Responses of dairy cows supplemented with somatotropin during weeks 5 through 43 of lactation

Beginning at wk 5 of lactation, 136 cows (34 per treatment) were supplemented daily for 38 wk with 0, 10.3, 20.6, or 41.2 mg of recombinantly derived bST monomer. Cows were obtained from University of Kentucky, University of Minnesota, University of Pennsylvania, and The Ohio State University. Nine cows (4 at 0 mg/d, 1 at 10.3 mg/d, 1 at 20.6 mg/d, and 3 at 41.2 mg/d) did not complete the experiment because of health problems. Data from these cows were included in the reproduction and health databases but not in the production database. Cows supplemented with bST produced more milk, consumed more feed, had lower rates of BW gain, and had improved efficiencies of milk production (conversion of feed and NEL to milk). Additional increases in productivity were modest at 20.6 and 41.2 mg/d versus productivity at 10.3 mg/d of bST. Concentrations of fat, protein, and TS in milk were unaffected. At 10.3 mg/d, bST did not adversely affect reproduction or health.     

Phase II trial of 9-aminocamptothecin administered as a 72-hour continuous infusion in metastatic colorectal carcinoma

PURPOSE: The camptothecin derivative irinotecan has demonstrated clinical activity in metastatic colorectal carcinoma in both chemotherapy-naive and fluorouracil-refractory patients. 9-Aminocamptothecin (9-AC; NSC 603071), another camptothecin derivative, was selected for clinical development based on preclinical activity, including cures in human tumor xenografts resistant to standard anticancer agents. We report a phase II trial of 9-AC in patients with previously untreated metastatic colorectal carcinoma. PATIENTS AND METHODS: Colorectal cancer patients with measurable disease, a performance status of 0 to 2 (Zubrod), and no prior chemotherapy for metastatic disease received 9-AC. A cycle of therapy was 35 microg/m2/h for 72 consecutive hours (840 microg/m2/d for 3 days) and rest on days 4 to 14; a course of therapy was defined as two cycles (28 days). Patients were assessed for response after two courses. RESULTS: Seventeen patients with metastatic colorectal cancer were entered onto this trial. No complete or partial responses were noted. Treatment was well tolerated; toxic effects consisted mainly of neutropenia, nausea, vomiting, stomatitis, fatigue, and anemia. Grade 3 to 4 toxicity was limited to neutropenia (grade 3 in four patients and grade 4 in six), anemia (grade 3 in two patients), and vomiting (grade 3 in two patients). No grade 3 or 4 diarrhea occurred. Only two patients had their 9-AC dose reduced to 30 microg/m2/h. The median nadir absolute granulocyte count (AGC) was 1,500/microL. The median number of courses given was two and the median time to disease progression was 8 weeks. CONCLUSION: At the dose and schedule used in this trial, 9-AC lacked antitumor activity in metastatic colorectal cancer. 9-AC infusion schedules of longer duration are currently being investigated in this disease.     

Introducing a Semi-Coated Model to Investigate Antibacterial Effects of Biocompatible Polymers on Titanium Surfaces

Peri-implant infections from bacterial biofilms on artificial surfaces are a common threat to all medical implants. They are a handicap for the patient and can lead to implant failure or even life-threatening complications. New implant surfaces have to be developed to reduce biofilm formation and to improve the long-term prognosis of medical implants. The aim of this study was (1) to develop a new method to test the antibacterial efficacy of implant surfaces by direct surface contact and (2) to elucidate whether an innovative antimicrobial copolymer coating of 4-vinyl-N-hexylpyridinium bromide and dimethyl(2-methacryloyloxyethyl) phosphonate (VP:DMMEP 30:70) on titanium is able to reduce the attachment of bacteria prevalent in peri-implant infections. With a new in vitro model with semi-coated titanium discs, we were able to show a dramatic reduction in the adhesion of various pathogenic bacteria (Streptococcus sanguinis, Escherichia coli, Staphylococcus aureus, Staphylococcus epidermidis), completely independently of effects caused by soluble materials. In contrast, soft tissue cells (human gingival or dermis fibroblasts) were less affected by the same coating, despite a moderate reduction in initial adhesion of gingival fibroblasts. These data confirm the hypothesis that VP:DMMEP 30:70 is a promising antibacterial copolymer that may be of use in several clinical applications.     

Reduction of the elongation at break of thermoplastic polyolefins through melt blending with polylactide and the influence of the amount of compatibilizers and the viscosity ratios of the blend components on phase morphology and mechanics

The objective of this work is the synthesis of a polypropylene/ethylene‐propylene‐rubber (TPO)/polylactide (PLA)/compatibilizer (PVM) blend to reduce the elongation at break of TPO by blending TPO with brittle PLA. Three TPO types with different viscosities were melt blended with PLA and an ethylene/n‐butylacrylate/glycidyl methacrylate terpolymer (PVM) as reactive compatibilizer. All blends had a constant PLA amount of 30 wt%. Two parameters were varied in the experiments, viscosity of the TPO types, and amount of PVM used in the blends. Both parameters played important roles in reducing the nominal elongation at break compared to pure TPO foils and influencing the phase morphology of extruded blend foils. The nominal elongation at break could be reduced by 100‐150% through blending TPO with PLA and PVM. Characterization regarding the blend morphology, especially the size and shape of the dispersed PLA phase in the TPO matrix was done by Environmental Scanning Electron Microscopy (ESEM) images. Investigations of the morphology showed that size and shape of dispersed PLA phases are dependent on the viscosity ratios of the blend components and on the amount of compatibilizer in the blend. AFM images of the polymer blends reveal soft rubbery layers around the dispersed PLA phases. POLYM. ENG. SCI., 56:905–913, 2016. © 2016 Society of Plastics Engineers     

Combined Blockade of TIGIT and CD39 or A2AR Enhances NK-92 Cell-Mediated Cytotoxicity in AML

This study aimed to characterize different natural killer (NK) cell phenotypes on bone marrow and peripheral blood cells from acute myeloid leukemia (AML) patients and healthy donors (HDs). Our data show that CD56^dimCD16⁻ and CD56^brightCD16⁻ NK cells represent the predominant NK cell subpopulations in AML, while the CD56^dimCD16⁺ NK cells are significantly reduced compared to HDs. Moreover, TIGIT⁺ and PVRIG⁺ cells cluster on the CD56^dimCD16⁺ subset whereas CD39⁺ and CD38⁺ cells do so on CD56^brightCD16⁻ NK cells in AML. Furthermore, functional effects of (co-)blockade of TIGIT and CD39 or A2AR on NK cell functionality were analyzed. These experiments revealed that the single blockade of the TIGIT receptor results in an increased NK-92 cell-mediated killing of AML cells in vitro. Combined targeting of CD39 or A2AR significantly augments the anti-TIGIT-mediated lysis of AML cells. Our data indicate that distinct NK cell subsets in AML exhibit different immunosuppressive patterns (via the TIGIT/PVRIG receptors and the purinergic pathway). In summary, we conclude that TIGIT, CD39, and A2AR constitute relevant inhibitory checkpoints of NK cells in AML patients. A combinatorial blockade synergistically strengthens NK-92 cell-mediated cytotoxicity. As inhibitors of TIGIT, CD39, and A2AR are clinically available, studies on their combined use could be conducted in the near future.     

A Mixed-Mode Analogue and Switch Level Simulator

This paper describes an experimental mixed-mode simulation system which couples an incremental time analogue simulator to an event-driven switch level simulator. the analogue timing programme uses a variable-step-size, multi-order (VSMO) numerical integration algorithm which detects and uses latency while maintaining wave-form synchronization. the switch level programme uses piecewise linear wave-forms rather than discrete states to model the operation of logical networks. A unified format in which time responses are events is used for communication between the two programmes. the mixed-mode simulator operates without backtracking or translation between logical states and analogue wave-forms.     

The Objective Conception of Context and Its Logic

In this paper, an objective conception of contexts based loosely upon situation theory is developed and formalized. Unlike subjective conceptions, which take contexts to be something like sets of beliefs, contexts on the objective conception are taken to be complex, structured pieces of the world that (in general) contain individuals, other contexts, and propositions about them. An extended first-order language for this account is developed. The language contains complex terms for propositions, and the standard predicate ist that expresses the relation that holds between a context and a proposition just in case the latter is true in the former. The logic for the objective conception features a global classical predicate calculus, a local logic for reasoning within contexts, and axioms for propositions. The specter of paradox is banished from the logic by allowing ist to be nonbivalent in problematic cases: it is not in general the case, for any context c and proposition p, that either ist(c,p) or ist(c, ¬ p). An important representational capability of the logic is illustrated by proving an appropriately modified version of an illustrative theorem from McCarthy's classic Blocks World example.