Controlling Individual Domain Walls in Ferromagnetic Nanowires for Memory and Sensor Applications

Controlled motion of 180o and 360o domain walls along planar nanowires is presented. Standard Landau – Lifshitz micromagnetic modeling has been used to simulate the response of the domain walls to the application of an external magnetic field. A 180o wall is quickly and easily moved with the application of an applied. field along the axis of the wire but a 360odomain wall is stationary in the same case. An oscillatory applied field can be used to continually move the wall along the wires axis. The speed at which the 360o domain wall is found to be several times slower than a similar 180o domain wall and is limited by interaction between the magnetization of the domain wall and the external field

Auswirkungen von PEN, einem Extrakt aus der Biomasse von Penicillium chrysogenum, auf Pathogene und Pflanzen

Der Ersatz von Kupfer und anderen Pestiziden ist eine der dringlichen Aufgaben der Forschung im biologischen Landbau. Beim direkten Pflanzenschutz stehen fungizid wirkende Substanzen, Biocontrol-Organismen und Pflanzenstärkungsmittel zur Diskussion. Das Konzept der Pflanzenstärkung ist seit langem im biologischen Landbau bekannt. Beispielsweise werden Kompostextrakte, Brennesselextrakte, aber auch kommerzialisierte Produkte aus Reynoutria sachalinensis oder Backpulver eingesetzt. Unter den Resistenzinduktoren (Elicitoren) sind vor allem diejenigen von grossem Interesse, die Resistenz gegen Pathogene auslösen, die ansonsten mit Kupfer bekämpft werden (Tamm, 2000). Der Dünger Agro Biosol (Biochemie GmbH, A-Kundl) weist nebst einer Düngerwirkung auch krankheitsvermindernde Eigenschaften auf. Dies legen Beobachtungen nahe, die bereits in den achtziger Jahren auf Grasflächen gemacht wurden, die mit Fusarium nivale befallen waren. Das aus der Penicillinproduktion gewonnene Trockenmycel ist frei von Penicillin. Agro Biosol enthält 6 % Gesamtstickstoff, 1 % Gesamtphosphor, 1 % Kali, sowie Spurenelemente und Vitamine (Naschberger, pers. Mitteilung). In der Schweiz ist Agro Biosol als Dünger im biologischen Landbau zugelassen (Tamm, Maurer & Alföldi, 2000). E. Mösinger (Sandoz Agro, CH - Witterswil) führte erste Versuche über die krankheitsunterdrückende Wirkung von Agro Biosol durch. Dazu wurde ein Extrakt des Trockenmycels von P. chrysogenum hergestellt, der die Kurzbezeichnung ‚PEN’ erhielt. Diese Untersuchungen von Mösinger und Mitarbeitern wiesen darauf hin, dass PEN an Tomaten und Gurken Resistenz induzieren kann. Ab 1997 wurde das Thema am FiBL weiterverfolgt. Mit den vorliegenden Untersuchungen wurden die Teilziele angestrebt (i) Verifizieren und Charakterisieren der resistenzinduzierenden Eigenschaften von PEN, (ii) Abklären des Potentials für eine Weiterentwicklung von PEN als kommerzialisierbaren Resistenzinduktor und (iii) Charakterisierung der phytotoxischen Eigenschaften von PEN als Ausgangspunkt für die Optimierung von Agro Biosol. Fazit: PEN, der Extrakt von Penicillium chrysogenum, kann bei zahlreichen Wirt- Pathogen-Systemen den Krankheitsbefall markant reduzieren. Dies ist insbesondere bei Krankheitserregern von Interesse, die ansonsten mit biotauglichen Produkten nur schwer kontrollierbar sind. Das Ausgangsmaterial wird als biotauglich eingeschätzt und steht in genügenden Mengen in konstanter Qualität zur Verfügung. Dies sind günstige Voraussetzungen, um einen neuartigen Resistenzinduktor für den biologischen Anbau bis zur Praxisreife zu entwickeln. PEN kann allerdings phytotoxische Effekte auslösen, die eine Praxisanwendung als Resistenzinduktor vorerst ausschliessen. Unsere Forschung hat gegenwärtig zwei Stossrichtungen. Einerseits werden die Effekte von PEN auf die Pflanzenphysiologie untersucht und die involvierten Stoffwechselprozesse detailliert abgeklärt. Andererseits suchen wir nach den aktiven Prinzipien, die für Resistenzinduktion und Phytotoxizität verantwortlich sind

A Comparison of Lung Function Values Among a SCUBA Diver Population and in Comparison to a Non-diver Population

The purpose of this study was to investigate possible correlations between lung function values (PEF, IRV, ERV, and FVC) among a diver population, as well as in comparison to a non-diver population. Independent variables for both populations were biological sex, age, and weekly physical activity. Independent variables for the diver population were dive tenure, number of logged dives, certification level, and gas mixture used. A spirometry test was conducted to collect lung function values of both populations. Data from this study suggest a statistically significant relationship between diver and non-diver sex and FVC, diver age and ERV, diver sex and ERV, and non-diver FVC and weekly physical activity

Ornithine uptake and the modulation of drug sensitivity in <i>Trypanosoma brucei</i>

Trypanosoma brucei, protozoan parasites that cause human African trypanosomiasis (HAT), depend on ornithine uptake and metabolism by ornithine decarboxylase (ODC) for survival. Indeed, ODC is the target of the WHO “essential medicine” eflornithine, which is antagonistic to another anti-HAT drug, suramin. Thus, ornithine uptake has important consequences in T. brucei, but the transporters have not been identified. We describe these amino acid transporters (AATs). In a heterologous expression system, TbAAT10-1 is selective for ornithine, whereas TbAAT2-4 transports both ornithine and histidine. These AATs are also necessary to maintain intracellular ornithine and polyamine levels in T. brucei, thereby decreasing sensitivity to eflornithine and increasing sensitivity to suramin. Consistent with competition for histidine, high extracellular concentrations of this amino acid phenocopied a TbAAT2-4 genetic defect. Our findings established TbAAT10-1 and TbAAT2-4 as the parasite ornithine transporters, one of which can be modulated by histidine, but both of which affect sensitivity to important anti-HAT drugs.—Macedo, J. P., Currier, R. B., Wirdnam, C., Horn, D., Alsford, S., Rentsch, D. Ornithine uptake and the modulation of drug sensitivity in Trypanosoma brucei

The Structure of Polyfulvenes

Cationic polymerisation of 6,6-disubstituted pentafulvenes yields highly unsaturated, reactive macromolecules of high mo- . lecular weight. The mechanistic pathways leading to the polymers are discussed, and the structure XIV of the polymers has been elucidated by a combination of spectroscopic methods as well as by comparison with model compounds. In contrast to reports in the literature, the main process in thermal oligomerisation of simple pentafulvenes at 20 °c is a Diels-Alder reaction giving products of type XXI. Anionic polymerisation of pentafulvenes is initiated by traces of sodium cyclopentadienide or phenylsodium respectively. The reaction products consist of a mixture of oligomers of the series (fulvene)n. This surprising result can be explained by structure elucidation of the fulvene dimers, which gives formula XX. The mechanistic aspects of the reaction are discussed

Thiopurine S -methyltransferase polymorphisms: efficient screening method for patients considering taking thiopurine drugs

Objective: More than 11% of the Caucasian population are heterozygous or homozygous carriers of thiopurine S-methyltransferase (TPMT) mutants and are at risk for toxic side effects when treated with thiopurine drugs. Therefore, screening for TPMT polymorphisms in a patient prior to prescribing these agents is recommended. The goal of this study was to determine a cut-off concentration of the TPMT activity assay beyond which genotyping of the TPMT gene should be performed. Methods: The TPMT activity of 240 unrelated Caucasian subjects was measured using high-performance liquid chromatography. Genotyping for the most frequent allelic variants, TPMT*2, *3A, *3B, *3C and *7 was performed by LightCycler technology and sequencing. Results: The inter-individual TPMT activity showed a range from 23nmol MTG/g*Hb*h−1 to 97nmol MTG/g*Hb*h−1 with a median of 56nmol MTG/g*Hb*h−1. Using a cut-off concentration of 45.5nmol MTG/g*Hb*h−1, a test sensitivity of 100% and a specificity of 89% were reached for heterozygous carriers of a TPMT mutation. We identified 1 carrier of TPMT*2, 14 carriers of TPMT*3A and 3 carriers of TPMT*3C, resulting in a TPMT heterozygosity prevalence of 7.5%. Conclusions: This study defines the cut-off value for the TPMT phenotyping assay at 45.5nmol/g*Hb*h−1, beyond which additional genotyping elucidates the individual risk for drug therapy. Using this cut-off concentration, the number of genotyping assays could be reduced by about 60

Cohort Profile: The HIV Atlanta Veterans Affairs Cohort Study (HAVACS).

The originally published version of this Profile contained an error in one of the author names. Vince D. Marconi should have read Vince C. Marconi. This has now been corrected

Nutrient availability regulates proline/alanine transporters in Trypanosoma brucei

Trypanosoma brucei is a species of unicellular parasite that can cause severe diseases in livestock and humans, including African trypanosomiasis and Chagas disease. Adaptation to diverse environments and changes in nutritional conditions is essential for T. brucei to establish an infection when changing hosts or during invasion of different host tissues. One such adaptation is the ability of T. brucei to rapidly switch its energy metabolism from glucose metabolism in the mammalian blood to proline catabolism in the insect stages and vice versa. However, the mechanisms that support the parasite's response to nutrient availability remain unclear. Using RNAseq and qRT-PCR, we investigated the response of T. brucei to amino acid or glucose starvation and found increased mRNA levels of several amino acid transporters, including all genes of the amino acid transporter AAT7-B subgroup. Functional characterization revealed that AAT7-B members are plasma membrane-localized in T. brucei and when expressed in Saccharomyces cerevisiae supported the uptake of proline, alanine, and cysteine, while other amino acids were poorly recognized. All AAT7-B members showed a preference for proline, which is transported with high or low affinity. RNAimediated AAT7-B downregulation resulted in a reduction of intracellular proline concentrations and growth arrest under low proline availability in cultured procyclic form parasites. Taken together, these results suggest a role of AAT7-B transporters in the response of T. brucei to proline starvation and proline catabolism

Association Between Gabapentin Receipt for Any Indication and Alcohol Use Disorders Identification Test-Consumption Scores Among Clinical Subpopulations With and Without Alcohol Use Disorder.

BACKGROUND: Current medications for alcohol use disorder (AUD) have limited efficacy and utilization. Some clinical trials have shown efficacy for gabapentin among treatment-seeking individuals. The impact of gabapentin on alcohol consumption in a more general sample remains unknown. METHODS: We identified patients prescribed gabapentin for ≥180 consecutive days for any clinical indication other than substance use treatment between 2009 and 2015 in the Veterans Aging Cohort Study. We propensity-score matched each gabapentin-exposed patient with up to 5 unexposed patients. Multivariable difference-in-difference (DiD) linear regression models estimated the differential change in Alcohol Use Disorders Identification Test-Consumption (AUDIT-C) scores during follow-up between exposed and unexposed patients, by baseline level of alcohol consumption and daily gabapentin dose. Analyses were stratified by AUD history. Clinically meaningful changes were a priori considered a DiD ≥1 point. RESULTS: Among patients with AUD, AUDIT-C scores decreased 0.39 points (95% confidence interval [CI] 0.05, 0.73) more among exposed than unexposed patients (p < 0.03). Potentially clinically meaningful differences were observed among those with AUD and exposed to ≥1,500 mg/d (DiD 0.77, 95% CI 0.15, 1.38, p < 0.02). No statistically significant effects were found among patients with AUD at doses lower than 1,500 mg/d or baseline AUDIT-C ≥4. Among patients without AUD, we found no overall difference in changes in AUDIT-C scores, nor in analyses stratified by baseline level of alcohol consumption. CONCLUSIONS: Patients exposed to doses of gabapentin consistent with those used in clinical trials, particularly those with AUD, experienced a greater decrease in AUDIT-C scores than matched unexposed patients

Polypharmacy in HIV: recent insights and future directions.

PURPOSE OF REVIEW: Update findings regarding polypharmacy among people with HIV (PWH) and consider what research is most needed. RECENT FINDINGS: Among PWH, polypharmacy is common, occurs in middle age, and is predominantly driven by nonantiretroviral (ARV) medications. Many studies have demonstrated strong associations between polypharmacy and receipt of potentially inappropriate medications (PIMS), but few have considered actual adverse events. Falls, delirium, pneumonia, hospitalization, and mortality are associated with polypharmacy among PWH and risks remain after adjustment for severity of illness. SUMMARY: Polypharmacy is a growing problem and mechanisms of injury likely include potentially inappropriate medications, total drug burden, known pairwise drug interactions, higher level drug interactions, drug--gene interactions, and drug--substance use interactions (alcohol, extra-medical prescription medication, and drug use). Before we can effectively design interventions, we need to use observational data to gain a better understanding of the modifiable mechanisms of injury. As sicker individuals take more medications, analyses must account for severity of illness. As self-report of substance use may be inaccurate, direct biomarkers, such as phosphatidylethanol (PEth) for alcohol are needed. Large samples including electronic health records, genetics, accurate measures of substance use, and state of the art statistical and artificial intelligence techniques are needed to advance our understanding and inform clinical management of polypharmacy in PWH