cssi/SciSciGPT-SciSciNet huggingface dataset:
Abstract 1337: Up-regulation of mannose 6-phosphate receptor induced by BRAF inhibitor PLX4720 is linked to phosphatidylserine externalization and shows positive effects for combination therapies

Proceedings: AACR 106th Annual Meeting 2015; April 18-22, 2015; Philadelphia, PA New therapies of metastatic melanoma, including BRAF inhibitors, check-point blockade or adoptive T-cell transfer, hold high promise. However, their efficacy remains unsatisfactory. Combination of different modalities offers an opportunity to enhance their effect. We studied mannose 6-phosphate receptor (MPR) previously implicated in synergistic effect of cancer chemotherapy and immunotherapy. Approximately 50% of human melanomas bear the activating mutation V600E in BRAF that can be selectively targeted with BRAF inhibitor PLX4720. We have observed that in vitro treatment of human V600E-positive melanoma cells 451Lu and WM983B leads to a dose-dependent up-regulation of mannose 6-phosphate receptor (MPR) in the cell surface. An increase in cell surface MPR, enhanced recombinant Granzyme B uptake, a requirements for effective combination with immunotherapy. This effect of PLX4720 on MPR expression was reproduced in a mouse model featuring xenograft 451Lu-derived subcutaneous tumors. This effect was limited only to sensitive cell lines, disappearing completely after resistance had been induced by extended treatment with growing doses of the drug. We have previously determined that autophagy has a key role in MPR up-regulation after chemotherapy or radiation therapy. However, in the case of PLX4720, autophagy occurs 1-2 days after the start of the treatment while membrane MPR was up-regulated not early than 3-4 and 10-14 days after the start of the treatment in 451Lu and WM983B cells respectively. In addition, autophagy was present independently of whether the cells were resistant to PLX4720 or not. These data indicate that autophagy was probably not responsible in PLX4720 inducible up-regulation of MPR. We observed a parallel changes in MPR up-regulation and phosphatidylserine (PS) externalization in live melanoma cells. PS and MPR co-localized on cell surface after the treatment with PLX4720. Co-incubation of PLX4720 with PS-specific antibody resulted in an ablation of the subsequent membrane MPR up-regulation. These observations help to explain the synergism between immunotherapy and targeted therapy of melanoma and to design clinical trials. Citation Format: Sergio Lavilla-Alonso, Rolf Brekken, Dmitry Gabrilovich. Up-regulation of mannose 6-phosphate receptor induced by BRAF inhibitor PLX4720 is linked to phosphatidylserine externalization and shows positive effects for combination therapies. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 1337. doi:10.1158/1538-7445.AM2015-1337
113. HSV Vector Development for Targeted Gene Delivery

Gene therapy often requires selective gene delivery to specific cellular subpopulations to provide the most effective therapeutic outcome and avoid off-target effects. This can be accomplished by viral vector targeting involving replacement of the natural virus-cell interactions that trigger virus entry, with novel cell-specific interactions, thereby permitting delivery of therapeutic transgenes to specific cell types. Strategies for full retargeting of HSV require (i) mutagenesis-mediated virus detargeting from its cognate receptors (HVEM and nectin1) recognized by the virus attachment/entry component glycoprotein D (gD) and (ii) the introduction of new ligands into gD that allow entry through recognition of cognate cellular receptors. To target an HSV vector for entry exclusively into cells expressing the receptors GFRa1 or TrkA, we employed the ligands GDNF and NGF, respectively. We replaced the signal peptide and HVEM binding domain of gD with pre-pro-(pp)GDNF to create a GFRa1 targeting protein, gD(Y38)_GDNF, that can still bind nectin1. Virus expressing gD(Y38)_GDNF was propagated on cells expressing nectin1 and purified virus was shown to enter nectin1-deficient cells in a GFRa1-dependent manner. Likewise, TrkA-dependent virus entry was observed using ppNGF as a targeting ligand. Although propagation of completely retargeted viruses (mutationally inactivated for both HVEM and nectin1 binding) can be achieved in complementing cell lines that express the target receptor, we observed differences among cell lines in retargeted virus spread. HSV receptor-deficient J1.1-2 and B78H1 cells engineered to express the target receptors allowed virus entry, but only B78H1 based cells displayed observable spread. U2OS cells engineered to express GFRa1 demonstrated the most robust virus entry and spread, but these cells express abundant nectin1, providing strong selective pressure for reversion of the nectin1 binding defect of fully retargeted viruses during propagation. In one approach to overcome this problem, we developed genetic selection methods to isolate retargeted virus variants that both entered and spread on J1.1-2 cells transduced with the target receptor. We found that selected variants had acquired mutations in other envelope glycoproteins, including one glycoprotein involved in envelope-cell fusion events (gH) and two that were previously shown to contribute to the spreading process (gE and gI). We expect that the combination of virus mutants and engineered cell lines for efficient production of stably retargeted HSV gene therapy vectors will allow us to achieve HSV retargeting to a broader range of receptors.
Use of the Quinolones in Skin and Skin Structure (Osteomyelitis) and Other Infections

Publisher Summary This chapter discusses the use of fluoroquinolones for the treatment of skin and skin-structure infections. Quinolones are highly effective and appropriate therapy for complex skin and soft tissue infections caused by the facultative Gram-negative bacilli , or these organisms in combination with the aerobic Gram-positive cocci. Additionally, ciprofloxacin is the recommended agent of choice for the treatment of osteomyelitis caused by the Enterobacteriaceae, except Serratia spp. The emergence and dissemination of staphylococci, particularly methicillin-resistant S. aureus and P. aeruginosa, that are resistant to quinolones may further limit their utility in these infections. The unpredictability of the antibacterial activity of newly available compounds against the anaerobic Gram-negative bacilli argues for caution in using these agents alone when severe infection due to the anaerobes is encountered. The combination of the quinolones and rifampin may hold great promise for the treatment of S. aureus osteomyelitis and for the eradication of staphylococcal infections involving prosthetic devices without obligatory device removal. The potency of quinolones against the Gram-negative bacilli and the bioavailability with oral administration allow significant simplification of therapy. Oral therapy can replace parenteral therapy, thus reducing hospitalization, avoiding complications of intravenous access, and reducing end-organ toxicities associated with parenteral β-lactam antimicrobials and aminoglycosides. The judicious use of quinolones in the treatment of skin and soft tissue infections and osteomyelitis can also help in achieving cost reduction.
Surveillance of long-term colorectal cancer survivors.

e20596 Background: Advances in the treatment of colorectal carcinoma (CRC) have contributed to an increase in long-term survivors. Despite the advances made in this cancer, there is relatively litt...
Urban Pressures and Innovations: Sustainability Commitment in the Face of Fragmentation and Inequality

Local government innovations occur within environments characterized by high service-need complexity and risk. The question of how broader environmental conditions influence governmental willingness or ability to innovate has been a long-standing concern within organizational, management, and policy scholarship. Although wealth and education are robust predictors of the propensity to engage in a wide range of local sustainability activities, the linkages among governmental fragmentation, social inequality, and sustainability policies are not well understood. This study focuses on the conditions both within and across city boundaries in urban regions which inhibit adoption of sustainable development innovations. We utilize a Bayesian item response theory approach to create a new scale measuring sustainability commitment by local governments in the United States. The analysis finds service-need complexity and capacity within local governments' organizational task environments have nonlinear influences on innovation in terms of both green building and social inclusion policy tools.
IKKβ and mutant huntingtin interactions regulate the expression of IL-34: implications for microglial-mediated neurodegeneration in HD.

Neuronal interleukin-34 (IL-34) promotes the expansion of microglia in the central nervous system—microglial activation and expansion are in turn implicated in the pathogenesis of Huntington‘s disease (HD). We thus examined whether the accumulation of an amyloidogenic exon-1 fragment of mutant huntingtin (mHTTx1) modulates the expression of IL-34 in dopaminergic neurons derived from a human embryonic stem cell line. We found that mHTTx1 aggregates induce IL-34 production selectively in post-mitotic neurons. Exposure of neurons to DNA damaging agents or the excitotoxin NMDA elicited similar results suggesting that IL-34 induction may be a general response to neuronal stress including the accumulation of misfolded mHTTx1. We further determined that knockdown or blocking the activity of IκB kinase beta (IKKβ) prevented the aggregation of mHTTx1 and subsequent IL-34 production. While elevated IL-34 itself had no effect on the aggregation or the toxicity of mHTTx1 in neuronal culture, IL-34 expression in a rodent brain slice model with intact neuron-microglial networks exacerbated mHTTx1-induced degeneration of striatal medium-sized spiny neurons. Conversely, an inhibitor of the IL-34 receptor reduced microglial numbers and ameliorated mHTTx1-mediated neurodegeneration. Together, these findings uncover a novel function for IKKβ/mHTTx1 interactions in regulating IL-34 production, and implicate a role for IL-34 in non-cell-autonomous, microglial-dependent neurodegeneration in HD.
Assessing Barriers to Therapeutic Regimens for Young People with Juvenile Idiopathic Arthritis.

The Health Belief Model (HBM) has been one of the most widely used theories in health behavior research over the past 5 decades1,2. Originally developed in the early 1950s to understand why people failed to take advantage of preventive health services (such as hypertension screening), the HBM was later extended to adherence to prescribed medical regimens3,4. The HBM posits 5 major sets of variables that predict or explain adherence: (1) perceived susceptibility (including the person’s perceived risk of contracting or re-contracting a condition or acceptance of an existing condition); (2) perceived severity (the person’s evaluation of the medical and social consequences of contracting an illness or not receiving treatment); (3) perceived benefits (the person’s judgment of the perceived benefits of taking a particular health action); (4) perceived barriers (the person’s perception of impediments to adhere to recommended treatments, … Address correspondence to Dr. M.A. Rapoff, 3901 Rainbow Blvd., Kansas City, Kansas 66103-7330, USA. E-mail: mrapoff{at}kumc.edu
Epidural Intracranial Pressure Monitoring: A New Method

Ten Years experience with the use of epidural intracranial pressure monitoring (Fiberoptic System) has proved this method to be both accurate and free from significant complications (Levin 1977). In over 500 cases the average duration of placement is now about two weeks, with the longest duration being over 40 days. There have been no primary infections. This is of special note in that we experience a high incidence of infection with external ventricular drains or catheters which are left in place for more than five days.
Financial Policies and Hedging

While firms commonly benchmark corporate financial policies against industry peers, empirically, some firms consistently deviate to pursue “rogue” policies with either a conservative or an aggressive bias. Using a panel of large U.S. firms between 1975 and 2008, we study the incidence, joint frequency distribution, and valuation effect of conservative and aggressive financial policies across four policy dimensions: leverage, payout, liquidity, and risk management. Consistent with a hedging effect, we find that conservative (aggressive) financial policies are generally associated with higher (lower) valuations. In addition, consistent with hedging theories, we find that firms with high growth opportunities which also face financial constraints benefit more from conservative financial policies. We also observe a time-variation in the valuation effects. For example, we find that conservative liquidity policies are associated with lower valuation benefits during periods of high economic growth while most aggressive policies are associated with even lower valuations as the average level of the policy increases. Finally, our tests of joint rogue policies provide evidence consistent with agency explanations. For example, firms which pursue both conservative leverage and conservative liquidity policies are valued at a discount, even though those that pursue a conservative leverage or a conservative liquidity policy on its own are valued at a premium.
Preventing anal cancer: Qualitative study among foreign-born Hispanic HIV-Infected Gay and Bisexual Men

Background This study explores foreign-born Hispanic HIV-infected gay and bisexual men's (GBM) anal cancer primary and secondary prevention understanding. These populations may be at greater risk for developing anal cancer given their reduced likelihood to engage and be sustained in HIV primary care. Methods Between August 2015 and December 2016 researchers conducted 33 semi-structured in-depth interviews with foreign-born Hispanic HIV-infected Hispanic GBM. Interview questions sought to determine participants’ perceived barriers and facilitators to anal cancer primary and secondary prevention. Researchers analyzed interview transcripts using a qualitative content analysis approach. Results For primary prevention, men reported lack of knowledge about the human papillomavirus (HPV) vaccine. However, for secondary prevention roughly 60% of participants had previously screened for anal dysplasia via anal Pap smear. Provider recommendation was the most common screening facilitator. Men reported stigma related to their HIV status, sexual orientation, and anal Pap smear procedures as barrier to HIV primary care retention and, in turn, anal cancer screening adherence. Participants reported willingness to use a self-screening anal Pap smear test if it were commercially available. Conclusions Health providers continue to be the leading source of health information. Therefore, provider recommendation for HPV vaccination and anal cancer screening among age-eligible Hispanic HIV-infected GBM is critical. More work is needed to destigmatize HIV and sexual orientation to influence positive health behaviors among this population. Future intervention research could test the effects of provider-led interventions and also media campaigns aimed at influencing HPV vaccine uptake and anal cancer screening among this population.
Breeze: User-Level Access to Non-Volatile Main Memories for Legacy Software

Non-volatile main memory (NVMM) technologies, such as phase change memory and 3D XPoint, offer DRAM-like performance and byte-addressable access to persistent data. A wide range of applications (e.g., key-value stores and database systems) stand to benefit from the performance potential of these technologies. These potential benefits are greatest when applications can access memory directly via load/store instructions rather than conventional file-based interfaces. This approach presents several challenges. In particular, applications need guaranteed consistency and safety semantics to protect their data structures in the face of system failures and programming errors. Implementing data structures that meet these requirements is challenging and error-prone. Researchers have proposed several libraries and programming language extensions that simplify this task, but, to date, all the proposed solutions either require pervasive changes to existing software or rely on special hardware support. As a result, porting legacy applications to leverage NVMM is likely to be prohibitively difficult and time consuming. We propose Breeze, a NVMM toolchain that minimizes the changes necessary to enable legacy code to reap the benefits of directly accessing NVMM. Breeze guarantees data consistency and validity of persistent pointers regardless of failures. The toolchain transparently detects and logs writes to NVMM and provides a simple mechanism for identifying atomic sections while avoiding complications common in previous systems such as special persistent pointer types. Porting Memcached and MongoDB to use Breeze only requires changes to 5% of the source code compared to 7-14% for NVML and NVM-Direct. Breeze also provides equal or superior performance compared to NVML and NVM-Direct, outperforming them by up to 10x.
Metalworking Fluids and Colon Cancer Risk: Longitudinal Targeted Minimum Loss-based Estimation.

Metalworking fluids (MWFs) are a class of complex mixtures of chemicals and oils, including several known carcinogens that may pose a cancer hazard to millions of workers. Reports on the relation between MWFs and incident colon cancer have been mixed. Methods We investigated the relation between exposure to straight, soluble, and synthetic MWFs and the incidence of colon cancer in a cohort of automobile manufacturing industry workers, adjusting for time-varying confounding affected by prior exposure to reduce healthy worker survivor bias. We used longitudinal targeted minimum loss-based estimation (TMLE) to estimate the difference in the cumulative incidence of colon cancer comparing counterfactual outcomes if always exposed above to always exposed below an exposure cutoff while at work. Exposure concentration cutoffs were selected a priori at the 90th percentile of total particulate matter for each fluid type: 0.034, 0.400, and 0.003 for straight, soluble, and synthetic MWFs, respectively. Results The estimated 25-year risk differences were 3.8% (95% confidence interval [CI] = 0.7, 7.0) for straight, 1.3% (95% CI = -2.3, 4.8) for soluble, and 0.2% (95% CI = -3.3, 3.7) for synthetic MWFs, respectively. The corresponding risk ratios were 2.39 (1.12, 5.08), 1.43 (0.67, 3.04), and 1.08 (0.51, 2.30) for straight, soluble, and synthetic MWFs, respectively. Conclusions By controlling for time-varying confounding affected by prior exposure, a key feature of occupational cohorts, we were able to provide evidence for a causal effect of straight MWF exposure on colon cancer risk that was not found using standard analytical techniques in previous reports.
Treatment of Advanced Prostate Cancer

The therapeutic landscape of prostate cancer has been transformed over the last decade by new therapeutics, advanced functional imaging, next-generation sequencing, and better use of existing therapies in early-stage disease. Until 2004, progression on androgen deprivation therapy for metastatic disease was treated with the addition of secondary hormonal manipulation; in the last decade, six systemic agents have been approved for the treatment of castration-resistant prostate cancer. We review clinical trials and survival benefit for these therapies and assess how the understanding of the disease shifted as these therapies were developed. We also discuss advances in noncastrate disease states, identification of biomarkers for prognosis and treatment selection, and opportunities in locoregional therapy to delay androgen deprivation therapy.
Cholinergic Rem Sleep Induction Response as a Marker of Endogenous Depression

At the present time the diagnosis of mental disorders is defined by operational criteria, which are primarily based on the presenting sysmptoms, i.e., Research Diagnostic Criteria (RDC) (18); Diagnostic and Statistics Manual III (2). This is also true for treatment decisions and prognosis. There is, however, a growing body of evidence that specific biological abnormalities that have both pathophysiological as well as diagnostic significance may be present, in disorders such as manic depressive illness.
How sweet it is: The coming of age of continuous glucose monitoring

“Think of me as your personal diabetes assistant. In this app, you and I are partners, so let's get started.” Those words are part of a greeting from the Sugar.IQ personal diabetes assistant, an app powered by IBM Watson's cognitive computing technology that is available to users of Medtronic's Guardian Connect mobile continuous glucose monitoring system. Indeed, we are in the midst of an era in which an increasing number of wearable continuous glucose monitors (CGMs) are receiving Food and Drug Administration (FDA) approval, and many of these systems come with app-based readers to enhance their convenience and facilitate the coordination of care for people with type 1 diabetes with their healthcare providers. A recent publication in Nature Biotechnology provides a comprehensive overview of …
Prevalence and Cause of Early Fontan Complications: Does the Lymphatic Circulation Play a Role?

Background Recent studies suggest that lymphatic congestion plays a role in development of late Fontan complications, such as protein‐losing enteropathy. However, the role of the lymphatic circulat...
Novel alkyd-type coating resins produced using cationic polymerization

Novel, partially bio-based poly(vinyl ether) copolymers derived from soybean oil and cyclohexyl vinyl ether (CHVE) were produced by cationic polymerization and investigated for application as alkyd-type surface coatings. Three different polymers were produced and cured clear coatings and free films characterized as a function of CHVE comonomer content and curing conditions. CHVE comonomer content was varied at 0, 25, and 50 wt%, and the three different curing conditions were 1 week at room temperature, 120°C for 1 h, and 150°C for 1 h. The results of the study showed that the thermal, mechanical, and physical properties of the coatings produced from these novel polymers varied considerably as a function of polymer composition and cure temperature. Overall, the results suggest a good potential for these novel copolymers to be used for coatings cured by autoxidation. Compared to conventional alkyd resins, which are produced by high temperature melt condensation polymerization, these poly(vinyl ether)s provide several advantages. These advantages include milder, more energy efficient polymer synthesis, elimination of issues associated with gelation during polymer synthesis, production of polymers with well-defined composition and relatively narrow molecular weight distribution, and elimination of film formation and physical property issues associated with entrained monomers, dimers, trimers, etc.
Why it's hard to see a dermatologist for a skin exam: the patient perspective.

In-office skin exams are recommended at least annually for patients who are diagnosed with a basal cell carcinoma or squamous cell carcinoma, but it is unknown what proportion of these patients are receiving skin exams. There are a multitude of reasons why patients have difficulty getting skin exams. To assess the proportion of patients at our institution who received a skin exam in the 12 months following removal of a basal cell carcinoma or squamous cell carcinoma by Mohs micrographic surgery and to assess the barriers to care that patients faced in receiving a skin exam. We conducted an IRB-approved online patient survey. 161 survey respondents said they were able to get a skin exam and 14 said they were not. Patients who did not receive a skin exam agreed significantly more often with the following barriers to care: patient’s own schedule, dermatologists’ availability, and not knowing a skin exam was recommended (p < 0.005). Patients who did not receive a skin exam said that a reminder text/email/phone call would make them more likely to receive a skin exam. Patients identify their own schedule, the provider’s schedule, and not knowing that a skin exam is recommended as factors making it more difficult for them to receive a skin exam. It is likely that further emphasis about the importance of skin exams, written instructions, or text/email/phone call reminders would make patients who have been previously diagnosed with basal cell carcinoma or squamous cell carcinoma more likely to receive skin exams.
Neuroticism as the intensity, reactivity, and variability in day-to-day affect

Abstract Neuroticism has been linked to typical levels of affect, affect reactivity to negative events, and variability in affect over time. However, the intercorrelations among these characteristics make it unclear whether neuroticism reflects unique variance in each of these aspects of emotional life. Data from two daily-diary samples revealed that neuroticism was associated with average levels and variability of positive and negative affect and reactivity of negative affect to stressors, but was only uniquely related to mean levels of positive and negative affect. Findings highlight the substantial overlap in affect indices, suggesting that mean levels of affect, at the very least, are at the core of neuroticism, and reveal the need for further research using more nuanced approaches.
Uniform and Gaussian-profile Beam Transmission for 2D Object across a Nonmagnetic Chiral Interface

Recent investigation of Fresnel coefficients (FCs) corresponding to a achiral/chiral (ACC) interface for p-polarization is extended to examine the transmitted amplitude profile of a 2D object/transparency under (a) uniform and (b) Gaussian-profile incident beams.
Multiplicity of dislocation pathways in a refractory multiprincipal element alloy

Refractory multiprincipal element alloys (MPEAs) are promising materials to meet the demands of aggressive structural applications, yet require fundamentally different avenues for accommodating plastic deformation in the body-centered cubic (bcc) variants of these alloys. We show a desirable combination of homogeneous plastic deformability and strength in the bcc MPEA MoNbTi, enabled by the rugged atomic environment through which dislocations must navigate. Our observations of dislocation motion and atomistic calculations unveil the unexpected dominance of nonscrew character dislocations and numerous slip planes for dislocation glide. This behavior lends credence to theories that explain the exceptional high temperature strength of similar alloys. Our results advance a defect-aware perspective to alloy design strategies for materials capable of performance across the temperature spectrum.
Characterization and quantification of necrotic regions and morphology in multicellular tumor spheroids using optical coherence tomography

Three-dimensional (3D) cell culture models are developed as a promising platform to screen anticancer therapeutics and treatments. However, current imaging techniques cannot provide 3D structures of tumor spheroids in situ. In this study, we employed label-free and noninvasive optical coherence tomography (OCT) for imaging and quantifying the 3D structures of tumor spheroids. We imaged ovarian cancer spheroids with OVCAR-8 cell line over a period of 10 days with 5,000 and 50,000 initial cell numbers. We successfully reconstructed the 3D necrotic regions via label-free intrinsic scattering attenuation contrast and evaluated the effect of Cisplatin treatment on tumor spheroids.
Cannabis Marketing and Problematic Cannabis Use Among Adolescents.

Objective:Health consequences of commercializing nonmedical cannabis remain unclear, but data suggest that youth may encounter unintended risks. This study examined whether cannabis marketing expos...
Identification of Clinical Predictors of Benefit of Palliative Thoracic Radiotherapy.

PURPOSE/OBJECTIVE(S) Palliative thoracic radiotherapy (PTRT) is frequently utilized for relief of pain, obstruction and hemoptysis from lung and bronchial primary tumors and metastatic disease. Historically, the prognosis for these patients has been dismal with radiotherapy (RT) often serving as a last line of therapy. However, with continued advancements in systemic therapies for non-small cell lung cancer (NSCLC), small cell lung cancer (SCLC) and other malignancies, PTRT may provide increased benefit both in relief of symptoms and prolongation of life for select patients. In this study, we sought to determine clinical predictors of benefit of PTRT in a contemporary cohort of patients with the goal of aiding in appropriate patient selection for escalation or de-escalation of RT in patients with locally advanced or metastatic disease. MATERIALS/METHODS Patients treated with standard palliative courses of RT, including 8 Gy/1 fx, 20 Gy/5 fx, and 30 Gy/10 fx, to the thoracic cavity between 2014 and 2020 were identified. Clinical information was collected, including age, ECOG PS, histology, stage, presence of brain metastases, presence of lung collapse, lines of previous systemic therapy, neutrophil-lymphocyte ratio (NLR), mutational status, and survival outcomes. Kaplan-Meier analyses were used for survival and sensitivity analyses. Cox regression was performed for multivariate analysis. RESULTS 161 evaluable patients were identified who received PTRT for various indications including dyspnea, SVC syndrome, hemoptysis, pain and obstruction/lung collapse. A majority of patients (61%) had a diagnosis of NSCLC, although SCLC (10%) and other histologies (29%) were also included. 94% of patients were metastatic at the time of receipt of PTRT. Multivariate analysis identified female sex, multi-fraction regimens, better baseline ECOG performance status, presence of an actionable mutation, absence of brain mets, and non-lung histologies as positive predictors of survival following PTRT (P < 0.05). Other factors including age, number of lines of systemic therapy and NLR were not identified as independent predictors in this cohort in either multivariate or univariate analyses. Notably, 14 patients failed to complete prescribed therapy all of whom had ECOG PS of 2 or greater at start of RT. CONCLUSION Patients with symptomatic lung disease derive differential benefit from PTRT with ECOG 0-1, absence of brain mets and presence of actionable mutations important clinical predictors of longer-term survival following treatment. Single fraction courses should be strongly considered for poor PS patients who may derive less significant survival benefit from PTRT and are at higher risk for early treatment discontinuation.
The Transformation of Mathematics in the Early Mediterranean World: From Problems to Equations

Acknowledgements Introduction 1. The problem in the world of Archimedes 2. From Archimedes to Eutocius 3. From Archimedes to Khayyam Conclusion References Index.
Effects of gust-induced and maneuvering acceleration stress on pilot-vehicle performance

Piloted motion simulator study of gust induced and maneuvering acceleration stress on pilot performance in low level mission
Understanding individual differences in language development across the school years

1. Background of the Study, J.B. Tomblin. 2. General Design and Methods, J.B. Tomblin. 3. The Character and Course of Individual Differences in Spoken Language, J.B. Tomblin, M.A. Nippold, M.E. Fey, X. Zhang. 4. Features of Language Impairment in the School Years, J.B. Tomblin, M. Nippold. 5. The Role of Processing in Children and Adolescents with Language Impairment, L.B. Leonard, S.E. Weismer, C. Weber-Fox, C.A. Miller. 6. The Relationship Between Language and Reading Abilities. H.W. Catts, M. Fey, S.E. Weismer, M.S. Bridges. 7. Educational and Psychosocial Outcomes of Language Impairment in Kindergarten, J.B. Tomblin.
Some Parameters Affecting the Performance of Pneumatic Tires on Wet Pavement

Runway condition and tire tread design in relation to pneumatic tire braking and directional control on wet pavement
Carcinoma of vagina 10 or more years following pelvic irradiation therapy

Gynecologic cancer records of 4,238 patients treated between 1956 and 1974 were reviewed. Sixteen patients developed noeplasia in the cervix or vagina 10 or more years following pelvic irradiation. Three patients had squamous carcinoma in situ; the other 13 patients had invasive squamous cancer involving the upper vagina. Only 1.26 per cent of invasive carcinoma of the cervix treated by radiation therapy from 1956 to 1966 presented with a late or recurrent or new primary tumor involving the vagina or cervix 10 or more years after primary treatment. The authors conclude that the risk of developing radiation-induced carcinoma in the upper vagina or cervix following pelvic irradiation is low. Follow-up Pap smears are indicated for all patients treated for cervical or vaginal malignancies by radiation therapy in order to detect vaginal neoplasia as well as recurrent carcinoma of the cervix.
Algebraic computer aided-design with Maple V2

This paper describes implicit_solids which implements implicit solid modeling (ISM) using MapleV2. Implicit solid modeling refers to the method that uses an implicit function to define a composite object. Various primitives are pre-defined and joined using Boolean operations to form the resulting implicit function [Storti et al. 1992].
Activation of the small GTPases, rac and cdc42, after ligation of the platelet PAR-1 receptor.

Stimulation of platelet PAR-1 receptors results in the rapid (10 to 30 seconds) and extensive (30% to 40% of total) guanosine triphosphate (GTP) charging of endogenous platelet rac, previously identified as a possible key intermediate in the signal pathway between PAR-1 and actin filament barbed-end uncapping, leading to actin assembly. During PAR-1–mediated platelet activation, rac distributes from the cell interior to the cell periphery, and this reorganization is resistant to the inhibition of PI-3-kinase activity. Rac, in resting or activated platelets, is Triton X-100 soluble, suggesting that it does not form tight complexes with actin cytoskeletal proteins, though its retention in octyl-glucoside-treated platelets and ultrastructural observations of activated platelets implies that rac binds to plasma membranes, where it can interact with phosphoinositide kinases implicated in actin assembly reactions. PAR-1 stimulation also rapidly and extensively activates cdc42, though, in contrast to rac, some cdc42 associates with the actin cytoskeleton in resting platelets, and the bound fraction increases during stimulation. The differences in subcellular distribution and previous evidence showing quantitatively divergent effects of rac and cdc42 on actin nucleation in permeabilized platelets indicate different signaling roles for these GTPases.
The Disruption Costs of Post–9–11 Security Measures and Cities’ Bids for Presidential Nominating Conventions

ABSTRACT:Over the past several decades, cities have increasingly built facilities and amenities to attract tourism, conventions, and mega-events. Mega-events bring cities tourism revenues and free media attention to brand themselves. We theorize regarding why cities seek to host presidential nominating conventions and why the increased disruption costs of the post–9–11 security environment have changed the way cities evaluate the branding opportunities of mega-events. Consistent with our predictions, larger and more tourism-dependent cities are less likely to need the branding opportunities of political conventions than their competitors and therefore are less willing to incur the disruption costs of political conventions after 9–11.
Humane Ecologist: Carl Sauer As Metaphor?

(1987). Humane Ecologist: Carl Sauer As Metaphor? The Professional Geographer: Vol. 39, No. 4, pp. 412-413.
Iterative improvement of a Gaussian classifier

Abstract In practical pattern recognition applications, the Gaussian classifier is often sub-optimal because some features are non-Gaussian or even discrete valued, the class statistics are only estimated, and the covariance matrix inversions can be ill-conditioned. We attack these problems by mapping the Gaussian classifier to a sigma-pi neural network, to which it is isomorphic. Back-propagation learning is then used to improve classifier performance. This approach is applied to the problem of hand-printed numeral recognition and to the problem of image texture classification. For both problems, significant improvement in classification error percentages are observed for both the training data and testing data. In addition, weights due to the mapping procedure are shown to be better than purely random initial weights.
The ARF Workstation: A new application of human-computer interface principles

Abstract The ARF Workstation is an interactive color workstation used by meteorologists to enter aviation weather forecasts for large geographic areas. Over the past six years, this Workstation has been iteratively designed, tested, and modified to develop a human-computer interface, which offers a flexible environment for entering precise weather forecasts in a timely manner. The result is an engineering model of workstations that will be placed in operational meteorological environments in the future. This paper presents this new Workstation's interface features and some of the human-computer interface principles that were effectively used in implementing these features.
Regime change and nation building: can donors restore governance in post-conflict states?

Foreign aid agencies and international assistance organisations are now heavily involved in nation building in post-conflict states. Their record of strengthening democratic governance in countries where civil war or military force replaced unpopular regimes is mixed. Experience suggests that a complex set of conditions must be created quickly in order to rebuild indigenous governance. Ensuring security, providing assistance through a transparent and coherent plan of action, coordinating donors' activities, establishing strong and legitimate national authority, strengthening democratic political processes, transferring responsibility and resources for development to a new government, stabilising the economy and strengthening social capital and human assets must all be done in quick succession. Achieving these goals requires a cadre of civilian and, sometimes, military personnel with expertise in post-conflict nation building. The frequency with which government aid programmes and international assistance organisations engage in post-conflict reconstruction also suggests the need for more explicit national and international policies and the creation of specialised nation-building agencies to undertake these difficult tasks. Copyright © 2005 John Wiley & Sons, Ltd.
Superquadric tensor glyphs

Tensor field visualization is a challenging task due in part to the multi-variate nature of individual tensor samples. Glyphs convey tensor variables by mapping the tensor eigenvectors and eigenvalues to the orientation and shape of a geometric primitive, such as a cuboid or ellipsoid. Though widespread, cuboids and ellipsoids have problems of asymmetry and visual ambiguity. Cuboids can display misleading orientation for tensors with underlying rotational symmetry. Ellipsoids differing in shape can be confused, from certain viewpoints, because of similarities in profile and shading. This paper addresses the problems of asymmetry and ambiguity with a new tunable continuum of glyphs based on superquadric surfaces. Superquadric tensor glyphs enjoy the necessary symmetry properties of ellipsoids, while also imitating cuboids and cylinders to better convey shape and orientation, where appropriate. The new glyphs are demonstrated on fields of diffusion tensors from the human brain.
Improvement of potato protein II. Selection for protein and yield

The improvement of potato protein appears feasible by selecting high protein parents and crossing them with adapted Group Tuberosum parents. Initial hybrids were obtained with about 10% protein which is double that of Red Pontiac. This protein is of high nutritional value when compared to whole egg protein. Some of the hybrids appear to have yields approaching standard varieties. Specific gravity values are also comparable.
National Trends in Psychotropic Medication Polypharmacy in Office-Based Psychiatry

Context Psychotropic medication polypharmacy is common in psychiatric outpatient settings and, in some patient groups, may have increased in recent years. Objective To examine patterns and recent trends in psychotropic polypharmacy among visits to office-based psychiatrists. Design Annual data from the 1996-2006 cross-sectional National Ambulatory Medical Care Surveys were analyzed to examine patterns and trends in psychotropic polypharmacy within nationally representative samples of 13 079 visits to office-based psychiatrists. Setting Office-based psychiatry practices in the United States. Participants Outpatients with mental disorder diagnoses visiting office-based psychiatrists. Main Outcome Measure Number of medications prescribed in each visit and specific medication combinations. Results There was an increase in the number of psychotropic medications prescribed across years; visits with 2 or more medications increased from 42.6% in 1996-1997 to 59.8% in 2005-2006; visits with 3 or more medications increased from 16.9% to 33.2% (both P Conclusions There has been a recent significant increase in polypharmacy involving antidepressant and antipsychotic medications. While some of these combinations are supported by clinical trials, many are of unproven efficacy. These trends put patients at increased risk of drug-drug interactions with uncertain gains for quality of care and clinical outcomes.
The thermal cycling effect on Ti-Ni-Cu shape memory alloy

Nearly equiatomic Ni-Ti alloys are known as the best shape memory alloys for their outstanding shape memory characteristics including shape memory effect and transformation pseudoelasticity. The present study was conducted to compare the transformation behaviors of Ni-Ti and Ti-Ni-Cu alloys during cycling. The samples were first subjected to one of the following 3 treatments: solution treatment; annealing after cold working; aging after solution treatment and then were thermal cycled under exactly the same conditions before they were examined by means of electrical resistivity measurements. One of the strengths of Ni-Ti alloy systems, besides good shape memory properties, has always been their high resistance to corrosion. This has made much practical use possible. Naturally, when the authors adopt the Cu-replacement approach in establishing with the new Ti-Ni-Cu systems, they want to make sure this resistance to corrosion will not be sacrificed. Tests to this effect were included in the experiment.
The perception of transcendent interest: Communication and identification in an emergent community

Abstract The interrelationships among five variables were analyzed in an effort to understand the process of community formation in a culturally plural metropolitan environment. The variables—perception of transcendent interest, perception of commonality, cooperative interaction, maintenance adaptation, and growth adaptation—were formulated by explicating and synthesizing the concepts of community, community identification, and coorientation. The perception of transcendent interest, described as the focal point of identification, and the basis of an emerging community, was found to correlate significantly with all the other four variables, but to be best predicted by cooperative interaction and maintenance adaptation. The study offers insight into the processes of acculturation and cultural group formation in a plural system.
β-Glucanase of yeast

Abstract The basal cell wall structure of yeasts which is responsible for the shape and rigidity of the yeast cell is a β-glucan, containing both β 1,3 and β 1,6 linkages (Phaff, 1963) . During conjugation, two yeast cells of opposite mating type fuse by dissolution of cell wall material between them, leading to a typical dumbbell-shaped zygote (Conti and Brock, in preparation). Because this morphogenetic process involves new protein synthesis (Brock, 1961) , it seems reasonable that enzymes which attack the basal cell wall structure are involved in the conjugation process, and attention has thus been focused on the β-glucanases of yeast. Although extensive work has been done on β-glucanases of filamentous fungi (Reese and Mandels, 1963) , mainly in relation to deterioration phenomena, no work has apparently been done on the yeast enzymes. The present paper will show that yeasts contain intracellular β-glucanase activity of a peculiar nature. In addition, this paper will show that yeast β-glucanase can be mistaken for β-glucosidase, since it hydrolyzes the chromogenic substrate p-nitrophenyl-β-D-glucoside (PNPG), although it does not hydrolyze other simple aryl and alkyl glucosides.
Greater pupillary escape differentiates central from peripheral visual field loss.

Abstract Objective To test whether pupil escape observed during a constant light stimulus was greater in eyes with central visual field loss compared to eyes with peripheral visual field loss and normal eyes. Design Comparative, observational case series. Participants Twenty-seven normal subjects, 5 patients with central field loss, 11 patients with peripheral field loss, and 8 patients with combined loss (central and peripheral visual field loss) were tested. Methods A dual-channel infrared pupillograph was used to simultaneously record the right and left pupil diameters at a rate of 60 Hz to characterize the initial, phasic pupil contraction, and the sustained, or prolonged, pupil contraction in response to a 5-second light stimulus. Full-field light stimuli with a diameter of 30° were presented to each eye at seven different intensities. Main outcome measures The amplitude of the phasic pupil contraction was compared with the amplitude of the sustained pupil contraction at the four brightest intensities (slope of phasic versus sustained contraction) in the normal eyes and in eyes with visual field loss in the center and the periphery. Results The sustained pupillary contraction showed a statistically greater reduction in proportion to the phasic component in eyes with central field loss compared to those with peripheral field loss, combination central and peripheral field loss, and normal eyes. Conclusions Afferent neurons from the central retina normally contribute a substantial component to the sustained pupil response. Eyes with central field loss can be distinguished from eyes with peripheral field loss by a relatively greater loss of the sustained response, causing greater pupil escape. This study showed that pupil movements in response to a nonperimetric full-field light stimulus may provide some degree of mapping of retinotopic sensitivity. This information may be of use in interpreting the pupillary movements during the swinging flashlight test and may help predict the pattern of visual field loss.
Does Parenting Shield Youth From Exposure to Violence During Adolescence? A 5-Year Longitudinal Test in a High-Poverty Sample of Minority Youth

Five waves of longitudinal data collected from 349 African American youth living in extreme poverty were used to determine if parental monitoring shielded youth from exposure to violence during adolescence. Semiparametric group— based modeling was used to identify trajectories of parental monitoring and exposure to violence from T1 to T5. Results from these analyses revealed (a) about 52% of youth had a trajectory of hypervigilant parental monitoring and (b) two out of the five distinct trajectories of exposure to violence were low and/or declining over the 5-year time period. Multivariate findings indicated that (a) youth with a trajectory of hypervigilant parenting were 109% more likely to have middle-declining exposure to violence, but hypervigilant parenting was unrelated to stable and low exposure to violence T1 to T5. The theoretical and policy implications of these findings as well as areas for future research are also discussed.