Postal card from J. A. Beattie

Postal card concerning a copy of the catalogue for Utah Agricultural College

Studies of a weak polyampholyte at the air-buffer interface: The effect of varying pH and ionic strength

We have carried out experiments to probe the static and dynamic interfacial properties of $\beta$--casein monolayers spread at the air-buffer interface, and analysed these results in the context of models of weak polyampholytes. Measurements have been made systematically over a wide range of ionic strength and pH. In the semi-dilute regime of surface concentration a scaling exponent, which can be linked to the degree of chain swelling, is found. This shows that at pH close to the isoelectric point, the protein is compact. At pH away from the isoelectric pH the protein is extended. The transition between compact and extended states is continuous. As a function of increasing ionic strength, we observe swelling of the protein at the isoelectric pH but contraction of the protein at pH values away from it. These behaviours are typical of a those predicted theoretically for a weak polyampholyte. Dilational moduli measurements, made as a function of surface concentration exhibit maxima that are linked to the collapse of hydrophilic regions of the protein into the subphase. Based on this data we present a configuration map of the protein configuration in the monolayer. These findings are supported by strain (surface pressure) relaxation measurements and surface quasi-elastic light scattering (SQELS) measurements which suggest the existence of loops and tails in the subphase at higher surface concentrations.Comment: Submitted to J. Chem. Phy

Preclinical efficacy of hK2 targeted [177Lu]hu11B6 for prostate cancer theranostics

Androgen ablating drugs increase life expectancy in men with metastatic prostate cancer, but resistance inevitably develops. In a majority of these recurrent tumors, the androgen axis is reactivated in the form of increased androgen receptor (AR) expression. Targeting proteins that are expressed as a down-stream effect of AR activity is a promising rationale for management of this disease. The humanized IgG1 antibody hu11B6 internalizes into prostate and prostate cancer (PCa) cells by binding to the catalytic cleft of human kallikrein 2 (hK2), a prostate specific enzyme governed by the AR-pathway. In a previous study, hu11B6 conjugated with Actinium-225 (225Ac), a high linear energy transfer (LET) radionuclide, was shown to generate an AR-upregulation driven feed-forward mechanism that is believed to enhance therapeutic efficacy. We assessed the efficacy of hu11B6 labeled with a low LET beta-emitter, Lutetium-177 (177Lu) and investigated whether similar tumor killing and AR-enhancement is produced. Moreover, single-photon emission computed tomography (SPECT) imaging of 177Lu is quantitatively accurate and can be used to perform treatment planning. [177Lu]hu11B6 therefore has significant potential as a theranostic agent. Materials and Methods: Subcutaneous PCa xenografts (LNCaP s.c.) were grown in male mice. Biokinetics at 4-336 h post injection and uptake as a function of the amount of hu11B6 injected at 72 h were studied. Over a 30 to 120-day treatment period the therapeutic efficacy of different activities of [177Lu]hu11B6 were assessed by volumetric tumor measurements, blood cell counts, molecular analysis of the tumor as well as SPECT/CT imaging. Organ specific mean absorbed doses were calculated, using a MIRD-scheme, based on biokinetic data and rodent specific S-factors from a modified MOBY phantom. Tumor tissues of treated xenografts were immunohistochemically (IHC) stained for Ki-67 (proliferation) and AR, SA-β-gal activity (senescence) and analyzed by digital autoradiography (DAR). Results: Organ-to-blood and tumor-to-blood ratios were independent of hu11B6 specific activity except for the highest amount of antibody (150 µg). Tumor accumulation of [177Lu]hu11B6 peaked at 168 h with a specific uptake of 29 ± 9.1 percent injected activity per gram (%IA/g) and low accumulation in normal organs except in the submandibular gland (15 ± 4.5 %IA/g), attributed to a cross-reaction with mice kallikreins in this organ, was seen. However, SPECT imaging with therapeutic amounts of [177Lu]hu11B6 revealed no peak in tumor accumulation at 7 d, probably due to cellular retention of 177Lu and decreasing tumor volumes. For [177Lu]hu11B6 treated mice, tumor decrements of up to 4/5 of the initial tumor volume and reversible myelotoxicity with a nadir at 12 d were observed after a single injection. Tumor volume reduction correlated with injected activity and the absorbed dose. IHC revealed retained expression of AR throughout treatment and that Ki-67 staining reached a nadir at 9-14 d which coincided with high SA- β-gal activity (14 d). Quantification of nuclei staining showed that Ki-67 expression correlated negatively with activity uptake. AR expression levels in cells surviving therapy compared to previous timepoints and to controls at 30 d were significantly increased (p = 0.017). Conclusions: This study shows that hu11B6 labeled with the low LET beta-emitting radionuclide 177Lu can deliver therapeutic absorbed doses to prostate cancer xenografts with transient hematological side-effects. The tumor response correlated with the absorbed dose both on a macro and a small scale dosimetric level. Analysis of AR staining showed that AR protein levels increased late in the study suggesting a therapeutic mechanism, a feed forward mechanism coupled to AR driven response to DNA damage or clonal lineage selection, similar to that reported in high LET alpha-particle therapy using 225Ac labeled hu11B6, however emerging at a later timepoint

Oxidative Heck desymmetrisation of 2,2-disubstituted cyclopentene-1,3-diones

Oxidative Heck couplings have been successfully developed for 2,2-disubstituted cyclopentene-1,3-diones. The direct coupling onto the 2,2-disubstituted cyclopentene-1,3-dione core provides a novel expedient way of enantioselectively desymmetrising all-carbon quaternary centres

Investigation Of Low GWP Refrigerant Interaction With Various Lubricant Candidates

Refrigerants used in various air conditioning and refrigeration industries are going through changes today and continued changes into the near future. These changes are being driven by environmental and energy efficiency regulations and could result in the use of refrigerants that require the investigation of new lubricants. One such change is the use of refrigerants that carry a lower global warming potential (GWP) value then current refrigerants used in the market. Some of these refrigerants present certain challenges over current refrigerants such as changes in flammability requirements, higher pressures or stability of the refrigerant in system operation. These refrigerants and the changes they represent may require different lubricants in order to maintain system optimization ensuring that energy efficiency and reliable requirements are met. The interaction between the refrigerant and the lubricant in any air conditioning or refrigeration system is a vital piece of information that is required to make certain optimal performance is achieved. The lubricant in a system is crucial to operation and needs to adequately lubricate the moving components in a system and return to the compressor when circulated. These conditions can drastically be affected by the refrigerant and lubricant interaction with improper choices resulting in consequences from lowering the overall performance to complete failure. This paper will look at some of the current and proposed low GWP refrigerants and their interaction with various lubricants. Evaluations will be made and certain properties will be presented that are essential to system operation. Of particular interest will be the refrigerant solubility factor of low GWP refrigerant candidates that can affect system performance and reliability; the stability of newer low GWP refrigerant candidates that maintain comparable current refrigerant system requirements; the miscibility of low GWP refrigerants with lubricants that can affect oil circulation; and how chemistry changes to various lubricants can help increase energy efficiency in systems operated with low GWP refrigerants. The information in this paper and the presentation will be a timely look at current and future needs for lubricants for various refrigerants that will help manufacturers in the air conditioning and refrigerant industry to evaluate the choices that need to be made in order to maintain the required system performance

Clinical surveillance of thrombotic microangiopathies in Scotland, 2003-2005

The prevalence, incidence and outcomes of haemolytic uraemic syndrome (HUS) and thrombotic thrombocytopaenic purpura (TTP) are not well established in adults or children from prospective studies. We sought to identify both outcomes and current management strategies using prospective, national surveillance of HUS and TTP, from 2003 to 2005 inclusive. We also investigated the links between these disorders and factors implicated in the aetiology of HUS and TTP including infections, chemotherapy, and immunosuppression. Most cases of HUS were caused by verocytotoxin-producing Escherichia coli (VTEC), of which serotype O157 predominated, although other serotypes were identified. The list of predisposing factors for TTP was more varied although use of immunosuppressive agents and severe sepsis, were the most frequent precipitants. The study demonstrates that while differentiating between HUS and TTP is sometimes difficult, in most cases the two syndromes have quite different predisposing factors and clinical parameters, enabling clinical and epidemiological profiling for these disorders

Improving competitive ability and herbicide options in domesticated oat production systems (Avena sativa L.)

Non-Peer ReviewedDomesticated oat (Avena sativa L.) is an economically important crop, ranking sixth in world cereal production and with production reaching approximately 25 million tonnes annually. It is largely utilized within the food industry and has increased in demand due to recent recognition of its health benefits attributed to beta-glucan. Oat yield reductions and poor grain seed quality have become more prevalent with increased resistant kochia populations. Multiple herbicide resistant (HR) kochia, along with a lack of herbicide registration for domesticated oat, have lead to a significant decrease in weed control efficacy. Thus, the initial objectives of this study are to quantify the efficacy of new herbicides for domesticated oat production. This project will be utilizing Group 2, 6, 14, and 28 PRE- and POST applicant herbicides. Oat yield and biomass was not significantly reduced within most treatments, indicating high crop tolerance. However, based on CWSS visual ratings, which were conducted after application indicated severe tissue damage and growth reductions attributed to several treatments. In contrast, fluthiacet-methyl, florasulam with bromoxynil, and pyrasulfotole with bromoxynil, and bentazon with 2,4-D could pose as alternative herbicide control options, as initial tissue damage was limited and provided reasonable kochia control. Future research is required to confirm efficacy of kochia control and oat tolerance, as apposing research indicates varying results

Sites of Biosynthesis of Outer and Inner Membrane Proteins of Neurospora crassa Mitochondria

Outer and inner membranes of Neurospora crassa mitochondria were separated by the combined swelling, shrinking, sonication procedure. Membranes were characterized by electron microscopy and by marker enzyme activities. A red carotenoid pigment was found to be concentrated in the outer membrane. The inner mitochondrial membrane was resolved into about 20 protein bands on polyacrylamide gel electrophoresis, whereas the outer membrane shows essentially one single protein band. Only negligible incorporation of radioactive amino acids occurs into outer membrane when isolated mitochondria are synthesizing polypeptide chains. In agreement with this observation labeling of outer membrane protein is almost entirely blocked, when whole Neurospora cells are incubated with radioactive amino acids in the presence of cycloheximide, an inhibitor of cytoplasmic protein synthesis. Finally, the essential electrophoretic protein band from outer membrane does not become labeled when mitochondria are incubated with radioactive amino acids either in vitro or in vivo in the presence of cycloheximide. It is concluded that the vast majority, if not all, of the outer membrane protein is synthesized by the cytoplasmic system and that polypeptide chains formed by the mitochondrial ribosomes are integrated into the inner mitochondrial membrane