The agricultural and industrial demand for corn

The World War marked a turning point in the history of corn production in the United States. Previous to the World War the trend of corn production in this country was steadily rising. Since 1920, however, it has declined because of decreases both in yield and acreage. From 1900 to 1920, the United States’ corn crop averaged 68 percent of the world crop of corn, the annual percentages fluctuating about a horizontal trend. Since the World War, however, the United States’ proportion of the world corn crop has been declining. The trend declined to 55 percent in 1933. Corn production has been increasing in other countries and decreasing in the United States. Gross and net exports of corn from the United States have been declining. During the past 10 years they have only once (in 1928-29) exceeded 1 percent of the total crop. Foreign importers of corn are buying more corn from our competitors and less from us. This trend was clearly evident before the AAA reduction program was instituted

Are genetic tests exceptional? Lessons from a qualitative study on thrombophilia

Policy makers have suggested that information about genetic risk factors, which are associated with low risk and for which preventive strategies exist, should not be considered “exceptional” and should not warrant special safeguards, such as data protection or specialist pre-test counselling. There is scant research on how such risk factors are perceived, and to explore this we conducted qualitative interviews with 42 participants who had undergone testing in the South West of England for a low risk genetic susceptibility to deep vein thrombosis (DVT). Generally the participants, who were mostly women, thought the test was less serious than a genetic test for a predisposition to breast cancer or a non-genetic, diagnostic test for diabetes. They had used the genetic information to reduce their risk of DVTs by avoiding oral contraceptives and hormone replacement therapy but had not changed their lifestyle. Many considered pre-test genetic counselling unnecessary. However, a subgroup of participants, who were often less educated or at a high risk, were distressed and/or confused about thrombophilia and thought pre-test counselling would have been helpful. The findings indicate an emerging interpretation of genetics not as revealing exceptional or “in depth” knowledge about one's health and identity but as occasionally relevant surface information, which participants use to make specific health decisions but not to transform their everyday lives. However, the views of the subgroup indicate that some participants interpret thrombophilia as serious and/or need special support

Association of immune response with efficacy and safety outcomes in adults with phenylketonuria administered pegvaliase in phase 3 clinical trials

Background: This study assessed the immunogenicity of pegvaliase (recombinant Anabaena variabilis phenylalanine [Phe] ammonia lyase [PAL] conjugated with polyethylene glycol [PEG]) treatment in adults with phenylketonuria (PKU) and its impact on safety and efficacy. Methods: Immunogenicity was assessed during induction, upward titration, and maintenance dosing regimens in adults with PKU (n = 261). Total antidrug antibodies (ADA), neutralizing antibodies, immunoglobulin (Ig) M and IgG antibodies against PAL and PEG, IgG and IgM circulating immune complex (CIC) levels, complement components 3 and 4 (C3/C4), plasma Phe, and safety were assessed at baseline and throughout the study. Pegvaliase-specific IgE levels were measured in patients after hypersensitivity adverse events (HAE). Findings: All patients developed ADA against PAL, peaking by 6 months and then stabilizing. Most developed transient antibody responses against PEG, peaking by 3 months, then returning to baseline by 9 months. Binding of ADA to pegvaliase led to CIC formation and complement activation, which were highest during early treatment. Blood Phe decreased over time as CIC levels and complement activation declined and pegvaliase dosage increased. HAEs were most frequent during early treatment and declined over time. No patient with acute systemic hypersensitivity events tested positive for pegvaliase-specific IgE near the time of the event. Laboratory evidence was consistent with immune complex-mediated type III hypersensitivity. No evidence of pegvaliase-associated IC-mediated end organ damage was noted. Interpretation: Despite a universal ADA response post-pegvaliase administration, adult patients with PKU achieved substantial and sustained blood Phe reductions with a manageable safety profile. Fund: BioMarin Pharmaceutical Inc. Keywords: Enzyme replacement therapy, Antidrug antibody, Circulating immune complex, Hypersensitivity, Phenylalanin

Radio Sources in Galaxy Clusters at 28.5 GHz

We present serendipitous detections of radio sources at 28.5 GHz (1 cm), which resulted from our program to image thermal Sunyaev-Zeldovich (SZ) effect in 56 galaxy clusters. We find 64 radio sources with fluxes down to 0.4 mJy, and within 250 arcseconds from the pointing centers. The spectral indices (S ~ \nu^-\alpha) of 54 sources with published low frequency flux densities range from -0.6 to 2 with a mean of 0.77, and a median of 0.84. Extending low frequency surveys of radio sources towards galaxy clusters CL 0016+16, Abell 665, and Abell 2218 to 28.5 GHz, and selecting sources with 1.4 GHz flux density greater than 7 mJy to form an unbiased sample, we find a mean spectral index of 0.71 and a median of 0.71. We find 4 to 7 times more sources predicted from a low frequency survey in areas without galaxy clusters. This excess cannot be accounted for by gravitational lensing of a background radio population by cluster potentials, indicating most of the detected sources are associated with galaxy clusters. For the cluster Abell 2218, the presence of unsubtracted radio sources with 28.5 GHz flux densities less than 0.5 mJy, can only contribute to temperature fluctuations at a level of 10 to 25 \muK. The corresponding error due to radio point source contamination in the Hubble constant derived through a combined analysis of 28.5 GHz SZ images and X-ray emission observations ranges from 1% to 6%.Comment: 18 pages, 8 figures, to appear in April 1998 issue of A

Identification of Leishmania major UDP-Sugar Pyrophosphorylase Inhibitors Using Biosensor-Based Small Molecule Fragment Library Screening

Leishmaniasis is a neglected disease that is caused by different species of the protozoan parasite Leishmania, and it currently affects 12 million people worldwide. The antileishmanial therapeutic arsenal remains very limited in number and efficacy, and there is no vaccine for this parasitic disease. One pathway that has been genetically validated as an antileishmanial drug target is the biosynthesis of uridine diphosphate-glucose (UDP-Glc), and its direct derivative UDP-galactose (UDP-Gal). De novo biosynthesis of these two nucleotide sugars is controlled by the specific UDP-glucose pyrophosphorylase (UGP). Leishmania parasites additionally express a UDP-sugar pyrophosphorylase (USP) responsible for monosaccharides salvage that is able to generate both UDP-Gal and UDP-Glc. The inactivation of the two parasite pyrophosphorylases UGP and USP, results in parasite death. The present study reports on the identification of structurally diverse scaffolds for the development of USP inhibitors by fragment library screening. Based on this screening, we selected a small set of commercially available compounds, and identified molecules that inhibit both Leishmania major USP and UGP, with a half-maximal inhibitory concentration in the 100 µM range. The inhibitors were predicted to bind at allosteric regulation sites, which were validated by mutagenesis studies. This study sets the stage for the development of potent USP inhibitors

Parsec-Scale Blazar Monitoring: Flux and Polarization Variability

We present analysis of the flux and polarization variability of parsec scale radio jets from a dual-frequency, six-epoch, VLBA polarization experiment monitoring 12 blazars. The observations were made at 15 and 22 GHz at bimonthly intervals over 1996. Here we analyze the flux, fractional polarization, and polarization position angle behavior of core regions and jet features, considering both the linear trends of these quantities with time and more rapid fluctuations about the linear trends. The dual frequency nature of the observations allows us to examine spectral evolution, to separate Faraday effects from changes in magnetic field order, and also to deduce empirical estimates for the uncertainties in measuring properties of VLBI jet features (abridged).Comment: 35 pages, 30 figures, accepted by the Astrophysical Journal (Changes from original version: typos corrected and a clarification in terminology

Structure and Magnetic Fields in the Precessing Jet System SS433 III. Evolution of the Intrinsic Brightness of the Jets from a Deep Multi-Epoch VLA Campaign

We present a sequence of five deep observations of SS433 made over the summer of 2007 using the VLA in the A configuration at 5 and 8 GHz. In this paper we study the brightness profiles of the jets and their time evolution. We also examine the spectral index distribution in the source. We find (as previously reported from the analysis of a single earlier image) that the profiles of the east and west jets are remarkably similar if projection and Doppler beaming are taken into account. The sequence of five images allows us to disentangle the evolution of brightness of individual pieces of jet from the variations of jet power originating at the core. We find that the brightness of each piece of the jet fades as an exponential function of age (or distance from the core), exp(-tau/tau'), where tau is the age at emission and tau' = 55.9 +- 1.7 days. This evolutionary model describes both the east and west jets equally well. There is also significant variation (by a factor of at least five) in jet power with birth epoch, with the east and west jets varying in synchrony. The lack of deceleration between the scale of the optical Balmer line emission (10^15 cm) and that of the radio emission (10^17 cm) requires that the jet material is much denser than its surroundings. We find that the density ratio must exceed 300:1.Comment: 26 pages, 13 Figures, Accepted for publication in the Astrophysical Journa