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Treatment of human epidermal growth factor receptor 2 (HER2/neu)-expressing breast cancer patients with a monoclonal antibody (mAb) directed against HER2/neu improves the outcome of chemotherapy. In cases in which remission is observed, antibody-dependent cell-mediated cytotoxicity (ADCC) seems to be one of the main mechanisms of anti-HER2/neu mAb action, implicating Fcγ receptors (FcγRs) in this tumoricidal activity. In vitro and in vivo studies have revealed that anti-HER2/neu-mediated ADCC is mainly accomplished by polymorphonuclear granulocytes (PMN). C5a, a cleavage product of the complement component C5, modulates FcγR expression via upregulation of activating and downregulation of inhibitory FcγRs. C5a also recruits PMNs to sites of inflammation and increases PMN survival. To enhance the recruitment and activation of C5a receptor–bearing cells into the tumor microenvironment, we developed antibody fusion proteins composed of a human IgG3 anti-HER2/neu antibody genetically fused to C5a [anti-HER2/neu IgG3-(C5a)] or to its derivative, C5adesArg [anti-HER2/neu IgG3-(C5adesArg)]. Both fusion proteins were expressed, properly assembled, and secreted by murine myeloma cells, and displayed chemotactic activity on human PMN. Under comparable conditions, anti-HER2/neu IgG3-(C5adesArg) increased the survival of PMN more efficiently than anti-HER2/neu IgG3-(C5a) or C5adesArg. Surprisingly, incubation of the fusion proteins with breast cancer cells that overexpress HER2/neu (SK-BR-3) induced cell death at a dose at which the anti-HER2/neu IgG3 antibody was innocuous. In the presence of human peripheral blood leukocytes as effector cells, both fusion proteins induced tumor cell death more efficiently than anti-HER2/neu IgG3. These data suggest that anti-HER2/neu IgG3-(C5a) and anti-HER2/neu IgG3-(C5adesArg) fusion proteins possess novel properties that could be useful in cancer immunotherapy. Mol Cancer Ther; 9(8); 2175–85. ©2010 AACR.

Supplementary Figure 1 from Decreased Survival of Human Breast Cancer Cells Expressing HER2/neu on In vitro Incubation with an Anti-HER2/neu Antibody Fused to C5a or C5adesArg

Supplementary Figure Legend from Decreased Survival of Human Breast Cancer Cells Expressing HER2/neu on In vitro Incubation with an Anti-HER2/neu Antibody Fused to C5a or C5adesArg

This study evaluates the partial replacement of steam-flaked corn (SFC) with increasing dried distillers grains plus solubles (DDGS) levels in growing-finishing diets for calf-fed Holstein steers. Two experiments were conducted. In trial 1, 100 Holstein calves (136 ± 7 kg) were used to evaluate the effect of DDGS as a metabolizable protein source on cattle growth performance, and dietary energetics of calf-fed Holstein steers during the initial 111 d growing phase. Four dietary levels of DDGS were evaluated (10, 15, 20, and 25%, dry matter basis), replacing SFC (flake density, 0.31 kg/L). In trial 2, four Holstein steers (368 ± 20 kg) with cannulas in the rumen and proximal duodenum were used to evaluate treatment effects on characteristics of ruminal and total tract digestion of organic matter (OM), neutral detergent fiber, nitrogen (N), and indispensable amino acid supply to the small intestine. The increasing level of DDGS did not affect (P ≥ 0.13) average daily gain, gain efficiency, and estimated dietary net energy values. Replacement of SFC with increasing levels of DDGS decreased (linear; P = 0.01) ruminal OM digestion. There was no treatment effect on the flow of microbial nitrogen to the small intestine (P = 0.34) and ruminal microbial efficiency (P = 0.79). However, increasing levels of DDGS in the diet increased (linear; P ≤ 0.04) flow of methionine, histidine, phenylalanine, threonine, leucine, isoleucine, and valine but did not affect (P = 0.74) intestinal supply of lysine. Increasing DDGS in the diet increased (linear, P < 0.01) flow of N to the small intestine but decreased (linear; P < 0.01) ruminal N efficiency. Replacing SFC with DDGS increased intake and amino acid leaving the abomasum. Still, this effect was not sufficient to increase the growth performance of calf-fed Holstein during the first 111 d on feed.

The objective of this study was to evaluate the influence of supplemental flavomycin on cattle growth performance, carcass characteristics, diet digestibility, and ruminal fermentation characteristics of calf-fed Holstein steers. One hundred Holstein steers (123 ± 7 kg) were balanced by weight and assigned to 20 pens. Dietary treatments consisted of a steam flaked corn-based diet supplemented with (dry matter basis): 1) control, no feed additive; 2) 6.6 mg/kg flavomycin; 3) 13.2 mg/kg flavomycin, and 4) 30 mg/kg monensin (MON). There were no treatment effects (P ≥ 0.17) on live weight, average daily gain (ADG), and gain efficiency. Flavomycin did not affect dry matter intake (DMI; P ≥ 0.24). Flavomycin supplementation did not affect (P ≥ 0.37) the ratio of observed vs. expected DMI. However, MON decreased (P = 0.02) observed vs. expected DMI by 3.7%. There were no treatment effects (P ≥ 0.44) on ruminal pH or temperature. Flavomycin did not affect (P ≥ 0.13) carcass characteristics and liver abscess among steers. Four Holstein steers (463 ± 20 kg) with ruminal cannulas were used in 4 × 4 Latin square experiment to study treatment effects on site and extent of digestion, ruminal pH, and volatile fatty acid (VFA) molar proportions. Dietary treatments were the same as experiment 1. Flavomycin tended to increase (linear effect, P = 0.07) ruminal organic matter (OM) digestion, associated with increased (linear effect, P < 0.01) ruminal starch digestion. Supplementing flavomycin at 13.2 mg/kg decreased net microbial N synthesis (quadratic effect, P = 0.03). Compared with control, MON tended to increase (P = 0.10) ruminal neutral detergent fiber (NDF) digestion and increased (P < 0.01) ruminal starch digestion. Monensin did not affect (P = 0.39) net microbial N synthesis, but decreased (P = 0.01) ruminal degradation of feed nitrogen (N). There were no treatment effects (P > 0.10) on total tract apparent digestion of DM, OM, NDF, and starch. Flavomycin decreased ruminal pH (quadratic effect, P < 0.01) measured 4 h postprandial. Compared with control, MON increased ruminal pH (P = 0.03). Flavomycin increased (linear effect, P = 0.03) ruminal propionate molar proportion and decreased (linear effect, P ≤ 0.04) ruminal molar proportions of acetate and butyrate, and decreased (linear effect, P = 0.02) acetate:propionate molar ratio and estimated methane production. We conclude that supplementing flavomycin at 6.6 or 13.2 mg/kg had no major effects on cattle growth performance, carcass characteristics, diet digestibility, and ruminal fermentation characteristics.

Objective Our objective was to examine the influence of timing of liver abscess control and early rumen-protected AA supplementation on cattle growth performance (Exp. 1) and digestive function (Exp. 2), and related responses on liver abscess incidence and AA supply to the small intestine of feedlot steers. Materials and Methods In Exp. 1, a total of 200 calves were used in a 321-d experiment. Four strategies for liver abscess control using virginiamycin (VM; 16 mg of VM/kg of diet DM, Phibro Animal Health) were used: (1) 0% VM; (2) VM supplementation during the initial 168 d; (3) VM supplementation during the final 153 d; and (4) VM supplemented continuously for 321 d. During the initial 168-d feeding period, 2 levels of rumen-protected Met and Lys (Smartamine ML: SML; 0 vs. 0.6% DM basis, Adisseo) were supplemented across VM treatments in a 2 × 4 factorial arrangement. In Exp. 2, 4 Holstein steers (382 ± 23 kg) with cannulas in the rumen and proximal duodenum were used in a 4 × 4 Latin square design to evaluate treatment effects on digestion. Results and Discussion Cattle growth performance was not affected (P ≥ 0.18) by VM supplementation strategy. Moreover, VM supplementation did not affect (P ≥ 0.10) carcass characteristics. Liver abscess incidence was low (4%) and not affected (P ≥ 0.62) by supplementation strategy. Supplemental VM did not affect characteristics of ruminal and total-tract digestion (P ≥ 0.27). Supplementation of SML during the first 168 d decreased (P = 0.02) DMI during the last 153 d of the experiment, and tended to decrease (P = 0.07) overall (321-d) DMI. Smartamine ML supplementation did not affect (P ≥ 0.11) ADG, G:F, carcass characteristics, percentage of abscessed liver, or characteristics of ruminal and total-tract digestion. Implications and Applications Timing of VM supplementation did not influence cattle growth performance or incidence of liver abscess, which was low (4%) regardless of VM treatment. Protected Met and Lys supplementation increased Met or Lys supply to the small intestine. However, MP and AA supplies of the basal diet, alone, were apparently adequate to achieve expected growth performance.

Our objective was to evaluate the interaction of supplemental essential oils (EO) and monensin (MON) on performance and digestion. Two levels of EO (0 vs 0.011% Xtract®) and two levels of MON (0 vs 33 mg/kg) were evaluated in a 2 × 2 factorial arrangement. Treatment effects on 216-d growth performance were evaluated in 96 Holstein steers. Supplemental MON enhanced (P ≤ 0.05) ADG, DMI and gain efficiency. Without EO, MON improved (P

Early childhood malignancies are driven by sparse genetic aberrations in oncogenes that often co-occur with large copy number variants (CNVs). The combination of these mutations is thought to transform developmentally pliant embryonic cells to initiate tumorigenesis. However, the mechanistic interactions between CNVs, oncogenes, and differentiation have not been systematically studied due to several obstacles: (i) CNVs cannot be engineered efficiently yet; (ii) transient embryonic progenitors are absent in full-grown tumors; and (iii) inter-species differences in lineage specification limit the applicability of animal models. To overcome these challenges, we used isogenic human embryonic stem cell (hESC) lines carrying gains of chromosome 17q/1q, which are prevalent in the embryonal tumor neuroblastoma (NB). We differentiated these cells toward trunk neural crest (NC) and their sympathoadrenal derivatives, the putative cells-of-origin of NB, and performed single-cell RNA sequencing and cell-biological assays at key differentiation stages. We found that CNVs impaired the specification of sympathoadrenal cell types and instead potentiated early Schwann-cell-precursor-like phenotypes. Additional overexpression of the oncogene MYCN (which is frequently amplified together with CNVs in high-risk NB tumors) exacerbated these differentiation defects, enabled tumourigenic cell proliferation, and generated cell states in vitro that transcriptionally resembled NB tumor cells. Finally, using epigenome analysis, we connected these states to a stepwise disruption of gene-regulatory networks centered on developmental transcription factors. Together, our results chart a mechanistic route to NB tumorigenesis and provide a general framework for the CNV-driven initiation of embryonal tumors, in which CNVs ‘prime’ embryonic cells for oncogenic transformation. The tumor-like cells in our model may serve as proxies to experimentally test therapeutic interventions during tumorigenesis. Citation Format: Ingrid M. Saldana-Guerrero, Luis F. Montano-Gutierrez, Christoph Hafemeister, Dylan Stavish, Lisa E. Shaw, Irfete S. Fetahu, Andrea Wenninger-Weinzierl, Caterina Sturtzel, Celine Souilhol, Sophia Tarelli, Mohamed R. Shoeb, Marie Bernkopf, Polyxeni Bozatzi, Maria Guarini, Eva Bozsaky, Michelle C. Buri, Eva M. Putz, Peter W. Andrews, Ivana Barbaric, Helen E. Bryant, Martin Distel, Sabine Taschner-Mandl, Matthias Farlik, Anestis Tsakiridis, Florian Halbritter. A stem cell model dissects detrimental effects of neuroblastoma-linked chromosomal aberrations on cell differentiation during neural crest development. [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 3542.

In experiment 1, 150 calf-fed Holstein steers (119 ± 6 kg) were used to evaluate the effects of level of supplemental condensed tannin (0, 14, and 28 g/kg diet DM) in a conventional steam-flaked corn-based growing-finishing diet on feedlot growth performance. There were no treatment effects on growth performance during the initial 56-d period. However, during the subsequent 56-d period, supplemental condensed tannin tended to increase average daily gain (ADG; linear effect, P = 0.09). The increase in ADG was consistent with the tendency for increased dry matter intake (DMI; linear effect, P = 0.08). Hence, differences in gain efficiency during the second 56-d period were not appreciably affected (P = 0.80). Supplemental condensed tannin did not affect overall (112-d) ADG, DMI, gain efficiency, or dietary NE. In a second experiment, six Holstein steers (179.4 ± 7.9 kg) with cannulas in the rumen and proximal duodenum were used in a replicated 3 × 3 Latin square design to evaluate treatment effects on characteristics of ruminal and total tract digestion. Treatments were the same as in Trial 1. Tannin supplementation decreased (linear effect, P = 0.03) ruminal OM digestion and tended to decrease (linear effect, P = 0.06) ruminal feed N degradation. Tannin supplementation decreased (linear effect, P = 0.03) ruminal pH, but did not affect (P > 0.20) ruminal molar proportions of volatile fatty acids and estimated methane production. In current study, supplemental tannin had marginal effects on overall growth performance of calf-fed Holstein steers, but reduced ruminal, postruminal, and total tract nitrogen digestion.

One hundred sixty-eight Holstein steer calves (133.4 ± 7.9 kg) were used to evaluate the influence of virginiamycin (VM) supplementation on cattle growth performance and liver abscess incidence, and the effect of feeding 100% vs. 87% of metabolizable protein (MP) requirements during the initial 112 d on growth performance, efficiency of energy utilization, and carcass characteristics. Steers were balanced by weight and assigned to 28 pens (6 steers/pen). During the initial 112-d feeding period, dietary treatments consisted of two levels of MP (100% vs. 87% of expected requirements) supplemented with or without 22.5 mg/kg VM in a 2 × 2 factorial arrangement. There were no VM × MP supplementation interactions (P ≥ 0.14) on any of the parameters measured in both experiments. Calf-fed Holstein steers supplemented with VM increased (P ≤ 0.03) overall average daily gain (ADG), feed efficiency (G:F), observed/expected net energy (NE) values for maintenance and gain, and final body weight (BW). Cattle fed VM also increased (P ≤ 0.04) carcass weight, dressing percent, and longissimus muscle area. However, there was no effect (P ≥ 0.22) of VM supplementation on any other carcass characteristics. Calf-fed Holstein steers fed 100% MP requirements during the initial 112-d feeding period had greater (P ≤ 0.02) ADG, G:F, observed/expected NE values for maintenance and gain, and live BW compared with steers fed 87% of the expected MP requirements. However, there was no effect (P ≥ 0.17) of MP supply during the initial 112-d period on overall (342 d) growth performance measurements. The incidence of liver abscesses was low (averaging 7.7%) and not affected by dietary treatments. We conclude that, independent of MP supplies, supplemental VM enhances overall growth performance and efficiency of energy utilization of calf-fed Holstein steers.

Objectives This study was conducted to examine the effect of urea fermentation potential (UFP) on digestive function, BUN, growth performance, and dietary energetics, in steers fed a finishing diet based on steam-flaked corn containing 15% dried distillers grains with solubles. Materials and Methods Four UFP levels were evaluated (−0.30, 0.10, 0.50, 0.90). The UFP levels were manipulated by dietary urea inclusion level of 1.20, 0.80, 0.40 and 0%, respectively (DM basis). Results and Discussion Dietary UFP did not affect (P > 0.10) ruminal digestion of feed N. Ruminal starch digestion decreased with increasing UFP (linear effect, P = 0.02). Ruminal digestion of starch and OM tended to be maximal (quadratic effect, P ≤ 0.07) at dietary UFP of 0.1%. Increasing UFP decreased flow to duodenum of nonammonia-N (linear effect, P = 0.04), and microbial N (linear effect, P = 0.05). Duodenal flow of feed N was not affected (P = 0.18) by dietary UFP. Increasing dietary UFP decreased total-tract digestion of OM (linear effect, P = 0.02), starch (linear effect, P = 0.03), and digestible energy (linear effect, P = 0.03). Increasing dietary UFP decreased ruminal pH (linear effect, P = 0.01) 1 h after feeding. Thereafter, the influence of dietary UFP on ruminal pH was not appreciable. Increasing dietary UFP decreased ruminal ammonia-N 1 h after feeding (linear effect, P Implications and Applications Even when finishing diet formulations otherwise exceed MP requirements, dietary UFP level remains a relevant factor to optimize dietary energy use. Dietary UFP levels greater than 0.50% could negatively affect digestion, gain efficiency, and dietary NE use.

Objectives The objective of this research was to evaluate the influence of rumen-protected methionine and lysine on growth performance of calf-fed Holstein steers during the initial 84-d feedlot phase and relate responses to measures of AA supply to the small intestine. Material and Methods Seventy-two Holstein steer calves (128 ± 9 kg) were blocked by weight and assigned to 12 pens (6 steers per pen). Steers were fed a diet based on steam-flaked corn formulated to provide 105% of theoretical MP requirements plus 0, 0.4, and 0.8% Smartamine ML (Adisseo, Alpharetta, GA; 55% l -lysine-HCl and 15% dl -methionine coated with a pH-sensitive polymer). Six Holstein steers (143 ± 13 kg) with cannulas in rumen and proximal duodenum were used in a crossover design to evaluate characteristics of digestion and AA supply to the intestine of the basal diet plus 0 versus 0.8% Smartamine ML. Results and Discussion Methionine and lysine supplementation did not affect DMI (P = 0.27) but enhanced ADG, gain efficiency (linear effect, P = 0.03), and estimated dietary NE (linear effect, P = 0.04). Amino acid supplementation increased (P Implications and Applications Supplementation with rumen-protected methionine and lysine may enhance gain efficiency and dietary energetics of growing Holstein calves during the early growing phase. The magnitude of the response is likely dependent on the otherwise general adequacy of nonspecific MP.

SummaryA common cellular task is to match gene expression dynamically to a range of concentrations of a regulatory molecule. Studying glucose transport in budding yeast, we determine mechanistically how such matching occurs for seven hexose transporters. By combining time-lapse microscopy with mathematical modelling, we find that levels of transporters are history-dependent and are regulated by a push-pull system comprising two types of repressors. Repression by these two types varies with glucose in opposite ways, and not only matches the expression of transporters by their affinity to a range of glucose concentrations, but also the expression of some to how glucose is changing. We argue that matching is favoured by a rate-affinity trade-off and that the regulatory system allows yeast to import glucose rapidly enough to starve competitors. Matching expression to a pattern of input is fundamental, and we believe that push-pull repression is widespread.

CD8+ T cell immunity to SARS-CoV-2 has been implicated in COVID-19 severity and virus control. Here, we identified nonsynonymous mutations in MHC-I-restricted CD8+ T cell epitopes after deep sequencing of 747 SARS-CoV-2 virus isolates. Mutant peptides exhibited diminished or abrogated MHC-I binding in a cell-free in vitro assay. Reduced MHC-I binding of mutant peptides was associated with decreased proliferation, IFN-γ production and cytotoxic activity of CD8+ T cells isolated from HLA-matched COVID-19 patients. Single cell RNA sequencing of ex vivo expanded, tetramer-sorted CD8+ T cells from COVID-19 patients further revealed qualitative differences in the transcriptional response to mutant peptides. Our findings highlight the capacity of SARS-CoV-2 to subvert CD8+ T cell surveillance through point mutations in MHC-I-restricted viral epitopes.

A feedlot growth-performance trial was conducted to evaluate the relative response to tempering when flake density (FD) of corn is increased from 0.31 kg/L (24 lb/bushel) to 0.39 kg/L (30 lb/bushel). Treatments were (1) non-tempered, FD = 0.31 kg/L; (2) non-tempered, FD = 0.39 kg/L; (3) tempered, FD = 0.31 kg/L and (4) tempered, FD = 0.39 kg/L. Tempering prior to flaking increased (21%, P

The objectives of this study were to evaluate the influence of level and source of supplemental Zn on growth performance and dietary energetics in calf-fed Holstein steers. A total of 168 steers (BW = 133 ± 7 kg) were used in a 336-d study. Treatments consisted of diets based on steam-flaked corn supplemented with (DM basis) (1) 20 mg of Zn/kg of DM as ZnSO4; (2) 10 mg of Zn/kg of DM as ZnSO4 plus 10 mg of Zn/kg of DM as Zn betaine; (3) 20 mg of Zn/kg of DM as Zn betaine; or (4) 40 mg of Zn/kg of DM as ZnSO4. Overall (d 1 to 336) there were no treatment effects (P > 0.10) on carcass-adjusted ADG, gain efficiency, and estimated dietary NE. At the 20 mg/kg level of Zn supplementation, the proportion of supplemental Zn provided as chelate did not influence overall ADG, gain efficiency, or dietary NE (P > 0.10). The proportion of Zn supplemented as chelate did not affect (P > 0.10) carcass weight, KPH, LM area, or marbling score. However, DP was greater (quadratic effect, P = 0.01) for steers receiving the 50:50 blend of ZnSO4 and Zn betaine. Carcass yield grade improved (linear component, P = 0.03) with proportion of supplemental Zn as chelate. We conclude that at a 20 mg/kg (DM basis) level of supplementation, Zn source does not affect growth performance of calf-fed Holstein steers. Increasing level of Zn supplementation (as ZnSO4) from 20 to 40 mg/kg will not further enhance overall performance responses.

Two experiments were conducted to examine the influence of kaolinite clay supplementation (0%, 1%, or 2% diet dry matter [DM] basis) on characteristics of digestion (Trial 1) and growth performance (Trial 2) in calf-fed Holstein steers fed a finishing diet. In Trial 1, 6 Holstein steers (539±15 kg) with ruminal and duodenal cannulas were used to evaluate treatment effects on characteristics of digestion. Kaolinite clay supplementation decreased total tract DM digestion (linear effect, p0.10) on average daily gain (ADG) and gain efficiency (ADG/dry matter intake). Kaolinite supplementation tended (linear effect, p = 0.08) to increase dietary net energy (NE) during the initial 112-d period. However, the overall (308-d) effect of supplementation dietary NE was not appreciable (p>0.20). However, due to the inertness of kaolinite, itself, the ratio of observed-to-expected dietary NE increased with kaolinite supplementation. This effect was more pronounced (linear effect, p 0.03) during the initial 224 d of the study. Overall (308 d), kaolinite supplementation tended to increase (linear effect, p = 0.07) dietary NE by 3% over expected. Kaolinite supplementation did not affect carcass weight, yield grade, longissimus area, kidney, pelvic and heart fat, and quality grade, but decreased (linear effect, p = 0.01) dressing percentage. It is concluded that kaolinite supplementation up to 2% of diet DM may enhance energetic efficiency of calf-fed Holstein steers in a manner independent of changes in characteristics of ruminal and total tract digestion.

Objective: This paper presents the obtained result of a study that realizes to associate a set of real and imputed single nucleotide polymorphisms (SNP) genotypes to the rear udder height in Holstein cows. Materials and methods: Forty-six Holstein cows from an arid zone of Mexico were phenotyped and genotyped for this study. Blood samples were used for DNA extraction, genotyping was per­formed with the Illumina BovineLD Bead chip which interrogates 6,912 SNPs genome-wide, and imputation was performed using the Findhap software. After QC filters, a total of 22,251 high quality and informative SNPs were inspected. Results: The results showed the detection of 76 significant SNPs throughout the complete genome. Significant SNPs fall inside 111 Quantitative Loci Traits related to protein percentage, milk yield, and fat, among others, in chromosomes 1, 2, 3, 5, 6, 9, 10, 11, 12, 13, 19, 20, 21, 23, 26, 27, and 29. Similarly, results confirm that a genotype imputation is a convenient option for genome-wide covering when selecting economic traits with low-density real SNP panels. Conclusion: This study contributes to establishing a low-cost and profitable strategy for applying genomic selection in developing countries. Adv. Vet. Anim. Res., 7(2): 234-241, June 2020

Two trials were conducted to evaluate the influence of virginiamycin (26 mg/kg) and monensin (34 mg/kg) supplementation of a steam-flaked corn-based finishing diet containing 15% distiller dried grains plus solubles (DDGS) on growth performance and digestive function. In Trial 1, 135 steers (257 ± 21 kg) were used to evaluate treatment effects on 145-d growth performance. There were no treatment effects (P > 0.20) on dry matter intake (DMI). Antibiotic supplementation tended to increase average daily gain (ADG; 7%, P = 0.07); increased gain efficiency (11%, P < 0.01) and estimated dietary net energy (NE; 10%, P < 0.01). Carcass marbling score was greater (12%, P = 0.04) for virginiamycin vs. monensin. In Trial 2, three Holstein steers (300 ± 7 kg) were used in a 3 × 3 Latin square to evaluate treatment effects on digestion. Both monensin and virginiamycin depressed ruminal digestion of organic matter (OM; 6%, P < 0.01) and feed nitrogen (N, 15%, P = 0.03) and microbial protein synthesis (15%, P = 0.03). T...

The majority of day laborers in the USA are Latinos. They are engaged in high-risk occupations and suffer high occupational injury rates.To describe on-the-job injuries reported by Latino day laborers, explore the extent that demographic and occupational factors predict injuries, and whether summative measures for total job types, job conditions, and personal protective equipment (PPE) predict injuries.A community survey was conducted with 327 participants at 15 corners in Houston, Texas. Hierarchical and multiple logistic regressions explored predictors of occupational injury odds in the last year.Thirty-four percent of respondents reported an occupational injury in the previous year. Education, exposure to loud noises, cold temperatures, vibrating machinery, use of hard hats, total number of job conditions, and total PPE significantly predicted injury odds.Risk for injury among day laborers is not only the product of a specific hazard, but also the result of their exposure to multiple occupational hazards.

Two trials were conducted to evaluate the influence of fines on the feeding value of steam-flaked corn (SFC) in finishing diets for feedlot cattle. Three levels (0, 333 and 667 g/kg) of re-rolled SFC replaced standard SFC (0.31 kg/L) in a corn-based finishing diet (DM basis). Diets were offered as total mixed rations. Re-rolled SFC consisted of standard air-dry SFC that was passed through the rollers a second time to simulate loss of flake integrity which can occur during feed-handling. In experiment one, the influence of fines in SFC on growth performance was evaluated in eighteen crossbred steers (294 ± 5 kg) in a replicated 3 × 3 Latin square design. Daily weight gain was similar (P>0.10) among treatments, averaging 1.31 kg/d. Dry matter intake tended to be greater (quadratic effect, P=0.06) for diets containing re-rolled steam-flaked corn. Gain efficiency and dietary NE were not influenced by dietary treatments (P>0.10). In experiment two, six Holstein steers (308 ± 17 kg) with cannulas in the rumen and proximal duodenum were used in a replicated 3 × 3 Latin square design to evaluate treatment effects on characteristics of digestion. Reductions in particle size of SFC due to rerolling did not influence ruminal or total tract digestion of OM, NDF, N, or starch (P>0.10). Likewise, there were no treatment effects (P>0.10) on ruminal microbial efficiency, ruminal pH, or ruminal VFA molar proportions. It is concluded that the impact of flake disintegration during conveyance and handling on feedlot cattle growth performance and characteristics of digestion will be marginal, if appreciable.

One hundred sixty Holstein steers (222 ± 1 kg) were used in a 264-d growing-finishing trial to evaluate the influence of forage aNDFom level (40 vs 80 g/kg DM) and source [ground forage (alfalfa, sudangrass, and rice straw) or pelletized rice straw] on growth performance. Forage source did not influence (P>0.10) gain efficiency or dietary net energy (NE). Daily weight gain (ADG) and dry matter intake (DMI) were similar (P>0.10) for alfalfa, sudangrass and ground rice straw. Pelletizing rice straw depressed ADG (P 0.10). Ruminal OM digestion was not affected by forage aNDFom level (P=0.96); however, it was greater (P=0.04) for sudangrass vs alfalfa supplemented diets. Microbial efficiency was not affected by forage aNDFom level (P=0.53); however, it was greater (P=0.02) for alfalfa vs sudangrass supplemented diets. Forage source did not affect total tract aNDFom digestion (P=0.86). However, aNDFom digestion was greater (P=0.08) for 80 vs 40 g/kg of forage aNDFom. There were interactions between forage aNDFom level and source on total tract OM digestion (P=0.03). With alfalfa, level of forage aNDFom did not affect OM digestion. With sudangrass, increasing forage aNDFom decreased (P 0.10) on ruminal OM digestion or microbial efficiency. Ruminal aNDFom digestion was greater (P=0.05) for pelletized vs ground rice straw. There were no treatment effects (P>0.10) on total tract aNDFom digestion. Pelletizing did not affect (P=0.78) total tract OM digestion. Tract OM digestion was greater (P=0.03) for 40 vs 80 g/kg of forage aNDFom. Level of forage aNDFom did not affect (P>0.10) ruminal pH or VFA molar proportions. Ruminal pH and acetate:propionate molar ratio were greater (P

Eight Holstein steers (216±48 kg body weight) fitted with ruminal and duodenal cannulas were used to evaluate effects of wheat straw processing (ground vs pelleted) at two straw inclusion rates (7% and 14%; dry matter basis) in dry rolled or steam-flaked corn-based finishing diets on characteristics of digestion. The experimental design was a split plot consisting of two simultaneous 4×4 Latin squares. Increasing straw level reduced ruminal (p0.10) by wheat straw level. Likewise, straw level did not influence ruminal acetate and propionate molar proportions or estimated methane production (p>0.10). Pelleting straw did not affect (p≥0.48) ruminal digestion of OM, NDF, and starch, or microbial efficiency. Ruminal feed N digestion was greater (7.4%; p = 0.02) for ground than for pelleted wheat straw diets. Although ruminal starch digestion was not affected by straw processing, post-ruminal (p0.14) by corn processing. However, microbial N flow to the small intestine and ruminal N efficiency (non-ammonia N flow to the small intestine/N intake) were greater (p

Nano Random Forests is a machine learning-based approach to extract valuable information about multiprotein complexes in collections of proteomics experiments. In mitotic chromosome data, it retrieves known relationships among kinetochore substructures and provides highly specific predictions about uncharacterized protein function., Ever-increasing numbers of quantitative proteomics data sets constitute an underexploited resource for investigating protein function. Multiprotein complexes often follow consistent trends in these experiments, which could provide insights about their biology. Yet, as more experiments are considered, a complex’s signature may become conditional and less identifiable. Previously we successfully distinguished the general proteomic signature of genuine chromosomal proteins from hitchhikers using the Random Forests (RF) machine learning algorithm. Here we test whether small protein complexes can define distinguishable signatures of their own, despite the assumption that machine learning needs large training sets. We show, with simulated and real proteomics data, that RF can detect small protein complexes and relationships between them. We identify several complexes in quantitative proteomics results of wild-type and knockout mitotic chromosomes. Other proteins covary strongly with these complexes, suggesting novel functional links for later study. Integrating the RF analysis for several complexes reveals known interdependences among kinetochore subunits and a novel dependence between the inner kinetochore and condensin. Ribosomal proteins, although identified, remained independent of kinetochore subcomplexes. Together these results show that this complex-oriented RF (NanoRF) approach can integrate proteomics data to uncover subtle protein relationships. Our NanoRF pipeline is available online.

Two corn hybrid varieties [normal yellow dent corn (NC) and high oil corn (HOC)] and two levels of supplemental fat (0 vs. 30 g yellow grease/kg diet, YG) were evaluated in two 4 × 4 Latin square experiments involving eight Holstein steers with ruminal and duodenal cannulas. In Experiment 1, corn varieties were processed by dry rolling. In Experiment 2, they were processed by steam flaking. Non fat-supplemented NC and HOC diets contained 2.7 and 4.8 g of fatty acids (FA)/kg diet, respectively. Fat supplementation increased FA content to 4.9 and 7.1 g FA/kg diet for NC and HOC diets, respectively. With dry rolled corn varieties (Experiment 1), there were no treatment interactions on ruminal, postruminal and total tract digestion of OM, starch and N. There were interactions (P≤0.05) between corn variety and supplemental YG on ruminal aNDFom and postruminal FA digestion. With dry rolled NC, supplemental YG decreased ruminal aNDFom digestion, and postruminal FA digestion. Whereas, with dry rolled HOC, supplemental YG increased ruminal aNDFom digestion, but did not affect postruminal FA digestion. YG decreased (P 0.05) total tract digestion of OM, starch, aNDFom and N, but increased (2.5%, P≤0.05) dietary DE. Ruminal (P 0.05) on ruminal, postruminal and total tract digestion of OM, aNDFom, starch and N. There were interactions (P≤0.05) between corn variety and supplemental YG on intestinal FA digestion. With the NC diets, YG decreased FA digestion; whereas with the HOC diets, supplemental YG increased FA digestion. Supplemental YG did not affect (P>0.05) ruminal digestion, postruminal, or total tract digestion of OM, aNDFom, starch, N. Diet DE value was greater (3.1%, P≤0.05) for YG supplemented diets. There were no corn variety effects (P>0.05) on ruminal, postruminal and total tract digestion of OM, aNDFom, starch and N. Postruminal FA digestion was greater (6.7%, P

Four Holstein steers (407 ± 4 kg) with cannulas in the rumen and proximal duodenum were used in a 4×4 Latin Square design experiment. Treatments consisted of a 755 g/kg steam-flaked corn-based finishing diet in which fungal infested steam-flaked corn replaced 0, 150, 300, and 450 g/kg of the control flaked corn. The yeast and mold counts averaged 2.9×102, and 1.2×104 CFU/g, respectively, for control flaked corn, and 7.0×105, and 6.2×106 CFU/g, respectively, for fungal infested flaked corn. There were no treatment effects (P>0.10) on ruminal pH or volatile fatty acids molar proportions. Ruminal digestion of organic matter (OM; linear component, P 0.10) on net microbial N synthesis. Amino acid intake increased linearly (P 0.10) by treatments. It is concluded that mold infestation diminishes the feeding value of steam-flaked corn. The consequence was not related to effects of fungal growth on characteristics of digestion, but rather, to loss of readily digestible nutrients (starch) through the spoilage process, and to a lesser extent, decreased N digestibility. On the other hand, the metabolizable protein value was greater for fungal infested flaked corn.

Montano, M.F., Loya-Olguin, J.L., Plascencia, A., Salinas Chavira, J. and Zinn, R.A. 2010. Effect of variation in supplement inclusion rate and laidlomycin propionate on growth performance of feedlot cattle. J. Appl. Anim. Res., 37: 83–87. One hundred twelve yearling steers (364±3.4 kg) were used in a 123-d finishing trial to evaluate the interaction of laidlomycin propionate and variation in supplement inclusion rate on growth performance and carcass characteristics. Two levels of laidlomycin propionate (0 vs. 10 mg/kg) and two levels of variation in daily supplement (12 g urea, 18 g limestone, 2 g Mg02 and 5 g trace mineralized salt) inclusion rate (O vs 20% coefficient of variation) were evaluated in a 2x2 factorial arrangement. Variation was produced by altering the inclusion rate of the supplement portion of the diet to achieve a 20% CV in supplement concentration of the complete mixed, as follows: on d 1 and 5 of each week the diet contained 125% of the specified amount of supplement; on d ...

Plascencia, A., Alvarez, E.G., Montanto, M., Salinas-Chavira, J. and Zinn, R.A. 2009. Effects of dietary calcium levels on growth-performance and digestive function in cattle fed a high-fat finishing diet. J. Appl. Anim. Res., 36: 179–184. A growth performance and digestion trial was conducted to evaluate the influence of dietary calcium level on the feeding value of a high-fat (11%) finishing diet. Treatments consisted of three levels of dietary Ca: 0.50, 0.70 and 0.90% (DM basis). Ca source was limestone and yellow grease was included as supplemental fat. There were no treatment effects (P>0.20) on DMI. Increasing dietary Ca level enhanced ADG (P 0.10) on total tract digestion of OM, ...

One hundred eight Holstein steer calves (114 ± 8 kg) were used to evaluate effects of phase feeding metabolizable amino acids (MAA) on growth performance and carcass characteristics. Three feeding strategies were evaluated: 1) control, single-phase feeding (steers were fed a single urea-based growing-finishing diet that meets the average MAA requirements for the overall feeding period); 2) 2-phase feeding (steers were fed a diet formulated to meet the average MAA requirements for the first 112 d on feed, and thereafter finished on the control urea-based diet); and 3) 3-phase feeding (2 diets were formulated to meet average MAA requirements during the first and second 56-d feedlot feeding periods, and thereafter cattle were finished on the control urea-based diet). Two-phase feeding and 3-phase feeding management strategies produced similar (P > 0.20) growth performance. Multiple-phase feeding increased ADG (18%, P 0.20) on growth performance; however, multiple-phase feeding increased overall (351-d) ADG (6.3%, P 0.20) of 3-phase vs. 2-phase feeding strategies on carcass characteristics. Multiple-phase feeding increased hot carcass weight (5.2%, P g was similar (96%) to that expected for the 2- and 3-phase programs during the first 112 d, but was only 83% of expected for the single-phase program. It was concluded that a 2-phase feeding program was needed to improve overall ADG, G:F, and energetic efficiency of calf-fed (placed in the feedlot as lightweight calf) Holstein steers compared with a conventional single-phase system. At a minimum, a 2-phase system would need to separately consider MAA requirements from feedlot placement to 280 kg BW (phase 1) and from 280 kg BW to harvest (phase 2). Methionine, Lys, and His appear to be the first limiting amino acids during the first feeding phase. During the second phase (280 kg to harvest), supply of all MAA acids will exceed requirements, even where urea is the sole source of supplemental N. Maximizing growth rate during the first feeding phase may enhance carcass dressing percent and LM area.

Forty-eight crossbred heifers (378.1±18 kg) were used in a 56-d feeding trial (four pens per treatment in a randomised complete block design) to evaluate the influence of ionophore supplementation on growth performance, dietary energetics and carcass characteristics in finishing cattle during a period of heat stress. Heifers were fed a diet based on steam-flaked corn (2.22 Mcal NEm/kg) with and without an ionophore. Treatments were: i) control, no ionophore; ii) 30 mg/kg monensin sodium (RUM30); iii) 20 mg/kg lasalocid sodium (BOV20), and iv) 30 mg/kg lasalocid sodium (BOV30). Both dry matter intake (DMI) and climatic variables were measured daily and the temperature humidity index (THI) was estimated. The maximum THI during the study averaged 93, while the minimum was 70 (THI average = 79.2±2.3). Compared to controls, monensin supplementation did not influence average daily gain, the estimated NE value of the diet, or observed-to-expected DMI, but tended (p = 0.07) to increase (4.8%) gain to feed. Compared to controls, the group fed BOV30 increased (p≤0.03) daily gain (11.8%), gain to feed (8.3%), net energy of the diet (5%), and observed-to-expected DMI (5.2%). Daily weight gain was greater (7.6%, p = 0.05) for heifers fed BOV30 than for heifers fed MON30. Otherwise, differences between the two treatments in DMI, gain to feed, and dietary NE were not statistically significant (p>0.11). Plotting weekly intakes versus THI, observed intake of controls was greater (p0.05) in the ionophores group (CV = 1.7%) than in the control group (CV = 4.5%). Inclusion of ionophores in the diet resulted in relatively minor changes in carcass characteristics. It is concluded that ionophore supplementation did not exacerbate the decline of DM intake in heat-stressed cattle fed a high-energy finishing diet; on the contrary, it stabilised feed intake and favoured feed efficiency. Ionophore supplementation reduced estimated maintenance coefficients around 10% in finishing cattle during a period of heat stress. This effect was greatest for heifers supplemented with 30 mg lasalocid/kg of diet.

The DELPHI experiment has already collected 2.5 million Z 0 decays with the ring imaging Cherenkov detector (RICH) operational. This detector, covering most of the solid angle, is designed to perform π K separation from 0.8 to 20 GeV/ c and K/p separation from 0.8 to 35 GeV/ c . After a brief detector description we discuss the actual operating conditions, the data monitoring and the signal treatment. The collected data from Z 0 decays and the detector response to signals from the calibration system are used to evaluate the performance of the RICH system.

The general purpose particle detector DELPHI at the Large Electron Positron collider at CERN was built to give the complete information of each event. DELPHI uses ring imaging Cherenkov counters to provide hadron identification in most of the momentum range below 45 GeV/ c and over almost the full solid angle. Charged particles traversing gaseous and liquid fluorocarbon radiators create photons used for Cherenkov angle reconstruction. Some of the design features of the detector will be presented, with emphasis on the experience which was gained in the operation of these large systems. The hadron identification power of the ring imaging Cherenkov detector closely meets the main design values. Data processing and performance of the detector will be discussed using dimuon events collected during 1994. Pion rejection factors for kaon tagging will be shown.

The ring imaging Cherenkov detector in the DELPHI Experiment at LEP allows hadron identification over a momentum range up to about 40 Gev/c over a near to 4π solid angle. Photons emitted by charged particles traversing gas and liquid radiators which are filled with UV-transparent perfluorocarbons, are used for Cherenkov angle reconstruction. Stable operation ensures that the detector is an efficient and powerful instrument. Monitoring of the detector parameters is of utmost importance to achieve good data quality and adequate data processing. The hadron identifying power of the ring imaging Cherenkov detector closely meets the main design values. Computerized control and monitoring features of the different subsystems will be presented. The interplay between detector parameters and the particle separating capacity of the detector will be discussed.

The Forward Ring Imaging Cherenkov detector covers both end-cap regions of the DELPHI experiment at LEP in the polar angle 15/spl deg/ >

The Forward Ring Imaging Cherenkov detector of the DELPHI experiment at LEP provides hadron identification at polar angles15° < θ < 35° and 145° < θ < 165°. Two radiator media, a layer of liquid C6F14 and a volume of gaseous C4F10, in combination provide coverage of momenta up to 40 GeV/c. A single array of photosensitive Time Projection Chambers registers the impact points of ultraviolet photons from both radiators. The design of the detector and of its readout system is described. First results obtained with a partly installed detector are reported.

One quarter of the Forward Ring Imaging Cherenkov (Forward RICH) detector has been installed and operated in the DELPHI experiment. The detector covers the forward-backward regions (15 degrees >

Two trials were conducted to evaluate the influence of supplemental urea withdrawal on characteristics of digestion (Trial 1) and growth performance (Trial 2) of feedlot cattle during the last 40 days on feed. Treatments consisted of a steam-flaked corn-based finishing diet supplemented with urea to provide urea fermentation potential (UFP) of 0, 0.6, and 1.2%. In Trial 1, six Holstein steers (160 ± 10 kg) with cannulas in the rumen and proximal duodenum were used in a replicated 3 × 3 Latin square experiment. Decreasing supplemental urea decreased (linear effect, P ≤ 0.05) ruminal OM digestion. This effect was mediated by decreases (linear effect, P ≤ 0.05) in ruminal digestibility of NDF and N. Passage of non-ammonia and microbial N (MN) to the small intestine decreased (linear effect, P = 0.04) with decreasing dietary urea level. Total tract digestion of OM (linear effect, P = 0.06), NDF (linear effect, P = 0.07), N (linear effect, P = 0.04) and dietary DE (linear effect, P = 0.05) decreased with decreasing urea level. Treatment effects on total tract starch digestion, although numerically small, likewise tended (linear effect, P = 0.11) to decrease with decreasing urea level. Decreased fiber digestion accounted for 51% of the variation in OM digestion. Ruminal pH was not affected by treatments averaging 5.82. Decreasing urea level decreased (linear effect, P ≤ 0.05) ruminal N-NH and blood urea nitrogen. In Trial 2, 90 crossbred steers (468 kg ± 8), were used in a 40 d feeding trial (5 steers/pen, 6 pens/ treatment) to evaluate treatment effects on final-phase growth performance. Decreasing urea level did not affect DMI, but decreased (linear effect, P ≤ 0.03) ADG, gain efficiency, and dietary NE. It is concluded that in addition to effects on metabolizable amino acid flow to the small intestine, depriving cattle of otherwise ruminally degradable N (RDP) during the late finishing phase may negatively impact site and extent of digestion of OM, depressing ADG, gain efficiency, and dietary NE.