A computationally efficient physics-based compact bipolar transistor model for circuit Design-part II: parameter extraction and experimental results

A compact bipolar transistor model was presented in Part I that combines the simplicity of the SPICE Gummel-Poon model (SGPM) with some major features of HICUM. The new model, called HICUM/L0, is more physics-based and accurate than the SGPM but at the same time, from a computational point of view, suitable for simulating large circuits. In Part II, a parameter determination procedure is described and demonstrated for a variety of SiGe process technologies.     

Effects of grain,fructose, and histidine feeding on endotoxin and oxidative stress measures in dairy heifers

Ruminal endotoxin and plasma oxidative stress biomarker concentrations were studied in dairy heifers challenged with grain, fructose, and histidine in a partial factorial study. Holstein-Friesian heifers [n = 30; average body weight (BW) of 359.3 ± 47.3 kg] were randomly allocated to 5 treatment groups: (1) control (no grain); (2) grain [crushed triticale at 1.2% of BW dry matter intake (DMI)]; (3) grain (0.8% of BW DMI) + fructose (0.4% of BW DMI); (4) grain (1.2% of BW DMI) + histidine (6 g/head); and (5) grain (0.8% of BW DMI) + fructose (0.4% of BW DMI) + histidine (6 g/head). Rumen samples were collected by stomach tube 5, 65, 115, 165, and 215 min after diet consumption and blood samples at 5 and 215 min after consumption. Rumen fluid was analyzed for endotoxin concentrations. Plasma was analyzed for concentrations of the following oxidative stress biomarkers: reactive oxygen metabolites (dROM), biological antioxidant potential (BAP), advanced oxidation protein products, and ceruloplasmin, and activity of glutathione peroxidase. Dietary treatment had no effect on concentrations of endotoxin or oxidative stress biomarkers. We observed no interactions of treatment by time. Ruminal concentrations of endotoxin decreased during the sampling period from 1.12 × 10⁵ ± 0.06 to 0.92 × 10⁵ endotoxin units/mL ± 0.05 (5 and 215 min after diet consumption, respectively). Concentrations of dROM and the oxidative stress index (dROM/BAP × 100) increased over the sampling period, from 108.7 to 123.5 Carratelli units (Carr U), and from 4.1 to 4.8, respectively. Ceruloplasmin concentrations markedly declined 5 min after the consumption of diets, from 190 to 90 mg/L over the 215-min sampling period. Overall, a single feeding challenge for dairy cattle with grain, fructose, and histidine, and combinations thereof, may not be sufficient to induce marked changes in endotoxin or oxidative stress biomarker concentrations.     

Effects of feed additives on rumen and blood profiles during a starch and fructose challenge

We evaluated the effect of feed additives on the risk of ruminal acidosis in Holstein heifers (n = 40) fed starch and fructose in a challenge study. Heifers were randomly allocated to feed additive groups (n = 8 heifers/group): (1) control (no additives); (2) virginiamycin (VM); (3) monensin + tylosin (MT); (4) monensin + live yeast (MLY); and (5) sodium bicarbonate + magnesium oxide (BUF). Heifers were fed 2.5% of body weight (BW) dry matter intake (DMI) per day of a total mixed ration (62:38 forage:concentrate) and feed additives for a 20-d adaptation period. Fructose (0.1% of BW/d) was included for the last 10 d of the adaptation period. On d 21, heifers were fed to target a DMI of 1.0% of BW of wheat, fructose at 0.2% of BW, and their feed additives. Rumen fluid samples obtained by stomach tube and blood samples were collected weekly as well as during a 3.6-h period on challenge day (d 21). Virginiamycin and BUF groups maintained a consistently high DMI across the 20-d adaptation period. The MLY heifers had low DMI of the challenge ration. Average daily gain and feed conversion ratio were not affected by feed additives. All rumen and plasma measures changed weekly over adaptation and over the challenge sampling period with the exception of rumen total lactate and histamine concentrations, plasma oxidative stress index, and ceruloplasmin. Substantial within- and between-group variation was observed in rumen and plasma profiles at challenge sampling. No significant group changes were observed in rumen total volatile fatty acids, propionate, acetate-to-propionate ratio, isobutyrate, caproate, isovalerate, total lactate, d- and l-lactate, and pH measures on challenge day. Acetate concentration was increased in the BUF and control groups on challenge day. Butyrate concentration was lower in the MLY and MT groups compared with other groups at challenge. Valerate concentrations were lowest in the control, VM, and BUF groups and lactate concentrations were numerically lower in the MLY, VM, and BUF groups. Total lactate concentrations were >10 mM for each group throughout the challenge. Ammonia concentrations were lower in the MLY and MT groups. Histamine concentrations were decreased in MLY and increased in the VM and BUF groups. Plasma oxidative stress measures were not influenced by feed additives weekly or on challenge day, except for an increase in biological antioxidant potential in the control, VM, and MT groups on challenge day. Despite the large within-animal variation, all feed additives modified rumen function and may influence the risk of acidosis by different mechanisms; however, none stabilized the rumen in all heifers.     

Time Resolved Imaging: From logical states to events,a new and efficient pattern matching method for VLSI analysis

Time Resolved Imaging (TRI) allows real time imaging of transitions in CMOS gates even for very deep submicron technologies at low power supply voltage. Anyway, the measured timing information differs from waveform measurement where logical states are easily extracted. We first introduce logical event with a 1 value when we have transition from one logical state to its complement (0–1 or 1–0) or 0 value when there is no change between 2 vectors. Events can be extracted from TRI database and then used for a very accurate and efficient pattern matching method. In this paper, we demonstrate how we move from logical state to events and the extreme accuracy of pattern matching. Results are shown on 45 nm CMOS technology.     

Reduction by indobufen of neutrophil activation in peripheral arterial occlusive disease

We evaluated the effectiveness of indobufen administration in reducing neutrophil activation in a clinical model of ischemia-reperfusion. Thirty stable patients with intermittent claudication due to occlusive peripheral arterial disease of the leg were randomly assigned to two groups. Patients in group I were treated with indobufen [200 mg orally twice daily (p.o. b.i.d.) for a week]; patients in group II received a placebo. Both groups of patients were submitted to standardized treadmill exercise until onset of claudication. Plasma levels of thromboxane B2 (TxB2) and 6-keto-prostaglandin F1alpha(6-k-PGF1alpha) neutrophil filterability, and neutrophil activation (by nitro-blue tetrazolium test) were assessed in blood samples from the femoral vein draining the ischemic leg. The values were obtained at rest and 5, 30, and 60 min after onset of claudication. Urinary albumin excretion was measured at rest and 1 h after onset of claudication. Plasma levels of TxB2 and 6-k-PGF1alpha increased significantly in the placebo group 5 min after onset of claudication, whereas only a slight nonsignificant increase was observed in the indobufen-treated group at the same timepoint.     

Sustained low-efficiency dialysis with filtration (SLEDD-f) in the management of acute sodium valproate intoxication

Hemodialysis is only infrequently used in drug overdosage situations. The efficacy of hemodialysis to remove the drug depends upon the pharmacokinetics and pharmacodynamics of the drug. At normal therapeutic concentrations, valproic acid is predominantly protein bound and therefore removal by hemodialysis is limited. In an overdose situation, protein binding is rapidly saturated and therefore the substantially larger quantities of the free drug can rapidly cause toxicity. Slow low-efficient daily diafiltration (SLEDD) has not previously been utilized in a drug overdose situation. We report the effective use of SLEDD to remove high toxic concentrations of valproic acid in an overdose situation. Slow low-efficient daily diafiltration also prevented the rebound phenomenon that can occur as the excess drug is released from its protein-bound stores. Hybrid dialysis therapies deserve further evaluation in the management of other poisonings where extra-corporeal therapy is indicated.     

Effects of prepartum dietary cation-anion difference and source of vitamin D in dairy cows: Vitamin D,mineral, and bone metabolism

Pregnant Holstein cows, 28 nulliparous and 51 parous, were blocked by parity and milk yield and randomly allocated to receive diets that differed in dietary cation-anion difference (DCAD), +130 or ?130 mEq/kg, and supplemented with either calcidiol or cholecalciferol at 3 mg/11 kg of dry matter from 255 d of gestation until parturition. Blood was sampled thrice weekly prepartum, and on d 0, 1, 2, 3, 6, 9, 12, 15, 18, 21, 24, 27, and 30 postpartum to evaluate effects of the diets on vitamin D, mineral and bone metabolism, and acid-base status. Blood pH and concentrations of minerals, vitamin D metabolites, and bone-related hormones were determined, as were mineral concentrations and losses in urine and colostrum. Supplementing with calcidiol increased plasma concentrations of 25-hydroxyvitamin D₃, 3-epi 25-hydroxyvitamin D₃, 25-hydroxyvitamin D₂, 1,25-dihydroxyvitamin D₃, and 24,25-dihydroxyvitamin D₃ compared with supplementing with cholecalciferol. Cows fed the diet with negative DCAD had lesser concentrations of vitamin D metabolites before and after calving than cows fed the diet with positive DCAD, except for 25-hydroxyvitamin D₂. Feeding the diet with negative DCAD induced a compensated metabolic acidosis that attenuated the decline in blood ionized Ca (iCa) and serum total Ca (tCa) around calving, particularly in parous cows, whereas cows fed the diet with positive DCAD and supplemented with calcidiol had the greatest 1,25-dihydroxyvitamin D₃ concentrations and the lowest iCa and tCa concentrations on d 1 and 2 postpartum. The acidogenic diet or calcidiol markedly increased urinary losses of tCa and tMg, and feeding calcidiol tended to increase colostrum yield and increased losses of tCa and tMg in colostrum. Cows fed the diet with negative DCAD had increased concentrations of serotonin and C-terminal telopeptide of type 1 collagen prepartum compared with cows fed the diet with positive DCAD. Concentrations of undercarboxylated and carboxylated osteocalcin and those of adiponectin did not differ with treatment. These results provide evidence that dietary manipulations can induce metabolic adaptations that improve mineral homeostasis with the onset of lactation that might explain some of the improvements observed in health and production when cows are fed diets with negative DCAD or supplemented with calcidiol.     

The Emerging Role of Extracellular Vesicles Detected in Different Biological Fluids in COPD

The pathogenesis of chronic obstructive pulmonary disease (COPD) is characterized by complex cellular and molecular mechanisms, not fully elucidated so far. It involves inflammatory cells (monocytes/macrophages, neutrophils, lymphocytes), cytokines, chemokines and, probably, new players yet to be clearly identified and described. Chronic local and systemic inflammation, lung aging and cellular senescence are key pathological events in COPD development and progression over time. Extracellular vesicles (EVs), released by virtually all cells both as microvesicles and exosomes into different biological fluids, are involved in intercellular communication and, therefore, represent intriguing players in pathobiological mechanisms (including those characterizing aging and chronic diseases); moreover, the role of EVs as biomarkers in different diseases, including COPD, is rapidly gaining recognition. In this review, after recalling the essential steps of COPD pathogenesis, we summarize the current evidence on the roles of EVs collected in different biological mediums as biomarkers in COPD and as potential players in the specific mechanisms leading to disease development. We will also briefly review the data on EV as potential therapeutic targets and potential therapeutic agents.     

Serum antibodies to benzo(a)pyrene diol epoxide-DNA adducts in the general population: effects of air pollution, tobacco smoking, and family history of lung diseases

Polycyclic aromatic hydrocarbons (PAHs) are almost ubiquitous pollutants that may interact with metabolic systems in human tissues and eventually cause cancer. PAH-adducted DNA becomes antigenic and antibodies anti-benzo(a)pyrene diol epoxide (BPDE)-DNA may be found in serum of PAH-exposed subjects. The presence of serum antibodies anti-BPDE-DNA adduct was investigated in 1345 individuals from family clusters of the general population of a small area in central Italy in whom information about smoking habits, site of residence, and personal and family history of lung diseases, including cancer, were obtained. Anti-BPDE-DNA antibodies in the sera were detected with a direct ELISA and the association of anti-BPDE-DNA antibodies with subjects' data from a standardized respiratory questionnaire including age, occupation, tobacco smoking habits, respiratory symptoms, and family history of respiratory diseases was subsequently tested by multivariate logistic regression analysis. The overall prevalence of subjects with anti-BPDE-DNA antibodies was 21.0% (n=283), with no differences between males and females. Anti-BPDE-DNA positivity was associated with living in the urban area [odds ratio (OR), 1.49; 95% confidence interval (CI), 1.16-1.92], with active tobacco smoking (OR, 1.25; 95% CI, 1.06-1.48), and with family history of lung cancer (OR, 1.30; 95% CI, 0.90-1.88), and positivity increased with the number of members in the family cluster positive to anti-BPDE-DNA antibodies (OR, 1.30; 95% CI, 1.03-1.65). This study on a large general population sample indicates that serum anti-BPDE-DNA antibodies may be considered as biomarkers of exposure to environmental carcinogens and of DNA damage. The genetic and familial components of their association with tobacco smoking lend further support to the argument about the familial predisposition to lung cancer.     

Traditional and innovative protective coatings for outdoor bronze: Application and performance comparison

A comparative evaluation of traditional and innovative coatings for outdoor bronze surfaces was carried out, including blending or pre‐treatment with non‐toxic corrosion inhibitors on bare and patinated bronze surfaces to simulate both as cast and aged surfaces. Coatings recently applied in bronze conservation practice, commercially available coatings and an innovative end‐capped poly(lactic acid) with a benzotriazole (BTA) moiety have been tested, as well as a triple‐layer system (wax/acrylic polymer/wax). BTA, single‐layer Soter wax, and double layer Incral44/Soter wax were used as a reference. The products were evaluated in terms of aesthetic features, molecular structure, and corrosion protection by means of colorimetric, spectroscopic, and electrochemical tests. All inhibitors showed similar or significantly better results compared to BTA. In particular, sodium oleate and tolyltriazole could be considered as promising lower‐toxicity alternatives to BTA, while the triple‐layer coating applied without pre‐filming inhibitors proved to give a very high protection against corrosion. © 2017 Wiley Periodicals, Inc. J. Appl. Polym. Sci. 2018 , 135, 46011.