Past production constrains current energy demands: persistent scaling in global energy consumption and implications for climate change mitigation

Climate change has become intertwined with the global economy. Here, we describe the importance of inertia to continued growth in energy consumption. Drawing from thermodynamic arguments, and using 38 years of available statistics between 1980 to 2017, we find a persistent time-independent scaling between the historical time integral $W$ of world inflation-adjusted economic production $Y$, or $W\left(t\right) = \int_0^t Y\left(t'\right)dt'$, and current rates of world primary energy consumption $\mathcal E$, such that $\lambda = \mathcal{E}/W = 5.9\pm0.1$ Gigawatts per trillion 2010 US dollars. This empirical result implies that population expansion is a symptom rather than a cause of the current exponential rise in $\mathcal E$ and carbon dioxide emissions $C$, and that it is past innovation of economic production efficiency $Y/\mathcal{E}$ that has been the primary driver of growth, at predicted rates that agree well with data. Options for stabilizing $C$ are then limited to rapid decarbonization of $\mathcal E$ through sustained implementation of over one Gigawatt of renewable or nuclear power capacity per day. Alternatively, assuming continued reliance on fossil fuels, civilization could shift to a steady-state economy that devotes economic production exclusively to maintenance rather than expansion. If this were instituted immediately, continual energy consumption would still be required, so atmospheric carbon dioxide concentrations would not balance natural sinks until concentrations exceeded 500 ppmv, and double pre-industrial levels if the steady-state was attained by 2030

Building the Holocene clinothem in the Gulf of Papua: An ocean circulation study

This paper investigates the role that tidal and wind-driven flows and buoyant river plumes play in the development of the Holocene clinothem in the Gulf of Papua. Time series data from bottom tripods and a mooring were obtained at four locations near the mouth of the Fly River during portions of 2003 and 2004. Flows in the Gulf of Papua during calendar year 2003 were hindcast every 3 h using the Navy Coastal Ocean Model (NCOM) with boundary conditions from the Navy Atmospheric Prediction System, the east Asian seas implementation of NCOM, and the OTIS Tidal Inversion System. Results show that tidal flows on the modern clinoform are strong and are landward and seaward directed. Peak spring tidal velocities can provide the shear stresses necessary to keep sediment up to sand size in motion as the wind-driven and baroclinic currents distribute it from the river mouths across and along the shelf in two circulation states. During the monsoon season, the clinoform topset is swept by a seaward surface flow and landward bottom flow, reflecting river plumes and coastal upwelling. Seaward, this structure evolves into a SW directed surface current over the clinothem foreset with accompanying landward directed near-bed currents that trend obliquely up the foreset to the WSW over much of the clinothem. During the trade wind season, the inner and outer topset are swept by NE directed, contour-parallel surface currents, underneath which lie obliquely landward near-bed currents. These modeled flows and complex gyres in shallow water coupled with wave- and current-supported gravity flows or river floods can explain the form, internal clinoform shapes, and mineralogy of the modern Gulf of Papua clinothem

Reduced Lentivirus Susceptibility in Sheep with TMEM154 Mutations

Visna/Maedi, or ovine progressive pneumonia (OPP) as it is known in the United States, is an incurable slow-acting disease of sheep caused by persistent lentivirus infection. This disease affects multiple tissues, including those of the respiratory and central nervous systems. Our aim was to identify ovine genetic risk factors for lentivirus infection. Sixty-nine matched pairs of infected cases and uninfected controls were identified among 736 naturally exposed sheep older than five years of age. These pairs were used in a genome-wide association study with 50,614 markers. A single SNP was identified in the ovine transmembrane protein (TMEM154) that exceeded genome-wide significance (unadjusted p-value 3×10−9). Sanger sequencing of the ovine TMEM154 coding region identified six missense and two frameshift deletion mutations in the predicted signal peptide and extracellular domain. Two TMEM154 haplotypes encoding glutamate (E) at position 35 were associated with infection while a third haplotype with lysine (K) at position 35 was not. Haplotypes encoding full-length E35 isoforms were analyzed together as genetic risk factors in a multi-breed, matched case-control design, with 61 pairs of 4-year-old ewes. The odds of infection for ewes with one copy of a full-length TMEM154 E35 allele were 28 times greater than the odds for those without (p-value<0.0001, 95% CI 5–1,100). In a combined analysis of nine cohorts with 2,705 sheep from Nebraska, Idaho, and Iowa, the relative risk of infection was 2.85 times greater for sheep with a full-length TMEM154 E35 allele (p-value<0.0001, 95% CI 2.36–3.43). Although rare, some sheep were homozygous for TMEM154 deletion mutations and remained uninfected despite a lifetime of significant exposure. Together, these findings indicate that TMEM154 may play a central role in ovine lentivirus infection and removing sheep with the most susceptible genotypes may help eradicate OPP and protect flocks from reinfection

Modeling screening, prevention, and delaying of Alzheimer's disease: an early-stage decision analytic model

<p>Abstract</p> <p>Background</p> <p>Alzheimer's Disease (AD) affects a growing proportion of the population each year. Novel therapies on the horizon may slow the progress of AD symptoms and avoid cases altogether. Initiating treatment for the underlying pathology of AD would ideally be based on biomarker screening tools identifying pre-symptomatic individuals. Early-stage modeling provides estimates of potential outcomes and informs policy development.</p> <p>Methods</p> <p>A time-to-event (TTE) simulation provided estimates of screening asymptomatic patients in the general population age ≥55 and treatment impact on the number of patients reaching AD. Patients were followed from AD screen until all-cause death. Baseline sensitivity and specificity were 0.87 and 0.78, with treatment on positive screen. Treatment slowed progression by 50%. Events were scheduled using literature-based age-dependent incidences of AD and death.</p> <p>Results</p> <p>The base case results indicated increased AD free years (AD-FYs) through delays in onset and a reduction of 20 AD cases per 1000 screened individuals. Patients completely avoiding AD accounted for 61% of the incremental AD-FYs gained. Total years of treatment per 1000 screened patients was 2,611. The number-needed-to-screen was 51 and the number-needed-to-treat was 12 to avoid one case of AD. One-way sensitivity analysis indicated that duration of screening sensitivity and rescreen interval impact AD-FYs the most. A two-way sensitivity analysis found that for a test with an extended duration of sensitivity (15 years) the number of AD cases avoided was 6,000-7,000 cases for a test with higher sensitivity and specificity (0.90,0.90).</p> <p>Conclusions</p> <p>This study yielded valuable parameter range estimates at an early stage in the study of screening for AD. Analysis identified duration of screening sensitivity as a key variable that may be unavailable from clinical trials.</p

pp32 (ANP32A) Expression Inhibits Pancreatic Cancer Cell Growth and Induces Gemcitabine Resistance by Disrupting HuR Binding to mRNAs

The expression of protein phosphatase 32 (PP32, ANP32A) is low in poorly differentiated pancreatic cancers and is linked to the levels of HuR (ELAV1), a predictive marker for gemcitabine response. In pancreatic cancer cells, exogenous overexpression of pp32 inhibited cell growth, supporting its long-recognized role as a tumor suppressor in pancreatic cancer. In chemotherapeutic sensitivity screening assays, cells overexpressing pp32 were selectively resistant to the nucleoside analogs gemcitabine and cytarabine (ARA-C), but were sensitized to 5-fluorouracil; conversely, silencing pp32 in pancreatic cancer cells enhanced gemcitabine sensitivity. The cytoplasmic levels of pp32 increased after cancer cells are treated with certain stressors, including gemcitabine. pp32 overexpression reduced the association of HuR with the mRNA encoding the gemcitabine-metabolizing enzyme deoxycytidine kinase (dCK), causing a significant reduction in dCK protein levels. Similarly, ectopic pp32 expression caused a reduction in HuR binding of mRNAs encoding tumor-promoting proteins (e.g., VEGF and HuR), while silencing pp32 dramatically enhanced the binding of these mRNA targets. Low pp32 nuclear expression correlated with high-grade tumors and the presence of lymph node metastasis, as compared to patients' tumors with high nuclear pp32 expression. Although pp32 expression levels did not enhance the predictive power of cytoplasmic HuR status, nuclear pp32 levels and cytoplasmic HuR levels associated significantly in patient samples. Thus, we provide novel evidence that the tumor suppressor function of pp32 can be attributed to its ability to disrupt HuR binding to target mRNAs encoding key proteins for cancer cell survival and drug efficacy

The Cysteine Rich Necrotrophic Effector SnTox1 Produced by Stagonospora nodorum Triggers Susceptibility of Wheat Lines Harboring Snn1

The wheat pathogen Stagonospora nodorum produces multiple necrotrophic effectors (also called host-selective toxins) that promote disease by interacting with corresponding host sensitivity gene products. SnTox1 was the first necrotrophic effector identified in S. nodorum, and was shown to induce necrosis on wheat lines carrying Snn1. Here, we report the molecular cloning and validation of SnTox1 as well as the preliminary characterization of the mechanism underlying the SnTox1-Snn1 interaction which leads to susceptibility. SnTox1 was identified using bioinformatics tools and verified by heterologous expression in Pichia pastoris. SnTox1 encodes a 117 amino acid protein with the first 17 amino acids predicted as a signal peptide, and strikingly, the mature protein contains 16 cysteine residues, a common feature for some avirulence effectors. The transformation of SnTox1 into an avirulent S. nodorum isolate was sufficient to make the strain pathogenic. Additionally, the deletion of SnTox1 in virulent isolates rendered the SnTox1 mutated strains avirulent on the Snn1 differential wheat line. SnTox1 was present in 85% of a global collection of S. nodorum isolates. We identified a total of 11 protein isoforms and found evidence for strong diversifying selection operating on SnTox1. The SnTox1-Snn1 interaction results in an oxidative burst, DNA laddering, and pathogenesis related (PR) gene expression, all hallmarks of a defense response. In the absence of light, the development of SnTox1-induced necrosis and disease symptoms were completely blocked. By comparing the infection processes of a GFP-tagged avirulent isolate and the same isolate transformed with SnTox1, we conclude that SnTox1 may play a critical role during fungal penetration. This research further demonstrates that necrotrophic fungal pathogens utilize small effector proteins to exploit plant resistance pathways for their colonization, which provides important insights into the molecular basis of the wheat-S. nodorum interaction, an emerging model for necrotrophic pathosystems

Taste evaluation of potato glycoalkaloids by the Aymara: A case study in human chemical ecology

A chemical ecological model can be the basis for defining testable hypotheses concerning human interactions with plants. Selection by Aymara subsistence cultivators against toxic glycoalkaloids in the ongoing domestication of the Bolivian potato cultigen Solanum X ajanhuiri was used as a specific case study of human interactions with phytochemicals. In taste perception tests, Aymara subjects were able to discriminate between concentrations of pure glycoalkaloids in solution only above 20 mg/100 ml. Taste panel tests of potato clones indicated that glycoalkaloid levels are important to the Aymara in determining quality only as part of a decision-making process involving two character states: too high or acceptable. Glycoalkaloids in potatoes are regarded as toxic to humans above 20 mg/100 g fresh weight. Among the Aymara, a breakpoint in the curve for glycoalkaloid preference appears to occur between 20–38 mg/100 g. This distinction is evident in the Aymara potato taxonomy which distinguishes bitter (luq'i ch'oke) from nonbitter (ch'oke) potatoes .Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/44480/1/10745_2004_Article_BF00888308.pd

Marketing as a means to transformative social conflict resolution: lessons from transitioning war economies and the Colombian coffee marketing system

Social conflicts are ubiquitous to the human condition and occur throughout markets, marketing processes, and marketing systems.When unchecked or unmitigated, social conflict can have devastating consequences for consumers, marketers, and societies, especially when conflict escalates to war. In this article, the authors offer a systemic analysis of the Colombian war economy, with its conflicted shadow and coping markets, to show how a growing network of fair-trade coffee actors has played a key role in transitioning the country’s war economy into a peace economy. They particularly draw attention to the sources of conflict in this market and highlight four transition mechanisms — i.e., empowerment, communication, community building and regulation — through which marketers can contribute to peacemaking and thus produce mutually beneficial outcomes for consumers and society. The article concludes with a discussion of implications for marketing theory, practice, and public policy

Finishing the euchromatic sequence of the human genome

The sequence of the human genome encodes the genetic instructions for human physiology, as well as rich information about human evolution. In 2001, the International Human Genome Sequencing Consortium reported a draft sequence of the euchromatic portion of the human genome. Since then, the international collaboration has worked to convert this draft into a genome sequence with high accuracy and nearly complete coverage. Here, we report the result of this finishing process. The current genome sequence (Build 35) contains 2.85 billion nucleotides interrupted by only 341 gaps. It covers ∼99% of the euchromatic genome and is accurate to an error rate of ∼1 event per 100,000 bases. Many of the remaining euchromatic gaps are associated with segmental duplications and will require focused work with new methods. The near-complete sequence, the first for a vertebrate, greatly improves the precision of biological analyses of the human genome including studies of gene number, birth and death. Notably, the human enome seems to encode only 20,000-25,000 protein-coding genes. The genome sequence reported here should serve as a firm foundation for biomedical research in the decades ahead