Plasma Metabolomics Analysis of Polyvinyl Chloride Workers Identifies Altered Processes and Candidate Biomarkers for Hepatic Hemangiosarcoma and Its Development

Background: High-level occupational vinyl chloride (VC) exposures have been associated with hepatic hemangiosarcoma, which typically develops following a long latency period. Although VC is genotoxic, a more comprehensive mode of action has not been determined and diagnostic biomarkers have not been established. The purpose of this study is to address these knowledge gaps through plasma metabolomics. Methods: Plasma samples from polyvinyl chloride polymerization workers who developed hemangiosarcoma (cases, n = 15) and VC exposure-matched controls (n = 17) underwent metabolomic analysis. Random forest and bioinformatic analyses were performed. Results: Cases and controls had similar demographics and routine liver biochemistries. Mass spectroscopy identified 606 known metabolites. Random forest analysis had an 82% predictive accuracy for group classification. 60 metabolites were significantly increased and 44 were decreased vs. controls. Taurocholate, bradykinin and fibrin degradation product 2 were up-regulated by greater than 80-fold. The naturally occurring anti-angiogenic phenol, 4-hydroxybenzyl alcohol, was down-regulated 5-fold. Top affected ontologies involved: (i) metabolism of bile acids, taurine, cholesterol, fatty acids and amino acids; (ii) inflammation and oxidative stress; and (iii) nicotinic cholinergic signaling. Conclusions: The plasma metabolome was differentially regulated in polyvinyl chloride workers who developed hepatic hemangiosarcoma. Ontologies potentially involved in hemangiosarcoma pathogenesis and candidate biomarkers were identified.     

A Soft,Fast and Versatile Electrohydraulic Gripper with Capacitive Object Size Detection

Soft robotic grippers achieve increased versatility and reduced complexity through intelligence embodied in their flexible and conformal structures. The most widely used soft grippers are pneumatically driven; they are simple and effective but require bulky air compressors that limit their application space and external sensors or computationally expensive vision systems for pick verification. In this study, a multi-material architecture for self-sensing electrohydraulic bending actuators is presented that enables a new class of highly versatile and reconfigurable soft grippers that are electrically driven and feature capacitive pick verification and object size detection. These electrohydraulic grippers are fast (step input results in finger closure in 50 ms), draw low power (6.5 mW per finger to hold grasp), and can pick a wide variety of objects with simple binary electrical control. Integrated high-voltage driving electronics are presented that greatly increase the application space of the grippers and make them readily compatible with commercially available robotic arms.     

Functional correction of renal defects in a mouse model for ARPKD through expression of the cloned wild-type Tg737 cDNA

Autosomal recessive polycystic kidney disease (ARPKD) is characterized by the formation of large collecting tubule and ductular cysts that often result in renal insufficiency within the first decade of life. Understanding the process leading to cyst formation will require the identification and characterization of genes involved in the etiology of this disease. In this regard, we previously described the generation of a mouse model (TgN737Rpw) for ARPKD and the cloning of a candidate gene. Here we show direct involvement of the Tg737 gene in collecting duct cyst formation by expressing the wild-type Tg737 cDNA as a transgene in TgN737Rpw mutants. In contrast to TgN737Rpw mutants, the "rescued" animals survive longer, have normal renal function and normal localization of the EGFr to the basolateral surfaces of collecting duct epithelium.     

SEBS elastomers for fabrication of microfluidic devices with reduced drug absorption by injection molding and extrusion

The majority of microfluidic devices used for cell culture, including Organ-on-a-Chips (Organ Chips), are fabricated using polydimethylsiloxane (PDMS) polymer because it is flexible, optically clear, and easy to mold. However, PDMS possesses significant challenges for high volume manufacturing and its tendency to absorb small hydrophobic compounds limits its usefulness as a material in devices used for drug evaluation studies. Here, we demonstrate that a subset of optically clear, elastomeric, styrenic block copolymers based on styrene-ethylene-butylene-styrene exhibit reduced absorption of small hydrophobic molecules and drug compounds compared to PDMS and that they can be fabricated into microfluidic devices with fine features and the flexibility required for Organ Chips using mass production techniques of injection molding and extrusion.     

Bilinear Accelerated Filter Approximation

Our method approximates exact texture filtering for arbitrary scales and translations of an image while taking into account the performance characteristics of modern GPUs. Our algorithm is fast because it accesses textures with a high degree of spatial locality. Using bilinear samples guarantees that the texels we read are in a regular pattern and that we use a hardware accelerated path. We control the texel weights by manipulating the u, v parameters of each sample and the blend factor between the samples. Our method is similar in quality to Cardinality‐Constrained Texture Filtering [ MS13 ] but runs two times faster.     

A method of assessing essential amino acid availability from microbial and ruminally undegraded protein in lactating dairy cows

The objective of this study was to extend a stable isotope-based assessment of AA absorption from rumen-degradable protein (RDP) sources to include determination of essential AA (EAA) availability from microbial protein (MCP). To demonstrate the technique, a study using a 2 × 2 factorial arrangement of treatments applied in a repeated 4 × 4 Latin square design was undertaken. Factors were high and low rumen-degradable protein and high and low starch. Twelve lactating cows were blocked into 3 groups according to days in milk and randomly assigned to the 4 treatment sequences. Each period was 14 d in length with 10 d of adaption followed by 4 d of ruminal infusions of ¹⁵N-labeled ammonium sulfate. On the last day of each period, a ¹³C-labeled AA mixture was infused into the jugular vein over a 6-h period to assess total AA entry. Rumen, blood, urine, and milk samples were collected during the infusions. Ruminal bacteria and blood samples were assessed for AA enrichment. Total plasma AA absorption rates were derived for 6 EAA from plasma ¹³C AA enrichment. Absorption of 6 EAA from MCP was calculated from total AA absorption based on ¹⁵N enrichment in blood and rumen bacteria. Essential AA absorption rates from total protein, MCP, and rumen-undegradable protein were derived with standard errors of the mean of 6, 14, and 14%, respectively. An average of 45% of absorbed EAA were from MCP, which varied among 6 EAA and was interactively affected by starch and RDP in diets. Microbial AA availability measured by isotope dilution method increased with the high RDP diets and was unaffected by starch level, except for Met, which decreased with high starch. Microbial protein outflow, estimated from urinary purine derivatives, increased with RDP and was not significantly affected by starch. This was consistent with measurements from the isotope dilution method. Total AA absorption rates measured from isotope dilution were similar to estimates from CNCPS (v. 6.55), but a lower proportion of absorbed AA was derived from MCP for the former method. Compared with the isotope and CNCPS estimates, the Fleming model underestimated microbial EAA and total EAA availability. An average of 58% of the absorbed EAA was converted into milk, which varied among individual AA and was interactively affected by starch and RDP in diets. The isotope dilution approach is advantageous because it provides estimates of EAA availability for individual EAA from rumen-undegradable protein and MCP directly with fewer errors of measurement than can be achieved with intestinal disappearance methods.     

Superplasticity in eutectoid steel

A eutectoid steel exhibited abnormally large tensile extensibility in three quite dissimilar circumstances: i) micrograin plasticity, defined by a strain-rate sensitivity exponent m = 0.42, was found at 716°C for straining the ferrite-cementite aggregate at the rate è = 4.4 x 10^-3 min^-1, giving 133 pct elongation; ii) at a much greater strain rate, ε = 25 min^-1, superplasticity appeared in austenite strained at 927°C, giving 142 pct elongation; iii) a new type of transformation plasticity was predicted and experimentally verified: 490 pct elongation resulted from thermal cycling 21 times across Ae₁. Plastic stability analysis distinguishes it from micrograin plasticity by showing that it owes to strain-hard ening during plastically stable flow; hence, there are no restrictions ε or m. Furthermore, it is not necessary to perform the straining during the transformation, since the strain-hardening capacity can be regenerated by thermal cycling through the phase transformation if the transformation serves to recover the flow stress. Additional work showed that straining during austenitizing fails to increase m above pretransformation levels. Formerly Graduate Student, Syracuse University, Syracuse, N. Y.     

Prestressed Ceramic Coatings for Enhanced Reliability of Silicon Wafer Fracture Strength

The objective of this paper is to investigate thin, solid, prestressed ceramic films as a means of enhancing the reliability of silicon semiconductor wafers stressed in bending. To characterize the effect of thin films on strength, one-micrometer ceramic films were deposited on wafers using plasma-enhanced chemical-vapor deposition. The modulus of rupture (MOR) of the coated wafers was determined from four-point bend testing of coated samples. Adhesion testing of the coated wafers primarily showed cohesive rather than adhesive failure. A series of residual stresses was introduced into the coating-silicon interface and the MOR was determined. The results showed that for a thin brittle coating (1 mum) on a silicon wafer (635 mum), the minimal shear stress at the surface led to dominance of the residual stress over intrinsic coating strength as the critical parameter affecting failure. A correlation between MOR and residual stress was established.