cssi/SciSciGPT-SciSciNet huggingface dataset:
18F-FDG PET/CT Monitoring of Response to Programmed Death Protein 1 Blockade in Metastatic Basal Cell Carcinoma.

ABSTRACT A 73-year-old woman with history of metastatic basal cell carcinoma presented with a large spinal mass demonstrating a high mutational burden of 111 mutations/Mb. She underwent T12 corpectomy and T10-L3 posterior spinal fusion followed by adjuvant radiation. After 2 years of surveillance, FDG PET/CT and a contrast-enhanced MRI revealed recurrence, prompting salvage therapy with the hedgehog signaling pathway inhibitor, sonidegib, which only transiently stabilized the disease. An off-label treatment with the programmed death protein 1 inhibitor, pembrolizumab, was initiated. Serial FDG PET/CT showed gradual decline in tumor metabolism over the next 12 months, leading to complete metabolic response.
Optimizing Benchmark-Based Portfolios with Hedge Funds

Hedge funds typically have non-normal return distributions marked by significant positive or negative skewness and high kurtosis. Mean-variance optimization models ignore these higher moments of the return distribution. This article introduces a new stochastic programming model which incorporates Monte Carlo simulation and optimization to examine the effects on the optimal allocation to hedge funds given benchmark related investment objectives such as expected shortfall and semi-variance. The results show that a substantial allocation—approximately 20% to hedge funds is justified. Specifically, the return distributions of portfolios constructed using the stochastic programming model skew to the right relative to those of the optimal mean-variance portfolios, resulting in higher Sortino ratios.
Apolipoproteins L1-6 share key cation channel-regulating residues but have different membrane insertion and ion conductance properties

The human apolipoprotein L gene family encodes the apolipoprotein L1–6 (APOL1–6) proteins, which are effectors of the innate immune response to viruses, bacteria and protozoan parasites. Due to a high degree of similarity between APOL proteins, it is often assumed that they have similar functions to APOL1, which forms cation channels in planar lipid bilayers and membranes resulting in cytolytic activity. However, the channel properties of the remaining APOL proteins have not been reported. Here, we used transient overexpression and a planar lipid bilayer system to study the function of APOL proteins. By measuring lactate dehydrogenase release, we found that APOL1, APOL3, and APOL6 were cytolytic, whereas APOL2, APOL4, and APOL5 were not. Cells expressing APOL1 or APOL3, but not APOL6, developed a distinctive swollen morphology. In planar lipid bilayers, recombinant APOL1 and APOL2 required an acidic environment for the insertion of each protein into the membrane bilayer to form an ion conductance channel. In contrast, recombinant APOL3, APOL4, and APOL5 readily inserted into bilayers to form ion conductance at neutral pH, but required a positive voltage on the side of insertion. Despite these differences in membrane insertion properties, the ion conductances formed by APOL1-4 were similarly pH-dependent and cation-selective, consistent with conservation of the pore-lining region in each protein. Thus, despite structural conservation, the APOL proteins are functionally different. We propose that these proteins interact with different membranes and under different voltage and pH conditions within a cell to effect innate immunity to different microbial pathogens.
Potentially Inappropriate Medication Use in Elderly Patients with Diffuse Large B-Cell Lymphoma Predicts Inferior Survival and Treatment-Related Toxicities

Abstract Background: Survival outcomes for older patients with diffuse large B-cell lymphoma (DLBCL) are disproportionally inferior to those of younger patients. While differences in tumor biology may play a role, older patients are often frail with comorbidities, polypharmacy, and use potentially inappropriate medications (PIM) such as anticholinergics and benzodiazepines. Methods: Using Cox proportional hazard and logistic regression models, we analyzed all DLBCL patients age ≥60 treated at our two affiliated hospitals from 2009-2014 to examine the association of polypharmacy and PIM use with progression-free survival (PFS), overall survival (OS), and treatment-related toxicities. Results: In this updated and final analysis, we included 132 patients with complete records from these two hospitals. They share similar demographic, clinical, and laboratory characteristics except for higher International Prognostic Index (IPI) in patients from one hospital. The median age was 70 years (range 65-76). At the time of diagnosis, 47% of patients used more than 4 medications (polypharmacy) and 48% used at least one PIM. Only 42% of patients received first-line chemotherapy of adequate relative dose intensity (>85% dosage), and 66% experienced ≥grade 3 toxicities. PIM use and polypharmacy were associated with shortened PFS and OS by log-rank test. Most importantly, PIM use remained an independent predictor of PFS, OS, and ≥grade 3 toxicities in multivariable analysis (Table 1). Conclusion: This is the first report of significantly adverse survival impacts of PIM use in elderly patients with DLBCL, presumably from drug-drug interactions that increase toxicities and impair the delivery of adequate chemotherapy dosage. Our findings support the use of evidence-based geriatric principles to guide meticulous medication management to improve outcome disparity for these patients. Download : Download high-res image (74KB) Download : Download full-size image Disclosures Diefenbach: Genentech: Consultancy, Honoraria, Research Funding.
Accessibility Matters: Universal Design and the Online Professional Practice Doctorate

Online doctoral programming geared toward working professionals can provide unprecedented flexibility in terms of time and place that affords greater access to a broader student demographic. At the same time, online learning poses its own unique set of challenges and limitations for students with and without disabilities. Universal Design (UD) is a framework built around the idea of proactively identifying and removing barriers to learning in the environment, pedagogical practices, and materials. In this essay, we highlight the necessity and relevance of UD to online doctoral programs and share insights related to its use in our program from faculty and student perspectives.
The Database of Award-Winning Children's Literature

Abstract This article describes the creation and features of the Database of Award-Winning Children's Literature (DAWCL), its users, how they use it, and what improvements are anticipated.
Unified Pharmacophoric Model for Cannabinoids and Aminoalkylindoles

Despite their obvious structural dissimilarities, the cannabinoids and aminoalkylindoles (AAIs) are known to exhibit similar in vitro and in vivo cannabimimetic activities1–6. This body of evidence suggests that the cannabinoids and AAIs interact with the same cannabinoid receptor and share at least some regions in common when bound to the receptor to elicit the cannabinoid activity. In support of this hypothesis, binding studies have shown that they compete for the same binding regions of the CB1 cannabinoid receptor7.
Seizures in adolescence. A review of patients admitted in an adolescent service.

The admissions of new seizure patients to an adolescent service over a 10-year period were retrospectively reviewed with regard to the patient's etiology, work-up, and outcome. Head trauma and pseudoseizures were common, 21% and 19%, respectively, In general, the outcome in adolescents appears to depend more on the underlying diagnosis than on how the seizure presents.
Theoretical considerations concerning the hammett equation — VIII

Abstract The resonance contribution, PR, to Hammett p values, and the Taft-Lewis parameter α have been calculated for five aromatic oxygen acids. The method of calculation consisted of a crude calculation by the LCAO MO method of the changes of charge distribution in an acid molecule effected by a substituent, and an assessment of the effect of this change on the free energy of dissociation by an electrostatic calculation. Values for πR and α were obtained using the calculated change in the free energy of dissociation. The electrostatic calculations were done by two methods, the Bjerrum method, and an approximate form of the Kirkwood-Westheimer method. Calculated values of πR and α are in reasonably good agreement with experimental values.
Understanding NAND’s Intrinsic Characteristics Critical Role in Solid State Drive (SSD) Design

The use of NAND flash-based SSDs in enterprises has grown at a ~33% compound annual growth rate [1] worldwide for the past three years. The majority of the growth comes from enterprise data center applications where the trend is to leverage the cost benefits of using MLC and TLC NAND flash memory by focusing on the use model behavior to optimize performance and life characteristics. In the data center, requirements for these MLC/TLC SSDs demand high sequential performance and reliability, moderate IOPS, and low power consumption along with maintaining 3 to 5 years of useful life. These challenges are tackled by tightening the links between the SSD’s operation, host operating environment, and intrinsic NAND memory behavior and by exploiting increasingly sophisticated controllers, firmware, and flash memory error management techniques.
Variation in Population and Life History Traits of the American Eel, Anguilla rostrata, in Four Rivers in Maine

We examined population traits of yellow American eels from nine sites with similar habitat characteristics in each of four rivers in Maine, U.S.A. Migrating silver eels were also collected to compare sex ratio, age and size at migration among the four rivers. Population density and biomass were not significantly different among rivers with mean ranges of 8.4–21.8 eels 100 m−2and 380–1485 g m−2. Pairwise comparisons of the slopes of weight–length relationships of log transformed data (pooled data: intercept = −6.007, slope = 3.094, r2= 0.99, and n = 3116) revealed no significant differences among rivers. Length–age relationships (pooled data: intercept = 87.826, slope = 23.444, r2= 0.76, and n = 2325) also showed no statistically significant pairwise differences in slopes among rivers. In all rivers, sexual differentiation was complete by 270 mm total length and age eleven. The sex ratios of migrating silver eels were not correlated with yellow eel sex ratios among the four rivers. Mean age at migration among the four rivers was significantly different for males only, with a range of 1.3 years. Both sexes had some significant differences in size at migration among rivers, but the biological importance of the differences is tenuous (male range: 15 mm, female range: 36 mm). The yellow and silver eel population traits from these four rivers showed little variation when riverine habitat was isolated. Variations in traits appeared to be greater when eels from non-riverine habitats may have been present.
High Precision Hypernuclear Spectroscopy Study by the (e,e'K) Reaction

Jefferson Lab experiment E89009 is the first experiment to study hypernuclear spectroscopy by (e,e' K{sup +}) reaction. The 12 / LambdaB spectrum was observed from carbon target with the best energy resolution ever achieved from direct measurement of hypernuclear spectrum. The comparisons of the 12 / LambdaB spectrum with theoretical predictions were provided in terms of excitation strength and level separations. The overall excitation is in accord with theoretical calculations. The binding energies of p-shell and s-shell Lambda states were extracted. The photo-production cross section of the 12 / LambdaB ground state was also extracted. The experiment is also the pioneer in detecting scattered electrons at near zero degrees. The benefit and lessons learned from this method was also discussed.
β-Galactosidase IN VIVO α-COMPLEMENTATION

Partial diploids were prepared from fourteen β-galactosidase nonsense mutant strains of Escherichia coli by adding an episomal element containing a β-galactosidase structural gene with a small deletion in the α region. Active enzyme was obtained from all strains with the exception of one in which the site of mutation is very close to the operator locus. The complemented enzyme was stable during growth. Dissociation in urea of a complemented enzyme followed by centrifugation showed heterogeneity of the prematurely terminated fragment, suggesting that an exposed overlapping segment had been subjected to proteolysis. The amount of complemented enzyme formed varied from strain to strain and was dependent in part on the tertiary structure of the nonsense fragment itself. The results are discussed in relation to the mechanism of folding of polypeptide chains.
The Retention Challenge—Should We Include Parents?

University campuses continue to see an increase in the number of helicopter parents, those parents who are hovering about the campus, ready to swoop down and rescue their children at the first sign of distress (Cartmell and McCullough 2014). Retention personnel on campus questioned whether it would be possible to develop initiatives that would intentionally guide parents in ways that help increase freshman retention rates. Research has been done and shown that students’ parents can serve as a safety net for their freshmen, increasing the students’ willingness to take on greater academic and social challenges (Kalsner and Pistole 2003). The difficulty for college campuses is how to capitalize on the untapped resource and determine whether it aids in greater retention and success of freshman students. Attachment theory is the basis for an innovative retention initiative that was developed at The University of Tennessee at Martin, which seeks to provide a landing pad for helicopter parents who want to be involved during their students’ first year. Incoming freshman parents are encouraged to take advantage of an online parent portal that contains academic resources and information about their child's college performance. The information provided on the portal is intended to help parents begin conversations with their students about how to succeed in the college arena. To measure the effectiveness of the initiative, a sample of 300 first-time, full-time freshmen from the fall 2012 entering freshman class was analyzed. Data were evaluated looking for student retention differences, as well as differences in the end-of-first-year grade point averages. Correlations were found between parent involvement and freshman retention, as well as grade point averages. Interestingly, the research also showed that there appears to be a point of diminishing returns associated to the amount of parental involvement.
Aligning expatriate managers’ expectations with complex global assignments

The purpose of this paper is to develop a theoretical, yet practical framework for managing unrealistic expectations of expatriate marketing managers relative to their role in complex global marketing assignments. The formation of these unrealistic expatriate marketing managers’ expectations is examined using relational contracting theory. We explore alternative HRM evaluation/support designs that can suppress the development of expatriate marketing managers’ entitlement process and thus enhance the reality of expatriate marketing managers’ expectations relative to the role in a subsidiary of the multinational enterprise.
Habitus, Scaffolding, and Problem-Based Learning: Why Teachers’ Experiences as Students Matter

Despite evidence that it can help students learn higher-order thinking skills and gain deep content knowledge, problem-based learning (PBL) is not deployed on a large scale in K-12 classrooms. This conceptual chapter explores teacher’s past experiences, and resulting habitus, to explain the minimal extent of PBL in K-12 schools. Central to teachers’ abilities to implement PBL is their ability to provide scaffolding, and their habitus may interfere with this process. Implications for teacher education and teacher change are discussed.
Family Work Through Time and Space: An Ecological Perspective

The goal of the current article is to describe how an ecological perspective could further our understanding of the division of labor in families. We consider how social contexts, or “space,” in conjunction with individual, family, social, and historical “time” influence the division of labor in families as well as its consequences for family members' well-being and relationship quality. Research is examined that explores how social class, race and ethnicity, family structure and life course issues directly and indirectly affect the division of labor in families. Using examples from current research, we show that at times the predictors and outcomes of the division of family labor differ as a function of the social context in which they occur and as a function of unique historical and social time periods. An ecological perspective provides a framework for considering how the complex power and influence processes in families play out in different ways as a function of social values and norms reflected in our race and ethnicity, social class, gender, life stage, and family structure.
Molecular diagnosis of sarcomas: chromosomal translocations in sarcomas.

Abstract Context.—Sarcomas are rare, numerous in type, and often difficult to definitively classify. Work in the last 2 decades has revealed that a significant subset of sarcomas are associated with specific chromosomal translocations producing chimeric (fusion) genes that play a role in the sarcomas' biology and are helpful in their differential diagnosis. Objective.—To briefly review the sarcomas associated with specific translocations presenting Ewing sarcoma and synovial sarcoma as archetypes and to further explain how cytogenetic and molecular biologic approaches are being used in the diagnosis of sarcomas. Data Sources.—This work is based on a selected review of the relevant medical and scientific literature and our extensive experience with molecular testing in sarcomas. Conclusions.—In addition to, and complementing, the traditional diagnostic methods of examination of hematoxylin-eosin stained slides, immunohistochemistry, and sound clinical-pathologic correlation, additional cytogenetic and mole...
Perfect fluidity of the quark gluon plasma core as seen through its dissipative hadronic corona

Abstract The agreement of hydrodynamic predictions of differential elliptic flow and radial flow patterns with Au + Au data at s N N = 200 GeV is one of the main lines of evidence suggesting the nearly perfect fluid properties of the strongly coupled quark–gluon plasma, sQGP, produced at RHIC. We study the sensitivity of this conclusion to different hydrodynamic assumptions on hadro-chemical and thermal freezeout after the sQGP hadronizes. We show that if chemical freezeout occurs at the hadronization time, as required to reproduce the observed hadron yields, then, surprisingly, the differential elliptic flow, v 2 ( p T ) , for pions continues to increase with proper time in the late hadronic phase until thermal freezeout and leads to a discrepancy with the v 2 ( p T ) data. In contrast, if both hadro-chemical and thermal equilibrium are maintained past the hadronization point, then the mean transverse momentum per pion increases in a way that accidentally preserves v 2 ( p T ) from the sQGP phase in agreement with the data, but at the cost of the agreement with the observed hadronic yields. In order that all the data on (1) hadronic ratios, (2) radial flow, as well as (3) differential elliptic flow be reproduced, the sQGP core must expand with a minimal viscosity, η ≈ T c 3 , that is however even greater than the viscosity, η H ≈ T / σ H , of its hadronic corona. However, because of the large entropy density difference of the two phases of QCD matter, the larger viscosity in the sQGP phase leads to nearly perfect fluid flow in that phase while the smaller entropy density of the hadronic corona strongly hinders the applicability of Euler hydrodynamics in that phase. The “perfect fluid” property of the sQGP is thus not due to a sudden reduction of the viscosity at the critical temperature T c , but to a sudden increase of the entropy density of QCD matter and is therefore an important signature of deconfinement.
A zero-one stochastic programming model for personnel scheduling solved by a sequential simulation procedure:

A sequential simulation procedure (which requires shorter com puter running time than a nonsequential one) is an effective method for solving stochastic personnel scheduling models. The time needed for a particular employee to perform a given activ ity is assumed to be a random number with a given distribution.
Knee flexor moments during propulsion in cycling—A creative solution to Lombard's Paradox

Abstract The function of two joint muscles in the human lower extremity was studied during a cycling task with efficiency of their action discussed in light of Lombard's Paradox. Special pedals were designed to monitor reaction forces parallel to the sagittal plane of the body. Net moments of force about the hip, knee and ankle and EMG patterns in selected lower extremity muscles were recorded in five subjects pedalling against a constant load. The most original aspect of this study was the clear difference in hip and knee action during the propulsive phase of the pedalling cycle. A knee flexor moment was consistently observed in all subjects starting approximately half way through the propulsive phase of crank rotation (0–180°) and presented as a creative solution to Lombard's Paradox.
Geonium theory: Physics of a single electron or ion in a Penning trap

A single charged particle in a Penning trap is a bound system that rivals the hydrogen atom in its simplicity and provides similar opportunities to calculate and measure physical quantities at very high precision. We review the theory of this bound system, beginning with the simple first-order orbits and progressively dealing with small corrections which must be considered owing to the experimental precision that is being achieved. Much of the discussion will also be useful for experiments with more particles in the trap, and several of the mathematical techniques have a wider applicability.
Using the Blankinship algorithm to find the general solution of a linear diophantine equation

This paper shows that the Blankinship algorithm, originally proposed to find the greatest common divisor of several integers and a solution of the associated linear diophantine equation, can be used to find the general solution of the equation. This yields a more efficient method to find the general solution than the one proposed by Bond. The modification of Blankinship's algorithm to avoid generating vectors with huge component values is also proposed.
Calculating proton uptake/release and binding free energy taking into account ionization and conformation changes induced by protein–inhibitor association: Application to plasmepsin, cathepsin D and endothiapepsin–pepstatin complexes

The protein-inhibitor binding energies of enzymes are often pH dependent, and binding induces either proton uptake or proton release. The proton uptake/release and the binding energy for three complexes with available experimental data were numerically studied: pepstatin-cathepsin D, pepstatin-plasmepsin II and pepstatin-endothiapepsin. Very good agreement with the experimental data was achieved when conformational changes were taken into account. The role of the desolvation energy and the conformational changes was revealed by modeling the complex, the separated molecules in the complex conformation and the free molecules. It was shown that the conformational changes induced by the complex formation are as important for the proton transfer as the loss of solvation energy caused by the burial of interface residues. The residues responsible for the proton transfer were identified and their contribution to the proton uptake/release calculated. These residues were found to be scattered along the whole protein rather than being localized only at the active site. In the case of cathepsin D, these residues were found to be highly conserved among the cathepsin D sequences of other species. It was shown that conformation and ionization changes induced by the complex formation are critical for the correct calculation of the binding energy. Taking into account the electrostatics and the van der Waals (vdW) energies within the Boltzmann distribution of energies and allowing ionization and conformation changes to occur makes the calculated binding energy more realistic and closer to the experimental value. The interplay between electrostatic and vdW forces makes the pH dependence of the binding energy smoother, because the vdW force acts in reaction to the changes of the electrostatic energy. It was found that a small fraction of the ionizable groups remain uncharged in both the free and complexed molecules. The sequence and structural position of these groups aligns well within the three proteases, suggesting that these may have specific role.
Epidemiology, risk factors and management of cardiovascular diseases in IBD

IBD is an established risk factor for venous thromboembolism. In the past few years, studies have suggested that patients with IBD might also be at an increased risk of coronary heart disease and stroke. The increased risk is thought to be similar to the level of risk seen in patients with other chronic systemic inflammatory diseases such as rheumatoid arthritis. The risk of developing these conditions is particularly increased in young adults with IBD, and more so in women than in men. Conventional cardiovascular risk factors are not over-represented in patients with IBD, so the increased risk could be attributable to inflammation-mediated atherosclerosis. Patients with IBD often have premature atherosclerosis and have biochemical and genetic markers similar to those seen in patients with atherosclerotic cardiovascular disease. The role of chronic inflammation in IBD-associated cardiovascular disease merits further evaluation. Particular attention should be given to the increased risk observed during periods of increased disease activity and potential modification of the risk by immunosuppressive and biologic therapies for IBD that can modify the disease activity. In addition, preclinical studies suggest that cardiovascular medications such as statins and angiotensin-converting enzyme inhibitors might also favourably modify IBD disease activity, which warrants further evaluation.
Search Engine Queries Used to Locate Electronic Theses and Dissertations: Differences for Local and Non-Local Users

Purpose – The purpose of this paper is to examine two research questions: What search engine queries lead users to the Auburn University electronic theses and dissertations (AUETDs) collection? Do these queries vary for users in different locations and, if so, how? Design/methodology/approach – Search engine queries used to locate the AUETDs collection were obtained from Google Analytics and were separated into groups based on user location. These queries were assigned to empirically derived categories based on their content. Findings – Most local users’ queries contained person names, variants for thesis or dissertation, and variants for Auburn University. Over a third were queries for the AUETDs collection, while the remainder were seeking theses and dissertations from specific Auburn researchers. Most out-of-state users’ queries contained title and subject keywords and appeared to be seeking specific research studies. Queries from users located within the state but outside of the local area were interm...
Modeling the Effects of Melanoma Education on Visual Detection: A Gradient Shift Analysis

Early detection is critical to successful treatment of melanoma, and at-risk individuals often are educated about melanoma by showing them examples of symptom-free and highly symptomatic lesions. We explain why, according to principles of stimulus control, this common practice could discourage the detection of newly developed symptoms and present an experiment modeling the predicted effects. Using images depicting a continuum of melanoma symptom severity, we familiarized participants with a symptomatic lesion (S+), and then conducted generalization tests to determine how often they would label other degrees of symptom severity as the same as (unchanged from) S+. During training for a group that was modeled after typical melanoma education efforts, S- was an asymptomatic lesion. For passive and active control groups, respectively, S- was either absent or a more severely symptomatic lesion. In generalization tests, gradient shift occurred such that stimuli similar to S- were especially unlikely to be called “same.” For the target group, this resulted in reduced labeling of mildly symptomatic lesions as symptomatic. We discuss the implications of these findings for melanoma education efforts.
Polypeptide stimulators of the Ms-Lon protease

Both the peptidase activity against small fluorescent peptide substrates and the ATPase activity of Lon (La) proteases are stimulated by unstructured proteins such as alpha-casein. This stimulation reveals the simultaneous interaction of Lon with two proteolytic substrates--alpha-casein and the peptide substrate. To understand the cellular function of this stimulation, it is important to determine the physical properties of Lon stimulators. The abilities of compositionally simple random copolymers of amino acids (rcAAs) to stimulate the peptidase and ATPase activities of the Lon protease from Mycobacterium smegmatis (Ms-Lon) and its N-terminal truncation mutant (N-E226) were determined. We report that cationic but not anionic rcAAs stimulated Ms-Lon's peptidase activity but were themselves poor substrates for the enzyme. Peptidase stimulation by rcAAs correlated approximately with the degree of hydrophobicity of these polypeptides and reached levels >10-fold higher than observed previously for Ms-Lon stimulators such as alpha-casein. In contrast to alpha-casein, which stimulates Ms-Lon's peptidase activity by 40% and ATPase activity by 150%, rcAAs stimulated peptidase activity without concomitant stimulation of ATPase activity. Active site labeling experiments suggested that both rcAAs and ATP increased peptidase activity by increasing accessibility to the peptidase active site. Peptidase activity assays in the presence of both alpha-casein and rcAAs revealed that interactions of rcAAs and alpha-casein with Ms-Lon are extremely complex and not mutually exclusive. Specifically, (1) additions of low concentrations of alpha-casein (<50 microg/mL) caused a further stimulation of Ms-Lon's rcAA-stimulated peptidase activity; (2) additions of higher concentrations of alpha-casein inhibited Ms-Lon's rcAA-stimulated peptidase activity; (3) additions of all concentrations of alpha-casein inhibited N-E226's rcAA-stimulated peptidase activity. We conclude the Ms-Lon can interact with an rcAA, alpha-casein, and a substrate peptide simultaneously, and that formation of this quaternary complex requires the N-terminal domain of Ms-Lon. These data support models of Ms-Lon that include two allosteric polypeptide binding sites distinct from the catalytic peptidase site.
SU‐FF‐T‐05: A Biological Model‐Based 4‐D Lung IMRT Plan Optimization Algorithm

Purpose: To spare the normal lung we developed a novel lungIMRT plan optimization algorithm that incorporates both biological model and respiratory motion. Method and Materials: We implemented a novel IMRToptimization algorithm on an in‐house IMRT planning system that interfaces with an Eclipse® workstation (Varian, Palo Alto, CA). The IMRT objective function is a combination of the normal lungtissue complication probability (NTCP), the equivalent uniform dose (EUD), and a penalty on tumor dose in‐homogeneity. A series of 4‐D CT scans were taken at different breath phases and a deformable registration was applied to trace voxel‐to‐voxel correspondence at each snapshot. The time averaged (4‐D) dose was utilized to calculate the NTCP and EUD in the optimization process. The proposed method was compared with the gated IMRT approach, which allowed a residual respiratory motion of 3mm and used a PTV defined as the union of the tumors at different phases within the gating window. The performance of the two approaches was evaluated via comparison of DVH at the exhale phase of the breathing cycle and quantitative parameters such as V20, V10, and the mean lung dose. Results: Five‐field 6MV IMRT beams were setup to deliver a total dose of 63Gy in 35 fractions. Each plan was renormalized such that the prescribed dose covers 95% of the tumor volume. Comparing with the gated IMRT plan, our proposed method resulted in a reduction of 4.3%, 4.4%, 2.2Gy and 11.2%, in terms of V10, V20, the mean dose and NTCP, respectively. Meanwhile, the EUD obtained by our method was 65.6Gy, slightly higher than 64.5Gy obtained by the gated IMRT approach. Conclusion: Compared with the gated lungIMRT approach, the proposed biological model‐based 4‐D lungIMRT plan optimization algorithm is able to further spare the healthy lungtissue while maintaining relatively homogeneous tumor coverage.
KLF6 allelic loss is associated with tumor recurrence and markedly decreased survival in head and neck squamous cell carcinoma

The Kruppel-like transcription factor (KLF6) gene is a tumor suppressor gene (TSG) reported to be dysregulated and inactivated through loss of heterozygosity (LOH) and/or somatic mutation in a number of major human cancers. The aim of the present study was to examine KLF6 gene status and expression in head and neck squamous cell carcinomas (HNSCC). A collection of 81 well-characterized oral and oropharyngeal HNSCC samples were analyzed for evidence of KLF6 LOH and mutation and differences in expression patterns between normal and cancerous tissues and these findings were correlated with clinicopathological variables. We also tested the effect of KLF6 inhibition in HNSCC cell lines on proliferation and p21 expression. LOH was found in approximately 30% of cases and was strongly correlated with cancer progression, tumor recurrence and decreased patient survival. Overall, median survival of patients with LOH was less than half (19 vs. 41 months, p = 0.036, stratified on stage) than those without loss. Risk of death for patients with LOH was 8 times greater independent of tumor size, nodal status, tobacco smoking or treatment modality (HR 7.89, 95% CI: 1.9–32.4). Subsequent analyses revealed KLF6 mutations in only 2 of 20 samples, but altered subcellular protein localization in 64% of tumors. Targeted stable reduction of KLF6 in HNSCC cell lines increased cellular proliferation while decreasing p21 expression. Taken together, these findings suggest that KLF6 LOH represents a clinically-relevant biomarker predicting patient survival and tumor recurrence and that dysregulation of KLF6 function plays an important role in HNSCC progression. © 2007 Wiley-Liss, Inc.
TTAA serves as the target site for TFP3 lepidopteran transposon insertions in both nuclear polyhedrosis virus and Trichoplusia ni genomes

We have analysed TFP3 transposable elements from five independently isolated FP mutants of the Autographa californica nuclear polyhderosis virus (AcMNPV). We also analysed genomic copies of TFP3 elements amplified from the DNAs of the Trichoplusia ni cell line (TN-368) and T. ni larvae using the polymerase chain reaction (PCR). The sequences of all the newly isolated TFP3 elements closely resemble the previously described TFP3/1 element. Each of the transposons isolated from the virus mutants duplicated a TTAA tetranucleotide target site upon insertion into the viral genome. Four of these TFP3 elements transposed into three different 'TTAA' target sites within the 25 K gene (FP locus, map units 36-37 of AcMNPV). The fifth TFP3 element inserted at a 'TTAA' site within the AcMNPV Hin dIII-E fragment. One genomic TFP3 element, amplified from the TN-368 cell line DNA by an inverse PCR method, duplicated a 'TTAA' tetranucleotide target site that is present only once in the homologous larval DNA sequence. These data suggest that mobilization of TFP3 into both viral and cellular sites is identical in specificity and mechanism.
Computer System Response Time and Psychophysiological Stress II

With the advent of time-shared interactive systems, the psychological impact of system response time (SRT) and SRT variability (SRTV) has become an important issue. Carbonell, et. al. (1968) have s...
Effect of elemental diet on albumin and urea synthesis: Comparison with partially hydrolyzed protein diet

Enhanced nitrogen utilization occurs when adults with gastrointestinal disease are fed partially hydrolyzed proteins instead of isonitrogenous, isocaloric crystalline amino acids. A controlled trial was conducted to determine if this difference was also seen in malnourished stressed cancer patients and to gain an understanding of the underlying mechanism. Sixteen malnourished patients with head and neck cancer were prospectively randomized to either crystalline amino acid-glucose (CAA-G) or partially hydrolyzed protein-glucose (PHP-G) diets. Patients were fed via an enteral tube for 10 days starting on the second postoperative day. Blood SMA-6 and amino acid levels were measured on Days 1 and 10. Daily calorie counts and fluid balance were obtained. Daily 24-hr urine and stools were analyzed for total N during the last 5 days of the study period. The daily positive N balance with both diets was the same (CAA-G = +7.8 +/- 0.8 vs PHP-G = +8.2 +/- 1.0 g; mean +/- SE) and 3-methylhistidine:creatinine ratio did not differ. Patients on PHP-G diet gained significantly more weight (+0.5 vs - 1.5 kg; P less than 0.01) and had significantly higher serum albumin (3.2 +/- 0.2 vs 2.8 +/- 0.1 g/dl; P = 0.5) by the end of the 10th study day. Weight changes were not due to fluid retention: serum Na+, K+, creatinine and mean fluid intake for the two groups remained the same during the study period. A significantly greater rise in BUN occurred on the CAA-G diet (from 9.2 +/- 1.7 to 15.4 +/- 1.4 mg/dl; P less than 0.05) while BUN remained unchanged on the PHP-G diet.(ABSTRACT TRUNCATED AT 250 WORDS)
The Court, the Jury, and the Facts: Hastie et al.'s Inside the Jury

The proper jury decision rule is the rule of unanimity. This is the key conclusion drawn from a set of jury experiments reported in a new book by Hastie, Penrod, and Pennington (at 238). Their findings contradict the key factual assertion of certain recent decisions of the United States Supreme Court, namely that there is functional equivalence between juries operating under unanimity and majority rules, as well as between juries of different sizes. Inside the Jury is not the first analysis to expose the errors of the Court, but it is among the most powerful. The book should receive serious attention in the judicial as well as in the social science community.
Scattering theory of distortion correction by phase conjugation

The correction of wave distortions by the technique of optical phase conjugation is examined first on the basis of a newly derived integral equation for scattering of monochromatic scalar waves in the presence of a phase-conjugate mirror. The solution is developed in an iterative series, and the first- and second-order terms are analyzed and illustrated diagrammatically. A generalization of the integral equation is then presented, which takes into account the electromagnetic nature of light. It is also shown that, if the conjugate wave is generated without losses or gains and with a complete reversal of polarization, a total elimination of distortions may be achieved by this technique under circumstances that frequently occur in practice.
Does It Matter How Targeted Costs Are Achieved

The actions taken to achieve target costs can have different effects on product costs, warns the author. So management must focus on how target costs are met—and not just achieving the costs themselves. © 2000 John Wiley & Sons, Inc.
Water profile navigation with an Acoustic Doppler Current Profiler

A novel navigation method is introduced using water current profiles measured by an Acoustic Doppler Current Profiler (ADCP) mounted on a moving vehicle. These current profiles are combined with measurements of vehicle attitude and depth to simultaneously estimate the local current and the vehicle velocity. This velocity estimate can be integrated directly to give a position estimate, or it can be fused with measurements from other navigation sensors, such as an Inertial Navigation System (INS), Long Baseline (LBL) or Ultra-Short Baseline (USBL) acoustic tracking system. The method allows an underwater vehicle to maintain an estimate of its global position throughout all phases of its mission, including descent and ascent.
Impact of biodiesel source material and chemical structure on emissions of criteria pollutants from a heavy-duty engine.

Biodiesel is an oxygenated diesel fuel made from vegetable oils and animal fats by conversion of the triglyceride fats to esters via transesterification. In this study we examined biodiesels produced from a variety of real-world feedstocks as well as pure (technical grade) fatty acid methyl and ethyl esters for emissions performance in a heavy-duty truck engine. The objective was to understand the impact of biodiesel chemical structure, specifically fatty acid chain length and number of double bonds, on emissions of NOx and particulate matter (PM). A group of seven biodiesels produced from real-world feedstocks and 14 produced from pure fatty acids were tested in a heavy-duty truck engine using the U.S. heavy-duty federal test procedure (transient test). It was found that the molecular structure of biodiesel can have a substantial impact on emissions. The properties of density, cetane number, and iodine number were found to be highly correlated with one another. For neat biodiesels, PM emissions were essentially constant at about 0.07 g/bhp-h for all biodiesels as long as density was less than 0.89 g/cm3 or cetane number was greater than about 45. NOx emissions increased with increasing fuel density or decreasing fuel cetane number. Increasing the number of double bonds, quantified as iodine number, correlated with increasing emissions of NOx. Thus the increased NOx observed for some fuels cannot be explained by the NOx/PM tradeoff and is therefore not driven by thermal NO formation. For fully saturated fatty acid chains the NOx emission increased with decreasing chain length for tests using 18, 16, and 12 carbon chain molecules. Additionally, there was no significant difference in NOx or PM emissions for the methyl and ethyl esters of identical fatty acids.
Systems nanotechnology: Identification, estimation, and control of nanoscale systems

Technological advancements in synthesizing devices at the nanoscale has produced a variety of analogues to classical systems elements, such as sensors, actuators, and control systems. We review recent experimental literature on nanoscale devices that have been produced to have useful systems functionality, as well as efforts to employ these devices in identification, estimation, and control. The integration of these components is also discussed.
Use of a chronic prefemoral lymphatic fistula for monitoring systemic capillary integrity in unanesthetized sheep.

Abstract Alterations in fluid and protein flux across the soft tissue capillary resulting in edema formation is a common occurrence in the critically ill patient. The pathophysiology and therapeutic modalities for treating edema are poorly defined in large part due to the difficulty of monitoring capillary integrity. We have described a preparation using lymph flow (Q L ) from the prefemoral efferent lymphatic in sheep, which we have found to accurately reflect changes in capillary fluid and protein flux. The lymph fistula is easy to prepare and chronic studies can be performed in the unanesthetized state. A lung lymph fistula can be formed in the same animal which allows for the comparison of the pulmonary and systemic capillary effects of injury. We have found that prefemoral Q L responds in a predictible manner to changes in Starling forces reflecting in changes in fluid flux. We also determined that the soft tissue capillary responds differently to different systemic insults, increasing both fluid and protein flux with a contralateral burn injury and demonstrating no effect from endotoxemia. Prefemoral and lung lymph flow also responded differently to the same insult indicating the importance of studying both capillary systems simultaneously. These findings reflect the need to monitor the systemic capillary. We consider this lymph preparation to be very useful for this purpose.
Differential Tissue Factor (TF) Expression by Endothelial Cells (ECs) from Human Umbilical Vein Vs. Human Microvasculature • 763

Differential Tissue Factor (TF) Expression by Endothelial Cells (ECs) from Human Umbilical Vein Vs. Human Microvasculature • 763
Epidermal I-J-Bearing Cells Are Responsible for Transferable Suppressor Cell Generation After Immunization of Mice with Ultraviolet Radiation-Treated Epidermal Cells

Subcutaneous immunization of mice with hapten-coupled, ultraviolet radiation (UVR)-treated epidermal cells (EC) results in a hyporesponsive delayed-type hypersensitivity (DTH) response associated with the appearance of afferent-acting, hapten-specific T suppressor (Ts) cells. Depletion of I-J-bearing cells from the EC population prior to UVR-exposure and hapten coupling prevents the appearance of these Ts cells. However, non- UVR-treated EC depleted of I-J-bearing cells and hapten-coupled are capable of immunizing mice for a DTH response. Therefore, the set of I-J-bearing EC appears to be distinct from classic Langerhans cells. A novel set of 1-J-bearing EC appears to be responsible for Ts activation after subcutaneous immunization with hapten-coupled UVR-treated EC.
Habituation of stimulus-elicited investigation in gerbils after olfactory bulbectomy.

Abstract Normal gerbils habituate rapidly when presented with a novel object in the stimulus-elicited investigation paradigm. In this paradigm, gentled gerbils are given a series of one minute trials with a novel object in a small arena. They are then given a series of similar trials in which the odor of strange male gerbils is under one of five holes in the floor of the same arena. Gerbils with bilateral olfactory bulbectomies habituated more slowly to the object than normal gerbils or those anosmized peripherally by unilateral bulbectomy combined with stitching of the contralateral naris. In contrast, the two anosmic groups habituated at the same rate as normal gerbils when tested for investigation of five holes and odor although neither group of anosmic gerbils selectively localized the odor. In comparison to normal gerbils with no specific odor present, habituation was delayed for both experimental groups. In addition, both anosmic groups habituated normally on an activity score. Therefore, it was concluded that habituation can be affected differentially by the surgical conditions dependent on the task being measured. These data support the hypotheses (a) that the olfactory bulbs have a role in behaviors that are not dependent on olfactory information and (b) that habituation is not a single process mediated uniformly for all behaviors.