Firm finances, weather derivatives and geography

This paper considers some intellectual, practical and political dimensions of collaboration between human and physical geographers exploring how firms are using relatively new financial products – weather derivatives – to displace any costs of weather-related uncertainty and risk. The paper defines weather derivatives and indicates how they differ from weather insurance products before considering the geo-political, cultural and economic context for their creation. The paper concludes by reflecting on the challenges of research collaboration across the human–physical geography divide and suggests that while such initiatives may be undermined by a range of institutional and intellectual factors, conversations between physical and human geographers remain and are likely to become increasingly pertinent. The creation of a market in weather derivatives raises a host of urgent political and regulatory questions and the confluence of natural and social knowledges, co-existing within and through the geography academy, provides a constructive and creative basis from which to engage with this new market and wider discourses of uneven economic development and climate change

Policing mining: In outer-space greed and domination vs. peace and equity a governance for humanity!

Staking claim and ownership has remained an antagonistic issue for nations, resulting in many international conflicts. This is particularly so in disputed territories or areas which are deemed the heritage of mankind. In the next 50-years mining in space is set to become a reality and rather than being used to become an asset to man/society and create an equitable world, it is likely to be a battleground for greed and sovereign dominance – an overspill from Earth. This paper researches the conflict between greed and dominance vs. peace and equity in respect to space - mineral resources, providing historical contextualization, opinion, thoughts and interpretation. Hence, consideration is given to international approaches and who should ‘police,’ plus the governance of, space riches. The research largely considers the stance of the USA in this respect. The relevance of travel and travel modes (particularly air) and ownership of the sky is reviewed, so as to provide comparison and (historical) contextualization – identifying issues previously encountered when man looks to both travel and acquire assets by these means. The latest position of asteroid mining is also explored and ‘lessons from Earth’ are revisited as part of this research – which is largely considered and undertaken from a legal (discipline) perspective

The Grizzly, September 8, 2011

President Fong Praises Liberal Arts • New Patterson Field Changes Game for UC Sports • Class of 2015 Arrives Early for Freshman Orientation • Students Faced with Room Damage Charges Urged to Take Better Care • Frosh Advice from Upperclassmen • Collegeville Welcomes Unique Movie Tavern • New Professor Plans to Boost Music Tech Program • Students and Administration Return, React to Renovations in Wismer • Internship Profile: Fox 29 • Opinions: An Open Letter to Freshman Women; Students Should Consider Pros of Off-Campus Living • Football Drops Season Opener to Albright, 24-17 • Women\u27s Soccer has Sight set on a Championship • Football\u27s Primetime Debut Foiled by Albright Collegehttps://digitalcommons.ursinus.edu/grizzlynews/1838/thumbnail.jp

Thienopyridone Drugs Are Selective Activators of AMP-Activated Protein Kinase β1-Containing Complexes

SummaryThe AMP-activated protein kinase (AMPK) is an αβγ heterotrimer that plays a pivotal role in regulating cellular and whole-body metabolism. Activation of AMPK reverses many of the metabolic defects associated with obesity and type 2 diabetes, and therefore AMPK is considered a promising target for drugs to treat these diseases. Recently, the thienopyridone A769662 has been reported to directly activate AMPK by an unexpected mechanism. Here we show that A769662 activates AMPK by a mechanism involving the β subunit carbohydrate-binding module and residues from the γ subunit but not the AMP-binding sites. Furthermore, A769662 exclusively activates AMPK heterotrimers containing the β1 subunit. Our findings highlight the regulatory role played by the β subunit in modulating AMPK activity and the possibility of developing isoform specific therapeutic activators of this important metabolic regulator

Genesis Mission to Return Solar Wind Samples to Earth

The Genesis spacecraft, launched on 8 August 2001 from Cape Canaveral, Florida, will be the first spacecraft ever to return from interplanetary space. The fifth in NASAs line of low-cost, Discovery-class missions, its goal is to collect samples of solar wind and return them to Earth for detailed isotopic and elemental analysis. The spacecraft is to collect solar wind for over 2 years, while circling the L1 point 1.5 million km Sunward of the Earth, before heading back for a capsule-style re-entry in September 2004. After parachute deployments mid-air helicopter recovery will be used to avoid a hard landing. The mission has been in development over 10 years, and its cost, including development, mission operations, and initial sample analysis, is approximately $209 million

Multi-site fungicides suppress banana Panama disease, caused by Fusarium oxysporum f. sp. cubense Tropical Race 4

Global banana production is currently challenged by Panama disease, caused by Fusarium oxysporum f.sp. cubense Tropical Race 4 (FocTR4). There are no effective fungicide-based strategies to control this soil-borne pathogen. This could be due to insensitivity of the pathogen to fungicides and/or soil application per se. Here, we test the effect of 12 single-site and 9 multi-site fungicides against FocTR4 and Foc Race1 (FocR1) in quantitative colony growth, and cell survival assays in purified FocTR4 macroconidia, microconidia and chlamydospores. We demonstrate that these FocTR4 morphotypes all cause Panama disease in bananas. These experiments reveal innate resistance of FocTR4 to all single-site fungicides, with neither azoles, nor succinate dehydrogenase inhibitors (SDHIs), strobilurins or benzimidazoles killing these spore forms. We show in fungicide-treated hyphae that this innate resistance occurs in a subpopulation of "persister" cells and is not genetically inherited. FocTR4 persisters respond to 3 μg ml-1 azoles or 1000 μg ml-1 strobilurins or SDHIs by strong up-regulation of genes encoding target enzymes (up to 660-fold), genes for putative efflux pumps and transporters (up to 230-fold) and xenobiotic detoxification enzymes (up to 200-fold). Comparison of gene expression in FocTR4 and Zymoseptoria tritici, grown under identical conditions, reveals that this response is only observed in FocTR4. In contrast, FocTR4 shows little innate resistance to most multi-site fungicides. However, quantitative virulence assays, in soil-grown bananas, reveals that only captan (20 μg ml-1) and all lipophilic cations (200 μg ml-1) suppress Panama disease effectively. These fungicides could help protect bananas from future yield losses by FocTR4

Ten-year safety of pluripotent stem cell transplantation in acute thoracic spinal cord injury.

OBJECTIVE: The purpose of this study was to evaluate the safety of oligodendrocyte progenitor cells (LCTOPC1) derived from human pluripotent stem cells administered between 7 and 14 days postinjury to patients with T3 to T11 neurologically complete spinal cord injury (SCI). The rationale for this first-in-human trial was based on evidence that administration of LCTOPC1 supports survival and potential repair of key cellular components and architecture at the SCI site. METHODS: This study was a multisite, open-label, single-arm interventional clinical trial. Participants (n = 5) received a single intraparenchymal injection of 2 × 106 LCTOPC1 caudal to the epicenter of injury using a syringe positioning device. Immunosuppression with tacrolimus was administered for a total of 60 days. Participants were followed with annual in-person examinations and MRI for 5 years at the time of this report and will be followed with annual telephone questionnaires for 6 to 15 years postinjection. The primary endpoint was safety, as measured by the frequency and severity of adverse events related to the LCTOPC1 injection, the injection procedure, and/or the concomitant immunosuppression administered. The secondary endpoint was neurological function as measured by sensory scores and lower-extremity motor scores as measured by the International Standards for Neurological Classification of Spinal Cord Injury examinations. RESULTS: No unanticipated serious adverse events related to LCTOPC1 have been reported with 98% follow-up of participants (49 of 50 annual visits) through the first 10 years of the clinical trial. There was no evidence of neurological decline, enlarging masses, further spinal cord damage, or syrinx formation. MRI results during the long-term follow-up period in patients administered LCTOPC1 cells showed that 80% of patients demonstrated T2 signal changes consistent with the formation of a tissue matrix at the injury site. CONCLUSIONS: This study provides crucial first-in-human safety data supporting the pursuit of future human embryonic stem cell-derived therapies. While we cannot exclude the possibility of future adverse events, the experience in this trial provides evidence that this cell type can be well tolerated by patients, with an event-free period of up to 10 years. Based on the safety profile of LCTOPC1 obtained in this study, a cervical dose escalation trial was initiated (NCT02302157)

SPACE: The race for mineral rights ‘The sky is no longer the limit’ Lessons from earth!

This research paper considers the ‘new space race’ – and the desire to extend sovereignty and ownership higher - the sky is no longer the limit. In 2015 the U.S. passed the Federal Space Resource Exploration and Utilization Act, which would permit mining in outer space; however, it remains highly controversial and in essence goes against the United Nations rationale that some areas are beyond the limits of national jurisdiction and cannot be claimed. This paper considers both the Bill and the final Act. Comparison analysis of other Treaties is considered and therefore the validity of State commercialization of assets deemed as being ‘mankind’s heritage’ is questioned. In doing so, the research provides comment on the similarities of lessons learnt from Earth and other UN International Treaties and Conventions, with correlation-reference made to the current situation in the South China Sea. The paper illustrates the U.S.’s reluctance to ratify any treaty, which does not allow the freedom …. of its competitive advantage

Durvalumab in Combination with Olaparib in Patients with Relapsed SCLC: Results from a Phase II Study

Purpose: Despite high tumor mutationburden, immune checkpoint blockade has limited efficacy in SCLC. We hypothesized that poly (ADP-ribose) polymerase inhibition could render SCLC more susceptible to immune checkpoint blockade. Methods: A single-arm, phase II trial (NCT02484404) enrolled patients with relapsed SCLC who received durvalumab, 1500 mg every 4 weeks, and olaparib, 300 mg twice a day. The primary outcome was objective response rate. Correlative studies included mandatory collection of pretreatment and during-treatment biopsy specimens, which were assessed to define SCLC immunephenotypes: desert (CD8-positive T-cell prevalence low), excluded (CD8-positive T cells in stroma immediately adjacent/within tumor), and inflamed (CD8-positive T cells in direct contact with tumor). Results: A total of 20 patients were enrolled. Their median age was 64 years, and most patients (60%) had platinum-resistant/refractory disease. Of 19 evaluable patients, two were observed to have partial or complete responses (10.5%), including a patient with EGFR-transformed SCLC. Clinical benefit was observed in four patients (21.1% [95% confidence interval: 6.1%–45.6%]) with confirmed responses or prolonged stable disease (≥8 months). The most common treatment-related adverse events were anemia (80%), lymphopenia (60%), and leukopenia (50%). Nine of 14 tumors (64%) exhibited an excluded phenotype; 21% and 14% of tumors exhibited the inflamed and desert phenotypes, respectively. Tumor responses were observed in all instances in which pretreatment tumors showed an inflamed phenotype. Of the five tumors without an inflamed phenotype at baseline, no during-treatment increase in T-cell infiltration or programmed death ligand 1 expression on tumor-infiltrating immune cells was observed. Conclusions: The study combination did not meet the preset bar for efficacy. Pretreatment and during-treatment biopsy specimens suggested that tumor immune phenotypes may be relevant for SCLC responses to immune checkpoint blockade combinations. The predictive value of preexisting CD8-positive T-cell infiltrates observed in this study needs to be confirmed in larger cohorts

Is Fetal Growth Restriction Associated with a More Severe Maternal Phenotype in the Setting of Early Onset Pre-Eclampsia? A Retrospective Study

BACKGROUND: Both pre-eclampsia and fetal growth restriction are thought to result from abnormal placental implantation in early pregnancy. Consistent with this shared pathophysiology, it is not uncommon to see growth restriction further confound the course of pre-eclampsia and vice versa. It has been previously suggested that superimposed growth restriction is associated with a more severe pre-eclamptic phenotype, however this has not been a consistent finding. Therefore, we set out to determine whether the presence of fetal growth restriction among women with severe early-onset pre-eclampsia was associated with more severe maternal disease compared to those without a growth-restricted fetus. METHODS AND FINDINGS: We undertook a retrospective cohort study of women presenting to a tertiary hospital with severe early-onset pre-eclampsia (<34 weeks' gestation) between 2005-2009. We collected clinical data, including severity of pre-eclampsia, maternal and neonatal outcomes. Of 176 cases of severe pre-eclampsia, 39% (n = 68) were further complicated by fetal growth restriction. However, no significant difference was seen in relation to the severity of pre-eclampsia between those with or without a growth-restricted baby. The presence of concomitant growth restriction was however associated with a significantly increased risk of stillbirth (p = 0.003) and total perinatal mortality (p = 0.02). CONCLUSIONS: The presence of fetal growth restriction among women with severe early-onset pre-eclampsia is not associated with increased severity of maternal disease. However the incidence of stillbirth and perinatal death is significantly increased in this sub-population