cssi/SciSciGPT-SciSciNet huggingface dataset:
OR46 Detecting low level clonal somatic mutation in HLA genes using next-generation sequencing in the presence of aplastic anemia

Aim Next-generation sequencing (NGS) has assisted in the full characterization of HLA alleles, allowing in-depth studies of how these genes can play a direct role in the pathophysiology of many diseases outside of the context of transplantation. Here, we sought to determine the degree to which NGS can be used to characterize clonal somatic mutations acquired in HLA genes during the progression of aplastic anemia. Methods Omixon’s Holotype Kit was used to sequence HLA-A, B, C and DRB1 on the Illumina MiSeq targeting an ultra-high depth of coverage of 10,000 across the length of each gene. Omixon’s Twin, GenDx’s NGSengine and a custom pipeline analyzed the HLA allele data. The custom pipeline applies GATK’s best practices and tunes the ploidy parameter to lower the detection threshold of somatic mutations in each HLA allele to 10% of the depth. Results The pathogenesis of aplastic anemia, an autoimmune disease where cytotoxic T lymphocytes (CTL) destroy hematopoietic stem cells (HSC), most likely includes the recognition of a self-antigen in the context of a particular HLA allele by CTLs. Loss of heterozygosity of HLA alleles has been shown to allow HSCs to escape recognition of the CTLs, gaining a selective advantage in the disease state. In one mechanism of immune escape, HSCs acquire loss of function somatic mutations in the HLA allele(s) targeted by CTLs. By sequencing the HLA alleles of aplastic anemia patients, persistent somatic mutations were able to be detected above the background noise level. The frequency of mutations found in this dataset varied, but the lowest frequency mutation found was at 9% depth of coverage compared to the germline HLA allele. Mutations observed in HLA genes include the loss of a single or multiple HLA alleles in an individual by either frameshift mutations with insertions/deletions in exons or point mutations that introduce premature stop codons or mutate the translation start site. Interestingly, we can detect instances of different clones of somatic mutations causing loss of function in the same HLA allele of a single patient. Conclusion The combination of NGS with the Holotype HLA kit and multiple analysis tools, enables detection of clinically significant loss of function somatic mutations present in at least 10% of the depth for the targeted HLA allele in confirmed aplastic anemia cases. D.S. Monos: Scientific/Medical Advisor; Company/Organization; Omixon. Other (Identify); Company/Organization; Royalty from Omixon .
Monoclonal Antibody Based Immunofluorescent Assay for Giardia and Cryptosporidium Detection in Water Samples

Cryptosporidium and Giardia are enteric dwelling parasites that cause diarrheal illness. These parasites are present in numerous animal species and the potential zoonotic transmission to man via water is of increasing concern. Water samples collected from recreational sites throughout the State of Arizona were assayed for the presence of Giardia cysts and Crypto-sporidium oocysts using a qualitative presence/absence immunofluorescent assay with cell wall specific monoclonal antibodies developed in our laboratory. Seven percent of the water samples were positive for Giardia cysts while 30% were positive for Crvptosporidium oocysts. In addition, a quantitative assay was performed on each water sample for Cryptosporidium oocysts. The presence/absence qualitative immunofluorescent assay method proved to be a more efficient, sensitive and reliable means to detect these parasites in surface waters.
The Joy of Science: Seven Principles for Scientists Seeking Happiness, Harmony, and Success

We live in an age where working in science or engineering offers tremendous professional opportunities - the pace of scientific development is truly breathtaking. Yet many researchers struggle with the pressures of the fast-paced academic workplace, and struggle to harmonize their work and personal lives. The result can be burnout, exhaustion, and stress on a personal level, and difficulty in recruiting and retaining talented, diverse people to science and engineering. This book, written for graduate students and researchers at all stages of their careers, aims to help scientists by identifying and questioning the core beliefs that drive a culture of overwork, and provides real-world examples and exercises for those wishing to do things differently. Written in a lively narrative style, and including interview excerpts from practicing scientists, social scientists, and engineers, this book serves as a guide for those seeking to practice the seven traits of the joyful scientist.
(2 +1 ) -d Georgi-Glashow model near critical temperature

We study correlation functions of magnetic vortices $V$ and Polyakov loop $P$ operators in the $(2+1)$-dimensional Georgi-Glashow model in the vicinity of the deconfining phase transition. In this regime, the (dimensionally reduced) model is mapped onto a free theory of two massive Majorana fermions. We utilize this fermionic representation to explicitly calculate the expectation values of $V$ and $P$ as well as their correlators. In particular, we show that the $VV$ correlator is large, and thus the anomalous breaking of the magnetic $U(1)$ symmetry is order 1 effect in the near critical region. We also calculate the contribution of magnetic vortices to the entropy and the free energy of the system.
Energy-Aware Memory Mapping for Hybrid FRAM-SRAM MCUs in Intermittently-Powered IoT Devices

Forecasts project that by 2020, there will be around 50 billion devices connected to the Internet of Things (IoT), most of which will operate untethered and unplugged. While environmental energy harvesting is a promising solution to power these IoT edge devices, it introduces new complexities due to the unreliable nature of ambient energy sources. In the presence of an unreliable power supply, frequent checkpointing of the system state becomes imperative, and recent research has proposed the concept of in-situ checkpointing by using ferroelectric RAM (FRAM), an emerging non-volatile memory technology, as unified memory in these systems. Even though an entirely FRAM-based solution provides reliability, it is energy inefficient compared to SRAM due to the higher access latency of FRAM. On the other hand, an entirely SRAM-based solution is highly energy efficient but is unreliable in the face of power loss. This paper advocates an intermediate approach in hybrid FRAM-SRAM microcontrollers that involves judicious memory mapping of program sections to retain the reliability benefits provided by FRAM while performing almost as efficiently as an SRAM-based system. We propose an energy-aware memory mapping technique that maps different program sections to the hybrid FRAM-SRAM microcontroller such that energy consumption is minimized without sacrificing reliability. Our technique consists of eM-map, which performs a one-time characterization to find the optimal memory map for the functions that constitute a program and energy-align, a novel hardware-software technique that aligns the system’s powered-on time intervals to function execution boundaries, which results in further improvements in energy efficiency and performance. Experimental results obtained using the MSP430FR5739 microcontroller demonstrate a significant performance improvement of up to 2x and energy reduction of up to 20% over a state-of-the-art FRAM-based solution. Finally, we present a case study that shows the implementation of our techniques in the context of a real IoT application.
Fast 3D magnetic resonance fingerprinting for a whole-brain coverage.

Purpose The purpose of this study was to accelerate the acquisition and reconstruction time of 3D magnetic resonance fingerprinting scans. Methods A 3D magnetic resonance fingerprinting scan was accelerated by using a single-shot spiral trajectory with an undersampling factor of 48 in the x-y plane, and an interleaved sampling pattern with an undersampling factor of 3 through plane. Further acceleration came from reducing the waiting time between neighboring partitions. The reconstruction time was accelerated by applying singular value decomposition compression in k-space. Finally, a 3D premeasured B1 map was used to correct for the B1 inhomogeneity. Results The T1 and T2 values of the International Society for Magnetic Resonance in Medicine/National Institute of Standards and Technology MRI phantom showed a good agreement with the standard values, with an average concordance correlation coefficient of 0.99, and coefficient of variation of 7% in the repeatability scans. The results from in vivo scans also showed high image quality in both transverse and coronal views. Conclusions This study applied a fast acquisition scheme for a fully quantitative 3D magnetic resonance fingerprinting scan with a total acceleration factor of 144 as compared with the Nyquist rate, such that 3D T1 , T2 , and proton density maps can be acquired with whole-brain coverage at clinical resolution in less than 5 min. Magn Reson Med 79:2190-2197, 2018. © 2017 International Society for Magnetic Resonance in Medicine.
Impact of Trajectory Planning With Susceptibility-Weighted Imaging for Intracranial Electrode Implantation.

BACKGROUND While T1-weighted gadolinium-enhanced (T1-Gd) magnetic resonance imaging (MRI) is the standard imaging sequence for trajectory planning of stereotactic procedures, including deep brain stimulation, stereoelectroencephalography, and laser interstitial thermal therapy, susceptibility-weighted imaging (SWI) has been reported to demonstrate increased sensitivity for the visualization of microvasculature. OBJECTIVE To determine the impact of SWI visualization on trajectory planning for electrode implantation and evaluate the relationship between the rate of vessel-electrode intersections and intracerebral hemorrhage (ICH). METHODS We conducted a retrospective study of 13 patients who underwent stereoelectroencephalography and laser interstitial thermal therapy placement between 2014 and 2015, using their preoperative T1-Gd and SWI scans, and postoperative MRI scans to determine the rate of vessel-electrode intersections seen on the 2 imaging modalities, the mean diameter and depth of the vessels identified, and the rate of ICH after implantation. RESULTS Among 13 patients, 106 electrodes were implanted. Sixty-three unique vessel-electrode intersections were identified on SWI with a mean of 4.85 intersections per patient. There were 13 intersections seen on T1-Gd with a mean of 1 intersection per patient. The intersected vessels visualized on SWI had a diameter of 1.49 ± 0.46 mm and those on T1-Gd were 2.01 ± 0.52 mm. There was no clear ICH observed in this series. CONCLUSION SWI allows for improved visualization of the smaller, deep vessels, whereas T1-Gd adequately detects superficial, larger vessels. Despite the larger number of vessel-electrode intersections seen on SWI, no clear evidence of ICH was identified. Increased detection of deep vasculature does not appear to significantly benefit trajectory planning for stereotactic intracranial procedures and may limit the number of trajectories perceived to be safe.
Overcoming Bulk Recombination Limits of Layered Perovskite Solar Cells with Mesoporous Substrates

The synthesis and characterization of a lead iodide layered perovskite, [NH2C(I)═NH2]2(CH3NH3)2Pb2I8, is described. The combination of an ideal bandgap of 1.61 eV and excellent compositional stability under ambient conditions make it a promising candidate for integration in solar cells. Planar solar cells utilizing [NH2C(I)═NH2]2(CH3NH3)2Pb2I8 exhibit two interesting phenomena in the photovoltaic performance: an exponential dependence of Jsc on incident light intensity and abnormal J–V response. To investigate the photophysical properties of [NH2C(I)═NH2]2(CH3NH3)2Pb2I8 perovskite planar solar cells, intensity-modulated photocurrent spectroscopy (IMPS) and electrochemical impedance spectroscopy (EIS) were conducted. It is found that the planar structured solar cells of the layered perovskite suffer from bulk recombination which limits the charge collection and photocurrent. Use of a mesoporous TiO2 scaffold layer largely overcomes the recombination limitations of the layered perovskite and significantly i...
Learning about systems that contain state variables

It is difficult to learn about systems that contain state variables when those variables are not directly observable. This paper formalizes this learning problem and presents a method called the iterative extension method for solving it. In the iterative extension method, the learner gradually constructs a partial theory of the state-containing system. At each stage, the learner applies this partial theory to interpret the I/O behavior of the system and obtain additional constraints on the structure and values of its state variables. These constraints can be applied to extend the partial theory by hypothesizing additional internal state variables. The improved theory can then be applied to interpret more complex I/O behavior. This process continues until a theory of the entire system is obtained. Several sufficient conditions for the success of this method are presented including (a) the observability and decomposability of the state information in the system, (b) the learnability of individual state transitions in the system, (c) the ability of the learner to perform synthesis of straight-line programs and conjunctive predicates from examples and (d) the ability of the learner to perform theory-driven data interpretation. The method is being implemented and applied to the problem of learning UNIX file system commands by observing a tutorial interaction with UNIX.
Characterization of Blau syndrome panuveitis with wide-field fluorescein angiography.

Abstract Purpose To describe a case of Blau panuveitis, characterized on both portable and tabletop wide-field fluorescein angiography, which resolved on systemic immunosuppression. Observations A 5-year-old female presented with bilateral eye pain, redness, and decreased visual acuity due to panuveitis and had a history of arthritis, tenosynovitis, and dermatitis. Similar ocular and systemic findings in the patient's mother and maternal half-brother prompted genetic testing that confirmed the diagnosis of the rare Blau syndrome. Portable Retcam and tabletop Optos wide-field fluorescein angiography congruently demonstrated retinal vascular and peripapillary leakage. The uveitis dramatically resolved after the addition of adalimumab to methotrexate. Quiescence was maintained with the substitution of infliximab for adalimumab. Conclusions and Importance To our knowledge, we are first to characterize Blau panuveitis retinal findings on wide-field fluorescein angiography and with the use of two different photography systems. Additionally, this report underscores the salient clinical findings of a rare disorder and suggests that robust systemic immunosuppression can effectively treat refractory ocular inflammation.
NASA's Space Launch System: Enabling a New Generation of Lunar Exploration

Following two decades of operational experience in low-Earth orbit (LEO), NASA has turned its focus once again to deep space exploration. The Agency is building the Space Launch System (SLS) to take astronauts and cargo to the Moon and send robotic spacecraft deep into the solar system. Offering unmatched performance, departure energy and payload capacity, SLS is designed to evolve into progressively more powerful configurations, enabling a new generation of human exploration of the Moon in preparation for future missions to Mars. The first build of the Block 1 vehicle is nearly complete for Exploration Mission-l (EM-1), the first integrated flight of SLS and the Orion crew vehicle. EM-l will send an uncrewed Orion to a distant retrograde lunar orbit in order to test and verify new systems, and along the way will deploy 13 6U-class CubeSats in deep space along the upper stage disposal trajectory after separation from Orion. The Agency's current plans call for the first three missions on the SLS manifest to utilize the Block 1 vehicle in crew and cargo configurations. A more powerful evolved vehicle, Block 1B, will provide additional mass and volume performance using a new Exploration Upper Stage (EUS). Block 1B will lift 34 to 40 metric tons (t) to translunar injection (TLI), depending on crew or cargo configuration. The Block 1B crew configuration will offer as much payload volume as industry-standard 5 m-diameter fairings to co-manifested payloads in a Universal Stage Adapter (USA). The Block 1B cargo variant will accommodate 8.4 m-diameter fairings in 62.7-foot (19.1 m) or 90-foot (27.4 m) lengths. Adding smallsat secondary payloads to ride along with primary and co-manifested payloads on future flights may be possible, depending on mass margins. Leveraging a flight-proven, well-understood propulsion system, SLS's flexible architecture, unmatched performance and expansive payload accommodations will open exciting new mission possibilities in deep space. Launches of habitat modules for NASA's new Gateway lunar outpost, the next generation of robotic spacecraft to the far reaches of the solar system, large-aperture deep space telescopes, probes to interstellar space and the return of astronauts to the Moon are all possible with SLS.
High capacity vanadium oxide electrodes: effective recycling through thermal treatment

This study demonstrates that thermal regeneration is an effective approach to convert degraded phases to functioning electroactive materials, restore functional delivered capacity and recover material crystallinity while retaining the integrity of the parent electrode. V2O5 nanowires were synthesized through a facile hydrothermal method and used to fabricate V2O5/carbon nanotube (CNT) binder free electrodes. Discharge of the V2O5–CNT electrodes coupled with operando energy dispersive X-ray diffraction shows no evidence of phase segregation throughout the 150 μm thick binder free electrodes indicating full utilization of a thick electrode. When V2O5 is highly electrochemically lithiated (x > 2 in LixV2O5), irreversible phase transformation to ω-LixV2O5 was observed, accompanied by a capacity decrease of ∼40% over 100 cycles. A simple thermal treatment of the entire electrode results in a delivered capacity equal to or higher than the original value. Both phase conversion and an increase in material crystallinity as a result of thermal treatment are observed where structural analysis indicates the formation of Li1V3O8. The electrode design approach with thick electrodes and functional thermal regeneration may provide a broader choice of electroactive materials through decreasing the environmental burden by extending the lifetime of energy storage systems.
The Mantle of Justice

F.A. Hayek famously argues that the concept of social justice is incoherent (Hayek 1976, Ch. 9). His argument is inseparable from his theory of spontaneous order. If 'social' in 'social justice' refers to the outcomes of a spontaneous process, social justice becomes meaningless. Hayek's rejection of social justice has also received substantial pushback or qualification in recent years from friendly thinkers who (at least nominally) embrace his concept of spontaneous order. This essay evaluates three sorts of responses to Hayek in order to determine which are successful.
Catalytic C-O bond hydrogenolysis of tetrahydrofuran-dimethanol over metal supported WOx/TiO2 catalysts

Abstract M-WOx/TiO2 (M = Pt-, Rh-, Pd-, and Ru) catalysts were prepared and studied for tetrahydrofuran-dimethanol (THFDM) hydrogenolysis. All catalysts have a small metal particle size (
Artificial Intelligence Systems Assisting Oncologists? Resist and Desist or Enlist and Coexist

The use of artificial intelligence (AI) has become an integral part of patient care, but there are concerns about the impact of non‐human decision assistance on patient outcomes. This commentary focuses on how AI can assist oncologists and benefit patients.
Generalized Modular Representation Framework for the Synthesis of Extractive Separation Systems

Abstract In this work, a systematic process synthesis and intensification method is presented for extractive separation based on the Generalized Modular Representation Framework (GMF). GMF employs a mass/heat exchange module-based superstructure representation, incorporating detailed thermodynamic model, to investigate conventional or intensified process options for nonideal azeotropic separation without a pre-postulation of plausible unit/flowsheet configurations. Orthogonal Collocation is also applied to enhance GMF representation to obtain intra-module operation information and module dimensionality estimation while maintaining model size compactness. Thus, entrainer selection, process synthesis, design, and intensification are examined within a single mixed-integer nonlinear optimization (MINLP) problem. A case study on the separation of ethanol-water mixture is presented to highlight the potential of the proposed approach in deriving optimal and verifiable extractive separation systems.
Medical diagnosis and treatment is NP-complete

There is great interest in the pursuit of process-driven, algorithmic allocation of health-care resources, including computer-aided medical diagnosis and treatment (MDT). Little is understood regar...
Proactive Personality and Creative Behavior: Examining the Role of Thriving at Work and High-Involvement HR Practices

This study examines the link between proactive personality and creative behavior by focusing on employee thriving at work as a mediator. Data from 438 employees and their supervisors were collected and examined by conducting structural equation modeling. This analysis revealed that employee thriving at work fully mediates the relationship between proactive personality and creative behavior. Additionally, the results showed that the perceived presence of high-involvement human resources (HR) practices in the organization enhances the tendency of proactive individuals to thrive at work. The paper concludes with a discussion of the implications for theory and practice as well as on directions for future research.
Clinical Analytics Prediction Engine (CAPE): Development, electronic health record integration and prospective validation of hospital mortality, 180-day mortality and 30-day readmission risk prediction models.

Background Numerous predictive models in the literature stratify patients by risk of mortality and readmission. Few prediction models have been developed to optimize impact while sustaining sufficient performance. Objective We aimed to derive models for hospital mortality, 180-day mortality and 30-day readmission, implement these models within our electronic health record and prospectively validate these models for use across an entire health system. Materials & methods We developed, integrated into our electronic health record and prospectively validated three predictive models using logistic regression from data collected from patients 18 to 99 years old who had an inpatient or observation admission at NorthShore University HealthSystem, a four-hospital integrated system in the United States, from January 2012 to September 2018. We analyzed the area under the receiver operating characteristic curve (AUC) for model performance. Results Models were derived and validated at three time points: retrospective, prospective at discharge, and prospective at 4 hours after presentation. AUCs of hospital mortality were 0.91, 0.89 and 0.77, respectively. AUCs for 30-day readmission were 0.71, 0.71 and 0.69, respectively. 180-day mortality models were only retrospectively validated with an AUC of 0.85. Discussion We were able to retain good model performance while optimizing potential model impact by also valuing model derivation efficiency, usability, sensitivity, generalizability and ability to prescribe timely interventions to reduce underlying risk. Measuring model impact by tying prediction models to interventions that are then rapidly tested will establish a path for meaningful clinical improvement and implementation.
The effect of mesenchymal stem cells and exosomes to treat idiopathic pulmonary fibrosis

Idiopathic Pulmonary Fibrosis IPF is a disease that consists of the scarring of the lungs It is the most common type of pulmonary fibrosis This disease is irreversible and becomes worse over time In patients with IPF treatment relies mostly on the clinical application of new drugs Unfortunately these drugs do not repair damaged lung tissue therefore these medications only have the ability to slow down disease progression With this dilemma stem cell treatment has become a popular alternative in the treatment of IPF specifically mesenchymal stem cells MSCs MSC therapy would repair damaged lung tissue thus not delaying the progression of the disease but instead repairing the lungs of the patient In addition the application of exosomes has also gained popularity because of their functionality in intracellular communication There is a need for regenerating the damaged lung tissue of patients with IPF which can be accomplished with stem cell therapy The clinical application of MSCs has been proven safe in patients with this degenerative disease thus this finding has justified more research for the application of stem cell therapy in patients with IPF
Securing Next-Generation Wireless Networks: Challenges and Opportunities (Extended Abstract)

This paper focuses on the security issues in next-generation wireless broadband networks. As such networks are expected to play a critical role in modern society, there is an increasing focus on their security and robustness. Such networks are expected to satisfy stringent security requirements and guarantee uninterrupted end-to-end service for diverse applications. The goal of this paper is to discuss long-term challenges in the design of such networks as well as new research opportunities in developing security mechanisms for such networks.
Enhancement of elastic modulus in North American southern yellow pine via reactive electrokinetic treatment

Abstract An electrokinetic treatment method was developed that reactively formed calcium silicate hydrate (C-S-H) within the pores of southern yellow pine. C-S-H is one of the binder materials of Ordinary Portland Cement (OPC). It is also formed by reaction of calcium ions with silica particles. In this work electrokinetic transport was used to draw negatively charged colloidal silica particles and positively charged calcium ions from opposing directions, enabling them to meet within the wood pores, where they could react to form C-S-H. The focus was to explore the formation of a ceramic phase that could be used to enhance mechanical properties and form the basis of effective retention of organic degradation inhibitors. In a treatment period of 7 days, a 30 V/m electric field provided delivery of calcium and silica throughout the 2.5 × 2.5 × 40 cm beam specimens studied. Scanning Electron Microscopy (SEM) revealed a radically altered microstructure. The modulus of elasticity was enhanced by 18% for the beam specimens and as much as 44% for 0.5 cm thick panels of Southern Yellow Pine (SYP). These enhancements achieved a modulus as well as a specific modulus of elasticity that was indistinguishable from North American Red Oak. The treatments reduced the porosity of the wood by ~1%. This work demonstrated that the anticipated success of a given treatment could be signaled by changes in treatment fluid clarity as well as the applied current density. Future work will examine the durability of mechanical properties as a function of weathering exposure.
A Novelty Search and Metamorphic Testing Approach to Automatic Test Generation

A common task in search-based testing is automatically identifying valuable test cases for software systems. However, existing approaches tend to either search for unique tests with regard to inputs or outputs (i.e., novelty search) or search for inputs that invalidate some expected proposition regarding the software (i.e., metamorphic testing). Problematically, verifying unique tests induces the oracle problem while an invalidated proposition results in a single test case. In this paper we utilize novelty search and metamorphic testing to discover a broad range of unique test cases that are directly verifiable via a metamorphic relation and invalidate such an expected proposition in fewer generations of an evolutionary algorithm than direct search. We apply this novelty search and metamorphic testing combination to discover errors in identifying the midpoint of a geodesic as a proof-of-concept.
Extracellular cAMP: The Past and Visiting the Future in cAMP-Enriched Extracellular Vesicles.

It is recently discovered that the cyclic nucleotide, cyclic adenosine monophosphate (cAMP) can be enriched in the extracellular vesicles (EVs) isolated from endothelial cells. In the current perspective a historical context for the discovery of the extracellular cAMP is provided. The story of extracellular cAMP through investigations addressing the molecule's role in the adenosine pathway is followed, which is widespread in mammalian physiology. The adenosine pathway mediates normal physiological conditions such as renin release, phosphate transport, etc., and participates in pathological conditions such as bronchoconstriction of the airways. Furthermore, adenosine mediated biological pathways are regulated via the receptor mediated intracellular cAMP pathway in mammalian cells. It then speculates on the question of whether cAMP enriched EVs could bypass typical receptor mediated cell signaling and directly activate cAMP signaling cascade in target cells. Preliminary studies to suggest cAMP enriched EVs are provided, added to naive endothelial cells, results in an increase in intracellular cAMP. An alternate mechanism is proposed, apart from the traditional adenosine pathway, that extracellular cAMP may exert its effects and put into perspective how it might consider circulating cAMP moving forward.
Calculation of Penetration

This paper provides an overview of the calculation of penetration. Particular emphasis is placed on numerical simulation of penetration. The predictive capability of current wave propagation codes for impact problems as well as requirements for improving their predictive capability are discussed.
The involvement of PCP proteins in radial cell intercalations during Xenopus embryonic development

The planar cell polarity (PCP) pathway orients cells in diverse epithelial tissues in Drosophila and vertebrate embryos and has been implicated in many human congenital defects and diseases, such as ciliopathies, polycystic kidney disease and malignant cancers. During vertebrate gastrulation and neurulation, PCP signaling is required for convergent extension movements, which are primarily driven by mediolateral cell intercalations, whereas the role for PCP signaling in radial cell intercalations has been unclear. In this study, we examine the function of the core PCP proteins Vangl2, Prickle3 (Pk3) and Disheveled in the ectodermal cells, which undergo radial intercalations during Xenopus gastrulation and neurulation. In the epidermis, multiciliated cell (MCC) progenitors originate in the inner layer, but subsequently migrate to the embryo surface during neurulation. We find that the Vangl2/Pk protein complexes are enriched at the apical domain of intercalating MCCs and are essential for the MCC intercalatory behavior. Addressing the underlying mechanism, we identified KIF13B, as a motor protein that binds Disheveled. KIF13B is required for MCC intercalation and acts synergistically with Vangl2 and Disheveled, indicating that it may mediate microtubule-dependent trafficking of PCP proteins necessary for cell shape regulation. In the neural plate, the Vangl2/Pk complexes were also concentrated near the outermost surface of deep layer cells, suggesting a general role for PCP in radial intercalation. Consistent with this hypothesis, the ectodermal tissues deficient in Vangl2 or Disheveled functions contained more cell layers than normal tissues. We propose that PCP signaling is essential for both mediolateral and radial cell intercalations during vertebrate morphogenesis. These expanded roles underscore the significance of vertebrate PCP proteins as factors contributing to a number of diseases, including neural tube defects, tumor metastases, and various genetic syndromes characterized by abnormal migratory cell behaviors.
Molecular control of stress transmission in the microtubule cytoskeleton

In this article, we will summarize recent progress in understanding the mechanical origins of rigidity, strength, resiliency and stress transmission in the MT cytoskeleton using reconstituted networks formed from purified components. We focus on the role of network architecture, crosslinker compliance and dynamics, and molecular determinants of single filament elasticity, while highlighting open questions and future directions for this work.
Management of Disorders of Water Metabolism in Patients with Pituitary Tumors

Disorders of body fluids, notably central diabetes insipidus (CDI) and the syndrome of inappropriate antidiuretic hormone secretion (SIADH), are relatively uncommon as a presenting symptom of sellar and suprasellar masses, but quite common following surgical resection of such lesions. It therefore behooves clinicians treating such patients to have a good understanding of the pathophysiology, the differential diagnosis and the management of these disorders. This review discusses some general issues concerning the pathogenesis, differential diagnosis, clinical manifestations and therapy of hyperosmolar and hypoosmolar syndromes, including CDI and SIADH, and then more specifically addresses the evaluation and treatment of pre- and postoperative disorders of water metabolism in patients with pituitary adenomas.
Monolithic pin photodetector and FT amplifier on GaAs-on-Si

The design, fabrication, and evaluation of GaAs-on-Si monolithic, lateral p-i-n photodetectors and MESFET amplifiers are described. The GaAs-on-Si was grown by OMCVD. The low-capacitance p-i-n detectors were fabricated directly on the GaAs high-resistivity buffer layer in a monolithic microwave integrated circuit (MMIC)-compatible process. Quantum efficiency results for the p-i-n detector and the 2- to 4-GHz frequency response of one- and two-stage p-i-n/FET preamplifiers are presented. >
Computation of the spray from an air-assisted fuel injector

Comparisons are discussed of computed and measured transient sprays from an air-assisted fuel injector. Although the measurements were extensive, they did not characterize fully the conditions at the nozzle exit which had to be obtained from a simple model of the flow within the injector. It is found that spray width, spray tip penetration, amount of spray found in the head vortex, and chamber fuel distribution are strong functions of the internal design of the fuel injector. Particularly important are the drop size distribution and the direction of the flow at the exit of the nozzle.
Anthrax lethal toxin-induced lung injury and treatment by activating MK2

Anthrax is associated with severe vascular leak, which is caused by the bacterial lethal toxin (LeTx). Pleural effusions and pulmonary edema that occur in anthrax are believed to reflect endothelial injury caused by the anthrax toxin. Since vascular leak can also be observed consistently in rats injected intravenously with LeTx, the latter might present a simple physiologically relevant animal model of acute lung injury (ALI). Such a model could be utilized in evaluating and developing better treatment for ALI or acute respiratory distress syndrome (ARDS), as other available rodent models do not consistently produce the endothelial permeability that is a major component of ARDS. The biological activity of LeTx resides in the lethal factor metalloprotease that specifically degrades MAP kinase kinases (MKKs). Recently, we showed that LeTx inactivation of p38 MAP kinase signaling via degradation of MKK3 in pulmonary vascular endothelial cells can be linked to compromise of the endothelial permeability barrier. LeTx effects were linked specifically to blocking activation of p38 substrate and MAP kinase-activated protein kinase 2 (MAPKAPK2 or MK2) and phosphorylation of the latter's substrate, heat shock protein 27 (HSP27). We have now designed a peptide that directly and specifically activates MK2, causing HSP27 phosphorylation in cells and in vivo. The MK2-activating peptide (MK2-AP) also blocks the effects of LeTx on endothelial barriers in cultured cells and reduces LeTx-induced pulmonary vascular leak in rats. Hence, MK2-AP has the therapeutic potential to counteract anthrax or pulmonary edema and vascular leak due to other causes.
Treatment of Shock: Practical Aspects

Irreversible shock is a rare circumstance in young and otherwise healthy patients if prompt and adequate blood replacement is performed. This is not necessarily true of the civilian population where cardiac, renal, cerebral, general vascular, and metabolic factors may alter not only the shock, but also its responsiveness to treatment and even to the form which that therapy must take. The basic treatment in traumatic shock is the replacement of blood, although plasma expanders of one type or another may suffice temporarily. The use of either blood or plasma expanders carries certain hazards which must be accepted as a compromise in treatment of shock. These hazards make it important not to administer blood or blood substitutes indiscriminately when a need does not exist. Steroids and vasoconstricting agents in general play a very limited role in shock therapy. One of the vicious cycles in shock that may be encountered is the development of acidosis; in acidosis there is lessened response to physiologic vasoconstriction and lessened cardiac ventricular contractile force. Nevertheless, the most likely cause of continued hypotension in the injured patient after a seemingly appropriate volume of blood has been given is still an unrecognized and uncontrolled site of hemorrhage. As a rule, this situation must be corrected by prompt surgical intervention.
Give Me Slack: Depression, Alertness, and Laziness in Seattle

This article is about alertness and depressive enactments in Seattle, Washington. It tracks depression and depressive disorder as something beyond a psychiatric diagnosis—more as a generative cultural analytic and mode of alertness that people use to track affect and a sense of ordinariness-gone-tilt. I argue that depressive enactments constitute a mode of alertness used to track something emergent, unknown, unpredictable, and often disruptive—affective currents that are sensed but not clearly understood. Based on 18 months of ethnographic fieldwork that I conducted in Seattle in 2003–2004, I draw on examples of the cultural performance and training of alertness across a range of registers and spaces—individual sufferers, community mental health clinic routines, and popular culture figures such as Kurt Cobain and the “slacker”— in order to demonstrate how disturbances in normative modes of alertness are contested and worked through. Alertness in Seattle operates as a window onto cultural impasses at work in ordinary habits and dispositions. Thus, I suggest that figures of mental illness, as well as the slacker, are enactments through which individuals disengage from the reiteration of those impasses and attempt to reshape and relearn habits.
Stability analysis of the fuzzy logic controller designed by the phase portrait assignment algorithm

The authors analyze the stability of a fuzzy logic controller, designed using the phase portrait assignment algorithm from a topological point of view. The fuzzy logic controller was designed for a simplified automobile engine which is a two-state dynamic model. The controller was designed using the automatic rule generation technique reported by G.J. Vachtsevanos et al. (1992). The general form of the rule is given. >
Antagonism of serotonin receptor 1B decreases viability and promotes apoptosis in the COS canine osteosarcoma cell line

Serotonin receptor 1B (5HTR1B) traditionally exhibits anti-proliferative activity in osteoblasts. We examined the expression and function of 5HTR1B in the COS canine osteosarcoma cell line and normal canine osteoblasts. Equal levels of 5HTR1B gene and protein expression were found between normal and malignant osteoblasts. Treatment with serotonin enhanced viability of osteosarcoma cells but not normal osteoblasts. Challenge with the 5HTR1B agonist anpirtoline caused no change in cell viability. Rather incubation with the specific receptor antagonist SB224289 caused reduction in osteoblast viability, with this effect more substantial in osteosarcoma cells. Investigation of this inhibitory activity showed 5HTR1B antagonism induces apoptosis in malignant cells. Evaluation of phosphorylated levels of CREB and ERK, transcriptional regulators associated with serotonin receptor signalling in osteoblasts, revealed aberrant 5HTR1B signalling in COS. Our results confirm the presence of 5HTR1B in a canine osteosarcoma cell line and highlight this receptor as a possible novel therapeutic target.
Rough-and-Tumble Play Behavior in Fischer-344 and Buffalo Rats: Effects of Social Isolation

Play behavior was assessed in two inbred strains of rats. Rats of the Fischer-344 strain (F344) were found to be less playful than Buffalo rats after social isolation, as evident from fewer pins and fewer playful attacks to the nape. When tested in same-strain pairings, overall defense of the nape did not differ between strains, although there were strain differences in the specific pattern of defense. When tested in cross-strain pairings, F344 rats were less likely to direct nape attacks toward a Buffalo play partner, and were also less likely to defend their nape when attacked by Buffalo rats. Although different levels of pinning and nape attacks in the two strains were dependent on the amount of isolation prior to the play period, differences in nape defense were not dependent on prior isolation. This pattern of results suggests that the neural mechanisms for playful attack differ from those underlying playful defense. These data also suggest that the F344 strain could be useful in better understanding the neural and genetic bases of mammalian playfulness.
The Unequal Group Size Problem in Discriminant Analysis

The technique of multiple discriminant analysis has seen widespread use in marketing studies. In assessing the predictive efficiency of the derived discriminant functions, the proportional chance criterion is frequently used. This criterion is adequate except in situations when the classification groups are of greatly unequal size. The purpose of this article is to illustrate a procedure which adjusts the groups' sizes so as to allow effective use of the proportional chance criterion under a wider range of circumstances. The article presents an actual problem situation experienced by the author and the procedure used to overcome it.
Flood pulse influences on terrestrial organic matter export from an agricultural watershed

[1] Riverine export of terrestrial organic carbon (TOC) plays an important role in the global C cycle through influences on coastal productivity, sedimentary preservation, and CO2 efflux. In order to examine the influence of hydrologic variability and upland processes on TOC export from a midwestern agricultural watershed, we applied lignin phenol and stable carbon isotope analyses to assess quantity, source, and relative degradation state of TOC in soils, sediments, and size-fractioned aquatic OC from stream water. Flood conditions exported 90 times more dissolved organic carbon (DOC) than baseflow owing to increases in both discharge and concentration, indicating mobilization of additional DOC pools. These observations are supported by increased TOC contributions to aquatic OC during flooding. Furthermore, stable carbon isotope values show that OC exported during flooding is enriched in C4-derived C by up to 38% (for high molecular weight DOC) with respect to baseflow, indicating different TOC sources are mobilized dependant on hydrologic conditions. Lignin phenols isolated from the colloid size fraction show progressive increases in the ratio of carboxylic acid to aldehyde functional groups (a measure of relative degradation state) with distance downstream suggesting selective partitioning to mineral surfaces and/or degradation to this size fraction. This study shows that TOC quantity, source, and relative degradation state can change dependant on hydrologic conditions and in-stream transport in a small agricultural watershed. Moreover, these results are important in showing variability in TOC source and chemistry exported from headwater systems that might otherwise not be detected in studies of larger rivers.
Identification of torque teno virus in culture-negative endophthalmitis by representational deep DNA sequencing

Purpose To test the hypothesis that uncultured organisms may be present in cases of culture-negative endophthalmitis by use of deep DNA sequencing of vitreous biopsies. Design Single-center, consecutive, prospective, observational study. Participants Aqueous or vitreous biopsies from 21 consecutive patients presenting with presumed infectious endophthalmitis and 7 vitreous samples from patients undergoing surgery for noninfectious retinal disorders. Methods Traditional bacterial and fungal culture, 16S quantitative polymerase chain reaction (qPCR), and a representational deep-sequencing method (biome representational in silico karyotyping [BRiSK]) were applied in parallel to samples to identify DNA sequences corresponding to potential pathogens. Main Outcome Measures Presence of potential pathogen DNA in ocular samples. Results Zero of 7 control eyes undergoing routine vitreous surgery yielded positive results for bacteria or virus by culture or 16S polymerase chain reaction (PCR). A total of 14 of the 21 samples (66.7%) from eyes harboring suspected infectious endophthalmitis were culture-positive, the most common being Staphylococcal and Streptococcal species. There was good agreement among culture, 16S bacterial PCR, and BRiSK methodologies for culture-positive cases (Fleiss' kappa of 0.621). 16S PCR did not yield a recognizable pathogen sequence in any culture-negative sample, whereas BRiSK suggested the presence of Streptococcus in 1 culture-negative sample. With the use of BRiSK, 57.1% of culture-positive and 100% of culture-negative samples demonstrated the presence of torque teno virus (TTV) sequences, compared with none in the controls ( P = 0.0005, Fisher exact test). The presence of TTV viral DNA was confirmed in 7 cases by qPCR. No other known viruses or potential pathogens were identified in these samples. Conclusions Culture, 16S qPCR, and BRiSK provide complementary information in presumed infectious endophthalmitis. The majority of culture-negative endophthalmitis samples did not contain significant levels of bacterial DNA. "Culture negativity" does not seem to be due to failure of growth of fastidious bacteria. The small DNA virus TTV was unexpectedly found in all culture-negative samples and some culture-positive samples. This study cannot distinguish whether TTV is a direct intraocular pathogen, an adjuvant for inflammation, a general marker of inflammation, or a commensal virus but provides a testable hypothesis for a pathogenic mechanism in culture-negative endophthalmitis.
Shikimate Dehydrogenase Structure Reveals Novel Fold

The structure of shikimate 5-dehydrogenase, the fourth enzyme in the shikimate biosynthesis pathway and a member of a large enzyme family without clear structural peer, reveals a novel topological fold for the substrate binding domain and, through homology modeling, expands the possibilities for antimicrobial and herbicide design.