Measurement of the thermal conductivity of helium up to 2100°K by the column method

The thermal conductivity of helium was measured at atmospheric pressure in the range 800–2100°K by the column method. The data could be correlated by the polynomial λ = 0.635×10−1+0.310×10−3T−0.244×10−7T2λ=0.635×10−1+0.310×10−3T−0.244×10−7T2, where λ is in watts per meters degrees Kelvin and T is in degrees Kelvin. The results obtained were compared with previous thermal conductivity measurements. The data of Desmond and Saxena and Saxena agree closely with the present results; the data of Timrot and Umanskii appear to be too low and those of Blais and Mann too high. Values for f = λ/ηCvf=λ∕ηCv, computed using measured thermal conductivities and available viscosity data, were found to agree well with classical results from kinetic theory.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/70040/2/JCPSA6-58-10-4080-1.pd

Design of a novel continuous flow reactor for low pH viral inactivation

Currently the Biopharamaceutical industry is moving from operating in batch mode to continuous manufacturing. Low pH viral inactivation is a highly effective and a common method used in monoclonal antibody purification processes. During this unit operation the product is pooled and held, presenting a major bottle neck to end-to-end continuous downstream processing. Moving from a holding tank to a tubular reactor would provide for a means of processing materials continuously. The major challenges with tubular reactors for this application include limiting and characterizing the axial dispersion to ensure sufficient incubation time. The main objective of this work was to design and characterization of the residence time distribution (RTD), exit age of fluid elements leaving the reactor, of a continuous tubular reactor (CTR) for low pH viral inactivation. The following CTR design criteria were generated to streamline integration into the downstream purification process: (1) a ≤ 5 psi pressure drop along the length of the tube, (2) radial mixing within the reactor without moving parts to minimize axial dispersion, (3) a minimum residence time (MRT) approach was used to ensure that the desired product holding time was met, (4) operating at the laminar flow regime to limit shear on the product and minimize the pressure drop along the tube length while operating at flow rates sufficient for a 100 L bioreactor continuous process. Curved pipes offer improved radial mixing due to the formation of Dean Vortices via centrifugal forces. Thus, to reduce axial dispersion, the reactor as designed to include curvature in flow path via alternating 270 turns which also induced changes in the flow direction with each turn or flow inversions. A modular design with incubation chambers that can be connected in series was generated and evaluated using computation fluid dynamic (CFD) simulation before a final design was 3D printed and experimentally evaluated. Comprehensive computational fluid dynamics modeling in ANSYS Fluent of the CTR via velocity profile and secondary flow streamlines show enhanced radial mixing due to secondary flows and changes in flow direction. CFD simulation results were validated by pulsed tracer experiments and were in sufficient agreement, RTD variance values within 6.7%, with the computational model. Scaling the CTR with length to ~115.1 m at 50 ml/min, resulted in a MRT of 70.4 ± 0.46 mins with a pressure drop of ~0.7 psi. With increased length the dimensionless RTD profiles become more symmetrical and tighter about the mean residence time, indicating a smaller deviation from plug flow with increased length. Further scalability of the design is currently under investigation via generation and CFD analysis of a geometrical scale-down model for viral clearance studies

The PPAR-Platelet Connection: Modulators of Inflammation and Potential Cardiovascular Effects

Historically, platelets were viewed as simple anucleate cells responsible for initiating thrombosis and maintaining hemostasis, but clearly they are also key mediators of inflammation and immune cell activation. An emerging body of evidence links platelet function and thrombosis to vascular inflammation. peroxisome proliferator-activated receptors (PPARs) play a major role in modulating inflammation and, interestingly, PPARs (PPAR [Formula: see text] / [Formula: see text] and PPAR [Formula: see text]) were recently identified in platelets. Additionally, PPAR agonists attenuate platelet activation; an important discovery for two reasons. First, activated platelets are formidable antagonists that initiate and prolong a cascade of events that contribute to cardiovascular disease (CVD) progression. Dampening platelet release of proinflammatory mediators, including CD40 ligand (CD40L, CD154), is essential to hinder this cascade. Second, understanding the biologic importance of platelet PPARs and the mechanism(s) by which PPARs regulate platelet activation will be imperative in designing therapeutic strategies lacking the deleterious or unwanted side effects of current treatment options

Characterization of an engineered human purine nucleoside phosphorylase fused to an anti-her2/neu single chain Fv for use in ADEPT

Abstract Background Antibody Directed Enzyme Prodrug Therapy (ADEPT) can be used to generate cytotoxic agents at the tumor site. To date non-human enzymes have mainly been utilized in ADEPT. However, these non-human enzymes are immunogenic limiting the number of times that ADEPT can be administered. To overcome the problem of immunogenicity, a fully human enzyme, capable of converting a non-toxic prodrug to cytotoxic drug was developed and joined to a human tumor specific scFv yielding a fully human targeting agent. Methods A double mutant of human purine nucleoside phosphorylase (hDM) was developed which unlike the human enzyme can cleave adenosine-based prodrugs. For tumor-specific targeting, hDM was fused to the human anti-HER2/neu single chain Fv (scFv), C6 MH3B1. Enzymatic activity of hDM with its natural substrates and prodrugs was determined using spectrophotomeric approaches. A cell proliferation assay was used to assess the cytotoxicity generated following conversion of prodrug to drug as a result of enzymatic activity of hDM. Affinity of the targeting scFv, C6 MH3B1 fused to hDM to Her2/neu was confirmed using affinity chromatography, surface plasmon resonance, and flow-cytometry. Results In vitro hDM-C6 MH3B1 binds specifically to HER2/neu expressing tumor cells and localizes hDM to tumor cells, where the enzymatic activity of hDM-C6 MH3B1, but not the wild type enzyme, results in phosphorolysis of the prodrug, 2-fluoro-2'-deoxyadenosine to the cytotoxic drug 2-fluoroadenine (F-Ade) causing inhibition of tumor cell proliferation. Significantly, the toxic small drug diffuses through the cell membrane of HER2/neu expressing cells as well as cells that lack the expression of HER2/neu, causing a bystander effect. F-Ade is toxic to cells irrespective of their growth rate; therefore, both the slowly dividing tumor cells and the non-dividing neighboring stromal cells that support tumor growth should be killed. Analysis of potential novel MHCII binding peptides resulting from fusion of hDM to C6 MH3B1 and the two mutations in hDM, and of the structure of hDM compared to the wild-type enzyme suggests that hDM-C6 MH3B1 should exhibit minimal immunogenicity in humans. Conclusion hDM-C6 MH3B1 constitutes a novel human based protein that addresses some of the limitations of ADEPT that currently preclude its successful use in the clinic

Vitamins A & D Inhibit the Growth of Mycobacteria in Radiometric Culture

The role of vitamins in the combat of disease is usually conceptualized as acting by modulating the immune response of an infected, eukaryotic host. We hypothesized that some vitamins may directly influence the growth of prokaryotes, particularly mycobacteria. complex).Vitamins A and D cause dose-dependent inhibition of all three mycobacterial species studied. Vitamin A is consistently more inhibitory than vitamin D. The vitamin A precursor, β-carotene, is not inhibitory, whereas three vitamin A metabolites cause inhibition. Vitamin K has no effect. Vitamin E causes negligible inhibition in a single strain.We show that vitamin A, its metabolites Retinyl acetate, Retinoic acid and 13-cis Retinoic acid and vitamin D directly inhibit mycobacterial growth in culture. These data are compatible with the hypothesis that complementing the immune response of multicellular organisms, vitamins A and D may have heretofore unproven, unrecognized, independent and probable synergistic, direct antimycobacterial inhibitory activity

Thermochronometer record of central Andean Plateau growth, Bolivia (19.5°S)

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/94850/1/tect1973.pd

Phylogeny and Taxonomy of the Round-Eared Sengis or Elephant-Shrews, Genus Macroscelides (Mammalia, Afrotheria, Macroscelidea)

The round-eared sengis or elephant-shrews (genus Macroscelides) exhibit striking pelage variation throughout their ranges. Over ten taxonomic names have been proposed to describe this variation, but currently only two taxa are recognized (M. proboscideus proboscideus and M. p. flavicaudatus). Here, we review the taxonomic history of Macroscelides, and we use data on the geographic distribution, morphology, and mitochondrial DNA sequence to evaluate the current taxonomy. Our data support only two taxa that correspond to the currently recognized subspecies M. p. proboscideus and M. p. flavicaudatus. Mitochondrial haplotypes of these two taxa are reciprocally monophyletic with over 13% uncorrected sequence divergence between them. PCA analysis of 14 morphological characters (mostly cranial) grouped the two taxa into non-overlapping clusters, and body mass alone is a relatively reliable distinguishing character throughout much of Macroscelides range. Although fieldworkers were unable to find sympatric populations, the two taxa were found within 50 km of each other, and genetic analysis showed no evidence of gene flow. Based upon corroborating genetic data, morphological data, near sympatry with no evidence of gene flow, and differences in habitat use, we elevate these two forms to full species

Self-archiving and the Copyright Transfer Agreements of ISI-ranked library and information science journals

A study of Thomson-Scientific ISI ranked Library and Information Science (LIS) journals (n = 52) is reported. The study examined the stances of publishers as expressed in the Copyright Transfer Agreements (CTAs) of the journals toward self-archiving, the practice of depositing digital copies of one\u27s works in an Open Archives Initiative (OAI)-compliant open access repository. Sixty-two percent (32) do not make their CTAs available on the open Web; 38% (20) do. Of the 38% that do make CTAs available, two are open access journals. Of the 62% that do not have a publicly available CTA, 40% are silent about self-archiving. Even among the 20 journal CTAs publicly available there is a high level of ambiguity. Closer examination augmented by publisher policy documents on copyright, self-archiving, and instructions to authors reveals that only five, 10% of the ISI-ranked LIS journals in the study, actually prohibit self-archiving by publisher rule. Copyright is a moving target, but publishers appear to be acknowledging that copyright and open access can co-exist in scholarly journal publishing. The ambivalence of LIS journal publishers provides unique opportunities to members of the community. Authors can self-archive in open access archives. A society-led, global scholarly communication consortium can engage in the strategic building of the LIS information commons. Aggregating OAI-compliant archives and developing disciplinary-specific library services for an LIS commons has the potential to increase the field\u27s research impact and visibility. It may also ameliorate its own scholarly communication and publishing systems and serve as a model for others