mutated in its CL4-binding region. C-CPE did not interact with BV and CL1-displaying BV. We used CL4-displaying BV to select CL4-binding phage in a mixture of a scFv-phage and C-CPE-phage. The percentage of C-CPE-phage in the phage mixture increased from 16.7% before selection to 92% after selection, indicating that CL-displaying BV may be useful for the selection of CL binders. We prepared a C-CPE phage library by mutating the functional amino acids. We screened the library for CL4 binders by affinity to CL4-displaying BV, and we found that the novel CL4 binders modulated the tight-junction barrier. These findings indicate that the CL-displaying BV system may be a promising method to produce a novel CL binder and modulator

Mechanisms Underlying Insulin Deficiency-Induced Acceleration of β-Amyloidosis in a Mouse Model of Alzheimer's Disease

Although evidence is accumulating that diabetes mellitus is an important risk factor for sporadic Alzheimer's disease (AD), the mechanisms by which defects in insulin signaling may lead to the acceleration of AD progression remain unclear. In this study, we applied streptozotocin (STZ) to induce experimental diabetes in AD transgenic mice (5XFAD model) and investigated how insulin deficiency affects the β-amyloidogenic processing of amyloid precursor protein (APP). Two and half months after 5XFAD mice were treated with STZ (90 mg/kg, i.p., once daily for two consecutive days), they showed significant reductions in brain insulin levels without changes in insulin receptor expression. Concentrations of cerebral amyloid-β peptides (Aβ40 and Aβ42) were significantly increased in STZ-treated 5XFAD mice as compared with vehicle-treated 5XFAD controls. Importantly, STZ-induced insulin deficiency upregulated levels of both β-site APP cleaving enzyme 1 (BACE1) and full-length APP in 5XFAD mouse brains, which was accompanied by dramatic elevations in the β-cleaved C-terminal fragment (C99). Interestingly, BACE1 mRNA levels were not affected, whereas phosphorylation of the translation initiation factor eIF2α, a mechanism proposed to mediate the post-transcriptional upregulation of BACE1, was significantly elevated in STZ-treated 5XFAD mice. Meanwhile, levels of GGA3, an adapter protein responsible for sorting BACE1 to lysosomal degradation, are indistinguishable between STZ- and vehicle-treated 5XFAD mice. Moreover, STZ treatments did not affect levels of Aβ-degrading enzymes such as neprilysin and insulin-degrading enzyme (IDE) in 5XFAD brains. Taken together, our findings provide a mechanistic foundation for a link between diabetes and AD by demonstrating that insulin deficiency may change APP processing to favor β-amyloidogenesis via the translational upregulation of BACE1 in combination with elevations in its substrate, APP