cssi/SciSciGPT-SciSciNet huggingface dataset:
MET as a Therapeutic Target: Have Clinical Outcomes Been “MET” in Lung Cancer?

Targeted therapy is an especially attractive approach for treating lung cancer since overactivation of oncogenic proteins often drives disease progression. In particular, dysregulation of the MET receptor tyrosine kinase (RTK) pathway via genetic mechanisms, such as gene amplification and exon 14 skipping mutations, has been identified. With significant advancements made in the realm of targeted therapeutics, such as small molecules and antagonistic antibodies, developing novel strategies to target MET is at the forefront of lung cancer treatment. This chapter will introduce the MET signaling pathway and various genetic abnormalities implicated in lung cancer. Then, the currently used MET-targeted therapies and investigative agents will be highlighted along with their status in clinical trials. The final section will shed light on preclinical data revealing possible mechanisms of resistance to MET-targeted therapy.
A Machine Learning Assisted Method of Coverage and Capacity Optimization (CCO) in 4G LTE Self Organizing Networks (SON)

Self-Organizing Network (SON) has been introduced more than a decade by the Next Generation Mobile Networks (NGMN) and later standardized by the 3rd Generation Partner-ship Project (3GPP). However, SON has ever never fully met the expectation from Mobile Network Operators (MNOs) since day one due to lack of suitable wireless based Machine Learning (ML) techniques which can empower SON with intelligence in the old days. The authors propose, validate, and productize a wireless ML based scheme ISO-SON to mitigate cell coverage and interference problems in 4G Long Term Evolution (LTE) networks. ISO-SON algorithm portfolio targets at maximally optimizing cell weak coverage and over-coverage collectively. To scale ISO-SON from a single pain-point optimization in a silo to joint optimization for a problem cell group, a novel clustering methodology is also developed in ISO-SON to identify the social network of the targeted problem cell through modeling neighbor cell closeness rate, pair-wised handoff frequencies between problem cell and neighbor cell candidates, and traffic density of neighbor cell candidates. Finally Sequentially Unconstrained Maximization Technique (SUMT) is applied to converge the ISO-SON loss function in a specific conditional range which is feasible for engineering implementation in tuning antenna angles, due to which the gap between 3GPP SON standards and actual operations is bridged through ISO-SON. ISO-SON is productized and now up and running on a tier-1 MNO’s 4G LTE networks. Reference Signal Received Power (RSRP), the coverage performance indicator, has been improved by 15% for the problem cells after ISO-SON is deployed.
Incident Heart Failure and Long-Term Risk for Venous Thromboembolism

Abstract Background Heart failure (HF) hospitalization places patients at increased short-term risk for venous thromboembolism (VTE). Long-term risk for VTE associated with incident HF, HF subtypes, or structural heart disease is unknown. Objectives In the ARIC (Atherosclerosis Risk In Communities) cohort, VTE risk associated with incident HF, HF subtypes, and abnormal echocardiographic measures in the absence of clinical HF was assessed. Methods During follow-up, ARIC identified incident HF and subcategorized HF with preserved ejection fraction or reduced ejection fraction. At the fifth clinical examination, echocardiography was performed. Physicians adjudicated incident VTE using hospital records. Adjusted Cox proportional hazards models were used to evaluate the association between HF or echocardiographic exposures and VTE. Results Over a mean of 22 years in 13,728 subjects, of whom 2,696 (20%) developed incident HF, 729 subsequent VTE events were identified. HF was associated with increased long-term risk for VTE (adjusted hazard ratio: 3.13; 95% confidence interval: 2.58 to 3.80). In 7,588 subjects followed for a mean of 10 years, the risk for VTE was similar for HF with preserved ejection fraction (adjusted hazard ratio: 4.71; 95% CI: 2.94 to 7.52) and HF with reduced ejection fraction (adjusted hazard ratio: 5.53; 95% confidence interval: 3.42 to 8.94). In 5,438 subjects without HF followed for a mean of 3.5 years, left ventricular relative wall thickness and mean left ventricular wall thickness were independent predictors of VTE. Conclusions In this prospective population-based study, incident hospitalized HF (including both heart failure with preserved ejection fraction and reduced ejection fraction), as well as echocardiographic indicators of left ventricular remodeling, were associated with greatly increased risk for VTE, which persisted through long-term follow-up. Evidence-based strategies to prevent long-term VTE in patients with HF, beyond time of hospitalization, are needed.
Annual Research Review: Defining and treating pediatric treatment-resistant depression.

Background Adolescent major depressive disorder (MDD) is a significant health problem, associated with substantial morbidity, cost, and mortality. Depression is a significant risk factor for suicide, which is now the second leading cause of death in young people. Up to twenty per cent of adolescents will experience MDD before adulthood, and while a substantial proportion will improve with standard-of-care treatments (psychotherapy and medication), roughly one third will not. Methods Here, we have reviewed the literature in order to discuss the concept of treatment-resistant depression (TRD) in adolescence, examine risk factors, diagnostic difficulties, and challenges in evaluating symptom improvement, and providing guidance on how to define adequate medication and psychotherapy treatment trials. Results We propose a staging model for adolescent TRD and review the treatment literature. The evidence base for first- and second-line treatments primarily derives from four large pediatric clinical trials (TADS, TORDIA, ADAPT, and IMPACT). After two medications and a trial of evidence-based psychotherapy have failed to alleviate depressive symptoms, the evidence becomes quite thin for subsequent treatments. Here, we review the evidence for the effectiveness of medication switches, medication augmentation, psychotherapy augmentation, and interventional treatments (i.e., transcranial magnetic stimulation, electroconvulsive therapy, and ketamine) for adolescent TRD. Comparisons are drawn to the adult TRD literature, and areas for future pediatric depression research are highlighted. Conclusions As evidence is limited for treatments in this population, a careful consideration of the known risks and side effects of escalated treatments (e.g., mood stabilizers and atypical antipsychotics) is warranted and weighed against potential, but often untested, benefits.
Working to Avoid Incarceration: Jail Threat and Labor Market Outcomes for Noncustodial Fathers Facing Child Support Enforcement

Child support enforcement is among several contexts in which work requirements are enforced by incarceration for noncompliance. Rather than creating barriers to employment, such incarceration threats may pressure subjects to work more, under worse conditions. We test for this using Fragile Families and Child Wellbeing Study data on respondents’ child support, labor market, and criminal justice experiences in twenty cities. We exploit intercity variation in absolute and relative reliance on different child support enforcement techniques, especially punitive ones, such as incarceration, versus financially extractive ones, such as wage garnishment. As predicted, heavier reliance on incarceration sanctions is associated with more hours of work and lower wages among noncustodial fathers most vulnerable to incarceration.
Standardized Outcome Measures in Stroke Rehabilitation and Falls After Discharge: A Cohort Study.

Introduction Individuals with stroke discharged from inpatient rehabilitation units (IRUs) are at increased risk for falls. In IRUs, standardized outcome measures (SOMs) have been used to predict falls, but the results have been mixed. Objective To examine the relationship between SOMs and the risk of falls in individuals with stroke within 6 months of discharge from an IRU. Design Prospective cohort study with 6-month follow-up. Setting IRU that was part of a large, urban academic medical center. Participants Individuals with stroke who underwent rehabilitation. Main outcome measures Self-reported falls within 6 months of discharge. Results The study included 105 participants who were discharged to their homes after inpatient rehabilitation and who responded to a 6-month follow-up (57% response rate) phone call. Twenty-nine participants (28%) reported falling. Significant odds ratios (ORs), adjusted for age, sex, and stroke severity, were found for the following measures: Berg Balance Scale (OR 0.95, 95% confidence interval [CI] 0.92-0.99), Activity Measure for Post-Acute Care basic mobility (OR 0.89, 95% CI 0.81-0.97), Motricity Index (OR 0.96, 95% CI 0.94-0.98), Functional Independence Measure mobility subscale (OR 0.89, 95% CI 0.80-0.98), and Trunk Control Test (OR 0.97, 95% CI 0.95-0.99). Areas under the curve ranged from .64 to .71. In samples of 82 to 90 patients who could complete the tests, gait speed, the Functional Reach Test, the 6-minute Walk Test, and Timed Up and Go did not result in significant ORs. Conclusions At discharge, SOMs were associated with the odds of falls within 6 months. The multifactorial nature of falls will continue to make prediction challenging but SOMs can be helpful. Lower extremity strength deserves more attention as a risk factor.
Approaches to Objectively Measure Antiretroviral Medication Adherence and Drive Adherence Interventions

Traditional methods to assess antiretroviral adherence, such as self-report, pill counts, and pharmacy refill data, may be inaccurate in determining actual pill-taking to both antiretroviral therapy (ART) or pre-exposure prophylaxis (PrEP). HIV viral loads serve as surrogates of adherence on ART, but loss of virologic control may occur well after decreases in adherence and viral loads are not relevant to PrEP. Pharmacologic measures of adherence, electronic adherence monitors, and ingestible electronic pills all serve as more objective metrics of adherence, surpassing self-report in predicting outcomes. Pharmacologic metrics can identify either recent adherence or cumulative adherence. Recent dosing measures include antiretroviral levels in plasma or urine, as well as emtricitabine-triphosphate in dried blood spots (DBS) for those on tenofovir-emtricitabine-based therapy. A urine tenofovir test has recently been developed into a point-of-care test for bedside adherence monitoring. Cumulative adherence metrics assess adherence over weeks to months and include measurement of tenofovir-diphosphate in peripheral blood mononuclear cells or DBS, as well as ART levels in hair. Electronic adherence monitors and ingestible electronic pills can track pill bottle openings or medication ingestion, respectively. New and objective approaches in adherence monitoring can be used to detect nonadherence prior to loss of prevention efficacy or virologic control with PrEP or ART, respectively.
Coexpression of αβ and γδ TCRs bridges innate and adaptive immunity

T cells coexpressing αβ and γδ TCRs demonstrate characteristics of both αβ and γδ T cells, providing a link between innate and adaptive immune responses.
The relative analgesic value of a femoral nerve block versus adductor canal block following total knee arthroplasty: a randomized, controlled, double-blinded study.

Background Multiple comparative studies report that adductor canal blocks provide similar pain relief to femoral nerve blocks following total knee arthroplasty. However, adductor canal blockade fails to anesthetize several important femoral nerve branches that contribute to knee innervation. We sought to clarify this anatomic discrepancy by performing both blocks in sequence, using patients as their own controls. We hypothesized that patients would experience additional pain relief following a superimposed femoral nerve block, demonstrating that these techniques are not equivalent. Methods Sixteen patients received continuous adductor canal block before undergoing knee arthroplasty under general anesthesia. In the recovery room, patients reported their pain score on a numeric scale of 0-10. Once a patient reached a score of five or greater, he/she was randomized to receive an additional femoral nerve block using 2% chloroprocaine or saline sham, and pain scores recorded every 5 min for 30 min. Patients received opioid rescue as needed. Anesthesiologists performing and assessing block efficacy were blinded to group allocation. Results Patients randomized to chloroprocaine versus saline reported significantly improved median pain scores 30 min after the femoral block (2.0 vs. 5.5, P = 0.0001). Patients receiving chloroprocaine also required significantly fewer morphine equivalents during the 30 min post-femoral block (1.0 vs. 4.5 mg, P = 0.03). Conclusions Adductor canal block is a useful technique for postoperative pain following total knee arthroplasty, but it does not provide equivalent analgesic efficacy to femoral nerve block. Future studies comparing efficacy between various block sites along the thigh are warranted.
Abstract IA21: Integrating head and neck cancer immunotherapy into locally advanced treatment

Recognition that the immune system plays an important role in the development and progression of cancer has permitted a renaissance in the testing of agents designed to stimulate antitumor immunity. Recent FDA approvals have validated that cancer immunotherapy is now established as a standard-of-care agent in many tumor types, primarily in the recurrent/metastatic (R/M) setting. For those with previously untreated, locally advanced disease, the future portends an exciting and rational approach to integrating this new type of therapy into conventional cancer treatment. We will present recent trials and biomarkers of targeted immunotherapy and correlation with response. Human papillomavirus associated (HPV+) oropharyngeal cancer (OPC) is an emerging entity with improved prognosis and distinct staging system from traditional HPV-negative HNSCC. The lecture will address how PD-1-based immunotherapy may represent deintensification without decreased survival for stage I patients at low or intermediate risk, or as an “add-on” strategy for intensification in conjunction with postoperative adjuvant radiation (RT) or chemoradiation (CRT). In addition, neoadjuvant approaches provide dynamic insight into immunosuppression and responses, and guide rational immunotherapeutic combinations for targeting immune checkpoint receptors and inflammatory agonists, including the development of predictive biomarkers to facilitate efficient patient selection. Indeed, a major deficiency of targeted immunotherapies is the lack of dynamic biomarkers to monitor alterations in the tumor microenvironment. Neoadjuvant “window of opportunity” trials present a useful method to obtain predictive biomarkers for patients receiving novel immunotherapeutic agents modulating tumor-infiltrating lymphocytes. Citation Format: Robert Ferris. Integrating head and neck cancer immunotherapy into locally advanced treatment [abstract]. In: Proceedings of the AACR-AHNS Head and Neck Cancer Conference: Optimizing Survival and Quality of Life through Basic, Clinical, and Translational Research; 2019 Apr 29-30; Austin, TX. Philadelphia (PA): AACR; Clin Cancer Res 2020;26(12_Suppl_2):Abstract nr IA21.
Sex-positive social work: by S. J. Dodd, New York, NY, Columbia University Press, 2020, 271 pp., $35.00 (softback), ISBN 978-0-231-18811-1

Dodd, an associate professor at Hunter College and founding director of the Silberman Center for Sexuality and Gender, has prepared a textbook for social work programs interested in developing a cl...
Risk Factors for Failure After Anterior Cruciate Ligament Reconstruction in a Pediatric Population: A Prediction Algorithm:

Background:Anterior cruciate ligament reconstruction (ACLR) in pediatric patients is becoming increasingly common. There is growing yet limited literature on the risk factors for revision in this d...
Challenging Passive Social Media Use: Older Adults as Caregivers Online

Older adults are often portrayed as passive social media users who consume content rather than actively posting content. However, this binary divide between active and passive social media use overlooks nuanced kinds of engagement online. Via an eye-tracking study of older adults' Facebook use, this work shows how not clicking or commenting on content can involve engaged kinds of social media use even if they are not visible to other users or to the platform. Older adults' decisions to not actively click or comment on social media content---an act which is often associated with non-engagement---can be intentional and relational acts of caregiving. We draw from feminist care theories to draw parallels between the invisibility of care work that older adults do on social media and the invisibility often rendered in their offline lives. We discuss theoretical, methodological, and design implications for supporting older adults as engaged participants in relational and intentional care work.
FireMarshal: Making HW/SW Co-Design Reproducible and Reliable

Reproducibility in the sciences is critical to reliable inquiry, but is often easier said than done. In the computer architecture community, research may require modifying systems from low-level circuits to operating systems and high-level applications. All of these moving parts make reproducible experiments on full-stack systems challenging to design. Furthermore, the computing ecosystem evolves quickly, leading to rapidly obsolete artifacts. This is especially true in the realm of software where applications are often updated on a monthly, or even daily, cadence. In this paper we introduce FireMarshal, a software workload management tool for RISC-V based full-stack hardware development and research. FireMarshal automates workload generation (constructing boot binaries and filesystem images), development (with functional simulation), and evaluation (with cycle-exact RTL simulation). It also ensures, to the extent possible, that the exact same software runs deterministically across all phases of development, providing confidence in correctness and accuracy while minimizing time spent on slow and expensive RTL-level simulation. To ease workload specification, FireMarshal provides sane defaults for common components like firmware and operating systems, freeing users to focus only on project-specific components. Beyond reproducibility, FireMarshal enables continued development of workloads through the use of inheritance, where new workloads can be derived from established and continually updated base workloads. Users communicate their designs through the use of simple JSON configuration files that can be easily version controlled, reused, and shared. In this paper, we describe the design of FireMarshal along with the associated software management methodology for architectural research and development.
On the Convergence of Overlapping Schwarz Decomposition for Nonlinear Optimal Control

We study the convergence properties of an overlapping Schwarz decomposition~algorithm for solving nonlinear optimal control problems (OCPs). The approach decomposes the time domain into a set of overlapping subdomains, and solves subproblems defined over such subdomains in parallel. Convergence is attained by updating primal-dual information at the boundaries of the overlapping regions. We show that the algorithm exhibits local linear convergence and that the convergence rate improves exponentially with the overlap size. Our convergence results rely on a sensitivity result for OCPs that we call "exponential decay of sensitivity" (EDS). Intuitively, EDS states that the impact of parametric perturbations at the boundaries of the domain (initial and final time) decays exponentially as one moves into the domain. We show that EDS holds for nonlinear OCPs under a uniform second-order sufficient condition, a controllability condition, and a uniform boundedness condition. We conduct numerical experiments using a quadrotor motion planning problem and a PDE control problem; and show that the approach is significantly more efficient than ADMM and as efficient as the centralized solver Ipopt.
Metabolic and immune markers for precise monitoring of COVID-19 severity and treatment

Abstract Deep understanding of the SARS-CoV-2 effects on host molecular pathways is paramount for the discovery of early biomarkers of outcome of coronavirus disease 2019 (COVID-19) and the identification of novel therapeutic targets. In that light, we generated metabolomic data from COVID-19 patient blood using high-throughput targeted nuclear magnetic resonance (NMR) spectroscopy and high-dimensional flow cytometry. We find considerable changes in serum metabolome composition of COVID-19 patients associated with disease severity, and response to tocilizumab treatment. We built a clinically annotated, biologically-interpretable space for precise time-resolved disease monitoring and characterize the temporal dynamics of metabolomic change along the clinical course of COVID-19 patients and in response to therapy. Finally, we leverage joint immuno-metabolic measurements to provide a novel approach for patient stratification and early prediction of severe disease. Our results show that high-dimensional metabolomic and joint immune-metabolic readouts provide rich information content for elucidation of the host’s response to infection and empower discovery of novel metabolic-driven therapies, as well as precise and efficient clinical action.
Malalcahuelloocaresi gen. & sp. n. (Elateridae, Campyloxeninae).

Malalcahuello ocaresi gen. n. & sp. n., from Chile, is described and compared with Campyloxenus pyrothorax Fairmaire & Germain, 1860.
The philosophy of Hegel

Acknowledgements Abbreviations Introduction 1. German Idealism and the young Hegel 2. The Phenomenology of Spirit 3. The Logic and Hegel's system 4. Ethics and politics 5. Hegel and the narrative task of history 6. Art, aesthetics and literary theory 7. Religion and philosophy Notes Further reading Bibliography Index
Central Disorders of Autonomic Function

Publisher Summary This chapter describes diseases caused by autonomic function disorder. The central autonomic disorders may result in syndromes of autonomic failure, characterized by orthostatic hypotension, anhidrosis, gastrointestinal dysmotility, neurogenic bladder, impotence, and Horner syndrome or syndromes of autonomic hyperactivity, resulting in cardiac arrhythmias, hypertension, hyperthermia or hypothermia, hyperhidrosis, myocardial damage, or neurogenic pulmonary edema. These manifestations may occur in isolation or in various combinations. Disorders of the hypothalamus or its connections produce complex autonomic manifestations, commonly associated with disturbances in endocrine, thirst, caloric balance, or sexual functions. Disorders of thermoregulation are important manifestations of hypothalamic disease. The syndrome of diencephalic autonomic hyperactivity was first described by Penfield in 1929. It commonly occurs as a complication of a closed head injury, producing widespread axonal injury and decortication. These patients may respond to opioids and bromocriptine. The other common cause is acute hydrocephalus, which most frequently occurs in the setting of subarachnoid hemorrhage or with mass lesions near the third ventricle.
The Cancún Climate Conference

The United Nations Climate Change Conference, held from November 29 to December 11, 2010, in Cancun, Mexico, relaunched the United Nation's multilateral facilitation role.
Knowledge Recognition, Rough Sets, and Formal Concept Lattices

As we have recently emphasized elsewhere (W. A. Sedelow & S. Y. Sedelow, 1993b), Knowledge Delivery globally at least compares with Health Care Delivery in social importance--which is to say that internationally it is one of the salient social problems of the present day. At this Conference we are concerned, by way of current and prospective interactions between research and researchers in the domains of Knowledge Discovery and of Rough Sets, to make technical contributions to the alleviation of that problem. Knowledge, it goes without saying, always has been in shorter supply than needed; but now the deficit in available, delivered knowledge has become an overriding concern around the world, in no small measure owing to the disarray in human lives occasioned by widespread disruption in more or less traditional and systemic relationships (W. A. Sedelow & S. Y. Sedelow, 1993a), thereby creating a necessity for working through to solution more problems in less time than ever previously has been required of the human species.
An Electrochemical Glucose Sensor Based on Zinc Oxide Nanorods

A glucose electrochemical sensor based on zinc oxide (ZnO) nanorods was investigated. The hydrothermal sol–gel growth method was utilized to grow ZnO nanorods on indium tin oxide-coated glass substrates. The total active area of the working electrode was 0.3 × 0.3 cm2 where titanium metal was deposited to enhance the contact. Well aligned hexagonal structured ZnO nanorods with a diameter from 68 to 116 nm were obtained. The excitonic peak obtained from the absorbance spectroscopy was observed at ~370 nm. The dominant peak of Raman spectroscopy measurement was at 440 cm−1, matching with the lattice vibration of ZnO. The uniform distribution of the GOx and Nafion membrane that has been done using spin coating technique at 4000 rotations per minute helps in enhancing the ion exchange and increasing the sensitivity of the fabricated electrochemical sensor. The amperometric response of the fabricated electrochemical sensor was 3 s. The obtained sensitivity of the fabricated ZnO electrochemical sensor was 10.911 mA/mM·cm2 and the lower limit of detection was 0.22 µM.
High temporal resolution 3D gadolinium-enhanced dynamic MR imaging of renal tumors with pharmacokinetic modeling: Preliminary observations

Purpose To assess dynamic contrast-enhanced (DCE) magnetic resonance imaging (MRI) tracer pharmacokinetic parameters obtained with Generalized Kinetic Model (GKM) and extended Shutter Speed Model (SSM2) in renal tumors stratified by histologic subtypes. Materials and Methods In all, 24 patients with renal tumors were imaged at 1.5 T utilizing DCE-MRI with high temporal resolution (1.2 sec/temporal frame) prior to surgery. Tracer kinetic analysis was performed for the entire tumor using individualized aortic input function. GKM and SSM2 were employed to generate transfer constant (Ktrans), plasma volume, and interstitial volume. These parameters, and ΔKtrans (KtransSSM2 − KtransGKM) were compared between tumors stratified by histologic subtype. Results There were 25 renal tumors: 15 clear cell, 4 papillary, 3 chromophobe, and 3 oncocytoma/oncocytic subtype. KtransGKM was significantly higher in chromophobe compared to other subtypes (P 1.0 min−1, chromophobe were diagnosed with 100% sensitivity and 90.9% specificity. KtransSSM2 was higher than KtransGKM for all renal tumors except for all chromophobe and two clear cell subtype. Using KtransGKM > 1.0 min−1 and Δ Ktrans < 0, chromophobe could be discriminated from other lesions with 100% accuracy. Conclusion Ktrans obtained with GKM and SSM2 analysis can potentially discriminate chromophobe from other renal lesions with high accuracy. J. Magn. Reson. Imaging 2013;38:802–808. © 2013 Wiley Periodicals, Inc.
Trivalent lanthanide compounds with fluorinated thiolate ligands: Ln-F dative interactions vary with Ln and solvent.

The fluorinated tris-thiolate compounds Ln(SC6F5)3 can be isolated as THF, pyridine, or DME coordination complexes. In THF, the larger Ce forms dimeric [(THF)3Ce(SC6F5)3]2 (1) with bridging thiolate ligands, while the smaller lanthanides (Ln = Ho (2), Er (3)) form monometallic (THF)3Ln(SC6F5)3 compounds. There is a tendency for fluoride to coordinate to Ln throughout the lanthanide series (Ce−Er). The cerium compound 1 contains a pair of bridging thiolates connecting two eight-coordinate Ce(III) ions. Of the two terminal thiolates, only one exhibits a distinct Ce−F bond. In contrast, the Ho derivative (THF)3Ho(SC6F5)3 is a molecular compound in the solid state, with two monodentate thiolates and one thiolate that again coordinates through both S and F atoms. Incorporation of a stronger Lewis base reduces but does not necessarily eliminate the tendency to form Ln−F bonds. Structural characterization of the eight-coordinate (pyridine)4Sm(SC6F5)3 (4) reveals a single, clearly defined Ln−F interaction, while ...
Ultrastructure of the distal retina of the adult zebrafish, Danio rerio.

Abstract The organization, morphological characteristics, and synaptic structure of photoreceptors in the adult zebrafish retina were studied using light and electron microscopy. Adult photoreceptors show a typical ordered tier arrangement with rods easily distinguished from cones based on outer segment (OS) morphology. Both rods and cones contain mitochondria within the inner segments (IS), including the large, electron-dense megamitochondria previously described (Kim et al.) Four major ultrastructural differences were observed between zebrafish rods and cones: (1) the membranes of cone lamellar disks showed a wider variety of relationships to the plasma membrane than those of rods, (2) cone pedicles typically had multiple synaptic ribbons, while rod spherules had 1–2 ribbons, (3) synaptic ribbons in rod spherules were ∼2 times longer than ribbons in cone pedicles, and (4) rod spherules had a more electron-dense cytoplasm than cone pedicles. Examination of photoreceptor terminals identified four synaptic relationships at cone pedicles: (1) invaginating contacts postsynaptic to cone ribbons forming dyad, triad, and quadrad synapses, (2) presumed gap junctions connecting adjacent postsynaptic processes invaginating into cone terminals, (3) basal junctions away from synaptic ribbons, and (4) gap junctions between adjacent photoreceptor terminals. More vitread and slightly farther removed from photoreceptor terminals, extracellular microtubule-like structures were identified in association with presumed horizontal cell processes in the OPL. These findings, the first to document the ultrastructure of the distal retina in adult zebrafish, indicate that zebrafish photoreceptors have many characteristics similar to other species, further supporting the use of zebrafish as a model for the vertebrate visual system.
Syntheses and crystal structures of new chain-containing iodometallate compounds: [H1,10-phen](H2O)1.41[AgI2], [H1,10-phen](H2O)1.42[CuI2]; [Co(tpy)2][Bi2I8], [Fe(tpy)2][Bi2I8]; [Co(1,10-phen)3][Pb3I8]·H2O, and [Fe(1,10-phen)3][Pb3I8]·0.5(H2O)

Abstract Three pairs of novel, isostructural polymeric iodometallate compounds, [H1,10-phen](H2O)1.41[AgI2] (1) ([H1,10-phen]+ = [1,10-phenanthrolinium]+), [H1,10-phen](H2O)1.42[CuI2] (2), [Co(tpy)2][Bi2I8] (3) (tpy = 2,2′:6′2″-terpyridine), [Fe(tpy)2][Bi2I8] (4), [Co(1,10-phen)3][Pb3I8]·H2O (5) (1,10-phen = 1,10-phenanthroline), and [Fe(1,10-phen)3][Pb3I8]·0.5(H2O) (6) have been synthesized solvothermally and characterized by single crystal X-ray diffraction. Compounds 1 and 2 are isostructural and crystallize in the orthorhombic space group Cmma with lattice parameters of a = 6.7063(7) A, b = 17.6051(18) A, c = 12.7088(13) A and a = 6.5770(3) A, b = 17.5245(8) A, c = 12.5515(6) A, respectively. The polymeric anionic chains in 1 and 2 are formed by edge-sharing MI4 (M = Ag, Cu) tetrahedra. Compounds 3 and 4 are isostructural and crystallize in the monoclinic space group P21/n with lattice parameters of a = 16.5085(7) A, b = 16.0392(7) A, c = 16.5115(7) A, β = 97.4710(10)° and a = 16.4478(6) A, b = 16.0645(6) A, c = 16.4498(6) A, β = 97.4490(10)°, respectively. Both structures contain the first observed, face-sharing [Bi2I8]2− anion cluster that is linked via corner sharing into infinite zig-zag anionic chains. Compounds 5 and 6 are isostructural and crystallize in the triclinic space group P 1 ¯ with lattice parameters of a = 11.8798(5) A, b = 15.2805(7) A, c = 16.1889(7) A, α = 63.9240(10)°, β = 74.0420(10)°, γ = 73.2540(10)° and a = 11.7889(5) A, b = 15.3224(6) A, c = 16.2584(6) A, α = 64.1920(10)°, β = 73.5600(10)°, and γ = 73.7120(10)°, respectively. Compounds 5 and 6 contain infinite [Pb3I8]2− chains in which the three crystallographically unique Pb2+ ions are found in sets of three trans face-sharing octahedra. These face-sharing trimers are observed in pairs that share three edges, and the pairs are further connected into 1-D chains by edge sharing with neighboring 2 × 3 units.
Spin trapping of superoxide radicals following stimulation of neutrophils with fMLP is temperature dependent.

Abstract Oxygen radical formation by human neutrophils stimulated with a chemotactic peptide, formyl-methionyl-leucyl-phenylalanine(fMLP), was studied through the use of spin trapping and superoxide dismutase-inhibitable reduction of oxidized cytochrome c . Both methods provided comparable data on temperature-dependent kinetics of superoxide radical formation, but hydroxyl radicals were also detected in spin-trapping experiments. When superoxide generation was monitored at 37°C, the respiratory burst lasted only a few minutes. If the neutrophils were stimulated at 37°C, but superoxide measurements were done at room temperature, the respiratory burst was again transient. However, neutrophils persistently generated superoxide when both stimulation and subsequent measurements were performed at room temperature. In the presence of the actin polymerization inhibitor, cytochalasin B , superoxide generation was persistent, even when measurements were conducted at 37°C. A possible explanation for these observations is that the fMLP receptor complexes quickly aggregate and are internalized at physiological temperature, but not at room temperature. Very little superoxide was formed if cells were kept at a temperature of 4°C for 1 h prior to fMLP addition, which is consistent with decreased expression of the fMLP receptor at cold temperatures.
Evolution of operative techniques for the treatment of single-suture metopic synostosis

Purpose:Primary orbitocranioplasty for metopic craniosynostosis encompasses a variety of techniques, with variable long-term success. The authors present a series illustrating the evolution of surgical techniques and its impact on surgical outcomes.Methods:All patients with single-suture metopic syn
Empirical research about same-sex intimate partner violence: a methodological review

This article presents a systematic review of empirical research examining intimate partner violence among same-sex couples. Seventeen studies that met the inclusion criteria were rated using a 15-item evaluation questionnaire. The results indicated that the existing body of research examining same-sex intimate partner violence demonstrates some common methodological strengths and limitations. The authors conclude with a list of recommendations for future research based on the results of this study.
Examination of blood clobazam levels and several pupillary measures in humans

Abstract The State‐Trait Anxiety Inventory was administered to 15 subjects before initiation of the experiment. Three subgroups of five subjects were defined by computing the unweighted sum of the state and trait anxiety scores. A 40‐mg dose of clobazam, a 1,5‐benzodiazepine, was administered to each subject and repeated with two additional dosage forms following a 2‐week washout period. Blood samples were withdrawn, and blood levels were determined by fluorometric analysis. Additionally, pupillary measures of critical flicker fusion, constriction, and dilation in response to a cognitive task were obtained at 0, 2, 4, and 6 hr. A repeated measures analysis of variance revealed that blood levels were, as expected, statistically different over time and dosage form. The pupillary constriction mirrored the blood levels in statistical patterns. The pupillary measure of cognition related to the anxiety state after the performance effects of the cognitive task were statistically removed. The results suggest that clobazam has less immediate human effect than does diazepam.
Computer-assisted provision of emergency contraception a randomized controlled trial.

Background Emergency contraception (EC) can prevent unintended pregnancy. However, many women continue to lack information needed to use EC effectively and clinician time to counsel women about EC is limited.
Forward genetic approaches in Chlamydia trachomatis.

Chlamydia trachomatis, the etiological agent of sexually transmitted diseases and ocular infections, remains poorly characterized due to its intractability to experimental transformation with recombinant DNA. We developed an approach to perform genetic analysis in C. trachomatis despite the lack of molecular genetic tools. Our method involves: i.) chemical mutagenesis to rapidly generate comprehensive libraries of genetically-defined mutants with distinct phenotypes; ii.) whole-genome sequencing (WGS) to map the underlying genetic lesions and to find associations between mutated gene(s) and a common phenotype; iii.) generation of recombinant strains through co-infection of mammalian cells with mutant and wild type bacteria. Accordingly, we were able to establish causal relationships between genotypes and phenotypes. The coupling of chemically-induced gene variation and WGS to establish correlative genotype–phenotype associations should be broadly applicable to the large list of medically and environmentally important microorganisms currently intractable to genetic analysis.
Maximal regularity of evolution equations on discrete time scales

We consider the question of Lp-maximal regularity for inhomogeneous Cauchy problems in Banach spaces using operator-valued Fourier multipliers. This follows results by L. Weis in the continuous time setting and by S. Blunck for discrete time evolution equations. We generalize the later result to the case of some discrete time scales (discrete problems with nonconstant step size). First we introduce an adequate evolution family of operators to consider the general problem. Then we consider the case where the step size is a periodic sequence by rewriting the problem on a product space and using operator matrix valued Fourier multipliers. Finally we give a perturbation result allowing to consider a wider class of step sizes.
2,4-Dinitrophenylhydrazone formation at the aldehyde derived by periodate cleavage of α-amanitin

10(-4) cleavage of alpha-amanitin after the procedure of Wieland & Fahrmeir (1) but without prior protective methylation of the 6'-hydroxyl of the tryptophan residue affords the alpha-amanitin aldehyde in 45% yield. The aldehyde was found to exhibit Ki = 3.0 and 12 microM for Drosophila melanogaster and wheat germ RNA polymerase II, respectively. This value is approximately 100-fold greater than for the parent alpha-amanitin. Treatment of the alpha-amanitin aldehyde with 2,4-dinitrophenylhydrazine in CH3OH, CH3CN, or dimethylsulfoxide yielded three products. Two of these did not contain the 2,4-dinitrophenyl moiety, showed Ki = 3.3 and 0.26 microM for wheat germ RNA polymerase II (alpha-amanitin, Ki = 0.09 microM), and accounted for 30-60% and 3% of the input alpha-amanitin aldehyde, respectively. The alpha-amanitin-2,4 dinitrophenylhydrazone was recovered in less than 10% yield regardless of reaction condition and showed a Ki = 0.26 microM on wheat germ RNA polymerase II. This hydrazone establishes that the amatoxin molecule can be modified in the dihydroxyisoleucine residue without disruption of binding to the RNA polymerase.
166 DEVELOPMENT CHANGES IN THE RESPONSE OF TYPE II CELLS TO PHOSPHATIDYLCHOLINE (PC) SECRETAGOGUES

PC secretion in adult rat type II cells can be stimulated by several agents acting via different signal-transduction mechanisms. To determine if these mechanisms also operate in developing lung we have compared the response of type II cells isolated from 21 day fetal and 1, 7 and 14 day old rats with those from adults to 36 uM terbutaline, 10 uM N-ethylcarboxamido-adenosine (NECA, adenosine analog), 1 mM ATP, 10 uM tetradecanoylphorbol acetate (TPA) and 25 nM ionomycin. Fetal cells were isolated by trypsin/collagenase digestion and differential adhesion and those from newborns and adults by elastase digestion and panning on IgG-coated dishes. The cells were cultured for 18-20 h with 3H-choline, washed in fresh medium and incubated ± agonists for 90 min after which 3H-PC in cells and medium was measured. The cells were 81-97% type II cells. The rate of basal secretion (PC in medium as % of total in cells + medium) was the same in all 5 groups. However, there was a developmental change in the response to the secretogogues. These data show that different signal-transduction pathways mature at different developmental stages in type II cells. Supported by NIH (HL-31175) and the DFG.
Pharmacokinetics and pharmacodynamics of insulin analogs in special populations with type 2 diabetes mellitus.

Introduction The goal of insulin therapy in patients with either type 1 diabetes mellitus (T1DM) or type 2 diabetes mellitus (T2DM) is to match as closely as possible normal physiologic insulin secretion to control fasting and postprandial plasma glucose. Modifications of the insulin molecule have resulted in two long-acting insulin analogs (glargine and detemir) and three rapid-acting insulins (aspart, lispro, and glulisine) with improved pharmacokinetic/pharmacodynamic (PK/PD) profiles. These agents can be used together in basal-bolus therapy to more closely mimic physiologic insulin secretion patterns.
A Robust Semi-Active Tuned Vibration Absorber for Reducing Vibrations in Force-Excited Structures

A passive TVA is only effective when it is tuned properly; otherwise, it can magnify the vibration levels. Often, inevitable off-tuning of a TVA occurs due to changes in the primary structure mass and stiffness for force-excited structural systems such as a floor. The main purpose of this study is to evaluate the robustness of semi-active groundhook TVAs to structure mass and stiffness off-tuning. In the case of floor systems, adding external mass to an existing floor, such as people and furniture, will increase the floor mass, and reduce the mass ratio. Theses changes result in off-tuning of the frequency ratio, which is defined by the ratio of the natural frequency of the TVA to the primary structure natural frequency. In order to study the effect of off-tuning, a force-excited equivalent model of a groundhook TVA is developed and its closed-form solutions are obtained for dynamic analysis of such systems. Moreover, the optimal design parameters of both passive and groundhook equivalent semiactive TVA models are obtained based on minimization of peak transmissibility. The two optimally tuned models are compared as the primary mass and primary structure stiffness changes. The results indicate that the peak transmissibility of the groundhook TVA is lower than that of passive, implying that the groundhook TVA is more effective in reducing vibration levels. The results further indicate that the groundhook TVA is more robust to changes in primary structure mass and stiffness.Copyright © 2002 by ASME
Selective facilitation of kindled seizures from the amygdala after hippocampal lesions induced by perforant path stimulation

Intermittent electrical stimulation of the perforant path (PPS) for 24 h in anesthetized rats results in impairment of paired pulse inhibition, neuronal loss in the dentate gyrus and hippocampus, and delayed spontaneous seizures. One week after PPS, animals showed a dramatic decrease in afterdischarge threshold and increase in afterdischarge duration from the basolateral amygdala, whereas no changes in after-discharge properties were observed from the dentate gyrus. Animals also showed a remarkable facilitation of amygdala kindling, but not of perforant path kindling. After amygdala kindling, some animals showed spontaneous seizures. PPS may recruit amygdala into the epileptogenic circuit, resulting in "latent' kindling and development of spontaneous seizures.
Injectable polymer microspheres enhance immunogenicity of a contraceptive peptide vaccine

Advanced contraceptive peptide vaccines suffer from the unavailability of adjuvants capable of enhancing the antibody response with acceptable safety. We sought to overcome this limitation by employing two novel poly(lactic-co-glycolic acid) (PLGA) microsphere formulations to deliver a synthetic human chorionic gonadotropin (hCG) peptide antigen co-synthesized with a T-cell epitope from tetanus toxoid (TT), C-TT2-CTP35: surface-conjugated immunogen to induce phagocytosis; and encapsulated peptide to provide a depot effect, with MgCO(3) co-encapsulated in the polymer to neutralize acidity from the biodegrading PLGA polyester. A single immunization of encapsulated peptide in rabbits elicited a stronger antibody response with equivalent duration relative to a positive control--three injections of the peptide administered in a squalene-based water-in-oil emulsion. Surface-conjugated peptide was less effective but enhanced antibody levels at 1/5 the dose, relative to soluble antigen. Most remarkable and unexpected was the finding that co-encapsulation of base was essential to attain the powerful adjuvant effect of the PLGA-MgCO(3) system, as the MgCO(3)-free microspheres were completely ineffective. A promising contraceptive hCG peptide vaccine with acceptable side effects (i.e., local tissue reactions) was achieved by minimizing PLGA and MgCO(3) doses, without significantly affecting antibody response.
Excited State Theory: Monosubstituted Benzenes Fluorescence and Phosphorescence

Abstract The fluorescence and phosphorescence band positions of mono substituted benzenes are recorded at 77°K in four solvents, and the band maxima are correlated with substituent effects. No correlation of the fluorescence band maxima is obtained until the electron donating substituents are separated from the electron acceptors. The phosphorescence band maxima do not correlate well with Hammett sigma constants. With the exception of N, N-dimethylaniline, the fluorescence maxima are independent of the nature of the solvent. Both good electron donor and acceptor groups diminish the fluorescence and phosphorescence transition energies. With good electron donor and acceptor groups, there is a significant red shift in phosphorescence on going from nonpolar solvents to acetonitrile. The phosphorescence results are interpreted in terms of intramolecular charge transfer (ICT) and charge transfer to solvent (CTTS) processes in competition with one another.
Measurement of the transport mean free path of diffusing photons.

We measure microwave intensity inside and transmission through random samples of polystyrene spheres with different output reflectors. We show that with appropriate boundary conditions diffusion theory gives an excellent description of transport from the interior to the output surface of a sample. From these measurements we determine the transport mean free path and the surface reflectivities without additional assumptions regarding the interface or the scattering form factor. From a comparison with a measurement of the diffusion coefficient we determine the transport velocity and find that it is smaller than the velocity in the high-index material.
The Ultimate Sin: Christianising Slaves in Barbados in the Seventeenth Century

My article traces the changing attitudes toward slave conversion in seventeenth-century Barbados – from hesitant discomfort in the mid-seventeenth century, to virulent rejection in 1680 – and argues that the attempted rebellion of 1675, which was widely blamed on Quaker proselytising efforts, played a pivotal role in the development of an antagonistic attitude toward missionaries in Barbados. The 1675 attempted rebellion, I suggest, linked slave conversion with slave rebellion in a new and decisive way that had repercussions throughout the British West Indies.