cssi/SciSciGPT-SciSciNet huggingface dataset:
Rice Cellulose SynthaseA8 Plant-Conserved Region Is a Coiled-Coil at the Catalytic Core Entrance.

The crystallographic structure of a rice (Oryza sativa) cellulose synthase, OsCesA8, plant-conserved region (P-CR), one of two unique domains in the catalytic domain of plant CesAs, was solved to 2.4 A resolution. Two antiparallel α-helices form a coiled-coil domain linked by a large extended connector loop containing a conserved trio of aromatic residues. The P-CR structure was fit into a molecular envelope for the P-CR domain derived from small-angle X-ray scattering data. The P-CR structure and molecular envelope, combined with a homology-based chain trace of the CesA8 catalytic core, were modeled into a previously determined CesA8 small-angle X-ray scattering molecular envelope to produce a detailed topological model of the CesA8 catalytic domain. The predicted position for the P-CR domain from the molecular docking models places the P-CR connector loop into a hydrophobic pocket of the catalytic core, with the coiled-coil aligned near the entrance of the substrate UDP-glucose into the active site. In this configuration, the P-CR coiled-coil alone is unlikely to regulate substrate access to the active site, but it could interact with other domains of CesA, accessory proteins, or other CesA catalytic domains to control substrate delivery.
A 7000-year history of coastal environmental changes from Mexico’s Pacific coast: A multi-proxy record from Laguna Mitla, Guerrero:

The lack of multi-millennial multi-proxy paleoenvironmental reconstructions from Mexico’s Pacific coast has limited our understanding of the regional response to climate change and sea-level rise. A 479-cm core covering the last 6900 years was extracted from Laguna Mitla in the state of Guerrero on Mexico’s Pacific coast. Beginning as a Rhizophora-dominated salt pan ~6900 yr BP, at ~6500 yr BP, the site transitioned to a mangrove swamp dominated by Laguncularia, which lasted about 300 years. The beach barrier formed from ~6200 to 5200 yr BP, during which time, the site existed as an intermittently sheltered bay, the result of large, rapid changes in wave energy associated with the shifting barrier location and changes in stability. After the beach barrier was stabilized at ~5200 yr BP, water level at the coring site became a function of precipitation rather than sea level. Since that time, deposition has alternated between peat, laid down in a mangrove swamp, and clay intervals characterized by high conce...
An All-Metal, 3-D-Printed CubeSat Feed Horn: An assessment of performance conducted at 118.7503 GHz using a robotic antenna range.

Three-dimensional (3-D) printing is finding applications across many areas and may be a useful technology for antenna fabrication for cube satellites (CubeSats). However, the quality of an antenna produced using 3-D printing must be considered if this technology can be relied upon. We present gain and far-field pattern results for the feed horn of the radiometer payload of the CubeSat PolarCube. The corrugated feed horn is constructed from AlSi10Mg alloy and fabricated using powder bead fusion (PBF). Measurements were performed at the atmospheric oxygen line of 118.7503 GHz with the National Institute of Standards and Technology (NIST) Configurable Robotic Millimeter-Wave Antenna (CROMMA) facility in Boulder, Colorado. A comparison of these measurements to theoretical predictions provides an assessment of the performance of the feed horn.
VARIABILITY IN LEFT VENTRICULAR EJECTION FRACTION BY RADIONUCLIDE MULTIGATED ACQUISITION SCAN VERSUS ECHOCARDIOGRAPHY: IMPLICATIONS FOR PRIMARY PREVENTION IMPLANTABLE CARDIOVERTER DEFIBRILLATORS

Background: In patients with a left ventricular ejection fraction (LVEF) ≤ 35%, randomized clinical trials have demonstrated the benefit of implantable cardioverter defibrillators (ICDs) in the primary prevention of sudden cardiac death. However, the modality for LVEF assessment was not mandated,
Use of SLICC criteria in a large, diverse lupus registry enables SLE classification of a subset of ACR-designated subjects with incomplete lupus.

Objective SLE is traditionally classified using the American College of Rheumatology (ACR) criteria. The Systemic Lupus International Collaborating Clinics (SLICC) recently validated an alternative system. This study examined large cohorts of subjects with SLE and incomplete lupus erythematosus (ILE) to compare the impact of ACR and SLICC criteria. Methods Medical records of subjects in the Lupus Family Registry and Repository were reviewed for documentation of 1997 ACR classification criteria, SLICC classification criteria and medication usage. Autoantibodies were assessed by indirect immunofluorescence (ANA, antidouble-stranded DNA), precipitin (Sm) and ELISA (anticardiolipin). Other relevant autoantibodies were detected by precipitin and with a bead-based multiplex assay. Results Of 3575 subjects classified with SLE under at least one system, 3312 (92.6%) were classified as SLE by both systems (SLE both ), 85 only by ACR criteria (SLE ACR-only ) and 178 only by SLICC criteria (SLE SLICC-only ). Of 440 subjects meeting 3 ACR criteria, 33.9% (149/440) were SLE SLICC-only , while 66.1% (n=291, designated ILE) did not meet the SLICC classification criteria. Under the SLICC system, the complement criterion and the individual autoantibody criteria enabled SLE classification of SLE SLICC-only subjects, while SLE ACR-only subjects failed to meet SLICC classification due to the combined acute/subacute cutaneous criterion. The SLICC criteria classified more African-American subjects by the leucopenia/lymphopenia criterion than did ACR criteria. Compared with SLE ACR-only subjects, SLE SLICC-only subjects exhibited similar numbers of affected organ systems, rates of major organ system involvement (∼30%: pulmonary, cardiovascular, renal, neurological) and medication history. Conclusions The SLICC criteria classify more subjects with SLE than ACR criteria; however, individuals with incomplete lupus still exist under SLICC criteria. Subjects who gain SLE classification through SLICC criteria exhibit heterogeneous disease, including potential major organ involvement. These results provide supportive evidence that SLICC criteria may be more inclusive of SLE subjects for clinical studies.
Associations between player age and club soccer coaches’ perceptions of injury risk and lower extremity injury prevention program use:

The use of a lower extremity injury prevention program by female soccer players before the completion of puberty may mitigate movement changes that develop during puberty and contribute to post-pub...
Enzymatic Synthesis of Pantothenic Acid by Escherichia Coli Cells

Pantothenic acid is a vitamin of importantance for human and animal nutrition. At present, it is commerically produced by chemical synthesis. Pantothenic acid is naturally produced from pantioc acid and (S-alanine by most microbial species, its formation being catalyzed by pantothenic acid synthetase (E.C. 6.3.2.1) (1,2). This enzyme required ATP which is converted to AMP during the enzyme reaction. It has been difficult to use these ATP-requiring enzymes in industry because of the cost of ATP. Attempts have been made to devise processes for ATP regeneration. One of these is the enzymatic regeneration of ATP from ADP using adenylate kinase, acetate kinase and acetyl phosphate (3,4). This method has been applied to the synthesis of gramicidin S by a cell-free enzyme system (5). This paper describes the enzymatic synthesis of pantothenic acid by Escherichia coli cells using ATP regeneration.
Effect of magnetic fields on spin glass dynamics

The effects of a magnetic field on spin glass dynamics are explored for a ${\mathrm{Cu}}_{0.887}{\mathrm{Mn}}_{0.113}$ thin film of thickness $\mathcal{L}=20$ nm in a multilayer configuration. An experimental protocol removes uncertainties associated with the time dependence of the field-cooled magnetization ${M}_{\text{FC}}(t,T)$. Activated dynamics is exhibited after the spin glass correlation length $\ensuremath{\xi}(t,T)$ has reached $\mathcal{L}$, creating a quasiequilibrium state. The activation energy depends upon the strength of the magnetic field $H$. The magnitude of the activation energy diminishes as ${H}^{2}$, the coefficient of which is proportional to the number of correlated spins. A quantitative fit requires a ``pancakelike'' correlated region, associated with the $T=0$ phase transition for a spin glass in $D=2$ dimensions.
Increased Microglial CSF1R Expression in the SIV/Macaque Model of HIV CNS Disease.

Chronic microglial activation and associated neuroinflammation are key factors in neurodegenerative diseases including HIV-associated neurocognitive disorders. Colony stimulating factor 1 receptor (CSF1R)-mediated signaling is constitutive in cells of the myeloid lineage, including microglia, promoting cell survival, proliferation, and differentiation. In amyotrophic lateral sclerosis and Alzheimers disease, CSF1R is upregulated. Inhibiting CSF1R signaling in animal models of these diseases improved disease outcomes. In our studies, CNS expression of the CSF1R ligand, colony-stimulating factor 1 (CSF1) was significantly increased in a SIV/macaque model of HIV CNS disease. Using a Nanostring nCounter immune panel, we found CSF1 overexpression was strongly correlated with upregulation of microglial genes involved in antiviral and oxidative stress responses. Using in situ hybridization, we found that CSF1R mRNA was only present in Iba-1 positive microglia. By ELISA and immunostaining with digital image analysis, SIV-infected macaques had significantly higher CSF1R levels in frontal cortex than uninfected macaques (p = 0.018 and p = 0.02, respectively). SIV-infected macaques treated with suppressive ART also had persistently elevated CSF1R similar to untreated SIV-infected macaques. Coordinate upregulation of CSF1 and CSF1R expression implicates this signaling pathway in progressive HIV CNS disease.
Multicast Virtual Network Services Embedding for Improved Disaster Recovery Support

Multicast virtual network (MVN) cloud services have tight restrictions in terms of coverage, delay, delay variation, and reliability. However large disasters impose key challenges, and there are no known solutions that incorporate stochastic multi-failure risk into the MVN embedding process. Hence, this letter presents novel proactive “risk-aware” MVN mapping algorithms to improve resiliency and also incorporate efficiency. Simulation results show that the proposed schemes yield substantial performance gains versus existing MVN survivability methods.
Anesthesia and the Immune System

Anesthesia and operation may impair the immune system so that bacterial growth and tumor spread may occur more readily, and host response to transplanted tissue and allergenic substances may be altered. Suggestions are presented regarding the anesthetic management of patients at risk from infection or tumor spread.
A screening version of the Dizziness Handicap Inventory (DHI-S).

Objective This study aimed to develop a screening version of the Dizziness Handicap Inventory (DHI). Study design Three separate prospective investigations are reported that assess: 1) the equivalency of the screening version of DHI (DHI-S) for the DHI; 2) the test-retest reliability of the DHI-S; and 3) whether abnormal performance on balance function testing is associated with greater scores on the DHI-S. Setting The investigation was conducted in the Balance Function Laboratory of the Division of Audiology at Henry Ford Hospital, which is a tertiary care setting. Patients There were 281 consecutive patients (for investigations 1 and 2) and 45 consecutive patients (for investigation 3) seen for balance function testing. Interventions There was a 1-week interval between test and retest administrations of the DHI-S. Main outcome measures Comparability of the DHI-S for the DHI and the test-retest reliability of the DHI-S were assessed with a Pearson Product-Moment correlation coefficient. Scores on the DHI-S for patients with and without abnormal balance function tests were assessed with an analysis of variance. Results Results showed that scores on the DHI-S had high comparability for the total score on the DHI (r=0.86). The short-term, test-retest reliability for the DHI was high (r=0.95). Abnormal performance on the sensory organization subtest of computerized dynamic posturography was associated with significantly greater scores on the DHI-S. Conclusions Results support the contention that DHI-S is a psychometrically robust screening measure of self-perceived dizziness disability-handicap.
K-ras Inhibitors and Pancreatic Cancer

The ras family includes a group of five guanosine triphosphate-binding proteins (H-ras, K-ras, M-ras, N-ras, and R-ras). In mammals ras-proto-oncogenes encode for four related and highly conserved proteins, H-ras, N-ras, K-ras 4A, and K-ras 4B ( 1 ). Ras proteins serve as important components of signaling pathways involved in a variety of cellular functions, including cell cycle control, cell adhesion, endocytosis, exocytosis, and apoptosis. In order for these proteins to perform their functions they need to bind guanosine triphosphate (GTP) ( 2 ). Guanosine triphosphate creates a conformational change allowing ras to attach more tightly to its intended target. Hydrolysis of GTP to guanosine diphosphate (GDP) inactivates ras. The ability of ras to exchange GDP for GTP is under the control of guanine nucleotide exchange factors (GEFs). The GEFs are activated by growth factors or cytokines and promote the release of GDP and therefore the binding of GTP. GTPase-activating proteins (GAPs) return ras to its inactive state. Although a variety of genetic modifications have been identified in pancreatic carcinoma, mutations of K-ras are by far the most commonly occurring mutation. Mutations are seen in >85% of pancreatic ductal carcinomas ( 3 ). The development of mutations in K-ras appear early in the development of pancreatic cancer, having been observed in precursor lesions within the pancreatic duct ( 4 ). The mutations in K-ras in pancreatic cancer are also unique in that it typically involves codon 12, but may also rarely involve codons 13 or 61 ( 5 , 6 ). These mutations in K-ras make it resistant to GAP and as a result lead to constitutive activation of downstream pathways, resulting in altered regulation of cellular proliferation. In preclinical studies, using the pancreatic cancer cell lines Panc-1 and MiaPaca-2, blocking activated K-ras resulted in increased apoptosis and loss of other malignant features supporting a pivotal role for K-ras in the development and maintenance the malignant phenotype. Based on the frequency and apparent critical role of K-ras in pancreatic cancer several approaches have been developed to block activated K-ras. This includes both farnesyl transferase inhibitors and antisense oligonucleotides.
EMR-based handoff tool improves completeness of internal medicine residents’ handoffs

Background The majority of adverse events in healthcare involve communication breakdown. Physician-to-physician handoffs are particularly prone to communication errors, yet have been shown to be more complete when systematised according to a standardised bundle. Interventions that improve thoroughness of handoffs have not been widely studied. Aim To measure the effect of an electronic medical record (EMR)-based handoff tool on handoff completeness. Intervention This EMR-based handoff tool included a radio button prompting users to classify patients as stable, a ‘watcher’ or unstable. It automatically pulled in EMR data on the patient’s 24-hour vitals, common lab tests and code status. Finally, it provided text boxes labelled ‘Active Issues’, ‘Action List (To-Dos)’ and ‘If/Then’ to fill in. Implementation and evaluation Written handoffs from general and specialty (haematology, oncology, cardiology) Internal Medicine resident-run inpatient wards were evaluated on a randomly chosen representative sample of days in April and May 2015 at Stanford University Medical Center, focusing on a predefined set of content elements. The intervention was then implemented in June 2015 with postintervention data collected in an identical fashion in August to September 2016. Results Handoff completeness improved significantly (p Conclusion A simple EMR-based handoff tool providing a mix of frameworks for completion and automatic pull-in of objective data improved handoff completeness. This suggests that EMR-based interventions may be effective at improving handoffs, possibly leading to fewer medical errors and better patient care.
TRAC Analysis of Loss-of-Fluid Test Non-Nuclear Test L1-4

The Transient Reactor Analysis Code (TRAC) is being developed at the Los Alamos Scientific Laboratory as an advanced best-estimate computer program for analyses of postulated accidents in light water reactors. As a part of the TRAC verification effort, a posttest analysis of loss-of-fluid test (LOFT) non-nuclear test L1-4 has been conducted. The results of this analysis show that TRAC accurately predicts the thermal-hydraulic response of the entire LOFT system, including the delayed effects from emergency core coolant injection into the cold leg.
Dimensions of the Nonprofit Sector

Cross-nationally, the introduction of New Public Management (NPM) (Barzelay, 2000; Ferlie, 1996; Hood, 1991) seems closely related to the growth of the nonprofit or third sector (see Salamon et al., 1999). The basic thesis of this paper is that the combination of growth and NPM amplified differentiation processes within the nonprofit sector, and that the dynamics of these processes vary across “nonprofit regime types.” Significantly, the growth has largely been an expansion of the economic dimension of nonprofit organizations as service providers, whereas other aspects like membership and volunteering have grown much less and have even stagnated in some instances. What is rarely understood is that the substantial expansion of the third sector may indeed call into question its long-term sustainability in its present form. Indeed, as this paper argues, the sector is becoming qualitatively different, and not only quantitatively larger. This paper wants to explore this thesis from a conceptual as well as methodological point of view by trying to “map” changes in the facets of the third sector in a cross-section of countries and over time to capture aspects of this quantitative-qualitative jump in nonprofit sector development.
Medical Business Law and Regulations

Healthcare organizations, healthcare administrators, and practitioners need to be cognizant of federal and state regulations and laws that apply to the healthcare business. Violations of some of these laws can result in criminal penalties, civil fines, exclusion from federal and state healthcare programs, loss of hospital privileges, or loss of a medical license from the state medical board. Some of the more significant fraud and abuse laws are the False Claims Act (FCA), the Anti-Kickback Statute (AKS), the Physician Self-Referral Law (Stark law), and the Civil Monetary Penalties Law (CMPL). Federal government agencies including the Office of the Inspector General, Department of Justice, Department of Health and Human Services, and Centers for Medicaid and Medicare Services have enforced these laws to healthcare organizations in every state. An understanding of these laws will help protect healthcare providers from fines, costly defenses, and possible prison time.
"A well spent day brings happy sleep": A dyadic study of capitalization support in military-connected couples

Among couples, sleep is theorized to be a dyadic process, within which relationship quality exerts a large influence (Troxel, Robles, Hall, & Buysse, 2007). In turn, research has shown that capitalization, or positive-event disclosure, influences relationship quality. The benefits of capitalization, however, are contingent on the receipt of a supportive response, here referred to as capitalization support (Reis & Gable, 2003). Accordingly, the current study examined daily capitalization support, loneliness, and intimacy as predictors of sleep (i.e., quality, duration, difficulty falling asleep). Post-9/11 military veterans and their spouses (N = 159) completed a 32-day internet-based survey assessing daily relationship experiences and health. Results of an actor-partner interdependence mediation model on aggregated daily data revealed actor indirect effects of capitalization support on sleep outcomes via loneliness and intimacy, for veterans and spouses. Partner indirect effects were observed for veteran capitalization support on spouse difficulty falling asleep and sleep quality, via spouse loneliness and intimacy. Lagged actor-partner models revealed similar actor effects for daily capitalization support on loneliness (spouses) and intimacy (spouses and veterans), which in turn uniquely predicted daily sleep. Partner effects were observed for veteran capitalization support on spouse intimacy, and veteran loneliness on spouse sleep quality. Results highlight potential new avenues for interventions to promote better sleep by promoting positive relationship functioning between romantic partners. Such work is especially important for high-risk individuals, including military veterans and their spouses for whom prolonged postdeployment sleep difficulties pose particular concern. (PsycINFO Database Record (c) 2018 APA, all rights reserved).
Chapter 16 – Irradiated Components

Publisher Summary In transfusion associated graft-versus-host (TA-GVHD) patients, the intensity of the mixed lymphocyte reaction can be decreased by either reducing the number of unirradiated responding cells or increasing the dose of gamma irradiation to responding cells. For an institutional policy of blood component irradiation to fulfill its preventive function, patients at risk for TA-GVHD must be reliably identified prospectively. Blood components that must be irradiated for categories of patients at risk include packed red blood cells (PRBCs), granulocytes, platelets, platelet-rich plasma, freshly separated plasma, and buffy coats used to treat neonatal sepsis. Frozen deglycerolized PRBCs can also be a source of immunocompetent lymphocytes capable of causing TA-GVHD and therefore must be irradiated for indicated categories of patients. Human leukocyte antigen (HLA)-matched apheresis platelets must always be irradiated. Donor lymphocyte infusions (DLIs) may or may not be irradiated 0depending on the indication for their use: those used to treat viral infections should be irradiated, while those used as therapy for disease recurrence post-allograft should not be irradiated. Although some variation in dosing of irradiation still exists, with centers using anywhere from 15 to 50 Gy, the data with respect to the ability of lymphocytes to proliferate in mixed lymphocyte cultures or in response to mitogens indicate that a small fraction of T-lymphocytes retain some proliferative capacity even at 30 Gy. Current standards require a dose not less than 25 Gy to the central midplane of the irradiation field, and this dose appears to be appropriate for clinical indications.
Design Novel Fuzzy Logic Controller of Photovoltaic Conversion Cascade Based Five Levels Inverter for Stand-Alone Applications

This paper presents a novel Fuzzy Logic Controller (FLC) for regulation of output voltage in photovoltaic conversion stand alone two stages cascade. The voltage reference vector module of five levels NPC inverter constituting the second stage of proposed cascade is calculated each period after determination of the new modulation index using the proposed FLC controller. Knowing that the NPC topology suffers from the problem of unbalanced DC voltage, authors proposes to applied Space Vector Modulation (SVM) and use the 36 redundant vectors of five levels space vector diagram to regulate capacitors voltages. The second fuzzy logic Maximum Power Point Tracking (MPPT) controller designed to control the boost converter (first stage) is capable of extracting maximum power from PV array. The simulation results show that the RMS output voltage is inside the band of +/−10V and with low total harmonic distortion despite irradiation change.
The total syntheses of JBIR-94 and two synthetic analogs and their cytotoxicities against A549 (CCL-185) human small lung cancer cells

Abstract We here disclose the total syntheses of the natural polyphenol JBIR-94 and two nonnatural analogs, whose structures are of interest for their bioactivity potential as radical scavengers. Although we initially attempted this by dually acylating both of putrecine’s amine nitrogens in a single pot, our endeavors with this method (which has been successfully reported by other groups) proved ineffectual. We accordingly opted for the lengthier approach of acylating each amine individually, which gratuitously prevailed and also aligns with separate literature precedent. Moreover, we here share our analysis of these target compounds’ cytotoxicities and IC50 values against A549 (CCL-185) human small lung cancer cells.
Feasibility and acceptability of a future-oriented empowerment program to prevent substance use and school dropout among school-disengaged youth

OBJECTIVE To evaluate the feasibility and acceptability of a health promotion program to prevent school dropout and substance use among middle school-aged youth who display early warning signs of school disengagement. INTERVENTION Youth Empowerment Solutions for Positive Futures (YES-PF), an intensive, theoretically driven, 5-week summer enrichment program, aims to prevent school dropout and substance use by promoting youth empowerment, school engagement, and future orientation. DESIGN AND SAMPLE Using a pre-post-intervention design, we test feasibility and acceptability with 6th and 7th grade students (n = 43) who exhibited early warning signs for school disengagement (e.g., chronic absenteeism) in two school districts. MEASURES Program evaluation components included: (a) program session forms completed by facilitators; (b) post-program interviews with facilitators; (c) post-intervention program evaluation surveys with youth; (d) attendance; and (e) baseline and post-intervention surveys with youth to assess behavioral and psychosocial outcomes. RESULTS Facilitators routinely delivered core component lesson activities. Acceptability and program satisfaction were evidenced in strong program attendance by youth. Youth participants reported higher levels of leadership efficacy (p < .05) and a greater sense of control over their lives and potential problems (p < .01). CONCLUSIONS YES-PF was feasible and acceptable to school personnel and youth. Program refinement, based on implementation findings, is discussed.
Communication: Using Structures to Send Information

Energy concepts are complex enough to begin with that they needn’t be handicapped with poor communications. Ideas are only as effective as their dissemination and eventual adoption. Structured communication improves getting the message across because it encodes the information into a familiar and logical progression. If the receiver recognizes the structure, it decreases the processing time for them to internalize and synthesize the information, enabling faster comprehension and decision-making. Energy strategists need to know how to simplify their message enough to get the gist across, but not too much as to become meaningless, vague generalities. A well-crafted message will strike the balance based on audience needs.
Anti-fatigue effects of Elaeagnus multiflora fruit extracts in mice

The fruit, leaves, and roots of Elaeagnus multiflora Thunb. have been used in traditional Chinese medicine to treat cough, diarrhea, and itching. However, the anti-fatigue effects of E. multiflora fruit (EMF) extract have not been studied in detail. The aim of this study was to examine the effect of EMF on fatigue and exercise performance in BALB/c mice. EMF was orally administered to mice at four doses (10, 50, 100, and 200 mg/kg/ day) for 2 weeks. The anti-fatigue activity was evaluated by determining the exhaustive swimming time. Blood lactate and glucose levels and serum lactate levels after a 10 min swimming time, as well as ammonia, creatine kinase (CK), blood urea nitrogen (BUN), lactate dehydrogenase (LDH), and glycogen contents after exhaustive swimming time were measured. The exhaustive swimming time of the EMF 200 group was significantly increased (p <0.01). The EMF groups showed significantly low levels of CK, BUN, LDH, and lactate compared with the control group (p <0.05). Increased liver glycogen was observed in the EMF 200 group (p <0.05). These results suggest that EMF can be utilized as an efficacious natural resource for its anti-fatigue effects.
Origins of Sex Differentiation of Brain and Behavior

Sex differences in adult brain and behavior are often established early in development when the brain is remarkably immature. In adults sex differences take on many forms including latent variables, dimorphisms, frequency, and more. Androgens and estrogens from the developing male fetal testis masculinize the brain, so that physiology and behavior are in synchrony and harmony with gonadal phenotype. This differentiation process occurs during a critical window in males, but females remain sensitive to exogenous steroid treatment for a longer developmental period. The cellular mechanisms of sexual differentiation are diverse but often involve inflammatory signaling molecules and immune cells. This may have consequences for the higher vulnerability of males to neurological and neuropsychiatric disorders of development.
Consensus Based Distributed Spectral Radius Estimation

A consensus based distributed algorithm to compute the spectral radius of a network is proposed. The spectral radius of the graph is the largest eigenvalue of the adjacency matrix, and is a useful characterization of the network graph. Conventionally, centralized methods are used to compute the spectral radius, which involves eigenvalue decomposition of the adjacency matrix of the underlying graph. Our distributed algorithm uses a simple update rule to reach consensus on the spectral radius, using only local communications. We consider time-varying graphs to model packet loss and imperfect transmissions, and provide the convergence characteristics of our algorithm, for both static and time-varying graphs. We prove that the convergence error is a function of principal eigenvector of adjacency matrix of the graph and reduces as $\mathcal {O}(1/t)$ , where $t$ is the number of iterations. The algorithm works for any connected graph structure. Simulation results supporting the theory are also presented.
Alignment and Representation in Computer Science: An Analysis of Picture Books and Graphic Novels for K-8 Students.

Many children’s books related to computer science have been published in the last five years, creating opportunities to integrate these texts into the classroom. Determine where the children’s book...
Plasma DNA as a "liquid biopsy" incompletely complements tumor biopsy for identification of mutations in a case series of four patients with oligometastatic breast cancer.

Circulating tumor DNA in plasma may present a minimally invasive opportunity to identify tumor-derived mutations to inform selection of targeted therapies for individual patients, particularly in cases of oligometastatic disease where biopsy of multiple tumors is impractical. To assess the utility of plasma DNA as a “liquid biopsy” for precision oncology, we tested whether sequencing of plasma DNA is a reliable surrogate for sequencing of tumor DNA to identify targetable genetic alterations. Blood and biopsies of 1–3 tumors were obtained from 4 evaluable patients with advanced breast cancer. One patient provided samples from an additional 7 tumors post-mortem. DNA extracted from plasma, tumor tissues, and buffy coat of blood were used for probe-directed capture of all exons in 149 cancer-related genes and massively parallel sequencing. Somatic mutations in DNA from plasma and tumors were identified by comparison to buffy coat DNA. Sequencing of plasma DNA identified 27.94 ± 11.81% (mean ± SD) of mutations detected in a tumor(s) from the same patient; such mutations tended to be present at high allelic frequency. The majority of mutations found in plasma DNA were not found in tumor samples. Mutations were also found in plasma that matched clinically undetectable tumors found post-mortem. The incomplete overlap of genetic alteration profiles of plasma and tumors warrants caution in the sole reliance of plasma DNA to identify therapeutically targetable alterations in patients and indicates that analysis of plasma DNA complements, but does not replace, tumor DNA profiling. Trial Registration: Subjects were prospectively enrolled in trial NCT01836640 (registered April 22, 2013).
Machiavelli’s Plebeian Constituent Power

As a theorist of extraordinary politics, Machiavelli was concerned primarily with the mutation of the constitutional order. In this paper I first analyze Machiavelli’s description of the founding of Rome by Romulus as a free republic based on limited government, and the kingly power that is necessary to bring a republic back to its beginning, as in the refounding of Sparta by Cleomenes, and then focus on Machiavelli’s ideas on the remodeling of republics depending on their degree of existing corruption. I dedicate the third section to Machiavelli’s arguments to incorporate instances of extraordinary political action into the basic order so to avoid corruption and the need for revolutionary reformers. I conclude by highlighting Machiavelli’s contributions to our understanding of constituent power from a republican, plebeian perspective.
Sounding the Alarm: Six Strategies for Medical Students to Champion Anti-Racism Advocacy

Every year, incoming medical students take the Hippocratic Oath and pledge that they: "will be an advocate for patients in need and strive for justice in the care of the sick," yet guidance on how to engage in community and public health advocacy is not a mandatory component of medical education. Therefore, students often feel insufficiently qualified to engage in advocacy efforts. As the nation has struggled with a viral pandemic (COVID-19) and witnessed an uprising against anti-Black racism and police brutality, it became immediately apparent that activism that marries medicine to anti-racism advocacy was needed. Further, we deduced that anti-racism activism at medical institutions would need to position medical students, often low in the medical hierarchy, as essential to the response. With the support of our leaders and mentors, we created a concerted series of strategies for medical students to become front and center in advocacy efforts. In this paper, we outline six strategies for medical students across the nation to champion anti-racism advocacy, based on our successful experiences in Central Ohio. This approach may have utility for other medical schools across the nation. These strategies include: embracing a common agenda; establishing formal structures; engaging affinity groups and allies; endorsing legislative advocacy; encouraging curricular reform; and enriching the pipeline. It is our hope that medical students will feel empowered and activated to lead and organize "good trouble" efforts that will ultimately improve the lives and health of the communities and patients they are being trained to serve.
Higher CSF sTNFR1-related proteins associate with better prognosis in very early Alzheimer’s disease

Neuroinflammation is associated with Alzheimer’s disease, but the application of cerebrospinal fluid measures of inflammatory proteins may be limited by overlapping pathways and relationships between them. In this work, we measure 15 cerebrospinal proteins related to microglial and T-cell functions, and show them to reproducibly form functionally-related groups within and across diagnostic categories in 382 participants from the Alzheimer’s Disease Neuro-imaging Initiative as well participants from two independent cohorts. We further show higher levels of proteins related to soluble tumor necrosis factor receptor 1 are associated with reduced risk of conversion to dementia in the multi-centered (p = 0.027) and independent (p = 0.038) cohorts of people with mild cognitive impairment due to predicted Alzheimer’s disease, while higher soluble TREM2 levels associated with slower decline in the dementia stage of Alzheimer’s disease. These inflammatory proteins thus provide prognostic information independent of established Alzheimer’s markers. Neuroinflammation is observed in Alzheimer’s disease. Here the authors show that 15 proteins related to inflammation found in CSF can potentially be used as a prognostic biomarker.
Non-amnestic Cognitive Impairment in Essential Tremor (ET): Defining the Phenotype (P6.057)

Objective: To define the clinical phenotype of ET patients with non-amnestic cognitive impairments. Background: ET is the most common movement disorder, affecting 0.3–5.6% of the general population. ET has a heterogeneous clinical presentation, including cognitive decline in some patients. Several ET patients in our movement disorder center had neuropsychological testing showing non-amnestic MCI. We aim to define features of their clinical presentations. Design/Methods: We identified all ET patients seen in the past 10 years by a neuropsychologist. They were referred as pre-surgical candidates or for cognitive complaints. Retrospective chart review was conducted on these cases. Cross sectional analysis using Chi square and t-tests were performed. Results: 25 patients were identified to review. Of these patients, 6 were found to have a non-amnestic cognitive impairment, 4 had amnestic impairment, 15 had normal cognition. Mean age of onset of motor symptoms and disease duration did not differ in non-amnestic MCI vs normal cognition. Patients with non-amnestic MCI were more likely to have depressive symptoms in neuropsychological testing (p Conclusions: ET patients with non-amnestic cognitive impairment are more likely to have a history of alcohol abuse, depression and clinical findings of parkinsonism compared to cognitively normal ET patients. Identifying characteristics in ET patients associated with cognitive impairment could lead to early cognitive assessment and diagnoses. Larger studies are warranted. Disclosure: Dr. Urval has nothing to disclose. Dr. Palmese has nothing to disclose. Dr Shanker has nothing to disclose.
Interpreting Quality Improvement When Introducing New Technology: A Collaborative Experience in ASD Device Closures

The objective of this study was to evaluate the impact of the regular introduction of new technologies into interventional cardiac catheterization procedures, in this case new atrial septal defect (ASD) closure devices, while conducting a multi-center collaborative initiative to reduce radiation usage during all procedures. Data were collected prospectively by 8 C3PO institutions between January 1, 2014 and December 31, 2017 for ASD device closure procedures in the cardiac catheterization lab during a quality improvement (QI) initiative aimed at reducing patient radiation exposure. Radiation exposure was measured in dose area product per body weight (µGy*m2/kg). Use of proposed practice change strategies at the beginning and end of the QI intervention period was assessed. Radiation exposure was summarized by institution and by initial type of device used for closure. This study included 602 ASD device closures. Without changes in patient characteristics, total fluoroscopy duration, or number of digital acquisitions, median radiation exposure decreased from 37 DAP/kg to 14 DAP/kg from 2014 to 2017. While all individual centers decreased overall median DAP/kg, the use of novel devices for ASD closure correlated with a temporary period of worsening institutional radiation exposure and increased fluoroscopy time. The introduction of new ASD closure devices resulted in increased radiation exposure during a QI project designed to reduce radiation exposure. Therefore, outcome assessment must be contextualized in QI projects, hospital evaluation, and public reporting, to acknowledge the expected variation during innovation and introduction of novel therapies.
Minimally Invasive Pediatric Neurosurgery

Pediatric neurosurgery, which by its nature overlaps multiple neurosurgical subspecialties, has benefited greatly from the advances in minimally invasive neurosurgical techniques. Not only can it take advantage of the progress in the areas of vascular, spine, trauma, and tumor neurosurgery, but as a subspecialty it has significantly advanced the minimally invasive treatment of hydrocephalus and intraventricular lesions.
Interstate migration in Mexico: Variations on the Todaro theme

Abstract This study of migration in Mexico is based upon a modified Todaro approach and utilizes census data in a simultaneous equations model of 13 variables. It is unique in several ways: (a) it introduces proxy variables for employment probability and cost of migration that have not heretofore been found in the literature, but for which data are often available; (b) it illustrates that in some important cases census data have advantages not available through surveys; and (c) it finds that in some sense land reform in Mexico may have operated perversely. Finally, the study opens a new avenue for the study of informal sector growth.
Lymphocyte receptors for polyclonal T mitogens. I. Concanavalin A binding to lymphocytes inhibits mitogenesis induced by galactose oxidase.

Abstract Mitogenic stimulation of mouse lymphocytes by the enzyme galactose oxidase (GO) is inhibited if Con A is present during the enzymatic oxidation. The mechanism of this inhibition appears to involve steric hindrance of GO action at cell surface sites which bind Con A because (a) similar pulse exposure of unoxidized cells to Con A does not affect their subsequent ability to respond to GO stimulation; (b) Con A binding to fetuin interferes with GO oxidation of that glycoprotein substrate; and (c) sodium dodecyl sulfate-polyacrylamide gel electrophoresis analysis of cells labeled by GO NaB 3 H 4 in the presence of Con A shows a selective inhibition of labeling of some high-molecular-weight glycoproteins compared to controls labeled in the absence of Con A.
Calculation of OTF, NPS, and DQE for oblique x-ray incidence on turbid granular phosphors

Digital breast tomosynthesis (DBT) is an imaging modality in which tomographic sections of the breast are generated from a limited range of x-ray tube angles One drawback of DBT is resolution loss in the oblique projection images The purpose of this work is to extend Swank's formulation of the transfer functions of turbid granular phosphors to oblique x-ray incidence, using the diffusion approximation to the Boltzmann equation to model the spread of light in the phosphor As expected, the modulation transfer function (MTF) and noise power spectra (NPS) are found to decrease with projection angle regardless of frequency By contrast, the dependence of detective quantum efficiency (DQE) on projection angle is frequency dependent DQE increases with projection angle at low frequencies, and only decreases with projection angle at high frequencies Importantly, the x-ray quantum detection efficiency (AQ) and the Swank information factor (AS) are also found to be angularly dependent.
Assembly of bacteriophage T4 tail fibers: II. Isolation and characterization of tail fiber precursors

Abstract Complete T4 tail fibers and four precursor structures (half fibers) were purified from lysates of mutant-infected Escherichia coli cells, using serum blocking assays for tail fiber antigens to monitor the isolation procedures. Each of the final preparations showed a single major electrophoretic component on polyacrylamide gels. The purified structures, designated whole fibers and A, BC′, BC, and C half fibers on the basis of their antigenic determinants, were further characterized by electron microscopy and assays for ability to produce viable phage in vitro when combined with appropriate extracts of mutant-infected cells. Purified whole fibers are similar in dimensions and appearance to the tail fibers seen on complete phage, and can be attached quantitatively to tail fiberless particles in vitro to produce active virus. The whole fiber is composed of one A and one BC′ half fiber, each about 690 A in length and 45 A in width, joined end to end at an angle of about 160 °. The isolated A half fiber carries a knob at one end, which is also visible at one end of the whole fiber. Since the A half is proximal to the tail in the completed phage, the knob presumably represents the point of tail fiber attachment to the baseplate. The A half fiber may not be a normal intermediate in whole fiber assembly, since it is not visible in most crude extracts containing A antigen, and retains little in vitro activity through the purification procedure. The BC′ half fiber, by constrast, appears to be the normal precursor of the distal half of the whole fiber; it is visible in crude extracts and retains its in vitro activity in the purified state. BC, the probable precursor of BC′, is inactive in vitro when purified but indistinguishable from BC′ in dimensions and serological properties. C, the probable precursor of BC, is also inactive in vitro when purified. Besides lacking the B antigen it is shorter than BC, being only 560 A in length.
Stimulation of Colonic Secretion of Water and Electrolytes by Hydroxy Fatty Acids

Recent reports have suggested that the diarrhea that accompanies steatorrhea may be related to fecal hydroxy fatty acids. Therefore, the effect of hydroxy fatty acids on colonic water and electrolyte movement was studied in the in vivo rat colon using a continuous perfusion technique. Perfusion with 2 mm ricinoleic acid resulted in net secretion of water, sodium, and chloride and is accompanied by a marked increase in mucosal permeability, as determined by inulin clearance, and a decrease in electrical potential difference. Oleic acid (2 mm), which did not cause secretion but did inhibit net absorption, induced similar alterations in electrical potential difference and inulin clearance. These results suggest that hydroxy fatty acids may be a mediator of the diarrhea of steatorrhea.
The Role of Transporters in Drug Development: Regulatory Science Perspectives from the FDA

Pharmacokinetic drug interactions can lead to altered systemic exposure and varied drug response. Evaluation of a new molecular entity’s (NME’s) drug–drug interaction (DDI) potential is therefore an integral part of drug development and regulatory review prior to its market approval. Transporters are expressed in varying abundance in all tissues in the body where they govern the access of molecules to cells or their exit from cells, thereby controlling the overall distribution of drugs to their intracellular site of action. Clinically relevant interactions mediated by transporters are of increasing interest in drug development. Research in this emerging area has revealed that drug transporters, acting alone or in concert with drug metabolizing enzymes, can play an important role in modulating drug absorption, distribution, metabolism, and excretion, thus affecting the pharmacokinetics and/or pharmacodynamics of a drug. The newly published draft drug interaction guidance by the Food and Drug Administration (FDA) in 2012 includes updated recommendations in addressing transporter-mediated drug interactions with various decision trees to help guide drug development and regulatory review. This chapter discusses, from a scientific perspective, role of transporters in drug development with a focus on transporter-mediated DDIs. First, transporter-related recommendations in the recent FDA’s draft drug interaction guidance are discussed. Second, additional transporters that are emerging to be important in drug disposition are discussed. Third, recent review examples and transporter-related labelings are presented. Finally, future directions are discussed.