Fortran for the nineties

Fortran has largely enjoyed prominence for the past few decades as the computer programming language of choice for numerically intensive scientific, engineering, and process control applications. Fortran's well understood static language syntax has allowed resulting parsers and compiler optimizing technologies to often generate among the most efficient and fastest run-time executables, particularly on high-end scalar and vector supercomputers. Computing architectures and paradigms have changed considerably since the last ANSI/ISO Fortran release in 1978, and while FORTRAN 77 has more than survived, it's aged features provide only partial functionality for today's demanding computing environments. The simple block procedural languages have been necessarily evolving, or giving way, to specialized supercomputing, network resource, and object-oriented paradigms. To address these new computing demands, ANSI has worked for the last 12-years with three international public reviews to deliver Fortran 90. Fortran 90 has superseded and replaced ISO FORTRAN 77 internationally as the sole Fortran standard; while in the US, Fortran 90 is expected to be adopted as the ANSI standard this summer, coexisting with ANSI FORTRAN 77 until at least 1996. The development path and current state of Fortran will be briefly described highlighting the many new Fortran 90 syntactic and semantic additions which support (among others): free form source; array syntax; new control structures; modules and interfaces; pointers; derived data types; dynamic memory; enhanced I/O; operator overloading; data abstraction; user optional arguments; new intrinsics for array, bit manipulation, and system inquiry; and enhanced portability through better generic control of underlying system arithmetic models. Examples from dynamical astronomy, signal and image processing will attempt to illustrate Fortran 90's applicability to today's general scalar, vector, and parallel scientific and engineering requirements and object oriented programming paradigms. Time permitting, current work proceeding on the future development of Fortran 2000 and collateral standards will be introduced

Purinergic signalling and immune cells

This review article provides a historical perspective on the role of purinergic signalling in the regulation of various subsets of immune cells from early discoveries to current understanding. It is now recognised that adenosine 5'-triphosphate (ATP) and other nucleotides are released from cells following stress or injury. They can act on virtually all subsets of immune cells through a spectrum of P2X ligand-gated ion channels and G protein-coupled P2Y receptors. Furthermore, ATP is rapidly degraded into adenosine by ectonucleotidases such as CD39 and CD73, and adenosine exerts additional regulatory effects through its own receptors. The resulting effect ranges from stimulation to tolerance depending on the amount and time courses of nucleotides released, and the balance between ATP and adenosine. This review identifies the various receptors involved in the different subsets of immune cells and their effects on the function of these cells

The effects of neuroleptics on facial action in schizophrenic patients

This paper describes the influence of neuroleptic therapy on facial action in drug-naive schizophrenics. In a comparative study of medicated and unmedicated schizophrenic patients, the coordinates of 12 small light-reflecting points, attached to subjects' faces, were computer-recorded and analyzed automatically during a semistandardized clinical interview. In addition, facial activity in videotaped interviews was coded using the Facial Action Coding System (FACS). Each sample group comprised of eight patients with the DSMIII- R diagnostic criteria "schizophrenia" or "schizophreniform disorder". Subjects were studied on two occasions, one shortly after admission to the hospital, the other three weeks later. Group I was unmedicated during the first session, whereas group2 was medicated throughout the study. Three weeks after the start of medication, at the second interview, both recording methods showed a reduction in facial activity and facial expression across all subjects in group 1. The facial action of patients in group2, however, remained unchanged.Ziel der vorliegenden Arbeit war die Untersuchung des Einflusses von Neuroleptika auf die Mimik von unmedizierten schizophrenen Patienten. Wiihrend eines halbstandardisierten klinischen Interviews worde die Beweglichkeit von zwolf kleinen, licht-reflektierenden Punkten, die in das Gesicht von medizierten und unmedizierten schizophrenen Patienten geklebt worden, automatisch im Zeitverlauf gemessen. Erganzend wurde der mirnische Ausdruck mit dem Facial Action Coding System (FACS) kodiert, wofiir die Patienten gleichzeitig mit Video aufgenommen worden. Jede der beiden Gruppen bestand aus acht Patienten mit den DSM-IIIR- Diagnosen "Schizophrenie" oder "Schizophrenieforme Storung". Die Patienten worden einmal direkt nach der stationaren Aufnahme und ein zweites Mal nach drei Wochen untersucht. Die Patienten der ersten Gruppe waren zum ersten Zeitpunkt nicht mit Neuroleptika mediziert, wiihrend die der zweiten Gruppe schon zu diesem Zeitpunkt entsprechende Medikamente einnahmen. Es konnte eine Reduktion der mimischen Beweglichkeit des gesamten Gesichtes im Sinne einer neuroleptisch bedingten Hypornimie der primiir Neuroleptika-unbehandelten Patienten bei der zweiten Untersuchung beobachtet werden. Die andere Gruppe Schizophrener, die zu beiden Zeitpunkten mit Neuroleptika behandelt waren, zeigte keine Veriinderung in ihrer mimischen Beweglichkeit

Adenosine-generating ovarian cancer cells attract myeloid cells which differentiate into adenosine-generating tumor associated macrophages - a self-amplifying, CD39- and CD73-dependent mechanism for tumor immune escape

Background Ovarian cancer (OvCA) tissues show abundant expression of the ectonucleotidases CD39 and CD73 which generate immunomodulatory adenosine, thereby inhibiting cytotoxic lymphocytes. Little, however, is known about the effect of adenosine on myeloid cells. Considering that tumor associated macrophages (TAM) and myeloid-derived suppressor cells (MDSC) constitute up to 20 % of OvCA tissue, we investigated the effect of adenosine on myeloid cells and explored a possible contribution of myeloid cells to adenosine generation in vitro and ex vivo. Methods Monocytes were used as human blood-derived myeloid cells. After co-incubation with SK-OV-3 or OAW-42 OvCA cells, monocyte migration was determined in transwell assays. For conversion into M2-polarized “TAM-like” macrophages, monocytes were co-incubated with OAW-42 cells. Ex vivo TAMs were obtained from OvCA ascites. Macrophage phenotypes were investigated by intracellular staining for IL-10 and IL-12. CD39 and CD73 expression were assessed by FACS analysis both on in vitro-induced TAM-like macrophages and on ascites-derived ex situ-TAMs. Myeloid cells in solid tumor tissue were analyzed by immunohistochemistry. Generation of biologically active adenosine by TAM-like macrophages was measured in luciferase-based reporter assays. Functional effects of adenosine were investigated in proliferation-experiments with CD4+ T cells and specific inhibitors. Results When CD39 or CD73 activity on OvCA cells were blocked, the migration of monocytes towards OvCA cells was significantly decreased. In vivo, myeloid cells in solid ovarian cancer tissue were found to express CD39 whereas CD73 was mainly detected on stromal fibroblasts. Ex situ-TAMs and in vitro differentiated TAM-like cells, however, upregulated the expression of CD39 and CD73 compared to monocytes or M1 macrophages. Expression of ectonucleotidases also translated into increased levels of biologically active adenosine. Accordingly, co-incubation with these TAMs suppressed CD4+ T cell proliferation which could be rescued via blockade of CD39 or CD73. Conclusion Adenosine generated by OvCA cells likely contributes to the recruitment of TAMs which further amplify adenosine-dependent immunosuppression via additional ectonucleotidase activity. In solid ovarian cancer tissue, TAMs express CD39 while CD73 is found on stromal fibroblasts. Accordingly, small molecule inhibitors of CD39 or CD73 could improve immune responses in ovarian cancer

Comparative assessment of climate change and its impacts on three coastal aquifers in the Mediterranean

A comparative study on climate change and its impacts on coastal aquifers is performed for three Mediterranean areas. Common climate scenarios are developed for these areas using the ENSEMBLES projections that consider the A1b scenario. Temperature and precipitation data of three climate models are bias corrected with two different methods for a historic reference period, after which scenarios are created for 2020–2050 and 2069–2099 and used to calculate aquifer recharge for these periods based on two soil water budget methods. These multiple combinations of models and methods allow incorporating a level of uncertainty into the results. Groundwater flow models are developed for the three sites and then used to integrate future scenarios for three different parameters: (1) recharge, (2) crop water demand, and (3) sea level rise. Short-term predictions are marked by large ranges of predicted changes in recharge, only showing a consistent decrease at the Spanish site (mean 23 %), particularly due to a reduction in autumn rainfall. The latter is also expected to occur at the Portuguese site, resulting in a longer dry period. More frequent droughts are predicted at the Portuguese and Moroccan sites, but cannot be proven for the Spanish site. Toward the end of the century, results indicate a significant decrease (mean [25 %) in recharge in all areas, though most pronounced at the Portuguese site in absolute terms (mean 134 mm/year) and the Moroccan site in relative terms (mean 47 %). The models further predict a steady increase in crop water demand, causing 15–20 % additional evapotranspiration until 2100. Scenario modeling of groundwater flow shows its response to the predicted decreases in recharge and increases in pumping rates, with strongly reduced outflow into the coastal wetlands, whereas changes due to sea level rise are negligible

Expression of PARK7 is increased in celiac disease

Recently, it has been suggested that the gene called Parkinson's disease 7 (PARK7) might be an upstream activator of hypoxia-inducible factor (HIF)-1α, which plays a major role in sustaining intestinal barrier integrity. Furthermore, PARK7 has been proposed to participate in the Toll-like receptor (TLR)-dependent regulation of the innate immune system. Our aim was to investigate the involvement of PARK7 in the pathogenesis of coeliac disease (CD). Duodenal biopsy specimens were collected from 19 children with untreated CD, five children with treated CD (maintained on gluten-free diet), and ten children with histologically normal duodenal biopsies. PARK7 mRNA expression and protein level were determined by real-time polymerase chain reaction (PCR) and Western blot, respectively. Localization of PARK7 was visualized by immunofluorescence staining. Protein level of PARK7 increased in the duodenal mucosa of children with untreated CD compared to children with treated CD or to control biopsies (p <0.03). We detected intensive PARK7 staining in the epithelial cells and lamina propria of the duodenal mucosa of children with untreated CD compared with that in control biopsies. Our finding that mucosal expression of PARK7 is increased suggests that PARK7 is involved in the pathogenesis of gastrointestinal diseases, notably CD. Our results suggest that PARK7 may alter processes mediated by HIF-1α and TLR4, which supports a role for PARK7 in the maintenance of epithelial barrier integrity, immune homeostasis, or apoptosis

The adenosine pathway in immuno-oncology

Cancer immunotherapy based on immune-checkpoint inhibition or adoptive cell therapy has revolutionized cancer care. Nevertheless, a large proportion of patients do not benefit from such treatments. Over the past decade, remarkable progress has been made in the development of ‘next-generation’ therapeutics in immuno-oncology, with inhibitors of extracellular adenosine (eADO) signalling constituting an expanding class of agents. Induced by tissue hypoxia, inflammation, tissue repair and specific oncogenic pathways, the adenosinergic axis is a broadly immunosuppressive pathway that regulates both innate and adaptive immune responses. Inhibition of eADO-generating enzymes and/or eADO receptors can promote antitumour immunity through multiple mechanisms, including enhancement of T cell and natural killer cell function, suppression of the pro-tumourigenic effects of myeloid cells and other immunoregulatory cells, and promotion of antigen presentation. With several clinical trials currently evaluating inhibitors of the eADO pathway in patients with cancer, we herein review the pathophysiological function of eADO with a focus on effects on antitumour immunity. We also discuss the treatment opportunities, potential limitations and biomarker-based strategies related to adenosine-targeted therapy in oncology.SCOPUS: er.jDecretOANoAutActifinfo:eu-repo/semantics/publishe