cssi/SciSciGPT-SciSciNet huggingface dataset:
Multimodal widefield fluorescence imaging with nonlinear optical microscopy workflow for noninvasive oral epithelial neoplasia detection: a preclinical study

Significance: Early detection of epithelial cancers and precancers/neoplasia in the presence of benign lesions is challenging due to the lack of robust in vivo imaging and biopsy guidance techniques. Label-free nonlinear optical microscopy (NLOM) has shown promise for optical biopsy through the detection of cellular and extracellular signatures of neoplasia. Although in vivo microscopy techniques continue to be developed, the surface area imaged in microscopy is limited by the field of view. FDA-approved widefield fluorescence (WF) imaging systems that capture autofluorescence signatures of neoplasia provide molecular information at large fields of view, which may complement the cytologic and architectural information provided by NLOM. Aim: A multimodal imaging approach with high-sensitivity WF and high-resolution NLOM was investigated to identify and distinguish image-based features of neoplasia from normal and benign lesions. Approach:In vivo label-free WF imaging and NLOM was performed in preclinical hamster models of oral neoplasia and inflammation. Analyses of WF imaging, NLOM imaging, and dual modality (WF combined with NLOM) were performed. Results: WF imaging showed increased red-to-green autofluorescence ratio in neoplasia compared to inflammation and normal oral mucosa (p < 0.01). In vivo assessment of the mucosal tissue with NLOM revealed subsurface cytologic (nuclear pleomorphism) and architectural (remodeling of extracellular matrix) atypia in histologically confirmed neoplastic tissue, which were not observed in inflammation or normal mucosa. Univariate and multivariate statistical analysis of macroscopic and microscopic image-based features indicated improved performance (94% sensitivity and 97% specificity) of a multiscale approach over WF alone, even in the presence of benign lesions (inflammation), a common confounding factor in diagnostics. Conclusions: A multimodal imaging approach integrating strengths from WF and NLOM may be beneficial in identifying oral neoplasia. Our study could guide future studies on human oral neoplasia to further evaluate merits and limitations of multimodal workflows and inform the development of multiscale clinical imaging systems.
Uterine Epithelial Neoplasia

Nonneoplastic lesions of the endometrium encompass a broad spectrum of epithelial alternations ranging from metaplasia, hormonal related changes, inflammatory processes, reparative conditions, endometrial polyps, and gestational alterations. Many of these conditions can mimic various malignant or premalignancy lesions of the endometrium, particularly when present in a small biopsy or curettage specimen. Endometrial hyperplasia and atypical hyperplasia are preneoplastic conditions that precede the most common endometrioid adenocarcinoma. Serous and clear cell carcinomas are high-grade carcinomas by definition and account for about 10–15% of endometrial malignancy. Other histological types are rare, including high neuroendocrine carcinomas, undifferentiated carcinomas, dedifferentiated carcinoma, and mixed carcinomas. Molecular classification of endometrial cancers may provide added diagnostic and prognostic information.
Stereoscopic three-dimensional (3D) slit-lamp photography using a compact 3D digital camera

We describe a novel method of stereoscopic 3D slit-lamp photography using a portable compact 3D digital camera. Thirteen eyes of 13 patients underwent slit-lamp photography using a Fujifilm 3D compact digital camera. We modified a universal smartphone microscope adapter to attach the camera to the slit-lamp. Photography was attempted on Zeiss and on HAAG-Streit slit-lamps. Success was defined as capturing a stereogram that consists of two simultaneous pictures, one from each slit-lamp ocular. Stereoscopic 3D slit-lamp photos could be captured in all 13 eyes in which they were attempted on Zeiss slit-lamps. Captured 3D media included external, eyelid, conjunctival, corneal, anterior chamber, lens, vitreous, and optic disc pathologies. Stereoscopic 3D photography could not be obtained using this Fujifilm 3D digital camera on Haag-Streit slit-lamps because of alignment incompatibility between the oculars of the slit-lamp and the camera. Digital stereoscopic 3D slit-lamp photography is feasible using a compact 3D digital camera and compatible slit-lamp design. Images obtained using this technique may be helpful in clinical education.
Association of Lewy Bodies With Age-Related Clinical Characteristics in Black and White Decedents

Objective The associations of Lewy bodies (LBs) with olfactory dysfunction, parkinsonism, and higher odds of dementia were assessed in Black and White community-dwelling elders and racial differences in these associations were tested. Methods Black decedents (n = 81) were matched 2-to-1 by age, sex, years of education, and follow-up time in the study with White decedents (n = 154) from 4 longitudinal studies of dementia and aging. Participants underwent uniform clinical examination and cognitive, motor, and olfactory testing. LBs were detected in 7 brain regions by α-synuclein immunohistochemistry and racial differences in their association with olfaction, parkinsonism, and odds of dementia were determined using regression analyses. Results The mean scores of the odor test, global parkinsonism signs, and global cognition were lower in Black than White decedents; the frequency of dementia was similar in both groups. The frequency of LBs was similar in Black and White decedents (∼25%), as was the frequency of LBs in individual brain regions, while the mean LB counts/mm2 were similar in all regions except the cingulate cortex, which showed higher mean LB counts in Black decedents. In regression analyses, LBs were associated with impaired olfaction (−2.23, 95% confidence interval [CI] −3.45 to −1.01) and higher odds of dementia (odds ratio 3.0, 95% CI 1.10–8.17) in both racial groups; an association with parkinsonism was stronger in Black than White decedents. Conclusions The frequency, distribution, and clinical manifestations of LBs are similar in Black and White elders.
Learning, Unlearning and Relearning--Knowledge Life Cycles in Library and Information Science Education.

The knowledge life cycle is applied to two core capabilities of library and information science (LIS) education – teaching, and research and development. The knowledge claim validation, invalidation and integration steps of the knowledge life cycle are translated to learning, unlearning and relearning processes. Mixed methods are used to determine the extent and nature of learning, unlearning and relearning among academic faculty in graduate level library and information science programs. Mixed methods include (1) targeted interviews, (2) manual review of curriculum scope and coverage at seven universities, (3) semantic analysis of the content of 1,711 course syllabi, and (4) machine based analysis of learning, unlearning and relearning semantic markers in 432 journal articles drawn from twelve peer-reviewed journals. The research results provide a foundation for an open and national survey of LIS faculty in 2015. Research results suggest that there is evidence of learning, relearning and unlearning in teaching methods, but only evidence of learning in curriculum and course development, and research. Unlearning practices appear to be scarce in the field. This has implications for the disciplines ability to generate new knowledge and remain competitive in the knowledge economy.
Toward an algorithmic metaphysics

There are writers in both metaphysics and algorithmic information theory (AIT) who seem to think that the latter could provide a formal theory of the former. This paper is intended as a step in that direction. It demonstrates how AIT might be used to define basic metaphysical notions such as object and property for a simple, idealized world. The extent to which these definitions capture intuitions about the metaphysics of the simple world, times the extent to which we think the simple world is analogous to our own, will determine a lower bound for basing a metaphysics for our world on AIT.
Gaskinetic Theory: Elementary transport theory

So far we have considered gases which were in kinematic equilibrium. It was always assumed that the molecules did not have any organized motion (bulk motion), and that the gas temperature and the number density of the molecules were constant everywhere. Under such conditions there is no net particle transport from one place to another. In this chapter we relax our earlier assumptions and let the macroscopic quantities (gas bulk velocity, temperature, pressure, concentration, etc.) have slow spatial variations. These configuration space gradients result in macroscopic transport phenomena, such as diffusion or heat flow. Fluid dynamics describes these transport phenomena using empirical transport coefficients, such as viscosity, diffusion coefficient or heat conductivity. In this chapter we shall use the elementary mean free path method to describe macroscopic transport phenomena and to calculate approximate values for the transport coefficients. This simple and remarkably successful method is quite general because it does not depend on the form of the distribution function and, therefore, does not assume equilibrium. The mean free path method is based on the assumption that the gas is not in equilibrium, but the deviation from equilibrium is so small that locally the distribution of molecular velocities can be approximated by Maxwellians. However, the macroscopic parameters of the local Maxwellians slowly vary with configuration space location. Mathematically this assumption can be translated into two basic conditions. The first condition is that the variation of all macroscopic quantities is small within a mean free path.
Designing and Detecting Trapdoors for Discrete Log Cryptosystems

Using a number field sieve, discrete logarithms modulo primes of special forms can be found faster than standard primes. This has raised concerns about trapdoors in discrete log cryptosystems, such as the Digital Signature Standard. Tins paper discusses the practical impact of these trapdoors, and how to avoid them.
Social network structure as a critical success condition for open source software project communities

In recent years, a surprising new phenomenon has emerged in which globally-distributed online communities collaborate to create useful and sophisticated computer software. These open source software groups are comprised of generally unaffiliated individuals and organizations who work in a seemingly chaotic fashion and who participate on a voluntary basis without direct financial incentive. The purpose of this research is to investigate the relationship between the social network structure of these intriguing groups and their level of output and activity, where social network structure is defined as (1) closure or connectedness within the group, (2) bridging ties which extend outside of the group, and (3) leader centrality within the group. Based on well-tested theories of social capital and centrality in teams, propositions were formulated which suggest that social network structures associated with successful open source software project communities will exhibit high levels of bridging and moderate levels of closure and leader centrality. The research setting was the SourceForge hosting organization and a study population of 143 project communities was identified. Independent variables included measures of closure and leader centrality defined over conversational ties, along with measures of bridging defined over membership ties. Dependent variables included source code commits and software releases for community output, and software downloads and project site page views for community activity. A cross-sectional study design was used and archival data were extracted and aggregated for the two-year period following the first release of project software. The resulting compiled variables were analyzed using multiple linear and quadratic regressions, controlling for group size and conversational volume. Contrary to theory-based expectations, the surprising results showed that successful project groups exhibited low levels of closure and that the levels of bridging and leader centrality were not important factors of success. These findings suggest that the creation and use of open source software may represent a fundamentally new socio-technical development process which disrupts the team paradigm and which triggers the need for building new theories of collaborative development. These new theories could point towards the broader application of open source methods for the creation of knowledge-based products other than software.
The Serials Librarian and Accreditation

All academic libraries are subject to accreditation by one or more accrediting agencies. This workshop provided an overview of the regional accreditation process for higher education, discussed the standards for academic libraries in six regions, and offered suggestions for the role of the serials librarian in the accreditation process.
Building a Geosocial Semantic Web for Military Stabilization and Reconstruction Operations

The United States and its Allied Forces have had tremendous success in combat operations. This includes combat in Germany, Japan and more recently in Iraq and Afghanistan. However not all of our stabilization and reconstruction operations (SARO) have been as successful. Recently several studies have been carried out on SARO by National Defense University as well as for the Army Science and Technology. One of the major conclusions is that we need to plan for SARO while we are planning for combat. That is, we cannot start planning for SARO after the enemy regime has fallen. In addition, the studies have shown that security, power and jobs are key ingredients for success during SARO. For example, it is essential that security be maintained. Furthermore, it is important to give powerful positions to those from the fallen regime provided they are trustworthy. It is critical that investments are made to stimulate the local economies. The studies have also analyzed the various technologies that are needed for successfully carrying out SARO which includes sensors, robotics and information management. In our research we are focusing on the information management component for SARO. As stated in the work by the Naval Postgraduate School, we need to determine the social, political and economic relationships between the local communities as well as determine who the important people are. This work has also identified the 5Ws (Who, When, What, Where and Why) and the (H).
Effect of Oxygen Tension, Mn(II) Concentration, and Temperature on the Microbially Catalyzed Mn(II) Oxidation Rate in a Marine Fjord.

We present evidence that the oxidation of Mn(II) in a zone above the O2/H2S interface in the water column of Saanich Inlet, British Columbia, Canada, is microbially catalyzed. We measured the uptake of 54Mn(II) in water samples under in situ conditions of pH and temperature and in the presence and absence of oxygen. Experiments in the absence of oxygen provided a measure of the exchange of the tracer between the dissolved and solid pools of Mn(II); we interpret the difference between experiments in the presence and absence of oxygen to be a measure of Mn(II) oxidation. Using this method we examined the effect of oxygen tension, Mn(II) concentration, and temperature on the initial in situ Mn(II) oxidation rate (V0). Mn(II) oxidation was almost twice as fast under conditions of 67% air saturation (V0=5.5 nM h−1) as with the in situ concentration of 15 μM (5% air saturation; V0=3.1 nM h−1). Additions of ca. 18 μM Mn(II) completely inhibited all Mn(II) oxidation at three different depths in the oxidizing zone, and there was a temperature optimum for Mn(II) oxidation of around 20°C. These results are consistent with biologically mediated Mn(II) oxidation and indicate that the rate is limited by both oxygen and the concentration of microbial binding sites in this environment.
Composite hydrogel scaffolds with controlled pore opening via biodegradable hydrogel porogen degradation

Poly(β-amino ester) (PBAE) biodegradable hydrogel systems have garnered much attention in recent years due to their appealing properties for biomedical applications. These hydrogel systems exhibit properties similar to natural soft tissue, degrade in aqueous environments, and have easily tunable properties that have been well studied and understood. In most cases, tissue engineering scaffolds must possess a three-dimensional interconnected porous network for tissue ingrowth and construct vascularization. Here, PBAE properties were explored and systems were selected to serve as both the pore-forming agent and the outer matrix of a scaffold that exhibits controlled pore opening upon degradation. To our knowledge, this is the first demonstration of a biodegradable hydrogel porogen system entrapped in a degradable hydrogel outer matrix. Scaffolds were prepared, and the degradation, compressive moduli, and porosity were analyzed. An added advantage of a degradable porogen is the potential for controlled drug release, and a model protein was released from the porogen particles to demonstrate this application. Finally, pluripotent cells seeded onto predegraded scaffolds were viable during the first 24 h of exposure, and furthermore, cell tracking confirmed the presence of cells within the pores of the scaffold. Overall, these present studies demonstrate the possibility of using these biodegradable hydrogel porogen-matrix systems as tissue engineering scaffolding materials. © 2013 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 102A: 400–412, 2014.
Development and flight test of an area monitoring system using Unmanned Aerial Vehicles and unattended ground sensors

This document describes the motivation, theoretical description, development, and flight test of a system that utilizes unmanned air vehicles (UAVs) and unattended ground sensors (UGSs) to detect and image intruders on a road network. The need for completely autonomous behavior drives the design of this system so that the UAV makes onboard decisions based upon inputs from off-board sensors (unattended ground sensors). A complete road surveillance system consisting of a UAV and over 30 UGSs was designed and simulated. The system was also flight tested in a realistic operating environment.
Toxoplasma antigens recognized by human immunoglobulin A antibodies.

The immunoglobulin A (IgA) antibody response to antigens of Toxoplasma gondii during the acute and chronic stages of T. gondii infection was studied by immunoblotting with a nonreduced antigen (NRA) preparation. Serum samples were from individuals with acute or chronic T. gondii infection, and sequential samples were from women who seroconverted during gestation or congenitally infected infants. IgA antibodies to a variety of antigens were present in sera from each of the groups, irrespective of the titer in an IgA enzyme-linked immunosorbent assay. The predominant NRA recognized by IgA antibodies in sera from each of the four groups had an approximate molecular weight of 30,000. Other prominent NRAs had approximate molecular weights of 35,000 and 5,000; however, the latter NRA was not present in sera of congenitally infected infants. Images
The Pain Reliever and Heroin Epidemic in the United States: Shifting Winds in the Perfect Storm

Aims: The abuse of prescription pain relievers and/or heroin is a significant public health concern. This article identifies the changes in this epidemic and estimates the extent of the gap between treatment availability and need. Method: This article uses the national data on opioid and heroin abuse to identify at-risk groups. Result: Findings include shifting from narcotic analgesics to heroin and demographic changes as well as changes in supply and new medication-assisted therapies. Conclusions: The number of persons dependent on pain relievers or heroin and new initiates is more than three times greater than the current capacity to deliver treatment.
Measurement of heat of adsorption of polyethylene oxide on dolomite, silica, and alumina by microcalorimetry

Abstract Direct measurements of the heat of adsorption of a 5 million molecular weight polyethylene oxide polymer on dolomite, quartz, and alumina were made using a microcalorimeter. Heat of adsorption was measured as a function of polymer dosage and temperature. The adsorption process was determined to be endothermic. It was observed that Δ H is a strong function of temperature and is affected also by polymer preparation time.
Characterisation of the contractile activity of eletriptan at the canine vascular 5-HT1B receptor

Abstract The functional activity of eletriptan (( R )-3-(1-methyl-2-pyrrolidinylmethyl)-5-[2-(phenylsulphonyl)ethyl]-1 H -indole) at the contractile serotonin (5-hydroxytryptamine; 5-HT) `1B-like' receptor in dog isolated saphenous vein and basilar artery was investigated. Eletriptan, like 5-HT and sumatriptan potently contracted saphenous vein (pEC 50 : 6.3, 6.9 and 6.1, respectively) and basilar artery (pEC 50 7.2, 7.5 and 6.8, respectively). The maximum responses evoked by eletriptan was, unlike sumatriptan, significantly lower than that to 5-HT (intrinsic activity saphenous vein: eletriptan 0.57, 5-HT 1.0, sumatriptan 0.85; basilar artery: eletriptan 0.77, 5-HT 0.98, sumatriptan 0.89). Contractions evoked by eletriptan were antagonised by the 5-HT 1B/1D receptor antagonist GR125743 ( N -[4-methoxy-3-(4-methyl piperazin-1-yl)phenyl]-3-methyl-4-(4-pyridyl)benzamide) with p A 2 values of 9.1 in saphenous vein and 9.4 in basilar artery. Affinity estimates (p K A ) for 5-HT and sumatriptan determined from receptor alkylation studies in saphenous vein were 6.6 and 6.3, respectively, compared to the apparent equilibrium dissociation constant (p K P ) for eletriptan of 6.8. The rank order of relative intrinsic efficacies ( e ) was 5-HT>sumatriptan>eletriptan. Thus, eletriptan required greater receptor occupancy (4.4-fold) to evoke an equivalent contraction to 5-HT and sumatriptan in dog isolated saphenous vein. These data demonstrate that eletriptan is a potent partial agonist at the canine vascular 5-HT 1B receptor.
Surface Analysis Studies of Yield Enhancements in Secondary Ion Mass Spectrometry by Polyatomic Projectiles

In this paper we examine the mechanism of secondary ion yield enhancements previously observed for polyatomic projectiles by measuring the weight loss, volume loss, and surface composition of poly(methyl methacrylate) (PMMA) films sputtered by keV SF5+ and Ar+ projectile ions. The sputter yieldthe amount of material removed from the surface by 3.0 keV SF5+ projectileswas found to be 2.2 ± 0.8 higher than for Ar+ projectiles, measured by weight loss in the PMMA film with a quartz crystal microbalance. This result is consistent with sputter yield measurements reported here using 5.5 keV ions and stylus profilometry. Thus, the >10× enhancement in secondary ion yield in secondary ion mass spectrometry observed for polyatomic ion projectiles is not attributable to the modest ∼2× enhancements observed in the sputter yields for this molecular solid. Surface chemical measurements by X-ray photoelectron spectroscopy also indicated fundamental differences in atomic versus polyatomic sputtering mechanisms at 3.0 keV...
Human ovarian cancer stem/progenitor cells are stimulated by doxorubicin but inhibited by Mullerian inhibiting substance

Women with late-stage ovarian cancer usually develop chemotherapeutic-resistant recurrence. It has been theorized that a rare cancer stem cell, which is responsible for the growth and maintenance of the tumor, is also resistant to conventional chemotherapeutics. We have isolated from multiple ovarian cancer cell lines an ovarian cancer stem cell-enriched population marked by CD44, CD24, and Epcam (3+) and by negative selection for Ecadherin (Ecad−) that comprises less than 1% of cancer cells and has increased colony formation and shorter tumor-free intervals in vivo after limiting dilution. Surprisingly, these cells are not only resistant to chemotherapeutics such as doxorubicin, but also are stimulated by it, as evidenced by the significantly increased number of colonies in treated 3+Ecad− cells. Similarly, proliferation of the 3+Ecad− cells in monolayer increased with treatment, by either doxorubicin or cisplatin, compared with the unseparated or cancer stem cell-depleted 3−Ecad+ cells. However, these cells are sensitive to Mullerian inhibiting substance (MIS), which decreased colony formation. MIS inhibits ovarian cancer cells by inducing G1 arrest of the 3+Ecad− subpopulation through the induction of cyclin-dependent kinase inhibitors. 3+Ecad− cells selectively expressed LIN28, which colocalized by immunofluorescence with the 3+ cancer stem cell markers in the human ovarian carcinoma cell line, OVCAR-5, and is also highly expressed in transgenic murine models of ovarian cancer and in other human ovarian cancer cell lines. These results suggest that chemotherapeutics may be stimulative to cancer stem cells and that selective inhibition of these cells by treating with MIS or targeting LIN28 should be considered in the development of therapeutics.
Safety and cost benefit of an accelerated infliximab infusion protocol in the treatment of ambulatory patients with inflammatory bowel diseases

Background: Infliximab is recommended to be infused over 2 h, but accelerated infusion rates of 30 min may improve efficiency, patient satisfaction and reduce nursing time and cost. The safety of this approach is not established. This study aims to assess the safety of accelerated infliximab infusion and determine the direct cost savings. Methods: The primary endpoint of the study was adverse events and the secondary endpoints were cost, time saving per infusion and patient satisfaction associated with an accelerated infusion protocol. Results: One hundred and thirty-six and 342 infusions were administered to 23 and 39 patients in the standard and accelerated protocols, respectively (mean infusion times 150 and 73.4 min, respectively, p < 0.0001). The adverse reaction rate of the standard protocol was 2.2% (95% confidence interval: 0.46 – 6.57) and accelerated protocol was 3.2% (95% CI: 1.74 – 5.73; p = 0.77). The odds ratio of adverse reaction for the 30-min infusion was 0.40 (95% CI: 0.09 – 1.82). The r...
New Directions for Academic Video Game Collections: Strategies for Acquiring, Supporting, and Managing Online Materials

Abstract The work of collection development in academic video game collections is at a crucial point of transformation—gaming librarians are ready to expand beyond console games collected in disc and cartridge format to the world of Internet games. At the same time, forms and genres of video games such as serious and independent games are increasingly important to university instruction and curricula, and the move to online gaming allows university and college libraries to give campus communities access to them. This essay reviews the most significant LIS literature on academic gaming collections and identifies new directions in gaming collection development. The authors then present specific resources and strategies they relied upon in their recent initiative to transform gaming collection development policies at the University of North Texas, a large, public, research university. Establishing a five-year plan to create a cutting-edge video game collection, the authors concentrated especially on adding new types of games to the collection, working through the logistics of providing online access, and providing opportunities for research and student learning within the university library through the creation of a gaming lab. The essay outlines in concrete terms the next steps academic gaming librarians can take to ensure the continuing relevance of their collections to campus communities, exploring how innovations in collection development can shape the future of this rapidly-transforming field.
Long-term stability of the Earth's climate.

Earth's climate has remained reasonably temperate for at least the last 3.5 billion years, despite a large increase in solar luminosity with time. The increase in solar flux has probably been offset by a decrease in atmospheric CO2 concentration caused by a negative feedback in the carbonate-silicate geochemical cycle. The same feedback mechanism implies that an Earth-like planet could remain habitable (i.e. possess liquid water) out to a least the orbit of Mars. The initial atmospheric CO2 concentration may have been much higher than the amount required to offset the lower solar output, in which case the Earth may have originally been much hotter than it is today. However, once the initial accretion period was over, Earth should have been stable against either a runaway greenhouse, that is, complete evaporation of the oceans, or against rapid loss of water. Long-term climatic evolution has thus far been studied only with one-dimensional, globally-averaged climate models. Although such models can provide a qualitative understanding of climate history, they rely on a number of assumptions that may not have been valid in the past. Some problems that deserve to be investigated with more sophisticated climate models are discussed.
Mineralization of Bones and Teeth

Bones and teeth consist of an inorganic calcium phosphate mineral approximated by hydroxylapatite and matrix proteins. The physical and chemical properties of these “bioapatite” crystals are different from those of geologic hydroxylapatite because of the way they are formed, and these unique properties are required for fulfilling the biological functions of bones and teeth. Recent biochemical studies provide insight into the factors controlling the formation and growth of bioapatite crystals and how alteration in the mineralization process can lead to diseases such as osteoporosis. New spectroscopic and microscopic techniques are enabling scientists to characterize changes in crystal properties in these diseases, providing potentially fruitful areas of collaboration among geochemists, mineralogists, and biological researchers and offering hope for the development of novel therapies.
Prostate-specific Antigen Testing and Prostate Cancer Screening

Prostate specific antigen (PSA) screening is an integral part of current screening for prostate cancer. Together with digital rectal examinations, it is recommended annually by the American Cancer Society. PSA screening has resulted in a significant stage migration in the past decades. Different forms of PSA, including free PSA, volume adjusted, complexed, intact, or pro-PSA, are being used in the screening process. Other aspects of the screening process include age at diagnosis, survival, overdiagnosis, and overtreatment. Recent studies have cast doubt on whether PSA screening positively affects mortality and how the quality of life of patients may be affected by screening. Future considerations include the need for more longitudinal studies as well as further study of the PSA components that may become more relevant in the future.
Adapter Proteins Activate Myosin-Va during Cargo Transport

Myosin-Va (myoVa), one of the best characterized actin-based molecular motors, transports a variety of intracellular cargos. In order to bind a specific cargo, myoVa forms a tri-partite complex with a Rab effector protein (i.e. adapter) and a Rab GTPase protein (e.g. Rab27a) that is inserted in the granule membrane. MyoVa delivers insulin granules to the plasma membrane in pancreatic beta-cells. Interestingly, there are four known adapter proteins expressed in beta-cells, i.e. Granuphilin-A/B, Rabphilin and MyRIP, all of which bind myoVa. The role of these adapter proteins in cargo transport is poorly understood.Using TIRF microscopy, we measured the speed, run-length and stepping behavior of myoVa in presence of Qdot-labeled adapter proteins. At 25 mM KCl, the adapter proteins do not show appreciable activation of the inhibited myoVa motor. However, at physiological salt concentration, the adapter proteins significantly increase the run-length and the run-frequency of myoVa on actin filaments. Specifically, in the presence of Granuphilin A, the myoVa run-frequency increases ∼6-fold, with an ∼3.5-fold run-length enhancement as the motor steps (72nm) normally, but at half the speed. By labeling Granuphilin-A and MyRIP with a Qdot, we observed binding of these adapters directly to actin filaments, suggesting that they enhance the motor's run-length and slow speed by a tethering mechanism, similar to Melanophilin (Sckolnick, et al., 2013). In contrast, Granuphilin-B and Rabphilin have little binding affinity for actin. Nonetheless, they bind to and activate myoVa, because the full-length myoVa step size becomes regular like the constitutively active, truncated myoVa-HMM. A common feature of these adapter proteins is that they ensure that the motor remains active while attached to the cargo. However, only some adapter proteins have actin-tethering capacity, which may enhance the long-range vesicle transport. These functional differences may play synergistic roles in the cell.
Application of three-parameter lognormal distribution in EM data analysis

The three-parameter lognormal distribution has been demonstrated for applications in electromigration data analysis, especially for Cu interconnect structures with insufficient redundancy. Examples are given on estimating parameter values from experimental data using the maximum likelihood method. Detailed analyses are presented on confidence bound estimations of the parameters and their propagation to lifetime projections.
Penetration of fluorescein into the brain: a sex difference.

Abstract Fluorescein was found to penetrate into the brain via the circumventricular organs. Fluorescein penetrates beyond the borders of the circumventricular organs into the surrounding neuropile. This relationship was found for the area postrema and the nucleus tractus solitarius, the organum vasculosum lamina terminalis and the rostral suprachiasmatic area, the median eminence and the arcuate nucleus. The choroid plexus appears to take up fluorescin, but fluoroscence does not appear in adjacent structures such as the corpus striatum and septum, but rather along the ependymal and plial surfaces. Fluorescein was found to accumulate to a greater extent in the brains of female as compared to male rats. This sex difference is not associated with the blood-brain barrier as cortex and cerebellum did not show increased fluorescence, but only midline structures containing circumventricular organs. Gonadectomy did not alter fluoroscein accumulation.
Solubility of E2050 at various pH: a case in which apparent solubility is affected by the amount of excess solid.

Abstract The solubility of E2050, supplied as a dihydrochloride salt, in aqueous solutions at different pHs was studied. Two p K a s controlling the equilibrium between the various protonated species were determined. The solubility–pH profile of E2050 is expected to be high in acidic solutions because protonated species are formed and to be low in alkaline conditions due to the formation of hydrophobic free base. The solubility is also affected by chloride ion, a common ion for this drug substance. Two solubility products ( K sp ) were determined corresponding to the solubility of di‐HCl salt and mono‐HCl salt. Based on the p K a s (3.10 and 7.71), the solubility products with chloride (2.92 and 3.77 as corresponding p K sp ), and the solubility of free base (2 × 10 −5 M), the solubility in solutions with different pH and different levels of chloride ion can be predicted. The prediction of the solubility change during the dilution of E2050 parenteral formulations by saline was also demonstrated. Furthermore, the present study presents an interesting example in which an apparent solubility can be different if varying (excess) amounts of salt are added to the solution. In this case, excess chloride ion suppresses the solubility in the pH region where mono‐HCl salt controls the solubility.
Processing and presentation of antigens by dendritic cells: implications for vaccines

Dendritic cells (DCs) are potent antigen-presenting cells that are specialized in initiation of T-cell immunity. DCs induce promising anti-tumor T-cell and clinical responses, apparently without significant toxicity. Under certain conditions, DCs even silence T-cell immune responses in vivo. This dual capacity to modulate the immune system uniquely positions DCs for the treatment of autoimmunity, cancer and chronic viral infections.
An interactive computer program for measurement of data obtained using the extra-stimulus technique during electrode-catheter studies

Abstract The extra-stimulus technique, used to determine the refractory period of the conduction system and to study tachyarrhythmias, has received wide application in clinical electrophysiology; but measuring the records obtained using this method is tedious and slow. To reduce the time required to make these measurements and to expand the range of intracardiac sites which reasonably can be measured, an interactive computer system has been developed to perform this task. This system uses the records made at the time of study, a Graf/Pen for digitizing the records, and immediate processing of the digitized data by computer. To validate the program, a study was done comparing measurements made by two cardiologists, each using manual and computer methods. Five hundred and sixty-one intervals, representing five intracardiac sites recorded during refractory period determinations in eight patients, were measured. Using the computer method, the mean absolute difference between measurements obtained by the two observers was 1.8 msec. The mean absolute differences between the measurements made by computer and manual methods by the two observers were 2.3 and 2.7 msec. Of special interest was the demonstration of the reproducibility of the measurement of intervals between ventricular electrograms recorded by the catheter recording the Bundle of His electrogram. This new system thus allows measurement of intervals recorded at multiple intracardiac sites with a great saving of time and with accuracy at least equal to that of conventional methods.
Mapping and expression of southern bean mosaic virus genomic and subgenomic RNAs.

Abstract The coat protein of the cowpea strain of southern bean mosaic sobemovirus (SBMV-C) is translated from a subgenomic RNA (sgRNA) that is synthesized in the virus-infected cell. Like the SBMV-C genomic RNA, the sgRNA has a viral protein (VPg) covalently bound to its 5′ end. The mechanism(s) by which ribosomes initiate translation on the SBMV-C RNAs is not known. To begin to characterize the translation of the sgRNA it was first necessary to precisely map its 5′ end. Primer extension was used to identify SBMV-C nucleotide (nt) 3241 as the transcription start site. As a control, the 5′ end of the genomic RNA was also mapped. Surprisingly, the 5′ terminal nt of this RNA was identified as SBMV-C nt 2. The primary structure of the 5′ ends of these two RNAs is therefore expected to be VPg-ACAAAA. Precise mapping of the 5′ end of the sgRNA of the bean strain of SBMV (SBMV-B) demonstrated that it has these same elements. Translation of coat protein from the SBMV-C sgRNA and p21 from the SBMV-C genomic RNA was compared using a cell-free system. The results of these experiments were consistent with translation of these proteins by a 5′ end-dependent scanning mechanism rather than by internal ribosome binding.
Protein Transport into Higher Plant Peroxisomes (In Vitro Import Assay Provides Evidence for Receptor Involvement)

Peroxisome biogenesis requires that proteins be transported from their site of synthesis in the cytoplasm to their final location in the peroxisome matrix or membrane. Glyoxysomes are a class of peroxisomes found primarily in germinating seedlings and are involved in mobilizing fatty acids via the glyoxylate cycle and the [beta]-oxidation pathway. We have used an in vitro assay to study the mechanism(s) of import of proteins into glyoxysomes. Results from this assay indicate that the transport process is time- and temperature- dependent and is specific for peroxisomal proteins. Isocitrate lyase, a glyoxysomal protein, and the leaf-type peroxisomal enzyme glycolate oxidase (GLO) were transported into pumpkin (Cucurbita pepo) glyoxysomes with no apparent differences in efficiency of import. Thus, this in vitro assay appears to be physiologically relevant and correlates well with expected in vivo conditions. Protein import was also energy-dependent and saturable. Nonradiolabeled GLO competed with radiolabeled, in vitro-synthesized GLO for components of the import machinery. Finally, pretreatment of the isolated glyoxysomes with protease virtually abolished subsequent import of GLO. Taken together, these results indicate that a proteinaceous receptor is involved in the import of peroxisomal proteins.
Evaluation of external radiation dosimetry records at the Savannah River Site, 1951-1989.

The Savannah River Site (SRS) is one of the largest facilities in the nation's nuclear weapons complex. To date, little information has been published regarding radiation risk estimates derived from epidemiological studies of SRS workers. As part of an ongoing epidemiological cohort study of SRS workers, we have assessed the suitability of the Site's personnel radiation dosimetry information for use in epidemiological analyses. This paper provides information on historical dosimetry methods, recording practices, and the completeness of computerized dosimetry information for workers employed at SRS during the period 1951–1989, when the site was operated by the du Pont Company. The study includes 18,883 workers hired at SRS between 1951 and 1987 who were employed for at least 90 days. Documents relating to external radiation dosimetry methods were reviewed, recorded doses were examined to evaluate recording practices, and the completeness of monitoring was assessed by comparing employment history and computerized dosimetry records, and by implementing a “nearby” procedure for estimating values for missing annual dosimetry records. Dosimeter technology evolved over this period from two-element film dosimeters to multielement thermoluminescent dosimeters. Dosimetry measurements were recorded consistently in 0.05 millisievert (mSv) increments. Prior to 1973, recording thresholds of 0.10–0.15 mSv were used while from 1973 to 1989 a recording threshold of 0.05 mSv was used. We abstracted nearly 3 person-Sv of dosimetry information that was available in hardcopy but not in computerized format. The collective dose from the computerized and abstracted records totaled 512.1 person-Sv. A “nearby” method was used to estimate dose values for 13,812 employment-years for which dosimetry information was not available. The average estimated value was 0.6 mSv and the assigned collective dose derived via the “nearby” procedure was 8.7 person-Sv. The consistency of dosimetry practices at SRS and the completeness of historical dosimetry records are supportive of their use in epidemiologic research.
Characterization of Ribeye Subunits in Zebrafish Hair Cells Reveals That Exogenous Ribeye B-Domain and CtBP1 Localize to the Basal Ends of Synaptic Ribbons

Synaptic ribbons are presynaptic structures formed by the self-association of RIBEYE–the main structural component of ribbon synapses. RIBEYE consists of two domains: a unique N-terminal A-domain and a C-terminal B-domain that is identical to the transcription co-repressor C-terminal binding protein 2 (CtBP2). Previous studies in cell lines have shown that RIBEYE A-domain alone is sufficient to form ribbon-like aggregates and that both A- and B- domains form homo-and heterotypic interactions. As these interactions are likely the basis for synaptic-ribbon assembly and structural plasticity, we wanted to examine how zebrafish Ribeye A- and B- domains interact with synaptic ribbons in vivo. To that end, we characterized the localization of exogenously expressed Ribeye A- and B- domains and the closely related protein, CtBP1, in the hair cells of transgenic zebrafish larvae. Unexpectedly, exogenously expressed Ribeye A-domain showed variable patterns of localization in hair cells; one zebrafish paralog of A-domain failed to self-associate or localize to synaptic ribbons, while the other self-assembled but sometimes failed to localize to synaptic ribbons. By contrast, Ribeye B-domain/CtBP2 was robustly localized to synaptic ribbons. Moreover, both exogenously expressed B-domain/CtBP2 and CtBP1 were preferentially localized to the basal end of ribbons adjacent to the postsynaptic density. Overexpression of B-domain/CtBP2 also appeared to affect synaptic-ribbon composition; endogenous levels of ribbon-localized Ribeye were significantly reduced as hair cells matured in B-domain/CtBP2 transgenic larvae compared to wild-type. These results reveal how exogenously expressed Ribeye domains interact with synaptic ribbons, and suggest a potential organization of elements within the ribbon body.
Effects of simulated functional loading conditions on dentin, composite, and laminate structures

Use of composite restorations continues to increase, tempered by more potential problems when placed in posterior dentition. Thus, it is essential to understand how these materials function under stress-bearing clinical conditions. Because mastication is difficult to replicate in the laboratory, cyclic loading is frequently used within in vitro evaluations but often employs traditional fatigue testing, which typically does not simulate occlusal loading because higher stresses and loading frequencies are used, so failure mechanisms may be different. This investigation utilized relevant parameters (specimen size, loading frequency) to assess the effects of cyclic loading on flexural mechanical properties and fracture morphology of (coronal) dentin, composite, and dentin-adhesive-composite "laminate" structures. Incremental monitoring of flexural modulus on individual beams over 60,000 loading cycles revealed a gradual increase across materials; post hoc comparisons indicated statistical significance only for 1 versus 60k cycles. Paired specimens were tested (one exposed to 60k loading cycles, one to static loading only), and comparisons of flexural modulus and strength showed statistically significantly higher values for cyclically loaded specimens across materials, with no observable differences in fracture morphology. Localized reorganization of dentin collagen and polymer chains could have increased flexural modulus and strength during cyclic loading, which may have implications toward the life and failure mechanisms of clinical restorations and underlying tooth structure.
Mucositis in the Cancer Patient and Immunosuppressed Host

Oral mucositis is a serious complication of cancer therapy and in severely immunosuppressed patients. In immunosuppressed patients, the signs and symptoms of infection often are muted because of limited host response, and accurate diagnosis and appropriate treatment may be difficult. Prevention of mucosal breakdown, suppression of microbial colonization, control of viral reactivation, and effective management of severe xerostomia are all critical steps to reducing the overall morbidity and mortality of oromucosal infections.
Gauge Theory Gravity with Geometric Calculus

A new gauge theory of gravity on flat spacetime has recently been developed by Lasenby, Doran, and Gull. Einstein’s principles of equivalence and general relativity are replaced by gauge principles asserting, respectively, local rotation and global displacement gauge invariance. A new unitary formulation of Einstein’s tensor illuminates long-standing problems with energy–momentum conservation in general relativity. Geometric calculus provides many simplifications and fresh insights in theoretical formulation and physical applications of the theory.