cssi/SciSciGPT-SciSciNet huggingface dataset:
Abstract 473: A tumor and immune related miRNA signature predicts progression-free survival of melanoma patients treated with ipilimumab

Background Patients with regionally advanced melanoma were treated with neoadjuvant ipilimumab in a previously reported study (Tarhini et al, PLOS One 2014). MicroRNA (miRNA) expression profiles of tumors of treated patients were investigated for their therapeutic predictive value. Methods Patients were treated with ipilimumab (10 mg/kg IV every 3 weeks x2 doses) bracketing surgery. Tumor specimens were obtained at baseline and following ipilimumab at definitive surgery (week 6-8). MiRNA expression profiling was performed on the tumor biopsies of 30 patients using Affymetrix miRNA array (v.4). Significance Analysis of Microarrays (SAM) was performed to test the association of each differentially expressed miRNA molecule with outcome. Targets of the selected miRNAs were obtained from miRTarBase (http://mirtarbase.mbc.nctu.edu.tw). Functional annotation analysis of the list of miRNA target genes were performed using DAVID (https://david.ncifcrf.gov). The FDR method was used to adjust for multiple testing in SAM and the functional analysis. Results An expression profile consisting of a 4-miRNA signature was associated with improved progression free survival. The signature consisted of miR-34c (previously reported to suppress cancer growth and invasion), miR-711 (reported as a prognostic marker in cutaneous T-cell lymphomas and to target and suppress Heat Shock Protein 70 highly expressed in melanoma), miR-641 (activates MAPK by targeting NF1 and cooperates with its host gene AKT2 in human cancer) and miR-22 (reported to function as a tumour suppressor). Functional annotation analysis of target genes for the 4-miRNA signature was statistically significantly enriched for various cancer-related pathways including regulation of cell proliferation (GO:0042147), regulation of apoptosis (GO:0042981), MAPK signaling pathway (hsa04010) and positive regulation of T cell activation (GO:0050870). Conclusions MiRNA expression profiling identified a 4-miRNA signature that is significantly associated with PFS in advanced melanoma patients treated with neoadjuvant ipilimumab. Preliminary results show that targets of these 4 miRNAs are biologically relevant and important. These findings warrant further investigation in relation to ipilimumab and other immunotherapeutics. Citation Format: Ahmad Tarhini, Priyanka Vallabhaneni, Theofanis Floros, William A. LaFramboise, Panayiotis V. Benos, Lucas Santana dos Santos. A tumor and immune related miRNA signature predicts progression-free survival of melanoma patients treated with ipilimumab. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr 473.
Normal, Regular and Standard: Scaling the Body through Fecal Microbial Transplants

In 2013, the National Institutes of Health (NIH) and the Food and Drug Administration (FDA) held a workshop to determine the risks and benefits associated with the experimental use of fecal microbial transplants to treat Clostridium difficile and other gastroenterological disorders. By focusing on the proceedings of the NIH-FDA workshop on the treatment of the human microbiome, the question of how medicine colonizes human bodies through microbial transplants raises questions about what an individual body is, how determinative of human health the microbiome is, and what the limits of molecular biomedicine are when the microbiome is taken into consideration. In the workshop presentations and discussion of this emerging treatment, experts used ideas about the normal, regular, and standard to move between scales of bodily analysis, from the microbial to the body politic, demonstrating how the individual and society are deeply influenced by the unruly community of microbial symbiotes that humans host.
Organization and Evolution of the Neural Control of the Hand in Primates: Motor Systems, Sensory Feedback, and Laterality

Hands play an important role in the lives of primates. They use their hands to explore their surroundings, obtain food, and interact with social partners. Although primates are very diverse, the capacity for dexterous control of the hands is one of the features that distinguish them from other mammals. There is no single brain area that is solely responsible for motor control of the hand, but rather a number of neural structures that are strongly interconnected, acting together to coordinate arm and hand movements. The neural control of the hand is hierarchically organized, with several structures of the brain contributing to different aspects of planning and execution of the hand movement sequences. In primates, there is significant variation in manual ability, with some species being more dexterous than others. These behavioral differences are related to variation in the complexity of the sensorimotor systems of these species. Lateralization of hand use is another manifestation of motor specialization in primates. Although very pronounced in humans, species-level handedness might not be restricted to us and may be evident in other species as well. Both human and nonhuman primate data show that asymmetry in hand use is related to both macrostructural and microstructural differences in the organization of the motor cortex. These differences may be important for neurobiological and cognitive developments that made possible tool use and manufacture in certain primate species, including humans.
Zebrafish Neurotoxicity Models

The field of neurotoxicology is confronted with two significant demands: the testing of an ever increasing list of chemicals, and resource limitations/ethical concerns associated with testing using traditional mammalian species. National and international government agencies have well-defined a need to reduce, refine or replace mammalian species in toxicological testing with alternative testing methods and non-mammalian models. Toxicological assays using alternative animal models may relieve some of this pressure by allowing testing of more compounds while reducing expense and using fewer mammals. Recent advances in genetic technologies and the strong conservation between human and non-mammalian genomes allow for the dissection of the molecular pathways involved in neurotoxicological responses using genetically tractable organisms such as zebrafish (Danio rerio). A constantly increasing database on basic developmental biology, gene transfers, and the rich foundation of molecular genetic and genomic data make zebrafish a powerful modeling system for revealing mechanisms in neurotoxicology. In contrast to the highly advanced knowledge base on molecular developmental genetics in zebrafish, the databases regarding pathologic lesions in zebrafish lag far behind the information available on most other domestic mammalian and avian species, particularly rodents. Therefore, to fully utilize the potential of zebrafish as an animal model for understanding neurotoxicological influences on human development and disease we must greatly advance our knowledge on zebrafish diseases and pathology.
Diagnostic Performance of SRU and ATA Thyroid Nodule Classification Algorithms as Tested With a 1 Million Virtual Thyroid Nodule Model.

Purpose The Society of Radiologists in Ultrasound (SRU 2005) and American Thyroid Association (ATA 2009 and ATA 2015) have published algorithms regarding thyroid nodule management. Kwak et al. and other groups have described models that estimate thyroid nodules’ malignancy risk. The aim of our study is to use Kwak’s model to evaluate the tradeoffs of both sensitivity and specificity of SRU 2005, ATA 2009 and ATA 2015 management algorithms. Materials and Methods 1,000,000 thyroid nodules were modeled in MATLAB. Ultrasound characteristics were modeled after published data. Malignancy risk was estimated per Kwak’s model and assigned as a binary variable. All nodules were then assessed using the published management algorithms. With the malignancy variable as condition positivity and algorithms’ recommendation for FNA as test positivity, diagnostic performance was calculated. Results Modeled nodule characteristics mimic those of Kwak et al. 12.8% nodules were assigned as malignant (malignancy risk range of 2.0-98%). FNA was recommended for 41% of nodules by SRU 2005, 66% by ATA 2009, and 82% by ATA 2015. Sensitivity and specificity is significantly different ( Conclusion SRU 2005, ATA 2009 and ATA 2015 algorithms are used routinely in clinical practice to determine whether thyroid nodule biopsy is indicated. We demonstrate significant differences in these algorithms’ diagnostic performance, which result in a compromise between sensitivity and specificity.
Analysis of ischemic muscle in patients with peripheral artery disease using X-ray spectroscopy.

Abstract Background Peripheral artery disease (PAD) is a vascular disease caused by atherosclerosis, resulting in decreased blood flow to the lower extremities. The ankle-brachial index (ABI) is a standard PAD diagnostic test but only identifies reduced blood flow based on blood pressure differences. The early signs of PAD manifest themselves not only at a clinical level but also at an elemental and biochemical level. However, the biochemical and elemental alterations to PAD muscle are not well understood. The objective of this study was to compare fundamental changes in intracellular elemental compositions between control, claudicating, and critical limb ischemia muscle tissue. Materials and methods Gastrocnemius biopsies from three subjects including one control (ABI ≥ 0.9), one claudicating (0.4 ≤ ABI Results This study revealed that intracellular magnesium and calcium were lower in PAD compared with control myofibers, whereas sulfur was higher. Magnesium and calcium are antagonistic, meaning, if magnesium concentrations go down calcium concentrations should go up. However, our findings do not support this antagonism in PAD. Our analysis found decreases in sodium and potassium, in PAD myofibers. Conclusions These findings may provide insight into the pathologic mechanisms that may operate in ischemic muscle and aid in the development of specialized preventive and rehabilitative treatment plans for PAD patients.
Management and Treatment of Iliocaval Thrombosis Using Endovascular Recanalization, Stenting, and Reconstruction: What All Practitioners Should Know

Abstract Thrombosis of the inferior vena cava and iliac veins is a significant cause of morbidity, with many patients suffering from painful lower extremity swelling, recurrent deep venous thrombosis, and venous stasis ulcers. Recanalization and stenting of the deep venous system has been shown to be a viable option for patients who fail conservative management. Clinical response and stent patency rates are encouraging for high-volume centers but are less so for smaller patient series, suggesting that the materials and techniques required are specialized and challenging. This article discusses the experience and current literature surrounding iliocaval reconstruction for the treatment of symptomatic iliocaval thrombosis, including preprocedural evaluation, interventional techniques, postprocedural care, and outcomes.
Securing U.S. Election Systems: Designating U.S. Election Systems as Critical Infrastructure and Instituting Election Security Reforms

The cyber intrusions by Russia into U.S. political parties’ servers and state electoral databases as well as the broad Russian disinformation campaign during the 2016 presidential election has put the issue of election security at the forefront. While these intrusions into the U.S.’s political process by a foreign adversary are extremely disconcerting, fortunately, the election itself was not hacked. The U.S. must respond to the increasing threat that future elections may be hacked, though, and take action to secure our election systems now. U.S. election systems face a variety of credible threats. Voter registration systems are the most vulnerable because these databases are often maintained online, which makes them susceptible to manipulation by illicit actors. Voting systems are also vulnerable to attacks to voting machines, overseas voting that occurs electronically, and the tabulation of votes. Threats to voting systems are most severe when there is no paper trail to recount or audit, and a number of states indeed use voting machines that do not produce any paper trail. The current security mechanisms are insufficient to defend against current and future threats. Designating U.S. election systems as critical infrastructure enables federal agencies involved in elections and cybersecurity to assist states and localities with assessing vulnerabilities, mitigating vulnerabilities, improving resilience, and improving coordination in cybersecurity. While some have alleged this designation is an unconstitutional assumption of power by the federal government, designating election systems as critical infrastructure is in fact constitutional. Also, states should make immediate improvements to election systems and develop contingency plans to enhance resilience in the event of a cyberattack. Further, the federal government should take additional actions to improve our election systems’ security across the country. Maintaining the integrity of our electoral process is vital to our democracy.
Membrane perturbation by bile acids causes signal transduction

2743 Bile acids have been implicated as tumor promoters that may be involved in colon tumorigenesis. We have demonstrated that bile acids are cytotoxic to the colonic epithelium and activate several signaling pathways in colon cancer-derived cell lines. We have examined the genesis of bile acid signaling and found that signaling may be activated by perturbing the plasma membrane. Here we examined the effect of bile acids on the membranes of HCT116 cells. Examination of caveolae, specialized membrane domains known to contain a variety of signaling molecules by density sucrose gradients revealed that deoxycholic acid (DCA) depleted the membrane of caveolin-1. In addition, β-actin a protein known to be localized in caveolae was also displaced upon treatment with DCA. In contrast, treating with ursodeoxycholic acid (UDCA), a chemopreventive bile acid, resulted in a slight increase of caveolin-1. Cholesterol, a major constituent of caveolae was also examined since an intermolecular interaction exists between cholesterol and caveolin-1, the coat protein of caveolae. A role for cholesterol was also suggested in DCA-induced signaling since DCA caused a sharp increase in membrane cholesterol and depleting membrane cholesterol with Methyl-β-Cyclodextrin suppressed DCA-induced apoptosis. Since bile acids are cholesterol derivatives, we hypothesize that bile acids may be acting on the membrane by displacing cholesterol and interfering with the negative regulatory function of caveolin-1 on signal transduction.
Water Transport across ADH-Sensitive Epithelia

Several epithelia are virtually water-impermeable under at least certain physiological or experimental conditions. In the mammalian urinary pathway examples include all segments of the renal tubule beyond the bend of the loop of Henle and all segments of the urinary tract from the renal pelvis to the urethra. In amphibia, epithelial preparations that exhibit a very low osmotic water permeability (Pos) under control conditions include the anuran epidermis and urinary bladder (e.g., of frog and toad). Under the action of a variety of peptide hormones collectively named antidiuretic hormones (ADHs), some of these epithelia increase their water permeability dramatically. In the presence of a favorable transepithelial difference in osmotic pressure, this change in permeability results in water reabsorption and is one of the major mechanisms of water conservation. Epithelia sensitive to ADH include the cortical and medullary collecting ducts of the mammalian kidney, the frog and toad urinary bladders and epidermis, and others. In mammals, both the thin and the thick ascending loop of Henle and also the epithelia of the urinary tract distal to the papillary duct do not respond to ADH with an increase in osmotic water permeability. However, salt transport by the thick ascending loop of Henle is sensitive to ADH.
Parallel Implementation of a Commonly Used Internal Combustion Engine Code

Abstract KIVA-3, a widely used computational fluid dynamics code for internal combustion engine simulations, was re-structured for parallel execution via one-dimensional domain decomposition. Communication between processors at the subdomain boundaries is carried out with MPI message-passing library which enabled significant flexibility in porting the distributed-memory implementation of KIVA-3 to various architectures ranging from SGI Origin 2000 to Cray T3E and recently a Beowulf cluster. Due to the complex features incorporated into KIVA-3, the parallelization was done in stages. This paper presents results from the first stage where the speedup and parallel efficiency of the parallel version of KIVA-3 are elucidated.
Reliability and Validity of a Two-Question Version of the World Health Organization's Alcohol, Smoking and Substance Involvement Screening Test: The ASSIST-FC.

Objective The Alcohol, Smoking and Substance Involvement Screening Test (ASSIST), developed for the World Health Organization (WHO), screens for risks associated with the use of tobacco, alcohol, and seven categories of drugs. Although the ASSIST has acceptable psychometric properties, it is relatively long for a screening test. This study was designed to identify a subset of questions from the full ASSIST instrument having comparable psychometric properties for the classification of low-, moderate-, and high-risk substance use. Method The study used three data sets from prior studies using the WHO ASSIST. Samples 1 and 3 were obtained from WHO multisite studies conducted in seven countries. Sample 2 included patient data from a U.S.-based screening and brief intervention program that incorporated the ASSIST into its clinical protocol. Samples 1 and 2 were used to conduct psychometric analyses for combinations of ASSIST items. Sample 3 was used to estimate sensitivity, specificity, and positive and negative predictive value for a two-item ASSIST. Results Based on correlation statistics, reliability metrics, and validation analyses, a new, two-item version is proposed. The ASSIST-FC contains one question about the frequency (F) of current use and a second question about current or past concern (C) expressed by others. The ASSIST-FC demonstrates no substantial loss in reliability, validity, and predictive ability when statistically compared with the full-length ASSIST. Conclusions The ASSIST-FC has advantages for clinical applications in settings where a brief, efficient, reliable screening test is needed to identify patients with hazardous and harmful substance use who would benefit from a brief intervention. It can also be used to identify patients who are manifesting symptoms of substance dependence that would require further diagnostic evaluation.
On the combinability of evidence in the Dempster-Shafer theory

In the current versions of the Dempster-Shafer theory, the only essential restriction on the validity of the rule of combination is that the sources of evidence must be statistically independent. Under this assumption, it is permissible to apply the Dempster-Shafer rule to two or more distinct probability distributions. An essential step in the Dempster-Shafer rule of combination of evidence is that of normalization. The validity of normalization is open to question, particularly in application to probability distributions (Zadeh, 1976). At this juncture, the validity of normalization is a controversial issue. In this paper, we construct a relational model for the Dempster-Shafer theory which greatly simplifies the derivation of its main results and cast considerable light on the validity of the rule of combination. The relational model is augmented with what is called the ball-box analogy, yielding an intuitively simple way of visualizing the concepts of belief and plausibility.
Superior Mesenteric Vein-First Approach for Robotic Salvage Surgery with Indocyanine Green Fluorescence Angiography

Inadequate lymphadenectomy is still a major concern in colon cancer surgery. The superior mesenteric vein (SMV)-first approach is a novel, standardized, reproducible method for robotic complete mesocolic excision surgery. Our aim was to present the application of the SMV-first approach principles to facilitate robotic salvage surgery for recurrent disease within the mesocolon. A 78-year-old female presented with a malignant lymph node deposit within residual right mesocolonic tissue, approximately 3 months following a laparoscopic right hemicolectomy for colon cancer. Dissection was initiated with a transverse curvilinear incision along the inferior aspect of the remaining ileocolic pedicle to identify the SMV. Dissection continued along the ventral aspect of the SMV in a cephalad direction to identify and expose the middle colic vessels at their origin. The use of idocyanine green (ICG) confirmed the vascular anatomy, demonstrating the right branch of the middle colic artery traversing the malignant deposit in the residual mesocolon. Following ligation at the origin of the right branch of the middle colic and ileocolic vessels, the retro-mesocolic plane dissection was completed to excise the malignant deposit and the residual mesocolon. The patient was discharged home the following day. The pathological specimen confirmed metastatic poorly differentiated adenocarcinoma in one of nine lymph nodes, and the vascular pedicle resection margin was negative for tumor. Following the SMV-first approach principles provides a safe plane for dissection, and, in conjunction with ICG, facilitates the delineation of the vascular anatomy, to enable robotic salvage surgery to be performed.1–3
Chapter 18 – Air Pollution: Atmospheric Wastes

Publisher Summary Air pollution is the presence of contaminants or substances in the air that interfere with human health or welfare, or produce other harmful environmental effects. This chapter focuses on the waste streams that affect the atmosphere. The predominant concern with atmospheric waste is chemical contamination, which presents a hazard to human health. Thus, public health is usually the principal driver for assessing and controlling air contaminants. However, air pollution abatement laws and programs have also recognized that effects beyond health are also important, especially welfare protection. One of the main welfare considerations is that ecosystems are important receptors of contamination. Another welfare concern is that contaminants impact structures and other engineered systems by corrosion. Thus, from an air pollution perspective, there is a cascade of hazards from human health to ecosystems to abiotic (i.e., nonliving) systems. As far as pollution control is concerned, air pollution control must be strategic and tactical. The former is the long-term reduction of pollution levels at all scales of the problem from local to global. Goals can be set for air quality improvement 5, 10, or 15 years ahead and plans can be made to achieve these improvements.
Identification of risk for posttraumatic stress disorder symptom clusters early after trauma

The current study examined how the injured trauma survivor screen (ITSS), a hospital-administered screener of posttraumatic stress disorder (PTSD) and depression, differentially predicted PTSD symptom cluster severity. Participants from a Level 1 trauma center (n = 220) completed the ITSS while inpatient and PTSD symptoms were assessed one-month post discharge. Perceived life threat and intentionality of injury were key predictors of avoidance, re-experiencing, and hyperarousal symptom clusters. However, negative alterations in mood and cognition cluster seemed best predicted by mood and cognitive risk factors. Therefore, the ITSS provides utility in differentially predicting symptom clusters and treatment planning after traumatic injury.
iSeeYou: disabling the MacBook webcam indicator LED

The ubiquitous webcam indicator LED is an important privacy feature which provides a visual cue that the camera is turned on. We describe how to disable the LED on a class of Apple internal iSight webcams used in some versions of MacBook laptops and iMac desktops. This enables video to be captured without any visual indication to the user and can be accomplished entirely in user space by an unprivileged (non-root) application. The same technique that allows us to disable the LED, namely reprogramming the firmware that runs on the iSight, enables a virtual machine escape whereby malware running inside a virtual machine reprograms the camera to act as a USB Human Interface Device (HID) keyboard which executes code in the host operating system. We build two proofs-of-concept: (1) an OS X application, iSeeYou, which demonstrates capturing video with the LED disabled; and (2) a virtual machine escape that launches Terminal.app and runs shell commands. To defend against these and related threats, we build an OS X kernel extension, iSightDefender, which prohibits the modification of the iSight's firmware from user space.
Augmenting looking, pointing and reaching gestures to enhance the searching and browsing of physical objects

In this paper we present a framework for attaching information to physical objects in a way that can be interactively browsed and searched in a hands-free, multi-modal, and personalized manner that leverages users' natural looking, pointing and reaching behaviors. The system uses small infrared transponders on objects in the environment and worn by the user to achieve dense, on-object visual feedback usually possible only in augmented reality systems, while improving on interaction style and requirements for wearable gear. We discuss two applications that have been implemented, a tutorial about the parts of an automobile engine and a personalized supermarket assistant. The paper continues with a user study investigating browsing and searching behaviors in the supermarket scenario, and concludes with a discussion of findings and future work.
Parenting Stress, Dinnertime Rituals, and Child Well-being in Working-Class Families

This study examined the extent to which family dinnertime rituals serve a protective role for families experiencing high levels of stress. Using data from a longitudinal study of working-class couples, the role of dinnertime rituals as a moderator of mothers' and fathers' parenting stress and child psychosocial outcomes was investigated. Greater dinnertime rituals reported by fathers moderated the effect of parenting stress on internalizing problems for girls, but not for boys. Fathers' reports of dinnertime rituals were related to fewer behavioral symptoms, internalizing problems and externalizing problems, and greater adaptive skills for girls. No significant interaction effects for mothers' parenting stress or rituals were found, but there were significant main effects of mothers' parenting stress and dinnertime rituals on child outcomes. These findings suggest that dinnertime rituals can potentially moderate the effects of parenting stress on child outcomes and fathers and daughters showed the greatest benefits of these family practices.
Therapy of acute rheumatic fever.

Sixty-two children with acute rheumatic fever were treated with either ACTH, cortisone, salicylates or bed rest alone. Data concerning the effect on acute symptoms and follow-up observations of residual cardiac murmurs are presented. In addition, similar follow-up data on 18 previously-reported patients treated with ACTH are presented. Joint symptoms responded somewhat more rapidly to ACTH or cortisone than to salicylates, but an impressive response occurred to all of the drugs. Fever subsided within a few hours to 2 days in almost all individuals treated with any of these drugs. Elevated erythrocyte sedimentation rates returned to normal much more rapidly in the ACTH (mean 16 days) and cortisone (mean, 12 days) groups than in the salicylate (mean, 43 days) or bed-rest (mean, 48 days) groups. Although laboratory evidence of "rebound" in the form of an elevation of erythrocyte sedimentation rate occurred in 52 per cent of patients in the hormone-treated groups upon reduction or withdrawal of therapy, clinical evidence of "rebound" was rare in these groups but relatively common among the salicylate-treated patients. After follow-up periods as long as 3 9/12 years, residual cardiac murmurs were rare in the hormone-treated patients as compared to those treated with salicylates or with bed rest alone. Three years after discharge from the hospital, 6 per cent of the hormone-treated patients and 82 per cent of those not treated with hormones had residual cardiac murmurs. Moreover, the appearance of new murmurs following discharge was rare in the hormone groups and the murmurs which appeared were not persistent. New, persistent murmurs were noted relatively commonly following treatment with salicylates or bed rest alone. The importance of adequate dosage and individualization in therapy of rheumatic fever with ACTH and cortisone is stressed. The conclusions drawn are: the optimal initial doses of ACTH and cortisone are at least 1 I.U. and 3 mg. per pound per day, respectively; the initial daily dose should be continued until all laboratory and clinical evidence of rheumatic activity has disappeared; and then therapy should be decreased gradually but only if the patient shows no evidence of reactivation of rheumatic fever.
A simplified method for postmortem coronary angiography using gastrograffin.

Abstract Objective.—To assess the adequacy of perfusion of the heart at autopsy with a gastrograffin and dye mixture to obtain rapid postmortem angiograms while simultaneously documenting the vascular distribution of the myocardium. Background.—Postmortem coronary angiography is occasionally used in the evaluation of suspected cardiac deaths. Angiography provides legal documentation and can serve to guide subsequent cardiac dissection. Multiple techniques have been suggested in the literature for coronary angiography using infusion of radio-opaque silicone or gelatin. These techniques are cumbersome and require equipment generally not available in autopsy suites. Methods.—Following removal of the heart, a mixture of gastrograffin and colored dyes is injected into each coronary artery via a syringe. The coronary arteries are ligated and radiographs are obtained. After fixation, the heart is dissected in the usual manner. Results.—Adequate postmortem coronary angiograms are routinely obtained with this meth...
Two different secondary metabolism gene clusters occupied the same ancestral locus in fungal dermatophytes of the arthrodermataceae.

Background: Dermatophyte fungi of the family Arthrodermataceae (Eurotiomycetes) colonize keratinized tissue, such as skin, frequently causing superficial mycoses in humans and other mammals, reptiles, and birds. Competition with native microflora likely underlies the propensity of these dermatophytes to produce a diversity of antibiotics and compounds for scavenging iron, which is extremely scarce, as well as the presence of an unusually large number of putative secondary metabolism gene clusters, most of which contain non-ribosomal peptide synthetases (NRPS), in their genomes. To better understand the historical origins and diversification of NRPS-containing gene clusters we examined the evolution of a variable locus (VL) that exists in one of three alternative conformations among the genomes of seven dermatophyte species. Results: The first conformation of the VL (termed VLA) contains only 539 base pairs of sequence and lacks protein-coding genes, whereas the other two conformations (termed VLB and VLC) span 36 Kb and 27 Kb and contain 12 and 10 genes, respectively. Interestingly, both VLB and VLC appear to contain distinct secondary metabolism gene clusters; VLB contains a NRPS gene as well as four porphyrin metabolism genes never found to be physically linked in the genomes of 128 other fungal species, whereas VLC also contains a NRPS gene as well as several others typically found associated with secondary metabolism gene clusters. Phylogenetic evidence suggests that the VL locus was present in the ancestor of all seven species achieving its present distribution through subsequent differential losses or retentions of specific conformations. Conclusions: We propose that the existence of variable loci, similar to the one we studied, in fungal genomes could potentially explain the dramatic differences in secondary metabolic diversity between closely related species of filamentous fungi, and contribute to host adaptation and the generation of metabolic diversity.
Local recovery and failure masking for stencil-based applications at extreme scales

Application resilience is a key challenge that has to be addressed to realize the exascale vision. Online recovery, even when it involves all processes, can dramatically reduce the overhead of failures as compared to the more traditional approach where the job is terminated and restarted from the last checkpoint. In this paper we explore how local recovery can be used for certain classes of applications to further reduce overheads due to resilience. Specifically we develop programming support and scalable runtime mechanisms to enable online and transparent local recovery for stencil-based parallel applications on current leadership class systems. We also show how multiple independent failures can be masked to effectively reduce the impact on the total time to solution. We integrate these mechanisms with the S3D combustion simulation, and experimentally demonstrate (using the Titan Cray-XK7 system at ORNL) the ability to tolerate high failure rates (i.e., node failures every 5 seconds) with low overhead while sustaining performance, at scales up to 262144 cores.
The impact of seasonality on the benthos as reflected in the assemblages of deep-sea foraminifera

A surface sediment study of benthic foraminiferal assemblages in the eastern Pacific (Loubere, 1994) yielded a regression equation for estimating surface ocean productivity from assemblage composition with an r2=0.98. This equation was tested with samples from locations outside the calibration data set area and yielded estimates with an error of about 11% of the estimate. The estimation equation has an r2=0.86 for the non-calibration data set samples. This equation was then applied to surface sediment samples from the Indian Ocean, which represent benthic conditions identical to those of the Pacific calibration data set, except that surface ocean productivity in the Indian Ocean is highly seasonal. There is relatively little seasonal variation in productivity over the areas sampled for the Pacific calibration data. Although it is difficult to quantify average annual surface ocean productivity in the Indian Ocean, it appears that the benthic foraminiferal transfer function yields estimates of only qualitative value. At highest productivities it is likely that the equation underestimates productivity. Using Discriminant Function Analysis to compare sample groups from the Pacific and Indian Oceans representing identical environmental conditions, except for seasonality, shows that the Indian Ocean samples are increasingly anomalous, or “no-analog”, from the Pacific Ocean perspective as productivity increases. At higher productivities, Indian Ocean samples are deficient in Uvigerina species, Chilostomella sp., Pullenia sp. and E. tumidulus while having an excess of E. exigua, C. hooperi, Gyroidina grp. species, B. mexicana and Nonion species, from the Pacific viewpoint. The differences in benthic foraminiferal assemblages between the two oceans can be ascribed to changes in benthic community structure that occur as organic carbon flux to the seabed becomes increasingly episodic or seasonal. Overall, Indian Ocean foraminiferal assemblages follow compositional trends similar to those seen in the Pacific Ocean as surface productivity changes. Hence, a Pacific based benthic foraminiferal transfer function can still reasonably estimate productivity gradients from Indian Ocean assemblages. However, there are 4 sufficient assemblage differences between the two oceans to make seasonality a variable that should be incorporated in a calibration data set, and to make estimation of paleo-seasonality a possibility.
Thymoma and parathyroid adenoma: false-positive imaging and intriguing laboratory test results.

Importance Parathyroid hormone (PTH)–secreting thymomas are an exceedingly rare entity. A PTH-secreting thymoma was discovered in the workup of a patient with primary hyperparathyroidism. A concomitant parathyroid adenoma was removed from the same patient. We present the intriguing clinical course and review the literature on this rare entity. In addition, we discuss the use of scanning with technetium Tc 99m sestamibi, the PTH assay, and cervical ultrasonography in the workup of a parathyroid adenoma. Observations Scanning with technetium Tc 99m sestamibi demonstrated false-positive uptake of the mediastinal thymoma and false-negative uptake of the true cervical parathyroid adenoma. After removal of the thymoma, the parathyroid adenoma demonstrated appropriate uptake on a follow-up scan. After removal of the parathyroid adenoma, the hyperparathyroidism was cured. Conclusions and Relevance Given the extremely rare incidence of a PTH-secreting thymoma with a concurrent parathyroid adenoma, we do not recommend alterations in the diagnostic algorithm for primary hyperparathyroidism. However, in this case, the need for 2 separate operations may have been avoided by obtaining an ultrasonogram to further explore the findings on the technetium Tc 99m sestamibi scan. We recommend that both studies be considered in unclear cases of primary hyperparathyroidism.
Postnatal development of neurogenic inflammation in the rat.

Abstract We have studied the development in the rat of neurogenic inflammatory mechanisms that mediate cutaneous plasma extravasation. At birth and at postnatal day 10, intradermal injection of substance P, histamine, and bradykinin produced no significant plasma extravasation. At day 13 through adulthood (days 42–49), all test agents produced significant plasma extravasation which increased with increasing age. In the adult rat, pretreatment with 6-hydroxydopamine, to eliminate sympathetic postganglionic nerve terminals, attenuated the plasma extravasation elicited by substance P, histamine and bradykinin. The possible role of the sympathetic postganglionic neuron in the age-dependent changes in neurogenic inflammation is discussed.
Identification of myeloid derived suppressor cells in the peripheral blood of tumor bearing dogs

Myeloid derived suppressor cells (MDSCs) are a recently described population of immune cells that significantly contribute to the immunosuppression seen in cancer patients. MDSCs are one of the most important factors that limit the efficacy of cancer immunotherapy (e.g. cancer vaccines) and MDSC levels are increased in cancer in multiple species. Identifying and targeting MDSCs is actively being investigated in the field of human oncology and is increasingly being investigated in veterinary oncology. The treatment of canine cancer not only benefits dogs, but is being used for translational studies evaluating and modifcying candidate therapies for use in humans. Thus, it is necessary to understand the immune alterations seen in canine cancer patients which, to date, have been relatively limited. This study investigates the use of commercially available canine antibodies to detect an immunosuppressive (CD11blow/CADO48low) cell population that is increased in the peripheral blood of tumor-bearing dogs. Commercially available canine antibodies CD11b and CADO48A were used to evaluate white blood cells from the peripheral blood cells of forty healthy control dogs and forty untreated, tumor-bearing dogs. Tumor-bearing dogs had a statistically significant increase in CD11blow/CADO48Alow cells (7.9%) as compared to the control dogs (3.6%). Additionally, sorted CD11blow/CADO48Alow generated in vitro suppressed the proliferation of canine lymphocytes. The purpose of this study was aimed at identifying potential canine specific markers for identifying MDSCs in the peripheral blood circulation of dogs. This study demonstrates an increase in a unique CD11blow/CADO48Alow cell population in tumor-bearing dogs. This immunophenotype is consistent with described phenotypes of MDSCs in other species (i.e. mice) and utilizes commercially available canine-specific antibodies. Importantly, CD11blow/CADO48Alow from a tumor environment suppress the proliferation of lymphocytes. These results provide a useful phenotype of cells increased in canine cancer patients that may serve as a useful prognostic marker for assessing immune status and functional response to cancer immunotherapies in dogs. Understanding MDSCs in dogs will allow for increased effectiveness of cancer immunotherapy in both dogs and humans.
The pc-1 phenotype of Chlamydomonas reinhardtii results from a deletion mutation in the nuclear gene for NADPH:protochlorophyllide oxidoreductase.

The pc-1 mutant of Chlamydomonas reinhardtii has been shown to be incapable of protochlorophyllide photoconversion in vivo and is thought to be defective in light-dependent NADPH:protochlorophyllide oxidoreductase activity. We have isolated and characterized the nuclear genes encoding this enzyme from wild-type and pc-1 mutant Chlamydomonas cells. The wild-type CRlpcr-1 gene encodes a 397 amino acid polypeptide of which the N-terminal 57 residues comprise the chloroplast transit sequence. The Chlamydomonas protochlorophyllide reductase has 66–70% identity (79–82% similarity) to the higher plant enzymes. Transcripts encoding protochlorophyllide reductase are abundant in dark-grown wild-type cells, but absent or at very low levels in cells grown in the light. Similarily, immunoreactive protochlorophyllide reductase protein is also present to a greater extent in dark-versus light-grown wild-type cells. Both pc-1 and pc-1 y-7 cells lack CRlpcr-1 mRNA and the major (36 kDa) immunodetectable form of protochlorophyllide reductase consistent with their inability to photoreduce protochlorophyllide. DNA sequence analysis revealed that the lpcr gene in pc-1 y-7 cells contains a two-nucleotide deletion within the fourth and fifth codons of the protochlorophyllide reductase precursor that causes a shift in the reading frame and results in premature termination of translation. The absence of protochlorophyllide reductase message in pc-1 and pc-1 y-7 cells is likely the consequence of this frameshift mutation in the lpcr gene. Introduction of the CRlpcr-1 gene into pc-1 y-7 cells by nuclear transformation was sufficient to restore the wild-type phenotype. Transformants contained both protochlorophyllide reductase mRNA and immunodetectable enzyme protein. These studies demonstrate that pc-1 was in fact a defect in protochlorophyllide reductase activity and provide the first in vivo molecular evidence that the lpcr gene product is essential for light-dependent protochlorophyllide reduction.
The relative effects of health and income on life satisfaction

The relative effects of health and income on life satisfaction were analyzed using data collected in three recent national surveys. Financial situation was a slightly stronger predictor of life satisfaction for persons under age sixty-five, whereas health condition had a stronger impact on the life satisfaction of persons over age sixty-four. An attempt was made to quantify the relative impact of health and income on life satisfaction through an analysis of conjoint influence with contingency tables.
The central amygdaloid nucleus innervation of the dorsal vagal complex in rat: a Phaseolus vulgaris leucoagglutinin lectin anterograde tracing study.

Abstract The central nucleus of amygdala (Ce) participates in expression of autonomic responses associated with fear or stress-related behaviors. The Ce can alter autonomie activity through its direct projection to the dorsal vagal complex [i.e., nucleus of the solitary tract (nTS) and the dorsal vagal nucleus]. In order to more precisely define the anatomical organization of the neurons within the Ce and their terminal fields within the dorsal vagal complex, the Phaseolus vulgaris leucoagglutinin lectin (PHA-L) anterograde tracing method was employed in rats. In cases where injections of PHA-L were centered within the medial Ce, dense axon terminal labeling was observed within the medial nTS at rostral levels. Terminal boutons were also observed within the ventral part of the lateral nTS, the dorsal vagal nucleus and contralateral medial nTS. At and just rostral to the obex, numerous axonal boutons were seen within the medial and commissural parts of the nTS and adjacent parts of the dorsal vagal nucleus. Contralateral axon terminal labeling was present within the medial and commissural parts of the nTS. Caudal to the obex, PHA-L immunoreactive boutons were concentrated bilaterally within the medial and commissural nTS and dorsal vagal nucleus. In cases where injections of PHA-L were centered within the lateral Ce moderate axon terminal labeling was observed throughout the rostrocaudal extent of the medial and commissural part of the nTS. Very few PHA-L immunoreactive terminals were observed within the ventral part of the lateral nTS, dorsal vagal nucleus and contralateral medial nTS. The results demonstrate that the medial Ce projects bilaterally to the medial and commissural subnuclei of the nTS and the dorsal vagal nucleus. The lateral Ce projects mainly to the ipsilateral medial and commissural nTS. Thus, both the medial and lateral Ce can directly influence regions of the nTS where peripheral cardiovascular, cardiopulmonary and gastric afferents terminate. The medial Ce can also directly affect vagal nerve outflow through its projection to neurons within the dorsal motor nucleus.
The Composition of Essential and Certain Nonessential Amino Acids in Selected Hawaii Fish

SUMMARY Essential amino acids were determined by column chromatography for 5 varieties of fish popular as food in Hawaii. Recoveries for the amino acids studied were good, ranging from 98.7 to 102.2%. The content of essential as well as certain nonessential amino. acids was uniform for all the fish investigated, and the values of valine were higher than cited by other authors. There was no marked difference in the essential amino acid composition of the octopus and the four vertebrates. The proportions of the essential amino acids were compared with the proportions in the FAO “Provisional Pattern” and whole egg protein, and the protein scores were calculated. Favorable comparisons were obtained with the FAO pattern. Leucine and phenylalanine were somewhat limiting for all fish when compared with whole egg protein. The content of nonessential amino acids (histidine, glycine, glutamic acid, alanine, and proline) was comparable with ranges reported for other fish.