cssi/SciSciGPT-SciSciNet huggingface dataset:
4-Hydroxy-7-oxo-5-heptenoic acid lactone is a potent inducer of brain cancer cell invasiveness that may contribute to the failure of anti-angiogenic therapies

Previously, we discovered that free radical-induced oxidative fragmentation of the docosahexaenoate ester of 2-lysophosphatidylcholine produces 4-hydroxy-7-oxo-5-heptenoic acid (HOHA) lactone that, in turn, promotes the migration and invasion of endothelial cells. This suggested that HOHA lactone might similarly promote migration and invasion of glioblastoma multiformae (GBM) brain cancer stem cells (CSCs). A bioinformatics analysis of clinical cancer genomic data revealed that matrix metalloproteinase (MMP)1 and three markers of oxidative stress - superoxide dismutase 2, NADPH oxidase 4, and carbonic anhydrase 9 - are upregulated in human mesenchymal GBM cancer tissue, and that MMP1 is positively correlated to all three of these oxidative stress markers. In addition, elevated levels of MMP1 are indicative of GBM invasion, while low levels of MMP1 indicate survival. We also explored the hypothesis that the transition from the proneural to the more aggressive mesenchymal phenotype, e.g., after treatment with an anti-angiogenic therapy, is promoted by the effects of lipid oxidation products on GBM CSCs. We found that low micromolar concentrations of HOHA lactone increase the cell migration velocity of cultured GBM CSCs, and induce the expression of MMP1 and two protein biomarkers of the proneural to mesenchymal transition (PMT): p65 NF-κβ and vimentin. Exposure of cultured GBM CSCs to HOHA lactone causes an increase in phosphorylation of mitogen-activated protein kinases and Akt kinases that are dependent on both protease-activated receptor 1 (PAR1) and MMP1 activity. We conclude that HOHA lactone promotes the PMT in GBM through the activation of PAR1 and MMP1. This contributes to a fatal flaw in antiangiogenic, chemo, and radiation therapies: they promote oxidative stress and the generation of HOHA lactone in the tumor that fosters a change from the proliferative proneural to the migratory mesenchymal GBM CSC phenotype that seeds new tumor growth. Inhibition of PAR1 and HOHA lactone are potential new therapeutic targets for impeding GBM tumor recurrence.
An Integrated Approach to Registration and Fusion of Hyperspectral and Multispectral Images

Combining a hyperspectral (HS) image and a multispectral (MS) image—an example of image fusion—can result in a spatially and spectrally high-resolution image. Despite the plethora of fusion algorithms in remote sensing, a necessary prerequisite, namely registration, is mostly ignored. This limits their application to well-registered images from the same source. In this article, we propose and validate an integrated registration and fusion approach (code available at https://github.com/zhouyuanzxcv/Hyperspectral ). The registration algorithm minimizes a least-squares (LSQ) objective function with the point spread function (PSF) incorporated together with a nonrigid freeform transformation applied to the HS image and a rigid transformation applied to the MS image. It can handle images with significant scale differences and spatial distortion. The fusion algorithm takes the full high-resolution HS image as an unknown in the objective function. Assuming that the pixels lie on a low-dimensional manifold invariant to local linear transformations from spectral degradation, the fusion optimization problem leads to a closed-form solution. The method was validated on the Pavia University, Salton Sea, and the Mississippi Gulfport datasets. When the proposed registration algorithm is compared to its rigid variant and two mutual information-based methods, it has the best accuracy for both the nonrigid simulated dataset and the real dataset, with an average error less than 0.15 pixels for nonrigid distortion of maximum 1 HS pixel. When the fusion algorithm is compared with current state-of-the-art algorithms, it has the best performance on images with registration errors as well as on simulations that do not consider registration effects.
Math anxiety and executive function: Neural influences of task switching on arithmetic processing

Math anxiety (MA) is associated with negative thoughts and emotions when encountering mathematics, often resulting in under-performance on math tasks. One hypothesized mechanism by which MA affects performance is through anxiety-related increases in working memory (WM) load, diverting resources away from mathematical computations. We examined whether this effect is specific to WM or whether the impact of MA extends to an overall depletion of executive function (EF) resources. In this fMRI experiment, we manipulated two separate factors known to impact EF demands-task-switching (TS) and increased WM load-in order to evaluate how MA relates to behavioral performance and neural activity related to mathematical calculations. Relative to a difficult non-math task (analogies), we observed MA-related deficits in math performance and reduced neural activity in a network of regions in the brain associated with arithmetic processing. In response to TS demands, higher levels of math anxiety were associated with a pattern of avoidance and disengagement. When switching from the control task, high math anxiety (HMA) was associated with disengagement from math trials, speeding through these trials, and exhibiting reduced neural activity in regions associated with arithmetic processing. The effects of math anxiety and WM were most pronounced at the lowest levels of WM load. Overall, the results of this study indicate that the effects of MA are broader than previously demonstrated and provide further insight into how EF deficits in MA might impact recruitment of neural resources that are important for successful math computations.
Comparison of serum cytokine concentrations between healthy dogs and canine osteosarcoma patients at the time of diagnosis

Systemic immune responses in cancer patients are of tremendous importance, both to advance understanding of disease mechanisms and for development of new diagnostic testing. Minimal published information is available on the systemic cytokine response in canine osteosarcoma (OS) patients. The goal of this study was to investigate serum cytokine alterations present in OS patients at the time of diagnosis. Serum samples from 22 canine OS patients at the time of diagnosis and 18 healthy control dogs were evaluated via multiplex immunoassay for 14 analytes. Significant increases in serum interleukin-8 (IL-8) and interleukin-12p40 (IL-12p40) concentrations were found in OS patients when compared to healthy controls. The results correlate with several published studies on serum cytokine alterations in human OS patients. These data add to the growing body of knowledge on immunologic alterations in OS, including potential immunomodulatory therapy of canine patients, and support future studies on serum cytokine testing to investigate diagnostic and prognostic utility.
Interdisciplinary communication to efficiently develop integrated pharmacotherapeutic sessions.

Abstract Introduction Integration of clinical, biomedical, social, administrative, and pharmaceutical sciences in a pharmacotherapeutics course is beneficial to student education. Unfortunately, the perceived increase in time, commitment, and workload required to produce integrated material often serves as a barrier to high level academic integration. This commentary discusses how interdisciplinary faculty communication started at the beginning of content development, using an initial brief planning session and ongoing unscheduled flexible methods, can efficiently produce integrated material without substantially increasing faculty workload compared to independently produced integrated course material. Commentary Content development can be streamlined during a short initial meeting to consider the relevant disciplines (e.g., pharmacology, medicinal chemistry, clinical sciences) for a topic and to collaboratively develop corresponding content outlines. To produce fully integrated material, collaborators should develop content using a cloud-based file sharing system and communicate using asynchronous, electronic means to ask questions and provide suggestions to collaborators. Implications Interdisciplinary communication is the foundation of integrated pharmacotherapeutic sessions, but supplemental meetings in addition to already required faculty meetings are both challenging to schedule and time consuming. With proper planning and the deliberate use of both continuous file sharing and asynchronous electronic communication, educators can produce parallel content emphasizing key concepts across disciplines without substantially increasing faculty workload.
Alveolitis in severe SARS-CoV-2 pneumonia is driven by self-sustaining circuits between infected alveolar macrophages and T cells

Abstract Some patients infected with Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2) develop severe pneumonia and the acute respiratory distress syndrome (ARDS) [1]. Distinct clinical features in these patients have led to speculation that the immune response to virus in the SARS-CoV-2-infected alveolus differs from other types of pneumonia [2]. We collected bronchoalveolar lavage fluid samples from 86 patients with SARS-CoV-2-induced respiratory failure and 252 patients with known or suspected pneumonia from other pathogens and subjected them to flow cytometry and bulk transcriptomic profiling. We performed single cell RNA-Seq in 5 bronchoalveolar lavage fluid samples collected from patients with severe COVID-19 within 48 hours of intubation. In the majority of patients with SARS-CoV-2 infection at the onset of mechanical ventilation, the alveolar space is persistently enriched in alveolar macrophages and T cells without neutrophilia. Bulk and single cell transcriptomic profiling suggest SARS-CoV-2 infects alveolar macrophages that respond by recruiting T cells. These T cells release interferon-gamma to induce inflammatory cytokine release from alveolar macrophages and further promote T cell recruitment. Our results suggest SARS-CoV-2 causes a slowly unfolding, spatially-limited alveolitis in which alveolar macrophages harboring SARS-CoV-2 transcripts and T cells form a positive feedback loop that drives progressive alveolar inflammation. This manuscript is accompanied by an online resource: https://www.nupulmonary.org/covid-19/ One sentence summary SARS-CoV-2-infected alveolar macrophages form positive feedback loops with T cells in patients with severe COVID-19.
Creating safe and healing environments: Innovative curriculum to support team members during patient and family escalations in a quaternary care pediatric hospital

Workplace violence in healthcare settings is at a crisis point. Healthcare organization have almost as many serious injuries from violence then all other industries combined (OSHA, 2013; Phillips, 2016). The costs of workplace violence have reached a crescendo provoking a response from several leading healthcare organizations including the Center for Disease Control, Occupational Safety and Health Administration, American Organization of Nurse Executives, American Nurse Association, and the Joint Commission who have all prioritized workplace violence initiatives. To address the issues of workplace violence our hospital embarked on a systematic change to improve the physical and psychological safety of faculty and team members. A multidisciplinary curriculum team developed the Creating Safe and Healing Environment course that introduces concepts to honor the unique demand on team members as they manage the intricacies of caring for others in a hospital setting. The team revisited the complex nature of the relationships and partnerships that are formed in healthcare between the team member, patients and families. The focus of this paper is to discuss the complex issue of workplace violence and review the development of curriculum that focuses the complexities of caring for pediatric patients, introduce the concepts of healing environments and teaches the skills and knowledge needed to co-create safe and healing environments for both care providers and their patients. This paper will also highlight the how a curriculum of this type is informed by the expertise of nursing theories including revisiting Nightengale ideals and incorporating Jean Watson's "Philosophy and Science of Human Caring".
The impact of learning Unified Medical Language System knowledge embeddings in relation extraction from biomedical texts.

OBJECTIVE We explored how knowledge embeddings (KEs) learned from the Unified Medical Language System (UMLS) Metathesaurus impact the quality of relation extraction on 2 diverse sets of biomedical texts. MATERIALS AND METHODS Two forms of KEs were learned for concepts and relation types from the UMLS Metathesaurus, namely lexicalized knowledge embeddings (LKEs) and unlexicalized KEs. A knowledge embedding encoder (KEE) enabled learning either LKEs or unlexicalized KEs as well as neural models capable of producing LKEs for mentions of biomedical concepts in texts and relation types that are not encoded in the UMLS Metathesaurus. This allowed us to design the relation extraction with knowledge embeddings (REKE) system, which incorporates either LKEs or unlexicalized KEs produced for relation types of interest and their arguments. RESULTS The incorporation of either LKEs or unlexicalized KE in REKE advances the state of the art in relation extraction on 2 relation extraction datasets: the 2010 i2b2/VA dataset and the 2013 Drug-Drug Interaction Extraction Challenge corpus. Moreover, the impact of LKEs is superior, achieving F1 scores of 78.2 and 82.0, respectively. DISCUSSION REKE not only highlights the importance of incorporating knowledge encoded in the UMLS Metathesaurus in a novel way, through 2 possible forms of KEs, but it also showcases the subtleties of incorporating KEs in relation extraction systems. CONCLUSIONS Incorporating LKEs informed by the UMLS Metathesaurus in a relation extraction system operating on biomedical texts shows significant promise. We present the REKE system, which establishes new state-of-the-art results for relation extraction on 2 datasets when using LKEs.
Examining the Effects of Anticipatory Robot Assistance on Human Decision Making

Collaborative robots that provide anticipatory assistance are able to help people complete tasks more quickly. As anticipatory assistance is provided before help is explicitly requested, there is a chance that this action itself will influence the person’s future decisions in the task. In this work, we investigate whether a robot’s anticipatory assistance can drive people to make choices different from those they would otherwise make. Such a study requires measuring intent, which itself could modify intent, resulting in an observer paradox. To combat this, we carefully designed an experiment to avoid this effect. We considered several mitigations such as the careful choice of which human behavioral signals we use to measure intent and designing unobtrusive ways to obtain these signals. We conducted a user study \((N=99)\) in which participants completed a collaborative object retrieval task: users selected an object and a robot arm retrieved it for them. The robot predicted the user’s object selection from eye gaze in advance of their explicit selection, and then provided either collaborative anticipation (moving toward the predicted object), adversarial anticipation (moving away from the predicted object), or no anticipation (no movement, control condition). We found trends and participant comments suggesting people’s decision making changes in the presence of a robot anticipatory motion and this change differs depending on the robot’s anticipation strategy.
Single Atoms at Crystal Ladder Steps

In this issue of Chem, Wu and co-workers report a freestanding ladder-like ZnO surface with abundant unsaturated step sites offering an attractive platform for selectively anchoring single-Au atom (Au1) with one-dimensional assembly. This opens a new strategy for the synthesis of single-atom sites with tunable arrangements for ultrasensitive sensing and highly active catalysis.
Principals’ Preferences in the Hiring Process: Is Everything Old New Again?

The purpose of the current study was to investigate urban school principals’ preferences for the types of teacher preparation programs completed, to understand their perceptions regarding factors t...
Electronic Wound Monitoring Using Fabric-Integrated Data Modulation

We propose a cost-efficient smart textile electronic (textronic) for wound healing assessment. This assessment is done by reflection of the modulated wound-data to the interrogator. The RF modulation of the data is done by a textile-based voltage-controlled oscillator (VCO) that takes the electric signal provided by electrochemical sensing of the uric acid found in the wound fluid. The assessment was done based on a threshold found to be 0.4 mM respect to which the severity or restoration of the damage wound is evaluated. The average sensitivity of this system is 44.67 MHz/mM and the maximum power consumption 0.38 mW. It uses low-cost materials and it is easy to manufacture and use by any patient or medical professional.
Bayesian Inference in Spatial Stochastic Volatility Models: An Application to House Price Returns in Chicago

In this study, we propose a spatial stochastic volatility model in which the latent log‐volatility terms follow a spatial autoregressive process. Though there is no spatial correlation in the outcome equation (the mean equation), the spatial autoregressive process defined for the log‐volatility terms introduces spatial dependence in the outcome equation. To introduce a Bayesian Markov chain Monte Carlo (MCMC) estimation algorithm, we transform the model so that the outcome equation takes the form of log‐squared terms. We approximate the distribution of the log‐squared error terms of the outcome equation with a finite mixture of normal distributions so that the transformed model turns into a linear Gaussian state‐space model. Our simulation results indicate that the Bayesian estimator has satisfactory finite sample properties. We investigate the practical usefulness of our proposed model and estimation method by using the price returns of residential properties in the broader Chicago Metropolitan area.
Open reduction of radial neck fractures in children: injury severity predicts the radiographic and clinical outcomes.

Background Radial neck fractures are the third most common elbow fracture in children. Open reduction may be required if closed or mini-open techniques are not successful in reducing the fracture. Previous reports on open reduction have noted poor outcomes and complications with this treatment approach. However, it is unknown whether it is the open procedure itself or the severity of the initial injury that leads to the poor results. The purpose of this study was to evaluate the correlation between intraoperative findings at the time of open reduction of radial neck fractures and the clinical and radiographic outcomes. Methods Data from patients who underwent open reduction for an acute radial neck fracture between January 2009 and December 2018 were abstracted and reviewed. Patients undergoing open treatment for a nonunion or malunion and those with inadequate follow-up were excluded. Demographic data, injury characteristics, treatment strategies, intraoperative findings, and clinical and radiographic outcomes were assessed. Results Twenty-two patients met the inclusion criteria. Of these patients, 14 were girls. The mean age was 9.7 ± 3 years, and the mean follow-up period was 15.8 months. Fifteen patients had a Judet grade IV displacement. Fair or poor outcomes were observed in 12 patients (55%). Ten reoperations were recorded during the study period. Age, weight, and associated injuries were not predictive of poor outcomes. Intraoperative findings of soft-tissue stripping and radial head comminution were the only significant predictors of fair or poor clinical outcomes (P Conclusion Our findings support the notion that the outcomes of open reduction of radial neck fractures are most closely correlated with the injury severity, with the intraoperative findings of complete soft-tissue stripping or comminution of the radial head fragment being significant predictors of poor clinical and radiographic outcomes. The choice of hardware and the quality of reduction achieved at the time of surgery have less significance than injury severity.
Positron annihilation lifetime spectroscopy: When is it feasible to decompose the spectrum?

Positron annihilation lifetime spectroscopy (PALS) has the potential to determine open volume defect identities and concentrations only if the spectrum can be accurately decomposed into its constituent parts. The intrinsic difficulty of decomposing PALS spectra into their constituent lifetimes and intensities is demonstrated, and it is shown that the global minimum of the objective function does not represent the true solution for a range of typical experimental scenarios. We show that the function currently employed in standard fitting methods cannot be improved upon with alternate weighting schemes. Resolution function width minimally impacts fit decomposition quality but errors are reduced with higher counts. A regression model is developed based on the experimental count, intensity of the defect component, and difference between the defect and bulk lifetime which predicts the anticipated intrinsic error of the objective function global minimum in estimating the fraction of positrons which annihilate in the bulk. This can be employed to determine whether a given PALS spectrum can be successfully decomposed into defect types and lifetimes.
Association of Increased Seizures During Rewarming With Abnormal Neurodevelopmental Outcomes at 2-Year Follow-up: A Nested Multisite Cohort Study.

Importance Compared with normothermia, hypothermia has been shown to reduce death or disability in neonatal hypoxic ischemic encephalopathy but data on seizures during rewarming and associated outcomes are scarce. Objective To determine whether electrographic seizures are more likely to occur during rewarming compared with the preceding period and whether they are associated with abnormal outcomes in asphyxiated neonates receiving hypothermia therapy. Design, setting, and participants This prespecified nested cohort study of infants enrolled in the Optimizing Cooling (OC) multicenter Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD) Neonatal Research Network trial from December 2011 to December 2013 with 2 years' follow-up randomized infants to either 72 hours of cooling (group A) or 120 hours (group B). The main trial included 364 infants. Of these, 194 were screened, 10 declined consent, and 120 met all predefined inclusion criteria. A total of 112 (90%) had complete data for death or disability. Data were analyzed from January 2018 to January 2020. Interventions Serial amplitude electroencephalography recordings were compared in the 12 hours prior and 12 hours during rewarming for evidence of electrographic seizure activity by 2 central amplitude-integrated electroencephalography readers blinded to treatment arm and rewarming epoch. Odds ratios and 95% CIs were evaluated following adjustment for center, prior seizures, depth of cooling, and encephalopathy severity. Main outcomes and measures The primary outcome was the occurrence of electrographic seizures during rewarming initiated at 72 or 120 hours compared with the preceding 12-hour epoch. Secondary outcomes included death or moderate or severe disability at age 18 to 22 months. The hypothesis was that seizures during rewarming were associated with higher odds of abnormal neurodevelopmental outcomes. Results A total of 120 newborns (70 male [58%]) were enrolled (66 in group A and 54 in group B). The mean (SD) gestational age was 39 (1) weeks. There was excellent interrater agreement (κ, 0.99) in detection of seizures. More infants had electrographic seizures during the rewarming epoch compared with the preceding epoch (group A, 27% vs 14%; P = .001; group B, 21% vs 10%; P = .03). Adjusted odd ratios (95% CIs) for seizure frequency during rewarming were 2.7 (1.0-7.5) for group A and 3.2 (0.9-11.6) for group B. The composite death or moderate to severe disability outcome at 2 years was significantly higher in infants with electrographic seizures during rewarming (relative risk [95% CI], 1.7 [1.25-2.37]) after adjusting for baseline clinical encephalopathy and seizures as well as center. Conclusions and relevance Findings that higher odds of electrographic seizures during rewarming are associated with death or disability at 2 years highlight the necessity of electroencephalography monitoring during rewarming in infants at risk. Trial registration ClinicalTrials.gov Identifier: NCT01192776.
Intergenerational Neuroimaging Study: Mother-Infant Functional Connectivity Similarity and the Role of Infant and Maternal Factors.

Mother and infant neural and behavioral synchrony is important for infant development during the first years of life. Recent studies also suggest that neural risk markers associated with parental psychopathology may be transmitted across generations before symptoms emerge in offspring. There is limited understanding of how early similarity in brain functioning between 2 generations emerges. In the current study, using functional magnetic resonance imaging, we examined the functional connectivity (FC) similarity between mothers and newborns during the first 3 months after the infant's birth. We found that FC similarity between mothers and infants increased as infant age increased. Furthermore, we examined whether maternal factors such as maternal socioeconomic status and prenatal maternal depressive symptoms may influence individual differences in FC similarity. For the whole-brain level, lower maternal education levels were associated with greater FC similarity. In previous literature, lower maternal education levels were associated with suboptimal cognitive and socioemotional development. Greater FC similarity may reflect that the infants develop their FC similarity prematurely, which may suboptimally influence their developmental outcomes in later ages.
ADN-analysis and development of distributed neural networks for intelligent applications

This article begins by explaining the concept of distributed neural networks. It then goes on to present a program library designed to support the development of such networks. In this context, distributed neural networks are seen as supernetworks comprising a number of subnetworks that can communicate with one another. Such supernetworks are intended to facilitate the modeling of complex and heterogeneous realities. Each subnetwork is trained independently of the others, according to the learning algorithm or algorithms that govern it. Once trained, the subnetworks are interconnected in such a way as to circulate information through the network as a whole. The distributed network library is an application of research in this area. It allows for the creation of distributed networks, the individual training of subnetworks, and communication between subnetworks. The library's interface makes it as much a tool for research as it is a program for neural network development for the uninitiated. >
Mechanism of mutagenicity by 5-hydroperoxymethyl-2'-deoxyuridine, an intermediate product of ionizing radiation, in bacteria. HPMdU bacterial mutagenicity and oxidation of DNA bases.

Abstract The specific objective was to find what processes are responsible for the mutagenicity of 5-hydroperoxymethyl-2′-deoxyuridine (HPMdU), which is a product of ionizing radiation, and what role transition metal ions play in those processes. We found that HPMdU is a more potent mutagen than its decomposition products 5-hydroxymethyl-2′-deoxyuridine (HMdU) and 5-formyl-2′-deoxyuridine (FdU) in the Salmonella typhimurium strains tested, with the TA100 strain being the most sensitive. HMdU exerted intermediate mutagenicity and FdU was the weakest of the three compounds. At 50 nmols/plate, HPMdU increased the number of revertants by 4-fold, whereas 1000 nmoles HMdU was required to enhance the number of revertants by 5-fold. Pretreatment of TA100 with o -phenanthroline, a membrane-permeable Fe and Cu chelator, caused an increase in mutagenicity of the low HPMdU doses but inhibited that of the 50 nmoles HPMdU/plate, while desferal, a membrane-impermeable Fe chelator, had virtually no effect. Azide (a catalase inhibitor) enhanced HPMdU mutagenicity, whereas f 3-amino-1,2,4-triazole (a catalase and peroxidase inhibitor) and ammonium formate (a hydroxyl radical scavenger) were protective. Preincubation of TA100 cells with 20 and 40 nM HPMdU caused dose-dependent formation of the oxidized DNA base derivatives HMdU, thymidine glycol and 8-hydroxy-2′-deoxyguanosine (8-OHdG), known hydroxyl radical-mediated oxidation products. Cumulatively, these results suggest that the genetic effects of HPMdU are due to its hydroperoxide moiety, which upon reacting with Fe generates hydroxyl radicals that in turn oxidize neighboring bases in cellular DNA. This also may be a mechanism by which ionizing radiation exerts its long-term effects.
Optimal taxation and firm formation

Abstract This paper analyzes non-linear optimal taxation under asymmetric information in a general equilibrium model with endogenous firm formation. It first shows, under a weak separability assumption on technologies, that output and input taxes are not necessary if profits are optimally taxed. It then examines the progressivity (or lack of it) of the optimal profit tax and describes the corresponding effects on the structure of the production sector relative to the first-best solution. Finally, the paper investigates conditions under which the provision of public goods can be decentralized.
Endoglin(CD105) is an effective target for an oral DNA vaccine against breast cancer

Proc Amer Assoc Cancer Res, Volume 46, 2005 6175 Growth and survival of breast tumor cells is well known to require angiogenesis, i.e., new blood vessel formation by proliferating endothelial cells. Expression of endoglin (CD105), a co-receptor of the TGF-beta receptor complex, is markedly enhanced on proliferating endothelial cells within the breast tumor microenvironments. Although CD105 is known to play an important role in regulating the survival of proliferating endothelial cells, its role as a target for DNA vaccines has not been extensively investigated. Thus, we established experimental systems to examine 1) the extent of anti-angiogenic/anti-tumor effects achieved with an oral DNA vaccine encoding murine CD105 carried by double attenuated (Dam-, AroA-) Salmonella typhimurium to secondary lymphoid organs, i.e., Peyer’s Patches, and 2) determine whether the knock-down of CD105 on highly metastatic murine 4T1 breast tumor cells achieved by specific siRNA affects their invasive and migratory characteristics. We demonstrate here that the breast carcinoma cell line, 4T1 strongly expresses endoglin on the cell surface, whereas another breast carcinoma cell line, D2F2 does not. However, even though the D2F2 cell line does not express endoglin, we found that in vivo proliferating endothelial cells within the D2F2 tumor microenvironment strongly express it. In fact, BALB/C mice immunized with a DNA vaccine encoding endoglin and co-expressing secretory chemokine CCL21 effectively suppressed D2F2 pulmonary metastases when compared to mice vaccinated with either endoglin or CCL21. In addition, D2F2 target cells stably transfected with endoglin were more sensitive to CTL killing than non-expressors. These results suggest that a DNA vaccine encoding both endoglin and secretory CCL21 is effective in inducing T-cell mediated immune responses against proliferating endothelial cells. In summary, we validated murine endoglin as an effective target for a DNA-based vaccine encoding it which markedly suppresses breast cancer metastases in a prophylactic setting.
Aerosol single scattering albedo dependence on biomass combustion efficiency: Laboratory and field studies

Single scattering albedo (ω) of fresh biomass burning (BB) aerosols produced from 92 controlled laboratory combustion experiments of 20 different woods and grasses was analyzed to determine the factors that control the variability in ω. Results show that ω varies strongly with fire-integrated modified combustion efficiency (MCEFI)—higher MCEFI results in lower ω values and greater spectral dependence of ω. A parameterization of ω as a function of MCEFI for fresh BB aerosols is derived from the laboratory data and is evaluated by field observations from two wildfires. The parameterization suggests that MCEFI explains 60% of the variability in ω, while the 40% unexplained variability could be accounted for by other parameters such as fuel type. Our parameterization provides a promising framework that requires further validation and is amenable for refinements to predict ω with greater confidence, which is critical for estimating the radiative forcing of BB aerosols.
Electrospray Ionization in Mass Spectrometry

Since the pioneering work of Fenn et al. in the 1980s, electrospray ionization (ESI) has increasingly become the ionization technique of choice for molecular mass spectrometry (MS) in a broad range of chemical and biological applications because of its ability to create intact, multiply charged gas-phase ions and its ready coupling with MS. Highly charged droplets generated by electrospray are known to undergo asymmetric fission at the Rayleigh charge limit to form smaller droplets. The generation of gas-phase ions in ESI follows two possible mechanisms as described by Dole’s charged residue model (CRM) and Iribarne and Thomson’s ion evaporation model (IEM). Many currently available ESI–MS technologies highlighted in this article have been developed to improve ionization efficiency in ESI and ion transmission efficiency through the ESI–MS interface and to reduce bias and ion suppression in the ESI process. New technologies are continually emerging to make ESI–MS even more sensitive and quantitative.
Saccharomyces cerevisiae SMT4 Encodes an Evolutionarily Conserved Protease With a Role in Chromosome Condensation Regulation

In a search for regulatory genes affecting the targeting of the condensin complex to chromatin in Saccharomyces cerevisiae, we identified a member of the adenovirus protease family, SMT4. SMT4 overexpression suppresses the temperature-sensitive conditional lethal phenotype of smc2-6, but not smc2-8 or smc4-1. A disruption allele of SMT4 has a prominent chromosome phenotype: impaired targeting of Smc4p-GFP to rDNA chromatin. Site-specific mutagenesis of the predicted protease active site cysteine and histidine residues of Smt4p abolishes the SMT4 function in vivo. The previously uncharacterized SIZ1 (SAP and Miz) gene, which encodes a protein containing a predicted DNA-binding SAP module and a Miz finger, is identified as a bypass suppressor of the growth defect associated with the SMT4 disruption. The SIZ1 gene disruption is synthetically lethal with the SIZ2 deletion. We propose that SMT4, SIZ1, and SIZ2 are involved in a novel pathway of chromosome maintenance.
A study of carbon monoxide in a series of laminar ethylene / air diffusion flames using tunable diode laser absorption spectroscopy

Abstract Tunable diode laser absorption spectroscopy has been used to map carbon monoxide concentrations and temperatures in a series of laminar ethylene/air, axisymmetric diffusion flames. As the quantity of soot increased, temperatures near the tip of the flames were observed to decrease. Carbon monoxide concentration profiles were found to depend on soot levels with the most dramatic differences apparent along the centerline beyond the stoichiometric surface. These measurements were combined with literature data to calculate oxidation rates for both soot and carbon monoxide. It was found that the oxidation rate for CO low in the flames was larger than that near the visible flame tip, which is attributable to both lower hydroxyl radical concentrations and temperatures at the tip. Further, soot oxidation, which is believed to form CO, occurs at a faster rate than CO oxidation processes at the visible flame tip, thus leading to carbon monoxide emission from the flame.
Convergence properties of the Harris density functional and the self-consistent atom fragment approximation

Describing materials properties and behavior over increasing scales of dimension and complexity requires an optimal balance of completeness and accuracy in solving the local density equations. In this study, the convergence properties of a set of schemes that aim to achieve increasing accuracy are systematically examined according to the hierarchical approximations upon which they are based. Specifically, the Harris density functional (HDF) and related schemes that express the total energy in terms of atomic densities and limited self-consistency are compared within a single consistent framework. Convergence of the HDF energy relative to input density is first tested by carrying out calculations within the non-self-consistent atom fragment and self-consistent atom fragment (SCAF) approximations and then by supplementing the SCAF density by increasing numbers of partial waves about each atomic site using the self-consistent partial wave (SCPW) method. The construct of the SCPW method, that solves the local density equations with controlled precision according to the number of partial waves in the site density expansions, enables this study. The rapid convergence of structural properties with an increasing number of partial waves on each site, sometimes even with only $L=0$ partial waves, provides additional justification for HDF-based tight-binding and molecular dynamics methods where the interatomic potentials are obtained from the superposition of atomiclike densities. The convergence of ground state structural properties is demonstrated by application to the set of molecules: carbon monoxide, water, orthosilicic acid $({\mathrm{H}}_{4}{\mathrm{SiO}}_{4})$, formamide $({\mathrm{HCONH}}_{2})$, iron pentacarbonyl $[\mathrm{Fe}(\mathrm{CO}{)}_{5}]$, and dimanganese decacarbonyl $[{\mathrm{Mn}}_{2}(\mathrm{CO}{)}_{10}]$.
Fundamental constants: The teamwork of precision.

A new value for the atomic mass of the electron is a link in a chain of measurements that will enable a test of the standard model of particle physics with better than part-per-trillion precision. See Letter p.467 The atomic mass of the electron is a key parameter for fundamental physics. A precise determination is a challenge because the mass is so low. Sven Sturm and colleagues report on a new determination of the electron's mass in atomic units. The authors measured the magnetic moment of a single electron bound to a reference ion (a bare nucleus of carbon-12). The results were analysed using state-of-the-art quantum electrodynamics theory to yield a mass value with a precision that exceeds the current literature value by more than an order of magnitude.
Analysis of DNA adducts formed in vivo in rats and mice from 1,2-dibromoethane, 1,2-dichloroethane, dibromomethane, and dichloromethane using HPLC/accelerator mass spectrometry and relevance to risk estimates.

Dihaloalkanes are of toxicological interest because of their high-volume use in industry and their abilities to cause tumors in rodents, particularly dichloromethane and 1,2-dichloroethane. The brominated analogues are not used as extensively but are known to produce more toxicity in some systems. Rats and mice were treated i.p. with 14C-dichloromethane, -dibromomethane, -1,2-dichloroethane, or -1,2-dibromoethane [5 mg (kg body weight)−1], and livers and kidneys were collected to rapidly isolate DNA. The DNA was digested using a procedure designed to minimize processing time, because some of the potential dihalomethane-derived DNA–glutathione (GSH) adducts are known to be unstable, and the HPLC fractions corresponding to major adduct standards were separated and analyzed for 14C using accelerator mass spectrometry. The level of liver or kidney S-[2-(N7-guanyl)ethyl]GSH in rats treated with 1,2-dibromoethane was ∼1 adduct/105 DNA bases; in male or female mice, the level was approximately one-half of this. ...
Alcohol, Tobacco, and Drug Use Disorders and Personality Disorder Symptoms.

In a nonclinical sample of 395 young adults, the authors evaluated the relations between major personality traits, Diagnostic and Statistical Manual of Mental Disorders (4th ed.; DSM-IV; American Psychiatric Association, 1994) personality disorder symptoms, and DSM-IV alcohol use disorders (AUDs). Consistent with previous findings, traits related to disinhibition and negative affectivity were consistently associated with AUDs, as were Cluster B personality disorder symptoms (especially antisocial and borderline disorder symptoms). Multivariate analyses revealed that Cluster B symptoms were significantly associated with AUDs above and beyond what was accounted for by personality traits. Further, the authors found differential patterns of relations between other substance use disorders (SUDs; i.e., tobacco dependence and drug use diagnoses) and personality disorder symptoms. Overall, these results suggest that personality disorder symptoms predict unique variance in SUDs that reflect maladaptive aspects of personality traits.
The role of the C-terminal helix of U1A protein in the interaction with U1hpII RNA

Previous kinetic investigations of the N-terminal RNA Recognition Motif (RRM) domain of spliceosomal A protein of the U1 small nuclear ribonucleoprotein particle (U1A) interacting with its RNA target U1 hairpin II (U1hpII) provided experimental evidence for a ‘lure and lock’ model of binding. The final step of locking has been proposed to involve conformational changes in an α-helix immediately C-terminal to the RRM domain (helix C), which occludes the RNA binding surface in the unbound protein. Helix C must shift its position to accommodate RNA binding in the RNA–protein complex. This results in a new hydrophobic core, an intraprotein hydrogen bond and a quadruple stacking interaction between U1A and U1hpII. Here, we used a surface plasmon resonance-based biosensor to gain mechanistic insight into the role of helix C in mediating the interaction with U1hpII. Truncation, removal or disruption of the helix exposes the RNA-binding surface, resulting in an increase in the association rate, while simultaneously reducing the ability of the complex to lock, reflected in a loss of complex stability. Disruption of the quadruple stacking interaction has minor kinetic effects when compared with removal of the intraprotein hydrogen bonds. These data provide new insights into the mechanism whereby sequences C-terminal to an RRM can influence RNA binding.
Incomplete capsule endoscopy examinations after Roux-en-Y gastric bypass

Video capsule endoscopy is an important tool for minimally invasive evaluation of the small bowel. Optimization of this imaging modality has focused on minimizing the rate of incomplete studies through appropriate patient selection. Recent data have shown an increased incidence of incomplete examinations in those with surgically altered gastrointestinal anatomy. We present 4 consecutive cases of post Roux-en-Y gastric bypass patients undergoing video capsule endoscopy. Three patients were referred for obscure gastrointestinal bleeding and one for diagnosis of Crohn’s disease; all 4 patients had incomplete studies. One patient experienced capsule retention in the gastric pouch. Two patients had repeated poor small bowel preparation despite compliance with preparatory methods. The fourth patient experienced delayed gastrointestinal transit despite satisfactory small bowel preparation. Patients with a history of Roux-en-Y surgery appear to be at increased risk for incomplete examination due to capsule retention and delayed gastric transit. Endoscopists may consider additional precursory testing or the use of alternative imaging methods in this population.
Transformation of immortalized woodchuck hepatic cell lines with the c-Ha-ras proto-oncogene.

Woodchuck hepatocytes were immortalized with the simian virus 40 T antigen (SV40 T-ag) oncogene and utilized in an oncogenic transformation assay. Transfection of these cell lines with an activated c-Ha-ras oncogene (EJ6.6) resulted in the transformation of cells to a phenotype characterized by anchorage-independent growth in soft agar. Colonies of transformed cells were subcloned and up to 80% were positive for oncoprotein expression detected by immunoblot and Northern blot procedures. When compared with the parental cell lines, ras-transformed derivatives were altered both morphologically and in growth rate. The tumorigenic potential of c-Ha-ras transformed cells was demonstrated in severe combined immunodeficient (SCID) mice. There was a latency period of 1 to 4 weeks before tumors were detectable and a period of over 7 weeks was required for tumors to reach a diameter of 1 cm. Histologically, tumors derived from cell lines fully transformed by the SV40 T-ag had the appearance of well-differentiated hepatocellular carcinoma (HCC) while tumors derived from c-Ha-ras transformed cell lines had the appearance of poorly differentiated HCC. The capacity to induce oncogenic transformation events in immortalized woodchuck hepatic cell lines should provide the opportunity to study the cooperative effects of hepadnaviral genes in hepatocarcinogenesis in vitro.
Reading newsprint but not headlines: pitfalls in measuring visual acuity and color vision in patients with bullseye maculopathy and other macular scotomas.

To illustrate the confounding factors when assessing visual acuity and color vision in a patient with a bullseye macular scotoma in one eye and a horseshoe of atrophy sparing the fovea in the fellow eye. Case report. Visual acuity, color vision, and scanning laser ophthalmoscope analysis. The patient with geographic atrophy from age-related macular degeneration in both eyes had visual acuity of 20/40– in the right eye and 20/40+ in the left eye. She reported that she could read newsprint but not news headlines. She could not identify any color plates, but had only minor errors using a color cap (large D-15) test. She had a macular ring scotoma (bullseye scotoma) in the right eye, and a horseshoe-shaped area of atrophy surrounding the fovea in the fellow eye. Scotomas surrounding but sparing the fovea can lead to difficulty reading large letters, because these letters do not fit in the spared foveal region. Care must be taken in measuring visual acuity in these patients so that the testing does not stop when the patient cannot read the largest letters. The presence of scotomas in the central field may not allow the whole figure on color plate testing to be integrated and identified, leading to a possible misdiagnosis of cone dystrophy. Color cap testing avoids this problem.
The range of intentions

Four groups of intentional action sentences can be distinguished. An intentional action sentence belongs in a given group as a consequence of the range of intentions, i.e. it may record an action in which someone intends that he should intentionally do something in a particular manner, for a particular purpose, to a particular object, or it may record an action in which someone intends that he should intentionally do something though he intends no particular manner or no manner at all and intends no particular object. Thus the range of intention affects entailments, compatibility and inconsistency among intentional action sentences. A fragment of a theory of the range of intentions is set out and some of its implications are examined.
Adaptive variable reordering for symbolic model checking

In this paper, we present an adaptive dynamic variable ordering paradigm which is application-dependent and intended for symbolic model checking applications. The impact of the adaptive variable reordering approach is demonstrated on circuits from Intel's next-generation micro-processors. On large circuits, in particular, our algorithms make verification tasks that would never end finish successfully in a reasonable amount of time. Our approach, to the best of our knowledge, pioneers in applying successfully ROBDD-independent and application-specific heuristics to the domain of dynamic variable reordering.