cssi/SciSciGPT-SciSciNet huggingface dataset:
gKaKs: The pipeline for genome level Ka/Ks calculation

Summary: gKaKs is a codon-based genome-level Ka/Ks computation pipeline developed and based on programs from four widely used packages: BLAT, BLASTALL (including bl2seq, formatdb and fastacmd), PAML (including codeml and yn00) and KaKs_Calculator (including 10 substitution rate estimation methods). gKaKs can automatically detect and eliminate frameshift mutations and premature stop codons to compute the substitution rates (Ka, Ks and Ka/Ks) between a well-annotated genome and a non-annotated genome or even a poorly assembled scaffold dataset. It is especially useful for newly sequenced genomes that have not been well annotated. We applied gKaKs to estimate the genome-wide substitution rates in five pairs of closely related species. The average Ka and Ks computed by gKaKs were consistent with previous studies. We also compared the Ka, Ks and Ka/Ks of mouse and rat orthologous protein-coding genes estimated by gKaKs and based on the alignments generated by PAL2NAL. Results from two methods are compatible. Availability and implementation: gKaKs is implemented in Perl and is
Silica-poor, mafic alkaline lavas from ocean islands and continents: Petrogenetic constraints from major elements

Strongly silica-poor (ne-normative), mafic alkaline lavas generally represented by olivine nephelinites, nephelinites, melilitites, and olivine melilitites have erupted at various locations during Earth's history. On the basis of bulk-rock Mg#, high concentrations of Na2O, TiO2, and K2O, and trace element geochemistry, it has been suggested that these lavas represent low-degree melts that have undergone little crystal fractionationen route to the surface. Many of these lavas also carry high-pressure mantle material in the form of harzburgite, spinel lherzolite, and variants of websterite xenoliths, and rare garnet-bearing xenoliths. However, phenocryst phases instead indicate that these magmas cooled to variable extents during their passage. We note subtle, yet important, differences in terms of CaO, Al2O3, CaO/AlP2O3, and CaO/MgO. High-pressure experimental melting studies in CMAS-CO2 (3-8 GPa) and natural lherzolitic systems (3GPa) demonstrate that at an isobar increasing F leads to a moderate decrease in CaO + MgO, whereas CaO/MgO and CaO/Al2O3 sharply decrease. Relatively high CaO/Al2O3 indicates melting in the presence of garnet (>- 85 km). Studies also demonstrate that CO2-bearing lherzolitic systems, when compared with anhydrous ones, also have higher CaO content in the coexisting melt at a given P and T. Comparison of the bulk-rock major-element chemistry of silica-poor, mafic alkaline lavas with experimentally determined high-pressure melts indicates that melting of anhydrous mantle lherzolite or garnet pyroxenite is not able to explain many of the major element systematics of the lavas. However, high-pressure partial melts of carbonated lherzolite have the right major element trends. Among ocean islands, lavas from Samoa and Hawaii are perhaps the products of very low degree of partial melting. Lavas from Gran Canaria and Polynesia represent products of more advanced partial melting. On continents, lavas from South Africa and certain localities in Germany are the products of a very low degree of partial melting, and those from Texas and certain other localities in Germany are products of a slightly more advanced degree of partial melting of a carbonated lherzolite. Lavas from Deccan, Czech Republic, and Freemans Cove are the products of even more advanced degree of partial melting. The mere presence of mantle xenoliths in some of these lavas does not necessarily mean that the erupted lavas represent direct mantle melts.
Structural and Intensity Changes of Hurricane Bret (1999). Part I: Environmental Influences

Hurricane Bret underwent a rapid intensification (RI) and subsequent weakening between 1200 UTC 21 August and 1200 UTC 22 August 1999 before it made landfall on the Texas coast 12 h later. Its minimum sea level pressure fell 35 hPa from 979 to 944 hPa within 24 h. During this period, aircraft of the National Oceanic and Atmospheric Administration (NOAA) flew several research missions that sampled the environment and inner core of the storm. These datasets are combined with gridded data from the National Centers for Environmental Prediction (NCEP) Global Model and the NCEP–National Center for Atmospheric Research (NCAR) reanalyses to document Bret’s atmospheric and oceanic environment as well as their relation to the observed structural and intensity changes. Bret’s RI was linked to movement over a warm ocean eddy and high sea surface temperatures (SSTs) in the Gulf of Mexico coupled with a concurrent decrease in vertical wind shear. SSTs at the beginning of the storm’s RI were approximately 29°C and steadily increased to 30°C as it moved to the north. The vertical wind shear relaxed to less than 10 kt during this time. Mean values of oceanic heat content (OHC) beneath the storm were about 20% higher at the beginning of the RI period than 6 h prior. The subsequent weakening was linked to the cooling of nearcoastal shelf waters (to between 25° and 26°C) by prestorm mixing combined with an increase in vertical wind shear. The available observations suggest no intrusion of dry air into the circulation core contributed to the intensity evolution. Sensitivity studies with the Statistical Hurricane Intensity Prediction Scheme (SHIPS) model were conducted to quantitatively describe the influence of environmental conditions on the intensity forecast. Four different cases with modified vertical wind shear and/or SSTs were studied. Differences between the four cases were relatively small because of the model design, but the greatest intensity changes resulted for much cooler prescribed SSTs. The results of this study underscore the importance of OHC and vertical wind shear as significant factors during RIs; however, internal dynamical processes appear to play a more critical role when a favorable environment is present.
Simultaneous Transmission of Wireless and Wireline Services Using a Single 60-GHz Radio-Over-Fiber Channel by Coherent Subcarrier Modulation

We proposed and experimentally demonstrated a novel hybrid subcarrier modulation (H-SCM) technique to generate a spectral-efficient 60-GHz optical millimeter-wave (mm-wave) that carries independent 2.5-Gb/s wireless and 10-Gb/s wireline signals using intensity and phase modulation, respectively. The frequency beating components of the 60-GHz channel due to interleaved and imbalanced optical path in H-SCM are numerically analyzed and experimentally measured in terms of timing jitter and amplitude fluctuation. The generated 60-GHz optical mm-wave signal using H-SCM with phase noise variance of about 0.5 is demonstrated in a radio-over-fiber testbed propagating through a combined distance of 25-km fiber and 4-m free space. The power penalties for the received wireless and wireline signals are 1 and 0.2 dB at 10-9 bit-error rate, respectively.
Promoting Affective Development in Physical Education: The Value of Journal Writing

(1996). Promoting Affective Development in Physical Education: The Value of Journal Writing. Journal of Physical Education, Recreation & Dance: Vol. 67, No. 7, pp. 19-23.
Biochemical characteristics and physiological significance of major DNA topoisomerases.

This review covers the basic biochemistry of the major topoisomerases from procaryotic and eucaryotic cells and attempts to enumerate their differences. Two companion reviews describing the methods used to study topoisomerases and examining the inhibitory effects of quinolone antibacterial agents on topoisomerases and related test systems will follow
Differential regulation of baboon SP-A1 and SP-A2 genes: structural and functional analysis of 5'-flanking DNA.

Surfactant protein (SP) A gene transcription is developmentally regulated and stimulated by hormones and factors that increase intracellular cAMP. The baboon (b) genome contains two highly similarS...
Complexity, parallel computation and statistical physics: Research Articles

The intuition that a long history is required for the emergence of complexity in natural systems is formalized using the notion of depth. The depth of a system is defined in terms of the number of parallel computational steps needed to simulate it. Depth provides an objective, irreducible measure of history that is applicable to systems of the kind studied in statistical physics. It is argued that physical complexity cannot occur in the absence of substantial depth and that depth is a useful proxy for physical complexity. The ideas are illustrated for a variety of systems in statistical physics. © 2006 Wiley Periodicals, Inc. Complexity 11: 46–64, 2006This paper was submitted as an invited paper resulting from the “Understanding Complex Systems” conference held at the University of Illinois–Urbana Champaign, May 2005
Irreversible Electroporation (IRE) in Renal Tumors

Small renal masses (SRMs) have been traditionally managed with surgical resection. Minimally invasive nephron-sparing treatment methods are preferred to avoid harmful consequences of renal insufficiency, with partial nephrectomy (PN) considered the gold standard. With increase in the incidence of the SRMs and evolution of ablative technologies, percutaneous ablation is now considered a viable treatment alternative to surgical resection with comparable oncologic outcomes and better nephron-sparing property. Traditional thermal ablative techniques suffer from unique set of challenges in treating tumors near vessels or critical structures. Irreversible electroporation (IRE), with its non-thermal nature and connective tissue-sparing properties, has shown utility where traditional ablative techniques face challenges. This review presents the role of IRE in renal tumors based on the most relevant published literature on the IRE technology, animal studies, and human experience.
Cystic pancreatic neuroendocrine tumors: endoscopic ultrasound and fine-needle aspiration characteristics.

Background and study aims: Limited data are available on the endoscopic ultrasound (EUS) and fine-needle aspiration (FNA) characteristics of cystic pancreatic neuroendocrine tumors (CPanNets). The aims of this study were to describe the EUS and FNA characteristics of pathologically confirmed CPanNets and to compare these characteristics with mucinous cysts from matched patients. Patients and methods: From an EUS – FNA database (between 1999 and 2011), 19 patients with a pathologically confirmed CPanNet were identified. Patient characteristics, cyst fluid carcinoembryonic antigen (CEA) levels, pathology, and EUS findings were analyzed. For comparison, age- and sex-matched patients with mucinous cysts were randomly chosen from the same database. Results: Of the 19 patients, two had multiple endocrine neoplasia type 1 and two had metastases. The median diameter of the lesions was 24 mm. EUS revealed unilocular lesions in 7 patients, thinly septated lesions with thin walls in 1, and mixed solid-cystic lesions in 11. EUS – FNA cytology confirmed neoplasm in 12 of the 19 patients (63.2 %). The median cyst fluid CEA level (n = 15) was 1.1 ng/mL (range 0.3 – 500 ng/mL). Compared with matched patients with mucinous cysts, the median cyst fluid CEA was lower (1.1 ng/mL vs. 400 ng/mL), thick walls were more common (66.7 % vs. 13.3 %), and diagnostic cytology was more likely (73.3 % vs. 20.0 %). Conclusions: Analysis of EUS and FNA results showed that the cyst fluid from CPanNets had a lower CEA concentration, a higher frequency of thick walls on EUS, and higher diagnostic cytology compared with mucinous cysts. These findings may aid in the diagnosis of CPanNets.
Immobilization of Metal-Organic Framework Copper(II) Benzene-1,3,5-tricarboxylate (CuBTC) onto Cotton Fabric as a Nitric Oxide Release Catalyst

Immobilization of metal-organic frameworks (MOFs) onto flexible polymeric substrates as secondary supports expands the versatility of MOFs for surface coatings for the development of functional materials. In this work, we demonstrate the deposition of copper(II) benzene-1,3,5-tricarboxylate (CuBTC) crystals directly onto the surface of carboxyl-functionalized cotton capable of generating the therapeutic bioagent nitric oxide (NO) from endogenous sources. Characterization of the CuBTC-cotton material by XRD, ATR-IR, and UV-vis indicate that CuBTC is successfully immobilized on the cotton fabric. In addition, SEM imaging reveals excellent surface coverage with well-defined CuBTC crystals. Subsequently, the CuBTC-cotton material was evaluated as a supported heterogeneous catalyst for the generation of NO using S-nitrosocysteamine as the substrate. The resulting reactivity is consistent with the activity observed for unsupported CuBTC particles. Overall, this work demonstrates deposition of MOFs onto a flexible polymeric material with excellent coverage as well as catalytic NO release from S-nitrosocysteamine at therapeutic levels.
Importância crítica em Cuba de O homem que amava os cães, de Leonardo Padura

The novel The man who loved dogs, by Leonardo Padura, brought to Cuban readers a strong review of the Soviet Stalinism and its machinery against Leon Trotski, and also a review of Soviet intervention in the Spanish Civil War. Both important facts of 20th-century history are connected with Cuban reality after 1959.
Duality Theory Revisited

Starting with the primal problem, let us $$ \begin{gathered} maxf(X) = C'X\quad s.t. \hfill \\ AX \leqq b, X \geqq 0, X\varepsilon {{R}^{n}}, \hfill \\ \end{gathered} $$ where A is of order (mxn) with rows α1,..., αm and b is an (m x 1) vector with components b1,…,b m . Alternatively, if $$\bar A = \left[ {\begin{array}{*{20}{c}}A\\\ldots \\{ - {I_n}}\end{array}} \right],\bar b = \left[ {\begin{array}{*{20}{c}}b\\\ldots \\0\end{array}} \right]$$ are respectively of order (m + n x n) and (m + n x 1), then we may $$\max f\left( x \right) = C'Xs.t.$$ $$\bar b - \bar AX0,$$ where X€R n is now unrestricted. In this formulation Xj ≥ 0, j = l,…,n,\(\bar b - \bar AX0,\) is treated as a structural constraint so that defines a region of feasibleor admissible solutions K ⊂ R n .
Cross-Linkage Between Mapillary Street Level Photos and OSM Edits

Mapillary is a VGI platform which allows users to contribute crowdsourced street level photographs from all over the world. Due to unique information that can be extracted from street level photographs but not from aerial or satellite imagery, such as the content of road signs, users of other VGI Web 2.0 applications start to utilize Mapillary for collecting and editing data. This study assesses to which extent OpenStreetMap (OSM) feature edits use Mapillary data, based on tag information of added or edited features and changesets. It analyzes how spatial contribution patterns of individual users vary between OSM and Mapillary. A better understanding of cross-linkage patterns between different VGI platforms is important for data quality assessment, since cross-linkage can lead to better quality control of involved data sources.
Early Manifestations of Autism Spectrum Disorders

Autism is a neuro-developmental disorder defined by deficits in social interaction and communication, and restricted interests and repetitive behaviors. Identification of the earliest signs of the disorder has important implications for understanding the developmental course and potential underlying neural mechanisms. It may also facilitate earlier identification of affected children and more timely and effective intervention. This chapter reviews the literature from both retrospective and prospective studies that identify early biomarkers and behavioral symptoms of atypical social motivation, delayed development of functional communication, and the onset of repetitive behaviors. The data suggest that signs of the disorder are not evident in the first six months of life, but emerge in the second half of the first year. The chapter closes with consideration of potential theoretical models of the available data and a brief discussion of the implications of these data for early diagnosis.
Cell density influences expression of pluripotency genes and differentiation in colorectal cancer cells

R understanding of colorectal tumours (along with other tumour cell types) indicates that they contain a small population of cancer stem cells (CSC) that are capable of self-renewal and generation of all the differentiated cell types in the tumour. Another feature of colorectal tumours is that the cells appear to undergo a transition at the invasive front, that endows the tumour cells with the ability to invade and metastasize. This process resembles the epithelialmesenchymal transition (EMT). A possible link between these two processes, has recently been identified when it was shown that normal mammary epithelial cells that were induced to undergo an EMT, acquired stem cell characteristics. An in vitro system that mimics the changes occurring in colorectal cancer cells during EMT would be significant in identifying factors involved in these changes. The colon cancer cell line, SW480, when grown to low or high cell density resembles cell populations at the invasive front (mesenchymal-like) and central mass (epithelial-like) of the tumour, respectively. We show that Brachyury, is differentially expressed in SW480 cells, being present in low density cells. We also show that Brachyury expression is regulated by the Wnt-signaling effector, beta-catenin in a density dependent manner. Brachyury/ Nanog expressing cells are also positive for colorectal cancer (CRC) stem cell (SC) marker. We propose a mechanism whereby expression of beta-catenin in low cell density cells induces the expression of Brachyury and Nanog, preventing differentiation. These Brachyury expressing cells may be the cancer stem cells as determined by CRC-SC marker expression.
Abstract B133: Metalloprotease-disintegrin ADAM12-L in breast cancer cells: Regulation of expression by microRNA-200b/c

ADAM12-L, a member of the cell surface ADAM metalloprotease family, is selectively up-regulated in claudin-low breast cancers and in residual breast tumors after conventional therapy. In vitro, ADAM12-L is enriched in breast cancer cells grown in suspension as mammospheres and after induction of epithelial-to-mesenchymal transition (EMT) by transforming growth factor β or Twist. The mechanisms responsible for this pattern of ADAM12-L expression are not known. The 39-UTR of ADAM12-L mRNA contains several predicted target sites for miR-200b/c, important regulators of EMT, tumor invasion, metastasis, and chemosensitivity. The mRNA splice variant encoding the secreted isoform ADAM12-S and lacking miRNA-200b/c target sites in the 39UTR shows a different expression pattern than ADAM12-L. The purpose of this study was to determine whether ADAM12-L expression in breast cancer cells is regulated by miR-200b/c. To achieve this goal, breast cancer cells with high expression of ADAM12-L and low levels of miR-200b/c (SUM159PT, SUM1315MO2, and Hs578T) were treated with miR-200b/c mimics. Cells with low expression of ADAM12-L and high levels of miR-200b/c (SUM225PT, SUM149PT, and MCF7) were treated with miR-200b/c inhibitors. To determine whether ADAM12-L mRNA is a direct target of miR-200b/c, we performed co-transfection experiments using miR-200b/c mimics/inhibitors and ADAM12-L 39UTR reporter constructs with intact or mutated miR-200b/c target sites. Our results indicate that miR-200b/c down-regulates ADAM12-L levels in breast cancer cells, but the mechanism does not seem to involve direct targeting of its 39UTR. As ADAM12-L is virtually not present in normal breast tissue, we propose that ADAM12-L may be considered as a novel cell surface marker of tumor cells undergoing EMT and/or as a read-out for miR-200b/c activity in breast tumors. Citation Format: Sara Duhachek-Muggy, Anna Zolkiewska. Metalloprotease-disintegrin ADAM12-L in breast cancer cells: Regulation of expression by microRNA-200b/c. [abstract]. In: Proceedings of the AACR Special Conference on Advances in Breast Cancer Research: Genetics, Biology, and Clinical Applications; Oct 3-6, 2013; San Diego, CA. Philadelphia (PA): AACR; Mol Cancer Res 2013;11(10 Suppl):Abstract nr B133.
Sensitivity for Diagnosing Group A Streptococcal Pharyngitis from Manufacturers is 10% Higher than Reported in Peer-Reviewed Publications.

OBJECTIVES Meta-analyses based on peer-reviewed publications report a sensitivity of approximately 85% for rapid antigen streptococcus tests to diagnose group A streptococcal (GAS) pharyngitis. Because these meta-analyses excluded package inserts, we examined the test characteristics of rapid antigen streptococcal tests and molecular methods that manufacturers report in their package inserts. METHODS We included tests available in the US market (Food and Drug Administration, period searched 1993-2015) and used package insert data to calculate pooled sensitivity and specificity. To examine quality, we used the Quality Assessment of Diagnostic Accuracy Studies-2. We excluded 26 tests having different trade names but identical methods and data. RESULTS The study design was prospective in 41.7% (10 of 24). The pooled sensitivity of the most commonly used method, lateral flow/immunochromatographic, was 95% (95% confidence interval [CI] 94-96) and the pooled specificity was 98% (96-98); 7108 patients. The pooled sensitivity of the polymerase chain reaction or molecular methods was 98% (95% CI 96-98) and the pooled specificity was 96% (95% CI 95-97); 5685 patients. CONCLUSIONS Package inserts include sponsored studies that overestimate the sensitivity of rapid tests to diagnose GAS pharyngitis by approximately 10%. Physicians should understand that package inserts overestimate diagnostic test utility; a negative test cannot be used to exclude GAS pharyngitis.
Integrating Usability Testing with Digital Rhetoric in OWI

Abstract While usability testing can help instructors improve the design of online writing instruction (OWI), its emphasis on student-users sometimes overlooks the networked rhetorical ecologies in which those student-users operate, tilting online composition pedagogy toward neoliberal models of higher education that cater to the student-as-consumer. In response, I propose augmenting usability testing in online writing education with the theories of digital rhetoric. In the context of OWI, usability theory and digital rhetoric share a similar emphasis on the student as a user or audience, but they also have at least two key differences. First, unlike digital rhetoric, usability testing typically elides the political and ideological implications of student-users’ experiences. Second, the usability theories of Jakob Nielsen, for example, tend to view online interfaces as static objects manipulated by users. Digital rhetoric, on the other hand, sees interfaces as dynamic, real-time interactions. Although both paradigms have their advantages, I argue that integrating usability testing with the theories of digital rhetoric can add complexity to researchers’ understanding of OWI by revealing not only how students use online writing environments but also how they use them rhetorically.
Angular Fokker-Planck decomposition and representation techniques

Two new methods for decomposing scattering cross sections into the forward-peaked and smooth components required for Boltzmann-Fokker-Planck calculations are presented. The first is slightly simpler than existing methods and offers the same level of effectiveness. The second is more expensive than existing methods, but is much more effective. Legendre moments that give a positive representation for the angular Fokker-Planck operator and can be used in standard S{sub n} codes are presented. Computational results are given that demonstrate the effectiveness of these new decomposition and representation techniques.
Moral and Logical Perspectives on Appealing to Pity

Any argument whose premises, rather than containing evidence having a direct bearing on the conclusion, instead gives reasons why acceptance of the conclusion would reduce someone’s misery. Attempting to persuade others of one’s point of view by appealing to their sympathy instead of presenting evidence. [A] Person who commits this fallacy is hoping his listeners will adopt a belief on the basis of an emotion he has instilled in them: . . . [e.g.,]. pity. . . .
The Status of End-User Computing Support: An Exploratory Study

End-User Computing (EUC) influences user productivity, information systems backlogs and user satisfaction. An exploratory study of 192 Midwest end-users was undertaken to investigate support services and end-user types superimposed on support sources. The results of this integrated review offer a richer understanding of end-user dynamics. Data collection occurred through a three-part questionnaire. End-user types were categorized using the Cotterman and Kumar (1989) classification scheme. Support categories were assessed using the Mirani and King (1994) instrument. The Govindarajulu and Reithel (1998) assessment instrument evaluated support services within information centers for local MIS staff and informal assistance. Results are presented from instrument validation procedures and descriptive data analysis that permit conclusions about EUC dynamics. Instrument validation was conducted using standard measures of internal consistency reliability and factor analysis, Cronbach’s alpha and a Principle Components Factor Analysis (PCFA), to facilitate factor loading. Descriptive data analysis employed conventional frequency distributions, scatterplots, descriptive data statistics, and other graphical data displays.
Exposure risks and ineffectiveness of total release foggers (TRFs) used for cockroach control in residential settings

The German cockroach, Blattella germanica, is one of the most challenging pests to eradicate from indoor environments. Professional pest control is often prohibitively expensive, prompting low-income residents to turn to over-the-counter consumer products, including total release foggers (TRFs, “bug bombs”). Despite their widespread use, little is known regarding either the associated pesticide exposure risks or the efficacy of TRFs. Cockroach-infested homes were recruited into the study. Wipe samples were collected from various surfaces before TRFs were discharged, immediately after, and one month later to determine pesticide exposure risks in 20 homes (divided equally among four different TRF products). Simultaneously, cockroach populations were monitored in all homes to assess the efficacy of TRFs. In parallel, 10 homes were treated with gel baits (divided equally between two bait products), to compare TRFs to a more targeted, low-risk, do-it-yourself intervention strategy. TRFs failed to reduce cockroach populations, whereas similarly priced gel baits caused significant declines in the cockroach populations. Use of TRFs resulted in significant pesticide deposits throughout the kitchen. Across all products, pesticides, and horizontal kitchen surfaces, pesticide residues following TRF discharge were 603-times (SEM ±184) higher than baseline, with a median increase of 85 times. The high risks of pesticide exposure associated with TRFs combined with their ineffectiveness in controlling German cockroach infestations call into question their utility in the marketplace, especially because similarly priced and much safer bait products are highly effective in the indoor environment.
Abstract CT064: Intranasal brain delivery using NEO100 for recurrent glioblastoma

NO CHANGES TO ORIGINAL ABSTRACT NEO100 is a GMP quality, purified perillyl alcohol (POH) which has been undergoing clinical trials under IND approval (144,595) entitled "Open label, Phase I/IIa dose escalation study of safety and efficacy of NEO100 in recurrent grade IV glioma." It was granted orphan drug and fast track status by the FDA. Inclusion criteria include temozolomide failure, bevacizumab naive, tumor less than 3x3 cm, and Karnofsky score greater than or equal to 60. Patients were enrolled from University of Southern California (USC), Cleveland Clinic, and University of Washington. Total number of patients to be enrolled for Phase I is 12 with four dose escalating cohorts of 3 patients per cohort. The remaining 31 patients would be enrolled after maximal tolerated dosage (MTD) for Phase IIa. The delivery is intranasal via a nasal nebulizer using the concept of nasal brain delivery via the olfactory and trigeminal nerves for delivery to the brain and tumor. To date, 8 patients have been enrolled. Cohort 1 received 96 mg/dose qid, Cohort 2 received 144 mg/dose qid, cohort 3 received 192 mg/dose qid, and cohort 4 will receive 288mg/dose qid. No toxicities were detected. Inhalation was very well tolerated. The duration of the trial is for 6 months. To date, 3 patients have not shown evidence of progression for greater than 6 months (one patient 1 year (cohort 2), one patient 7 months (cohort 3), one patient 6 months) (cohort 3). This is the first FDA approved trial for intranasal delivery to malignant gliomas. Although preliminary, we are encouraged by the progression free survival of 3/8 patients in this dose escalation trial. Citation Format: Thomas C. Chen, Naveed Wagle, David Peereboom, Lynne Taylor. Intranasal brain delivery using NEO100 for recurrent glioblastoma [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2019; 2019 Mar 29-Apr 3; Atlanta, GA. Philadelphia (PA): AACR; Cancer Res 2019;79(13 Suppl):Abstract nr CT064.
Diffusive Transport of Volatile Pollutants in Nonaqueous-Phase Liquid Contaminated Soil: A Fractal Model

Volatile organic chemicals from nonaqueous phase liquids trapped in soil spread quickly both into the atmosphere and the groundwater system, resulting in long-lasting pollution of the environment. The extent and speed of spread is strongly influenced by the heterogeneities present in the soil, which interact with the various mechanisms of transport in a complex manner. A semi-analytical model is presented to investigate the effect of soil-heterogeneities on the spreading of pollutants from a nonaqueous phase liquid trapped in a soil. Based on field evidence, soil heterogeneities are modeled as a self-similar fractal process, and diffusive transport of organic chemicals in such a substrate is studied. Various mechanisms of, and resistance to, transport of these contaminants are considered, and it is illustrated how each of these are altered by the presence of heterogeneities. More specifically, it is shown that, while the transport processes at early time are governed by volatilization and dissolution and are quite unaffected by the heterogeneities, the transport processes at late time are strongly dependent on the heterogeneities of the soil and its sorption characteristics. In addition, how failure to recognize these heterogeneities in the soil may result in unsuccessful design of appropriate remediation techniques is discussed.
Exploring the Intersections of Web Science and Accessibility

In this paper, we survey several ongoing research threads that can be applied to web accessibility solutions. We focus on the challenges with automatically evaluating the accessibility violations in websites that are built primarily with JavaScript. There are several research efforts that – in aggregate – provide insight into how users interact with websites; how to automate and simulate user interactions; how to record the results of user interactions; and how to analyze, evaluate, and map resulting website content to determine the relative accessibility. We close with a discussion on the convergence of these threads and the future of automated, web-based accessibility evaluation, and assurance.
Messenger RNA therapy as an option for treating metabolic disorders.

The use of messenger RNA (mRNA) therapy by systemic delivery to treat metabolic disorders has long been hampered by poor stability, immunogenicity, inefficient delivery, and hepatic toxicity. In contrast, other molecular therapies such as viral gene and enzyme replacement therapy (Fig. 1) have been effectively employed to successfully treat rare metabolic diseases in both animals and humans. However, viral gene therapy is not without concerns of genotoxicity, transgene persistence, packaging constraints, production scalability, and preexisting immunity to the viral capsid (1). Similarly, enzyme replacement therapy can be difficult to deliver to some tissues and cellular compartments, and immune responses to the enzyme can occur (2). Advancements in lipid nanoparticle (LNP)-mediated mRNA therapy have greatly improved the ability to systemically deliver mRNA to the liver and to express high levels of protein coded by the therapeutic mRNA (3). The greatest remaining concern surrounding LNP-mRNA therapy is that it supplies only a short period of transgene expression in comparison to other therapies, but transgene expression from an LNP-mRNA vector can be extended with repetitive treatment. This emerging therapeutic option for genetic diseases has been used to treat a small but growing number of murine models of metabolic disorders (4⇓⇓–7). A report in PNAS by Truong et al. (8) examines the use of LNP-mRNA therapy to treat arginase deficiency (AD) and illustrates how LNP-mRNA therapy might be used to effectively treat this disease as well as other metabolic diseases of the liver. Fig. 1. Cellular entry and processing of different molecular therapies. Adeno-associated virus (AAV) uses receptor binding to gain cell entry. The AAV needs to traffic to the nucleus for the AAV’s single-stranded DNA (ssDNA) to be converted to double-stranded DNA and transcribed into messenger RNA (mRNA), which is then exported from the nucleus and translated to protein. Enzyme replacement … [↵][1]1Email: rchandler{at}mail.nih.gov. [1]: #xref-corresp-1-1
GP163 Improving patient experience through the use of a short stay observation unit in a pediatric hospital, a pilot study

The Emergency Department (ED) at Children’s University Hospital, Temple Street is constantly running at maximum capacity due to limited space and in-patient beds, as well as inadequate staffing. This leads to a number of issues including: reduced patient flow, department overcrowding, unacceptable patient experience times and possible adverse events. A short stay observation unit (SSOU) was introduced to improve flow and patient experience. The RCPCH (2017) have defined a short stay unit as a ‘dedicated facility providing assessment, observation and treatment of an illness, without the need for inpatient admission and can be a safe and efficient way of managing their care.’ Our aim was to utilize beds in a different way to improve patient safety and patient flow in the ED, therefore improving PET times and patient satisfaction. We developed a local implementation group that met weekly to progress and change as necessary. We developed set admission criteria and standard operating procedures for the department. Weekly audits for patient length of stay in the SSOU, ED trolley wait times monitored weekly, parent and staff satisfaction surveys, PET times monitored weekly. Over the duration of the 8 week pilot study; Average length of stay in the SSOU was 11.7 hours 164 patients through the SSOU in 8 weeks, at 1.2 patients per available bed/day Trolley wait times have dropped to the previous 2 years Satisfaction surveys showed that the SSOU positively affected patients hospital experience and the ED staffs workload The utilisation of beds and resources in a different way can have a positive impact on patient care. Parent satisfaction and patient flow can be greatly improved from implementing a permanent SSOU. The ED can be used more efficiently and patient safety improved through effective use of resources. Welcomed changes can have a big impact on staff morale. We recommend that for future use, the SSOU be run as a standalone unit by the ED staff on a daily basis for the entirety of its opening hours. The SSOU should be in operation for at minimum the busy winter period, that being from late September to early May.
Detection Methods for Human Papillomavirus (HPV) in Head and Neck Cancers

The escalating incidence of squamous cell carcinoma of the oropharynx and base of the tongue (OPC) is associated with remote exposure to hrHPV and thereby indicates that the increasing numbers of these cancers will be seen in the clinical setting. HPV status in OPC impacts a range of clinical factors including primary site determination, extent of surgery, adjuvant treatment, and prognosis. Thus, accurate and reproducible methods to determine HPV status will be needed for an increasing volume of patients. For OPC, p16 is now considered to be a reliable surrogate for detection of hrHPV, but its use will likely wane as molecular testing such as in situ hybridization becomes more widespread and laboratories become more comfortable with application and interpretation of these methodologies.
A generalization of the Bollob\'as set pairs inequality

The Bollobas set pairs inequality is a fundamental result in extremal set theory with many applications. In this paper, for $n \geq k \geq t \geq 2$, we consider a collection of $k$ families $\mathcal{A}_i: 1 \leq i \leq k$ where $\mathcal{A}_i = \{ A_{i,j} \subset [n] : j \in [n] \}$ so that $A_{1, i_1} \cap \cdots \cap A_{k,i_k} \neq \emptyset $ if and only if there are at least $t$ distinct indices $i_1,i_2,\dots,i_k$. Via a natural connection to a hypergraph covering problem, we give bounds on the maximum size $\beta_{k,t}(n)$ of the families with ground set $[n]$.
Effect of Sirolimus levels between days 11 and 20 after allogeneic stem cell transplantation on the risk of hepatic sinusoidal obstruction syndrome.

Sinusoidal obstruction syndrome (SOS) is a serious complication of hematopoietic stem cell transplantation (HSCT). Sirolimus plus tacrolimus is an accepted regimen for graft-versus-host disease (GVHD) prophylaxis, with both agents implicated as risk factors for SOS. We analyzed 260 consecutive patients who underwent allogeneic HSCT following myeloablative conditioning using total body irradiation (TBI)-based (n = 151) or chemotherapy only (n = 109) regimens, with sirolimus plus tacrolimus for GVHD prophylaxis. SOS occurred in 28 patients at a median of 22 (range, 12–58) days. Mean sirolimus trough levels were higher between days 11 and 20 following transplant in patients who developed SOS (10.3 vs. 8.5 ng/ml, P = 0.008), with no significant difference in mean trough levels between days 0 and 10 (P = 0.67) and days 21–30 (P = 0.37). No differences in mean tacrolimus trough levels during the same time intervals were observed between those developing SOS and others. On multivariable analysis, a mean sirolimus trough level ≥ 9 ng/ml between days 11 and 20 increased the risk of SOS (hazard ratio 3.68, 95% CI: 1.57–8.67, P = 0.003), together with a longer time from diagnosis to transplant (P = 0.004) and use of TBI (P = 0.006). Our results suggest that mean trough sirolimus levels ≥ 9 ng/mL between days 11 and 20 post transplant may increase the risk of SOS and should be avoided.
Quantization and scattering in the IIB SL(2,Bbb Z) covariant superstring

We rewrite the SL(2,) covariant worldsheet action for the IIB string proposed by Townsend in a Polyakov form. In a flat background the formalism yields separate (p,q) sectors. In each one the action is that of the IIB string action with the string slope parameter ?' replaced by its SL(2,) analogue ?pq'. SL(2,) invariant graviton scattering amplitudes are obtained from those of the fundamental (1,0) string by summing over the different sectors. The tree-level four-graviton amplitude in this formalism differs from a previously conjectured non-perturbative form; both yield the same expansion in order ?'3.
Coronavirus Disease 2019 in Kidney Transplant Recipients: Single-Center Experience and Case-Control Study.

Background Kidney transplant recipients (KTR) are considered high-risk for morbidity and mortality from coronavirus disease 2019 (COVID-19). However, some studies did not show worse outcomes compared to non-transplant patients and there is little data about immunosuppressant drug levels and secondary infections in KTR with COVID-19. Herein, we describe our single-center experience with COVID-19 in KTR. Methods We captured KTR diagnosed with COVID-19 between March 1, 2020 and May 18, 2020. After exclusion of KTR on hemodialysis and off immunosuppression, we compared the clinical course of COVID-19 between hospitalized KTR and non-transplant patients, matched by age and sex (controls). Results Eleven KTR were hospitalized and matched with 44 controls. One KTR and 4 controls died (case fatality rate: 9.1%). There were no significant differences in length of stay or clinical outcomes between KTR and controls. Tacrolimus or sirolimus levels were >10 ng/mL in 6 out of 9 KTR (67%). Bacterial infections were more frequent in KTR (36.3%), compared with controls (6.8%, P = .02). Conclusions In our small case series, unlike earlier reports from the pandemic epicenters, the clinical outcomes of KTR with COVID-19 were comparable to those of non-transplant patients. Calcineurin or mammalian target of rapamycin inhibitor (mTOR) levels were high. Bacterial infections were more common in KTR, compared with controls.
Endovascular Considerations in Traumatic Injury of the Carotid and Vertebral Arteries

Cervical carotid and vertebral artery traumatic injuries can have a devastating natural history. This article reviews the epidemiology, mechanisms of injury, clinical presentation, and classification systems pertinent to consideration of endovascular treatment. The growing role of modern endovascular techniques for the treatment of these diseases is presented to equip endovascular surgeons with a framework for critically assessing patients presenting with traumatic cervical cerebrovascular injury.
TES-1/Tes protects junctional actin networks under tension from self-injury during epidermal morphogenesis in the C. elegans embryo

During embryonic morphogenesis, the integrity of epithelial tissues depends on the ability of cells in tissue sheets to undergo rapid changes in cell shape while preventing self-injury to junctional actin networks. LIM domain-containing repeat (LCR) proteins are recruited to sites of strained actin filaments in cultured cells [1-3], and are therefore promising candidates for mediating self-healing of actin networks, but whether they play similar roles in living organisms has not been determined. Here, we establish roles for Caenorhabditis elegans TES-1/Tes, an actin-binding LCR protein present at apical junctions, during epithelial morphogenesis. TES-1::GFP is recruited to apical junctions during embryonic elongation, when junctions are under tension; in embryos in which stochastic failure of cell elongation occurs, TES-1 is only strongly recruited to junctions in cells that successfully elongate, and recruitment is severely compromised in genetic backgrounds in which cell shape changes do not successfully occur. tes-1 mutant embryos display junctional F-actin defects, and loss of TES-1 strongly enhances tension-dependent injury of junctional actin networks in hypomorphic mutant backgrounds for CCC components, suggesting that TES-1 helps to prevent self-injury of junctional actin networks during rapid cell shape change. Consistent with such role, a fragment of TES-1 containing its LIM domains localizes to stress fiber strain sites (SFSS) in cultured vertebrate cells. Together, these data establish TES-1 as a tension-sensitive stabilizer of the junctional actin cytoskeleton during embryonic morphogenesis.
Vacancy Formation Energies and Migration Barriers in Multi-Principal Element Alloys

Multi-principal element alloys (MPEAs) continue to garner interest as structural and plasma-facing materials due to their structure stability and increased resistance to radiation damage. Despite sensitivity of mechanical behavior to irradiation and point-defect formation, there has been scant attention on understanding vacancy stability and diffusion in refractory-based MPEAs. Using density-functional theory, we examine vacancy stability and diffusion barriers in body-centered cubic (Mo0.95W0.05)0.85Ta0.10(TiZr)0.05. The results in this MPEA show strong dependence on environment, originating from local lattice distortion associated with charge-transfer between neighboring atoms that vary with different chemical environments. We find a correlation between degree of lattice distortion and migration barrier: (Ti, Zr) with less distortion have lower barriers, while (Mo, W) with larger distortion have higher barriers, depending up local environments. Under irradiation, our findings suggest that (Ti, Zr) are significantly more likely to diffuse than (Mo, W) while Ta shows intermediate effect. As such, material degradation caused by vacancy diffusion can be controlled by tuning composition of alloying elements to enhance creep strength at extreme operating temperatures and harsh conditions.
Positioning System Accuracy Assessment for the Runway Incursion Prevention System Flight Test at the Dallas/Ft. Worth International Airport

NASA/Langley Research Center collaborated with the Federal Aviation Administration (FAA) to test a Runway Incursion Prevention System (RIPS) at the Dallas Fort Worth International Airport (DFW) in October 2000. The RIPS combines airborne and ground sensor data with various cockpit displays to improve pilots' awareness of traffic conditions on the airport surface. The systems tested at DFW involved surface radar and data systems that gather and send surface traffic information to a research aircraft outfitted with the RIPS software, cockpit displays, and data link transceivers. The data sent to the airborne systems contained identification and GPS location of traffic. This information was compared with the own-ship location from airborne GPS receivers to generate incursion alerts. A total of 93 test tracks were flown while operating RIPS. This report compares the accuracy of the airborne GPS systems that gave the own-ship position of the research aircraft for the 93 test tracks.
The RX Knowledge Base: An Overview

In the previous chapter I discussed the concept and structure of a database schema. A schema in the RX knowledge base (KB) is similar in format to a schema in the database. Consider their similarities.
Chapter 3. Antidepressant Agents

Publisher Summary This chapter discusses the several recent reviews that cover various aspects of depression and antidepressant research. The research on selective inhibitors of serotonin (5HT) uptake relative to their effects on the uptake of dopamine (DA) or norepinephrine (NE) has led to the successful development of selective serotonin reuptake inhibitors (SRIs) as antidepressants. The results with fluoxetine seem to characterize the SRIs as a whole, efficacy equivalent to tricyclic antidepressants (TCAs), but often with better toleration because of a different spectrum of side effects. The advantage offered by fluoxetine, therefore, relates to a more benign side effect profile that makes it a more useful agent for some depressed patients. Semaline has proven to be a well tolerated and efficacious antidepressant in a number of trials and its preclinical biology has been reviewed. Paroxetine, one of the more potent 5HT uptake inhibitors in vitro , has shown antidepressant activity in a controlled clinical trial. It is also observed that SRIs produce positive results in treating obsessive compulsive disorder. Although one of the oldest classes of antidepressants, irreversible monoamine oxidase inhibitors (MAO), such as phenelzine and tranylcypromine, have had limited use because of a severe hypertensive crisis. However, recent reviews have appeared that cover the current biological understanding of MAO and the role of MAO inhibition in the treatment of depression. Current research now suggests that reversible and selective inhibition of MAO-A will afford antidepressant activity without hypertensive side effects. Buspirone, gepirone, SM-3997, and ipsapirone represent a new class of non-benzodiazepine anxiolytics that have also demonstrated promise as antidepressants. Further reports on rolipram, the prototype of this new class of antidepressants, have been encouraging. The potential for new therapies of depression and affective disorders has emerged from research around lithium, corticotropin-releasing factor (CRF), and S-adenosyl methionine.