cssi/SciSciGPT-SciSciNet huggingface dataset:
Experimental Prediction of the Evolution of Ceftazidime Resistance in the CTX-M-2 Extended-Spectrum Beta-Lactamase

We applied in vitro evolution to an Escherichia coli strain containing bla(CTX-M-2) and obtained 10 independent mutant bla(CTX-M-2) alleles that confer elevated resistance to ceftazidime (MIC > or = 32 microg/ml) but lost the ability to confer resistance to cefepime. All alleles had a Pro-to-Ser substitution at position 167.
Lysophosphatidic Acid Mediates Activating Transcription Factor 3 Expression Which Is a Target for Post-Transcriptional Silencing by miR-30c-2-3p

Although microRNAs (miRNAs) are small, non-protein-coding entities, they have important roles in post-transcriptional regulation of most of the human genome. These small entities generate fine-tuning adjustments in the expression of mRNA, which can mildly or massively affect the abundance of proteins. Previously, we found that the expression of miR-30c-2-3p is induced by lysophosphatidic acid and has an important role in the regulation of cell proliferation in ovarian cancer cells. The goal here is to confirm that ATF3 mRNA is a target of miR-30c-2-3p silencing, thereby further establishing the functional role of miR-30c-2-3p. Using a combination of bioinformatics, qRT-PCR, immunoblotting and luciferase assays, we uncovered a regulatory pathway between miR-30c-2-3p and the expression of the transcription factor, ATF3. Lysophosphatidic acids triggers the expression of both miR-30c-2-3p and ATF3, which peak at 1 h and are absent 8 h post stimulation in SKOV-3 and OVCAR-3 serous ovarian cancer cells. The 3´-untranslated region (3´-UTR) of ATF3 was a predicted, putative target for miR-30c-2-3p, which we confirmed as a bona-fide interaction using a luciferase reporter assay. Specific mutations introduced into the predicted site of interaction between miR-30c-2-3p and the 3´-UTR of ATF3 alleviated the suppression of the luciferase signal. Furthermore, the presence of anti-miR-30c-2-3p enhanced ATF3 mRNA and protein after lysophosphatidic acid stimulation. Thus, the data suggest that after the expression of ATF3 and miR-30c-2-3p are elicited by lysophosphatidic acid, subsequently miR-30c-2-3p negatively regulates the expression of ATF3 through post-transcriptional silencing, which prevents further ATF3-related outcomes as a consequence of lysophosphatidic acid signaling.
Bioavailability and activity of phytosome complexes from botanical polyphenols: the silymarin, curcumin, green tea, and grape seed extracts.

Plant-derived polyphenols are increasingly receiving attention as dietary supplements for the homeostatic management of inflammation, to support detoxification, and for anticancer, weight loss, and other benefits. Their pro-homeostatic effects on genes, transcription factors, enzymes, and cell signaling pathways are being intensively explored, but the poor bioavailability of some polyphenols likely contributes to poor clinical trial outcomes. This review covers four polyphenol preparations with poor bioavailability and their complexation into phytosomes to bypass this problem. Silybin and the other silymarin flavonolignans from milk thistle conserve tissue glutathione, are liver-protective, and have anticancer potential. Curcumin and its related diphenolic curcuminoids have potent antioxidant, anti-inflammatory, and anti-carcinogenic properties. The green tea flavan-3-ol catechins have antioxidant, anti-inflammatory, cardio- and neuro-protective effects, and anti-carcinogenic benefits, with fat oxidation effects coupled to weight loss. The complex grape seed proanthocyanidin mix (including catechin and epicatechin monomers and oligomers) counters oxidative stress and protects the circulatory system. For each of these preparations, conversion into phytosomes has improved efficacy without compromising safety. The phytosome technology creates intermolecular bonding between individual polyphenol molecules and one or more molecules of the phospholipid, phosphatidylcholine (PC). Molecular imaging suggests that PC molecule(s) enwrap each polyphenol; upon oral intake the amphipathic PC molecules likely “usher” the polyphenol through the intestinal epithelial cell outer membrane, subsequently accessing the bloodstream. PC itself has proven clinical efficacy that contributes to phytosome in vivo actions. As a molecular delivery vehicle, phytosome technology substantially improves the clinical applicabilities of polyphenols and other poorly absorbed plant medicinals. (Altern Med Rev 2009;14(3):226-246)
Influence of Product Co2 on the Overall Reaction Network in the Oxidative Coupling of Methane

Abstract This paper details an investigation using steady-state isotopic transient kinetic analysis (SSITKA) of the influence of product CO 2 on readsorption phenomena and surface carbon reaction networks on Li/MgO and Sm 2 O 3 catalysts during the oxidative coupling of methane. Results show that all Li/MgO active sites can adsorb CO 2 with egual probability with none of the relative site activities being affected. The results for Li/MgO suggest that all sites are egually active for both selective and nonselective oxidation. No significant interaction of the carbon of gas phase CO 2 with Sm 2 O 3 active sites was seen.
Current approach to classification of membranoproliferative glomerulonephritis

Membranoproliferative glomerulonephritis (MPGN) is a pattern of injury, which historically has been classified using light and electron microscopic morphologic features. Primary (idiopathic) MPGN was divided into types I, II (dense deposit disease) and III, respectively defined by the presence of subendothelial deposits with capillary double contours, intramembranous electron dense material, or subepithelial and/or intramembranous deposits with or without basement membrane irregularities and subendothelial deposits. Secondary MPGN was associated with underlying diseases including infection, lymphoplasmacytic disorders, autoimmune disease, and malignancy. However, this classification encompasses entities with overlapping pathogenesis, clinical features, and treatment approaches. Therefore, classification of MPGN based on pathogenesis and associated immunofluorescence findings has been suggested. MPGN is divided into immune complex (IC)-mediated (immunoglobulin and complement deposition), complement (C)-mediated (C deposition) and non-IC, non-C-mediated forms. IC-mediated MPGN results from chronic antigenemia, including those previously designated type I, type III and secondary. C-mediated MPGN includes type II (dense deposit disease) and C3 glomerulonephritis, the latter with features of MPGN types I or III. Non-IC, non-C MPGN is secondary to few underlying causes, predominantly thrombotic microangiopathy of any cause. This classification allows for improved prognostic information and optimized approach to therapy. As pathogenesis is better understood, primary MPGN may cease to exist.
Gas/particle partitioning of 2-methyltetrols and levoglucosan at an urban site in Denver.

In this study, a medium volume sampler incorporating quartz fiber filters (QFFs) and a polyurethane foam (PUF)/XAD/PUF sandwich (PXP) was used to collect 2-methyltetrols (isoprene tracer) and levoglucosan (biomass burning tracer) in gaseous and particle (PM2.5) phases. The measured gas/particle (G/P) partitioning coefficients (Kp,OMm) of 2-methyltetrols and levoglucosan were calculated and compared to their predicted G/P partitioning coefficients (Kp,OMt) based on an absorptive partitioning theory. The breakthrough experiments showed that gas-phase 2-methyltetrols and levoglucosan could be collected using the PXP or PUF adsorbent alone, with low breakthrough; however, the recoveries of levoglucosan in PXP samples were lower than 70% (average of 51.9–63.3%). The concentration ratios of 2-methyltetrols and levoglucosan in the gas phase to those in the particle phase were often close to or higher than unity in summer, indicating that these polar species are semi-volatile and their G/P partitioning should be ...
Time Dependent Stress Fields Ahead of the Interface Cracks in Creep Regime

In this study the behavior of stationary interface cracks in layered materials at creep regime in plane-strain condition and pure opening dominated mode-I load state was studied numerically. The results indicate that the introduction of a transitional layer to the interface of the elastic-creeping bimaterials significantly elevates the stress values ahead of the interface cracks under identically applied load levels at creep regime.
Introduction to Sequencing the Brain Transcriptome

High-throughput next-generation sequencing is now entering its second decade. However, it was not until 2008 that the first report of sequencing the brain transcriptome appeared (Mortazavi, Williams, Mccue, Schaeffer, & Wold, 2008). These authors compared short-read RNA-Seq data for mouse whole brain with microarray results for the same sample and noted both the advantages and disadvantages of the RNA-Seq approach. While RNA-Seq provided exon level resolution, the majority of the reads were provided by a small proportion of highly expressed genes and the data analysis was exceedingly complex. Over the past 6 years, there have been substantial improvements in both RNA-Seq technology and data analysis. This volume contains 11 chapters that detail various aspects of sequencing the brain transcriptome. Some of the chapters are very methods driven, while others focus on the use of RNA-Seq to study such diverse areas as development, schizophrenia, and drug abuse. This chapter briefly reviews the transition from microarrays to RNA-Seq as the preferred method for analyzing the brain transcriptome. Compared with microarrays, RNA-Seq has a greater dynamic range, detects both coding and noncoding RNAs, is superior for gene network construction, detects alternative spliced transcripts, and can be used to extract genotype information, e.g., nonsynonymous coding single nucleotide polymorphisms. RNA-Seq embraces the complexity of the brain transcriptome and provides a mechanism to understand the underlying regulatory code; the potential to inform the brain–behavior–disease relationships is substantial.
Comparison of fluorine-18-fluorodeoxyglucose and tritiated fluoromisonidazole uptake during low-flow ischemia.

UNLABELLED Fluorine-18-fluoromisonidazole (FMISO) is trapped in hypoxic but viable canine myocardium. Because of the potential for its use as a marker of myocardial viability, we compared FMISO activity to [18F]fluorodeoxyglucose (FDG) activity in the same myocardial samples from eight dogs subjected to 3 hr of moderate regional myocardial ischemia. METHODS Tritiated FMISO was injected 15-30 min after onset of regional ischemia (40%-70% reduction in systolic wall thickening) which was maintained for 3 hr. FDG was injected after 2 hr of ischemia. Myocardial blood flow (MBF) was measured by the radiolabeled microsphere technique at the time of each radiotracer injection. At 3 hr of ischemia, the heart was excised and cut into short-axis slices. One slice encompassing both ischemic and normal tissue was cut into 64 samples. FMISO and FDG activity in each sample were normalized to the mean normal zone activity and further expressed as a function of regional MBF. RESULTS FMISO uptake was consistently greater than FDG uptake, although this was significantly different only for MBF, between 40%-60% of normal. When analyzed relative to endocardial-epicardial location, endocardial FMISO uptake was significantly greater in all hypoperfused samples. CONCLUSION These results suggest that FMISO is as sensitive as FDG for detecting myocardial ischemia and could be used for identification of viable myocardium.
Molecular beam epitaxy of interband cascade structures with InAs/GaSb superlattice absorbers for long-wavelength infrared detection

The interfaces of InAs/GaSb superlattices (SLs) were studied with the goal of improving interband cascade infrared photodetectors (ICIPs) designed for the long-wavelength infrared region. Two ICIP structures with different SL interfaces were grown by molecular beam epitaxy, one with a ~1.2 monolayer (ML) InSb layer inserted intentionally only at the GaSb-on-InAs interfaces and another with a ~0.6 ML InSb layer inserted at both InAs-on-GaSb and GaSb-on-InAs interfaces. The material quality of the ICIP structures was similar according to characterization by differential interference contrast microscopy, atomic force microscopy, and x-ray diffraction. The performances of the ICIP devices were not substantially different despite the different interface structure. Both ICIPs had a peak detectivity of >3.7 × 1010 Jones at 78 K with a cutoff wavelength near 9.2 μm. The maximum operation temperatures of both ICIPs were as high as ~250 K, although the structures were not fully optimized. This suggests that the two interface arrangements may have a similar effect on structural, optical and electrical properties. Alternatively, the device performance of the ICIPs may be limited by mechanisms unrelated to the interfaces. In either case, the arrangement of dividing a thick continuous InSb layer at the GaSb-on-InAs interface into thinner InSb layers at both interfaces can be used to achieve strain balance in SL detectors for longer wavelengths. This suggests that with further improvements ICIPs should be able to operate at higher temperatures at even longer wavelengths.
Cognitive processing speed mediates the effects of cardiovascular disease on executive functioning.

Objective The goal of this study was to examine the hypothesized mediating role of cognitive processing speed (CPS) in the relationship between cardiovascular disease (CVD) and executive functioning (EF). We investigated whether the processing-speed hypothesis in aging also explains the unique contribution that CPS may have to EF deficits in CVD patients. Method A neuropsychological assessment, including multiple measures of CPS and EF, was administered to 21 older adults with a history of CVD and 73 older adults with no history of CVD. Structural equation models were used to measure the indirect associations between CVD and 6 EF task outcomes through a CPS factor. Competing indirect links were assessed using the product-of-coefficients (α*β) approach with bias-corrected bootstrap confidence intervals. Results CVD was significantly, negatively related to CPS (β = -.239, 95% CI [-.457, -.021]). CPS was significantly, positively related to an EF composite score (β = .566, 95% CI [.368, .688]). CVD was significantly, negatively related to the EF composite score (β = -.137, 95% CI [-.084, -.211]). The indirect links from CVD to the individual measures of the EF composite score via CPS were all significant. CVD most adversely affected tasks of cognitive flexibility and inhibition indirectly through CPS. Conclusion With the present study, we have demonstrated that the processing-speed hypothesis in aging extends to older adult patients with CVD. Reduced CPS significantly underlies the link between CVD status and poorer EF. Individuals with CVD demonstrated poorer CPS and EF than those without CVD, and CPS was specifically implicated as a CVD-related mechanism leading to worse EF. (PsycINFO Database Record
Beyond the Headlines: Insights on Potassium Supplementation for the Treatment of Hypertension From the Canadian Hypertension Education Program Guidelines (CHEP).

The Canadian Hypertension Education Program guidelines (CHEP) are the first major recommendations that incorporate SPRINT (Systolic Blood Pressure Intervention Trial) results for clinical practice. These changes will certainly have a major impact on the treatment of blood pressure for individuals with a high cardiovascular disease risk. However, what may be equally noteworthy, although seemingly less provocative, is the recommendation for the nonpharmacological treatment of blood pressure with dietary potassium intake for patients who are not at high risk for hyperkalemia.1 Increased potassium intake is included as a healthy behavior and receives the only Grade A recommendation in this section other than sodium reduction. The CHEP guidelines base their recommendation largely on the evidence from a meta-analysis of 22 studies in which potassium supplementation reduced systolic blood pressure (SBP) by 3.5 mm Hg and diastolic blood pressure by 2.0 mm Hg.2 However, participants with hypertension had a SBP reduction of 5.3 mm Hg, those taking antihypertensive medications had a 5.9 mm Hg reduction, and those with >4 g of sodium intake per day had a 6.9 mm Hg reduction. Increased potassium intake is also particularly efficacious in black persons with as little as 20 meq resulting in a 7 mm Hg SBP reduction.3 Therefore, potassium supplementation can be expected to …
Circulating myeloid-derived suppressor cells in pediatric solid tumor patients.

9565 Background: Cure rates have reached a plateau for many pediatric solid tumors. Identifying new therapeutic targets, biomarkers of response and prognostic indicators should improve clinical out...
Navigating Genetic and Phenotypic Uncertainty in Left Ventricular Noncompaction.

Once called spongiform cardiomyopathy for its distinct lace-like morphology, left ventricular noncompaction (LVNC) describes a ventricular wall with a prominent noncompacted layer; the excessive trabeculations and deep intertrabecular recesses are separated by thin compacted myocardium.1,2 The diagnosis of LVNC is made primarily by imaging studies to index the thickness of the trabeculated layer to that of the compacted layer. With the advent of cardiac magnetic resonance allowing for high-resolution imaging of the myocardium, hypertrabeculation in the LV has become increasingly recognized in clinical practice. Significant individual variability exists in the extent of trabeculation, however, making its diagnosis extremely challenging. In addition, LVNC frequently occurs in association with other cardiomyopathies,2 congenital heart defects,3 neuromuscular disorders, and genetic syndromes. As a result, there has been ongoing debate as to whether LVNC is an independent disease entity, a clinical phenotype shared among various cardiomyopathies, or a mere bystander.2 Contributing to this debate is the little data on the genetic architecture underlying LVNC. Although the next-generation sequencing has facilitated comprehensive and cost-effective approaches to identify potentially causative genetic variation in LVNC, the ability to identify such variation has outpaced our capacity to clearly interpret its clinical significance. Thus, in this era of rapidly evolving clinical imaging and sequencing technologies, there is a pressing need to integrate the accumulating imaging and genetic data in a large cohort, to better understand the entity that is LVNC. See Article by Author In this issue of Circulation: Cardiovascular Genetics , Jefferies et al4 expand on the known genetic causes of LVNC and provide insights into the genetic landscape of LVNC and LV hypertrabeculation (LVHT) in the largest prospective cohort to date. By leveraging whole exome sequencing and cardiac magnetic resonance, the research team has assembled a deeply genotyped and phenotyped study …
Learning the American Way: Sports International and American Soft Power

From 1962 to 1968, the United States Government along with private entities funded the training of athletes from developing nations through a non-profit organization named Sports International. Led...
Niobium-Titanium Superconducting Materials

Niobium-titanium superconducting composites have quite a long history in the era of applied superconductivity, having been introduced about fifteen years ago. Virtually all the superconducting magnets constructed have used Nb-Ti superconductor, the principal exception being small high-field solenoids of fields greater than about 9 tesla which are made of Nb3Sn tape. At present, filamentary (FM)Nb3Sn appears ready to become widely used, provided that the engineering marketplace can accommodate to its brittle nature in the way that has been possible in the research laboratory. However, at present the number of applications of Nb3Sn is small.
Theoretical Qualifications and Extensions

In this chapter, we will review theoretical qualifications and extensions in the attribution area that were prominent in the 1970s and early 1980s. Our treatment will be general and selective. We will describe a continuation of theoretical and empirical work based on the beginning foundation writings of Heider, Jones and colleagues, Kelley, and Bem. We will note how much of this continuation work has generated a good deal of research, debate, and, in some cases, clarification of basic process issues. But we also will point out how these theoretical qualifications and extensions of the 1970s, for the most part, have not led to the type of broad, systematic analyses of attributional phenomena that might have been expected in light of Heider’s (1958) magnum opus and the rush of theoretical work in the mid- and late 1960s.
Adaptive controllers for uncertain dynamical systems

The fundamental feedback control problem of obtaining desired system behavior in the presence of uncertainties is considered for a class of uncertain systems described by differential equations.
Efficient realignment: Managing uncertainty and equivocality in the entrepreneurial process

This study addresses a paradox faced by new technology ventures. To survive in uncertain and dynamic environments, organizations must adjust their operations and strategies to align with changing k...
Modeling the risk of progression in smoldering multiple myeloma.

8607 Background: Smoldering multiple myeloma (SMM) is a precursor state to multiple myeloma (MM) with a highly variable risk of progression to active MM. Identifying patients at risk of imminent pr...
Evaluation of a Passive Optical Fiber Daylighting System for Plant Growth

Current farming practices deplete resources and energy including water, soil, and electricity. Alternative farming methods such as indoor agriculture are possible solutions, however, current methods utilize a considerable amount of electricity to provide plants with artificial light. Optical fiber daylighting systems (OFDs) offer a way to direct sunlight indoors over long distances and can therefore reduce electricity usage. Currently, the market mostly includes active OFDs that use a motor and sun-tracking mechanism. This can be complicated and expensive to develop and operate. Therefore, our research focuses on developing and optimizing a passive OFD system. Passive OFDs are static structures that use their geometry and the laws of optics to redirect light. Optical simulation software, CAD software, additive manufacturing, and waterjet tools were used to develop an optimal passive OFD prototype for data collection. Vegetative plant growth requires a photosynthetic photon flux density (PPFD) of 250 and higher. Our prototype design provided a photoperiod of 210 minutes at a high (above 250 PPFD) level, 179 minutes at a medium (above 170 and less than 250 PPFD) level, and 175 minutes at a low (below 170 PPFD) level. This research supports the development and implementation of an effective passive OFD system for indoor farming operations at a significantly reduced cost, with increased feasibility in a more environmentally friendly approach.
Ring-Closing Metathesis Approach to Dictyostatin†

An esterification/ring-closing metathesis approach to dictyostatin and discodermolide is introduced. The approach provides for facile fragment coupling of two main segments of these natural products at the C10−C11 alkene with high to complete Z-selectivity.
Abstract 5262: Lipidomic profiling of neuroblastoma cells after treatment with novel withalongolide A 4, 19, 27-triacetate (WGA-TA)

Introduction: Neuroblastoma (NB) is a pediatric solid tumor that affects approximately 700 children every year in the United States. Despite advances in treatment, the cure rate for high risk advanced NB having N-myc amplification has a poor response of 40-50%. Standard of care treatment for high risk NB patient consists of surgery, intensive chemotherapy and radiotherapy. Recently, we and others have shown that withanolide treatment of NB induce apoptosis of NB cells, through several mechanism including lipid oxidation, down regulation of N-myc and suppression of Akt/mTOR/NF-κB activation. Therefore, we hypothesized that mass spectrometric analysis of untargeted lipidomic profiling after treatment of NB cells with withanolide WGA-TA will identify novel prognostic and diagnostic biomarkers of NB. Methods: Validated neuroblastoma cell lines IMR32 (N-myc amplified) and SH-EP (N-myc non-amplified) were grown in 2D culture in appropriate growth medium. Lipids were extracted from cells using modified Bligh and Dyer method. Lipidomic profiling was carried out using LC MS/MS. Principal component analysis (PCA) was used to identify differentially regulated metabolites. Results: Principal component analysis of NB cell lines and WGA-TA treatment showed complete separation of samples as well as internal controls. Initial analysis of lipid profiling of IMR32 and SH-EP cells showed differential regulation of several lipids. N-myc non-amplified SH-EP cells have upregulation of phospholipids such as phosphocholine (PC), phosphor ethanol amine (PE), sphingomyelin (SM) and free fatty acid, whereas glycerol lipid diacyl glycerol (DG) is down regulated in SH-EP cells compared to IMR32 cells. Treatment of IMR32 cells with WGA-TA led to up regulation of phospho lipids such as PC, phosphoserine (PS), SM, Lyso PE, free fatty acids just like N-myc non-amplified cells. But, triglycerides (TG) were up regulated after treatment with WGA-TA in both IMR32 and SH-EP cells. Conclusions: WGA-TA treatment of N-myc amplified cells led to upregulation of phospholipids similar to that of N-myc non-amplified cells indicating that CDP-Choline pathway lipids might play an important role in NB. Further analysis is needed to unravel the link between N-myc and lipid metabolism in NB. Citation Format: Chitra Subramanian, Rajendiran Thekkelnaycke, Tanu Soni, Valerie P. Opipari, Barbara N. Timmermann, Mark S. Cohen. Lipidomic profiling of neuroblastoma cells after treatment with novel withalongolide A 4, 19, 27-triacetate (WGA-TA) [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 5262.
The Neuro Radialist

Trans-radial approach (TRA) has been used in cardiac and peripheral interventional radiology practices for decades, because of safety and patient comfort. There is interest in TRA in the cerebrovascular field, with potential to replicate benefits over trans-femoral approach. TRA is technically more challenging and has a learning curve, which hinders its use as the first-line approach; however, as more neuro-interventionalists embrace TRA, techniques are being optimized simultaneously for supra-aortic vessel catheterization. This article describes advantages, patient selection, conventional and distal radial access, and detailed techniques of trans-radial catheterization for diagnostic angiography, as well as cerebrovascular interventions and its current limitations.
Understanding Blindness: An Integrative Approach

In this single volume, information on blindness derived from many research areas is explained and critically evaluated. Among the subjects covered are: causes of blindness; blindness and the brain; effects of blindness on perception and cognition; attitudes toward blindness; the rehabilitation process; and blindness in infancy and childhood. For those directly involved or interested in the subject of blindness, Professor Hollins gathers all the basic information on blindness into a single source. Uniting research and data produced in different disciplines, Understanding Blindness advocates empiricism and experimental science and describes the methodologies as well as the experiments. Understanding Blindness is written for readers with no prior experience or technical background in the study of blindness, defining terms and explaining technical concepts as they are introduced.
Test–Retest Reliability of Functional Magnetic Resonance Imaging Activation for a Vergence Eye Movement Task

Vergence eye movements are the inward and outward rotation of the eyes responsible for binocular coordination. While studies have mapped and investigated the neural substrates of vergence, it is not well understood whether vergence eye movements evoke the blood oxygen level-dependent signal reliably in separate experimental visits. The test–retest reliability of stimulus-induced vergence eye movement tasks during a functional magnetic resonance imaging (fMRI) experiment is important for future randomized clinical trials (RCTs). In this study, we established region of interest (ROI) masks for the vergence neural circuit. Twenty-seven binocularly normal young adults participated in two functional imaging sessions measured on different days on the same 3T Siemens scanner. The fMRI experiments used a block design of sustained visual fixation and rest blocks interleaved between task blocks that stimulated eight or four vergence eye movements. The test–retest reliability of task-activation was assessed using the intraclass correlation coefficient (ICC), and that of spatial extent was assessed using the Dice coefficient. Functional activation during the vergence eye movement task of eight movements compared to rest was repeatable within the primary visual cortex (ICC = 0.8), parietal eye fields (ICC = 0.6), supplementary eye field (ICC = 0.5), frontal eye fields (ICC = 0.5), and oculomotor vermis (ICC = 0.6). The results demonstrate significant test–retest reliability in the ROIs of the vergence neural substrates for functional activation magnitude and spatial extent using the stimulus protocol of a task block stimulating eight vergence eye movements compared to sustained fixation. These ROIs can be used in future longitudinal RCTs to study patient populations with vergence dysfunctions.
Chondrocyte Cell Fate Analysis

Abstract As a unique connective tissue, cartilage is made of only one cell type, chondrocytes, and their secreted extracellular matrix (ECM), of which the most abundant are type II collagen and proteoglycans. Despite its simple cell composition, cartilage as a tissue is quite heterogenic and varies in origin, structure, matrix proteins, developmental and physiological roles. While in some invertebrates, such as cartilaginous fish (elasmobranches) like sharks, cartilage tissues are permanent in order to support the major organs of the body, most cartilage tissues in vertebrates have only a temporary existence, serving as a template for the arising bony skeleton via a highly spatiotemporally regulated process termed “endochondral ossification.” This type of mechanism is responsible for the formation of all long bones of the axial skeleton (vertebrae and ribs) and the appendicular skeleton (limbs). During this process, mesenchymal progenitor cells first move to the future bone sites and then differentiate into chondrocytes to form a cartilage anlage. Next, chondrocytes undergo sequential stages of proliferation, prehypertrophy, hypertrophy, and finally mineralization. Eventually the terminally differentiated chondrocytes, along with their surrounding cartilage matrix, have to be removed and replaced by bone matrix produced by osteoblasts. In adults, bone fracture healing adopts a similar mechanism. During repair, an initial soft cartilage callus is later replaced by a hard, bony callus for further remodeling into cortical bone. Not all chondrocytes differentiate unidirectionally. At the cartilage anlage stage of development, chondrocytes at future joint sites undergo de-differentiation to mesenchymal progenitors and then re-differentiate into multiple joint tissues, including cartilage chondrocytes. Recently, the fate of terminally differentiated chondrocytes has become controversial. Instead of apoptosis, as suggested by the conventional view, more and more evidence demonstrates that some hypertrophic chondrocytes undergo transdifferentiation into osteogenic lineage cells. In this article, we present the up-to-date knowledge about how chondrocytes in transient cartilage are formed, differentiated, and eventually removed during skeletal development and repair, with a focus on regulatory transcription factors and growth factors. We use the hindlimb as a primary example but the mechanisms also apply to other long bones.
Enumeration of additive manufacturing toolpaths using Hamiltonian paths

Abstract Toolpath choice in metal-based additive manufacturing (AM) affects local thermal environment. We use Hamiltonian paths to systematically enumerate time- and space-continuous toolpaths on example n × n grid geometries. This framework broadens the toolpath design space by establishing a finite and searchable number of AM toolpaths for any discretized geometry. We characterize toolpaths by extracting toolpath internal structures, e.g., the number of corners and pairs of parallel tracks. The enumerated toolpaths serve as an input to thermal simulations to obtain solidification cooling rate statistics, which strongly correlate to the number of internal structures. Hence, toolpath can be linked to microstructural predictions.
Pediatric Asthma Is Associated With Poorer 3-Year Academic Achievement in Urban Elementary and Middle-School Students.

Abstract Objective Asthma has been associated with worse academic performance in a single school year, yet this association may be magnified over time as students with asthma continue to fall behind. This study examined the relationship between asthma and standardized test performance aggregated across 3 school years, including whether performance varied by likelihood of having significant asthma. Methods Data were from students in grades K-8 at 2 urban public schools in the Northeastern United States (2015–2018). Asthma was based on parent- and self-report and school health center records. Standardized test performance was assessed using Measures of Academic Progress (MAP) and Partnership for Assessment of Readiness for College and Careers (PARCC). Mixed effects linear and logistic regression models were used to evaluate the relationship between asthma and performance during 3 school years. Results Any asthma was associated with worse MAP performance across the 3 academic years. Students with the most significant asthma demonstrated worse performance on MAP and PARCC. Aggregating across 3 school years, students scored 3.17 points worse on MAP reading (95% confidence interval [CI]: 0.7–5.63; P = .012) and 3.56 points worse on MAP mathematics (95% CI: 0.52–6.6; P = .022); they had 48.8% (95% CI: 1.9%–73.2%; P = .044) and 58.0% (95% CI: 21%–78%; P = .007) lower odds of proficiency on PARCC English/Language Arts and Mathematics, respectively compared to those without asthma. Conclusions The relationship between asthma and poorer academic achievement in 1 school year may be magnified over multiple years, particularly among those with more significant asthma. School-based asthma interventions may support academic growth and more equitable health outcomes.
A robust non-iterative algorithm for multi-body dynamics and vehicle–structure interaction analysis

This paper presents a novel, non-iterative, general formulation for the transient analysis of interacting elastodynamic systems in contact that may exhibit relative motion with respect to each othe...
N-acetylcysteine as an adjunctive treatment for bipolar depression: A systematic review and meta-analysis of randomized controlled trials.

Objectives Previous studies and meta-analyses suggested that N-acetylcysteine (NAC) was superior to placebo in improving depression in bipolar disorder. However, more recent data, including two larger trials, found that NAC was no more effective than placebo. We conducted a meta-analysis to appraise the possible efficacy of NAC in treating bipolar depression. Methods A systematic review and meta-analysis of double-blind, placebo-controlled trials of NAC as a treatment augmentation strategy for bipolar depression was carried out in PubMed (1966-2020). We utilized random-effect analysis to evaluate improvement in depressive symptoms from baseline to endpoint as the primary efficacy measure. Results Six trials including 248 patients were included. Treatment augmentation with NAC showed a moderate effect size favoring NAC over placebo (d = 0.45, 95% C.I.: 0.06-0.84). There was substantial heterogeneity (I2 = 49%). Meta-regression analyses did not identify any moderator that might explain variation in heterogeneity, including baseline depressive symptom scores, mean NAC dose, or duration of study. Conclusions Results from six clinical trials suggest that treatment augmentation with NAC for bipolar depression appears to be superior to placebo, with a moderate effect size, but a large confidence interval. Larger clinical trials, investigating possible moderating factors, such as NAC dose, treatment duration, baseline depression severity, or chronicity of illness, are warranted.
Exploiting manifolds of L1 halo orbits for end-to-end Earth–Moon low-thrust trajectory design

Abstract In this work, end-to-end low-thrust transfers from a GTO orbit to a low-altitude lunar orbit by exploiting the manifolds of a chosen Earth–Moon L 1 halo orbit has been studied. The practicality of piece-wise, minimum-time transfers that exploit halo orbit manifolds is demonstrated, which offers more flexibility to meet mission objectives. It is known that the structure of the manifolds varies substantially due to the presence of the Sun and its contribution has to be considered to obtain more realistic trajectories. To incorporate Sun’s perturbation, we study (1) manifolds’ behavior within a Bi-Circular Problem (BCP) dynamics and (2) Sun’s impact on the previously converged trajectories obtained using the standard Circular Restricted Three-Body Problem (CR3BP). Comparisons of the resulting trajectories using the CR3BP and BCP are presented.
The Plastoquinone/Plastoquinol Oxidoreductase Sites of the Chloroplast Cytochrome b/f Complex

The chloroplast cytochrome b/f complex is an intrinsic membrane protein consisting of a 35kD cytochrome/, a 20kD Rieske type iron-sulfur protein, a 23kD polypeptide containing both a high and low potential cytochrome b 6 (cytochrome b-563), and a 17 kD polypeptide of unknown function (1–4). The complex functions in the transfer of reducing equivalents from photosystem II reduced plastoquinol to plastocyanin, translocating 2H+/e-across the thylakoid membrane, and is also functional in a cyclic pathway around photosystem I. Essential to these roles are two sites of plastoquinone/plastoquinol oxidoreductase activity thought to be functional in the complex. At the so called “QZ” site, plastoquinol is oxidized by the iron sulfur protein, and the remaining unstable low potential plastosemiquinone reduces one of the cytochrome b-563 hemes. The “Qc” site is thought to be where the other cytochrome £-563 heme can transfer reducing equivalents to another plastoquinone molecule (5,6).
Saline groundwater as an aquaculture medium: physiological studies on the red drum, Sciaenops ocellatus

Physiological responses of the euryhaline red drum, Sciaenops ocellatus, to chloride salt addition, low salinity, and high sulfate concentration were measured. Survival was increased by addition of calcium chloride (CaCl2) or magnesium chloride (MgCl2) to dilute artificial seawater (0.2 ppt salinity). Although survival and routine metabolic rates were greater in MgCl2 treatments, growth and feed efficiency were greater in CaCl2 treatments. Marginal metabolic scope increased when CaCl2 or MgCl2 were added to dilute artificial seawater. There was a strong positive linear relationship (p=0.0001, r=0.91) between fish survival and salinity of artificial seawater dilutions over the salinity range 0.1 to 3.0 ppt. Monovalent ion concentrations in red drum plasma varied; whereas, divalent ion concentrations were relatively constant. Survival and growth were not affected by high sulfate concentrations (2000 mg l-1) in 3.0 ppt artificial seawater supplemented with either sodium sulfate or magnesium sulfate. Routine metabolic rate and marginal metabolic scope of red drum exposed to high sulfate concentrations were slightly, but not significantly, lower than those of red drum in 3 ppt artificial seawater.
El comienzo de la crisis en el comercio colonial: La Nueva Granada 1796-1801

Traza las caracteristicas esenciales del comercio neogranadino entre 1783 y 1796 y sus incipientes relaciones con los extranjeros, hechos que aconsejaban al gobierno espanol un entendimiento con Inglaterra. Luego describe la desaparicion del comercio con Espana durante la guerra de 1796-1801 y su facil reemplazo por una red de contrabando que los ingleses apoyaron. Por ultimo trata sobre los fugases esfuerzos por restablecer el comercio exclusivista de Espana con la Nueva Granada una vez declarada la paz en diciembre de 1801, esfuerzos que fracasaron al volver a declararse la guerra a Inglaterra en diciembre de 1804, acelerando de esta manera la marcha hacia la vinculacion de la Nueva Granada en la economia europea.
ON THE EFFICACY OF A COMPUTER‐BASED PROGRAM TO TEACH VISUAL BRAILLE READING

Scheithauer and Tiger (2012) created an efficient computerized program that taught 4 sighted college students to select text letters when presented with visual depictions of Braille alphabetic characters and resulted in the emergence of some braille reading. The current study extended these results to a larger sample (n = 81) and compared the efficacy and efficiency of the instructional program using 2 different response modalities. One variation of the program required a response in a multiple-choice format, and the other variation required a keyed response. Both instructional programs resulted in increased braille letter identification and braille reading. These skills were maintained at a follow-up session 7 to 14 days later. The mean time needed to complete the program was 22.8 min across participants. Implications of these results for future research, as well as practical implications for teaching the braille alphabet, are discussed.
Photographic Higher Education in the United States

That crazy feeling in America when the sun is hot on the streets and music comes out of the jukebox or from a nearby funeral, that is what Robert Frank has captured in tremendous photographs taken as he traveled on the road around practically forty-eight states in an old used car (on Guggenheim Fellowship) and with agility, mystery, genius, sadness, and strange secrecy of a shadow photographed scenes that have never been seen before on film .
Novel Biotransformations of 7-Ethoxycoumarin by Streptomyces griseus

Biotransformation of 7-ethoxycoumarin by Streptomyces griseus resulted in the accumulation of two metabolites which were isolated and identified as 7-hydroxycoumarin and 7-hydroxy-6-methoxycoumarin. A novel series of biotransformation reactions is implicated in the conversion of the ethoxycoumarin substrate to these products, including O-deethylation, 6-hydroxylation to form a 6,7-dihydroxycoumarin catechol, and subsequent O-methylation. Either 7-hydroxycoumarin or 6,7-dihydroxycoumarin was biotransformed to 7-hydroxy-6-methoxycoumarin by S. griseus. Trace amounts of the isomeric 6-hydroxy-7-methoxycoumarin were detected when 6,7-dihydroxycoumarin was used as the substrate. Efforts to obtain a cell-free catechol-O-methyltransferase enzyme system from S. griseus were unsuccessful. However, [methyl-14C]methionine was used with cultures of S. griseus to form 7-hydroxy-6-[14C]methoxycoumarin.
Measurement of interfacial area per volume for drainage and imbibition

[1] We investigate experimentally the functional relationship between capillary pressure, P c , wetting phase saturation, S w , and interfacial area per volume between the wetting and nonwetting phases, a wn , for drainage and imbibition processes in micromodels of two-dimensional pore structures. Within the experimental and analysis error (around 10-15%), the resulting P c -S w -a wn surfaces were the same. This suggests that data obtained from either the drainage process or the imbibition process are sufficient to generate the complete functional relationship among P c -S w -a wn and that the observed hysteresis in P c -S w -a wn can be modeled by including interfacial area as an additional state variable.
Entropy data analysis

Entropy Data Analysis (EDA) is a new approach to the analysis of data. It embodies a framework which encompasses many classical statistical concepts; yet it goes beyond the classical framework both in the generality of its concepts and the correctness of its results. This paper provides an introduction to Entropy Data Analysis. Technical details can be found in the referenced papers.
Multiple Constituent Mentoring: A Policy for Capitalizing on Authentic Learning Contexts in University Curricula.

In this article we propose a policy intended to alleviate the typical problems of student internships and improve the usefulness and relevancy of any partnership. We extend previous ideas about professional development schools or partnerships to eliminate the disconnect between K–12 schools and universities and add a component of multiple constituent mentoring necessary for effective music teacher and music teacher educator training. A partnership with multiple mentors—K–12 students, K–12 teachers, undergraduate students, graduate students, and university music education faculty—can provide the most benefits to the greatest number of people. The policy presented in this article will likely require the implementation of philosophical and curricular changes, but these efforts would be well worth the investment of time and resources.
Triple-helical transition state analogues: a new class of selective matrix metalloproteinase inhibitors.

Alterations in activities of one family of proteases, the matrix metalloproteinases (MMPs), have been implicated in primary and metastatic tumor growth, angiogenesis, and pathological degradation of extracellular matrix (ECM) components, such as collagen and laminin. Since hydrolysis of the collagen triple-helix is one of the committed steps in ECM turnover, we envisioned modulation of collagenolytic activity as a strategy for creating selective MMP inhibitors. In the present study, a phosphinate transition state analog has been incorporated within a triple-helical peptide template. The template sequence was based on the α1(V)436-450 collagen region, which is hydrolyzed at the Gly439~Val440 bond selectively by MMP-2 and MMP-9. The phosphinate acts as a tetrahedral transition state analog, which mimics the water-bound peptide bond of a protein substrate during hydrolysis. The phosphinate replaced the amide bond between Gly-Val in the P1-P1′ subsites of the triple-helical peptide. Inhibition studies revealed Ki values in the low nanomolar range for MMP-2 and MMP-9 and low to middle micromolar range for MMP-8 and MMP-13. MMP-1, MMP-3, and MT1-MMP/MMP-14 were not inhibited effectively. Melting of the triple-helix resulted in a decrease in inhibitor affinity for MMP-2. The phosphinate triple-helical transition state analog has high affinity and selectivity for the gelatinases (MMP-2 and MMP-9), and represents a new class of protease inhibitors that maximizes potential selectivity via interactions with both prime and non-prime active site subsites as well as with secondary binding sites (exosites).
Introducing ease of access into IBM

IBM has a long history of addressing the issues of employees and customers with disabilities through hiring and workplace practices, and through research and productisation of accessibility technologies. In 1999 IBM established an Accessibility Center with a focus on making our offerings accessible, exploiting accessibility technologies developed in IBM Research, and improving IBM's internal IT tools and work environment for employees with disabilities. IBM's product development organisations have made significant progress enabling their offerings and addressing some of the more difficult architectural issues associated with product accessibility.