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Author(s): Arielle S. Gillman [sup.1] , Liz Scharnetzki [sup.2] , Patrick Boyd [sup.1] , Rebecca A. Ferrer [sup.1] , William M. P. Klein [sup.1] , Paul K. J. Han [sup.1] [...], The COVID-19 crisis has exposed the public to considerable scientific uncertainty, which may promote vaccine hesitancy among individuals with lower tolerance of uncertainty. In a national sample of US adults in May-June 2020, we examined how both perceptions of uncertainty about COVID-19 and trait-level differences in tolerance of uncertainty arising from various sources (risk, ambiguity, and complexity) are related to vaccine hesitancy-related outcomes, including trust in COVID-19 information, COVID-19 vaccine intentions, and beliefs that COVID-19 vaccines should undergo a longer testing period before being released to the public. Overall, perceptions of COVID-19 uncertainty were not associated with trust in information, vaccine intentions, or beliefs about vaccine testing. However, higher tolerance of risk was associated with lower intentions to get vaccinated, and lower tolerance of ambiguity was associated with lower intentions to get vaccinated and preferring a longer period of vaccine testing. Critically, perceptions of COVID-19 uncertainty and trait-level tolerance for uncertainty also interacted as predicted, such that greater perceived COVID-19 uncertainty was more negatively associated with trust in COVID-19 information among individuals with lower tolerance for risk and ambiguity. Thus, although perceptions of uncertainty regarding COVID-19 may not reduce trust and vaccine hesitancy for all individuals, trait-level tolerance of uncertainty arising from various sources may have both direct and moderating effects on these outcomes. These findings can inform public health communication or other interventions to increase COVID-19 vaccination uptake.

Author(s): Arielle S. Gillman [sup.1] , Irina A. Iles [sup.2] , William M. P. Klein [sup.2] , Barbara B. Biesecker [sup.3] , Katie L. Lewis [sup.4] , Leslie G. Biesecker [...], Future-oriented emotions such as anticipatory affect (i.e., current affect experienced regarding a potential future outcome) and anticipated affect (i.e., expectations about potential future affect), are uniquely associated with health decision-making (e.g., electing to receive results of genomic testing). This study investigated the degree to which negative anticipated and anticipatory emotions predict health decision making over time, and whether such emotions predict social, emotional, and behavioral responses to anticipated information (e.g., genomic testing results). 461 participants (M age = 63.9, SD = 5.61, 46% female) in a genomic sequencing cohort who elected to receive genomic sequencing (carrier) results were included in the current study. Anticipated and anticipatory affect about sequencing results were assessed at baseline. Psychological and behavioral responses to sequencing results, including participants' reported anxiety, decisional conflict, and distress about sequencing results, whether they shared results with family members, and their intentions to continue learning results in the future, were collected immediately, one month, and/or six months after receiving results. More negative anticipated and anticipatory affect at baseline was significantly and independently associated with lower intentions to continue learning results in the future, as well as higher levels of anxiety and uncertainty at multiple time points after receiving results. Anticipated negative affect was also associated with greater decisional conflict, and anticipatory negative affect was also associated with greater distress after receiving results. Future-oriented emotions may play an important role in decisions that unfold over time, with implications for genomic testing, behavioral medicine, and health decision-making broadly.

Author(s): Chloe O. Huelsnitz [sup.1] , Erin Turbitt [sup.2] , Jennifer M. Taber [sup.3] , Katie L. Lewis [sup.4] , Leslie G. Biesecker [sup.4] , Barbara B. Biesecker [sup.5] , [...], Although romantic couple concordance has been demonstrated across a wide array of health behaviors, little research has examined dyadic concordance in health beliefs. This study examined the extent to which cohabitating romantic dyads' attitudes and beliefs coincide (i.e., dyadic concordance) in addition to how well they predict intentions to learn genomic sequencing results. The actor-partner interdependence model was applied to cross-sectional data from 81 dyads in an exome sequencing study who were surveyed about their risk perceptions, worry, information avoidance, attitudes, and intentions toward learning carrier results. Information avoidance tendencies were positively correlated between partners, but there was low concordance on other beliefs. Individuals' attitudes and information avoidance predicted their own intentions to learn results. Additionally, partners' information avoidance tendencies predicted their partner's intentions to learn results. Future research should explore mechanisms through which one's partner's information avoidance may affect one's own intentions and behaviors.

Author(s): Jerry Suls [sup.1] , Rebecca A. Ferrer [sup.2] , William M. P. Klein [sup.2] Author Affiliations: (1) grid.416477.7, 0000 0001 2168 3646, Feinstein Institutes for Medical Research, Northwell Health, [...], This study examined temporal and social comparisons of physical health status. Participants in two waves of the MIDUS cohort ranging in age from young adult to young-old (N = 2,408) rated current, past, and future physical health, as well as peer health. Past health was generally rated as better than current health (particularly among young adults). Young adults expected better future health; young-old adults expected declining health. All groups recalled their health as better than they reported a decade earlier. Middle-aged and young-old respondents expected more decline than they reported ten years later; young adults' ratings were consistent. The two older groups believed they were healthier than same-age peers, whereas younger respondents believed they were less healthy (though as healthy as the other age groups). The nature and trajectories of temporal and social comparisons of physical health across the lifespan suggest the need to examine their consequences for health behaviors.

Author(s): Charlotte J. Hagerman [sup.1] , Michelle L. Stock [sup.1] , Brianne K. Molloy [sup.1] , Janine B. Beekman [sup.1] , William M. P. Klein [sup.2] , Nicole Butler [sup.1] [...], The current study tested whether self-affirmation or self-compassion exercises, shown to increase message acceptance, could maximize the benefit of a UV photo intervention on skin protection cognitions. College women (N = 167) were randomly assigned to: (1) view a UV photo or Black and White (no-UV) photo of their face and (2) write a self-affirmation, self-compassion, or neutral essay. Participants who saw their UV photo reported healthier cognitions, including greater perceived vulnerability and intentions to protect skin. Within the self-compassion condition, participants who saw their UV photo were also more likely to take the sunscreen packets offered. However, neither self-affirmation nor self-compassion enhanced the effect of the UV photo. Within the UV condition, women who completed these exercises had similar (and occasionally less healthy) cognitions and behavior as those who wrote a neutral essay. The benefits of self-affirmation and self-compassion in conjunction with health messages may be limited to higher risk groups who experience more message defensiveness than the current sample.

Author(s): Chan L. Thai [sup.1] , Elise L. Rice [sup.2] , Jennifer M. Taber [sup.3] , Annette R. Kaufman [sup.4] , William M. P. Klein [sup.5] Author Affiliations: (1) grid.263156.5, [...], Many cigarette smokers make multiple attempts to quit before they are successful. Implicit theories of smoking (ITS)-beliefs about whether smoking behavior is something that is changeable (incremental belief) or fixed (entity belief)-may play a role in quitting. Four iterations of the cross-sectional, nationally-representative Health Information National Trends Survey (HINTS) were used in logistic regression analyses to examine how smokers' ITS relates to (1) attempts to quit in the past 12 months; (2) considering quitting in the next 6 months; and (3) the interaction between ITS and past quit attempts on considering quitting. Greater incremental beliefs were not significantly associated with having tried to quit in the past year ([beta] = .27, p = .055); however, greater incremental beliefs were associated with greater likelihood of considering quitting in the next 6 months ([beta] = .22, p = .04). Past quit attempts did not moderate the association between ITS and considering quitting ([beta] = .59, p = .10). Results suggest that incremental beliefs are associated with increased intentions to quit.

Author(s): Alejo E. Rodriguez-Fraticelli [sup.1] [sup.2] [sup.3] [sup.4] , Caleb Weinreb [sup.5] , Shou-Wen Wang [sup.5] , Rosa P. Migueles [sup.6] , Maja Jankovic [sup.1] [sup.2] , Marc Usart [sup.1] [...], Bone marrow transplantation therapy relies on the life-long regenerative capacity of haematopoietic stem cells (HSCs).sup.1,2. HSCs present a complex variety of regenerative behaviours at the clonal level, but the mechanisms underlying this diversity are still undetermined.sup.3-11. Recent advances in single-cell RNA sequencing have revealed transcriptional differences among HSCs, providing a possible explanation for their functional heterogeneity.sup.12-17. However, the destructive nature of sequencing assays prevents simultaneous observation of stem cell state and function. To solve this challenge, we implemented expressible lentiviral barcoding, which enabled simultaneous analysis of lineages and transcriptomes from single adult HSCs and their clonal trajectories during long-term bone marrow reconstitution. Analysis of differential gene expression between clones with distinct behaviour revealed an intrinsic molecular signature that characterizes functional long-term repopulating HSCs. Probing this signature through in vivo CRISPR screening, we found the transcription factor TCF15 to be required and sufficient to drive HSC quiescence and long-term self-renewal. In situ, Tcf15 expression labels the most primitive subset of true multipotent HSCs. In conclusion, our work elucidates clone-intrinsic molecular programmes associated with functional stem cell heterogeneity and identifies a mechanism for the maintenance of the self-renewing HSC state. Using single-cell lineage tracing, the authors identify TCF15 as a novel regulator of haematopoietic stem cell quiescence and self-renewal.

Author(s): Lisa E. Mash [sup.1] , Raymond M. Klein [sup.2] , Jeanne Townsend [sup.1] [sup.3] Author Affiliations: (1) San Diego State University/University of California, San Diego Joint Doctoral Program in [...], Attentional impairments are among the earliest identifiable features of autism spectrum disorders (ASDs). Three attention networks have been extensively studied using the attention network test (ANT), but this long and repetitive task may pose challenges for individuals with ASDs. The AttentionTrip was developed as a more engaging measure of attention network efficiency. In 20 adults with ASDs and 20 typically developing controls, both tasks produced typical network scores (all p 0.78). Reaction time was less variable in the AttentionTrip than the ANT, possibly reflecting improved task engagement. Although the AttentionTrip elicited more consistent responses throughout an experimental session, anomalously low split-half reliability for its executive control network suggests that some changes may be needed.

Author(s): Nikhil Sharma [sup.1] [sup.2] , Kali Flaherty [sup.1] [sup.2] , Karina Lezgiyeva [sup.1] [sup.2] , Daniel E. Wagner [sup.3] , Allon M. Klein [sup.3] , David D. Ginty [sup.1] [...], More than twelve morphologically and physiologically distinct subtypes of primary somatosensory neuron report salient features of our internal and external environments.sup.1-4. It is unclear how specialized gene expression programs emerge during development to endow these subtypes with their unique properties. To assess the developmental progression of transcriptional maturation of each subtype of principal somatosensory neuron, we generated a transcriptomic atlas of cells traversing the primary somatosensory neuron lineage in mice. Here we show that somatosensory neurogenesis gives rise to neurons in a transcriptionally unspecialized state, characterized by co-expression of transcription factors that become restricted to select subtypes as development proceeds. Single-cell transcriptomic analyses of sensory neurons from mutant mice lacking transcription factors suggest that these broad-to-restricted transcription factors coordinate subtype-specific gene expression programs in subtypes in which their expression is maintained. We also show that neuronal targets are involved in this process; disruption of the prototypic target-derived neurotrophic factor NGF leads to aberrant subtype-restricted patterns of transcription factor expression. Our findings support a model in which cues that emanate from intermediate and final target fields promote neuronal diversification in part by transitioning cells from a transcriptionally unspecialized state to transcriptionally distinct subtypes by modulating the selection of subtype-restricted transcription factors. Neuronal targets mediate the emergence of somatosensory neuron subtypes by altering the expression of neuronal transcription factors.

Abstract. In McCoy v. Louisiana, the U.S. Supreme Court recognized an expanded Sixth Amendment autonomy right for capital defendants, allowing them to maintain their factual innocence at trial at all [...]

Author(s): Susan M. Czajkowski [sup.1], William T. Riley [sup.2], Catherine M. Stoney [sup.3], William M. P. Klein [sup.1], Robert T. Croyle [sup.1] Author Affiliations: (1) 0000 0001 2297 5165, grid.94365.3d, [...], The National Institutes of Health (NIH) has played a major role in promoting behavioral medicine research over the past 40 years through funding, review, and priority-setting activities and programs including scientific conferences, meetings, workgroups, intramural research, and training opportunities. In this review of NIH activities in support of behavioral medicine over the past four decades, we highlight key events, programs, projects, and milestones that demonstrate the many ways in which the NIH has supported behavioral and social sciences research and advanced the public health while contributing to the evolution of behavioral medicine as a scientific field.

ABSTRACT Mobile systems equipped with remote sensing instruments capable of simultaneous profiling of temperature, moisture, and wind at high temporal resolutions can offer insights into atmospheric phenomena that the operational [...]

ABSTRACT Recommendations are presented for in situ and remote sensing instruments and capabilities needed to advance the study of convection and turbulence in the atmosphere. These recommendations emerged from a [...]

Author(s): Anke M. Klein [sup.1] [sup.2] , Elske Salemink [sup.2] , Eva de Hullu [sup.3] , Esther Houtkamp [sup.1] , Marlissa Papa [sup.1] , Mariët van der Molen [sup.1] Author [...], The goal of this study was to examine the effects of Cognitive Bias Modification training for Interpretation (CBM-I) in socially anxious adolescents with Mild Intellectual Disabilities (MID). A total of 69 socially anxious adolescents with MID were randomly assigned to either a positive or a neutral control-CMB-I-training. Training included five sessions in a 3-week period, and each session consisted of 40 training items. Adolescents in the positive training group showed a significant reduction in negative interpretation bias on the two interpretation bias tasks after training compared to adolescents in the control-training group. Furthermore, in contrast to the control-training group, adolescents in the positive training reported a significant reduction of their social anxiety symptoms 10 weeks post-training.

Author(s): Jennifer K. Scheideler [sup.1] , Jennifer M. Taber [sup.2] , Rebecca A. Ferrer [sup.1] , Emily G. Grenen [sup.3] , William M. P. Klein [sup.1] Author Affiliations: (1) National [...], Although the gap is narrowing, Americans are more likely to be diagnosed with and die from heart disease than cancer, and yet many believe cancer is more common and their personal risk of cancer is higher than their heart disease risk. Using nationally representative 2013 Health Information National Trends Survey data, we assessed such beliefs and examined sociodemographic and psychological factors and health behaviors associated with these beliefs. 42.8% of participants rated cancer as more common and 78.5% rated their own cancer risk as equal to or exceeding their heart disease risk. These misperceptions were only modestly correlated. Beliefs about relative population risk were associated with various psychological factors, whereas beliefs about relative personal risk were not. Both beliefs were inconsistently associated with health behaviors. Accuracy in beliefs about cancer and heart disease relative risk and prevalence is low and future research should explore antecedents and consequences of these beliefs.

The central Great Plains region in North America has a nocturnal maximum in warm-season precipitation. Much of this precipitation comes from organized mesoscale convective systems (MCSs). This nocturnal maximum is [...]

Author(s): Susan Persky[sup.1] , Rebecca A. Ferrer[sup.2] , William M. P. Klein[sup.3] Author Affiliations: (1) Social and Behavioral Research Branch, National Human Genome Research Institute, Building 31, Rm. B1B36, 31 [...], It is crucial to examine patient reactions to genomics-informed approaches to weight management within a clinical context, and understand the influence of patient characteristics (here, emotion and race). Examining nonverbal reactions offers a window into patients' implicit cognitive, attitudinal and affective processes related to clinical encounters. We simulated a weight management clinical interaction with a virtual reality-based physician, and experimentally manipulated patient emotional state (anger/fear) and whether the physician made genomic or personal behavior attributions for weight. Participants were 190 overweight females who racially identified as either Black or White. Participants made less visual contact when receiving genomic information in the anger condition, and Black participants exhibited lowered voice pitch when receiving genomic information. Black participants also increased their interpersonal distance when receiving genomic information in the anger condition. By studying non-conscious nonverbal behavior, we can better understand the nuances of these interactions. Trial registry clinicaltrials.gov NCT01888913.

Author(s): Jennifer M. Taber[sup.1] , William M. P. Klein[sup.1] , Rebecca A. Ferrer[sup.1] , Paul K. J. Han[sup.2] , Katie L. Lewis[sup.3] , Leslie G. Biesecker[sup.3] , Barbara B. Biesecker[sup.3] [...], Many variants that could be returned from genome sequencing may be perceived as ambiguous-lacking reliability, credibility, or adequacy. Little is known about how perceived ambiguity influences thoughts about sequencing results. Participants (n = 494) in an NIH genome sequencing study completed a baseline survey before sequencing results were available. We examined how perceived ambiguity regarding sequencing results and individual differences in medical ambiguity aversion and tolerance for uncertainty were associated with cognitions and intentions concerning sequencing results. Perceiving sequencing results as more ambiguous was associated with less favorable cognitions about results and lower intentions to learn and share results. Among participants low in tolerance for uncertainty or optimism, greater perceived ambiguity was associated with lower intentions to learn results for non-medically actionable diseases; medical ambiguity aversion did not moderate any associations. Results are consistent with the phenomenon of "ambiguity aversion" and may influence whether people learn and communicate genomic information.

Author(s): Lindsey W. Plasschaert [sup.1] [sup.5] , Rapolas Zilionis [sup.2] [sup.3] , Rayman Choo-Wing [sup.1] [sup.5] , Virginia Savova [sup.2] [sup.6] , Judith Knehr [sup.4] , Guglielmo Roma [sup.4] , [...], The functions of epithelial tissues are dictated by the types, abundance and distribution of the differentiated cells they contain. Attempts to restore tissue function after damage require knowledge of how physiological tasks are distributed among cell types, and how cell states vary between homeostasis, injury-repair and disease. In the conducting airway, a heterogeneous basal cell population gives rise to specialized luminal cells that perform mucociliary clearance.sup.1. Here we perform single-cell profiling of human bronchial epithelial cells and mouse tracheal epithelial cells to obtain a comprehensive census of cell types in the conducting airway and their behaviour in homeostasis and regeneration. Our analysis reveals cell states that represent known and novel cell populations, delineates their heterogeneity and identifies distinct differentiation trajectories during homeostasis and tissue repair. Finally, we identified a novel, rare cell type that we call the 'pulmonary ionocyte', which co-expresses FOXI1, multiple subunits of the vacuolar-type H.sup.+-ATPase (V-ATPase) and CFTR, the gene that is mutated in cystic fibrosis. Using immunofluorescence, modulation of signalling pathways and electrophysiology, we show that Notch signalling is necessary and FOXI1 expression is sufficient to drive the production of the pulmonary ionocyte, and that the pulmonary ionocyte is a major source of CFTR activity in the conducting airway epithelium.Single-cell RNA sequencing analysis is used to identify cell types in the tracheal epithelium, including previously unidentified ionocytes, which express high levels of the cystic fibrosis transmembrane conductance regulator, CFTR.

Introduction Reducing childhood exposure to lead is a top environmental public health priority among state and federal agencies. Young children exposed to lead can suffer damage to the brain and [...], Recent literature has shown that analyzing newborn dried blood spots (DBS) may be effective in assessing some prenatal environmental exposures, such as exposure to lead. The purpose of this study was to evaluate the relationship between prenatal exposure to lead (as measured by newborn DBS results) and blood lead levels (BLLs) in infants 6 months of age or younger, using public health registry data for infants born in Texas from July 2002 through July 2006. The Texas Child Lead Registry (TCLR) was used to identify infants with documented elevated BLLs of 10 [micro]g/dL or higher as well as infants with documented low BLLs. BLLs for these children were compared to their corresponding newborn DBS results using Pearson correlation coefficients and exact logistic regression models. Overall, a significant but weak positive correlation was found between infant BLLs and corresponding newborn DBS lead levels (r = 0.48). However, the odds of an infant with an elevated newborn DBS lead level having an elevated BLL at 6 months of age or younger were much greater than for an infant with a low newborn DBS lead level of < 5 [micro]g/dL (adjusted odds ratio 27.95, 95% CI: 5.52-277.28). Although an association was observed between newborn DBS lead levels and BLLs in infants tested between 0 to 6 months of age, our findings suggest that prenatal exposure may not be the only significant source of lead exposure for infants [less than or equal to] 6 months of age. Keywords Dried blood spots * Newborn screening * Prenatal lead exposure * Blood lead levels * Childhood lead poisoning

With the capacity for rapid self-renewal and regeneration, the intestinal epithelium is stereotypical of stem cell--supported tissues. Yet the pattern of stem cell turnover remains in question. Applying analytical methods from population dynamics and statistical physics to an inducible genetic labeling system, we showed that done size distributions conform to a distinctive scaling behavior at short times. This result demonstrates that intestinal stem cells form an equipotent population in which the toss of a stern cell is compensated by the multiplication of a neighbor, leading to neutral drift dynamics in which clones expand and contract at random until they either take over the crypt or they are lost. Combined with long-term clonal fate data, we show that the rate of stern cell replacement is comparable to the cell division rate, implying that neutral drift and symmetrical cell divisions are central to stem cell homeostasis. 10.1126/science.1196236

Inhibition of Return (IOR, slower reaction times to previously cued or inspected locations) is observed both when eye movements are prohibited, and when the eyes move to the peripheral location and back to the centre before the target appears. It has been postulated that both effects are generated by a common mechanism, the activation of the oculomotor system. In strong support of this claim, IOR is not observed when attention is oriented endogenously and covertly, but it has been observed when eye movements are endogenously prepared, even when not executed. Here, we aimed to replicate and extend the finding that endogenous saccade preparation produces IOR. In five experiments using different paradigms, IOR was not observed when participants endogenously prepared an eye movement. These results lead us to conclude that endogenous saccade preparation is not sufficient to produce IOR. Keywords: inhibition of return, oculomotor activation, endogenous saccade preparation DOI: 10.1037/a0019951

UV B (UVB) radiation induces clones of cells mutant for the p53 tumor suppressor gene in human and murine epidermis. Here we reanalyze large datasets that report the fate of clones in mice subjected to a course of UVB radiation, to uncover how p53 mutation affects epidermal progenitor cell behavior. We show that p53 mutation leads to exponential growth of clones in UV-irradiated epidermis; this finding is also consistent with the size distribution of p53 mutant clones in human epidermis. Analysis of the tail of the size distribution further reveals that the fate of individual mutant cells is stochastic. Finally, the data suggest that ending UVB exposure results in the p53 mutant cells adopting the balanced fate of wild-type cells: the loss of mutant cells is balanced by proliferation so that the population of preneoplastic cells remains constant. We conclude that preneoplastic clones do not derive from long-lived, self-renewing mutant stem cells but rather from mutant progenitors with random cell fate. It follows that ongoing, low-intensity UVB radiation will increase the number of precancerous cells dramatically compared with sporadic, higher-intensity exposure at the same cumulative dose, which may explain why nonmelanoma skin cancer incidence depends more strongly on age than on radiation dosage. Our approach may be applied to determine cell growth rates in clonally labeled material from a wide range of tissues including human samples. cancer | stem cells | stochastic fate www.pnas.org/cgi/doi/10.1073/pnas.0909738107

The Rapid Automatized Naming (RAN) test involves rapidly naming sequences of items presented in a visual array. RAN has generated considerable interest because RAN performance predicts reading achievement. This study sought to determine what elements of RAN are responsible for the shared variance between RAN and reading performance using a series of cognitive tasks and a latent variable modelling approach. Participants performed RAN measures, a test of reading speed and comprehension, and six tasks, which tapped various hypothesised components of the RAN. RAN shared 10% of the variance with reading comprehension and 17% with reading rate. Together, the decomposition tasks explained 52% and 39% of the variance shared between RAN and reading comprehension and between RAN and reading rate, respectively. Significant predictors suggested that working memory encoding underlies part of the relationship between RAN and reading ability. Keywords: reading, rapid automatized naming, RAN, latent variability, individual differences

What do airport security, organ transplants, nano-processes, bio-inspired self-healing assembly systems and risk mitigation in supply chains all have in common? Each employ operations research to solve a difficult and […]

Temperature and wind data from a rural micronet and nearby site of the Oklahoma Mesonet are analyzed to study the frequency, strength, and formation processes of cold-pool events in a region with gentle terrain. Spatial analyses were performed for a 2-yr-long temperature record from 26 temperature/humidity surface stations, deployed across a 120 m x 320 m micronet located in a region of gently sloped terrain with maximum elevation changes of ~25 m. Cold pools frequently formed at the base of a gentle slope in a small depression of only ~6-m depth that is also sheltered by trees. The strength of each cold-pool event was classified according to a cold-pool index based on average nocturnal temperature perturbations within the cold-pool region. Wind data collected with sonic anemometers on a 15-m-tall tower at the micronet for a period of three months (spring 2005) suggest that flow sheltering by vegetation plays an important role in the cold-pool formation. The wind data also show signatures of katabatic flow for about 50% of the strong cold-pool events. However, a heat budget analysis for these nights suggested that the katabatic flows were associated with warm-air advection along the slope and that if katabatic jets had penetrated the cold pool, they would have produced substantial warming in the region of the cold pool. Since such warming was not observed, it is concluded that the katabatic jets did not actually penetrate the cold pool but likely flowed over it. An analysis of Richardson numbers demonstrates that cold-pool formation frequently occurs under strongly stable conditions that tend to suppress vertical turbulent mixing in the surface layer. Observations that significant temperature changes can occur even with elevation changes on the order of 6 m have important implications in agriculture as well as in data assimilation.

The Lake Thunderbird Micronet is a dense network of environmental sensors and a meteorological tower situated on ~10 acres of rural land in central Oklahoma. The Micronet was established in the spring of 2002 as part of a grassroots effort by a team of faculty and researchers at the University of Oklahoma to provide unique training and research opportunities for undergraduate and graduate students in meteorology and related environmental sciences. The history and design of the Micronet and use of the Micronet in undergraduate and graduate student training and research are described. Examples of interesting phenomena sampled at the Micronet are also presented.

Cleanroom processes can be used for fabricating microscale and nanoscale structures, and such structures, when bioconjugated, can be used for detecting low levels of cancer-specific circulating antigens. The concentration of such circulating antigens in human serum continues to increase with cancer progression, and therefore, detection of cancer at very early stages of the disease can be facilitated by monitoring small increases in circulating antigen concentration. Therefore, fabrication and bioconjugation are the first steps in the development of bio-assays for cancer detection. In this work, microscale and nanoscale Au/Cr thin film structures have been fabricated on Si substrate using dc sputtering and electron-beam (e-beam) evaporation in combination with photo and e-beam lithography. Using the fabricated device material stack (Au/Cr/Si), we have assessed the binding affinity of Au, Cr, and Si with Protein G, and antibodies for prostate specific antigen and cancer antigen 125, an ovarian cancer-associated antigen. Based on our experiments, we see that the thin gold layer of the Au/Cr/Si samples provides increased biomaterial binding affinity, and the chromium layer has a similar, if not less, binding affinity compared with the silicon chip alone. Thus, this work demonstrates that the fabricated material stack provides an appropriate platform for antigen detection. [DOI: 10.1115/1.3103937] Keywords: antigen detection, cancer diagnosis, microscale and nanoscale structures

Visual search is a favourite paradigm for researchers interested in attention because of its ease of implementation and interpretation. Typically, visual search requires the participant to indicate the presence or absence of a prespecified target. Although the slope ratio for present versus absent trials is no longer considered to be indicative of whether search is serial or not, target detection remains a staple amongst studies examining theoretical and empirical aspects of attention. The current study sought to compare within subjects three tasks in a visual search paradigm, detection, localisation, and identification, using identical stimuli. Detection differed in both pattern of error rates and slope from both identification and localisation. Moreover, the slopes from identification and localisation were significantly correlated, whilst neither was significantly correlated with slopes from the detection task. These results suggest that researchers interested in using slopes to estimate search efficiency should use localisation or identification, rather than target detection. Keywords: visual search, detection, localization, identification, slope

Targeting of viral vectors is a major challenge for in vivo gene delivery, especially after intravascular application. In addition, targeting of the endothelium itself would be of importance for gene-based therapies of vascular disease. Here, we used magnetic nanoparticles (MNPs) to combine cell transduction and positioning in the vascular system under clinically relevant, nonpermissive conditions, including hydrodynamic forces and hypothermia. The use of MNPs enhanced transduction efficiency of endothelial cells and enabled direct endothelial targeting of lentiviral vectors (LVs) by magnetic force, even in perfused vessels. In addition, application of external magnetic fields to mice significantly changed LV/MNP biodistribution in vivo. LV/MNP-transduced cells exhibited superparamagnetic behavior as measured by magnetorelaxometry, and they were efficiently retained by magnetic fields. The magnetic interactions were strong enough to position MNP-containing endothelial cells at the intima of vessels under physiological flow conditions. Importantly, magnetic positioning of MNP-labeled cells was also achieved in vivo in an injury model of the mouse carotid artery. Intravascular gene targeting can be combined with positioning of the transduced ceils via nanomagnetic particles, thereby combining gene- and cell-based therapies. cell positioning | gene transfer | vector targeting

Author(s): Betsabeh Khoramian Tusi [1]; Samuel L. Wolock [2]; Caleb Weinreb [2]; Yung Hwang [1]; Daniel Hidalgo [1]; Rapolas Zilionis [2]; Ari Waisman [3]; Jun R. Huh [4]; Allon M. [...], The formation of red blood cells begins with the differentiation of multipotent haematopoietic progenitors. Reconstructing the steps of this differentiation represents a general challenge in stem-cell biology. Here we used single-cell transcriptomics, fate assays and a theory that allows the prediction of cell fates from population snapshots to demonstrate that mouse haematopoietic progenitors differentiate through a continuous, hierarchical structure into seven blood lineages. We uncovered coupling between the erythroid and the basophil or mast cell fates, a global haematopoietic response to erythroid stress and novel growth factor receptors that regulate erythropoiesis. We defined a flow cytometry sorting strategy to purify early stages of erythroid differentiation, completely isolating classically defined burst-forming and colony-forming progenitors. We also found that the cell cycle is progressively remodelled during erythroid development and during a sharp transcriptional switch that ends the colony-forming progenitor stage and activates terminal differentiation. Our work showcases the utility of linking transcriptomic data to predictive fate models, and provides insights into lineage development in vivo.

Author(s): Alejo E. Rodriguez-Fraticelli [1, 2]; Samuel L. Wolock [3]; Caleb S. Weinreb [3]; Riccardo Panero [4]; Sachin H. Patel [1]; Maja Jankovic [1]; Jianlong Sun [1, 2]; Raffaele A. [...]

The Galapagos triple junction is a ridge-ridge-ridge triple junction where the Cocos, Nazca, and Pacific plates meet around the Galapagos microplate. Directly north of the large scarps of the Cocos-Nazca Rift, a 250-km-long and 50-km-wide band of northwest-southeast-trending cracks with volcanics at their western ends crosscuts and blankets the north-south-trending abyssal hills of the East Pacific Rise. It appears that the roughly northeast-southwest extension of East Pacific Rise-generated seafloor has been accommodated by a succession of minor rifts that, during at least the past 4 m.y., had their triple junctions with the East Pacific Rise at distances of 50-100 km north of the tip of the propagating Cocos-Nazca Rift. We propose that the rift locations are controlled by stresses associated with the dominant Cocos-Nazca Rift, and scaled by the distance of its tip to the East Pacific Rise. We speculate that similar ephemeral rifts occurred south of the Cocos-Nazca Rift and were instrumental in the origin of the rotating Galapagos microplate ca. 1.5 Ma. Keywords: Galapagos triple junction, plate boundaries, lithospheric stress.

AND WE THINK TODAY'S REPORTERS HAVE IT TOUGH. Picture this: To land a job, the journalistic aspirant known to history as Nellie Bly agrees to feign mental illness in order [...]

The yeast ABC transporter Pdr5 plays a major role in drug resistance against a large number of structurally unrelated compounds. Although Pdr5 has been extensively studied, many important aspects regarding its molecular mechanisms remain unresolved. For example, a striking degeneration of conserved amino acid residues exists in the nucleotide binding domains (NBDs), but their functional relevance is unknown. Here, we performed in vivo and in vitro experiments to address the functional asymmetry of NBDs. It became evident by ATPase activity and drug transport studies that catalysis at only one of the two NBD composite sites is crucial for protein function. Furthermore, mutations of the proposed 'catalytic carboxylate' (E1036) and the 'catalytic dyad histidine' (H1068) were characterized. Although a mutation of the glutamate abolished ATPase activity and substrate transport, mutation of H1068 had no influence on ATP consumption. However, the H1068A mutation abolished rhodamine transport in vivo and in vitro, while leaving the transport of other substrates unaffected. By contrast to mammalian P-glycoprotein (P-gp), the ATPase activity of yeast Pdr5 is not stimulated by the addition of substrates, indicating that Pdr5 is an uncoupled ABC transporter that constantly hydrolyses ATP to ensure active substrate transport. Taken together, our data provide important insights into the molecular mechanism of Pdr5 and suggest that not solely the transmembrane domains dictate substrate selection. ATPase activity | multidrug resistance | substrate recognition

When skilled readers search for a target letter while reading for comprehension, they miss the target letter more often when it is embedded in high-frequency function words than in less frequent content words. The magnitude of this 'missing-letter effect' (MLE) was investigated among 180 first- to fifth-grade students as a function of their reading skills as assessed with the reading subtest of the Wide Range Achievement Test (WRAT-3). Results revealed that good readers from grades 1 to 4 showed a larger missing-letter effect than poor readers with all tested materials. In addition, the size of the missing-letter effect was correlated with reading skills even after controlling for grade level. For fifth graders, the relation between the size of the missing-letter effect and reading skills was restricted to the contrast involving the function word the. Overall, results support the attentional-disengagement model of the missing-letter effect as well as other models of this effect and general models of reading., When reading a prose passage for comprehension while at the same time searching for a target letter, readers miss more target letters embedded in high-frequency function words than in lower [...]