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Delivery of limit-fed, complete rations requires significant capital investment, and creates logistical challenges for producers. Deconstruction and separate delivery of roughage and concentrate portions of diets may decrease feeding cost. Two experiments were conducted to evaluate the potential of separately limit-feeding roughage and concentrate. In Experiment 1, 4 ruminally cannulated steers (371 ± 12 kg bodyweight) were used in a 4 × 4 Latin square to evaluate the effects of time of concentrate delivery in deconstructed diets. Intake was restricted to 80% of predicted NEm requirements of a diet consisting of wheat straw (35%), cracked corn (29%), and distillers' grains (27%) formulated to contain 1.58 Mcal NEm/kg. Treatments were: concentrate fed 2 h prior to wheat straw (–2S), concentrate and wheat straw fed as total mixed ration (TMR), concentrate fed 2 h after wheat straw (+2S), and concentrate fed 12 h after wheat straw (+12S). In Experiment 2, 95 mid- to late-gestation cows (503 ± 151 kg) were used in a 112-d trial to evaluate feeding system on cow performance. Cows were assigned to 1 of 12 pens. Treatments were limit-fed the complete diet from Experiment 1 (TMR), fed roughage and concentrate portions of the deconstructed TMR 12 h apart (SEP), and ad libitum bermudagrass hay (HAY). Bodyweight (BW), BCS, and back fat measures were collected every 28 d. In Experiment 1, treatment did not affect DM or OM digestion (P ≥ 0.88), rate of particulate passage (P ≥ 0.55), or ruminal DM fill (P ≥ 0.19). Fill averaged 3.8 kg DM. Nadir of ruminal pH occurred 4–8 h after concentrate was delivered, but mean ruminal pH was not different among treatments (P = 0.22) ranging from 6.4 to 6.6 for +2S and 12S, respectively. In Experiment 2, treatment did not affect final BW (518 kg; P = 0.72) or final BCS (5.6; P = 0.67), but limit-fed strategies tended (P = 0.06) to have greater final RE (137.1, 98.9, and –14.6 Mcal for TMR, SEP, and HAY, respectively). Delivering forage and concentrate separately did not change digestion, and timing of concentrate delivery had only minor effects on ruminal fermentation. Limit-feeding a TMR or separate delivery of roughage and concentrate sustained cow performance compared to ad libitum hay consumption. [ABSTRACT FROM AUTHOR]

We report optically detected magnetic resonance (ODMR) experiments at pressures up to 40 kbar for p-benzoquinone (BQ) in dibromobenzene (DBB) and for a deep x-trap in a BQ-d4 neat crystal. It is known from previous works that the phosphorescent triplet state (3B1g) of these systems is vibronically coupled to a nearby 3Au state, such that the former exhibits a double-minimum potential well. The zero-field splitting (ZFS) parameter D of both systems changes by several gigahertz over our pressure range. The greatest slope occurs at zero pressure, and the rate of change slows down exponentially at higher pressure. In addition, we observed a phase transition in BQ-d4 crystals at 6 kbar, which causes a huge step-discontinuity in both D and E. In contrast to the enormous change in D, the E-value is not sensitive to pressure except for the step-change during the phase transition. Triplet state kinetics and phosphorescence spectra are used to establish the existence of an in-plane distortion at least in the high-pressure phase. A model is proposed to interpret these results based on the pressure-dependent vibronic interaction, leading to a reduction of the spin–orbit coupling contribution to the ZFS. [ABSTRACT FROM AUTHOR]

We hypothesized that abomasal infusion of glucose would promote de novo fatty acid biosynthesis from glucose in vitro in bovine intramuscular (i.m.) and subcutaneous (s.c.) adipose tissues to a greater extent than ruminal infusion of acetate, propionate, or glucose. Angus crossbred steers (n = 24), 22 mo of age, were fitted with ruminal cannulas, and steers were adapted to another corn/sorghum finishing diet over a 2-wk period while recovering from the placement of the cannulas. After the adaptation period, the steers were fed the second finishing diet at 130% of their voluntary intake and were infused with isocaloric amounts (3.76 Mcal/d) of glucose, propionate, or acetate for 35 d. Glucose was infused either into the rumen or into the abomasum, whereas propionate and acetate were infused into the rumen. Acetate infusion decreased DM and DE intakes (P < 0.05). The 5th to 8th longissimus muscle section was removed immediately and transported to the laboratory within 10 min post-exsanguination in 38 °C, oxygenated Krebs Henseleit buffer containing 5 mM glucose and 5 mM acetate. Intramuscular and s.c. adipose tissues were dissected from the muscle and incubated in vitro in 5 mM glucose plus 5 mM acetate (containing [U-14C]glucose or [1-14C] acetate). Lipid content was lower (P = 0.04) in i.m. adipose tissue of the acetate-infused steers than in the other treatment groups, and i.m. adipocytes from acetate-infused steers were smaller (P = 0.01) than those from propionate-infused steers. The rate of incorporation of acetate into glyceride-fatty acids (GFA) in i.m. and s.c. adipose tissues was greater (P < 0.03) in steers receiving ruminal or abomasal infusions of glucose than in adipose tissues from steers infused with acetate. The greatest rates of GFA synthesis were observed in s.c. adipose tissue from steers infused ruminally with propionate or abomasally infused with glucose (P < 0.001). In i.m. and s.c. adipose tissues, the proportion of acetyl units from acetate incorporated into GFA was greater in steers receiving glucose infusion in the rumen or abomasum than in steers receiving acetate or propionate infusion (P < 0.05). Contrary to our hypothesis, abomasal glucose infusion did not promote greater fatty acid biosynthesis from glucose in i.m. adipose tissue than ruminal glucose infusion. However, glucose infusion caused the greatest production of acetyl units from acetate in i.m. and s.c. adipose tissues. [ABSTRACT FROM AUTHOR]

Abstract: With a novel thermooptical measuring device (TOM) dimensional changes are investigated during sintering of components and samples up to 50mm in size. Sintering shrinkage is measured without contact using an optical method. This optical method additionally enables the monitoring of warpage, cracking and caking phenomena which often occur in developing new sintering processes. Creep, caused by uniaxial loading of the samples, can also be measured in the axial and transverse direction. Simultaneously, thermal diffusivity and heat transfer coefficients are measured by the laser-flash technique. Material properties are obtained by an inverse simulation of the temperature distribution in the sample. [Copyright &y& Elsevier]

BACKGROUND Whether vaccination during pregnancy could reduce the burden of respiratory syncytial virus (RSV)—associated lower respiratory tract illness in newborns and infants is uncertain. METHODS In this phase 3, double-blind trial conducted in 18 countries, we randomly assigned, in a 1:1 ratio, pregnant women at 24 through 36 weeks' gestation to receive a single intramuscular injection of 120 tg of a bivalent RSV prefusion F protein—based (RSVpreF) vaccine or placebo. The two primary efficacy end points were medically attended severe RSV-associated lower respiratory tract illness and medically attended RSV-associated lower respiratory tract illness in infants within 90, 120, 150, and 180 days after birth. A lower boundary of the confidence interval for vaccine efficacy (99.5% confidence interval [CI] at 90 days; 97.58% CI at later intervals) greater than 20% was considered to meet the success criterion for vaccine efficacy with respect to the primary end points. RESULTS At this prespecified interim analysis, the success criterion for vaccine efficacy was met with respect to one primary end point. Overall, 3682 maternal participants received vaccine and 3676 received placebo; 3570 and 3558 infants, respectively, were evaluated. Medically attended severe lower respiratory tract illness occurred within 90 days after birth in 6 infants of women in the vaccine group and 33 infants of women in the placebo group (vaccine efficacy, 81.8%; 99.5% CI, 40.6 to 96.3); 19 cases and 62 cases, respectively, occurred within 180 days after birth (vaccine efficacy, 69.4%; 97.58% CI, 44.3 to 84.1). Medically attended RSV-associated lower respiratory tract illness occurred within 90 days after birth in 24 infants of women in the vaccine group and 56 infants of women in the placebo group (vaccine efficacy, 57.1%; 99.5% CI, 14.7 to 79.8); these results did not meet the statistical success criterion. No safety signals were detected in maternal participants or in infants and toddlers up to 24 months of age. The incidences of adverse events reported within 1 month after injection or within 1 month after birth were similar in the vaccine group (13.8% of women and 37.1% of infants) and the placebo group (13.1% and 34.5%, respectively). CONCLUSIONS RSVpreF vaccine administered during pregnancy was effective against medically at-tended severe RSV-associated lower respiratory tract illness in infants, and no safety concerns were identified. (Funded by Pfizer; MATISSE ClinicalTrials.gov number, NCT04424316.) [ABSTRACT FROM AUTHOR]

Abstract: A special thermooptical measuring system was used to determine mechanical, thermal and sintering properties during firing simultaneously. Combining customary and novel in situ measuring methods, a complete dataset was obtained which includes elastic and viscous moduli, thermal conductivity and coefficients of heat transfer, specific heat, reaction and sintering data and gas permeability. Using finite element methods (FEM) the temperature fields in large components were simulated for various time temperature cycles. From the temperature field local reaction and shrinkage rates were calculated. The corresponding stresses were obtained using FEM again. The time temperature cycle was optimized taking into account both a sufficient safety margin to the respective strength of the sintering material and the economic requirement for a short firing cycle. The use of the methods was demonstrated considering as example a large high voltage porcelain insulator, which undergoes a number of phase transformations during firing. [Copyright &y& Elsevier]

Protein biosynthesis and extracellular secretion are essential biological processes for therapeutic protein production in mammalian cells, which offer the capacity for correct folding and proper post-translational modifications. In this study, we have generated bispecific therapeutic fusion proteins in mammalian cells by combining a peptide and an antibody into a single open reading frame. A neutralizing peptide directed against interleukin- 17A (IL17A) was genetically fused to the N termini of an anti-IL22 antibody, through either the light chain, the heavy chain, or both chains. Although the resulting fusion proteins bound and inhibited IL22 with the same affinity and potency as the unmodified anti-IL22 antibody, the peptide modality in the fusion scaffold was not active in the cell-based assay due to the N-terminal degradation. When a glutamine residue was introduced at the Nterminus, which can be cyclized to form pyroglutamate in mammalian cells, the IL17A neutralization activity of the fusion protein was restored. Interestingly, the mass spectroscopic analysis of the purified fusion protein revealed an unexpected O-linked glycosylation modification at threonine 5 of the anti-IL17A peptide. The subsequent removal of this post-translational modification by site-directed mutagenesis drastically enhanced the IL17A binding affinity and neutralization potency for the resulting fusion protein. These results provide direct experimental evidence that post-translational modifications during protein biosynthesis along secretory pathways play critical roles in determining the structure and function of therapeutic proteins produced by mammalian cells. The newly engineered peptide-antibody genetic fusion is promising for therapeutically targeting multiple antigens in a single antibody-like molecule. [ABSTRACT FROM AUTHOR]