The High Energy Solar Physics mission (HESP): Scientific objectives and technical description

The High Energy Solar Physics mission offers the opportunity for major breakthroughs in the understanding of the fundamental energy release and particle acceleration processes at the core of the solar flare problem. The following subject areas are covered: the scientific objectives of HESP; what we can expect from the HESP observations; the high energy imaging spectrometer (HEISPEC); the HESP spacecraft; and budget and schedule

Preterm Premature Rupture of Membranes in Human Immunodeficiency Virus-Infected Women: A Novel Case Series

Objective. To evaluate the management and outcomes of a series of human immunodeficiency virus-(HIV-) infected women whose pregnancies were complicated by preterm premature rupture of membranes (PPROM). Study design. We conducted a retrospective chart review of all women with confirmed HIV infection who had a pregnancy complicated by PPROM remote from term. PPROM remote from term was defined as rupture of membranes prior to 32-week gestation. Collective cases from two centers (Hennepin County Medical Center and The University of Alabama at Birmingham) were reviewed and data on management and outcomes were abstracted. Results. Of the HIV-positive women, we identified 291 pregnancies having occurred in the study interval from two institutions. Of these pregnancies, 7 (2.4%) developed PPROM remote from term with subsequent delivery from 25- to 32-week gestation. Vertical HIV transmission was noted in 2 of 6 children whose long-term followup status was confirmed (33%) of these cases. However, both of these cases occurred in women with either no antepartum/intrapartum antiviral therapy or where only zidovudine monotherapy was used. Importantly, in spite of expectant management, no cases of vertical HIV transmission occurred in women who were receiving either multidrug or highly active antiviral therapy (HAART) at the time of PPROM and who had a cesarean delivery in cases where the predelivery viral load > 1000 copies/mL. Conclusion. Our limited observations raise the question as to whether in the current era of multidrug therapy immediate delivery should be undertaken in HIV+ pregnancies complicated by PPROM at an early gestational age. This case series further suggests that in those pregnancies that lend themselves to expectant management, such a strategy may be considered appropriate

The fibrinolytic system facilitates tumor cell migration across the blood-brain barrier in experimental melanoma brain metastasis

BACKGROUND: Patients with metastatic tumors to the brain have a very poor prognosis. Increased metastatic potential has been associated with the fibrinolytic system. We investigated the role of the fibrinolytic enzyme plasmin in tumor cell migration across brain endothelial cells and growth of brain metastases in an experimental metastatic melanoma model. METHODS: Metastatic tumors to the brain were established by direct injection into the striatum or by intracarotid injection of B16F10 mouse melanoma cells in C57Bl mice. The role of plasminogen in the ability of human melanoma cells to cross a human blood-brain barrier model was studied on a transwell system. RESULTS: Wild type mice treated with the plasmin inhibitor epsilon-aminocaproic acid (EACA) and plg(-/- )mice developed smaller tumors and survived longer than untreated wild type mice. Tumors metastasized to the brain of wild type mice treated with EACA and plg(-/- )less efficiently than in untreated wild type mice. No difference was observed in the tumor growth in any of the three groups of mice. Human melanoma cells were able to cross the human blood-brain barrier model in a plasmin dependent manner. CONCLUSION: Plasmin facilitates the development of tumor metastasis to the brain. Inhibition of the fibrinolytic system could be considered as means to prevent tumor metastasis to the brain

Positive selection of novel peroxisome biogenesis-defective mutants of the yeast Pichia pastoris

We have developed two novel schemes for the direct selection of peroxisome-biogenesis-defective (pex) mutants of the methylotrophic yeast Pichia pastoris. Both schemes take advantage of our observation that methanol-induced pex mutants contain little or no alcohol oxidase (AOX) activity. AOX is a peroxisomal matrix enzyme that catalyzes the first step in the methanol-utilization pathway. One scheme utilizes allyl alcohol, a compound that is not toxic to cells but is oxidized by AOX to acrolein, a compound that is toxic. Exposure of mutagenized populations of AOX-induced cells to allyl alcohol selectively kills AOX-containing cells. However, pex mutants without AOX are able to grow. The second scheme utilizes a P. pastoris strain that is defective in formaldehyde dehydrogenase (FLD), a methanol pathway enzyme required to metabolize formaldehyde, the product of AOX. AOX-induced cells of fld1 strains are sensitive to methanol because of the accumulation of formaldehyde. However, fld1 pex mutants, with little active AOX, do not efficiently oxidize methanol to formaldehyde and therefore are not sensitive to methanol. Using these selections, new pex mutant alleles in previously identified PEX genes have been isolated along with mutants in three previously unidentified PEX group

Induction of fish biomarkers by synthetic-based drilling muds

The study investigated the effects of chronic exposure of pink snapper (Pagrus auratus Forster), to synthetic based drilling muds (SBMs). Fish were exposed to three mud systems comprised of three different types of synthetic based fluids (SBFs): an ester (E), an isomerized olefin (IO) and linear alpha olefin (LAO). Condition factor (CF), liver somatic index (LSI), hepatic detoxification (EROD activity), biliary metabolites, DNA damage and stress proteins (HSP-70) were determined. Exposure to E caused biologically significant effects by increasing CF and LSI, and triggered biliary metabolite accumulation. While ester-based SBFs have a rapid biodegradation rate in the environment, they caused the most pronounced effects on fish health. IO induced EROD activity and biliary metabolites and LAO induced EROD activity and stress protein levels. The results demonstrate that while acute toxicity of SBMs is generally low, chronic exposure to weathering cutting piles has the potential to affect fish health. The study illustrates the advantages of the Western Australian government case-by-case approach to drilling fluid management, and highlights the importance of considering the receiving environment in the selection of SBMs

Hybridizing Discrete- and Continuous-Time Models for Batch Sizing and Scheduling Problems

This paper proposes a new hybrid technique called “partial parameter uniformization” (hereafter PPU). The technique simplifies problems by ignoring the different values that certain problem parameters can take, which may facilitate the solution of some hard combinatorial optimization problems. PPU is applied to complex batch sizing and scheduling problems. Some information can be obtained from a discrete-time model in which job durations have been made uniform. This information is then exploited by a more detailed continuous-time model to generate feasible solutions and further improve these solutions. Good, or optimal solutions to the Westenberger and Kallrath Benchmark problems have been obtained in this way, at relatively low computational cost, as have solutions to the newer problems of Blömer and Günther

Computed Tomography Screening for Early Lung Cancer, COPD and Cardiovascular Disease in Shanghai:Rationale and Design of a Population-based Comparative Study

Rationale and Objectives: To describe the rational and design of a population-based comparative study. The objective of the study is to assess the screening performance of volume-based management of CT-detected lung nodule in comparison to diameter-based management, and to improve the effectiveness of CT screening for chronic obstructive pulmonary disease (COPD) and cardiovascular disease (CVD), in addition to lung cancer, based on quantitative measurement of CT imaging biomarkers in a Chinese screening setting. Materials and Methods: A population-based comparative study is being performed, including 10,000 asymptomatic participants between 40 and 74 years old from Shanghai urban population. Participants in the intervention group undergo a low-dose chest and cardiac CT scan at baseline and 1 year later, and are managed according to NELCIN-B3 protocol. Participants in the control group undergo a low-dose chest CT scan according to the routine CT protocol and are managed according to the clinical practice. Epidemiological data are collected through questionnaires. In the fourth year from baseline, the diagnosis of the three diseases will be collected. Results: The unnecessary referral rate will be compared between NELCIN-B3 and standard protocol for managing early-detected lung nodules. The effectiveness of quantitative measurement of CT imaging biomarkers for early detection of lung cancer, COPD and CVD will be evaluated. Conclusion: We expect that the quantitative assessment of the CT imaging biomarkers will reduce the number of unnecessary referrals for early detected lung nodules, and will improve the early detection of COPD and CVD in a Chinese urban population

Predictive Models for Assessing Patients’ Response to Treatment in Metastatic Prostate Cancer:A Systematic Review

Background and objective: The treatment landscape of metastatic prostate cancer (mPCa) has evolved significantly over the past two decades. Despite this, the optimal therapy for patients with mPCa has not been determined. This systematic review identifies available predictive models that assess mPCa patients’ response to treatment. Methods: We critically reviewed MEDLINE and CENTRAL in December 2022 according to the Preferred Reporting Items for Systematic Reviews and Meta-analyses statement. Only quantitative studies in English were included with no time restrictions. The quality of the included studies was assessed using the PROBAST tool. Data were extracted following the Checklist for Critical Appraisal and Data Extraction for Systematic Reviews criteria. Key findings and limitations: The search identified 616 citations, of which 15 studies were included in our review. Nine of the included studies were validated internally or externally. Only one study had a low risk of bias and a low risk concerning applicability. Many studies failed to detail model performance adequately, resulting in a high risk of bias. Where reported, the models indicated good or excellent performance. Conclusions and clinical implications: Most of the identified predictive models require additional evaluation and validation in properly designed studies before these can be implemented in clinical practice to assist with treatment decision-making for men with mPCa. Patient summary: In this review, we evaluate studies that predict which treatments will work best for which metastatic prostate cancer patients. We found that existing studies need further improvement before these can be used by health care professionals.</p