cssi/SciSciGPT-SciSciNet huggingface dataset:
Animations for computer networking protocols

This paper introduces several collections of computer networking protocol animations that can be used in conjunction with classroom instruction. Some of these animations allow users to change parameters and settings, thereby enhancing the interactive learning. Additionally, this paper discusses in detail two computer networking protocol animations that were written by students at Park University. These animations have been made publicly available in the student resource website [2] of Kurose and Ross' Computer Networking book [1] and have been used around the globe for several years.
Alluvial stratigraphic evidence for channel incision during the Mediaeval Warm Period on the central Great Plains, USA

Alluvial valley fills from tributaries to the upper Republican River, southwest Nebraska, USA, provide soil- and morpho-stratigraphic evidence for an episode of channel incision that occurred betwe...
Epigenomics and breast cancer

Breast carcinogenesis involves genetic and epigenetic alterations that cause aberrant gene function. Recent progress in the knowledge of epigenomics has had a profound impact on the understanding of mechanisms leading to breast cancer, and consequently the development of new strategies for diagnosis and treatment of breast cancer. Epigenetic regulation has been known to involve three mutually interacting events – DNA methylation, histone modifications and nucleosomal remodeling. These processes modulate chromatin structure to form euchromatin or heterochromatin, and in turn activate or silence gene expression. Alteration in expression of key genes through aberrant epigenetic regulation in breast cells can lead to initiation, promotion and maintenance of carcinogenesis, and is even implicated in the generation of drug resistance. We currently review known roles of the epigenetic machinery in the development and recurrence of breast cancer. Furthermore, we highlight the significance of epigenetic alterations as predictive biomarkers and as new targets of anticancer therapy.
Distributed QoS guarantees for realtime traffic in ad hoc networks

In this paper, we propose a new cross-layer framework, named QPART (QoS protocol for ad hoc realtime traffic), which provides QoS guarantees to real-time multimedia applications for wireless ad hoc networks. By adapting the contention window sizes at the MAC layer, QPART schedules packets of flows according to their unique QoS requirements. QPART implements priority-based admission control and conflict resolution to ensure that the requirements of admitted real time flows is smaller than the network capacity. The novelty of QPART is that it is robust to mobility and variances in channel capacity and imposes no control message overhead on the network.
Microbial cycling of DMSP and DMS in coastalandoligotrophicseawater

The rates and concentration dependence of microbial dimethylsulfide (DMS) and dimethylsulfoniopropionate (DMSP) cycling were assessed in Vineyard Sound, Massachusetts, and the Sargasso Sea. Net rates of dissolved DMSP loss, DMS production from DMSP, and DMS consumption were measured at ambient and near-ambient substrate levels. Turnover times of dissolved DMSP, based on loss rates, were short, usually ranging from 1.5 d to several hours. However, the specific process of DMSP cleavage to form DMS accounted for only a portion of total DMSP turnover. Short-term variability obscured possible regional or seasonal trends in these data. Dissolved DMSP removal and cleavage exhibited saturable kinetics in spring in Vineyard Sound and in winter in the Sargasso Sea. In fall and spring in the Sargasso Sea, where dissolved DMSP levels ranged from 2 to 9 nM, DMSP cleavage did not saturate at DMSP levels as high as 1 PM. Kinetic parameters of DMSP uptake appeared to increase with proximity to summer, as did the proportion of DMSP uptake resulting in DMS production. The tertiary sulfonium compound dimethylsulfoniopropionate (DMSP), synthesized by marine algae, is a ubiquitous component of particulate matter in seawater and is the major precursor of marine dimethylsulfide (DMS). As a zwitterion, DMSP is presumably released to the dissolved pool from grazed (Dacey and Wakeham 1986) or senescent (Matrai and Keller 1993) algal cells,
Intraspecific Variation in Life-History Traits of the White-Tailed Jackrabbit (Lepus townsendii)

The population structure and pattern of individual growth of white-tailed jack-rabbits ( Lepus townsendii ) was studied in Wyoming and compared with results for more easterly populations in North America. The density of white-tailed jackrabbits in Wyoming was ca. 7/km2 and relatively constant during 1985–1987. Sex ratios of adults and young of the year were near 1:1. Age distributions of each sex were similar, with younger animals predominant. Typical lifespans of wild white-tailed jackrabbits were estimated to be 90% of the variance in age-specific body masses was explained by fitting von Bertalanffy, Gompertz, logistic, or Richards sigmoid equations to data. Postnatal growth rates of white-tailed jackrabbits were 18–30 g/day during the linear phase of growth (20–80 days). A comparison of these results with those for other regions indicated little geographic variation occurs among populations of L. townsendii .
Validating SAT Solvers Using an Independent Resolution-Based Checker: Practical Implementations and Other Applications

As the use of SAT solvers as core engines in EDA applications grows, it becomes increasingly important to validate their correctness. In this paper, we describe the implementation of an independent resolution-based checking procedure that can check the validity of unsatisfiable claims produced by the SAT solver zchaff. We examine the practical implementation issues of such a checker and describe two implementations with different pros and cons. Experimental results show low overhead for the checking process. Our checker can work with many other modern SAT solvers with minor modifications, and it can provide information for debugging when checking fails. Finally we describe additional results that can be obtained by the validation process and briefly discuss their applications.
Structures of archaebacterial membrane lipids.

Structural data on archaebacterial lipids is presented with emphasis on the ether lipids of the methanogens. These ether lipids normally account for 80–95% of the membrane lipids with the remaining 5–20% of neutral squalenes and other isoprenoids. Genus-specific combinations of various lipid core structures found in methanogens include diether-tetraether, diether-hydroxydiether, or diether-macrocyclic diether-tetraether lipid moieties. Some species have only the standard diether core lipid, but none are known with predominantly tetraether lipids as found in certain sulfur-dependent archaebacteria. The relative proportions of these lipid cores are known to vary in relation to growth conditions inMethanococcus jannaschii andMethanobacterium thermoautotrophicum. Polar headgroups in glycosidic or phosphodiester linkage to thesn-1 orsn-1′ carbons of glycerol consist of polyols, carbohydrates, and amino compounds. The available structural data indicate a close similarity among the polar lipids synthesized within the species of the same genus. Detection of lipid molecular ions by mass spectrometry of total polar lipid extracts is a promising technique to provide valuable comparative data. Since these lipid structures are stable within the extreme environments that many archaebacteria inhabit, there may be specific applications for their use in biotechnology.
RF System for a 1 GeV Pulse Stretcher Ring

A design study has been completed for the RF system of a pulse stretcher ring to be operated in conjunction with the Bates Linear Accelerator (BLA). The 390m circumference ring is to operate from 300 MeV to 1 GeV, with 80 mA injected current and 1 msec extraction time. The stretcher ring is for nuclear physics research and has radiation damping time and quantum lifetime long compared to the extraction time. The special requirements of the RF system have been considered. Dynamic behavior at the fundamental frequency has been investigated by computer simulation. Higher-order mode impedance limitation has been specified by an investigation of transverse multi-bunch multi-turn instabilities.
A syntaxin 10–SNARE complex distinguishes two distinct transport routes from endosomes to the trans-Golgi in human cells

Mannose 6-phosphate receptors (MPRs) are transported from endosomes to the Golgi after delivering lysosomal enzymes to the endocytic pathway. This process requires Rab9 guanosine triphosphatase (GTPase) and the putative tether GCC185. We show in human cells that a soluble NSF attachment protein receptor (SNARE) complex comprised of syntaxin 10 (STX10), STX16, Vti1a, and VAMP3 is required for this MPR transport but not for the STX6-dependent transport of TGN46 or cholera toxin from early endosomes to the Golgi. Depletion of STX10 leads to MPR missorting and hypersecretion of hexosaminidase. Mouse and rat cells lack STX10 and, thus, must use a different target membrane SNARE for this process. GCC185 binds directly to STX16 and is competed by Rab6. These data support a model in which the GCC185 tether helps Rab9-bearing transport vesicles deliver their cargo to the trans-Golgi and suggest that Rab GTPases can regulate SNARE–tether interactions. Importantly, our data provide a clear molecular distinction between the transport of MPRs and TGN46 to the trans-Golgi.
Outcomes of primary surgical cytoreduction in patients with BRCA-associated high-grade serous ovarian carcinoma

Objective BRCA-associated and sporadic ovarian cancers have different pathologic and clinical features. Our goal was to determine if BRCA mutation status is an independent predictor of residual tumor volume following primary surgical cytoreduction.
Matched filtering of ultrashort pulses

The need to detect a small signal obscured by a large amount of noise is like the problem Prince Charming faced in his search for Cinderella. Fortunately, he had the magic glass slipper that perfectly fit only her. In signal detection and estimation theory, such a magic glass slipper that perfectly fits only the signal of interest is called a “matched filter.” Because every change in the signal shape requires a change of the matched filter, it would be highly advantageous for the filter to be dynamically reconfigured according to the expected signal. For ultrashort (<100 ps) electrical signals that are near the limits of today's electronics, such reconfigurable matched filters become extremely challenging to make. On page 1343 of this issue, Ataie et al. ( 1 ) show how optical signal processing could help to achieve this goal. They demonstrate the detection of a single 80-ps pulse in the presence of a large amount of noise by converting electrical signals to optical signals and subsequently approximating the matched filter with a potentially reconfigurable optical scheme.
A Review of the Evidence on Strategies for Teaching Children Who Are DHH Grapheme–Phoneme Correspondence

Generally, learning to decode printed English has been a difficult skill to master for children who are deaf or hard of hearing (DHH). The purpose of this review was to examine the literature regar...
The Three Crises in Mathematics: Logicism, Intuitionism and Formalism

Crises in classical philosophy reveal doubts about mathematical and philosophical criteria for a satisfactory foundation for mathematics.
The Evolution of a Reliable Gas Turbine

This paper presents the evolution of a reliable and cost effective heavy duty gas turbine. Its pedigree is discussed, including the correction of deficiencies in an earlier turbine design. Specific topics addressed include the correction of field developed design deficiencies in the earlier turbine, the prototype and field validation of these earlier turbine deficiencies and the prototype and field validation of the new turbine which was scaled from the earlier design.Copyright © 1982 by ASME
Callus culture of embryos in Sophora japonica and analysis on isoflavones content

Objective To establish the callus culturing system of embryos in Sophora japonica,and to analyze the contents of isoflavones in callus.Methods Through adding the plant growth regulators of different kinds and at different concentration,the optimal media for callus induction,suspension cell culture,and the highest isoflavone content were obtained.Results The optimal medium for callus induction of embryos in S.japonica was B5 + 2,4-D(1.0 mg/L) + 6-BA(0.2 mg/L) + sucrose(20 mg/L).In solid medium,the callus was growing rapidly after 7 d,and the yield reached to the highest on the day 35(fresh weight 7.413 7 g),but the isoflavone content had no significant changes.In suspension culture,the yield of callus reached to the highest on the day 24(fresh weight 11.563 8 g),and the callus turned into decline phase after 24 d,in which the fresh and dry callus weights were descending.With continuous culture,the cells were browning gradually,aging,and dying at last,but the isoflavone content was opposite to growth curve,and reached its lowest point(4.826 mg/g) on the day 24.Conclusion The induction and cultivation of embryos callus in S.japonica and the isoflavone content have a larger correlation with the plant growth regulators of the kinds and the concentration.
Detection of a human hematopoietic progenitor cell capable of forming blast cell containing colonies in vitro.

A progenitor cell CFU-B1 (blast cell colony forming unit) present in human bone marrow and capable of producing blast cell containing colonies in vitro was detected using a serum containing semisolid culture system. The CFU-Bl has the capacity not only to undergo self-renewal, but also commitment to a number of hematopoietic lineages. This progenitor cell therefore has characteristics which suggest that it is identical to or closely related to the human pluripotent hematopoietic stem cell. Pretreatment of marrow cells with 5 fluorouracil facilitated detection of CFU-Bl derived colonies. The formation of CFU-Bl derived colonies was dependent upon the addition of media conditioned by the human bladder carcinoma cell line 5637. The ability of 5637 CM (conditioned media) to support blast cell colony formation was in part but not totally ablated by pretreatment of the CM with an IL-lα (interleukin-1) neutralizing antibody. This data suggests that IL-lα plays a role in the regulation of primitive events occuring during human hematopoiesis. IL-lα might be exerting these effects by either acting directly on the CFU-Bl, causing marrow accessory cells to elaborate other cytokines or by synergizing with cytokines already present in 5637 CM.
Family Forest Ownerships of the United States, 2013: Findings from the USDA Forest Service's National Woodland Owner Survey

There are an estimated 10.7 million family forest ownerships across the United States who collectively control 36% or 290 million acres of the nation's forestland. The US Department of Agriculture Forest Service National Woodland Owner Survey (NWOS) provides information on the characteristics, attitudes, and behaviors of these ownerships. Between 2011 and 2013, 8,576 randomly selected family forest ownerships with at least 10 acres of forestland participated in the NWOS. Results show: amenity values are the dominant reasons for owning; owners tend to be active on their land, but most are not engaged in traditional forestry programs; and owners are relatively old. Although the general ownership patterns and reasons for owning are the same between the 2002–2006 and current iterations of the NWOS, participation in some management activities changed (some increased and some decreased) and the percentage of female primary decision makers increased.
The development, safety and efficacy of pacritinib for the treatment of myelofibrosis.

ABSTRACTIntroduction: Dysregulation of janus kinase (JAK)/signal transducer and activator of transcription (STAT) pathway has been described in myelofibrosis (MF). Currently, there is an unmet need for agents that have the benefit of JAK inhibition, yet also are safe and effective in patients with thrombocytopenia.Areas covered: We discuss the various preclinical and clinical studies describing pacritinib, a selective JAK2/FLT3 inhibitor. So far, it has shown promising results, without significant thrombocytopenia. A PubMed search, using keywords ‘pacritinib’, ‘SB 1518’ and ‘myelofibrosis’ was conducted. Published abstracts from recent national and international meetings were also reviewed for unpublished data.Expert commentary: Currently, pacritinib is on hold by Food and Drugs Administration. It would be imperative to understand if there is a treatment related toxicity that would limit its use. If a safe path is found for this agent, it could have a significant benefit in various settings, based on the ...
Modeling and observer-based compensation of slip in a friction drive for servo positioning

This paper studies slip in friction drives in the context of a precision servo positioner equipped with a twist-roller friction drive. The servo positioner is modeled using a two-mass model that includes the experimentally-identified nonlinear slip dynamics of the friction drive. The model is then used to design an observer-based compensation scheme aimed at reducing the slip-induced performance degradation of the servo positioner's linear time invariant controller. The compensation scheme is validated in simulations and experiments using state feedback controllers. Tracking performance with the proposed slip compensation scheme, compared with the original controller and an intuitive high pass filter approach, is shown to improve considerably.
Exploration of the Innate Immune System of Styela clava: Zn2+ Binding Enhances the Antimicrobial Activity of the Tunicate Peptide Clavanin A.

Tunicates have been used as primitive models for understanding cell-mediated and humoral immunity. Clavanin A (ClavA) is one member of a family of antimicrobial peptides produced by the solitary tunicate Styela clava. In this work, we demonstrate that ClavA utilizes Zn2+ ions to potentiate its antimicrobial activity not only by reducing the concentration at which the peptide inhibits the growth of bacteria but also by increasing the rate of killing. Membrane depolarization, β-galactosidase leakage, and potassium leakage assays indicate that ClavA is membrane active, forms small pores, but induces cell death by targeting an intracellular component. ClavA and ClavA-Zn2+ added to Escherichia coli and imaged by confocal microscopy translocate across the cell membrane. E. coli mutants lacking the functional Zn2+ import system are less susceptible to ClavA, suggesting that the synergistic activity between ClavA and Zn2+ has a cytoplasmic target, which is further supported by its nucleolytic activity. Overall, t...
Inverse Limits on Intervals

This chapter provides an introduction to inverse limits for anyone who hascompleted a basiccourse in topology. We begin with some of the fundamental properties of inverse limits on the interval [0, 1] and we include numerous instructive examples. This introductionculminates with a brief study of inverse limits on [0, 1] with a single bonding map. Much of the remainder of thechapter is devoted to inverse limits as they relate to dynamical systems. We begin this with a look at period 3 showing that an inverse limit on [0, 1] with a single bonding map having a periodic point of period 3contains an indecomposablecontinuum. We investigate inverse limits with unimodal bonding maps, logistic bonding maps, tent maps as bonding maps, andcertain other families of bonding maps. For thecontinuum theorists reading thischapter we prove that inverse limits on [0, 1] are characterized bychainability. However, this proof provides insight into the geometric realization of inverse limits ascontinua and, as such,can increase one’s understanding of the variety andcomplexity of the objects produced by the inverse limitconstruction. Weclose thechapter with a proof that the inverse limit of acertain unimodal map is the familiar sin(1/x)-curve.
Insights from Large-Scale Cancer Genome Sequencing

The basic catalog of DNA-based alterations that contribute to the onset and progression of cancer has been largely elucidated due to the results obtained from the combination of massively parallel sequencing and computational analysis methods applied to thousands of cancer samples. These combined approaches have provided novel and surprising insights into the myriad ways that DNA-level disruptions lead to activation and inactivation of cellular pathways, thereby altering the carefully controlled growth and division of normal cells and rendering them cancerous. This review presents genomic insights gained from these large-scale studies and highlights how this new knowledge will be translated in the future into improved clinical care and monitoring of cancer patients.
Genotoxicity of the histone deacetylase inhibitor trichostatin A: Evidence for both aneugenic and clastogenic effects

806 Histone deacetylase inhibitors (HDACi) are a class of putative chemotherapeutic agents for which the mechanism of toxicity remains largely unknown. The possibility that HDACis may be genotoxic has not been thoroughly investigated. To explore this possibility we exposed human lymphoblastoid TK6 cells to the HDACi trichostatin A (TSA) and analyzed various measures of genetic damage. Numerical and structural chromosomal aberrations were analyzed using the kinetochore-antibody micronucleus assay and non-banding metaphase chromosome analysis while DNA strand breaks were investigated with the alkaline comet assay. Significant increases in structural chromosomal aberrations and kinetochore-negative micronuclei were detected at the 100 and 200nM TSA doses, whereas significant levels of aneuploidy were only observed at the 200nM dose using metaphase analysis. Therefore TSA is a clastogenic agent that also induces aneuploidy via non-dysjunction in the TK6 cell line. Increased olive tail moments of TK6 cells exposed to TSA add supportive data that TSA is a DNA damaging agent. Patterns obtained from flow cytometric analysis of annexin V staining TK6 cells indicated that genotoxicity occurs in the absence of apoptosis at all but the highest concentration of TSA suggesting that the observed genotoxicity is not a byproduct of apoptosis, but rather may be the cause of it. Flow cytometric analysis of asynchronous TK6 cells stained with propidium iodide demonstrated that TSA causes a G1 arrest prior to the occurrence of apoptosis, further evidence to indicate that TSA is a genotoxic agent. Current studies are focusing on the temporal relationship between the TSA-induced genotoxicity, cell cycle arrest, and apoptotic signals to identify if the apoptosis is due to a genotoxic-dependent or -independent mechanism. We conclude that TSA causes both chromosomal breakage and non-dysjunction in TK6 cells and postulate that the TSA-induced apoptosis observed at high doses may partially be due to this genotoxicity.
Zooarchaeology’s Basic Counting Units

This chapter is the first of two chapters on methods for counting archaeofaunal specimens. It introduces NSP, the number of specimens, identifiable or not, and NISP, the number of taxonomically identifiable specimens in a sample, MNE (minimum number of elements), MNI (minimum number of individuals), and MAU (minimum animal units), the last three counts all being derived from NISP. It introduces the advantages and limitations in their application, which will be discussed in greater detail in Chap. 18. Since counting and comparison are inevitable in zooarchaeology, and since no one of these measures is perfectly suitable for all situations, researchers must give thought to which will most reliably accomplish their research goals. This chapter stresses that these measure should be assessed and applied according to the nature of the site(s), state of the archaeofauna materials, and research questions, providing some examples.
Transition-metal-free diboration of non-activated olefins: A reaction mechanism revisited

Abstract Density functional theory (M06-2X/6-31+G∗) calculations were used to examine a mechanism (B2(1,1)) proposed by Fernandez et al. (2011) that tries to rationalize the high SYN-stereoselectivity observed in their discovered transition-metal-free diboration of non-activated olefins. The results show that B2(1,1) incorrectly predicts ANTI-addition of bulky diboron esters, however correctly predicts less bulky and catecholic diboron esters. Alternative mechanisms (B2′(1,1), B2(1,2), and B3), which help rationalize the stereochemistry of all studied diboron esters were examined.
Endothelial Cell Tumor Prevention with Berry Extracts: Clinical Problems, Molecular Mechanisms and Therapeutic Opportunities

Endothelial cell tumors are the most common soft tissue tumors in infants. The majority of these tumors occur in the head and neck region, so even a small tumor causes an obvious physical deformity. Approximately 10% of these lesions can threaten normal development or even the life of the affected child when they are located near vital structures such as the eyes, neck, or mouth. The most effective treatment options are high dose steroids, interferon-α, and propanolol. All of them are used over the course of several months, all have potentially life-threatening side effects, and none have defined mechanisms of action in endothelial cell tumors. This chapter will review mechanistic studies that show how the production of reactive oxygen species by the nox-4 subunit of NADPH oxidase stimulates expression of monocyte chemoattractant protein-1 to drive endothelial cell tumor formation. It will also discuss how blueberry extract can inhibit tumorigenic responses of EOMA cells in vitro and inhibit endothelial cell tumor formation in vivo.
TRANSPORTERS | Glutamate Transporters in Epilepsy

Disruption of glutamate homeostasis is a contributing factor to brain injury in several pathological conditions including epilepsy. Excitatory amino acid transporters, or EAATs, are responsible for maintaining levels of extracellular glutamate below pathological levels in the human brain, offering a potential therapeutic target. Recent pharmacological investigations have revealed the structure of the ligand binding site on EAATs and suggest new directions for the design of transported and nontransported inhibitors. Advances in techniques for assessing protein structure have further expanded our understanding in this field. Unique targeting and trafficking pathways for EAATs play a critical role in EAAT dynamics and new advances in these technologies will further our understanding of glutamate homeostasis in the healthy and injured brain.
Analyzing the Sentiment of Crowd for Improving the Emergency Response Services

Twitter is an extremely popular micro-blogging social platform with millions of users, generating thousands of tweets per second. The huge amount of Twitter data inspire the researchers to explore the trending topics, event detection and event tracking which help to postulate the fine-grained details and situation awareness. Obtaining situational awareness of any event is crucial in various application domains such as natural calamities, man made disaster and emergency responses. In this paper, we advocate that data analytics on Twitter feeds can help improve the planning and rescue operations and services as provided by the emergency personnel in the event of unusual circumstances. We take a different approach and focus on the users' emotions, concerns and feelings expressed in tweets during the emergency situations, and analyze those feelings and perceptions in the community involved during the events to provide appropriate feedback to emergency responders and local authorities. We employ sentiment analysis and change point detection techniques to process, discover and infer the spatiotemporal sentiments of the users. We analyze the tweets from recent Las Vegas shooting (Oct. 2017) and note that the changes in the polarity of the sentiments and articulation of the emotional expressions, if captured successfully can be employed as an informative tool for providing feedback to EMS.
The affinity of MhuD for heme is consistent with a heme degrading function in vivo

MhuD is a protein found in mycobacteria that can bind up to two heme molecules per protein monomer and catalyze the degradation of heme to mycobilin in vitro. Here the Kd1 for heme dissociation from heme-bound MhuD was determined to be 7.6 ± 0.8 nM and the Kd2 for heme dissocation from diheme-bound MhuD was determined to be 3.3 ± 1.1 μM. These data strongly suggest that MhuD is a competent heme oxygenase in vivo.
SPARSE ERROR CORRECTION FOR PMU DATA UNDER GPS SPOOFING ATTACKS

Time-synchronized phasor measurements from phasor measurement units (PMUs) are valuable for real time monitoring and control. However, their reliance on civilian GPS signals makes them vulnerable to GPS signal spoofing attacks which can be launched by an adversary to falsify PMU data entries. In this paper, we consider the problem of correcting PMU data to mitigate the impact of GPS spoofing attacks. We exploit the unique structure of how GPS spoofing attacks affect PMU data as well as the sparse nature of attacked PMUs. We formulate PMU data correction as a sparse optimization problem that incorporates the unique structure of GPS spoofing attacks. We develop an iterative greedy algorithm to recover tampered PMU measurements and demonstrate its efficacy using simulations with the IEEE RTS-96 test case under both observable and unobservable power network settings.
Clinician Perspectives on the Potential Utility of a Patient Reported Outcomes Measure for Pediatric Heart Failure

Purpose Patient-reported outcome measures (PROM) have become an integral part of the assessment of adult but not pediatric heart failure (PHF) patients. We sought to evaluate the need for and identify the challenges to developing a useful PROM for PHF by surveying pediatric HF clinicians. Methods A cross-sectional survey of PHF clinicians attending a 2018 international pediatric HF and ventricular assist device (VAD) summit was performed. Results 148 PHF providers completed the survey of whom 45% were physicians, 17% advanced practice providers, 10% trainees, 18% nurses, 3% surgeons, and 7% other. Among all respondents, 63% considered PHF as their primary specialty, with a mean of 9 years of PHF practice experience. Among pediatric cardiologists, 86% routinely use one or more existing symptom scales (e.g. NYHA class, AHA Stage) but just 22% have used a PROM routinely in the past year. Overall, 60% of PHF cardiologists are dissatisfied or extremely dissatisfied with PHF severity scales. Most providers (73%) agree or strongly agree a useful PHF PROM does not currently exist, and >94% agree or strongly agree that a useful PROM would be utilized clinically and as an endpoint for clinical trials. The most significant barriers to developing a useful PHF PROM are the lack of relevance of adult instrument items to children, need for different instruments across age groups, difficulty incorporating PROMs into clinical workflow, and sedation limiting PROMs in sicker patients. The most important symptoms to capture in a PROM are GI symptoms, respiratory symptoms, and exercise intolerance/fatigue, with the relative importance of each varying by age group (Figure 1). Conclusion Most clinicians believe that a PHF PROM would be useful for clinical assessment and regulatory evaluation of pediatric drugs and devices. While a variety of challenges in developing a useful PHF PROM exist, a simple tool incorporating GI, respiratory, and fatigue/activity symptoms would cover important elements in children with HF.
In search of an observational quantum signature of the primordial perturbations in slow-roll and ultraslow-roll inflation

In the standard inflationary paradigm, cosmological density perturbations are generated as quantum fluctuations in the early Universe, but then undergo a quantum-to-classical transition. A key role in this transition is played by squeezing of the quantum state, which is a result of the strong suppression of the decaying mode component of the perturbations. Motivated by ever improving measurements of the cosmological perturbations, we ask whether there are scenarios where this decaying mode is nevertheless still observable in the late Universe, ideally leading to a “smoking gun” signature of the quantum nature of the perturbations. We address this question by evolving the quantum state of the perturbations from inflation into the postinflationary Universe. After recovering the standard result that in slow-roll (SR) inflation the decaying mode is indeed hopelessly suppressed by the time the perturbations are observed (by ∼115 orders of magnitude), we turn to ultraslow-roll (USR) inflation, a scenario in which the usual decaying mode actually grows on superhorizon scales. Despite this drastic difference in the behavior of the mode functions, we find also in USR that the late-Universe decaying mode amplitude is dramatically suppressed, in fact by the same ∼115 orders of magnitude. We finally explain that this large suppression is a general result that holds beyond the SR and USR scenarios considered and follows from a modified version of Heisenberg’s uncertainty principle and the observed amplitude of the primordial power spectrum. The classical behavior of the perturbations is thus closely related to the classical behavior of macroscopic objects drawing an analogy with the position of a massive particle, the curvature perturbations today have an enormous effective mass of order m²_(pl)/H²₀∼10¹²⁰, making them highly classical.
The Biokinetic Database

It is almost axiomatic that time is the least appreciated dimension in biology. We can grasp at the idea that passage of time is relative, and not the same thing to a shrew as to a sloth, a mouse, or a man. This relativity of duration may be related to the rate at which electrons derived from foodstuffs are utilized in our mitochondria, such that one marker of time’s passing is irreparable oxidative damage to the genetic code in our somatic cells, a process to which we are insensible. Even admitting that time is relative, it seems that there may be evolutionary advantages to experiencing it quickly, and other advantages (and drawbacks) to perceiving the passage of time slowly. For this reason alone, the dimension should be of interest to the biologist, and all the more when one develops an interest in biological rhythms and the process of aging, however nebulous it may seem.
Perturbative theory for Brownian vortexes

Brownian vortexes are stochastic machines that use static nonconservative force fields to bias random thermal fluctuations into steadily circulating currents. The archetype for this class of systems is a colloidal sphere in an optical tweezer. Trapped near the focus of a strongly converging beam of light, the particle is displaced by random thermal kicks into the nonconservative part of the optical force field arising from radiation pressure, which then biases its diffusion. Assuming the particle remains localized within the trap, its time-averaged trajectory traces out a toroidal vortex. Unlike trivial Brownian vortexes, such as the biased Brownian pendulum, which circulate preferentially in the direction of the bias, the general Brownian vortex can change direction and even topology in response to temperature changes. Here we introduce a theory based on a perturbative expansion of the Fokker-Planck equation for weak nonconservative driving. The first-order solution takes the form of a modified Boltzmann relation and accounts for the rich phenomenology observed in experiments on micrometer-scale colloidal spheres in optical tweezers.
Before this decade is out: a student project to place a telescope on the internet

This paper describes a student project to place a telescope on the internet: such a telescope can be pointed via a web interface, and images from it displayed on a user's computer. We discuss recent developments in astronomy hardware and computer software that place this still challenging project within the realm of the possible.
Evaluating Endogenous Carbon Monoxide (CO) Production as an Indicator for Pulmonary Function Testing (PFT)

Background: Chronic lung diseases, such as COPD and asthma, are associated with considerable morbidity and mortality and involve chronic inflammation and oxidative stress. However, the diseases are not diagnosed and treated efficiently in routine clinical practice because of the difficulties in monitoring inflammation. Consequently, it is often too late to alter respiratory dysfunction when patients’ referral for pulmonary function testing is delayed. The purpose of this study was to explore the possible associations between pulmonary function test (PFT) measurements and exhaled carbon monoxide (eCO) levels as an indicator of generalized inflammation. Data analysis was conducted to determine a potential level of eCO to use as an indicator for conducting PFT. Methods: A sample of 343 subjects, who were referred by their physicians for a routine care PFT, were recruited from the Queen’s Medical Center Pulmonary Lab in Honolulu, Hawaii. A study-specific information sheet was provided to the subjects as part of the informed consent process, and the subjects’ data were collected through a Demographic Data Questionnaire. Exhaled carbon monoxide (eCO) levels were measured with a portable carbon monoxide analyzer (MicroCO Meter), and the maximum values from three successive measurements were used in all calculations. Results: FVC, FEV1, FEV1/FVC, and FEF25-75% decreased with elevated concentrations of eCO. In females, decreased lung volumes (TLC, FRC, and RV) were associated with increased eCO levels. In males, increased lung volumes were associated with increased eCO levels. Diffusion capacity of lungs for carbon monoxide (DLCO) and eCO levels also showed the opposite correlation between females and males. DLCO of female subjects markedly decreased with increased levels of eCO while DLCO of male subjects mildly increased. Appropriate cut-off points of eCO levels also were examined to determine the most efficient use of eCO as an indicator for PFT. The present study found that a cut-off point for eCO of 6 ppm provided the best relationship between sensitivity and specificity in predicting the need for PFT. Conclusions: eCO measurement, which is noninvasive, quick, inexpensive, and easily administered by primary care physicians, could serve as a useful biomarker for monitoring patients with pulmonary diseases. Therefore, eCO measurement may be clinically useful as a diagnostic tool to identify inflammation and to serve as an indicator of the need to conduct PFT.
Developing Cyclic Peptomers as Broad-Spectrum Gram negative Bacterial Type III Secretion System Inhibitors

ABSTRACT Antibiotic resistant bacteria are an emerging global health threat. New antimicrobials are urgently needed. The injectisome type III secretion system (T3SS), required by dozens of Gram-negative bacteria for virulence but largely absent from non-pathogenic bacteria, is an attractive antimicrobial target. We previously identified synthetic cyclic peptomers, inspired by the natural product phepropeptin D, that inhibit protein secretion through the Yersinia Ysc and Pseudomonas aeruginosa Psc T3SSs, but do not inhibit bacterial growth. Here we describe identification of an isomer, 4EpDN, that is two-fold more potent (IC50 4 μM) than its parental compound. Furthermore, 4EpDN inhibited the Yersinia Ysa and the Salmonella SPI-1 T3SSs, suggesting that this cyclic peptomer has broad efficacy against evolutionarily distant injectisome T3SSs. Indeed, 4EpDN strongly inhibited intracellular growth of Chlamydia trachomatis in HeLa cells, which requires the T3SS. 4EpDN did not inhibit the unrelated Twin arginine translocation (Tat) system, nor did it impact T3SS gene transcription. Moreover, although the injectisome and flagellar T3SSs are evolutionarily and structurally related, the 4EpDN cyclic peptomer did not inhibit secretion of substrates through the Salmonella flagellar T3SS, indicating that cyclic peptomers broadly but specifically target the injestisome T3SS. 4EpDN reduced the number of T3SS basal bodies detected on the surface of Y. enterocolitica, as visualized using a fluorescent derivative of YscD, an inner membrane ring with low homology to flagellar protein FliG. Collectively, these data suggest that cyclic peptomers specifically inhibit the injectisome T3SS from a variety of Gram-negative bacteria, possibly by preventing complete T3SS assembly. IMPORTANCE Traditional antibiotics target both pathogenic and commensal bacteria, resulting in a disruption of the microbiota, which in turn is tied to a number of acute and chronic diseases. The bacterial type III secretion system (T3SS) is an appendage used by many bacterial pathogens to establish infection, but is largely absent from commensal members of the microbiota. In this study, we identify a new derivative of the cyclic peptomer class of T3SS inhibitors. These compounds inhibit the T3SS of the nosocomial ESKAPE pathogen Pseudomonas aeruginosa and enteropathogenic Yersinia and Salmonella. The impact of cyclic peptomers is specific to the T3SS, as other bacterial secretory systems are unaffected. Importantly, cyclic peptomers completely block replication of Chlamydia trachomatis, the causative agent of genital, eye, and lung infections, in human cells, a process that requires the T3SS. Therefore, cyclic peptomers represent promising virulence blockers that can specifically disarm a broad spectrum of Gram-negative pathogens.
Methodological and institutional considerations for the use of 360-degree video and pet animals in human subject research: An experimental case study from the United States.

Head-mounted virtual-reality headsets and virtual-reality content have experienced large technological advances and rapid proliferation over the last years. These immersive technologies bear great potential for the facilitation of the study of human decision-making and behavior in safe, perceptually realistic virtual environments. Best practices and guidelines for the effective and efficient use of 360-degree video in experimental research is also evolving. In this paper, we summarize our research group’s experiences with a sizable experimental case study on virtual-reality technology, 360-degree video, pet animals, and human participants. Specifically, we discuss the institutional, methodological, and technological challenges encountered during the implementation of our 18-month-long research project on human emotional response to short-duration 360-degree videos of human-pet interactions. Our objective in this paper is to contribute to the growing body of research on 360-degree video and to lower barriers related to the conceptualization and practice of research at the intersection of virtual-reality experiences, 360-degree video, live animals, and human behavior. Practical suggestions for human-subject researchers interested in utilizing virtual-reality technology, 360-degree videos, and pet animals as a part of their research are discussed.
Differentially expressed genes in cotyledon of ewes fed mycotoxins

Ergot alkaloids (E+) are mycotoxins produced by the endophytic fungus, Epichloe coenophiala, in tall fescue that are associated with ergotism in animals. Exposure to ergot alkaloids during gestation reduces fetal weight and placental mass in sheep. These reductions are related to vasoconstrictive effects of ergot alkaloids and potential alterations in nutrient transport to the fetus. Cotyledon samples were obtained from eight ewes that were fed E+ (n = 4; E+/E+) or E- (endophyte-free without ergot alkaloids; n = 4; E−/E-) seed during both mid (d 35 to 85) and late (d 85–133) gestation to assess differentially expressed genes associated with ergot alkaloid induced reductions in placental mass and fetal weight, and discover potential adaptive mechanisms to alter nutrient supply to fetus. Ewes fed E+/E+ fescue seed during both mid and late gestation had 20% reduction in fetal body weight and 33% reduction in cotyledon mass compared to controls (E−/E-). Over 13,000 genes were identified with 110 upregulated and 33 downregulated. Four genes had a |log2FC| > 5 for ewes consuming E+/E+ treatment compared to controls: LECT2, SLC22A9, APOC3, and MBL2. REViGO revealed clusters of upregulated genes associated glucose, carbohydrates, lipid, protein, macromolecular and cellular metabolism, regulation of wound healing and response to starvation. For downregulated genes, no clusters were present, but all enriched GO terms were associated with anion and monocarboxylic acid transport. The complement and coagulation cascade and the peroxisome proliferator-activated receptor signaling pathway were found to be enriched for ewes consuming E+/E+ treatment. Consumption of ergot alkaloids during gestation altered the cotyledonary transcriptome specifically related to macronutrient metabolism, wound healing and starvation. These results show that ergot alkaloid exposure upregulates genes involved in nutrient metabolism to supply the fetus with additional substrates in attempts to rescue fetal growth.
Security of Cyber Physical Systems: Vulnerabilities, Attacks and Countermeasure

Recently, cyber physical system (CPS) has become one of the most useful computer systems used in critical infrastructure. The CPS has been effectively applied in many areas such as power systems, transportation, and robotics. The main focus of this paper is to review integrating the physical components with cyberspaces, avoiding some security issues, and ensuring system stability. In this review, we address what the CPS is, its architecture and why security is essential. This paper introduces some issues that result because of the integration. Also, this paper will be discussing some solutions that are used to enhance the security and protection of CPS, assessing the vulnerabilities in the CPS, detecting attacks to CPS and countermeasures.
Probing the Substellar Regime with SIRTF

One of the main scientific drivers of the Space InfraRed Telescope Facility (SIRTF) is the search for brown dwarfs and extrasolar superplanets. We discuss observational strategies for identification of these objects, and conclude that an optimal strategy is a wide IRAC survey (18 deg$^2$) with a 5 $\sigma$ sensitivity of 3.9 $\mu$Jy in channel 2 (M$\sim19.1^m$). For this sensitivity, we provide estimates of the number of low mass brown dwarfs and isolated planets detected per square degree for power-law mass functions with $\alpha$=1.5, and 1.0. Shallower surveys covering a larger area are inefficient because of large overheads and detector noise. Deeper surveys covering a smaller area become more and more affected by crowding with galaxies. A survey like the one that we propose would determine the field mass function down to a few Jupiter masses through the identification of a large sample of brown dwarfs and isolated planets. The proposed SIRTF survey would also allow the first detection of ultracool substellar objects with temperatures between 700 K and 200 K. The cooling curves of substellar objects with masses less than 20 Jupiters imply that they should spend most of their lifetimes at temperatures below 700 K. Preliminary models indicate that their atmospheres could be dominated by water clouds, which would diminish their optical and near-infrared fluxes. The properties of those objects are still completely unexplored.
Impacts of ES

In this chapter, impacts of embedded systems on society, economy, human, and environment are discussed. Open questions are raised regarding privacy and security concerns, ethical issues, and economical concerns.