When Process Affects Punishment: Differences in Sentences After Guilty Plea, Bench Trial, and Jury Trial in Five Guidelines States

The research reported in this Essay examines process discounts-differences in sentences imposed for the same offense, depending upon whether the conviction was by jury trial, bench trial, or guilty plea-in five states that use judicial sentencing guidelines. Few guidelines systems expressly recognize plea agreement as an acceptable basis for departure, and none authorizes judges to vary sentences based upon whether or not the defendant waived his right to a jury trial and opted for a bench trial. Nevertheless, we predicted that because of the cost savings resulting from waivers, judges and prosecutors in any sentencing system would ensure that guilty plea convictions would generate the lowest sentences, with bench trial sentences averaging higher than plea-based sentences for the same offense, and sentences following jury trials averagingt he highest of all, even after controllingf or otherf actors associated with sentence severity. We found that a significant plea discount is evident for most offenses in all five states. Waiving a jury in favor of a bench trial has less consistent punishment consequences. Among states and even within a single state, the prevalence of process discounts is extraordinarily varied, as are the causes and methods of discounting. The Essay explores how these findings might inform sentencing reform and discusses the use of bench trials in sentencing guidelines systems generally

Modeling the Effects of Star Formation Histories on Halpha and Ultra-Violet Fluxes in Nearby Dwarf Galaxies

We consider the effects of non-constant star formation histories (SFHs) on Halpha and GALEX far ultra-violet (FUV) star formation rate (SFR) indicators. Under the assumption of a fully populated Chabrier IMF, we compare the distribution of Halpha-to-FUV flux ratios from ~ 1500 simple, periodic model SFHs with observations of 185 galaxies from the Spitzer Local Volume Legacy survey. We find a set of SFH models that are well matched to the data, such that more massive galaxies are best characterized by nearly constant SFHs, while low mass systems experience bursts amplitudes of ~ 30 (i.e., an increase in the SFR by a factor of 30 over the SFR during the inter-burst period), burst durations of tens of Myr, and periods of ~ 250 Myr; these SFHs are broadly consistent with the increased stochastic star formation expected in systems with lower SFRs. We analyze the predicted temporal evolution of galaxy stellar mass, R-band surface brightness, Halpha-derived SFR, and blue luminosity, and find that they provide a reasonable match to observed flux distributions. We find that our model SFHs are generally able to reproduce both the observed systematic decline and increased scatter in Halpha-to-FUV ratios toward low mass systems, without invoking other physical mechanisms. We also compare our predictions with those from the Integrated Galactic IMF theory with a constant SFR. We find that while both predict a systematic decline in the observed ratios, only the time variable SFH models are capable of producing the observed population of low mass galaxies ($M_{*}$ < 10$^{7}$ Msun) with normal Halpha-to-FUV ratios. These results demonstrate that a variable IMF alone has difficulty explaining the observed scatter in the Halpha-to-FUV ratios. We conclude by considering the limitations of the model SFHs, and discuss the use of additional empirical constraints to improve future SFH modeling efforts.Comment: 15 pages, 11 Figures. Accepted for publication in Ap

Power-to-hydrogen and hydrogen-to-X:Which markets? Which economic potential? Answers from the literature

Research carried out within the framework of Task 38 of the Hydrogen Implementing Agreement of the International Energy Agency. The task is coordinated by the Institute for techno-economics of energy systems (I-tésé) of the CEA, supported by the ADEME. The file attached to this record is the author's final peer reviewed version. The Publisher's final version can be found by following the DOI link.With the expansion of renewable energy’s contribution to the energy mix, balancing the electricity grid is becoming increasingly challenging. Alongside other solutions, Power-to-Hydrogen concepts are gaining significant interest. In this paper, the “Task 38”, initiated by the Hydrogen Implementing Agreement of the International EnergyAgency, presents the first of a two-step literature review regarding Power-to-Hydrogen and Hydrogen-to-X concepts with a focus on prospective market and economic potential. The study reveals a large scope of literature that shows a considerable variety ofsuggested implementation schemes. The transportation sector is identified as the most promising consumer market. Hydrogen-to-Gas pathways will require subsidies in order to be profitable. Hydrogen-to-Power becomes an economically promising option in the context of systems with high shares of renewables and a need for longer-term storages. Additionally, key enablers for Power-to-Hydrogen concepts are identified; namely support policies, concurrently with ongoing progress on the development and implementation of industry standard

Analysis of the Aspergillus fumigatus Proteome Reveals Metabolic Changes and the Activation of the Pseurotin A Biosynthesis Gene Cluster in Response to Hypoxia

The mold Aspergillus fumigatus is the most important airborne fungal pathogen. Adaptation to hypoxia represents an important virulence attribute for A. fumigatus. Therefore, we aimed at obtaining a comprehensive overview about this process on the proteome level. To ensure highly reproducible growth conditions, an oxygen-controlled, glucose-limited chemostat cultivation was established. Two-dimensional gel electrophoresis analysis of mycelial and mitochondrial proteins as well as two-dimensional Blue Native/SDS-gel separation of mitochondrial membrane proteins led to the identification of 117 proteins with an altered abundance under hypoxic in comparison to normoxic conditions. Hypoxia induced an increased activity of glycolysis, the TCA-cycle, respiration, and amino acid metabolism. Consistently, the cellular contents in heme, iron, copper, and zinc increased. Furthermore, hypoxia induced biosynthesis of the secondary metabolite pseurotin A as demonstrated at proteomic, transcriptional, and metabolite levels. The observed and so far not reported stimulation of the biosynthesis of a secondary metabolite by oxygen depletion may also affect the survival of A. fumigatus in hypoxic niches of the human host. Among the proteins so far not implicated in hypoxia adaptation, an NO-detoxifying flavohemoprotein was one of the most highly up-regulated proteins which indicates a link between hypoxia and the generation of nitrosative stress in A. fumigatus

Primary Xenografts of Human Prostate Tissue as a Model to Study Angiogenesis Induced by Reactive Stroma

Characterization of the mechanism(s) of androgen-driven human angiogenesis could have significant implications for modeling new forms of anti-angiogenic therapies for CaP and for developing targeted adjuvant therapies to improve efficacy of androgen-deprivation therapy. However, models of angiogenesis by human endothelial cells localized within an intact human prostate tissue architecture are until now extremely limited. This report characterizes the burst of angiogenesis by endogenous human blood vessels in primary xenografts of fresh surgical specimens of benign prostate or prostate cancer (CaP) tissue that occurs between Days 6–14 after transplantation into SCID mice pre-implanted with testosterone pellets. The wave of human angiogenesis was preceded by androgen-mediated up-regulation of VEGF-A expression in the stromal compartment. The neo-vessel network anastomosed to the host mouse vascular system between Days 6–10 post-transplantation, the angiogenic response ceased by Day 15, and by Day 30 the vasculature had matured and stabilized, as indicated by a lack of leakage of serum components into the interstitial tissue space and by association of nascent endothelial cells with mural cells/pericytes. The angiogenic wave was concurrent with the appearance of a reactive stroma phenotype, as determined by staining for α-SMA, Vimentin, Tenascin, Calponin, Desmin and Masson's trichrome, but the reactive stroma phenotype appeared to be largely independent of androgen availability. Transplantation-induced angiogenesis by endogenous human endothelial cells present in primary xenografts of benign and malignant human prostate tissue was preceded by induction of androgen-driven expression of VEGF by the prostate stroma, and was concurrent with and the appearance of a reactive stroma phenotype. Androgen-modulated expression of VEGF-A appeared to be a causal regulator of angiogenesis, and possibly of stromal activation, in human prostate xenografts

Met-Independent Hepatocyte Growth Factor-mediated regulation of cell adhesion in human prostate cancer cells

BACKGROUND: Prostate cancer cells communicate reciprocally with the stromal cells surrounding them, inside the prostate, and after metastasis, within the bone. Each tissue secretes factors for interpretation by the other. One stromally-derived factor, Hepatocyte Growth Factor (HGF), was found twenty years ago to regulate invasion and growth of carcinoma cells. Working with the LNCaP prostate cancer progression model, we found that these cells could respond to HGF stimulation, even in the absence of Met, the only known HGF receptor. The new HGF binding partner we find on the cell surface may help to clarify conflicts in the past literature about Met expression and HGF response in cancer cells. METHODS: We searched for Met or any HGF binding partner on the cells of the PC3 and LNCaP prostate cancer cell models, using HGF immobilized on agarose beads. By using mass spectrometry analyses and sequencing we have identified nucleolin protein as a novel HGF binding partner. Antibodies against nucleolin (or HGF) were able to ameliorate the stimulatory effects of HGF on met-negative prostate cancer cells. Western blots, RT-PCR, and immunohistochemistry were used to assess nucleolin levels during prostate cancer progression in both LNCaP and PC3 models. RESULTS: We have identified HGF as a major signaling component of prostate stromal-conditioned media (SCM) and have implicated the protein nucleolin in HGF signal reception by the LNCaP model prostate cancer cells. Antibodies that silence either HGF (in SCM) or nucleolin (on the cell surfaces) eliminate the adhesion-stimulatory effects of the SCM. Likewise, addition of purified HGF to control media mimics the action of SCM. C4-2, an LNCaP lineage-derived, androgen-independent human prostate cancer cell line, responds to HGF in a concentration-dependent manner by increasing its adhesion and reducing its migration on laminin substratum. These HGF effects are not due to shifts in the expression levels of laminin-binding integrins, nor can they be linked to expression of the known HGF receptor Met, as neither LNCaP nor clonally-derived C4-2 sub-line contain any detectable Met protein. Even in the absence of Met, small GTPases are activated, linking HGF stimulation to membrane protrusion and integrin activation. Membrane-localized nucelolin levels increase during cancer progression, as modeled by both the PC3 and LNCaP prostate cancer progression cell lines. CONCLUSION: We propose that cell surface localized nucleolin protein may function in these cells as a novel HGF receptor. Membrane localized nucleolin binds heparin-bound growth factors (including HGF) and appears upregulated during prostate cancer progression. Antibodies against nucleolin are able to ameliorate the stimulatory effects of HGF on met-negative prostate cancer cells. HGF-nucleolin interactions could be partially responsible for the complexity of HGF responses and met expression reported in the literature

Differences in the Tumor Microenvironment between African-American and European-American Breast Cancer Patients

Background: African-American breast cancer patients experience higher mortality rates than European-American patients despite having a lower incidence of the disease. We tested the hypothesis that intrinsic differences in the tumor biology may contribute to this cancer health disparity. Methods and Results: Using laser capture microdissection, we examined genome-wide mRNA expression specific to tumor epithelium and tumor stroma in 18 African-American and 17 European-American patients. Numerous genes were differentially expressed between these two patient groups and a two-gene signature in the tumor epithelium distinguished between them. To identify the biological processes in tumors that are different by race/ethnicity, Gene Ontology and disease association analyses were performed. Several biological processes were identified which may contribute to enhanced disease aggressiveness in African-American patients, including angiogenesis and chemotaxis. African-American tumors also contained a prominent interferon signature. The role of angiogenesis in the tumor biology of African-American