cssi/SciSciGPT-SciSciNet huggingface dataset:
Single chain Fc-dimer-human growth hormone fusion protein for improved drug delivery

Fc fusion protein technology has been successfully used to generate long-acting forms of several protein therapeutics. In this study, a novel Fc-based drug carrier, single chain Fc-dimer (sc(Fc)2), was designed to contain two Fc domains recombinantly linked via a flexible linker. Since the Fc dimeric structure is maintained through the flexible linker, the hinge region was omitted to further stabilize it against proteolysis and reduce FcγR-related effector functions. The resultant sc(Fc)2 candidate preserved the neonatal Fc receptor (FcRn) binding. sc(Fc)2-mediated delivery was then evaluated using a therapeutic protein with a short plasma half-life, human growth hormone (hGH), as the protein drug cargo. This novel carrier protein showed a prolonged in vivo half-life and increased hGH-mediated bioactivity compared to the traditional Fc-based drug carrier. sc(Fc)2 technology has the potential to greatly advance and expand the use of Fc-technology for improving the pharmacokinetics and bioactivity of protein therapeutics.
A case of myopic strabismus fixus “Fixed” with loop myopexy

Myopic strabismus fixus is a rare condition seen in high myopes and presents with sudden onset of strabismus. This case report describes a high myopic patient who presented with acute onset strabismus and was successfully treated with loop myopexy of superior rectus and lateral rectus muscles.
In Patients with Critical Limb Ischemia Does Bypass Improve Limb Salvage and Quality of Life When Compared to Endovascular Revascularization

Lower extremity critical limb ischemia (CLI) is a morbid condition that is marked by intractable foot or ankle pain at rest and/or the presence of ischemic ulcerations or necrotic tissue. It is associated with limb amputation, diminution of quality of life, and mortality. Although CLI is treated with limb revascularization it is unclear whether patients benefit more from open surgical repair or endovascular intervention. Although a number of studies have compared outcomes between open and endovascular approaches to treat CLI most have been hampered by retrospective design, lack of controls, lack of standardization of treatment modalities, sponsor and operator bias, inclusion of claudicants, and short or incomplete follow-up. One randomized trial (BASIL) demonstrated no difference in the quality of life associated with these two interventions, although, amputation free survival was higher with bypass in patients who survived 2 years after randomization. Further randomized trials are needed to compare the role of endovascular therapy and surgical bypass in CLI.
Master Maker: Understanding Gaming Skill Through Practice and Habit From Gameplay Behavior.

The study of expertise is difficult to do in a laboratory environment due to the challenge of finding people at different skill levels and the lack of time for participants to acquire mastery. In this paper, we report on two studies that analyze naturalistic gameplay data using cohort analysis to better understand how skill relates to practice and habit. Two cohorts are analyzed, each from two different games (Halo Reach and StarCraft 2). Our work follows skill progression through 7 months of Halo matches for a holistic perspective, but also explores low-level in-game habits when controlling game units in StarCraft 2. Players who played moderately frequently without long breaks were able to gain skill the most efficiently. What set the highest performers apart was their ability to gain skill more rapidly and without dips compared to other players. At the beginning of matches, top players habitually warmed up by selecting and re-selecting groups of units repeatedly in a meaningless cycle. They exhibited unique routines during their play that aided them when under pressure.
Postinfarct Ventricular Arrhythmias: Should We Calm the Renal Nerves?

The risk of sudden death from ventricular arrhythmias (VAs) in the early post–myocardial infarction period is well appreciated by clinicians who are often faced with varying degrees of uncertainty when it comes to assessing arrhythmic risk in their patients.1 Effectively reducing this risk, therefore, has important clinical implications. In this issue of Circulation: Cardiovascular Interventions , we are directed by Jackson et al2 to look once again in the direction of renal arterial denervation (RDN) as an approach to addressing this risk. Modulating the sympathetic nervous system to reduce cardiac dysrhythmias is well supported by several preclinical and clinical reports.3–7 Cervical sympathectomy, for example, is one such modality that has been effectively used in the treatment of refractory VAs in certain clinical situations.7 However, the pursuit of RDN for its antiarrhythmic properties has waned over the recent years in light of the negative SYMPLICITY HTN-3 trial (Renal Denervation in Patients With Uncontrolled Hypertension).8 See Article by Jackson et al In the present study, the authors present a preclinical, …
Gendered Pathways: How Mathematics Ability Beliefs Shape Secondary and Postsecondary Course and Degree Field Choices.

Do mathematics ability beliefs explain gender gaps in the physical science, engineering, mathematics, and computer science fields (PEMC) and other science fields? We leverage U.S. longitudinal, nationally representative data to estimate gendered differences in girls’ and boys’ perceptions of mathematics ability with the most difficult or challenging material. Our analyses examine the potentially interacting effects of gender and these ability beliefs on students’ pathways to scientific careers. Specifically, we study how beliefs about ability with challenging mathematics influence girls' and boys' choices to pursue PEMC degrees, evaluating educational milestones over a six year period: advanced science course completion in secondary school and postsecondary major retention and selection. In doing so, we review our recently published findings and present additional findings further demonstrating gender differences in secondary school mathematics ability beliefs in relation to objective ability measures and the consequences of these beliefs for students’ chosen degree fields.
A comparison of different NDE signal processing techniques based on waveform entropies applied to long fiber-graphite/epoxy-plates

This study compares diﬀerent approaches for imaging the internal architecture of graphite/epoxy composites using backscattered ultrasound. Two cases are studied. In the first, near-surface defects in a thin graphite/epoxy plates are imaged. The backscattered waveforms were used to produce peak-to-peak, logarithm of signal energy, as well as entropy images of diﬀerent types. All of the entropy images exhibit better border delineation and defect contrast than either the peak-to-peak or the logarithm of signal energy. The best results are obtained using the joint entropy of the backscattered waveforms with a reference function. Two diﬀerent references are examined. The first is a reflection of the insonifying pulse from a stainless steel reflector. The second is an approximate optimum obtained from an iterative parametric search. The joint entropy images produced using this reference exhibit three times the contrast obtained in previous studies. These plates were later destructively analyzed to determine size and location of near-surface defects and the results are found to agree with the defect location and shape as indicated by the entropy images. In the second study, images of long carbon fibers (50% by weight) in polypropylene thermoplastic were obtained as a first step toward ultrasonic determination of the distributions of fiber position and orientation.
Utility of Broad-Range PCR Testing in Suspected CNS Infections (P6.317)

OBJECTIVE: To investigate utility of broad-range bacterial, fungal and mycobacterial polymerase chain reaction (PCR) to identify organisms in suspected CNS infections. BACKGROUND: Broad-range PCR uses primers in conserved regions of micro-organisms, followed by DNA sequencing, to identify microbes. In infective endocarditis it has been shown that broad-range PCR of heart valves is more sensitive than valve culture to identify the organism (90[percnt] vs 31[percnt]), with fewer false positives (3[percnt] vs 33[percnt]). Broad-range PCR is not well studied in neurologic infections. DESIGN/METHODS: Retrospective chart review of adult patients admitted to our tertiary-care center for presumed CNS infection from 2011-2012 who underwent broad-range PCR from CSF or CNS tissue. RESULTS: Forty-three cases were reviewed. Mean age was 51.8 years. Forty-nine percent were female. Presentation included headache (42[percnt]), fever (23[percnt]), seizures (7[percnt]) or a combination of two of the previous symptoms (19[percnt]). Three PCRs were positive; Propionibacterium acnes in two cases and Staphylococcus saphrophyticus , which were considered contaminants rather than pathogens. Final diagnoses: viral meningoencephalitis (7[percnt]), chronic meningitis (9[percnt]), brain abscess (7[percnt]), post-surgical meningitis (2[percnt]) and non-infectious entities (47[percnt]) included demyelination, autoimmune/inflammatory and neoplasm. Total of 28[percnt] of cases did not have a definitive diagnosis. CONCLUSIONS: In our series the most common reason for a positive broad-range PCR result was contamination. Unlike endocarditis, in suspected CNS infections broad-range PCR was not useful, probably because the etiologies are often viruses (which are not amenable to broad-range PCR) or non-infectious. CSF might not be the ideal specimen for intra parenchymal processes. Further research is needed to identify which syndromes and specimen source would be ideal for broad-range PCR in CNS infection. Disclosure: Dr. Koffman has nothing to disclose. Dr. Bernatowicz has nothing to disclose. Dr. Shrestha has nothing to disclose. Dr. Bhimraj has nothing to disclose.
Transcription factor-microRNA associations and their impact on colorectal cancer survival.

MicroRNAs (miRNAs) and Transcription Factors (TFs) both influence messenger RNA (mRNA) expression, disrupting biological pathways involved in carcinogenesis and prognosis. As many miRNAs target multiple mRNAs, thus influencing a multitude of biological pathways, deciphering which miRNAs are important for cancer development and survival is difficult. In this study, we (i) determine associations between TF and survival (N = 168 colon cancer cases); (ii) identify miRNAs associated with TFs related to survival; and (iii) determine if factors derived from TF-specific miRNA principal component analysis (PCA) influence survival. Cox Proportional hazard models were run for each PCA factor to determine Hazard Ratios (HR) and 95% Confidence Intervals (CI) adjusting for age, center, and AJCC stage. Thirty TFs improved survival when differential expression increased; 27 of these were associated significantly with normal colonic mucosa expression of 65 unique miRNAs when an FDR q-value of <0.05 was applied. Five factors, comprising 21 miRNAs, altered survival in rectal cancer subjects; four of these five factors improved survival and one factor reduced survival. One factor comprising four miRNAs reduced survival in colon cancer subjects. In summary, our data suggest that expression of TFs and their related miRNAs influence survival after diagnosis with colorectal cancer.
Patterns of axillary evaluation in older patients with breast cancer and associations with adjuvant therapy receipt

Although axillary lymph node status has traditionally been a key factor in informing adjuvant breast cancer therapy recommendations, this information may be less relevant as our focus shifts more towards tumor biology, particularly in older patients where comorbidity influences treatment decisions and nodal staging and/or surgery may not improve outcomes. We examined patterns of axillary surgery and associations between axillary surgery and receipt of adjuvant treatment in older breast cancer patients. Women aged ≥ 65 years with clinically node-negative, stage I–II breast cancer treated between 2012 and 2013 were identified using the National Cancer Data Base. Using multivariable logistic regression, we examined associations between axillary surgery and age, adjusting for patient, clinical, and facility factors. We also examined receipt of adjuvant treatment by nodal surgery. Among 68,205 women, 40.1% were aged 65–70, 24.5% were 71–75, 17.4% were 76–80, and 18.0% were > 80. Overall, 91.2% had axillary surgery (67.8% sentinel lymph node biopsy, 11.7% axillary lymph node dissection, 11.7% unspecified/unknown axillary surgery); 88.0% of those aged ≥ 70 with lower risk, hormone receptor-positive tumors underwent axillary surgery. In adjusted analyses, compared to patients aged 65–70, increasing age was associated with lower odds of any axillary surgery (ages 71–75: OR 0.64, 95% CI 0.57–0.71; ages 76–80: OR 0.33, 95% CI 0.30–0.37; age > 80: OR 0.08, 95% CI 0.07–0.08). Axillary surgery was associated with higher odds of receipt of radiation after breast conservation and receipt of chemotherapy in human epidermal growth factor 2-positive disease. In a large nationwide dataset, the vast majority of older women with clinically node-negative breast cancer underwent axillary staging despite uncertainty about its impact on survival, particularly for those with lower-risk disease. Further study on how to tailor node assessment in older patients is warranted.
CLEO ® /Europe-EQEC 2017 thin-disk Ti:Sapphire laser arrays for many-beam generation and power scaling

Laser array research has predominantly focused on arrays of VCSELs because of several beneficial features, most notably their integrability into electronic systems [1]. Single-chip VECSEL arrays have also been demonstrated, using a method similar to what is presented here [2]. Non-semiconductor laser arrays, however, have received very little attention in comparison. Fiber arrays face scaling difficulties because each array element is a separate gain medium that requires alignment, while other solid-state arrays have so far required pumping with a VCSEL array to achieve multiple beams [3]. We have demonstrated the first many-beam, solid-state laser array, with the specific advantages of using a single gain medium and pump beam. The configuration is easy to align, uses a straightforward method of scaling the array size and power, and can utilize gain media that have not been previously considered for laser arrays.
Burial and exhumation history of the Xigaze forearc basin, Yarlung suture zone, Tibet

Abstract The Cretaceous–Eocene Xigaze forearc basin is a crucial data archive for understanding the tectonic history of the Asian continental margin prior to and following collision with India during the early Cenozoic Era. This study reports apatite and zircon (U–Th)/He thermochronologic data from fourteen samples from Albian-Ypresian Xigaze forearc strata to determine the degree and timing of heating (burial) and subsequent cooling (exhumation) of two localities along the Yarlung suture zone (YSZ) near the towns of Saga and Lazi. Thirty-seven individual zircon He ages range from 31.5 ± 0.8 Ma to 6.06 ± 0.18 Ma, with the majority of grains yielding ages between 30 Ma and 10 Ma. Twenty apatite He ages range from 12.7 ± 0.5 Ma to 3.9 ± 0.3 Ma, with the majority of grains yielding ages between 9 Ma and 4 Ma. These ages suggest that the Xigaze forearc basin was heated to 140–200 °C prior to cooling in Oligocene–Miocene time. Thermal modeling supports this interpretation and shows that the samples were buried to maximum temperatures of ∼140–200 °C by 35–21 Ma, immediately followed by the onset of exhumation. The zircon He and apatite He dataset and thermal modeling results indicate rapid exhumation from ∼21 Ma to 15 Ma, and at ∼4 Ma. The 21–15 Ma thermochronometric signal appears to be regionally extensive, affecting all the lithotectonic units of the YSZ, and coincides with movement along the north-vergent Great Counter Thrust system. Thrusting, coupled with enhanced erosion possibly related to the paleo-Yarlung River, likely drove Early Miocene cooling of the Xigaze forearc basin. In contrast, the younger phase of rapid exhumation at ∼4 Ma was likely driven by enhanced rock uplift in the footwall of north-striking rifts that cross-cut the YSZ.
Probing Solid–Solid Interfacial Reactions in All-Solid-State Sodium-Ion Batteries with First-Principles Calculations

We present an exposition of first-principles approaches to elucidating interfacial reactions in all-solid-state sodium-ion batteries. We will demonstrate how thermodynamic approximations based on assumptions of fast alkali diffusion and multispecies equilibrium can be used to effectively screen combinations of Na-ion electrodes, solid electrolytes, and buffer oxides for electrochemical and chemical compatibility. We find that exchange reactions, especially between simple oxides and thiophosphate groups to form PO43–, are the main cause of large driving forces for cathode/solid electrolyte interfacial reactions. A high reactivity with large volume changes is also predicted at the Na anode/solid electrolyte interface, while the Na2Ti3O7 anode is predicted to be much more stable against a broad range of solid electrolytes. We identify several promising binary oxides, Sc2O3, SiO2, TiO2, ZrO2, and HfO2, that are similarly or more chemically compatible with most electrodes and solid electrolytes than the common...
IRF1 Is a Transcriptional Regulator of ZBP1 Promoting NLRP3 Inflammasome Activation and Cell Death during Influenza Virus Infection.

Innate immune sensing of influenza A virus (IAV) induces activation of various immune effector mechanisms, including the nucleotide and oligomerization domain, leucine-rich repeat–containing protein family, pyrin domain containing 3 (NLRP3) inflammasome and programmed cell death pathways. Although type I IFNs are identified as key mediators of inflammatory and cell death responses during IAV infection, the involvement of various IFN-regulated effectors in facilitating these responses are less studied. In this study, we demonstrate the role of IFN regulatory factor (IRF)1 in promoting NLRP3 inflammasome activation and cell death during IAV infection. Both inflammasome-dependent responses and induction of apoptosis and necroptosis are reduced in cells lacking IRF1 infected with IAV. The observed reduction in inflammasome activation and cell death in IRF1-deficient cells during IAV infection correlates with reduced levels of Z-DNA binding protein 1 (ZBP1), a key molecule mediating IAV-induced inflammatory and cell death responses. We further demonstrate IRF1 as a transcriptional regulator of ZBP1. Overall, our study identified IRF1 as an upstream regulator of NLRP3 inflammasome and cell death during IAV infection and further highlights the complex and multilayered regulation of key molecules controlling inflammatory response and cell fate decisions during infections.
Nonprice Effects of Mergers: Issues and Evidence

Antitrust analysis of mergers focuses heavily—some would say, almost exclusively—on price effects. That focus does not reflect the lesser importance of quality, variety, cost, and technological pro...
The Dissonance of “Civil” Religion in Religious-Political Memetic Discourse During the 2016 Presidential Elections:

This article explores the interrelationship between religion and politics as presented through memetic discourse surrounding the 2016 presidential election. Based on a study of 150 Internet memes o...
The One-Atom Ideal Gas

The following three Lectures present a first example of the power of classical statistical mechanics, namely a treatment of the ideal gas. For mathematical simplicity, this Lecture considers a system which contains only one gas atom, Aside A shows what happens if the system contains two atoms. Lecture 5 extends the treatment to N-atom systems, while Lecture 6 treats atom-wall interactions, thereby obtaining the gas pressure. The calculations reproduce many important results of nineteenth-century kinetic theory, culminating in a microscopic derivation of the ideal gas law. The quantum (Bose-Einstein and Fermi-Dirac) ideal gases will be taken up separately, in Part II, Lecture 13.
Autoimmune Bullous Skin Diseases-Pemphigus and Pemphigoid

The group of autoimmune bullous skin diseases encompasses a number of specific disorders in which an autoimmune response is directed against skin adhesion molecules leading to blister formation. These disorders can be divided into two general groups: pemphigus and pemphigoid. Broadly defined, the pemphigus group includes those diseases in which the blisters occur within the epidermis (intraepidermal blister formation). The pemphigoid group includes those diseases in which the blisters occur at the junction of the epidermis and dermis (subepidermal blister formation). Each specific disease has unique clinical and immunological features, antigenic targets, and pathophysiology. This chapter highlights the three most common autoimmune bullous skin diseases: pemphigus vulgaris, pemphigus foliaceus, and bullous pemphigoid.
Classification of Alzheimer’s Disease, Mild Cognitive Impairment and Normal Control Subjects Using Resting-State fMRI Based Network Connectivity Analysis

This paper proposes a robust method for the Alzheimer’s disease (AD), mild cognitive impairment (MCI), and normal control subject classification under size limited fMRI data samples by exploiting the brain network connectivity pattern analysis. First, we select the regions of interest (ROIs) within the default mode network and calculate the correlation coefficients between all possible ROI pairs to form a feature vector for each subject. Second, we propose a regularized linear discriminant analysis (LDA) approach to reduce the noise effect due to the limited sample size. The feature vectors are then projected onto a one-dimensional axis using the proposed regularized LDA. Finally, an AdaBoost classifier is applied to carry out the classification task. The numerical analysis demonstrates that the purposed approach can increase the classification accuracy significantly. Our analysis confirms the previous findings that the hippocampus and the isthmus of the cingulate cortex are closely involved in the development of AD and MCI.
Future Talk: Accounting for the Technological and Other Future Discourses in Daily Life

Popular visions of futurity largely focus on one kind of future—that of technology. In this article, I consider how these conceptions and their implications are not fully grasped without accounting for nontechnical futures as well. Drawing on qualitative research with parents of children with developmental disabilities, centering on discussions of their child’s media and technology use, I introduce “future talk” as a conceptual framework for identifying how discourses of the future and of technology co-constitute one another to bring about particular future orientations. Four discourses of future talk were found: individual, societal, technological, and “nonfuture” projections. In short, individuals not only orient themselves to technological futures, but also orient technology to their personal understandings of the future. I close with a discussion of how “future talk” might be used by communication scholars to map how ordinary conversations about the future manifest in everyday life.
The Influence of Diverse Youth Development Models on Student Engagement and Academic Outcomes

Abstract After-school programs have a rich history of enriching and complementing traditional school experiences for participating youth, and there is mounting evidence that engagement in high-quality out-of-school programs can lead to positive academic outcomes. These programs balance multiple goals that include academic support, social–emotional learning, physical activity, and specialized curricula. As a result, some programs organize direct academic intervention (tutoring and structured homework time), some provide indirect educational support (study skills training), and others promote spillover effects for youth that originate in out-of-school programs that transfer to school settings (social–emotional learning and development). This chapter describes examples of different youth development models and programs that have been found to positively influence student engagement and academic outcomes. Specifically, it highlights school-based (21st Century Community Learning Centers), comprehensive (Boys & Girls Clubs), service-based (PeaceJam), and mentoring programs (Young Women’s Leadership Program). Given the diversity in approaches, aims, and outcomes, more information on the relationship between in-school and out-of-school learning is needed to inform policy, research, and practice.
Cassini-Huygens’ exploration of the Saturn system: 13 years of discovery

The Cassini-Huygens mission to Saturn provided a close-up study of the gas giant planet, as well as its rings, moons, and magnetosphere. The Cassini spacecraft arrived at Saturn in 2004, dropped the Huygens probe to study the atmosphere and surface of Saturn’s planet-sized moon Titan, and orbited Saturn for the next 13 years. In 2017, when it was running low on fuel, Cassini was intentionally vaporized in Saturn’s atmosphere to protect the ocean moons, Enceladus and Titan, where it had discovered habitats potentially suitable for life. Mission findings include Enceladus’ south polar geysers, the source of Saturn’s E ring; Titan’s methane cycle, including rain that creates hydrocarbon lakes; dynamic rings containing ice, silicates, and organics; and Saturn’s differential rotation. This Review discusses highlights of Cassini’s investigations, including the mission’s final year.
Microwave Shock Synthesis beyond Thermodynamic Equilibrium

Tuning the defect level in reduced graphene oxide (RGO) with proper level of polar groups and π-conjugation can render highly efficient absorption of microwave and extremely short thermal shock up to 1,600 K in just 100 ms, opening a pathway for rapid processing of nanoparticles, clusters, and individually dispersed atoms beyond thermal equilibrium.
Historical Origins of Firm Ownership Structure: The Persistent Effects of the African Slave Trade

This paper uses evidence from the historical African slave trade to extend prior theory linking modern firm ownership structure to institutions and social capital. We argue that institutions and so...
Role of p53-Mediated Apoptosis in Limiting Metastasis

p53 is a transcription factor known to play important roles in limiting tumorigenesis, including controlling the induction of pro-apoptotic genes and apoptosis in response to oncogenic stress. Using ChIP-Seq and RNA-Seq, our lab has identified p53 binding sites potentially responsible for p53-mediated induction of pro-apoptotic genes following DNA damage. Using CRISPR Cas9, we have generated fly strains with deletions or mutations within the p53 binding motif located in the experimentally verified p53 binding site. This deletion blocked DNA damage induced apoptosis. To study the functionality of the motif in limiting tumorigenesis, we introduced the deletion into a genetic tumorigenesis and metastasis model, where the tumor-suppressor cell polarity gene scribble was knocked down via shRNAi in the non-essential tissue compound eye and introduced together with strong oncogenic mutation that can lead to neoplasia and metastasis. We developed a scoring scale to quantify the severity of neoplasia and metastasis, where 0 indicates a wild type phenotype and 5 indicates the most severe metastatic phenotype. Results show that the p53BSKO predominantly displayed a score of 5 (39%). However, our preliminary results also suggested that the severity of this model may also subject to genetic background besides the p53 binding motif.
Dietary Intake of Upper Midwest and Southwest Native American Adults.

Limited information on current dietary patterns of Native American (NA) adults exists. This paper describes the dietary intake of 582 NA adults, aged 19–75 years, living in six communities in New M...
Scalable analysis of interaction threats in IoT systems

The ubiquity of Internet of Things (IoT) and our growing reliance on IoT apps are leaving us more vulnerable to safety and security threats than ever before. Many of these threats are manifested at the interaction level, where undesired or malicious coordinations between apps and physical devices can lead to intricate safety and security issues. This paper presents IoTCOM, an approach to automatically discover such hidden and unsafe interaction threats in a compositional and scalable fashion. It is backed with auto-mated program analysis and formally rigorous violation detection engines. IoTCOM relies on program analysis to automatically infer the relevant app’s behavior. Leveraging a novel strategy to trim the extracted app’s behavior prior to translating them to analyzable formal specifications,IoTCOM mitigates the state explosion associated with formal analysis. Our experiments with numerous bundles of real-world IoT apps have corroborated IoTCOM’s ability to effectively detect a broad spectrum of interaction threats triggered through cyber and physical channels, many of which were previously unknown, and to significantly outperform the existing techniques in terms of scalability.
Expression of a Tardigrade Dsup Gene Enhances Genome Protection in Plants

DNA damage is one of the most impactful events in living organisms, leading to DNA sequence changes (mutation) and disruption of biological processes. A study has identified a protein called Damage Suppressor Protein (Dsup) in the tardigrade Ramazzotius varieornatus that has shown to reduce the effects of radiation damage in human cell cultures (Hashimoto in Nature Communications 7:12808, 2016). We have generated tobacco plants that express the codon-optimized tardigrade Dsup gene and examined their responses when treated with mutagenic chemicals, ultraviolet (UV) and ionizing radiations. Our studies showed that compared to the control plants, the Dsup-expressing plants grew better in the medium containing mutagenic ethylmethane sulfonate (EMS). RT-qPCR detected distinct expression patterns of endogenous genes involved in DNA damage response and repair in the Dsup plants in response to EMS, bleomycin, UV-C and X-ray radiations. Comet assays revealed that the nuclei from the Dsup plants appeared more protected from UV and X-ray damages than the control plants. Overall, our studies demonstrated that Dsup gene expression enhanced tolerance of plants to genomutagenic stress. We suggest the feasibility of exploring genetic resources from extremotolerant species such as tardigrades to impart plants with tolerance to stressful environments for future climate changes and human space endeavors.
Enhanced toughness in ceramic-reinforced polymer composites with herringbone architectures

Abstract Crack deflection is often used as evidence of substantive fracture toughness in both natural and synthetic composites. The associated microstructures of these tough composites are often highly anisotropic, exhibiting both easy and hard directions for crack propagation. Cracks generally deflect away from hard directions to propagate instead in easy directions tying the overall fracture toughness to its weak axis. Instead, enhanced fracture toughness can be realized when cracks are forced to propagate along the hard directions. Recent advances in composite manufacturing including 3D magnetic printing have enabled the creation of detailed microstructures that can locally tune the fracture toughness anisotropy. In this work, we investigate a family of architectures reminiscent of a herringbone pattern, in which propagating cracks are effectively trapped along the spine between two regions. Along this spine, a crack can be inhibited from deflecting and forced to propagate along a relatively hard direction, resulting in a significant boost in initial and overall fracture toughness. We expand these realizations to generate beautiful herringbone mosaics that exhibit isotropic and enhanced fracture toughness. We have approached this problem with both numerical and experimental modalities to systematically test and characterize this new class of composite architectures.
A CASE STUDY OF SMALL-SCALE STRUCTURE FORMATION IN THREE-DIMENSIONAL SUPERNOVA SIMULATIONS

It is suggested in observations of supernova remnants that a number of large- and small-scale structures form at various points in the explosion. Multi-dimensional modeling of core-collapse supernovae has been undertaken since SN1987A, and both simulations and observations suggest/show that Rayleigh-Taylor (RT) instabilities during the explosion is a main driver of the formation of structure in the remnants. We present a case study of structure formation in three dimensions in a 15 M ☉ supernova for different parameters. We investigate the effect of moderate asymmetries and different resolutions of the formation and morphology of the RT unstable region, and take first steps toward determining typical physical quantities (size, composition) of arising clumps. We find that in this progenitor the major RT unstable region develops at the He/OC interface for all cases considered. The RT instabilities result in clumps that are overdense by one to two orders of magnitude with respect to the ambient gas, have size scales on the level of a few percent of the remnant diameter, and are not diffused after the first ~30 yr of the remnant evolution, in the absence of a surrounding medium.
48019 Create a mouse model of chronic sleep deprivation by specific-neuron targeted ablation

ABSTRACT IMPACT: A mouse model of minimally-invasive chronic sleep deprivation is essential for elucidating the impact of sleep deprivation on various health issues, and it would lead to the possibility of sleep as a therapeutic target. OBJECTIVES/GOALS: The lack of sleep has been associated with various health conditions. In mice, sleep deprivation has been achieved mainly by physical disturbances, which raises concern about confounding effects by stresses. Without physical disturbance, targeted neuron ablation can address this methodological flaw. METHODS/STUDY POPULATION: AdultVgat-IRES-cre mice undergo a stereotaxic injection of adeno-associated virus (AAV) vector containing mCherry-dtA to bilateral parafacial zone (PZ) to perform GABAergic neuron-specific cell ablation. Control mice receive an injection of AAV vector containing hSyn-DIO-mCherry. All mice are implanted with electroencephalogram and electromyogram (EEG/EMG) electrodes for sleep-wake analysis. After 7-10 days of the postoperative recovery period, mice are kept individually in a cage for sleep-wake state recording. EEG/EMG and video recording are used to measure total wake time, total sleep time, percent of rapid eye movement (REM) and non-REM sleep, and detailed characterization with spectral analysis. RESULTS/ANTICIPATED RESULTS: We anticipate that the ablation of GABAergic neurons in bilateral PZ decreases the fraction of sleep state in mice, especially non-REM sleep. In the Vgat-IRES-cre mice that received the injection of AAV vector containing mCherry-dtA, total sleep time is expected to be decreased constantly during the 8-week observation period. Sleep-wake staging by video activity recording is anticipated to be closely correlated with the gold standard staging by EEG/EMG. Possible stresses caused by the restriction of physical activity and handling of mice for EEG/EMG recording can be further minimized by the sleep-wake staging performed with the video activity recording. DISCUSSION/SIGNIFICANCE OF FINDINGS: The lack of sleep has been associated with negatively affecting overall health and is implicated in major health conditions including obesity, diabetes, and cardiovascular diseases. This chronic sleep deprivation mouse model can be used to understand the mechanisms of such detrimental effects on health, and would improve many health conditions.
Profiling the Tox21 Chemical Collection for Acetylcholinesterase Inhibition.

Background: Inhibition of acetylcholinesterase (AChE), a biomarker of organophosphorous and carbamate exposure in environmental and occupational human health, has been commonly used to identify pot...
Bounded Linear Functionals and Best Approximation from Hyperplanes and Half-Spaces

In this chapter we study the dual space of all bounded linear functionals on an inner product space. Along with the metric projections onto Chebyshev subspaces, these functionals are the most important linear mappings that arise in our work. We saw in the last chapter that every element of the inner product space X naturally generates a bounded linear functional on X (see Theorem 5.18). Here we give a general representation theorem for any bounded linear functional on X (Theorem 6.8). This implies the Frechet-Riesz representation theorem (Theorem 6.10), which states that in a Hilbert space every bounded linear functional has a “representer.” This fact can be used to show that every Hilbert space is equivalent to its dual space. In general (incomplete) inner product spaces we can characterize the bounded linear functionals that are generated by elements, or representers, in X. They are precisely those that “attain their norm” (Theorem 6.12). We should mention that many of the results of this chapter—particularly those up to Theorem 6.12—can be substantially simplified or omitted entirely if the space X is assumed complete, i.e., if X is a Hilbert space. Because many of the important spaces that arise in practice are not complete, however (e.g., C2[a, b]), we have deliberately avoided the simplifying assumption of completeness. This has necessitated developing a somewhat more involved machinery to handle the problems arising in incomplete spaces.
Cloning and Characterization of Polyphosphate Kinase and Exopolyphosphatase Genes from Pseudomonas aeruginosa 8830

Pseudomonas aeruginosa accumulates polyphosphates in response to nutrient limitations. To elucidate the function of polyphosphate in this microorganism, we have investigated polyphosphate metabolism by isolating from P. aeruginosa 8830 the genes encoding polyphosphate kinase (PPK) and exopolyphosphatase (PPX), which are involved in polyphosphate synthesis and degradation, respectively. The 690- and 506-amino-acid polypeptides encoded by the two genes have been expressed in Escherichia coli and purified, and their activities have been tested in vitro. Gene replacement was used to construct a PPK-negative strain of P. aeruginosa 8830. Low residual PPK activity in the ppk mutant suggests a possible alternative pathway of polyphosphate synthesis in this microorganism. Primer extension analysis indicated that ppk is transcribed from a ςE-dependent promoter, which could be responsive to environmental stresses. However, no coregulation between ppk and ppx promoters has been demonstrated in response to osmotic shock or oxidative stress.
A 102-dB spurious-free DR /spl Sigma//spl Delta/ ADC using a dynamic dither scheme

A sigma-delta analog-to-digital converter (ADC) using dynamic dither to achieve a tone-free dynamic range of 102 dB in an audio bandwidth is presented. The design was implemented using a third-order 2:1 cascade architecture with an oversampling ratio of 128. The ADC modulator consumes 22 mW from a 3.0 V power supply, and was fabricated in 0.6-/spl mu/m CMOS (analog portion) and 0.3-/spl mu/m CMOS (digital portion) using multichip-module technology.
Holonic Simulation of a Design System for Performance Analysis

In this paper, we present our approach to assess the performance of an engineering design system in the field of microelectronics using a holonic simulation. Instead of measuring some input and output parameters of the system and applying some metrics to them as common performance assessment approaches do, we build a model of the entire system and simulate the course of the design process using a multi agent system. The performance metrics are then applied to the detailed results of this simulation. The main focus of this paper thereby lies in the simulation part of the approach which we designed to have two parts: a planning phase and an execution phase.
Abstract 72: Long Non-coding RNAs Mediate Cerebrovascular Endothelial Pathologies in Ischemic Stroke

The structural and functional changes in the cerebral endothelium during cerebral ischemia are well-known to affect the extent of ischemic brain injury and stroke outcome. Therefore, the brain endothelium becomes an important therapeutic target for the inhibition of cerebrovascular dysfunction in ischemic stroke. However, the regulatory mechanisms of cerebral endothelial dysfunction after cerebral ischemia remain largely unexplored. Previously we have documented the important regulatory roles of microRNAs in the cerebral vasculature, in particular the cerebral vascular endothelium. However, the functional significance and molecular mechanisms of other classes of non-coding RNAs in the regulation of cerebrovascular endothelial pathophysiology after stroke are completely unknown. Using RNA-sequencing technology, we profiled long non-coding RNAs (lncRNAs) expressional signatures in primary brain microvascular endothelial cells (BMECs) after oxygen-glucose deprivation (OGD). After 16h of OGD exposure, the expression levels for 362 of the 10,677 lncRNAs analyzed changed significantly, including a total of 147 lncRNAs increased and 70 lncRNAs decreased by more than 2-fold. Interestingly, metastasis associated lung adenocarcinoma transcript 1 (Malat1) is one of the most highly upregulated OGD-responsive endothelial lncRNAs, which has been initially discovered as a tumor-associated lncRNA involved in epigenetic control of gene expression. Increased Malat1 levels were further confirmed in cultured BMECs after OGD as well as isolated cerebral microvessels in mice after 1h MCAO and 24h reperfusion by qPCR. Of note, Malat1 was not pathologically increased in whole mouse brains in response to the same ischemic insult. The expression and nuclear localization of Malat1 were also shown in BMECs by in situ hybridization. Furthermore, loss-of-Malat1 function by LNA-GapmeR significantly increased OGD-induced loss of endothelial markers and endothelial inflammation in BMECs, implying Malat1 a critical role in protecting the cerebral microvasculature from cerebral ischemic insults. These findings suggest that lncRNAs may function as a class of novel master regulators in cerebrovascular endothelial pathologies after ischemic stroke.
Automatically Generated DAML Markup for Semistructured Documents

The semantic web is becoming a realizable technology due to the efforts of researchers to develop semantic markup languages such as the DARPA Agent Markup Language (DAML). A major problem that faces the semantic web community is that most information sources on the web today lack semantic markup. To fully realize the potential of the semantic web, we must find a way to automatically upgrade information sources with semantic markup. We have developed a system based on the STALKER algorithm that automatically generates DAML markup for a set of documents based on previously seen labeled training documents. Our rule-learning approach to semantic markup is highly effective when dealing with semistructured documents.
High Temperature Structure and Properties of Grain Boundaries - Insights Obtained from Atomic Level Simulations

Molecular-dynamics simulations of grain boundaries in Si and fcc metals reveal that high-energy boundaries are disordered, even at low temperatures, with their local atomic structure very similar to that of bulk amorphousmaterial. By contrast, low energy grain boundaries are crystalline all the way up to the melting point. Upon heating intergranular "confined amorphous" structures of high-energy grain boundaries exhibit reversible transition into universal, highly confined, liquid-like structure. High-temperature properties, such as the grain boundary diffusion therefore involve liquid-like mechanisms, with activation energies related to the diffusion process in the melt. By contrast to Si and fcc metals, high-energy diamond grain boundaries are more ordered structurally, but contain coordination disorder resulting from ability of carbon to change its hybridization from sp 3 to sp 2 character. Based on the insights obtained from our simulation of individual grain boundaries we were able to design nanocrystalline 3D microstructures, which allow to study grain boundary diffusion creep process by molecular-dynamics simulations. In order to prevent grain growth and thus to enable steady-state diffusion creep to be observed on a time scale accessible to molecular-dynamics simulations (of typically 10 - 9 s), our input microstructures were tailored to (i) have a uniform grain shape and a uniform grain size of nm dimensions and (ii) contain only high-energy grain boundaries that, consistently with our studies of individual, bicrystalline grain boundaries, exhibit rather fast, liquid-like self-diffusion at high temperatures. Our simulations reveal that under relatively high tensile stresses these microstructures, indeed, exhibit steady-state diffusion creep that is homogeneous with a strain rate that agrees quantitatively with that given by the Coble-creep formula.
Replication of Mengovirus in HeLa Cells Preinfected with Nonreplicating Poliovirus

Abstract The replication of mengovirus in HeLa cells preinfected with poliovirus in the presence of 10−3 M guanidine was investigated. Although host cell protein synthesis is inhibited by the presence of nonreplicating poliovirus, it is found that mengovirus ribonucleic acid (RNA) and protein synthesis proceed normally under the same conditions. Furthermore, no effects on mengovirus growth by poliovirus can be detected either when Mengo protein synthesis is interrupted by Acti-Dione or when its RNA synthesis is reduced by incubation at 28 C. It is suggested that the poliovirus inhibitory factor may be able to distinguish between an RNA element required in the protein-synthesizing apparatus of the host cell and a comparable element in that of the heterologous virus.
Numerical finite element formulation of the Schapery non-linear viscoelastic material model

This study presents a numerical integration method for the non-linear viscoelastic behaviour of isotropic materials and structures. The Schapery's three-dimensional (3D) non-linear viscoelastic material model is integrated within a displacement-based finite element (FE) environment. The deviatoric and volumetric responses are decoupled and the strain vector is decomposed into instantaneous and hereditary parts. The hereditary strains are updated at the end of each time increment using a recursive formulation. The constitutive equations are expressed in an incremental form for each time step, assuming a constant incremental strain rate. A new iterative procedure with predictor–corrector type steps is combined with the recursive integration method. A general polynomial form for the parameters of the non-linear Schapery model is proposed. The consistent algorithmic tangent stiffness matrix is realized and used to enhance convergence and help achieve a correct convergent state. Verifications of the proposed numerical formulation are performed and compared with a previous work using experimental data for a glassy amorphous polymer PMMA. Copyright © 2003 John Wiley & Sons, Ltd.
Muscarinic M1 Receptors Mediate the Increase in Pulmonary Resistance during Vagus Nerve Stimulation in Dogs

The physiologic roles of the 2 muscarinic receptors (M1 and M2) in the vagal control of pulmonary resistance were studied by comparing the effects of pirenzepine (PZ, M1-blocker), gallamine (GAL, M2-blocker), and atropine (AT, M1- and M2-blocker) on the increase in pulmonary resistance (Rl) and on the reduction in heart rate (HR) during bilateral cervical vagus nerve stimulation in 18 anesthetized (chloralose and urethane) and paralyzed (vecuronium) dogs. PZ, AT, and GAL all inhibited the reduction in HR during vagus nerve stimulation, although the inhibition required relatively high doses of PZ and GAL. AT and PZ inhibited the increase in Rl during vagus nerve stimulation. The ratio of the dose needed to inhibit by 50% the HR response to the dose needed to inhibit by 50% the Rl response was approximately 45:1 for PZ, 12:1 for AT, and < 0.4:1 for GAL. Thus, compared with AT, PZ is a more selective blocker of vagally induced increases in Rl, indicating that M1 receptors are present in the airway smooth mus...