cssi/SciSciGPT-SciSciNet huggingface dataset:
Issues in the Design and Conductance of Clinical Trials

Publisher Summary Clinical trials are conducted to determine the therapeutic efficacy, effectiveness, safety, and tolerability of interventions for clinical disorders. The best clinical trials are designed to do this efficiently with minimal potential for bias. This chapter focuses on the clinical trials of pharmacological interventions for psychiatric disorders, in particular, how translational models can improve the quality of these trials. The implementation of clinical trials is fraught with hazard. Present methods are incapable of assuring that the best patients are included in trials and that the true effects of assigned treatments are consistently captured. Inference making should be cautious and restrained. Only after multiple trials are completed by several groups of investigators using differing methodologies produce concordant results whether it should be believed that the findings are well supported and are to be used in the practice. As the back and forth process of developing translational models of pathophysiology and pharmacological actions in laboratory and clinical settings proceeds, clinical trials will become more objective and this will hasten the development of clinically useful medicines. Re-engaging dedicated clinical investigators will enhance the quality of this process.
Attitude Control System Design for CubeSats Configured with Exo-Brake Parachute

This paper develops a novel attitude control strategy for an Earth orbiting CubeSat spacecraft by utilizing the exo-brake parachute to modulate the atmospheric drag forces as a source of attitude control authority, enabling orbital exo-sail maneuvers. In particular, the spacecraft attitude controls can be realized through the two dimensional exo-sail maneuvers in pitch and yaw directions. The uncertain atmospheric drag induced disturbance torque is estimated through an adaptive parameter estimation process which makes use of the adaptive least-squares minimization techniques. The covariance updating law with a variable forgetting factor is adopted and it can be shown that the convergent rate for the estimation errors can be chosen at the same level as the forgetting factor, in order to meet the design needs. The proposed approach is best suited for Earth orbiting micronano-satellite applications, which are configured with exo-brake parachute. With integration of exo-sail actuation mechanism and disturbance estimation, we demonstrate through simulations that exo-sail induced control torque for CubeSat attitude maneuver is feasible.
Rates of performance loss and neuromuscular activity in men and women during cycling: evidence for a common metabolic basis of muscle fatigue.

Although men and women differed considerably in their absolute cycling performances, there was no sex difference in the metabolically based exponential time constant that described the performance-...
Benefits of adjacent habitat patches to the distribution of a crayfish population in a hydro-dynamic wetland landscape

Aquatic macrophyte patches are natural features of wetland ecosystems that serve as habitat for aquatic animals. Previous studies suggest animal densities in Everglades, USA, wetlands are generally less numerous in sawgrass ridges than in deeper lily sloughs. We studied the density distribution of a population of Procambarus fallax in ridge and slough habitat types over a 2-year period, spanning two wet–dry cycles and estimated growth and survival rates under flooded conditions to understand comparative value of each to the crayfish population. Procambarus fallax individuals inhabited and recruited in both marsh habitats. During periods of high water, crayfish densities were similar in both habitats; however, densities in both habitats varied seasonally, leading us to postulate some degree of population redistribution in response to fluctuating water depths. Analysis of size distributions over time revealed juveniles in both habitats and two major recruitment periods each year; distinct juvenile cohorts were present in early winter (Nov–Dec) and mid-summer (July–Aug). An in situ experiment of juvenile growth demonstrated that slough habitat type supported faster growth over ridge habitat. To understand habitat-specific mortality risk, a tethering study during flooded conditions indicated that relative predation risk by aquatic predators was greater in sloughs for all sizes and higher for smaller individuals in both habitats. The comparative importance of ridge and slough balances growth potential and survival probability during flooded conditions. This is the first study through time and across both habitat types analyzing the distribution and size structure of P. fallax population in the Everglades.
Mechanical Concepts Applied in Congenital Heart Disease and Cardiac Surgery

All biological processes are governed by principles of physics that dictate the pathophysiology and even the treatment of congenital heart diseases. In this review, basic concepts such as flow, pressure, resistance, and velocity are introduced, followed by more complex laws that describe the relationship between these variables and the disease processes. Finally, physical phenomena such as turbulence, steal and runoff phenomenon, and energy loss are discussed. By application of these principles, one can accurately quantify modifications undertaken to treat diseases, for example, the size of a patch that augments a vessel and the angle of an anastomosis to allow a certain flow.
The golden retriever model of Duchenne muscular dystrophy

Duchenne muscular dystrophy (DMD) is an X-linked disease caused by mutations in the DMD gene and loss of the protein dystrophin. The absence of dystrophin leads to myofiber membrane fragility and necrosis, with eventual muscle atrophy and contractures. Affected boys typically die in their second or third decade due to either respiratory failure or cardiomyopathy. Despite extensive attempts to develop definitive therapies for DMD, the standard of care remains prednisone, which has only palliative benefits. Animal models, mainly the mdx mouse and golden retriever muscular dystrophy (GRMD) dog, have played a key role in studies of DMD pathogenesis and treatment development. Because the GRMD clinical syndrome is more severe than in mice, better aligning with the progressive course of DMD, canine studies may translate better to humans. The original founder dog for all GRMD colonies worldwide was identified in the early 1980s before the discovery of the DMD gene and dystrophin. Accordingly, analogies to DMD were initially drawn based on similar clinical features, ranging from the X-linked pattern of inheritance to overlapping histopathologic lesions. Confirmation of genetic homology between DMD and GRMD came with identification of the underlying GRMD mutation, a single nucleotide change that leads to exon skipping and an out-of-frame DMD transcript. GRMD colonies have subsequently been established to conduct pathogenetic and preclinical treatment studies. Simultaneous with the onset of GRMD treatment trials, phenotypic biomarkers were developed, allowing definitive characterization of treatment effect. Importantly, GRMD studies have not always substantiated findings from mdx mice and have sometimes identified serious treatment side effects. While the GRMD model may be more clinically relevant than the mdx mouse, usage has been limited by practical considerations related to expense and the number of dogs available. This further complicates ongoing broader concerns about the poor rate of translation of animal model preclinical studies to humans with analogous diseases. Accordingly, in performing GRMD trials, special attention must be paid to experimental design to align with the approach used in DMD clinical trials. This review provides context for the GRMD model, beginning with its original description and extending to its use in preclinical trials.
Some Procedural Effects in Operant Discrimination Reversal

In Experiment I pigeons were rewarded for 20 pecks to one color and not rewarded for pecking an alternate stimulus which terminated when responding ceased for 20 sec. Stimuli were interchanged daily. After 50 days performance was unaffected by reversal of colors. More frequent reverals and interpolated time-outs were studied. “Errorless reversal” was taken as indicating discrimination of procedural cues. In Exp. II the key color remained unchanged, and brief stimuli indicated schedule alternation. Schedule control did not reach the level of Exp. I. In Exp. Ill the schedules occurred in a mixed order separated by time-outs and again associated with colors that reversed daily. Schedule control developed rapidly, but “errorless reversals” never occurred. Interpretation of “errorless reversals” as involving procedural discriminations is discussed. Some results regarding contrast and time-out remain uninterpreted.
A "Real-World" Approach to Coursework in Sales Management

Educators and practitioners agree that coursework should help students understand the actual business environment. This article describes an innovative approach to teaching business courses which addresses the functions of a position and also how to be effective, gain power and recognition, play the corporate "game," and move up the ladder.
High-speed dynamic-mode atomic force microscopy imaging of polymers: an adaptive multiloop-mode approach.

Adaptive multiloop-mode (AMLM) imaging to substantially increase (over an order of magnitude) the speed of tapping-mode (TM) imaging is tested and evaluated through imaging three largely different heterogeneous polymer samples in experiments. It has been demonstrated that AMLM imaging, through the combination of a suite of advanced control techniques, is promising to achieve high-speed dynamic-mode atomic force microscopy imaging. The performance, usability, and robustness of the AMLM in various imaging applications, however, is yet to be assessed. In this work, three benchmark polymer samples, including a PS–LDPE sample, an SBS sample, and a Celgard sample, differing in feature size and stiffness of two orders of magnitude, are imaged using the AMLM technique at high-speeds of 25 Hz and 20 Hz, respectively. The comparison of the images obtained to those obtained by using TM imaging at scan rates of 1 Hz and 2 Hz showed that the quality of the 25 Hz and 20 Hz AMLM imaging is at the same level of that of the 1 Hz TM imaging, while the tip–sample interaction force is substantially smaller than that of the 2 Hz TM imaging.
Mammalogy is for everyone

This is the publisher's version, which may also be found at: http//:dx.dio.org/10.2307/1311591
Isolation of nuclei using hexylene glycol.

Publisher Summary This chapter describes a general procedure for the isolation of nuclei in buffered 2-methyl-2,4-pentanediol (hexylene glycol) solutions that meets the requirements of nuclear purity and general applicability. The hexylene glycol-PIPES buffer is efficacious both in vivo and in vitro . The tissues from mouse brain, chicken liver, rat liver, rat uterus, chick oviduct, hen oviduct, rabbit oviduct, and Novikoff hepatoma ascites cells and from the tissue culture cell lines Chinese hamster ovary and HeLa are chosen to demonstrate the minor modifications necessary for general applicability of the isolation method. The purity and morphology of the hexylene glycol-isolated nuclei is established using several criteria. Phase microscopic observations indicate that the preparations are not contaminated with cytoplasmic structures, and electron microscopy shows that the nuclear fine structure is well preserved. Chemical composition data indicates that the RNA/DNA, protein/DNA, acid-soluble protein/DNA, and phospholipid/DNA ratios are similar to those reported for nuclei obtained by other isolation methods.
An approximate theory for velocity profiles in the near wake of a flat plate

The determination of the velocity distributions along, and in the near wake of, a flat plate in steady laminar incompressible flow has been of great interest for nearly three-quarters of a century. Goldstein’s [1] analysis using the Blasius (1908) solution for the flat-plate boundary layer as the initial velocity profile for the wake flow is the classical seminal treatment of this problem (described by at least one investigator, with whom many would agree, as one of the most significant contributions in the 20th century to the theory of fluid mechanics).
Land cover and land use change analysis using multi-spatial resolution data and object-based image analysis

Abstract Remote sensing data and techniques are reliable tools for monitoring and studying urban land cover and land use (LCLU) change. Fine spatial resolution (FRes) commercial satellite image in conjunction with geographic object-based image change analysis (GEOBICA) methods have been used to generate detailed and accurate urban LCLU maps. The integration of a backdating approach improves LCLU change classification results for the first date of a bi-temporal image sequences. Conversely, moderate spatial resolution satellite images such as those from Landsat sensors may not allow for detailed urban land use and land cover mapping. The objective of this study is to test a new bi-temporal change identification approach that integrates image classification of fine spatial resolution satellite imagery at time-2 and moderate spatial resolution satellite imagery (Landsat) at time-1, in a backdating and GEOBICA framework for mapping urban land use change. We compare the results from this approach to those of a GEOBICA approach based on fine spatial resolution imagery in both periods. The overall accuracy of the time-1 Landsat image classification is 0.82 and that of the fine spatial resolution image is 0.87. Moreover, the overall accuracy of the areal change data estimated from the pixel-wise spatial overlay of bi-temporal FRes LCLU maps is 0.80 while that from overlaying a time-2 FRes-generated map to that from a Landsat time-1 image is 0.81. The proposed method can be used in areas that lack FRes data due to limited coverage in the early 2000s.
Thin Films of YBaCuO Prepared by Multilayer Evaporation Process

Thin films of YBaCuO were prepared as a superlattice of three constituents from three electron guns using a computer-controlled evaporator. After annealing, the multilayer films are converted to the homogeneous superconducting phase. Highly epitaxial thin films with: (1) the a-axis perpendicular to (100) SrTiO3; (2) the c-axis perpendicular to (100) SrTiO3; and (3) the [110] axis perpendicular to (110) SrTiO3 were confirmed by x-ray diffraction as well as scanning electron microscopy and high resolution electron microscopy. Both the a-axis oriented and the c-axis oriented films exhibit zero resistance at 91K. The [110] oriented film shows the sharpest transition with a transition width of 1K and zero resistance at 85K. The zero field critical current density, Jc, determined magnetically, is in excess of 107A/cm2 at 4.4K and 1.04 x 106A/cm2 at 77K for the c-axis oriented film; for the a-axis oriented film we obtained 6.7 x 106A/cm2 at 4.4K and 1.2 x 105A/cm2 at 77K. The orientation dependence of the critical current density in the basal plane of the a-axis oriented film was studied. The largest Jc’s occur along the in-plane axes of the substrate.
Enzymes Catalysing Formation of Pyridoxal Phosphate From Vitamin B6

The evolutionary retention of homologous portions of pyridoxal kinases, both broadly and narrowly specific, and the occurrence of a highly conserved region of pyridoxine (pyridoxamine) phosphate oxidase with catalytically involved residues, emphasize the importance of these enzymes that are potential agents for release of pharmalogic effectors.
Stability of Perturbed Systems

In this section, we suppose that L satisfies the conditions of Section 17; namely, that the representation (17.2) holds. Furthermore, if $$\left| {{\rm{L}}\left( {{\rm{t}},{\rm{\phi }}} \right)} \right| \le \ell \left( {\rm{t}} \right)\left| {\rm{\phi }} \right|,{\rm{t}} \in {\rm{R}}^ + ,{\rm{\phi }} \in {\rm{C,}}$$ (18.1) then there is a constant l1such that $$\int_{\rm{t}}^{{\rm{t}} + {\rm{r}}} {\ell \left( {\rm{s}} \right){\rm{ds}} \le \ell _1 ,{\rm{t}} \in {\rm{R}}^ + }$$ (18.2) .
Time-filtering particle simulations with ωpe Δt ⪢ 1

The application of a time-filtering algorithm to particle simulations including low-frequency electron dynamics with time steps ..delta..t satisfying the condition ..omega../sub p/e..delta..t>>1, where ..omega../sub p/e denotes the electron plasma frequency, is presented. The implicit determination of the electric field required in these simulations is achieved by using the continuity and momentum equations in conjunction with the Poisson equation in a manner guaranteeing numerical stability for long wavelengths satisfying the condition k/sub max/v/sub the/..delta..t<<1, where k/sub max/ is the largest wave number included in the computations and v/sub the/ is the electron thermal velocity. Several classical examples, involving two-stream instabilities, ion-acoustic oscillations and plasma expansion into vacuum are given, and the effects of aliases and of beaming instabilities are analyzed.
Advanced Methods for Screening and Identification of Methicillin-Resistant Staphylococcus aureus

Methicillin-resistant Staphylococcus aureus (MRSA) is among the most important causes of human infections in the twenty-first century and is found in both hospitals and communities. Early and accurate detection and characterization of MRSA are essential for appropriate therapeutic treatment as well as for infection control. This review focuses on the utility and performance of currently available advanced techniques for rapid and accurate screening and identification of MRSA, especially on evolving rapid nucleic acid amplification-based methods.
Complex Salt Dependence of Polymer Diffusion in Polyelectrolyte Multilayers.

Polyelectrolyte multilayers (PEMs) have significant potential in many technologies, yet the dynamics of the constituent polymer chains remains poorly understood. We used total internal reflection fluorescence microscopy to observe microscopic single-molecule transport of fluorescently labeled poly-l-lysine (PLL) diffusing within the bulk of a PEM composed of PLL and poly(2-acrylamido-2-methyl-1-propanesulfonic acid) (PAMPS) when exposed to NaCl solutions ranging in concentration from 0 to 2 M. Statistical analysis of PLL trajectories revealed motion that was nonergodic, subdiffusive, and temporally anticorrelated under all conditions. In contrast with previous macroscopic measurements of polymer diffusion within PEMs, the microscopic diffusion was 2–3 orders of magnitude faster and varied nonmonotonically with salt concentration in a way that was similar to trends previously associated with PEM swelling and viscoelastic properties. This trend in the anomalous diffusion was attributed to complex salt-depen...
Optical coherence tomography for diagnosing optic neuritis: Are we there yet?

Acute optic neuritis (ON) results in rapid and prominent peripapillary retinal nerve fiber layer (RNFL) and composite ganglion cell and inner plexiform layer (GCIPL) thinning, as measured with optical coherence tomography (OCT). However, the degree of thinning within these layers following ON is heterogeneous, varying across patients, even within the same disease state.1 Moreover, OCT measures in healthy individuals have a broad range, creating difficulties establishing an absolute diagnostic cutoff for prior ON with good sensitivity and specificity. Whereas earlier generation time-domain OCT could be insensitive to subtle RNFL changes following ON,2 and less sensitive than visual evoked potentials for confirming prior ON,3 later generation spectral-domain OCT has improved resolution and reliability, in addition to the ability to measure the advantageous GCIPL, as well as other discrete retinal layers.1,4
Controlling Nitrogen Doping in Graphene with Atomic Precision: Synthesis and Characterization

Graphene provides a unique platform for the detailed study of its dopants at the atomic level. Previously, doped materials including Si, and 0D-1D carbon nanomaterials presented difficulties in the characterization of their dopants due to gradients in their dopant concentration and agglomeration of the material itself. Graphene’s two-dimensional nature allows for the detailed characterization of these dopants via spectroscopic and atomic resolution imaging techniques. Nitrogen doping of graphene has been well studied, providing insights into the dopant bonding structure, dopant-dopant interaction, and spatial segregation within a single crystal. Different configurations of nitrogen within the carbon lattice have different electronic and chemical properties, and by controlling these dopants it is possible to either n- or p-type dope graphene, grant half-metallicity, and alter nitrogen doped graphene’s (NG) catalytic and sensing properties. Thus, an understanding and the ability to control different types of nitrogen doping configurations allows for the fine tuning of NG’s properties. Here we review the synthesis, characterization, and properties of nitrogen dopants in NG beyond atomic dopant concentration.
Interior of a unitarily evaporating black hole

Author(s): Nomura, Y | Abstract: We study microscopic operators describing the experience of an observer falling into the horizon of a unitarily evaporating black hole. For a young black hole, these operators can be taken to act only on the degrees of freedom in the black hole region: the soft - or stretched horizon - modes as well as the semiclassical modes in the zone region. On the other hand, for an old black hole, the operators must also involve radiation emitted earlier; the difference between the two cases comes from statistics associated with the coarse graining performed to obtain the effective theory of the interior. We find that the operators relevant for the interior theory can be defined globally as standard linear operators throughout the microstates, which obey the correct algebra up to corrections exponentially suppressed in the ratio of excitation energy to the Hawking temperature. We conjecture that the existence of such global operators is required for the emergence of the semiclassical picture. We also elucidate the relation between the present construction and entanglement wedge reconstruction of the interior.
Ultra-Low Power Physical Unclonable Function with Nonlinear Fixed-Resistance Crossbar Circuits

The proliferation of networked mobile devices and smart gadgets in the IoT landscape has accelerated the demand for lightweight, low power and operationally compatible cryptographic solutions. As a result, emergent hardware-intrinsic security architecture must demonstrate manufacturability, power efficiency and platform compatibility, in addition to robust security performance. Here we present a novel design of physical unclonable function, called VRPUF, and prototype it using unformed 4K-ReRAM passive crossbar circuits fabricated with a CMOS-compatible process, suitable for the back-end-of-line (BEOL) integration. The architecture utilizes intrinsic process variations in crossbar circuits, manifested as variations in device I-V nonlinearities and the leakage currents, and allows for extremely large (~1025) number of challenge-response pairs (CRPs). The VRPUF design does not require forming/ programming crosspoint devices, which simplifies peripheral circuits, leading to ~ 4× better density compared to the architectures which rely on switching the states of ReRAM devices. Moreover, uniform I-Vs of the virgin-state devices, coupled with lower conductance and stronger static nonlinearity, allow for ~100× improvement in power consumption and more robust security metrics. The intrinsic reliability of VRPUF primitives is also ~4× better compared to CMOS architectures, which can be further improved via selective de-enrolling of worst-case CRPs prior to deployment.
A simple and efficient method for generating human retinal organoids

Purpose Retinal organoids (ROs) derived from human pluripotent stem cells largely recapitulate key features of in vivo retinal development, thus permitting the study of retinogenesis, disease modeling, and therapeutic development. However, the complexities of current protocols limit the use of this in vitro system in applications requiring large-scale production of organoids. Currently, widely used methods require the isolation of presumed optic vesicle-like structures from adherent cultures by dissection, a labor-intensive and time-consuming step that involves extensive practice and training. Method We report a simple and efficient method for generating ROs by scraping the entire adherent culture and growing the resulting cell aggregates in a free-floating condition. Results Within 1 to 7 days following the procedure, emerging morphologically well-defined optic vesicles can be identified and harvested with ease. The transition from two-dimensional (2D) to 3D culture condition favored the formation of ROs from areas devoid of typical optic vesicle-like structures, thus increasing the RO yield. Moreover, ROs generated by this approach were more often associated with the pigment epithelium. Conclusions This improved, robust, and efficient protocol should facilitate large-scale differentiation of pluripotent stem cells into retinal organoids in support of human disease modeling and therapy development.
The Pragmatic Impact of Frailty on Outcomes of Coronary Artery Bypass Grafting.

Background Although not formalized into current risk assessment models, frailty has been associated with negative postoperative outcomes in many specialties. Using administrative coding, we evaluated the impact of frailty on in-hospital death, complications, and resource use in a nationally representative cohort of patients undergoing isolated coronary artery bypass grafting (CABG). Methods Patients aged 18 years and older who underwent isolated CABG across the United States were identified using the 2005 to 2016 National Inpatient Sample. Frailty was defined using a derivative of the validated Johns Hopkins Adjusted Clinical Groups frailty-defining diagnosis indicator. Mortality, length of stay, inflation-adjusted costs, and postoperative complications were evaluated using multilevel multivariable regression. Results Of an estimated 2,137,618 patients undergoing isolated CABG, 85,879 (4.0%) were considered frail. The proportion of frail patients increased over the study period (nonparametric test for trend P = .002), while annual mortality rates declined (nonparametric test for trend P Conclusions Frailty, as identified by administrative coding, serves as a strong independent predictor of death and complications after CABG. Incorporation of frailty into risk models may aid in counseling patients about operative risk and benchmarking outcomes.
State of States: Landscape of University-Based Pathways to the Principalship:

This study describes the landscape of school leadership preparation programs in the United States, including pathways to the principalship (master’s, certification, educational specialist) and the ...
Cracking prediction of asphalt concrete using fracture and strength tests

Strength and fracture-based tests have been developed to assess the cracking potential of asphalt concrete (AC). The major difference between them is the presence of a notch in fracture tests. The ...
Dynamic Combustion of Functionally Graded Additively Manufactured Composite Solid Propellant

Typically, the burning surface of a composite solid propellant is controlled through grain geometry and formulation. However, combustion studies of grains constructed from different propellant form...
Analysis of GP-designed metamaterial using equivalent circuit model and Prony’s method

Prior Artificial Magnetic Conductor (AMC) designs using Genetic Programming (GP) showed that GP-based designs are competitive and often exceed those based on human expertise. However, the resultant...
What Does Freedom Mean

In this paper, we review definitions of freedom. All of the definitions we have found include limits on behavior as part of the definition. For this reason, freedom lacks a coherent meaning. Further, we suggest that freedom must be rejected as a political goal in order to create a democracy.
Measures of Location

After a set of data has been collected, it must be organized and condensed or categorized for purposes of analysis. In addition to graphical summaries, numerical indices can be computed that summarize the primary features of the data set. One is an indicator of location or central tendency that specifies where the set of measurements is “located” on the number line; it is a single number that designates the center of a set of measurements. In this chapter we consider several indices of location and show how each of them tells us about a central point in the data.
Understanding Citizens' Direct Policy Suggestions to the Federal Government: A Natural Language Processing and Topic Modeling Approach

We report on our initial efforts to make sense of e-petitions as policy suggestions by using the NLP technique of "topic modeling" to identify the "topics" that emerge in e-petitions. Using a sample of petitions submitted to the Obama Administration's WtP petitioning system as a case study, we produced 30 emergent topics. 21 out of the 30 topics were initially coded as high-quality topics. Upon qualitative investigation, all but one of these 21 topics were determined to have a coherent theme. Our results imply that topic modeling has the potential to enable the interpretation of large quantities of citizen generated policy suggestions through a largely automated process, with potential application to research on e-participation and policy informatics.
Ovulation and Fertilization in the Hormone-Stimulated Calf,

Summary Thirty-two veal calves, of unknown age but varying in weight between 90 and 180 pounds, were subjected to a series of subcutaneous injections of gonadotropic extracts predominantly of follicle-stimulating activity, followed by an intravenous injection of luteinizing extract and artificial insemination. Moderate to extreme follicular stimulation was induced in all but one animal, but corpora lutea were formed in only 50 per cent of the calves. Thirtyfive ova were recovered from ten animals, but only seven (representing two individuals) showed evidence of fertilization.
Clinical considerations for neutron capture therapy of brain tumors.

In welcoming this Workshop on Neutron Capture Therapy to Boston, it would be appropriate to reflect upon the fact that, at the turn of the century, Boston was a major center for the development and use of x-rays to cure cancer. This was summarized by Dr. Francis H. Williams in his book entitled, “The Roentgen Rays in Medicine and Surgery as an Aid in Diagnosis and as a Therapeutic Agent,” published in 1901. Dr. Williams published some of the first photographs documenting the curative potential of the then newly discovered x-rays for the treatment of skin cancers. In the ensuing decades, the science and technology of ionizing radiation has been developed and expanded to effectively treat a wide variety of tumors. For many, radiation therapy as a primary or adjuvant treatment either leads to cure of their disease or is a highly effective means of palliation. However, the results of even modern radiotherapy for the management of primary brain tumors and tumor metastases to the brain from primaries arising elsewhere in the body have been extremely disappointing. In spite of significant advances in our understanding of tumor biology and technical advances in radiation delivery, the results of radiotherapy for these tumors have not changed significantly during the past twenty years. We are, therefore, very excited at the potential clinical impact of neutron capture therapy (NCT).
Control system analysis of the leech neural control system

Presents our approach and achievements toward addressing the limitations of neural networks in control systems. We show that by modeling the neural control system of the leech, using control system techniques, we are able mitigate current limitations and develop neural network paradigms specifically for control systems. We begin by presenting an overview of the leech neural control system which we modeled. We then show that techniques from large-scale control systems provide insight into the architecture and parameters of the leech neural control system. These insights establish a basis for the development of neural control paradigms. >
Strengthening the Link

Abstract Through exploration of definitional issues and current migration realities, this article discusses ways in which emphasis on the international dimensions of social work with immigrants and refugees offers opportunities to improve practice and to enhance the relevance of international social work to the profession. The international character of present day migration is illustrated through discussion of the transnational family and the economic and other relationships that tie immigrants to their countries of origin. The paper concludes with recommendations for increased cross-national professional collaboration.
A Mutation in a New Gene, bglJ Activates the bgl Operon in Escherichia coli K-12

A new mutation, bglJ4 , has been characterized that results in the expression of the silent bgl operon. The bgl operon encodes proteins necessary for the transport and utilization of the aromatic β-glucosides arbutin and salicin. A variety of mutations activate the operon and result in a Bgl + phenotype. Activating mutations are located upstream of the bgl promoter and in genes located elsewhere on the chromosome. Mutations outside of the bgl operon occur in the genes encoding DNA gyrase and in the gene encoding the nucleoid associated protein H-NS. The mutation described here, bglJ4 , has been mapped to a new locus at min 99 on the Escherichia coli K-12 genetic map. The putative protein encoded by the bgygene has homolgy to a family of transcriptional activators. Evidence is presented that increased expression of the bglJ product is needed for activation of the bgl operon.
Special histologic stains are rarely beneficial for the evaluation of HIV-related gastrointestinal infections.

During a 28-month period, endoscopic mucosal biopsy specimens from all HIV-infected patients were submitted for routine histologic evaluation. Immunoperoxidase staining for cytomegalovirus and herpesvirus antigens (esophagus), mycobacterial and fungal staining, and Gram staining of mucosal biopsy specimens were done. Special fungal and acid-fast stains were selectively performed in patients with absolute CD4 cell counts of less than 200 cells per microliter (200 x 106/L) and/or with diarrhea and or wasting syndrome. Treatment was based on the endoscopic and histologic findings, and long-term follow-up was performed. The 121 symptomatic HIV-infected patients underwent 221 upper and/or lower endoscopies with 285 biopsy sites. The sensitivity and specificity of H&E staining for the diagnosis of gastrointestinal cytomegalovirus were 97% and 100%, respectively. The results of fungal and mycobacterial stains neither altered therapy nor identified previously undiagnosed infections in any patient. Long-term follow-up revealed no patient in whom an infection was missed on routine H&E, which affected outcome. Routine H&E staining is accurate for the diagnosis of gastrointestinal opportunistic infections in HIV-infected patients. Special histologic stains for fungal, mycobacterial, and viral infections did not increase the diagnostic yield or alter medical therapy but doubled the costs.
Combined hypertrophic pyloric stenosis and duodenal web in Down syndrome : Sonographic and radiographic diagnosis

Gastrointestinal anomalies associated with Down syndrome have been recognized for a long time. Major anomalies reported include duodenal atresia or stenosis, annular pancreas, gastroesophageal reflux, imperforate anus, Hirschsprung disease, malrotation, bile duct atresia, esophageal atresia or tracheoesophageal fistula, and HPS. 1-3 We report the clinical and imaging features of a combination of HPS and a duodenal web in a 2 month old boy with Down syndrome.
Generation of Few-Cycle 2.2-mJ Pulses at 2.05 μm by Type II Optical Parametric Amplification in BBO

We demonstrate the production of 2.2-mJ, 87-fs mid-infrared laser pulses at 2.05 μm by a two-stage type-II BBO optical parametric amplifier pumped by a 10-Hz commercial Ti:sapphire laser system.
The determination of optimal faculty staffing for a university

Abstract A finite difference model has been developed for the distribution over time of a university faculty divided into I cohorts. These models have been solved both for the transient and steady-state cases. These models have also been incorporated into optimization models to determine optimal policies with respect to reaching or maintaining a faculty at a given size subject to the constraints that exist at an institution. For the steady-state case, this problem turns out to be a linear programming problem. An example of an actual application of the model to a particular university is also given.
Abstract P1-03-01: Generation of a NovelIn VivoModel of Patient-Derived Chemoresistant Breast Cancers:

Background: Breast cancer patients who have significant residual cancer after neoadjuvant chemotherapy (NCT) are at high risk of relapse. There is a pressing need to identify novel therapeutics that can be offered to these patients. In vivo models available to test new agents are limited. We hypothesized that tumors from patients with poor response to NCT can be transplanted into nude mice to establish xenografts, providing a novel in vivo model to study therapies for chemoresistant tumors. Materials and Methods: After informed consent, excess tumor was taken from the mastectomy specimens from six patients who had either disease progression during NCT or significant residual disease after NCT. On surgical pathologic evaluation, average tumor size was 8.6 ± 3.2 cm (range 4.5-12 cm), and average number of positive lymph nodes was 6.2 ± 6.8 (range 0-18). Patients had RECIST criteria of partial response (n=2), stable disease (n= 1) or progressive disease (n=3). For each patient, tumors were implanted subcutaneously into the flanks of five nude mice. Tumors were passaged to successive generations when they reached 1.5 cm in diameter. In vivo tumor growth and the ability to serially passage tumors were assessed. Patient and tumor characteristics, and patient outcomes were evaluated. Results: Three patients had ER+HER2- tumors and three had ER-HER2- tumors. Serially transplanted xenografts were established from all six patients (100%); see Figure 1. Within each group of five mice implanted with the human tumors, 60 ± 26% developed tumor. Time to tumor size of 1.5 cm diameter was 4.2 ± 2.6 months (range 1.5-7.8 months). Two mice also developed tumors at a location distant from the implantation site (Met). These tumors were separately engrafted, also with 100% take, reaching 1.5 cm diameter at 1.5 and 1.7 months. Of the six patients, one had metastatic disease at surgery and underwent palliative mastectomy. Of the other five patients, four (80%) developed metastatic disease 4-8.4 months after surgery. Mice developed passagable tumors at least 2 months before the donor patients developed distant recurrence. The one patient who remains distant disease-free had the longest time to tumor passage (8.4 months). Figure 1. Time to passage of tumor to next generation of mice. Flank tumors xenografts were derived from patients with chemoresistant breast cancers. When tumors reach 1.5 cm in diameter, they are passaged to the next generation of 5 mice. X-axis depicts time to reach 1.5 cm with each passage. Discussion: Patients with progression or significant residual disease after NCT are at very high risk of distant relapse. Their chemoresistant tumors can be used to create serially transplantable xenografts. This in vivo model of chemoresistant breast cancer may be utilized to allow individualization of additional adjuvant or metastatic breast cancer treatment. Citation Information: Cancer Res 2010;70(24 Suppl):Abstract nr P1-03-01.
Predictor-corrector type of intersection algorithm for C 2 parametric surfaces

Abstract A predictor-corrector type of intersection algorithm is developed for free-form parametric surfaces with C 2 continuity. A surface-surface intersection is solved as a number of curve-surface intersections in which each of the curves is defined in the parameter space of the ‘primary surface’ as a straight line, passing through an initial point and pointing at an ‘engaging direction’. Concepts from differential geometry are employed to predict the initial points and the engaging directions before the Newton-Raphson iterations are performed to compute the actual intersection points. The algorithm proceeds in a predictor-corrector type of way with the propagation steps controlled by the user-specified tolerance. The computer implementation of the algorithm has presented quite satisfying results.
The dichroic tensor of flexible helices

A statistical theory of the linear dichroism of DNA-like chains is presented for two models which are discrete versions of the wormlike coil. In the final form the linear dichroism of the entire chain is related directly to the dichroic properties of a chain segment (base pair). Though the derivations are somewhat complicated, the result [Eq. (28)] is simple and the required statistical parameters can be easily calculated for either model from measured values of the persistence length. In fact, for molecules as stiff as double-stranded DNA, the results can be reduced with good accuracy to the form showing that the “optical persistence” given on the left is directly proportional to the structural persistence, P∞/l. As in previous theories the results are restricted to chains in their Gaussian limit.
INFERENCE AND UNCERTAINTY PROPAGATION OF ATOMISTICALLY INFORMED CONTINUUM CONSTITUTIVE LAWS, PART 2: GENERALIZED CONTINUUM MODELS BASED ON GAUSSIAN PROCESSES

Constitutive models in nanoscience and engineering often poorly represent the physics due to significant deviations in model form from their macroscale counterparts. In Part 1 of this study, this problem was explored by considering a continuum scale heat conduction constitutive law inferred directly from molecular dynamics (MD) simulations. In contrast, this work uses Bayesian inference based on the MD data to construct a Gaussian process emulator of the heat flux as a function of temperature and temperature gradient. No assumption of Fourier-like behavior is made, requiring alternative approaches to assess the well-posedness and accuracy of the emulator. Validation is provided by comparing continuum scale predictions using the emulator model against a larger all-MD simulation representing the true solution. The results show that a Gaussian process emulator of the heat conduction constitutive law produces an empirically unbiased prediction of the continuum scale temperature field for a variety of time scales, which was not observed when Fourier’s law is assumed to hold. Finally, uncertainty is propagated in the continuum model and quantified in the temperature field so the impact of errors in the model on continuum quantities can be determined.
A patch hierarchy approach to modeling surface and subsurface hydrology in complex flood-plain environments

Geomorphology interacts with surface- and ground-water hydrology across multiple spatial scales. Nonetheless, hydrologic and hydrogeologic models are most commonly implemented at a single spatial scale. Using an existing hydrogeologic computer model, we implemented a simple hierarchical approach to modeling surface- and ground-water hydrology in a complex geomorphic setting. We parameterized the model to simulate ground- and surface-water ﬂow patterns through a hierarchical, three-dimensional, quantitative representation of an anabranched montane alluvial ﬂood plain (the Nyack Flood Plain, Middle Fork Flathead River, Montana, USA). Comparison of model results to ﬁeld data showed that the model provided reasonable representations of spatial patterns of aquifer recharge and discharge, temporal patterns of ﬂood-water storage on the ﬂood plain, and rates of ground-water movement from the main river channel into a large lateral spring channel on the ﬂood plain, and water table elevation in the alluvial aquifer. These results suggest that a hierarchical approach to modeling ground- and surface-water hydrology can reproduce realistic patterns of surface- and ground-water ﬂux on alluvial ﬂood plains, and therefore should provide an excellent ‘quantitative laboratory’ for studying complex interactions between geomorphology and hydrology at and across multiple spatial scales. Copyright © 2004 John Wiley & Sons, Ltd.
CHLOROPHYLL PHOTOSENSITIZED ELECTRON TRANSFER IN PHOSPHOLIPID BILAYER VESICLE SYSTEMS: EFFECTS OF CHOLESTEROL ON RADICAL YIELDS AND KINETIC PARAMETERS*

The quenching of the triplet state of chlorophyll a (Chl) by asymmetrically located electron acceptors was examined in vesicle systems containing egg yolk phosphatidylcholine and 0–50 mole % cholesterol. The incorporation of cholesterol had two main effects: (1) the distribution of Chl within the vesicle wall shifted from one favoring the inner monolayer to one favoring the outer monolayer, and (2) the Chi molecules (both ground and excited states) became more accessible to water and to the quencher molecules. This latter property was probably due to the creation of space between the phospholipid head groups by insertion of cholesterol. These phenomena required cholesterol concentrations in excess of 15 mol %. In general, the addition of cholesterol caused increases in the apparent bimolecular rate constant for triplet quenching, in the probability that quenching produced radicals, and in the rate of radical recombination. Some of the specific effects of cholesterol depended upon whether or not the quencher molecules were amphiphilic.
On the effects of viscous dissipation and pressure work in free convection loops

Abstract The effects of viscous dissipation and pressure work are examined theoretically for laminar free convection loops. The appropriate governing equations are derived. Whereas previous work has considered only dissipation effects, the present paper shows that dissipation and pressure work effects are of comparable magnitude and must be considered together. Analytical solutions are presented for several open and closed loops. Both constant flux and constant temperature heating conditions are examined. Viscous dissipation and pressure work effects are found to have opposing influences on the flow in a loop. The former can enhance a flow for certain heating orientations, but the latter is usually dominant and retards a flow.
When scaling prevention means scaling demand: Voluntary medical male circumcision in Nyanza Province, Kenya

Abstract Implementation lessons • Generating demand is an important part of the care delivery value chain. When new health interventions are designed based on recent clinical trial findings, demand generation activities prove all the more critical. • Demand generation activities need to iterate on their design, and tailor to the risk profile of target populations. • Leaders need to balance fidelity to a model and local innovation. • Cultural and contextual factors must be considered in designing public health campaigns.