cssi/SciSciGPT-SciSciNet huggingface dataset:
The core clock gene Per1 phases molecular and electrical circadian rhythms in SCN neurons

The brain's biological clock, the suprachiasmatic nucleus (SCN), exhibits endogenous 24-hour rhythms in gene expression and spontaneous firing rate; however, the functional relationship between these neuronal rhythms is not fully understood. Here, we used a Per1::GFP transgenic mouse line that allows for the simultaneous quantification of molecular clock state and firing rate in SCN neurons to examine the relationship between these key components of the circadian clock. We find that there is a stable, phased relationship between E-box-driven clock gene expression and spontaneous firing rate in SCN neurons and that these relationships are independent of light input onto the system or of GABAA receptor-mediated synaptic activity. Importantly, the concordant phasing of gene and neural rhythms is disrupted in the absence of the homologous clock gene Per1, but persists in the absence of the core clock gene Per2. These results suggest that Per1 plays a unique, non-redundant role in phasing gene expression and firing rate rhythms in SCN neurons to increase the robustness of cellular timekeeping.
IMMUNE RESPONSE TO LEUKEMIA VIRUSES IN MICE

Publisher Summary This chapter focuses on the immune response to leukemia viruses in mice. Mouse antibodies are directed against four of the seven major viral proteins. Two of these proteins, gp70 and gp45, are glycosylated and are constituents of the viral envelope. One of the non-glycosylated antigens also is presumed to be located on the surface of the virion, although it is not considered to be as prominently exposed as the two glycoproteins. Antigens detected by mouse sera are group-specific determinants, and are demonstrable on both Moloney and Gross MuLV. Immunization of mice with leukemic cells increases the titer of antibody to MuLV; in one instance resulted in the stimulation of antibody against the major core protein of the virus. The presence of antibody against MuLV in mouse serum that can cause cytotoxic reactions with tumor cells indicates that particular caution should be used during the typing of sarcomas or leukemias for cell surface antigens, as mouse antisera may yield cytotoxicity based on anti-MuLV specificities, rather than on anticipated antigens.
Robust Transgene Expression from Bicistronic mRNA in the Green Alga Chlamydomonas reinhardtii

The unicellular green alga Chlamydomonas reinhardtii is a model organism that provides an opportunity to understand the evolution and functional biology of the lineage that includes the land plants, as well as aspects of the fundamental core biology conserved throughout the eukaryotic phylogeny. Although many tools are available to facilitate genetic, molecular biological, biochemical, and cell biological studies in Chlamydomonas, expression of unselected transgenes of interest (GOIs) has been challenging. In most methods used previously, the GOI and a selectable marker are expressed from two separate mRNAs, so that their concomitant expression is not guaranteed. In this study, we developed constructs that allow expression of an upstream GOI and downstream selectable marker from a single bicistronic mRNA. Although this approach in other systems has typically required a translation-enhancing element such as an internal ribosome entry site for the downstream marker, we found that a short stretch of unstructured junction sequence was sufficient to obtain adequate expression of the downstream gene, presumably through post-termination reinitiation. With this system, we obtained robust expression of both endogenous and heterologous GOIs, including fluorescent proteins and tagged fusion proteins, in the vast majority of transformants, thus eliminating the need for tedious secondary screening for GOI-expressing transformants. This improved efficiency should greatly facilitate a variety of genetic and cell-biological studies in Chlamydomonas and also enable new applications such as expression-based screens and large-scale production of foreign proteins.
The Comparative Effects of Electoral Laws on Voter Rationality: Plurality versus Proportional Election Rules

Electoral rules inherently structure the development of not only a political party system, but also create incentives and disincentives for individuals to participate in politics. Few scholars study the interaction between various electoral arrangements and how they encourage or discourage voting based on the characteristics of individuals. This research uses the Comparative Study of Electoral Systems to investigate the relationship between plurality and proportional electoral arrangements, on the one hand, and how they influence levels of political knowledge, sophistication, and the likelihood to vote, on the other hand. The countries studied are the United States which uses simple plurality rules, Australia which employs the alternative vote with compulsory voting, and Ireland which uses the single transferable vote. We find that plurality electoral arrangements result in consistently lower levels of political knowledge and voter sophistication. Furthermore, low levels of knowledge but not sophistication reduce turnout in plurality systems. These decreased turnout levels are greatest among individuals with the lowest levels of political knowledge, where individuals experience the highest burdens of voting. Strikingly, turnout among the highest educated citizens in the United States is still lower than participation by the least educated in Ireland.
Induction of Gamma Globin and Erythrocyte Anion Exchane Protein in BFU-E Cultured in the Presence of Hydroxyurea.

Abstract Hydroxyurea (HU) an S-phase specific cytotoxic agent has been used for the treatment of patients with sickle cell hemoglobinopathy and beta-thalassemias. The clinical efficacy of HU is due primarily to increases in fetal hemoglobin (HbF) levels. HU increases the %HbF and the %F cells. The HU reactive mechanism(s) in erythroid cells, however, have not been clearly defined. Patients receiving HU therapy develop subpopulations of macrocytic erythrocytes. Our previous studies demonstrate that sickle cell patients treated with HU develop subpopulations of RBCs that express greater relative levels of the erythrocyte anion exchange protein (AE1) per cell as compared with untreated individuals. We propose that part of the HU reactive mechanism will include the upmodulation of non-gamma globin erythroid proteins that contribute to the macrocytic structures. As part of our investigation of the development of RBCs expressing increased band 3 protein per cell, we have examined the possibility that HU induced AE1 synthesis can be detected in vitro using cultured erythroid progenitors. To investigate HU induced protein synthesis as a function of HU concentration, erythroid progenitors were cultured in semisolid media containing different concentrations of HU [0–40 micromolar] then assayed for AE1(band 3) and gamma globin. BFU-E were scored and harvested after 15 days in culture, then assayed. The change in the frequency of cells positive for band 3 protein was determined by flow cytometry, these cells were then assessed by laser scanning confocal microscopy. Results show that the frequency of cells positive for band 3 protein was greater in colonies grown in hydroxyurea as compared to controls. The band-3 upmodulation appears to plateau at 12.5 micromolar HU. These cells were assessed for dual and single stains by laser scanning confocal microscopy. Both band-3 protein and spectrin were detected. Laser scanning confocal microscopy revealed spectrin in the majority of cells; both band 3 and spectrin were detected in forty percent of the cells cultured in 12.5 micromolar HU. Band 3 protein detected by Western blots was increased [1–1.5 fold] over untreated control BFU-E harvested during the same time period. Secondly, the presence of band 3 protein and gamma globin in BFU-E was detected using two-color flow cytometry. BFU-E were cultured in increasing concentrations of HU. Colonies were permeabilized, and then labeled with tricolor-conjugated-anti-gamma globin. These cells were subsequently labeled with monoclonal anti-band 3 and PE-labeled anti-mouse antibody. Results show 2–3 fold increase in the % band 3 plus gamma globin positive cells over untreated cells. Collectively, these results suggest that part of the mechanism of HU action in erythroid cells involves the induction of erythroid structural proteins concordant with the induction of gamma globin.
Edge caching and nearest replica routing in information-centric networking

Information-centric networking (ICN) promises to improve content-oriented services by enabling in-network caching and supporting optimal content request forwarding. To achieve this goal, different content caching and request forwarding schemes are proposed in multiple ICN architectures. However, they differ from each other in whether pervasive caching is adopted, and whether nearest-replica routing is supported. In this work, we evaluate these options through extensive simulation over both single domain tree network and multi-domain network scenarios. Our evaluation shows that pervasive caching is not fundamentally better than edge caching; compared with pervasive caching, nearest replica routing brings more benefits, especially in a large network. Based on the observations, we propose a caching system built upon MobilityFirst architecture, in which edge caching is adopted, and nearest replica routing is supported through a global name resolution service. Additional evaluation shows that our proposal retains the advantages of ICN (e.g., requests served from "best" location), and is feasible to deploy globally.
Frequency of prescription opioid misuse and suicidal ideation, planning, and attempts.

Abstract The goal of this study was to examine the relationship between past-year frequency of prescription opioid misuse and past-year suicidal ideation, suicide planning, and suicide attempts. Secondary data analyses were conducted using data from 41,053 participants of the 2014 National Survey of Drug Use and Health. Past-year frequency of prescription opioid misuse was grouped into 4 categories: none, less than monthly (1–11 times), monthly to weekly (12–51 times), and weekly or more (52 times or more). Binomial logistic regression analyses adjusted for demographics, overall health rating, depression, anxiety, and substance use disorders to test the associations between frequency of prescription opioid misuse and suicide-related variables. Compared to those who did not endorse prescription opioid misuse in the past year, prescription opioid misuse was significantly associated with suicidal ideation, suicide planning, and suicide attempts for each frequency of use category in unadjusted models (p
Live birth outcomes after adolescent and young adult breast cancer.

Reproductive outcomes are an important survivorship concern for women diagnosed with cancer as adolescents and young adults (AYAs). We examined the incidence of live birth and the prevalence of adverse birth outcomes according to tumor and treatment characteristics among AYAs with breast cancer. Women diagnosed with breast cancer at ages 15-39 during 2000-2013 were identified using the North Carolina Central Cancer Registry (n = 4,978). Cancer registry records were linked to state birth certificate files from 2000 to 2014 to identify births to women with and without a breast cancer history. The breast cancer cohort was followed until live birth, death, age 46, or December 31, 2014, whichever occurred first. For each birth to breast cancer survivors (n = 338), we sampled 20 births to women without a recorded cancer diagnosis, with frequency matching on maternal age and year of delivery. The cumulative incidence of live births after breast cancer was 8% at 10 years. Births were less common among women treated with chemotherapy. Overall, the prevalence of preterm birth, low birth weight, small-for-gestational age (SGA) and Cesarean delivery did not differ substantially between births to women with and without breast cancer. However, births to women with ER-negative disease were more likely to be preterm (PR = 1.84; 95% CI: 1.11-3.06). In this population-based study, <10% of AYA breast cancer survivors had a live birth within 10 years of their diagnosis. The increase in risk of preterm delivery among ER-negative survivors in our cohort warrants further investigation in larger studies.
Effects of Gastric Bypass Surgery on Bone Mass and Microarchitecture Occur Early and Particularly Impact Postmenopausal Women

Roux-en-Y gastric bypass (RYGB) surgery is a highly effective treatment for obesity but negatively affects the skeleton. Studies of skeletal effects have generally examined areal bone mineral density (BMD) by dual-energy X-ray absorptiometry (DXA), but DXA may be inaccurate in the setting of marked weight loss. Further, as a result of modestly sized samples of mostly premenopausal women and very few men, effects of RYGB by sex and menopausal status are unknown. We prospectively studied the effects of RYGB on skeletal health, including axial and appendicular volumetric BMD and appendicular bone microarchitecture and estimated strength. Obese adults (N = 48; 27 premenopausal and 11 postmenopausal women, 10 men) with mean ± SD body mass index (BMI) 44 ± 7 kg/m2 were assessed before and 6 and 12 months after RYGB. Participants underwent spine and hip DXA, spine QCT, radius and tibia HR-pQCT, and laboratory evaluation. Mean 12-month weight loss was 37 kg (30% of preoperative weight). Overall median 12-month increase in serum collagen type I C-telopeptide (CTx) was 278% (p < 0.0001), with greater increases in postmenopausal than premenopausal women (p = 0.049). Femoral neck BMD by DXA decreased by mean 5.0% and 8.0% over 6 and 12 months (p < 0.0001). Spinal BMD by QCT decreased by mean 6.6% and 8.1% (p < 0.0001); declines were larger among postmenopausal than premenopausal women (11.6% versus 6.0% at 12 months, p = 0.02). Radial and tibial BMD and estimated strength by HR-pQCT declined. At the tibia, detrimental changes in trabecular microarchitecture were apparent at 6 and 12 months. Cortical porosity increased at the radius and tibia, with more dramatic 12-month increases among postmenopausal than premenopausal women or men at the tibia (51.4% versus 18.3% versus 3.0%, p < 0.01 between groups). In conclusion, detrimental effects of RYGB on axial and appendicular bone mass and microarchitecture are detectable as early as 6 months postoperatively. Postmenopausal women are at highest risk for skeletal consequences and may warrant targeted screening or interventions. © 2017 American Society for Bone and Mineral Research.
Meaning, modulation, and context: a multidimensional semantics for truth-conditional pragmatics

The meaning that expressions take on particular occasions often depends on the context in ways which seem to transcend its direct effect on context-sensitive parameters. ‘Truth-conditional pragmatics’ is the project of trying to model such semantic flexibility within a compositional truth-conditional framework. Most proposals proceed by radically ‘freeing up’ the compositional operations of language. I argue, however, that the resulting theories are too unconstrained, and predict flexibility in cases where it is not observed. These accounts fall into this position because they rarely, if ever, take advantage of the rich information made available by lexical items. I hold, instead, that lexical items encode both extension and non-extension determining information. Under certain conditions, the non-extension determining information of an expression e can enter into the compositional processes that determine the meaning of more complex expressions which contain e. This paper presents and motivates a set of type-driven compositional operations that can access non-extension determining information and introduce bits of it into the meaning of complex expressions. The resulting multidimensional semantics has the tools to deal with key cases of semantic flexibility in appropriately constrained ways, making it a promising framework to pursue the project of truth-conditional pragmatics.
Book review: Prolog for Programmers by Feliks Kluzniak and Stanislaw Szpakowicz (Academic Press)

Prolog for Programmers (PP) delivers what it promises by introducing Prolog to programmers from other languages; I know of no better introduction for this audience. (The dialect used is a slight variant of DEC-10 Prolog.) Yet even the experienced Prolog programmer can gain from PP's first-rate treatment of data structures, control, programming techniques, and implementation. The style is clear and concise, and a dry wit makes it fun to read. PP could be used as language text in an introductory Al course; for example, we have used it along with Genesereth and Nilsson's Logical Foundations of Artificial Intelligence. PP also addresses broader issues such as language extensibility with a chapter on definite-clause grammars; database with a case study of relational databases in Prolog; planning with an analysis of a STRIPS problem in WARPLAN; and implementation and optimization with a discussion of the authors' own Prolog interpreter. PP furnishes source for the interpreter and case studies in listings as well as on a floppy diskette.
Slow seeing and the environment: connections and meanings in beyond Fordlândia

“Slow Violence” is the key concept in the ecocritical thought of Rob Nixon and it has been an inspiration for the documentary Beyond Fordlândia. Slow Violence is defined as “a violence that occurs gradually and out of sight, a violence of delayed destruction that is dispersed across time and space, an attritional violence that is typically not viewed as violence at all” (NIXON, 2011).
Statins Suppress Ebola Virus Infectivity by Interfering with Glycoprotein Processing

Ebola virus (EBOV) infection is a major public health concern due to high fatality rates and limited effective treatments. Statins, widely used cholesterol-lowering drugs, have pleiotropic mechanisms of action and were suggested as potential adjunct therapy for Ebola virus disease (EVD) during the 2013-2016 outbreak in West Africa. Here, we evaluated the antiviral effects of statin (lovastatin) on EBOV infection in vitro Statin treatment decreased infectious EBOV production in primary human monocyte-derived macrophages and in the hepatic cell line Huh7. Statin treatment did not interfere with viral entry, but the viral particles released from treated cells showed reduced infectivity due to inhibition of viral glycoprotein processing, as evidenced by decreased ratios of the mature glycoprotein form to precursor form. Statin-induced inhibition of infectious virus production and glycoprotein processing was reversed by exogenous mevalonate, the rate-limiting product of the cholesterol biosynthesis pathway, but not by low-density lipoprotein. Finally, statin-treated cells produced EBOV particles devoid of the surface glycoproteins required for virus infectivity. Our findings demonstrate that statin treatment inhibits EBOV infection and suggest that the efficacy of statin treatment should be evaluated in appropriate animal models of EVD.IMPORTANCE Treatments targeting Ebola virus disease (EVD) are experimental, expensive, and scarce. Statins are inexpensive generic drugs that have been used for many years for the treatment of hypercholesterolemia and have a favorable safety profile. Here, we show the antiviral effects of statins on infectious Ebola virus (EBOV) production. Our study reveals a novel molecular mechanism in which statin regulates EBOV particle infectivity by preventing glycoprotein processing and incorporation into virus particles. Additionally, statins have anti-inflammatory and immunomodulatory effects. Since inflammation and dysregulation of the immune system are characteristic features of EVD, statins could be explored as part of EVD therapeutics.
Chalcogenide fibers for improved reliability of active infrared sensing systems (Conference Presentation)

Defense sensing systems must be both productive and robust to accomplish their mission. Active infrared sensing devices consist of many components such as the active medium, mirrors, beam-splitters, modulators, gratings, detectors, etc. Each of these components is subject to damage by the laser beam itself or environmental factors. Misalignment of these components due to vibration and temperatures changes can also reduce performance. The result is a complex and expensive system subject to multiple points of degradation or complete failure. However, beam confinement or “no free-space optics” via fiber transmission and even component assembly within the fiber itself can achieve reliability and low cost for sensing systems with reduced component count and less susceptibility to misalignment. We present measurements of high-power infrared laser beam transmission in chalcogenide fibers. The fiber compositions were As39S61 for the core and As38.5S61:5 for the cladding, resulting in a numerical aperture of 0.2. A polyetherimide jacket provided structural support. Multiwatt CW transmission was demonstrated in near single-mode 12 micron core fiber. Efficient coupling of quantum cascade lasing into anti-reflection coated chalcogenide fiber was also demonstrated. Efficient beam transport without damage to the fiber required careful coupling only into core modes. Beams with M2 ≥ 1.4 and powers higher than 1 W produced damage at the fiber entrance face. This was most likely due to heating of the highly absorptive polymer jacket by power not coupled into core modes. We will discuss current power limitations of chalcogenide fiber and schemes for significantly increasing power handling capabilities.
Intracranial Aneurysms: Clinical Assessment and Treatment Options

Intracranial aneurysms (IA) represent a challenging pathological entity ubiquitous in 2–6% percent of the population which may present occasionally with a devastating and often fatal intracranial bleed. While the understanding of the pathophysiological mechanisms governing their genesis and rupture are still being elucidated, advancements in the imaging techniques have enabled radiologists to accurately characterize their morphology and relationship with the neighboring vasculature. The past few decades have seen a refinement in the microneurosurgical techniques and made possible permanent exclusion of the aneurysm from the circulation. The development of detachable platinum microcoils to embolize the aneurysmal sac led to the dawn of an era of minimally invasive endovascular surgery. This branch has seen phenomenal progress with the development of an assortment of medical devices. These include guidewires and catheters for access, improvements in the embolic coil design, endovascular balloons, neurovascular stents and flow diverting devices that facilitate obliteration of the aneurysm. Recently concluded clinical trials attest to the remarkable safety profile of endovascular occlusion. However, there is a concern over the durability of treatment necessitating mandatory follow up imaging and retreatments for aneurysm recanalization. Also, controversy exists over the indications for offering treatment for the incidentally discovered IA. Future research into the identification of factors influencing the aneurysms predisposition to rupture and development of markers to assess that risk, will hopefully address this issue.
Post-treatment with SR49059 Improves Outcomes Following an Intracerebral Hemorrhagic Stroke in Mice

Intracerebral hemorrhage (ICH) is a devastating stroke subtype characterized by severe brain edema formation leading to cerebral blood flow compromise and parenchymal damage. Arginine vasopressin (AVP), a non-peptide antidiuretic hormone, has recently been implicated as a modulator of brain edema following injury. In this study, we investigated the effects of SR49059, a highly specific AVP V1a receptor antagonist, on brain injury outcomes following ICH, specifically assessing the ability of SR49059 in reducing brain edema and improving neurobehavioral deficits. Male CD1 mice (n = 35) were randomly assigned to the following groups: sham, ICH, ICH with SR49059 at 0.5 mg/kg, and ICH with SR49059 at 2 mg/kg. ICH was induced by using the collagenase injection model, and treatment was given 1 h after surgery. Post-assessment was conducted at 24 and 72 h after surgery, and included brain water content and neurobehavioral testing. The study found that SR49059 significantly reduced cerebral edema at 24 and 72 h post-ICH injury and improved neurobehavioral deficits at 72 h. Our study suggests that blockage of the AVP V1a receptor is a promising treatment target for improving ICH-induced brain injury. Further studies will be needed to confirm this relationship and determine future clinical direction.
Human Modeling: Kinematics

Chapter 2 focuses on the formulation of the kinematics of the human body. Various segments of the body are modeled as rigid elements that are connected by revolute joints. A 55 degree-of-freedom skeletal model of the human body, called Santos®, is described. Various branches of the model are explained, forming an open-loop mechanism for the entire system. A systematic approach of linking various segments of the model using 4×4 homogeneous transformation matrices is detailed. The approach is based on the Denavit–Hartenberg representation method of linking one coordinate system with another, and providing a rigorous and systematic method for representing any chain of segmental links. Using this formulation, displacement, velocity and acceleration of any link or any point on the body can be calculated. The approach is illustrated with example problems.
Histone deacetylase inhibition alters tumor phenotype and stimulates a productive anti-tumor immune response in preclinical models of ovarian cancer.

5585Background: Ovarian cancer remains the most deadly gynecologic malignancy. Chemotherapy and surgical reduction are initially effective but most patients relapse with chemoresistant disease. Imm...
Factors Influencing Colon and Rectal Surgery Residency Program Selection.

Abstract Background Little information exists to help colon and rectal surgery residency programs determine which factors applicants find important when selecting a training program. Our aim was to identify factors applicants find pertinent in the selection of their desired colon and rectal surgery residency program. Methods After the 2016 and 2017 National Resident Matching Program (The Match), a 58-question anonymous web-based survey was sent to all trainees who applied to our colon and rectal surgery residency program to determine factors applicants find important in selecting colon and rectal surgery residency training programs. Results Of 196 invitation emails sent, a total of five were returned with unidentifiable addresses leaving 191 surveys for possible completion. The survey response rate was 62.8% (n = 120). The top 10 areas identified as strongly to moderately influential in residency program selection included faculty experience, balanced training, operative volume, operative complexity, autonomy, faculty reputation, employment opportunities, Accreditation Council for Graduate Medical Education index case volumes, office/clinic complexity, and current resident/fellow input. Conclusions Multiple elements were identified as strongly to moderately influential when selecting a training program. Training programs can use these named factors for resident recruitment, development, and self-assessment.
Categorizing and Inferring the Relationship between the Text and Image of Twitter Posts.

Text in social media posts is frequently accompanied by images in order to provide content, supply context, or to express feelings. This paper studies how the meaning of the entire tweet is composed through the relationship between its textual content and its image. We build and release a data set of image tweets annotated with four classes which express whether the text or the image provides additional information to the other modality. We show that by combining the text and image information, we can build a machine learning approach that accurately distinguishes between the relationship types. Further, we derive insights into how these relationships are materialized through text and image content analysis and how they are impacted by user demographic traits. These methods can be used in several downstream applications including pre-training image tagging models, collecting distantly supervised data for image captioning, and can be directly used in end-user applications to optimize screen estate.
Preoperative and Postoperative Nursing Considerations for the Oncoplastic and Reconstructive Patient

Reconstruction and oncoplastic options are available for women who undergo partial or complete mastectomy. The goal of these surgeries is to restore the appearance of a natural breast and for patients to regain a sense of physical and emotional wholeness. Patients undergoing these surgical procedures will require proper preoperative and postoperative education and nursing care to ensure positive outcomes. The role of the breast and plastic surgical nurse is to educate and advocate throughout the continuum of care.
The syntax of the addressee in imperatives: What Levantine Arabic attitude datives bring to the table

The imperative subject constitutes a special category compared to the subjects of other types of clauses in that it is required to be the addressee. Zanuttini (2008) argues that this requirement follows from a special syntactic status: imperative subjects enter the computation with gender and number but no person features. They acquire a second-person specification later by entering an agreement relation with the head of a jussive phrase, a functional projection that is unique for imperative clauses and that occupies the left periphery. This paper provides independent evidence from attitude dative constructions in Levantine Arabic in support of this approach. Attitude datives are optional pronominal elements that make pragmatic contributions to utterances without altering their meaning. The paper shows that attitude datives whose referent coincides with the referent of the subject are less restricted in terms of the interpretation they may receive in imperative versus other types of clauses. Imperative clauses are more permissive, a characteristic that follows from the special status of their subject.
Current Landscape of Personalized Therapy

Almost a half of patients diagnosed with nonesmall-cell lung cancer (NSCLC) present with incurable disease, and a significant number of patients who are treated with curative intent for early-stage disease will eventually recur. Systemic therapy is selected based on tumor histology, squamous versus nonsquamous NSCLC, molecular testing, and PD-L1 score. Depending on PD-L1 score, patients are eligible for immunotherapy alone or in combination with chemotherapy in the first-line setting. Oncogenic driver mutations can be detected in approximately 50% of patients with nonsquamous NSCLC of which several can be targeted therapeutically with small molecular inhibitors. Continued research is needed for more specific agents with less toxicity and better central nervous system penetration, and agents to treat patients who develop resistance against targeted treatments and immunotherapy.
In Vivo Single-Molecule Detection of Nanoparticles for Multiphoton Fluorescence Correlation Spectroscopy to Quantify Cerebral Blood Flow

We present the application of multiphoton in vivo fluorescence correlation spectroscopy (FCS) of fluorescent nanoparticles for the measurement of cerebral blood flow with excellent spatial and temporal resolution. Through the detection of single nanoparticles within the complex vessel architecture of a live mouse, this new approach enables the quantification of nanoparticle dynamics occurring within the vasculature along with simultaneous measurements of blood flow properties in the brain. In addition to providing high resolution blood flow measurements, this approach enables real-time quantification of nanoparticle concentration, degradation, and transport. This method is capable of quantifying flow rates at each pixel with submicron resolution to enable monitoring of dynamic changes in flow rates in response to changes in the animal's physiological condition. Scanning the excitation beam using FCS provides pixel by pixel mapping of flow rates with subvessel resolution across capillaries 300 μm deep in the brains of mice.
Modeling suicide risk among parents during the COVID-19 pandemic: Psychological inflexibility exacerbates the impact of COVID-19 stressors on interpersonal risk factors for suicide.

Abstract Public health researchers have raised the concern that both the 2019 coronavirus disease (COVID-19) pandemic and the ensuing public health response will increase interpersonal stressors associated with suicide risk. The Acceptance and Commitment Therapy (ACT) framework conceptualizes psychological flexibility as an important way to reduce the impact of painful and even catastrophic events on psychological suffering. The current study examines psychological flexibility as a potential moderator of the prevailing interpersonal model of suicide risk. METHODS: A sample of 1003 parents (73% female, 82% Caucasian 86% in romantic relationships) were recruited as part of a larger study on the COVID-19 pandemic and family functioning from Mach 27th to the end of April 2020, the height of the United States’ “first wave.” Participants completed measures of psychological flexibility (the Multidimensional Psychological Flexibility inventory; MPFI), interpersonal constructs (perceived burdensomeness and thwarted belongingness), desire for death, COVID-19 related stressors (resource strain and loss due to COVID-19). RESULTS: Moderated-mediation path models highlighted a significant indirect association between COVID-19 stressors and desire for death mediated by perceived burdensomeness to others. This indirect pathway was moderated by psychological inflexibility such that links were strongest at high levels of inflexibility and weak or non-significant at low levels of inflexibility. Results were generally consistent across five of the six facets of inflexibility. DISCUSSION: The findings highlight the value of targeting psychological inflexibility as an important strategy to reduce suicide risk during the COVID-19 pandemic. Implications of patterns of results across different facets for treatment approach are discussed.
Effect of angiotensin receptor blockers and angiotensin-converting enzyme 2 on plasma equilibrium angiotensin peptide concentrations in cats with heart disease.

Background The pathophysiology of heart failure involves maladaptive angiotensin peptides (APs) and enzymes, including angiotensin 2 (AT2) and angiotensin converting enzyme (ACE), as well as recently described alternative components, such as angiotensin 1-7 (Ang1-7) and angiotensin converting enzyme 2 (ACE2). The relative effects of different neurohormonal-targeting drugs on balance of APs in dogs with heart disease are unknown. Hypothesis/objectives Plasma AP concentrations differ in dogs receiving angiotensin converting enzyme inhibitors (ACEIs) vs angiotensin receptor blockers (ARBs) and recombinant human ACE2 (rhACE2) will further increase these differences. Animals Eight dogs with degenerative mitral valve disease (DMVD). Methods Prospective open-label trial. Equilibrium concentrations of APs from plasma during PO ACEI treatment and then after 14 days of PO ARB treatment using telmisartan were measured using liquid chromatography-tandem mass spectroscopy before and after in vitro incubation with rhACE2. Results Concentration of Ang1-7 was increased during ARB treatment (Ang1-7: 443 pg/mL; 95% confidence interval [CI] = 247-794 pg/mL) vs ACEI (Ang1-7: 182 pg/mL; 95% CI = 66.2-503 pg/mL; P = .01). Incubation with rhACE2 decreased traditional APs while increasing beneficial alternative APs, and Ang1-7 was significantly higher in the ARB + rhACE2 (880 pg/mL; 95% CI = 560-1383 pg/mL) vs ACEI + rhACE2 (455 pg/mL; 95% CI = 188-1104 pg/mL; P = .03) group. The most favorable theoretical AP profile was achieved in the ARB + rhACE2 group. Conclusions and clinical importance The AP profile during telmisartan treatment is associated with higher plasma Ang1-7 as compared with during ACEI. This favorable shift is potentiated in vitro by combination of ARB + rhACE2. These data support potential AP-targeting strategies and drugs in dogs with DMVD.
Influence of Monobloc/Le Fort III Surgery on the Developing Posterior Maxillary Dentition and Its Resultant Effect on Orthognathic Surgery.

Background Timing of frontofacial surgery for the syndromic craniosynostosis as it relates to various surgical risks has not been adequately studied. The purpose of this study was to investigate posterior dental complications of midface advancement in patients with syndromic craniosynostosis undergoing surgery at different ages and the effects on subsequent orthognathic surgery. Methods A retrospective chart review of patients with syndromic craniosynostosis treated with midface advancement (monobloc or Le Fort III) from 1999 to 2018 was carried out. Patient demographics, records, and imaging studies were reviewed. A subanalysis of those patients who were also treated with orthognathic surgery from 2014 to 2018 with imaging studies available for analysis was also performed. Results Thirty-seven patients met the inclusion criteria. Sixty-four percent of the patients had radiographic evidence of maxillary molar dental abnormality. Older age at the time of surgery was significantly associated with a lower odds of sustaining dental injury (OR, 0.55; p = 0.034). The odds of damaging second or third maxillary molars was significantly higher with a younger age at the time of surgery (p = 0.021 and p = 0.034). The odds of sustaining dental injury increased moving posteriorly, showing the risk of abnormal pattern of M3 greater than M2 greater than M1. Advanced age at the time of surgery was significantly associated with decreased odds of dental injury (OR, 0.55; p = 0.034). Conclusions Damage to the developing permanent maxillary molars may affect orthodontic management, mastication, and potentially maxillary development. Delaying frontofacial surgery until development of the permanent maxillary dentition should be considered if other indications do not mandate earlier intervention.
What Is “Probabilistic” Diophantine Approximation?

We discuss some surprising new developments concerning \(\sqrt{ 2}\), and in general the class of quadratic irrationals. We use \(\sqrt{ 2}\) as the representative for the whole class. These results provide some rigorous evidence for a mysterious general phenomenon that we call the Giant Leap. In a nutshell, it is about the unexpected randomness of explicit sequences (Giant Leap to full-blown randomness). The reader may jump ahead to Sect. 2.5 for a detailed discussion of this issue.
Active Inductor-Based Ultra-Wideband Low Noise Amplifier for Rejection of Wireless LAN Interference

This paper presents a low noise amplifier (LNA) for the ultra-wideband (UWB) application in the range 3.1–10.6 GHz based on active inductor topology. The LNA is designed to provide a flat gain and to reject wireless local area networking interference at 5–6 GHz band. An active inductor based on the feedback resistor topology is proposed in this work and integrated with the LNA. The use of an active inductor instead of a conventional CMOS spiral inductor provides advantages over the area, quality factor, and inductance. The active inductor provides a relatively uniform inductance at 5–6 GHz and is used to design an on-chip notch filter circuit, which achieves a maximum attenuation of 45 dB at the center frequency of ~5.6 GHz. The LNA is designed and processed in the standard 0.18 μm CMOS technology. The simulated LNA exhibits the gain of 20 dB and a noise figure of less than 3.7 dB in the non-interfering bands. The input (S11) and output return losses (S22) are less than –10 and –12 dB, respectively, in the allocated UWB frequency spectrum, and amplifier occupies a chip area of 0.54 μm2. The proposed LNA has a superior flat gain, excellent interference rejection, minimum return losses, and a low noise figure in the intended operation band. This LNA finds important application in the radiofrequency front-end devices for UWB application.
Niche explosion

The following syndrome of features occurs in several groups of phytophagous insects: (1) wingless females, (2) dispersal by larvae, (3) woody hosts, (4) extreme polyphagy, (5) high abundance, resulting in status as economic pests, (6) invasiveness, and (7) obligate parthenogenesis in some populations. If extreme polyphagy is defined as feeding on 20 or more families of hostplants, this syndrome is found convergently in several species of bagworm moths, tussock moths, root weevils, and 5 families of scale insects. We hypothesize that extreme polyphagy in these taxa results from “niche explosion”, a positive feedback loop connecting large population size to broad host range. The niche explosion has a demographic component (sometimes called the “amplification effect” in studies of pathogens) as well as a population-genetic component, due mainly to the increased effectiveness of natural selection in larger populations. The frequent origins of parthenogenesis in extreme polyphages are, in our interpretation, a consequence of this increased effectiveness of natural selection and consequent reduced importance of sexuality. The niche explosion hypothesis makes detailed predictions about the comparative genomics and population genetics of extreme polyphages and related specialists. It has a number of potentially important implications, including an explanation for the lack of observed trade-offs between generalists and specialists, a re-interpretation of the ecological correlates of parthenogenesis, and a general expectation that Malthusian population explosions may be amplified by Darwinian effects.
Stable sampling in repeated games

Abstract This paper considers finitely repeated games played by procedurally rational players, who sample their available alternatives and use realized payoffs as a basis for strategy selection. The corresponding solution concept is that of (payoff) sampling equilibrium, which is a distribution over strategies that is self-replicating under the sampling procedure. Sampling equilibria are rest points of a disequilibrium dynamic process, and stability with respect to this process can be used as an equilibrium selection criterion. The structure of stable sampling equilibria in symmetric, finitely repeated games is characterized, and illustrated with applications to cooperation and coordination over time.
Gas Chromatography/Mass Spectrometry in Water Pollution Studies

Interest and activity in a field of research or application can be gauged by the frequency with which developments are reviewed. By this criterion, application of gas chromatography/mass spectrometry/computer (GC/MS/COMP) techniques to the analysis of aqueous matrices must be at an all-time high, with no indication that interest in the use of the combined technique is waning. The application of GC/MS/COMP to the qualitative and quantitative analysis of organic water pollutants has been reviewed, and recent reviews have also stressed the value of capillary gas chromatography coupled with automated data-handling techniques and accumulation of spectral reference data for organic trace pollutants in water.(1–6) Special techniques interfaced to GC/MS/COMP systems (e.g., purge and trap methods) have been reviewed. Bishop has discussed recent modifications in the purge and trap procedure.(7)
Intimacy and Sexuality in the Age of Shakespeare

Introduction: interiority, futurity, and affective relations in Renaissance literature 1. Intimacy and narrative closure in Christopher Marlowe's Hero and Leander 2. A funny thing happened on the way to the altar: the anus, marriage, and narrative in Shakespeare 3. Social status and the intimacy of masochistic sexual practice in Beaumont and Fletcher and Middleton 4. Nuns and nationhood: intimacy in convents in Renaissance drama 5. Female homoeroticism, race, and public forms of intimacy in the works of Lady Mary Wroth Epilogue: invitation to a queer life.
On the Global Geometric Structure of the Dynamics of the Elastic Pendulum

We approach the planar elastic pendulum as a singular perturbation of the pendulum to show that its dynamics are governed by global two-dimensional invariant manifolds of motion. One of the manifolds is nonlinear and carries purely slow periodic oscillations. The other one, on the other hand, is linear and carries purely fast radial oscillations. For sufficiently small coupling between the angular and radial degrees of freedom, both manifolds are global and orbitally stable up to energy levels exceeding that of the unstable equilibrium of the system. For fixed value of coupling, the fast invariant manifold bifurcates transversely to create unstable radial oscillations exhibiting energy transfer. Poincare sections of iso-energetic manifolds reveal that only motions on and near a separatrix emanating from the unstable region of the fast invariant manifold exhibit energy transfer.
Exploring Best Management Practices for Geospatial Data in Academic Libraries

Due to the exponential growth of spatial information, effective management and curation of geospatial data has become a central concern for GIS libraries. Although geospatial data are often generated based on a set of well-established standards and protocols, best management practices in geospatial data services are still limited. In this paper, the authors review the common challenges of geospatial data management and curation, which include the application of big data, the emergence of Web GIS, and the advancement of cyberinfrastructures. A spatial education project is used as an example to discuss potential best management practices to address these challenges. It is demonstrated that librarians need to be involved at the early stage of a research project and work closely with researchers at all stages of the data life cycle for effective data management. With early involvement of a GIS librarian in the full project development process, all three challenges can be addressed by using best management pra...
Application of Two Time-Domain Convolutive Blind Source Separation Algorithms to the 2008 Signal Separation Evaluation Campaign (SiSEC) Data

This paper describes the application of two time-domain convolutive blind source separation algorithms --- the scaled natural gradient algorithm [1] and the spatio-temporal FastICA algorithm with symmetric orthogonality constraints [2] --- to a portion of the determined and overdetermined acoustic data sets created for the 2008 Signal Separation Evaluation Campaign (SiSEC). As the 2008 SiSEC competition provides no ground truth data and thus no a priori method for numerical performance calculation, our approach to determining overall performance is a decoding of the contents of the recorded sources used to create the data through the two algorithms used. Information about the sources themselves, such as the instrumentation and structure of the musical selections chosen, the qualities of the voices and written transcripts of what is spoken, and additional information about the signals extracted, are provided without our ever having heard the sources in isolation. A qualitative performance comparison of the two approaches is also provided.