cssi/SciSciGPT-SciSciNet huggingface dataset:
High cell-free virus load and robust autologous humoral immune responses in breast milk of simian immunodeficiency virus-infected African green monkeys

The design of immunologic interventions to prevent postnatal transmission of human immunodeficiency virus (HIV) will require identification of protective immune responses in this setting. Simian immunodeficiency virus (SIV)-infected rhesus monkeys (RMs), a species that develops an AIDS-like illness following experimental infection, transmit the virus at a high rate during breastfeeding. In contrast, postnatal transmission of SIV occurs rarely or not at all in natural, asymptomatic primate hosts of SIV. These contrasting transmission patterns provide a unique opportunity to study mechanisms that evolved to protect suckling infants from SIV infection. We compared the virologic and immunologic properties of milk of SIV-infected and uninfected natural hosts of SIV, African green monkeys (AGMs), to that of RMs. Interestingly, despite a low number of milk CD4+ T lymphocytes in uninfected AGMs, milk virus RNA load in SIV-infected AGMs was comparable to that of SIV-infected RMs and that in AGM plasma. This observation is in contrast to the relatively low virus load in milk compared to that in plasma of SIV-infected RMs and HIV-infected women. Milk of SIV-infected AGMs also displayed robust virus-specific cellular immune responses. Importantly, an autologous challenge virus-specific neutralization response was detected in milk of five of six SIV-infected AGMs that was comparable in magnitude to that in plasma. In contrast, autologous challenge virus neutralization was not detectable in milk of SIV-infected RMs. The autologous virus-specific adaptive immune responses in breast milk of AGMs may contribute to impedance of virus transmission in the infant oral/gastrointestinal tract and the rarity of postnatal virus transmission in natural hosts of SIV.
Interpersonal influences on adolescent materialism: A new look at the role of parents and peers

Abstract What causes adolescents to be materialistic? Prior research shows parents and peers are an important influence. Researchers have viewed parents and peers as socialization agents that transmit consumption attitudes, goals, and motives to adolescents. We take a different approach, viewing parents and peers as important sources of emotional support and psychological well-being, which increase self-esteem in adolescents. Supportive parents and peers boost adolescents' self-esteem, which decreases their need to turn to material goods to develop positive self-perceptions. In a study with 12–18 year-olds, we find support for our view that self-esteem mediates the relationship between parent/peer influence and adolescent materialism.
The Perils of Mandatory Parental Controls and Restrictive Defaults

Government regulation mandating restrictive parental control defaults for media devices would likely have unintended consequences and would not achieve the goal of better protecting children from objectionable content, whereas increased consumer education efforts would be more effective in helping parents control their child's media consumption.Restrictive defaults on parental control tools are not already widely in place in the market since there may not be a large demand for such restrictive tools where many parents already monitor their child's media consumption through household rules or self-monitoring. Sill, in light of evidence that most consumers would not opt for default parental controls, the reaction from consumers would be predictably less than favorable. And when consumers are unhappy about a service feature - but companies are not permitted to address that unhappiness by turning off the higher settings - a likely result could be for companies to weaken or even not offer parental controls altogether. Mandated defaults could also discourage consumers from purchasing new devices that could contain superior parental control tools.Mandating restrictive defaults could cause industry to suspend use of their voluntary rating systems altogether. After all, it is important to remember that the ratings and controls that government is seeking to regulate here are voluntary and private; there is no reason they couldn't be abandoned tomorrow. For the government to use these voluntary ratings systems as a basis for law or legal liability also raises constitutional concerns.Finally, mandated controls could actually cause parents to become less involved in their child's media consumption and might lull some parents into a false sense of security. If parents came to believe that because a filter was installed they need do nothing more to help their children go online safely, or become engaged in their media choices, that would be an extremely troubling outcome.
GENETIC SUBDIVISIONS AMONG SMALL CANIDS: MITOCHONDRIAL DNA DIFFERENTIATION OF SWIFT, KIT, AND ARCTIC FOXES.

Gene flow can effectively suppress genetic divergence among widely separated populations in highly mobile species. However, the same may not be true of species that typically disperse over shorter distances. Using mtDNA restriction-site and sequence analyses, we evaluate the extent of divergence among populations of two small relatively sedentary North American canids, the kit and swift foxes (genus Vulpes). We determine the significance of genetic differentiation among populations separated by distance and those separated by discrete topographic barriers. Our results show the among-population component of genetic variation in kit and swift foxes is large and similar to that of small rodents with limited dispersal ability. In addition, we found two distinct groupings of genotypes, separated by the Rocky Mountains, corresponding to the traditional division between kit and swift fox populations. Previous workers have characterized these morphologically similar populations either as separate species or subspecies. Our mtDNA data also suggest that kit and swift fox populations hybridize over a limited geographic area. However, the sequence divergence between kit and swift foxes is similar to that between these taxa and the arctic fox (Alopex lagopus), a morphologically distinct species commonly placed in a separate genus. This result presents a dilemma for species concepts, and we conclude that kit and swift foxes should be recognized as separate species.
X-ray and Transport Studies of Ruthenium-Iridium Bicrystal Superlattices

The stacking structure and epitaxial ordering are studied in MBE-grown Ru-Ir superlattices of wavelengths λ = 41\ and 62\. These samples span the fcc-hcp crossover previously found to occur when the Ir component is thinner than about 10 monolayers. Evidence for a new stacking sequence of period 3λ is found in the λ=41\ sample, possibly resulting from stacking faults in the Ir layers. The superconducting transition temperature is significantly higher in the 41\ sample (T c =0.19K) than in the 62\ sample (T c =0.15K).
Targeting the Right Level of Socio-Cognitive Analysis: Complex Problem Solving in High Performance Networks

Our study focuses on network engineers' experiences when they troubleshoot complex problems in distributed data and communication networks. Currently, these troubleshooters lack truly useful support for this complex problem solving. To identify socio-cognitive demands of this nonroutine troubleshooting, we conducted interviews with advanced network troubleshooters and analyzed transcripts of real time troubleshooting and post-mortem discussions among troubleshooters from diverse domains. Findings show that ad hoc cross domain collaborations are vital to the success of complex troubleshooting and that collaborators need better support for discussing responsibility in human and organizational terms and for recognizing strategic gaps, detailed issues and trade-offs they must negotiate for problem conditions.
Tunable fluidic intraocular lens in human eye model

Tunable fluidic lenses with deformable surfaces were tested in human eye models as intraocular lenses (IOLs). Fluidic IOL shows superior performance because of its wide accommodation range and similar working principle to the crystalline lens.
A Survey on Interactive System and Operation Patterns of Intelligent Power Utilization

Interactive technology of intelligent power utilization is an important constituent in overall architecture of smart grid.Based on business requirement of smart grid,several key problems in interactive technology system of intelligent power utilization,including typical business scenarios such as consumer information and marketing,the technical route of connotation and development of interactive technologies such as energy utilization management,grid-connection of distributed generation and charging/ discharging of electric vehicles,the interactive structural system of intelligent power utilization based on the architectures of business,data,technique and integration,the interactive business patterns of intelligent power utilization and corresponding business model and risk aversion mechanism,are summarized,and the interactive business patterns of intelligent power utilization as well as their commercial operation modes suitable for China's national situation are discussed.
Comprehensively Defending High Risk Events with Low Probability

Cascading disasters of earthquake and tsunami gave rise to blackout and further nuclear leakage in East Japan in 2011.Cognitive deficiencies on small probability events with very high risk are introspected from a viewpoint on risk.Principles coping with such incidents are also proposed.The construction,operation and management of integrated defense systems are discussed,as well as the improvements urgently needed.Finally,the important roles played by strong smart grid in energy security and ecological security are well indicated.
Marek's disease lymphomas

Publisher Summary This chapter discusses the lymphogenesis of Marek's disease (MD) lymphomas. The clinical signs of MD can be attributed to the nature of the MD lymphoma, which causes organ dysfunction. The lymphomas can be gross or visceral. In classical MD, gross lymphomas predominate in the peripheral nerves; lymphomas of the brachial and lumbo-sacral neural plexuses cause paralysis. Gross lymphomas are the incidental consequences of increasing the state of activation, lifespan, and proliferative potential of latently infected lymphocytes. Evidence shows that similar numbers of neoplastically transformed cells occur in both MD-resistant and MD-susceptible chickens immediately after Marek's disease virus (MDV) infection. Somehow the neoplastically transformed cells die in MD-resistant chickens but survive and proliferate in MD-susceptible chickens. The most logical explanation for MDV-induced neoplastic transformation of lymphocytes is persistence in the host. The visceral lymphomas, typical of acute MD, commonly occur in the adrenal gland, heart, intestine, kidney, liver, lung, ovary, proventriculus, serosa, skeletal muscle, spleen, and thymus. Lymphomas consist predominantly of heterogeneous accumulations of T lymphocytes and lymphoblasts; however, B lymphocytes, macrophages, and reticulum cells are present as minorities. The frequency and severity to which each organ is affected vary and depend on the chicken genotype and MDV strain. This survival is despite the expression of the largest amounts of the MDV Meq protein and high major histocompatibility complex (MHC) class I and II expression.
Stable Iridium(IV) Complexes of an Oxidation-Resistant Pyridine-Alkoxide Ligand: Highly Divergent Redox Properties Depending on the Isomeric Form Adopted.

The preparation of the facial and meridional isomers of [Ir(pyalk)3] (pyalk = 2-(2-pyridyl)isopropanoate), as model complexes for a powerful water oxidation catalyst, is reported. The strongly donating N3O3 ligand set is very oxidation-resistant, yet promotes facile metal-centered oxidation to form stable Ir(IV) compounds. The IrIII/IV reduction potentials of the two isomers differ by 340 mV despite the identical ligand set. A ligand field rationalization is advanced and supported by DFT calculations.
When More is Less: Base Value Neglect and Consumer Preferences for Changes in Price and Quantity

In a series of studies, we document an advantage in sales volume for a bonus pack relative to an economically equivalent price discount. We provide evidence that consumers’ preferences for quantity changes (including bonus packs and quantity decreases) are due to their tendency toward neglecting the base value of percentages.
Formulation studies of InhA inhibitors and combination therapy to improve efficacy against Mycobacterium tuberculosis.

Previously, structure-based drug design was used to develop substituted diphenyl ethers with potency against the Mycobacterium tuberculosis (Mtb) enoyl-ACP reductase (InhA), however, the highly lipophilic centroid compound, SB-PT004, lacked sufficient efficacy in the acute murine Mtb infection model. A next generation series of compounds were designed with improved specificity, potency against InhA, and reduced cytotoxicity in vitro, but these compounds also had limited solubility. Accordingly, solubility and pharmacokinetics studies were performed to develop formulations for this class and other experimental drug candidates with high logP values often encountered in drug discovery. Lead diphenyl ethers were formulated in co-solvent and Self-Dispersing Lipid Formulations (SDLFs) and evaluated in a rapid murine Mtb infection model that assesses dissemination to and bacterial burden in the spleen. In vitro synergy studies were performed with the lead diphenyl ether compounds, SB-PT070 and SB-PT091, and rifampin (RIF), which demonstrated an additive effect, and that guided the in vivo studies. Combinatorial therapy in vivo studies with these compounds delivered in our Self-Micro Emulsifying Drug Delivery System (SMEDDS) resulted in an additional 1.4 log10 CFU reduction in the spleen of animals co-treated with SB-PT091 and RIF and an additional 1.7 log10 reduction in the spleen with animals treated with both SB-PT070 and RIF.
A performance evaluation of an installed photovoltaic system without energy storage. Case study: IRI premises

Lebanon has a significant potential for the installation of photovoltaic systems. This technology of renewable energy is ecological, supplants other sources of energy and is widely attainable. The objective of this paper is to examine and evaluate the performance of an installed PV generator during three years 2013–2015. This case study of the integration of 56 kWp at the Industrial Research Institute (IRI) includes accurate data for solar radiation, energy production, benefits in fuel savings and reduction in CO 2 emissions. The results can be used at any place with similar climatic conditions where these types of data are either missing or unavailable. All the data collected from this study will grant us an opportunity for installing and integrating a photovoltaic system into any industrial and residential building in Lebanon. It comes in accordance to the vision of the general directorate of the institute to help the industrial institutions in all aspects of apprehension, studies and researches.
Towards large-scale MR thigh image analysis via an integrated quantification framework

In this paper, we focus on large scale magnetic resonance (MR) thigh image analysis via accurately quantifying major tissue composition in the thigh by a novel integrated framework. Specifically, the framework is able to distinguish muscular tissue and different types of adipose tissues, i.e. subcutaneous adipose tissue(SAT), inter- and intra-muscular adipose tissue (IMAT and IAMAT), efficiently. Deformable models and learning based techniques are integrated in the novel framework to enable robust quantification. Importantly, extensive evaluations are conducted on a large set of 3D MR thigh volumes from longitudinal studies of hundreds of subjects to investigate radiographic osteoarthritis (OA) related changes of muscular and adipose tissue volumes. The analysis is constructed by two subcohorts (G1 and G2). G2 has 61 patients which keep healthy at baseline (BL) and 48 months (M48), while G1's 85 patients are healthy at BL but have knee OA at M48. Paired t-tests are used to investigate the changes of these tissue size over time passing with/without pathological progression. The experimental results show that, in G1, patients' IMAT and IAMAT are statistically significant respectively, yet G2 has no such variation in the same tissue type. Thus we conclude from the statistical analysis that age may not directly affect thigh tissues, but IMAT and IAMAT may have obvious changes in patients with knee OA.
Study of the photodegradation of a fragrance ingredient for aquatic environmental fate assessment

Abstract Photodegradation is an important abiotic degradation process to be taken into account for more accurate assessment of the fate of chemicals in the aquatic environment, especially those that are not readily biodegradable. Although the significant role of indirect photodegradation in the environmental fate of chemicals has been revealed in recent research, because of the many confounding factors affecting its kinetics, no straightforward approaches can be used to investigate this degradation process for environmental fate assessment. The indirect photodegradation of a fragrance ingredient named Pamplewood was studied in this work for its fate assessment. Indirect photodegradation rates under various indoor and outdoor conditions were measured by using an LC-MS method. Although the half-lives varied from 4 to 13 days, they collectively indicated that Pamplewood is intrinsically photolabile and can undergo rapid photodegradation. Results from quencher experiments revealed that ⋅OH was the main reactive intermediate responsible for indirect photodegradation, with a half-life of about 18 days in sunlit surface water, based on the experimentally determined second-order rate constant (8.48 ± 0.19 × 109 M−1 s−1). Photodegradation products of Pamplewood were also studied by GC-MS, LC-MS and total organic carbon content analyses. The results indicated that intermediates of Pamplewood photodegradation continued to photodegrade into smaller and more polar species. Complete mineralization of Pamplewood was observed when it was reacted with hydroxyl radicals in an aqueous solution. This novel approach can be applied for a more realistic environmental fate assessment of other non-readily biodegradable, hydrolysis-resistant, and non-sunlight-absorbing fragrance ingredients.
An 143nW relaxation oscillator for ultra-low power biomedical systems

This work presents a near zero power relaxation oscillator for biomedical applications. Relaxation oscillators have now become a potential candidate for on-chip clock references due to their miniaturized sizes and integrating capability. In order to be suitable for biomedical applications, accurate and energy-efficient oscillators are required. An ultra-low power relaxation oscillator with 20kHz oscillating frequency is implemented with 0.13μm CMOS process. A switched-current technique is proposed to reduce the power consumption without compromising the overall performance. The relaxation oscillator consumes 143nW power and has a temperature coefficient of 19.1ppm/° C with a phase noise of −93dBc/Hz at 1kHz offset frequency.
Will Catholic hospitals survive without government reimbursements

This brief essay will begin to address the feasibility of operating a Catholic healthcare system without reimbursement from government healthcare programs such as Medicare and Medicaid. This questi...
On-Body Long-Range Wireless Backscattering Sensing System Using Inkjet-/3-D-Printed Flexible Ambient RF Energy Harvesters Capable of Simultaneous DC and Harmonics Generation

A novel wearable and flexible energy autonomous on-body sensing network is proposed featuring full operability through energy harvesting from a hand-held 464.5-MHz UHF two-way talk radio. Three different functions are provided utilizing the hand-held two-way talk radio as the only energy source for our proposed system. There are two types of energy harvesters (EHs) proposed for the presented system. The first EH that is mounted on the sensing capable backscattering RFID tags harvests the 464.5-MHz signal energy to drive the tags; the second EH that can be worn on hands harvests the same 464.5-MHz signal to produce both the dc power and the carrier signal. The second EH is more efficient than conventional ambient RF energy harvesting architectures because for the first time, both the dc and the second harmonics generated by the rectifier are utilized to enable two additional functions. The generated second harmonic is used to interrogate backscattering RFID tags for on-body sensing, while the dc power is used to power an RF amplifier in order to enhance the second harmonic to effectively extend the sensing and communication range. For the proof-of-concept demonstration, the measured dc and the second harmonic, 929 MHz, output power from the proposed EH are 17.5 and 1.43 dBm, respectively, while a two-way talk radio is 9 cm away. The measured second harmonic output power is increased to 13 dBm utilizing the harvester-powered RF amplifier, and the reading range of the custom backscattering sensor tag is extended to more than 70 m. Also, the interrogation of multiple sensor tags and the wireless detection of ammonia gas utilizing an inkjet printed flexible ammonia sensor are demonstrated showing the wide range of applications of the proposed approach.
Informal Mentoring of Adolescents about Computing: Relationships, Roles, Qualities, and Impact

Influencing adolescent interest in computing is key to engaging diverse teens in computer science learning. Prior work suggests that informal mentorship may be a powerful way to trigger and maintain interest in computing, but we still know little about how mentoring relationships form, how mentors trigger and maintain interest, or what qualities adolescents value in informal mentors. In a 3-week career exploration class with 18 teens from underrepresented groups, we had students write extensively about their informal computing mentors. In analyzing their writing, we found that most teens had informal computing mentors, that mentors were typically teachers, friends, and older siblings (and not parents or school counselors), and that what teens desired most were informal mentors that were patient, helpful, inspiring, and knowledgeable. These findings suggest that computing mentors can come in many forms, that they must be patient, helpful, and inspiring, but that they also require content knowledge about computing to be meaningful. Future work might explore what knowledge of computing is sufficient to empower teachers, parents, peers, and family to be effective computing mentors.
Elevated cerebrospinal fluid total Tau levels reflects predominant cortical involvement in Alzheimer’s disease (P1.093)

Objective: To investigate the clinical characteristics of Alzheimer’s disease (AD) patients with highly elevated cerebrospinal fluid (CSF) total tau (T-tau). Background: The level of CSF T-tau is thought to reflect the intensity of the neuronal damage. The highest increase is found in disorders with severe neuronal degeneration, such as Creutzfeldt-Jakob disease or acute stroke, with a moderate increase in AD. Very high levels of T-tau have been previously reported in rapidly progressive forms of AD (Brain.2015; 138:1009–22). Design/Methods: Retrospective analyses on data from the Cleveland Clinic Center for Brain Health Biobank, 2013–2016. 70 patients with symptom onset within three years of CSF evaluation, and with clinical signs and CSF biomarkers levels indistinguishable from AD were analyzed. 14 patients had T-Tau >1000pg/ml. We compared the age, sex, education, APOɛ4, Montreal cognitive Assessment (MOCA) scores and predominant clinical symptom between the High T-Tau (HT-Tau, n=14) and Low T-Tau (LT-Tau, n=56) (HT-Tau >1000pg/ml.) MRI measures of hippocampus, inferior lateral ventricle and cortical gray matter volumes corrected for intracranial volume were also compared for 5 HT-Tau and 32 LT-Tau with volumetric data. Results: The HT-Tau and LT-Tau did not differ on age, education, APOɛ4, and duration of symptoms. The HT-Tau group was more likely to have aphasia as an early clinical sign (χ 2 test p=0.02), trended towards having an initial non-amnestic presentation (χ 2 test p=0.07), and a lower MOCA score (13.5 vs 16.8, Mann Whitney p=0.04). In the MRI exploratory analysis, the HT-Tau had significantly lower cortical gray matter volume on the right (Mann Whitney p=0.036). Conclusions: Elevated CSF Tau levels in AD patients could be surrogate biomarker for AD subtypes with predominant early cortical symptoms and atrophy. There is a need for a systematic prospective unbiased follow-up to see if rapid clinical progression in AD is related to elevated T-Tau and distinct AD subtypes. Disclosure: Dr. Pillai has nothing to disclose. Dr. Khrestian has nothing to disclose. Dr. Bekris has nothing to disclose. Dr. Safar has nothing to disclose. Dr. Leverenz has received personal compensation for activities with Axovant, GE Healthcare and Navidea Biopharmaceuticals as a consultant.
Pearl River Delta and Guangzhou (Canton) China

By 2015, the Pearl River Delta urban agglomeration had overtaken Tokyo as the world’s largest megacity. The Pearl River Delta is sinking at an average rate of 2.5 mm/year. This subsidence, combined with rising sea level, increased intensity of impact from typhoons and storm surge and projections for increased urban expansion have placed Guangzhou at, or near the top of the list of the world’s most threatened coastal cities.
Rheology and Processing Experience of New Metallocene Polyolefins

The so-called metallocene revolution has created new families of polyolefins with unprecedented properties. Very high comonomer content in polyethylenes results in low modulus, high flexibility, and in some cases, thermoplastic elastomeric properties. The ability to incorporate short chain branches homogeneously has created polyethylenes of excellent optical clarity. This property is very important in medical and food packaging. This chapter presents a rheological comparison on these polyolefins, related to actual large-scale processing experiences. A broad based rheology and processing study is conducted on a series of single site and metallocene polyethylenes using high pressure low-density polyethylene (LDPE) and ethylene vinyl acetate (EVA) as references.
Slit Ventricle Syndrome or Syndromes: Diagnosis and Management

The term “slit ventricle syndrome” (SVS) is widely used to describe a condition of severe, usually intermittent, headaches suffered by patients with longstanding ventricular shunting for hydrocephalus [15,16,20]. It is important to differentiate this condition from the smaller than normal, even almost nonexistent ventricles seen in some patients on routine imaging studies. The finding of radiographic slit ventricles occurs in at least 85% of children who are shunted and has been said to be a “goal” of shunting (M.L. Walker, personal communication, 1986). Most of these patients are asymptomatic and require no intervention. Only when patients begin to suffer from a severe headache disorder that interferes with their normal lives does the presence of radiographic slit ventricles lead to the diagnosis of the SVS.
Food for thought: How trade agreements impact the prospects for a national food policy

This article examines the prospect for a national food policy through the lens of trade agreements and the concept of policy space. It traces the shrinking of domestic policy space in recent decades as a result of trade agreements. Advocates such as Food Secure Canada seek a “coherent” food policy that supports a sustainable, more domestically-focused, food system. This article argues that the prospects for such a policy are constrained, based on Canada’s past history, under both Liberal and Conservative governments, as well as recent bilateral and regional agreements. It examines the Canada-European Union Comprehensive Economic and Trade Agreement (CETA), the Transpacific Partnership Agreement (TPP) which included the United States, and the subsequent Comprehensive and Progressive Agreement for Trans-Pacific Partnership (CPTPP) negotiated by the remaining eleven partners after the US departure. Focussing on market access, standards, regulatory harmonization and procurement, I argue that provisions in these agreements, along with what we might expect in future trade negotiations, pose challenges for the development of a national food policy.
Introduction from the New Editor-in-Chief

I am honored to be following Jody Langdon as the next editor-in-chief for the International Journal of Kinesiology in Higher Education (IJKHE). Having worked with Jody for the past three years on t...
Magnetic-field control of ionic bonds on ferroelectric surfaces

It is shown theoretically that applying magnetic fields can modulate the strength of ionic bonds on the surface of a ferroelectric film via field-induced strains from a magnetostrictive substrate. The ionic bonds form between oppositely charged polyelectrolytes that are bonded to the ferroelectric surface via the Coulomb interaction. The calculations show that applying a magnetic field can tune the activation energy of bond dissociation up by ∼50% or down to zero. This large modulation results from the high sensitivity of ferroelectric surface polarization to strain variation near ferroelectric phase transitions, which occur in epitaxial BaTiO3 films at experimentally accessible residual strains. Our results suggest an opportunity for tailoring the ionic bond strength on ferroelectric surfaces both statically and dynamically via strain engineering.
Patients with Unusual Congenital Heart Defects and/or Intracardiac Shunts

This chapter presents data drawn from a number of interesting and informative cases focusing on patients with unusual congenital heart defects and/or intracardiac shunts.
Evaluation of synergy between host and pathogen-directed therapies against intracellular Leishmania donovani.

Visceral leishmaniasis (VL) is associated with treatment complications due to the continued growth of resistant parasites toward currently available pathogen-directed therapeutics. To limit the emergence and combat resistant parasites there is a need to develop new anti-leishmanial drugs and alternative treatment approaches, such as host-directed therapeutics (HDTs). Discovery of new anti-leishmanial drugs including HDTs requires suitable in vitro assay systems. Herein, we modified and evaluated a series of resazurin assays against different life-stages of the VL causing parasite, Leishmania donovani to identify novel HDTs. We further analyzed the synergy of combinatorial interactions between traditionally used pathogen-directed drugs and HDTs for clearance of intracellular L. donovani. The inhibitory concentration at 50% (IC50) of the five evaluated therapies [amphotericin B (AMB), miltefosine, paromomycin, DNER-4, and AR-12 (OSU-03012)] was determined against promastigotes, extracellular amastigotes, and intracellular amastigotes of L. donovani via a resazurin-based assay and compared to image-based microscopy. Using the resazurin-based assay, all evaluated therapies showed reproducible anti-leishmanial activity against the parasite's different life-stages. These results were consistent to the traditional image-based technique. The gold standard of therapy, AMB, showed the highest potency against intracellular L. donovani, and was further evaluated for combinatorial effects with the HDTs. Among the combinations analyzed, pathogen-directed AMB and host-directed AR-12 showed a synergistic reduction of intracellular L. donovani compared to individual treatments. The modified resazurin assay used in this study demonstrated a useful technique to measure new anti-leishmanial drugs against both intracellular and extracellular parasites. The synergistic interactions between pathogen-directed AMB and host-directed AR-12 showed a great promise to combat VL, with the potential to reduce the emergence of drug-resistant strains.
Urban Burial Reform in William Wordsworth’s “Village Churchyard”

Katherine E. Blake “Urban Burial Reform in William Wordsworth’s ‘Village Churchyard’” (pp. 279–304) This essay looks at the relationship between space and class in nineteenth-century English burials in order to shed new light on William Wordsworth’s Essays upon Epitaphs (1810, 1876) and “The Brothers” (1800). While Wordsworth’s work dwells on pastoral images of burial, I argue that his representations in fact align more closely with the cultural practices and values underpinning urban burial conventions. Through his representation of burial space, Wordsworth’s work plays out urban concerns about burial in the countryside. Ultimately, this essay argues that the exportation of urban concerns to imaginary rural sites accounts for the utility of Wordsworth’s work to mid-nineteenth-century burial reformers, and particularly to Edwin Chadwick, a utilitarian known for his work on the 1832 Poor Law and sanitary guidelines for burial. By reevaluating what prior studies have said about Chadwick’s reforms in light of recent work on his economic theories, I argue that Chadwick’s citation of Wordsworth’s first “Essay upon Epitaphs” transforms the latter’s pastoral vision into an endorsement of a national cemetery. I explore the extent to which Wordsworth’s early-nineteenth-century ideas are and are not compatible with Chadwick’s mid-century reforms.
Quality of Life Following Molecular Marker Testing for Indeterminate Thyroid Nodules.

Objective: Thyroid cancer has a disproportionately negative effect on quality of life (QOL) compared to malignancies with a worse prognosis. QOL of patients with indeterminate thyroid nodules has not been previously evaluated. We aimed to assess the impact of molecular test results on QOL of patients with indeterminate thyroid nodules. Methods: A short version of the Thyroid-Related Patient-Reported Outcome (ThyPro-39) assessed QOL of patients who underwent thyroid fine needle aspiration (FNA) biopsy throughout UCLA Health from May 2016 to June 2017. All patients with indeterminate biopsy results underwent molecular testing with either Afirma Gene Expression Classifier (GEC) or ThyroSeq v2 at the time of the initial biopsy. QOL associated with symptoms of goiter, anxiety, depression, and impaired daily life were analyzed. Results: Of 825 consented patients, 366 completed the assessment (44.4% response rate). FNA results included 76% benign, 7% malignant, and 17% indeterminate. There were no differences in QOL between patients with a benign FNA and patients with an indeterminate result with benign molecular testing. In patients with an indeterminate FNA, symptoms of goiter (20.5 vs. 10.4, P = 0.033) and depression (33.3 vs. 21.0, P = 0.026) were worse for patients with suspicious versus benign molecular test results; however, no significant differences were observed in anxiety or impaired daily life. Conclusions: A benign molecular test result may provide reassurance for patients with indeterminate thyroid nodules that the risk of malignancy is low. Long-term follow-up is necessary to determine if benign molecular test results maintain improved QOL.
Benoxacor is enantioselectively metabolized by rat liver subcellular fractions.

Abstract This study investigated the enantioselective metabolism of benoxacor, an ingredient of herbicide formulations, in microsomes or cytosol prepared from female or male rat livers. Benoxacor was incubated for ≤30 min with microsomes or cytosol, and its enantioselective depletion was measured using gas chromatographic methods. Benoxacor was depleted in incubations with active microsomes in the presence and absence of NADPH, suggesting its metabolism by hepatic cytochrome P450 enzymes (CYPs) and microsomal carboxylesterases (CESs). Benoxacor was depleted in cytosolic incubations in the presence of glutathione, consistent with its metabolism by glutathione S-transferases (GSTs). The depletion of benoxacor was faster in incubations with cytosol from male than female rats, whereas no statistically significant sex differences were observed in microsomal incubations. The consumption of benoxacor was inhibited by the CYP inhibitor 1-aminobenzotriazole, the CES inhibitor benzil, and the GST inhibitor ethacrynic acid. Estimates of the intrinsic clearance of benoxacor suggest that CYPs are the primary metabolic enzyme responsible for benoxacor metabolism in rats. Microsomal incubations showed an enrichment of the first eluting benoxacor enantiomer (E1-benoxacor). A greater enrichment occurred in incubations with microsomes from female (EF = 0.67 ± 0.01) than male rats (EF = 0.60 ± 0.01). Cytosolic incubations from female rats resulted in enrichment of E1-benoxacor (EF = 0.54 ± 0.01), while cytosolic incubations from male rats displayed enrichment of the second eluting enantiomer (E2-benoxacor; EF = 0.43 ± 0.01). Sex-dependent differences in the metabolism of benoxacor in rats could significantly impact ecological risks and mammalian toxicity. Moreover, changes in the enantiomeric enrichment of benoxacor may be a powerful tool for environmental fate and transport studies.
Protecting synapses from amyloid β-associated degeneration by manipulations of Wnt/planar cell polarity signaling

ABSTRACT Synapse loss is an early event in Alzheimer’s disease and is thought to be associated with amyloid pathology and caused by Amyloid β (Aβ) oligomers. Whether and how Aβ oligomers directly target signaling pathways for glutamatergic synapse maintenance is unknown. Glutamatergic synapse development is controlled by the opposing functions of Celsr3 and Vangl2, core components of the Wnt/planar cell polarity (PCP) signaling pathway, functioning directly in the synapses. Celsr3 promotes synapse formation, whereas Vangl2 inhibits synapse formation. Here we show that oligomeric Aβ binds to Celsr3 and assists Vangl2 in disassembling synapses by disrupting the intercellular Celsr3/Frizzled3-Celsr3 complex, essential for PCP signaling. Together with Vangl2, a Wnt receptor, Ryk, is also required for Aβ oligomer-induced synapse loss in a mouse model of Alzheimer’s disease, 5XFAD, where conditional Ryk knockout protected synapses and preserved cognitive function. Our study reveals a fine balance of Wnt/PCP signaling components in glutamatergic synapse maintenance and suggests that overproduced Aβ oligomers may lead to excessive synapse loss by tipping this balance. Together with previous reports that an inhibitor of Wnt/Ryk signaling, WIF1, is found reduced in Alzheimer’s disease patients, our results suggest that the imbalance of PCP signaling in these patients may contribute to synapse loss in Alzheimer’s disease and manipulating Wnt/PCP signaling may preserve synapses and cognitive function.
U.S. space policy: Multilateral mining.

In their Policy Forum “U.S. policy puts the safe development of space at risk” (9 October, p. 174), A. Boley and M. Byers claim that U.S. plans to purchase a small amount of commercial Moon resources put the safe development of space at risk. To the contrary, U.S. actions are poised to help jumpstart a new age of space innovation that has the potential to bring scientific and economic benefits to the whole world. There is no global consensus on international regulation of space mining. The Moon Agreement and other related recent attempts have been widely rejected. The United States has led negotiations on the Artemis Accords on a bilateral basis, but it will be a multilateral agreement, with Japan, Canada, the United Kingdom, Italy, Australia, Luxembourg, and the United Arab Emirates joining in October ([ 1 ][1]). The Accords can form a foundation for a future global framework, which ensures all nations can access the resources of outer space. Environmental management and standards are essential to space mining but are not guaranteed by international regulatory models. International space law already requires, or encourages, national regulation with regard to planetary protection, avoiding harmful contamination, and discouraging harmful interference ([ 2 ][2]). U.S. leadership in the space environment can help ensure that sustainability is engrained in the space mining industry from the start. Early national regulation can facilitate sustainable space mining innovation; it does not inhibit it. Boley and Byers point to the management of the deep seabed by the United Nations Convention on the Law of the Sea as an alternative global model for sustainable resource use. However, decades later, that model has still not been successful. No commercial deep-sea mining has occurred in the High Seas, the benefit sharing mechanism is not established, and the system has struggled to define environmental management standards. A global approach may eventually emerge, but it is better to begin by stimulating the market and implementing imperfect regulation than to wait. 1. [↵][3]National Aeronautics and Space Administration (NASA), “NASA, international partners advanced cooperation with first signings of the Artemis Accords” (2020). 2. [↵][4]1. S. W. Anderson, 2. K. Christensen, 3. J. LaManna , J. Energ. Nat. Resourc. Law 37, 227 (2019). [OpenUrl][5] [1]: #ref-1 [2]: #ref-2 [3]: #xref-ref-1-1 "View reference 1 in text" [4]: #xref-ref-2-1 "View reference 2 in text" [5]: {openurl}?query=rft.jtitle%253DJ.%2BEnerg.%2BNat.%2BResourc.%2BLaw%26rft.volume%253D37%26rft.spage%253D227%26rft.genre%253Darticle%26rft_val_fmt%253Dinfo%253Aofi%252Ffmt%253Akev%253Amtx%253Ajournal%26ctx_ver%253DZ39.88-2004%26url_ver%253DZ39.88-2004%26url_ctx_fmt%253Dinfo%253Aofi%252Ffmt%253Akev%253Amtx%253Actx
Simposio 1: Diabetes secundaria a diferentes tipos de trasplante

Symposium 1: When diabetes is not autoimune Diabetes secondary to different types of transplantation Post-Transplantation Diabetes Mellitus (PTDM) is a broadly reported complication that occurs following organ transplantation. The incidence of PTDM is estimated between 10-20% in kidney recipients and 30-40 in solid organ recipients, although significant variability has been reported. It has variably been reported to be associated with increased morbidity and mortality. PTDM Incidence is affected by risk factors directly and indirectly associated to transplantation. Predisposing factors such as age, life style, genetic, family history, obesity contribute to increase the incidence of PTDM, however, factors related to the transplant setting are also to be considered as a causative factors.
Towards rapid detection and mapping of powdery mildew in apple orchards

Powdery mildew (PM) in apples is a critical fungal disease that adversely affects yield and fruit quality. Conventional PM identification techniques are laborious. This study evaluated the suitability of non-destructive low altitude imaging in the visible (RGB) and multispectral domain for PM detection in apple orchards. Imagery snapshots were acquired at known locations of PM infestation in apple trees using two small unmanned aerial systems (UAS). One UAS employed a consumer grade RGB camera while other UAS had a five-band multispectral imaging sensor. Custom image processing algorithms were developed for RGB and multispectral imagery analysis. The RGB images were classified using k-means and resulted in PM detection accuracy of 76.4%. A strong agreement was also observed between the number of actual PM clusters and clusters that were classified (R2 = 0.94). Seven vegetation indices (VIs) were extracted from the multispectral imagery as the potential chlorophyll variation indicators. Such indices showed significant difference (p < 0.05) for PM infected leaves and the healthy leaves. Modified Simple Ratio-Red, Modified Simple Ratio-Blue and Optimized Soil Adjusted Vegetation Index were the key differentiators showing low values for PM (Mean: 0.01–0.05) and high values for healthy leaves (Mean: 0.51–0.84). Overall, results showed the potential to detect and quantify PM infestation in apple orchards at high spatial resolution. Additional efforts are needed to translate these results to map PM infestation at the orchard block level that could aid in site-specific remedial measures.
On studying extreme values and systematic risks with nonlinear time series models and tail dependence measures

This review paper discusses advances of statistical inference in modeling extreme observations from multiple sources and heterogeneous populations. The paper starts briefly reviewing classical univ...
Scavenger Receptor A1 Mediates the Uptake of Carboxylated and Pristine Multi-Walled Carbon Nanotubes Coated with Bovine Serum Albumin

Previously, we noted that carboxylated multi-walled carbon nanotubes (cMWNTs) coated with Pluronic® F-108 (PF108) bound to and were accumulated by macrophages, but that pristine multi-walled carbon nanotubes (pMWNTs) coated with PF108 were not (Wang et al., Nanotoxicology2018, 12, 677). Subsequent studies with Chinese hamster ovary (CHO) cells that overexpressed scavenger receptor A1 (SR-A1) and with macrophages derived from mice knocked out for SR-A1 provided evidence that SR-A1 was a receptor of PF108-cMWNTs (Wang et al., Nanomaterials (Basel) 2020, 10, 2417). Herein, we replaced the PF108 coat with bovine serum albumin (BSA) to investigate how a BSA corona affected the interaction of multi-walled carbon nanotubes (MWNTs) with cells. Both BSA-coated cMWNTs and pMWNTs bound to and were accumulated by RAW 264.7 macrophages, although the cells bound two times more BSA-coated cMWNT than pMWNTs. RAW 264.7 cells that were deleted for SR-A1 using CRISPR-Cas9 technology had markedly reduced binding and accumulation of both BSA-coated cMWNTs and pMWNTs, suggesting that SR-A1 was responsible for the uptake of both MWNT types. Moreover, CHO cells that ectopically expressed SR-A1 accumulated both MWNT types, whereas wild-type CHO cells did not. One model to explain these results is that SR-A1 can interact with two structural features of BSA-coated cMWNTs, one inherent to the oxidized nanotubes (such as COOH and other oxidized groups) and the other provided by the BSA corona; whereas SR-A1 only interacts with the BSA corona of BSA-pMWNTs.
The Effects of Chemotherapeutics on the Ovarian Cancer Microenvironment

High-grade serous ovarian cancer (HGSOC) is characterized by a complex and dynamic tumor microenvironment (TME) composed of cancer-associated fibroblasts (CAFs), immune cells, endothelial cells, and adipocytes. Although most approved therapies target cancer cells, a growing body of evidence suggests that chemotherapeutic agents have an important role in regulating the biology of the diverse cells that compose the TME. Understanding how non-transformed cells respond and adapt to established therapeutics is necessary to completely comprehend their action and develop novel therapeutics that interrupt undesired tumor-stroma interactions. Here, we review the effects of chemotherapeutic agents on normal cellular components of the host-derived TME focusing on CAFs. We concentrate on therapies used in the treatment of HGSOC and synthesize findings from studies focusing on other cancer types and benign tissues. Agents such as platinum derivatives, taxanes, and PARP inhibitors broadly affect the TME and promote or inhibit the pro-tumorigenic roles of CAFs by modifying the bidirectional cross-talk between tumor and stromal cells in the tumor organ. While most chemotherapy research focuses on cancer cells, these studies emphasize the need to consider all cell types within the tumor organ when evaluating chemotherapeutics.