Concurrent Design and Manufacturing for Mechanical Systems

The conventional product development process employs a design-build-break philosophy. The sequentially executed product development process often results in a prolonged lead-time and an elevated product cost. The proposed concurrent design and manu facturing (CDM) paradigm employs physics-based computational methods together with computer graphics techniques for product de sign. This proposed approach employs Virtual Prototyping (VP) technology to support a cross-functional team in analyzing product per formance, reliability, and manufacturing cost early in the product development stage; and in conducting quantitative trade-off for design decision making. Physical prototypes of the product design are then produced using Rapid Prototyping (RP) technique primarily for de sign verification purposes. The proposed CDM approach holds potential for shortening the overall product development cycle, improving product quality, and reducing product cost. A software tool environment that supports CDM for mechanical systems is being built at the Concurrent Design and Manufacturing Research Laboratory (http://cdm.ou.edu) at the University of Oklahoma. A snapshot of the envi ronment is illustrated using a two-stroke engine example. This paper presents three unique concepts and methods for product develop ment : (1) bringing product performance, quality, and manufacturing cost together in early design stage for design considerations, (2) supporting design decision-making through a quantitative approach, and (3) incorporating rapid prototyping for design verification through physical prototypes.Yeshttps://us.sagepub.com/en-us/nam/manuscript-submission-guideline

Genome-wide analysis of the cis-regulatory modules of divergent gene pairs in yeast

AbstractIn budding yeast, approximately a quarter of adjacent genes are divergently transcribed (divergent gene pairs). Whether genes in a divergent pair share the same regulatory system is still unknown. By examining transcription factor (TF) knockout experiments, we found that most TF knockout only altered the expression of one gene in a divergent pair. This prompted us to conduct a comprehensive analysis in silico to estimate how many divergent pairs are regulated by common sets of TFs (cis-regulatory modules, CRMs) using TF binding sites and expression data. Analyses of ten expression datasets show that only a limited number of divergent gene pairs share CRMs in any single dataset. However, around half of divergent pairs do share a regulatory system in at least one dataset. Our analysis suggests that genes in a divergent pair tend to be co-regulated in at least one condition; however, in most conditions, they may not be co-regulated

Primordial black holes from second order density perturbations as probes of the small-scale primordial power spectrum

We investigate the second order energy density perturbation $\delta^{(2)}$ induced by small-scale Gaussian and local-type non-Gaussian primordial curvature perturbations. The relative abundance of primordial black hole is calculated in terms of the probability density function of total energy density perturbation $\delta_r=\delta^{(1)}+\frac{1}{2}\delta^{(2)}$. The effects of second order density perturbation greatly reduce the upper bounds of small-scale power spectra of primordial curvature perturbations by one to two orders of magnitude. For log-normal primordial power spectrum, its amplitude $A_{\zeta}$ is constrained to be about $A_{\zeta}\sim 3\times10^{-3}$. And for local-type non-Gaussianity with $f_{\mathrm{NL}}=10$, the upper bound of $A_{\zeta}$ is about $2.5\times10^{-4}$.Comment: 5 pages, 4 figure

The microbial antibodies secretion expression platform with scale down fermentors

Therapeutic antibodies have become one of the most effective therapeutics for human diseases such as cancer, inflammation and viral infection. The production of antibody-based drugs using microbial expression systems is more cost effective with ease of gene manipulation compared to mammalian expression systems. In our team, antibody fragments (ex: BsAb, scFv and Fab) were produced from methylotrophic yeast Pichia pastoris secretion expression system with the AOX1 as driven promoter or E. coli secretion expression system. To achieve high production yield for both system, we investigated fermentation parameter such as base medium, induction medium, induction condition, feeding strategy and pH. For the 250 ml fermentor Pichia system, the nitrogen have been add into glycerol fed medium and/or methanol induction medium and also compared base-medium, buffered glycerol-complex medium (BMGY) and basal salt medium (BS). The highest scFv production was yielded from the basal salt medium as base medium, glycerol fed medium plus nitrogen and multiple carbon source methanol induction medium. This process can yielded over 500 mg/L scFv. After scale-up from 250 ml fermentor to 5L fermentor, the methanol fed-back control system also applied on the 5 L fermentor, can achieve 1.7 g/L scFv in 5 days. The E. coli expression process has passed through screening for high production yield clones in 2 ml deep-well then confirmed by using 250 ml flask scale. Feeding medium, DO, pH etc, parameters were investigated by parallel 250 ml-fermenter. The parameters from 250 ml fermentor were validated by using 5 L fermenter. Under this scale-up procedure, the antibody Fab was 100 folds production yield, production deep well stage at 1 mg/L, production from 250 ml fermentor stage is 50-100 mg/L and production 5 L fermentor stage is over 35-90 mg/L. Although different antibodies will result in different production yield, building a reliable platform to predict production yield from antibody cell clones under deep well and shake flask stage serves a good scale-down model for future scale-up prediction

THE UPPER LIMB EMG ACTIVITY COMPARISON OF DIFFERENT TABLE TENNIS FOREHAND DRIVES

The purpose of this study was to combine dynamics and surface EMG methods to analyze the movements of table tennis forehand drives by Taiwan elite table tennis players performing straight and cross court forehand drives from topspin and backspin serves. The kinematical data were collected by 10 Vicon MX13+ high-speed cameras and one Biovision system was used to record the EMG signal of seven muscles groups on the dominate hand. The results showed that there were significant differences among the four table tennis drives. The players exerted greater muscular activity in the wrist extensors, the biceps and the triceps for the backspin serve forehand drive than when returning the topspin serve forehand drive, not only on the straight but also on the cross court strokes

Enhancement of Cancer Immunotherapy Using Immune Modulating Peptides

poster abstractImmune Peptide Therapeutics (IPT) LLC, an Indiana-based small business and its research partner Indiana University previously identified a novel property of lunasin as a distinct class of immune modulating agent that enhances anti-tumor immunity, which may promote disease-free survival by limiting tumor progression, and thus prolong lives of cancer patients. Lunasin, a synthetic 43-amino acid peptide, was originally isolated from soybeans. Our studies have demonstrated that lunasin exerts robust synergistic effects with cytokines on augmenting IFNγ and granzyme B expression by Natural Killer (NK) cells, which is associated with increased tumoricidal activity of NK cells. In addition, this combination regimen is capable of rescuing IFNγ production ex vivo by NK cells from chemotherapy-treated Non-Hodgkin’s Lymphoma (NHL) patients who are immunocompromised with acquired immune deficiency. The long-term goal is to develop an efficacious immunotherapy which will impact the treatment and improve the clinical outcomes for NHL patients. The dose-response study indicates the optimum concentration of lunasin is at the range of μM, which would undermine its use in clinical studies. To enhance the medicinal value lunasin must be optimized for in vitro and in vivo efficacy. The objective is to develop a second generation of lunasin, which will increase its potency to improve the performance. In this study we have implemented several strategies to design and modify the prototype. The newly developed peptide called IPT.103 has 15 amino acids that are in the D-isoform configuration. Activity of IPT.103 has been tested in vitro with EC50 of 0.78 μM as compared to 4.54 μM for lunasin. IPT.103 also has in vivo activity on enhancing the serum levels of IFNγ production using a mouse model. Taken together, we have developed a peptide derivative (IPT.103) that deviates from its parental type lunasin to increase intellectual merit for commercialization as well as support clinical application

Modulating NK-mediated Immunity by Lunakine

poster abstractDespite the plethora of immune modulating agents available in cancer treatment, their effectiveness relies on a functional immune system. However, the adverse side effects by chemotherapy impede the therapeutic benefits from immunotherapy. It remains a major challenge to prevent relapse for cancer patients who have already undergone rigorous chemotherapy. Lunasin, a 43-amino acid peptide, was originally isolated from soybeans. Our team has recently discovered a novel function of lunasin as an immune modulating agent that exerts robust synergistic effects imposed by several therapeutic cytokines. Such synergism strongly augments IFNγ and granzyme B expression by Natural Killer (NK) cells, which is associated with increased tumoricidal activity. The combination regimen with lunasin and cytokine is capable of restoring NK activation from lymphoma patients with chemotherapy-induced immune dysfunction. Our results support the potential application of lunasin to improve the therapeutic effects of existing cytokine treatment that has been used to eliminate residual tumors cells from lymphoma patients after chemotherapy. We designate lunakine as new formulation by combing lunasin and selected cytokine (filed for US Patent Cooperation Treat). In working with Indiana University and Technology Corporation (IURTC), we have started a startup company, Immune Peptide Therapeutics (IPT), LLC. Our mission is to develop a more efficacious immunotherapy that prevents relapse and confers progression-free survival for cancer patients. With the support from FORCES, our team has successfully developed a second generation of lunasin called IPT.103 that deviates from its parental type. Activity of IPT.103 has been tested in vitro with EC50 of 0.78 μM as compared to 4.54 μM for lunasin, indicating an improved potency to induce IFNγ production by NK cells. The newly developed peptide IPT.103 is expected to strengthen the intellectual property (IP) position for commercialization. We are currently working on tumor models for preclinical assessment of IPT’s regimens in immunotherapy for lymphoma

An investigation on influential factors of patient-controlled epidural analgesic requirement over time for upper abdominal surgeries

Abstract Background: Patient-controlled epidural analgesia (PCEA) is commonly used to relieve postoperative pain for upper abdominal surgeries. However, there is still a lack of studies exploring factors associated with PCEA consumption over time after upper abdominal surgery; our study intended to provide further elucidation about this issue. Methods: This study retrospectively evaluated postoperative PCEA consumption over time after upper abdominal surgery. Cumulative PCEA consumption in the first four 12-hour intervals was directly retrieved from the data recorded by infusion pumps. Potentially influential factors of PCEA requirements, including demographic variables and infusion pump settings, were also collected. A linear mixed model was applied to investigate the relationships between these factors and PCEA consumption over time. A backward elimination strategy was used to select independent factors significantly associated with PCEA consumption. Results: A total of 1001 patients were included in the analysis. On average, PCEA consumption after upper abdominal surgery peaked during the 2 nd 12-hour interval and then decreased gradually over time. After the model selection processes were completed, four independent factors were identified to have significant effects on PCEA consumption. Surgery for malignant disease and background infusion rate were positively associated with PCEA consumption and did not interact with time. Additionally, female patients tended to consume less and less PCEA over time relative to males. Age had a negative effect on PCEA consumption, which peaked during the 2 nd 12-hour interval and then decreased gradually over time. The final selected model exhibited acceptable predictive power relative to the observed data. Conclusion: Our analyses provided valuable information about the factors associated with PCEA consumption over time after upper abdominal surgery. However, the mechanism of how these factors interact over the course of time awaits further investigation