The Atacama Rover Astrobiology Drilling Studies (ARADS) Project.

With advances in commercial space launch capabilities and reduced costs to orbit, humans may arrive on Mars within a decade. Both to preserve any signs of past (and extant) martian life and to protect the health of human crews (and Earth's biosphere), it will be necessary to assess the risk of cross-contamination on the surface, in blown dust, and into the near-subsurface (where exploration and resource-harvesting can be reasonably anticipated). Thus, evaluating for the presence of life and biosignatures may become a critical-path Mars exploration precursor in the not-so-far future, circa 2030. This Special Collection of papers from the Atacama Rover Astrobiology Drilling Studies (ARADS) project describes many of the scientific, technological, and operational issues associated with searching for and identifying biosignatures in an extreme hyperarid region in Chile's Atacama Desert, a well-studied terrestrial Mars analog environment. This paper provides an overview of the ARADS project and discusses in context the five other papers in the ARADS Special Collection, as well as prior ARADS project results.

Homogeneity assessment of the SuperCam calibration targets onboard rover perseverance.

The SuperCam instrument, onboard the Perseverance rover (Mars 2020 mission) is designed to perform remote analysis on the Martian surface employing several spectroscopic techniques such as Laser Induced Breakdown Spectroscopy (LIBS), Time-Resolved Raman (TRR), Time-Resolved Fluorescence (TRF) and Visible and Infrared (VISIR) reflectance. In addition, SuperCam also acquires high-resolution images using a color remote micro-imager (RMI) as well as sounds with its microphone. SuperCam has three main subsystems, the Mast Unit (MU) where the laser for chemical analysis and collection optics are housed, the Body Unit (BU) where the different spectrometers are located inside the rover, and the SuperCam Calibration Target (SCCT) located on the rover's deck to facilitate calibration tests at similar ambient conditions as the analyzed samples. To perform adequate calibrations on Mars, the 22 mineral samples included in the complex SCCT assembly must have a very homogeneous distribution of major and minor elements. The analysis and verification of such homogeneity for the 5-6 replicates of the samples included in the SCCT has been the aim of this work. To verify the physic-chemical homogeneity of the calibration targets, micro Energy Dispersive X-ray Fluorescence (EDXRF) imaging was first used on the whole surface of the targets, then the relative abundances of the detected elements were computed on 20 randomly distributed areas of 100 × 100 µm. For those targets showing a positive Raman response, micro-Raman spectroscopy imaging was performed on the whole surface of the targets at a resolution of 100 × 100 µm. The %RSD values (percent of relative standard deviation of mean values) for the major elements measured with EDXRF were compared with similar values obtained by two independent LIBS set-ups at spot sizes of 300 µm in diameter. The statistical analysis showed which elements were homogeneously distributed in the 22 mineral targets of the SCCT, providing their uncertainty values for further calibration. Moreover, nine of the 22 targets showed a good Raman response and their mineral distributions were also studied. Those targets can be also used for calibration purposes of the Raman part of SuperCam using the wavenumbers of their main Raman bands proposed in this work.

Feralisation targets different genomic loci to domestication in the chicken.

Feralisation occurs when a domestic population recolonizes the wild, escaping its previous restricted environment, and has been considered as the reverse of domestication. We have previously shown that Kauai Island's feral chickens are a highly variable and admixed population. Here we map selective sweeps in feral Kauai chickens using whole-genome sequencing. The detected sweeps were mostly unique to feralisation and distinct to those selected for during domestication. To ascribe potential phenotypic functions to these genes we utilize a laboratory-controlled equivalent to the Kauai population-an advanced intercross between Red Junglefowl and domestic layer birds that has been used previously for both QTL and expression QTL studies. Certain sweep genes exhibit significant correlations with comb mass, maternal brooding behaviour and fecundity. Our analyses indicate that adaptations to feral and domestic environments involve different genomic regions and feral chickens show some evidence of adaptation at genes associated with sexual selection and reproduction.

Mixed ancestry and admixture in Kauai's feral chickens: invasion of domestic genes into ancient Red Junglefowl reservoirs.

A major goal of invasion genetics is to determine how establishment histories shape non-native organisms' genotypes and phenotypes. While domesticated species commonly escape cultivation to invade feral habitats, few studies have examined how this process shapes feral gene pools and traits. We collected genomic and phenotypic data from feral chickens (Gallus gallus) on the Hawaiian island of Kauai to (i) ascertain their origins and (ii) measure standing variation in feral genomes, morphology and behaviour. Mitochondrial phylogenies (D-loop & whole Mt genome) revealed two divergent clades within our samples. The rare clade also contains sequences from Red Junglefowl (the domestic chicken's progenitor) and ancient DNA sequences from Kauai that predate European contact. This lineage appears to have been dispersed into the east Pacific by ancient Polynesian colonists. The more prevalent MtDNA clade occurs worldwide and includes domesticated breeds developed recently in Europe that are farmed within Hawaii. We hypothesize this lineage originates from recently feralized livestock and found supporting evidence for increased G. gallus density on Kauai within the last few decades. SNPs obtained from whole-genome sequencing were consistent with historic admixture between Kauai's divergent (G. gallus) lineages. Additionally, analyses of plumage, skin colour and vocalizations revealed that Kauai birds' behaviours and morphologies overlap with those of domestic chickens and Red Junglefowl, suggesting hybrid origins. Together, our data support the hypotheses that (i) Kauai's feral G. gallus descend from recent invasion(s) of domestic chickens into an ancient Red Junglefowl reservoir and (ii) feral chickens exhibit greater phenotypic diversity than candidate source populations. These findings complicate management objectives for Pacific feral chickens, while highlighting the potential of this and other feral systems for evolutionary studies of invasions.

Does employee safety influence customer satisfaction? Evidence from the electric utility industry.

PROBLEM: Research on workplace safety has not examined implications for business performance outcomes such as customer satisfaction. METHOD: In a U.S. electric utility company, we surveyed 821 employees in 20 work groups, and also had access to archival safety data and the results of a customer satisfaction survey (n=341). RESULTS: In geographically-based work units where there were more employee injuries (based on archival records), customers were less satisfied with the service they received. Safety climate, mediated by safety citizenship behaviors (SCBs), added to the predictive power of the group-level model, but these two constructs exerted their influence independently from actual injuries. In combination, two safety-related predictor paths (injuries and climate/SCB) explained 53% of the variance in customer satisfaction. DISCUSSION: Results offer preliminary evidence that workplace safety influences customer satisfaction, suggesting that there are likely spillover effects between the safety environment and the service environment. Additional research will be needed to assess the specific mechanisms that convert employee injuries into palpable results for customers. IMPACT ON INDUSTRY: Better safety climate and reductions in employee injuries have the potential to offer payoffs in terms of what customers experience.

Mental models of safety: do managers and employees see eye to eye?

PROBLEM: Disagreements between managers and employees about the causes of accidents and unsafe work behaviors can lead to serious workplace conflicts and distract organizations from the important work of establishing positive safety climate and reducing the incidence of accidents. METHOD AND RESULTS: In this study, the authors examine a model for predicting safe work behaviors and establish the model's consistency across managers and employees in a steel plant setting. Using the model previously described by Brown, Willis, and Prussia (2000), the authors found that when variables influencing safety are considered within a framework of safe work behaviors, managers and employees share a similar mental model. The study then contrasts employees' and managers' specific attributional perceptions. Findings from these more fine-grained analyses suggest the two groups differ in several respects about individual constructs. Most notable were contrasts in attributions based on their perceptions of safety climate. When perceived climate is poor, managers believe employees are responsible and employees believe managers are responsible for workplace safety. However, as perceived safety climate improves, managers and employees converge in their perceptions of who is responsible for safety. IMPACT ON INDUSTRY: It can be concluded from this study that in a highly interdependent work environment, such as a steel mill, where high system reliability is essential and members possess substantial experience working together, managers and employees will share general mental models about the factors that contribute to unsafe behaviors, and, ultimately, to workplace accidents. It is possible that organizations not as tightly coupled as steel mills can use such organizations as benchmarks, seeking ways to create a shared understanding of factors that contribute to a safe work environment. Part of this improvement effort should focus on advancing organizational safety climate. As climate improves, managers and employees are likely to agree more about the causes of safe/unsafe behaviors and workplace accidents, ultimately increasing their ability to work in unison to prevent accidents and to respond appropriately when they do occur. Finally, the survey items included in this study may be useful to organizations wishing to conduct self-assessments.

Adjunctive therapies in the cath lab. Successful medical therapy of left main thrombosis: value of serial coronary angiography.

Acute coronary syndromes (ACS), including unstable angina, non-Q wave myocardial infarctions (MI) and Q-wave MIs, are usually the result of plaque rupture and subsequent thrombus formation. Commonly, patients with ACS have significant underlying coronary artery disease (CAD) demonstrable by coronary angiography and are candidates for prompt revascularization. In many cases, however, ACS are due to coronary thrombosis in the absence of obstructive CAD and therefore aggressive medical therapy may be sufficient. Coronary angiography is an invaluable resource for individualized treatment decisions. We describe a patient with thrombosis of the left main coronary artery successfully treated with aggressive and prolonged antiplatelet and anticoagulant therapy under the guidance of serial coronary angiography.

Two-dimensional imaging of electronic wavefunctions in carbon nanotubes.

The drive towards the development of molecular electronics is placing increasing demands on the level of control that must be exerted on the electronic structure of materials. Proposed device architectures ultimately rely on tuning the interactions between individual electronic states, which amounts to controlling the detailed spatial structure of the electronic wavefunctions in the constituent molecules. Few experimental tools are available to probe this spatial structure directly, and the shapes of molecular wavefunctions are usually only known from theoretical investigations. Here we present scanning tunnelling spectroscopy measurements of the two-dimensional structure of individual wavefunctions in metallic single-walled carbon nanotubes; these measurements reveal spatial patterns that can be directly understood from the electronic structure of a single graphite sheet, and which represent an elegant illustration of Bloch's theorem at the level of individual wavefunctions. We also observe energy-dependent interference patterns in the wavefunctions and exploit these to directly measure the linear electronic dispersion relation of the metallic single-walled carbon nanotube.

The prevalence of bacteriuria in older institutionalized patients.

We set out to determine the prevalence of bacteriuria in elderly patients institutionalised in 10 homes in Northumberland. Single mid-stream urine (MSU) specimens were collected from 161 asymptomatic patients aged 64-101 years. Thirty-four (21%) samples had > 100 white blood cells (WBC/microliter) on microscopy as well as a significant bacteriuria of > 10(8) bacteria/l, being suggestive of a true urinary tract infection. A total of 115(71%) samples had < 100 WBC. Seventy-five (46%) samples could be described as 'contaminated' or 'infection unlikely' but of these only 31 (19.2% of all samples) were reported as 'contaminated' by the laboratory. This study confirms previous work in America to indicate the high level of bacteriuria in institutionalised elderly patients as well as the very high number (46%) who may show bacteriuria but no rise in the number of WBC suggesting contamination only. Nurses and GPs must be very cautious in interpreting MSU results from such patients.

Cell proliferation in type C gastritis affecting the intact stomach.

AIMS: Type C gastritis caused by bile reflux has a characteristic appearance, similar to that seen in other forms of chemical gastritis, such as those associated with NSAIDs or alcohol. An increase in mucosal cell proliferation increases the likelihood of a neoplastic clone of epithelial cells emerging, particularly where there is chronic epithelial injury associated with bile reflux. It has been shown previously that type C gastritis is associated with increased cell proliferation in the postsurgical stomach. The aim of this study was to determine cell proliferation in type C gastritis caused by bile reflux affecting the intact stomach. METHODS: Specimens from 15 patients with a histological diagnosis of type C gastritis on antral biopsy were obtained from the pathology archives between 1994 and 1997. A control group of nine normal antral biopsies was also selected and all underwent MIB-1 immunostaining. The gastric glands were divided into three zones (zone 1, gastric pit; zone 2, isthmus; and zone 3, gland base) and the numbers of positively staining nuclei for 500 epithelial cell nuclei were counted in each zone to determine the percentage labelling index (LI%). RESULTS: Cell proliferation was significantly higher in all three zones of the gastric glands with type C gastritis compared with controls as follows: zone 1, median LI% in type C gastritis 64.7 (range, 7.8-99.2), controls 4.7 (range, 2.0-11.3); zone 2, median LI% in type C gastritis 94.7 (range, 28.8-98.7), controls 40.2 (range, 23.1-70.3); and zone 3, median LI% in type C gastritis 20.0 (range, 1.3-96.0), controls 2.6 (range, 0.9-8.7). CONCLUSIONS: Bile reflux is thought to act as a promoter of gastric carcinogenesis in the postsurgical stomach. The same may be true in the intact stomach.

Frequency and prognostic significance of pericardial effusion in primary pulmonary hypertension. PPH Study Group. Primary pulmonary hypertension.

Pericardial effusion was noted in 43 of 79 patients (54%) with severe primary pulmonary hypertension. Larger effusion was associated with hemodynamic and echocardiographic evidence of right heart failure, impaired exercise tolerance, and a poor 1-year prognosis.

Antagonists of the platelet P2T receptor: a novel approach to antithrombotic therapy.

The platelet P2T receptor plays a major role in platelet aggregation, and its antagonists are predicted to have significant therapeutic potential as antithrombotic agents. We have explored analogues of adenosine triphosphate (ATP), which is a weak, nonselective but competitive P2T receptor antagonist. Modification of the polyphosphate side chain to prevent breakdown to the agonist adenosine diphosphate (ADP) and substitution of the adenine moiety to enhance affinity and selectivity for the P2T receptor led to the identification of 10e (AR-C67085MX), having an IC50 of 2.5 nM against ADP-induced aggregation of human platelets. Compound 10e was the first very potent antagonist of the P2T receptor, with a selectivity for that subtype of the P2 receptor family of >1000-fold. Further modification of the structure produced compound 10l (AR-C69931MX) having an IC50 of 0.4 nM. In vivo, at maximally effective antithrombotic doses, there is little prolongation of bleeding time (1.4-fold), which is in marked contrast to the 5-6-fold found with GPIIb/IIIa antagonists.

Cell proliferation in the post-surgical stomach, dietary salt, and the effect of H pylori eradication.

AIMS: To study the epithelial kinetics of the post-surgical stomach with reference to dietary salt intake and H pylori. METHODS: Endoscopic biopsies of the antrum/anastomosis and corpus were taken for histology and MIB-1 immunostaining. The labelling index (LI%) was determined in the three zones of the gastric glands (zone 1 = surface + gastric pit; zone 2 = isthmus; zone 3 = gland base) in patients with vagotomy and pyloroplasty (n = 12), gastroenterostomy + vagotomy (n = 4), partial gastrectomy (n = 3), and Billroth I operation (n = 3). Dietary salt was determined by urinary sodium/creatinine ratio. Twelve patients were H pylori positive (10 vagotomy and pyloroplasty; 2 partial gastrectomy) and had a repeat biopsy three months after antihelicobacter treatment (10 were H pylori negative after treatment). RESULTS: There was no correlation between salt intake and antrum/anastomosis (r = -0.34; p = 0.2) or corpus (r = -0.16; p = 0.2) labelling indices. Gastric mucosal proliferation is increased in the antrum/ anastomosis compared to the corpus in H pylori positive (p = 0.014) but not H pylori negative subjects (p = 0.084). This may reflect the different types of post-surgical stomach in each group. Gastric mucosal proliferation is reduced in antrum/anastomosis (p = 0.002) and corpus (p = 0.016) following H pylori eradication. CONCLUSIONS: Dietary salt does not influence gastric mucosal proliferation in the post-surgical stomach but H pylori may have a role in gastric stump carcinogenesis.

Restoration of insulin-like growth factor I action in skeletal muscle of old mice.

This study examined the effects of long-term chronic voluntary wheel exercise on the ability of insulin-like growth factor I (IGF-I) to stimulate rates of protein synthesis in the soleus muscle of old C57Bl/6 mice. Factors contributing to any changes in hormone action were analyzed at the level of hormone receptor binding, protein content, and gene expression. Chronic exercise resulted in an increased skeletal muscle mass (10-22%) and a 56% increase in IGF-I-stimulated rates of protein synthesis (P < 0.05). IGF-I receptor mRNA was increased 46%, IGF-I receptor protein was increased 65%, and the binding capacity of the IGF-I high-affinity site was increased sixfold (P < 0.05) with chronic wheel exercise. Insulin receptor protein content was decreased 35% (P < 0.05), whereas GLUT-4 content was increased 47% with chronic exercise (P < 0.05). This study demonstrates that old animals retain a plasticity for IGF I receptor and glucose transporter expression that may have valuable physiological consequences.

Role of cytokines in the mechanism of action of amlodipine: the PRAISE Heart Failure Trial. Prospective Randomized Amlodipine Survival Evaluation.

OBJECTIVES: We sought to determine whether the beneficial effects of amlodipine in heart failure may be mediated by a reduction in tumor necrosis factor-alpha (TNF-alpha) and interleukin-6 (IL-6) levels. We postulated that TNF-alpha and IL-6 levels may also have predictive value in patients with congestive heart failure (CHF). BACKGROUND: The molecular mechanism for progression of CHF may involve cytokine overexpression. The effect of amlodipine on cytokine levels in patients with CHF is unknown. METHODS: In the Prospective Randomized Amlodipine Survival Evaluation (PRAISE) trial, we used enzyme-linked immunosorbent assay to measure plasma levels of TNF-alpha in 92 patients and IL-6 in 62 patients in New York Heart Association functional classes III and IV randomized to receive amlodipine (10 mg/day) or placebo. Blood samples were obtained for cytokine measurement at baseline and at 8 and 26 weeks after enrollment. RESULTS: The baseline amlodipine and placebo groups did not differ in demographics and cytokine levels. Mean (+/- SD) plasma levels of TNF-alpha were 5.69 +/- 0.32 pg/ml, and those of IL-6 were 9.23 +/- 1.26 pg/ml at baseline. These levels were elevated 6 and 10 times, respectively, compared with those of normal subjects (p < 0.001). Levels of TNF-alpha did not change significantly over the 26-week period (p = 0.69). However, IL-6 levels were significantly lower at 26 weeks in patients treated with amlodipine versus placebo (p = 0.007 by the Wilcoxon signed-rank test). An adverse event-CHF or death-occurred more commonly in patients with higher IL-6 levels. CONCLUSIONS: Amlodipine lowers plasma IL-6 levels in patients with CHF. The beneficial effect of amlodipine in CHF may be due to a reduction of cytokines such as IL-6.

Effects of long-term infusion of prostacyclin (epoprostenol) on echocardiographic measures of right ventricular structure and function in primary pulmonary hypertension. Primary Pulmonary Hypertension Study Group.

BACKGROUND: Right heart failure is an important cause of morbidity and mortality in primary pulmonary hypertension. In a recent prospective, randomized study of severely symptomatic patients, treatment with prostacyclin (epoprostenol) produced improvements in hemodynamics, quality of life, and survival. This article describes the echocardiographic characteristics of participants in this trial; the relationship of echocardiographic variables to hemodynamic parameters, exercise capacity, and quality of life; and the echocardiographic changes associated with prostacyclin therapy. METHODS AND RESULTS: The 81 patients enrolled in this multicenter trial were randomized to treatment with a long-term infusion of prostacyclin in addition to conventional therapy (n = 41) or conventional therapy alone (n = 40) for 12 weeks. Echocardiograms and assessments of hemodynamics, exercise capacity, and quality of life were performed before and after the treatment phase. On baseline evaluation, patients had marked right ventricular dilatation and dysfunction, abnormal septal curvature, and significant tricuspid regurgitation with a high regurgitant velocity. Pericardial effusions were common. More pronounced abnormalities in right heart structure and function were associated with higher pulmonary arterial and mean right atrial pressures, lower cardiac index, and impaired exercise capacity but had no predictable relationship to quality-of-life indicators. The 12-week infusion of prostacyclin had beneficial effects on right ventricular size, curvature of the interventricular septum, and maximal tricuspid regurgitant jet velocity. CONCLUSIONS: The echocardiographic manifestations of severe primary pulmonary hypertension reflect abnormalities in hemodynamics and exercise capacity. Prostacyclin has beneficial effects on right heart structure and function that may contribute to the clinical improvement and prolonged survival observed with this drug.

Acute exercise attenuates age-associated resistance to insulin-like growth factor I.

This study examined the influence of acute exercise on the ability of insulin-like growth factor I (IGF-I) to stimulate protein synthesis in an isolated in vitro soleus muscle preparation in female C57Bl/6 mice aged 5, 12, and 24 mo. Gastrocnemius muscles were analyzed for IGF-I receptor mRNA levels, IGF-I receptor number, and IGF-I receptor binding capacities and affinity constants. IGF-I (20 nM) was unable to stimulate rates of protein synthesis in the 12- and 24-mo-old control animals. These animals demonstrated declines in IGF-I receptor protein. After acute exercise, IGF-I receptor mRNA was elevated, IGF-I receptor protein levels were unaffected, and rates of protein synthesis were stimulated by IGF-I in the 12- and 24-mo-old animals. Acute exercise significantly increased IGF-I receptor binding capacity and affinity constants in the 24- but not the 12-mo-old animals. We conclude that acute exercise can restore the action of IGF-I in aged muscle, potentially by increasing the IGF-I receptor binding capacity and affinity or as a result of factors downstream of the IGF-I receptor.

Obesity, adiposity, and lengthening of the QT interval: improvement after weight loss.

OBJECTIVES: To determine the prevalence of QT interval prolongation in patients referred to an outpatient clinic for treatment of obesity; and to describe the change in the QT interval during rapid weight loss with a very-low-calorie diet. DESIGN: Retrospective and prospective review of charts and electrocardiograms. SUBJECTS: Five hundred twenty-two obese patients (411 female, 112 males) with a mean age 44 (18-78 y) and a mean initial weight of 116 kg (63-285 kg) completing 26 weeks of treatment between September, 1989 through to December, 1993. MEASUREMENTS: We reviewed the EKGs of all patients and serially monitored the QTc if greater than 0.44 s or if more than 23 kg was lost during treatment. The QTc interval was calculated with Bazzett's formula using both a manual method and an automated software program. In some patients, body composition was measured by hydrodensitometry. RESULTS: The QTc interval before treatment was 0.42 +/- 0.026 s by manual measurement and 0.41 +/- 0.021 s by automated measurement. Forty-one to 53% of patients showed a QTc interval of greater than 0.42 s and 10-24% demonstrated moderate prolongation (> 0.44 s). In those patients for whom repeat EKG were performed, QTc showed shortening with weight loss by both methods (mean +/- s.e. of 0.42 +/- 0.003 to 0.41 +/- 0.003 s, P < 0.01 manually and 0.41 +/- 0.003 to 0.40 +/- 0.003 s, p < 0.005 by automated program). Analyses were repeated excluding 179 patients with a cardiovascular-related diagnosis or intraventricular block and the results were similar. By regression analysis, gender and fat mass (FM) percentage above normal predicted the QTc. CONCLUSIONS: QT Interval prolongation is common in obesity. For each 50% increase in FM% above normal, there is a 5 ms increase in the QTc above a 'normal' upper limit of 0.40 and 0.38 s in women and men, respectively. Moreover, the QT interval shortens with weight loss. This change may represent an additional benefit of weight loss along with the improvement in other cardiovascular risk factors.