Symposium Review: \u3cem\u3eAmish and Old Order Mennonite Schools: A Concise History\u3c/em\u3e—Joseph Stoll; and The School by the Cornfield—Samuel Coon

Joseph Stoll, in Amish and Old Order Mennonite Schools: A Concise History, and Samuel Coon, in The School by the Cornfield, provide two very different perspectives on the struggle to establish Anabaptist schools. The books contrast primarily in their geographic and chronological scope. However, both write about parochial schools with a voice sympathetic to the vision of Amish and Mennonite school founders. They use similar sources, drawing on newspaper accounts, published Amish schools’ histories, and Amish and Mennonite periodicals, as well as personal recollections from individuals involved in school conflicts. [First paragraph.

Monetary discounting and ventral striatal dopamine receptor availability in nontreatment-seeking alcoholics and social drinkers

RATIONALE: Dopamine (DA) in the ventral striatum (VST) has long been implicated in addiction pathologies, yet its role in temporal decision-making is not well-understood. OBJECTIVES: To determine if VST DA D2 receptor availability corresponds with greater impulsive choice in both nontreatment-seeking alcoholics (NTS) and social drinkers (SD). METHODS: NTS subjects (n = 10) and SD (n = 13) received PET scans at baseline with the D2/D3 radioligand [(11)C]raclopride (RAC). Outside the scanner, subjects performed a delay discounting procedure with monetary rewards. RAC binding potential (BPND) was estimated voxelwise, and correlations were performed to test for relationships between VST BPND and delay discounting performance. Self-reported impulsivity was also tested for correlations with BPND. RESULTS: Across all subjects, greater impulsive choice for $20 correlated with lower BPND in the right VST. NTS showed greater impulsive choice than SD and were more impulsive by self-report. Across all subjects, the capacity of larger rewards to reduce impulsive choice (the magnitude effect) correlated negatively (p = 0.028) with problematic alcohol use (AUDIT) scores. Self-reported impulsivity did not correlate with BPND in VST. CONCLUSIONS: Preference for immediate reinforcement may reflect greater endogenous striatal DA or lower D2 number, or both. Alcoholic status did not mediate significant effects on VST BPND, suggesting minimal effects from alcohol exposure. The apparent lack of BPND correlation with self-reported impulsivity highlights the need for objective behavioral assays in the study of the neurochemical substrates of behavior. Finally, our results suggest that the magnitude effect may be more sensitive to alcohol-induced problems than single discounting measures

Diabetes reduces bone marrow and circulating porcine endothelial progenitor cells, an effect ameliorated by atorvastatin and independent of cholesterol

Bone marrow derived endothelial progenitor cells (EPCs) are early precursors of mature endothelial cells which replenish aging and damaged endothelial cells. The authors studied a diabetic swine model to determine if induction of DM adversely affects either bone marrow or circulating EPCs and whether a HMG-CoA reductase inhibitor (statin) improves development and recruitment of EPCs in the absence of cholesterol lowering. Streptozotocin was administered to Yorkshire pigs to induce DM. One month after induction, diabetic pigs were treated with atorvastatin (statin, n = 10), ezetimibe (n = 10) or untreated (n = 10) and evaluated for number of bone marrow and circulating EPCs and femoral artery endothelial function. There was no effect of either medication on cholesterol level. One month after induction of DM prior to administration of drugs, the number of bone marrow and circulating EPCs significantly decreased (P < 0.0001) compared to baseline. Three months after DM induction, the mean proportion of circulating EPCs significantly increased in the atorvastatin group, but not in the control or ezetimibe groups. The control group showed progressive reduction in percentage of flow mediated vasodilatation (no dilatation at 3 months) whereas the atorvastatin group and ezetimibe exhibited vasodilatation, 6% and 4% respectively. DM results in significant impairment of bone marrow and circulating EPCs as well as endothelial function. The effect is ameliorated, in part, by atorvastatin independent of its cholesterol lowering effect. These data suggest a model wherein accelerated atherosclerosis seen with DM may, in part, result from reduction in EPCs which may be ameliorated by treatment with a statin

Differences in IV alcohol-induced dopamine release in the ventral striatum of social drinkers and nontreatment-seeking alcoholics

Background Striatal dopamine (DA) has been implicated in alcohol use disorders, but it is still unclear whether or not alcohol can induce dopamine release in social drinkers. Furthermore, no data exist on dopamine responses to alcohol in dependent drinkers. We sought to characterize the DA responses to alcohol intoxication in moderately large samples of social drinkers (SD) and nontreatment-seeking alcoholics (NTS). Methods Twenty-four SD and twenty-one NTS received two [11C]raclopride (RAC) PET scans; one at rest, and one during an intravenous alcohol infusion, with a prescribed ascent to a target breath alcohol concentration (BrAC), at which it was then “clamped.” The alcohol clamp was started 5 min after scan start, with a linear increase in BrAC over 15 min to the target of 80 mg%, the legal threshold for intoxication. Target BrAC was maintained for 30 min. Voxel-wise binding potential (BPND) was estimated with MRTM2. Results IV EtOH induced significant increases in DA in the right ventral striatum in NTS, but not SD. No decreases in DA were observed in either group. Conclusions Alcohol intoxication results in distinct anatomic profiles of DA responses in SD and NTS, suggesting that in NTS, the striatal DA system may process effects of alcohol intoxication differently than in SD

U.S. Billion-ton Update: Biomass Supply for a Bioenergy and Bioproducts Industry

The Report, Biomass as Feedstock for a Bioenergy and Bioproducts Industry: The Technical Feasibility of a Billion-Ton Annual Supply (generally referred to as the Billion-Ton Study or 2005 BTS), was an estimate of “potential” biomass within the contiguous United States based on numerous assumptions about current and future inventory and production capacity, availability, and technology. In the 2005 BTS, a strategic analysis was undertaken to determine if U.S. agriculture and forest resources have the capability to potentially produce at least one billion dry tons of biomass annually, in a sustainable manner—enough to displace approximately 30% of the country’s present petroleum consumption. To ensure reasonable confidence in the study results, an effort was made to use relatively conservative assumptions. However, for both agriculture and forestry, the resource potential was not restricted by price. That is, all identified biomass was potentially available, even though some potential feedstock would more than likely be too expensive to actually be economically available. In addition to updating the 2005 study, this report attempts to address a number of its shortcoming

Universal non-adiabatic control of small-gap superconducting qubits

Resonant transverse driving of a two-level system as viewed in the rotating frame couples two degenerate states at the Rabi frequency, an amazing equivalence that emerges in quantum mechanics. While spectacularly successful at controlling natural and artificial quantum systems, certain limitations may arise (e.g., the achievable gate speed) due to non-idealities like the counter-rotating term. Here, we explore a complementary approach to quantum control based on non-resonant, non-adiabatic driving of a longitudinal parameter in the presence of a fixed transverse coupling. We introduce a superconducting composite qubit (CQB), formed from two capacitively coupled transmon qubits, which features a small avoided crossing -- smaller than the environmental temperature -- between two energy levels. We control this low-frequency CQB using solely baseband pulses, non-adiabatic transitions, and coherent Landau-Zener interference to achieve fast, high-fidelity, single-qubit operations with Clifford fidelities exceeding $99.7\%$. We also perform coupled qubit operations between two low-frequency CQBs. This work demonstrates that universal non-adiabatic control of low-frequency qubits is feasible using solely baseband pulses

A voz dos bandos: colectivos de justiça e ritos da palavra portuguesa em Timor Leste colonial

Este artigo examina as relações entre o discurso da justiça e a prática do ritual nos bandos do governo colonial português em Timor Leste, entre a segunda metade do século XIX e as primeiras décadas do século XX. Os bandos consistiam em ordens e instruções de comando emanadas pelo governador português em Díli, e comunicadas de forma cerimonial por oficiais às populações dos diversos reinos timorenses dispersos pelo país. Bandos eram um instrumento por excelência de governação colonial dos assuntos indígenas, servindo para arbitrar conflitos, punir transgressões e, em geral, instituir realidades no mundo timorense. Contudo, esta instituição assumiu igualmente uma singular expressão nos usos timorenses, servindo bandos para comunicar também as ordens de autoridades tradicionais, os liurais. O artigo acompanha as variações coloniais e indígenas que os bandos adquiriram em Timor Leste, conceptualizando-os enquanto colectivos de justiça. Ao considerar assim os bandos como colectivos – formações heterogéneas em que elementos linguísticos e não linguísticos se combinam na produção de efeitos de poder sobre as populações – o artigo propõe uma via conceptual alternativa às perspectivas linguísticas e literárias de análise do discurso colonial

Generating spatially entangled itinerant photons with waveguide quantum electrodynamics

Realizing a fully connected network of quantum processors requires the ability to distribute quantum entanglement. For distant processing nodes, this can be achieved by generating, routing, and capturing spatially entangled itinerant photons. In this work, we demonstrate the deterministic generation of such photons using superconducting transmon qubits that are directly coupled to a waveguide. In particular, we generate two-photon N00N states and show that the state and spatial entanglement of the emitted photons are tunable via the qubit frequencies. Using quadrature amplitude detection, we reconstruct the moments and correlations of the photonic modes and demonstrate state preparation fidelities of 84%. Our results provide a path toward realizing quantum communication and teleportation protocols using itinerant photons generated by quantum interference within a waveguide quantum electrodynamics architecture

Tumor exome sequencing and copy number alterations reveal potential predictors of intrinsic resistance to multi-targeted tyrosine kinase inhibitors

Multi-targeted tyrosine kinase inhibitors (TKIs) have broad efficacy and similar FDA-approved indications, suggesting shared molecular drug targets across cancer types. Irrespective of tumor type, 20-30% of patients treated with multi-targeted TKIs demonstrate intrinsic resistance, with progressive disease as a best response. We conducted a retrospective cohort study to identify tumor (somatic) point mutations, insertion/deletions, and copy number alterations (CNA) associated with intrinsic resistance to multi-targeted TKIs. Using a candidate gene approach (n=243), tumor next-generation sequencing and CNA data was associated with resistant and non-resistant outcomes. Resistant individuals (n=11) more commonly harbored somatic point mutations in NTRK1, KDR, TGFBR2, and PTPN11 and CNA in CDK4, CDKN2B, and ERBB2 compared to non-resistant (n=26, p<0.01). Using a random forest classification model for variable reduction and a decision tree classification model, we were able to differentiate intrinsically resistant from non-resistant patients. CNA in CDK4 and CDKN2B were the most important analytical features, implicating the cyclin D pathway as a potentially important factor in resistance to multi-targeted TKIs. Replication of these results in a larger, independent patient cohort has potential to inform personalized prescribing of these widely utilized agents

siRNA Screening of a Targeted Library of DNA Repair Factors in HIV Infection Reveals a Role for Base Excision Repair in HIV Integration

Host DNA repair enzymes have long been assumed to play a role in HIV replication, and many different DNA repair factors have been associated with HIV. In order to identify DNA repair pathways required for HIV infection, we conducted a targeted siRNA screen using 232 siRNA pools for genes associated with DNA repair. Mapping the genes targeted by effective siRNA pools to well-defined DNA repair pathways revealed that many of the siRNAs targeting enzymes associated with the short patch base excision repair (BER) pathway reduced HIV infection. For six siRNA pools targeting BER enzymes, the negative effect of mRNA knockdown was rescued by expression of the corresponding cDNA, validating the importance of the gene in HIV replication. Additionally, mouse embryo fibroblasts (MEFs) lacking expression of specific BER enzymes had decreased transduction by HIV-based retroviral vectors. Examining the role BER enzymes play in HIV infection suggests a role for the BER pathway in HIV integration