cssi/SciSciGPT-SciSciNet huggingface dataset:
Histologic Grade Is Predictive of Incidence of Epidermal Growth Factor Receptor Mutations in Metastatic Lung Adenocarcinoma

Activating epidermal growth factor receptor (EGFR) mutations in metastatic non-small cell lung cancer (NSCLC) are associated with a high response rate to EGFR tyrosine kinase inhibitor (TKI). The current guidelines recommend routine EGFR mutational analysis prior to initiating first line systemic therapy. The clinical characteristics including smoking status, histologic type, sex and ethnicity are known to be associated with the incidence of EGFR mutations. We retrospectively analyzed 277 patients with metastatic NSCLC within Kaiser Permanente Northern California (KPNC); among these patients, 83 were positive for EGFR mutations. We performed both univariate and multivariable logistic regressions to identify predictors of EGFR mutations. We found that histologic grade was significantly associated with the incidence of EGFR mutation, regardless of ethnicity, sex and smoking status. In grade I (well differentiated) and II (moderately differentiated), histology was associated with significantly higher incidence of EGFR mutations compared to grade II-III (moderate-to-poorly differentiated) and III (poorly differentiated). Ever-smokers with grade III lung adenocarcinoma had 1.8% incidence of EGFR mutations. This study indicates that histologic grade is a predictive factor for the incidence of EGFR mutations and suggests that for patients with grade II-III or III lung adenocarcinoma, prompt initiation of first-line chemotherapy or immunotherapy is appropriate while awaiting results of EGFR mutational analysis, particularly for patients with history of smoking.
Factors Affecting the Selection of Refrigerating Equipment in the Citrus Industry: Refrigeration for Frozen Concentrated Citrus Juices

To the Refrigerating Engineer, the Citrus Industry presents a challenging and interesting array of problems. The tremendous acceptance of Air Conditioning coupled with the wide use of refrigeration in processes of all types has led to development of many acceptable refrigerants and refrigerating machines. For the concentration, freezing, and storage of citrus juices, refrigeration is required at various temperature levels.Paper published with permission.Compilation Copyright © 2018 ASME
The Electromotive Force in Different Reference Frames

The electromotive force (EMF) is the work per unit charge around a wire loop caused by a time-varying magnetic flux threading the loop. It is due to a force moving the charges around the loop. This is true whether the change in flux is due to the wire loop being stationary and the field changing in time, or the loop moving through a spatially varying field. In the first case, we say that the time-varying magnetic field induces an electric field that provides the force; in the second, we say that the force is due to the magnetic field acting on the charges in the moving loop. The theory of relativity states that both viewpoints must be equivalent, but it is sometimes difficult to harmonize them.
Electrophysiological mapping and neuroimaging

Although electrical activity recorded from the exposed cerebral cortex of a monkey was reported in 1875 [1], it was not until 1929 that Hans Berger, a psychiatrist in Jena, Germany, first recorded noninvasively rhythmic electrical activity from the human scalp [2], which has subsequently known as electroencephalography (EEG). Since then, EEG has become an important tool for probing brain electrical activity and aiding in clinical diagnosis of neurological disorders, due to its excellent temporal resolution in the order of msec. The first recording of magnetic fields from the human brain was reported in 1972 by David Cohen at the Massachusetts Institute of Technology [3], which led to the development of magnetoencephalography (MEG). Like EEG, MEG also enjoys high temporal resolution in detecting brain electrical activity. EEG and MEG have become two prominent methods for noninvasive assessment of brain electrical activity, providing unsurpassed temporal resolution, in neuroscience research and clinical applications such as epilepsy or sleeping disorders.
Internet of Things-enabled smart cities: State-of-the-art and future trends

Abstract The dramatic spread of urbanization in modern cities requires smart solutions to address critical issues such as mobility, healthcare, energy, and civil infrastructure. The Internet of Things (IoT) is one of the most promising enabling technologies for tackling these challenges by creating a massive world-wide network of interconnected physical objects embedded with electronics, software, sensors, and network connectivity. Arguably, IoT is becoming the building block for next generation smart cities owing to its potential in exploiting sustainable information and communication technologies. The rapid development of the IoT is impacting several scientific and engineering application domains. This paper presents a comprehensive literature review of key features and applications of the IoT paradigm to support sustainable development of smart cities. An emphasis is placed on concomitance of the IoT solutions with other enabling technologies such as cloud computing, robotics, micro-electromechanical systems (MEMS), wireless communications, and radio-frequency identification (RFID). Furthermore, a case study is presented to demonstrate how an affordable and suitable IoT-based working prototype can be designed for real-time monitoring of civil infrastructure. Finally, challenges and future directions for IoT-based smart city applications are discussed.
Torsades de Pointes in Intravenous Drug Abuse-Associated Infective Endocarditis.

Intravenous drug abuse rates in the United States have increased exponentially in recent years. Ohio is one of 5 states with the highest age-adjusted drug overdose death rates, with drug overdose causing 39.1 of every 100,000 deaths. In patients who survive, the associated morbidity poses a significant public health burden. Infective endocarditis, defined as an infection of the endocardium of the heart, is a potentially lethal consequence of bacteremia related to intravenous drug abuse. Methicillin-sensitive Staphylococcus aureus (MSSA) is the most commonly implicated organism and may affect the tricuspid valve. Indications for surgery include failure of medical management, worsening embolization, heart failure, and arrhythmias—typically bradyarrhythmias from infectious extension into the conduction system. Vegetation size and type of infection, such as drug-resistance pattern, fungal infection, and presence of prosthetic material, are becoming known risk factors for complications. Studies have demonstrated that early surgery tends to have a better prognosis than delayed intervention. Established guidelines for right-sided surgery are slowly evolving. Tricuspid valve surgery is becoming more common in these cases, but there is known risk for heart block owing to proximity of the conduction system to the tricuspid valve annulus. If patients develop complete heart block postoperatively, pacemaker placement may be indicated. There may be reluctance to implantation because of the risk of device infection with infective endocarditis. In addition, many may recover conduction as infection and edema resolve. Generally, bradyarrhythmias are well tolerated. However, we present 2 cases of torsades de pointes related to post-tricuspid-valve-replacement bradyarrhythmia. Torsades de pointes is a potentially lethal form of polymorphic ventricular arrhythmia associated with QT interval prolongation. Post-tricuspid-valve- replacement mortality may be secondary to induced lethal ventricular arrhythmias.
Fretting-corrosion in hip implant modular junctions: New experimental set-up and initial outcome

Modern hip prostheses feature a modular implant design with at least one tapered junction. This design can lead to several complications due to the introduction of additional interfaces, which are subjected to various loading conditions and micromotion. The main objective of current study is to develop a fretting corrosion apparatus, which is able characterize the mechanical and electrochemical behaviour of various existing metal alloy couples during fretting motion. This study describes the design and the main considerations during the development of a novel fretting corrosion apparatus, as well as determination of the machine compliance and the initial testing results. Machine compliance considerations and frictional interactions of the couples are discussed in detail. For the preliminary tests, metal alloy pins, made of Ti6Al4V and wrought high-carbon CoCrMo were mechanically polished to a surface roughness of less than 20nm. 2 pins (Diameter = 11mm) of either Ti6Al4V or CoCrMo were loaded onto a Ti6Al4V alloy rod at a normal force of 200N. The interface types included: Ti6Al4V-Ti6Al4V-Ti6Al4V, Ti6Al4V-Ti6Al4V-CoCrMo, and CoCrMo-Ti6Al4V-CoCrMo. The Ti6Al4V rod articulated against the metal alloy pins in a sinusoidal fretting motion with a displacement amplitude of ±50μm. Bovine calf serum (30g/L of protein content) was selected as a lubricant and tested at 2 different pH levels (pH 3.0 and 7.6). In all cases, current and friction energy were monitored during the fretting process. The results indicated distinct, material-specific current evolutions and friction energies. No significant differences were observed in electrochemical or mechanical behaviour in response to pH change. In general, Ti6Al4V-Ti6Al4V-Ti6Al4V couples displayed the earliest passivation and superior electrochemical behaviour compared to Ti6Al4V-Ti6Al4V-CoCrMo and CoCrMo-Ti6Al4V-CoCrMo under fretting conditions. In addition, fluctuations in current were observed in specific regions at all instances where Ti6Al4V was coupled with Ti6Al4V. These fluctuations were not observed in instances where Ti6Al4V was coupled with CoCrMo. These findings suggest transitions in the degradation mechanisms at the modular junction as a function of material couples/contacts. The findings may assist in improving the current hip modular junctions.
Nitrogen in the Earth: abundance and transport

The terrestrial nitrogen budget, distribution, and evolution are governed by biological and geological recycling. The biological cycle provides the nitrogen input for the geological cycle, which, in turn, feeds some of the nitrogen into the Earth’s interior. A portion of the nitrogen also is released back to the oceans and the atmosphere via N2 degassing. Nitrogen in silicate minerals (clay minerals, mica, feldspar, garnet, wadsleyite, and bridgmanite) exists predominantly as NH4+. Nitrogen also is found in graphite and diamond where it occurs in elemental form. Nitrides are stable under extremely reducing conditions such as those that existed during early planetary formation processes and may still persist in the lower mantle. From experimentally determined nitrogen solubility in such materials, the silicate Earth is nitrogen undersaturated. The situation for the core is more uncertain, but reasonable Fe metal/silicate nitrogen partition coefficients (> 10) would yield nitrogen contents sufficient to account for the apparent nitrogen deficiency in the silicate Earth compared with other volatiles. Transport of nitrogen takes place in silicate melt (magma), water-rich fluids, and as a minor component in silicate minerals. In melts, the N solubility is greater for reduced nitrogen, whereas the opposite appears to be the case for N solubility in fluids. Reduced nitrogen species (NH3, NH2−, and NH2+) dominate in most environments of the modern Earth’s interior except the upper ~ 100 km of subduction zones where N2 is the most important species. Nitrogen in magmatic liquids in the early Earth probably was dominated by NH3 and NH2−, whereas in the modern Earth, the less reduced, NH2+ functional group is more common. N2 is common in magmatic liquids in subduction zones. Given the much lower solubility of N2 in magmatic liquids compared with other nitrogen species, nitrogen dissolved as N2 in subduction zone magmas is expected to be recycled and returned to the oceans and the atmosphere, whereas nitrogen in reduced form(s) likely would be transported to greater depths. This solubility difference, controlled primarily by variations in redox conditions, may be a factor resulting in increased nitrogen in the Earth’s mantle and decreasing abundance in its oceans and atmosphere during the Earth’s evolution. Such an abundance evolution has resulted in the decoupling of nitrogen distribution in the solid Earth and the hydrosphere and atmosphere.
Reasons for Tobacco Use and Perceived Tobacco-Related Health Risks in an Inpatient Psychiatric Population

People with mental illness (MI) have a disproportionate tobacco-related disease burden and mortality. Tobacco-use rates in people with MI are nearly twice that of the general population. Reasons fo...
The Application of Experiential Avatar-based Sales and Service Training in International Business Curriculums: A Practical Guide for Instructors

The use of avatar technology allows faculty to replicate human interaction in a number of International Business (IB) courses. In this chapter, we provide instructors the pedagogy for the application of avatars in global sales and service settings. This allows the instructor to better prepare students for internships and entry-level positions. Once mastered, the technology is transferable to other business disciplines.
Predictors of intracranial hypertension in children undergoing ICP monitoring after severe traumatic brain injury

Intracranial hypertension (ICH) is a common and treatable complication after severe traumatic brain injury (sTBI) in children. Describing the incidence and risk factors for developing ICH after sTBI could impact clinical practice. Retrospective cohort study from 2006 to 2015 at two university-affiliated level I pediatric trauma centers of children admitted with accidental or abusive TBI, a post-resuscitation Glasgow Coma Score (GCS) of 8 or less, and an invasive intracranial pressure (ICP) monitor. Bivariate and multivariable logistic regression analysis were performed to identify demographic, injury, and imaging characteristics in patients who received ICP directed therapies for ICH (ICP > 20 mmHg). Eight to 5% (271/321) of monitored patients received ICP directed therapy for ICH during their PICU stay. Ninety-seven percent of patients had an abnormality on CT scan by either the Marshall or the Rotterdam score. Of the analyzed clinical and radiologic variables, only presence of hypoxia prior to PICU arrival, female sex, and a higher Injury Severity Score (ISS) were associated with increased risk of ICH (p < 0.05). In this retrospective study of clinical practice of ICP monitoring in children after sTBI, the vast majority of children had an abnormal CT scan and experienced ICH requiring clinical intervention. Commonly measured clinical variables and radiologic classification scores did not significantly add to the prediction for developing of ICH and further efforts are needed to define low-risk populations that would not develop ICH.
Transformation Importance with Applications to Cosmology.

Machine learning lies at the heart of new possibilities for scientific discovery, knowledge generation, and artificial intelligence. Its potential benefits to these fields requires going beyond predictive accuracy and focusing on interpretability. In particular, many scientific problems require interpretations in a domain-specific interpretable feature space (e.g. the frequency domain) whereas attributions to the raw features (e.g. the pixel space) may be unintelligible or even misleading. To address this challenge, we propose TRIM (TRansformation IMportance), a novel approach which attributes importances to features in a transformed space and can be applied post-hoc to a fully trained model. TRIM is motivated by a cosmological parameter estimation problem using deep neural networks (DNNs) on simulated data, but it is generally applicable across domains/models and can be combined with any local interpretation method. In our cosmology example, combining TRIM with contextual decomposition shows promising results for identifying which frequencies a DNN uses, helping cosmologists to understand and validate that the model learns appropriate physical features rather than simulation artifacts.
An Inventory of Existing Neuroprivacy Controls

Brain-Computer Interfaces (BCIs) facilitate communication between brains and computers. As these devices become increasingly popular outside of the medical context, research interest in brain privacy risks and countermeasures has bloomed. Several neuroprivacy threats have been identified in the literature, including brain malware, personal data being contained in collected brainwaves and the inadequacy of legal regimes with regards to neural data protection. Dozens of controls have been proposed or implemented for protecting neuroprivacy, although it has not been immediately apparent what the landscape of neuroprivacy controls consists of. This paper inventories the implemented and proposed neuroprivacy risk mitigation techniques from open source repositories, BCI providers and the academic literature. These controls are mapped to the Hoepman privacy strategies and their implementation status is described. Several research directions for ensuring the protection of neuroprivacy are identified.
Doped WS 2 transistors with large on-off ratio and high on-current

Doping of two-dimensional (2D) transition metal dichalcogenides (TMDs) is needed to adjust the threshold voltage (V T ) and to increase the current drive by reducing both the channel and sheet resistances [1] . However, doping in TMDs often results in a sharp degradation in the on-off ratio of the field-effect transistors (FETs) [2] , [3] . Tungsten disulfide (WS 2 ) is a layered TMD with a large band-gap (> 2 eV in bilayers [4] ). We show a stable n-type doping technique using sub-stoichiometric Aluminum oxide (AlO X ) [5] in exfoliated bilayer WS 2 transistors which results in the highest reported per-layer on-current for WS 2 (80 µA/µm per layer) while retaining the high on-off ratio (10 8 ) and low off-current (≈ 5x10 -13 A/μm). Modelling these devices reveals a large interfacial trap density (1×10 13 cm 2 eV -1 ) and a high Schottky barrier height (SBH) at the contacts (0.4 eV).
High‐Throughput Label‐Free Enzymatic Assays Using Desorption Electrospray‐Ionization Mass Spectrometry

High-throughput (HT) enzymatic assays, which typically rely on labeled compounds and plate readers, are important for drug discovery. Mass spectrometry (MS) provides an alternative method of performing HT label-free assays. Here we demonstrate the use of a HT platform based on desorption electrospray ionization (DESI) MS for the label-free study of enzymatic reactions directly from the bioassay matrix with an effective analysis time of 0.3 s per sample. This system allows for thorough analysis of the enzymatic process through monitoring of its substrate and product after an external calibration. We show the platform capabilities by an in-depth study of the acetylcholinesterase assay, including kinetic parameter determination, rapid inhibitor screening, and further characterization of positive hits (that is, IC50 and Ki ), as well as inhibition-reactivation assays. We anticipate that the expansion of this platform has high potential impact in label-free enzymology as well as in drug discovery.
Versatile Nickel(II) Scaffolds as Coordination-Induced Spin-State Switches for 19 F Magnetic Resonance-Based Detection.

19 F magnetic resonance (MR) based detection coupled with well-designed inorganic systems shows promise in biological investigations. Two proof-of-concept inorganic probes that exploit a novel mechanism for 19 F MR sensing based on converting from low-spin (S=0) to high-spin (S=1) Ni2+ are reported. Activation of diamagnetic NiL1 and NiL2 by light or β-galactosidase, respectively, converts them into paramagnetic NiL0 , which displays a single 19 F NMR peak shifted by >35 ppm with accelerated relaxation rates. This spin-state switch is effective for sensing light or enzyme expression in live cells using 19 F MR spectroscopy and imaging that differentiate signals based on chemical shift and relaxation times. This general inorganic scaffold has potential for developing agents that can sense analytes ranging from ions to enzymes, opening up diverse possibilities for 19 F MR based biosensing.
Picking Gifts for Picky People

Abstract Shoppers report that 39% of their holiday gift-purchases are for someone “picky.” However, despite the ubiquity of shopping for picky people, little research has examined how people choose gifts for picky people. In the present research, we define the “picky gift recipient” as someone perceived to have narrow and unpredictable preferences, and we show how shopping for someone picky alters gift giving behavior. We find that although gift giving norms prescribe that gift givers spend effort, time, and money on gifts to strengthen their social ties, an exception to this rule occurs when a gift recipient is picky. When shopping for someone picky, givers believe that increasing their resources on a gift will not result in greater recipient-satisfaction with the gift itself—a lay belief that ultimately demotivates givers, causing them to spend fewer resources on picky people (even picky friends). That said, we find that consumers are more willing to spend money on superficial gift-features for picky people, such as professional wrapping, to “dress up” their gifts. Based on this preference, we developed and tested a novel promotion strategy that retailers could implement to recoup some of the lost spending by consumers who are shopping for picky people. In all, this research contributes to the literature on gift giving dynamics, and provides insights more broadly into how shoppers negotiate the burden of shopping for someone whom they anticipate will not like their choice.
Luck Has Nothing To Do With It: Prevailing Uncertainty and Responsibilities of Due Care

We are surrounded by threats of environmental harm whose actual dangers to public health are scientifically unverified. It is widely presumed that under conditions of uncertainty, when it is not po...
Water quality for livestock in northern Great Plains rangelands

Abstract Dissolved solids can negatively impact livestock drinking water. To characterize dissolved solid concentrations in the northern Great Plains, we studied 45 water sources over 11 yr. Ca, F, Mg, Na, and total solids sometimes exceeded recommended levels but rarely reached levels empirically shown to negatively impact livestock. Fe often attained concentrations that reduce water consumption, which can reduce feed intake and weight gain. Excessive Fe was likeliest in creeks and reservoirs. SO4 sometimes reached concentrations that reduce weight gain but rarely reached concentrations causing health problems. Excessive SO4 was least likely in reservoirs. A safeguard against water quality problems is ensuring livestock can access multiple water source types (e.g., wells and reservoirs) so that they can use taste and smell to choose acceptable water. Where this is impossible, water quality monitoring is of greater importance. Inexpensive electrical conductivity meters roughly estimate water quality and can identify watering locations requiring more detailed monitoring.
Hybrid fixation in anatomic shoulder arthroplasty: surgical technique and review of the literature

Hybrid constructs have been used as a primary fixation technique in primary anatomic total shoulder arthroplasty for more than a decade. A highly porous metal central peg, metal cage, or coatings attached to the surface of cemented polyethylene glenoid component have been used with the concept of providing an additional adjunct in promoting osseointegration, preventing glenoid component loosening, and promoting longer-term success. The purpose of this article is to analyze the published results, complications, as well as rate of revision using this form of glenoid fixation. In addition, key aspects of the surgical technique that may be considered to facilitate optimal results when hybrid fixation is considered in total shoulder arthroplasty are also reviewed.
Transcultural Entanglements and Disentanglements: Growing Impacts and Influences of Innovation, Religion, Sustainable Development and Information Technology (Presentation Slides)

Why do concepts such as innovation, creativity, sustainable development and religion have profound and increasingly important impacting roles on modern societies – as well as processes involving “transcultural entanglements and disentanglements”? An underlying notion and belief of ancient Egyptians was that your behavior in life determined your fate in “the after-life” and this is considered by several archaeologists and Egyptologists as having impacted other religions in respect of preparations for the after-life. Even though such beliefs can be associated and do identify with many other religions, there are differences in importance attached to concepts of the soul, body and spirit – the spirit being fundamental and core to Christian beliefs and the life after. The preservation of the physical body in “the after life” was particularly very important to ancient Egyptians. Such preservation of the body being very important to ancient Egyptians because they believed that the soul needed to return to the body – and therefore, it was important to preserve the body in the best possible condition, through the process of “mummification” – “such that the body could be recognized by the soul”. This paper aims to explains how innovation, creativity, sustainable development and particularly religion, are shaping modern societies and also identify those limitations and challenges encountered by religion to completely bring some stability or rather, serve as a stabilizing and organising force in the process of transcultural disentanglement. Such limitations owing to the need for consideration of other driving forces such as climate change and their impact on relationships – as well as human and social behaviors. Religion – its power to unify differences and its ability to incorporate stability in dynamic societies – and a particularly continuously changing and adapting world, is also limited in some way by a force and concept from which it derives much of its impact – politics. Politics within religious institutions and bodies have had such impact that its self serving purposes and characteristics have to an extent, undermined the potential of religion in its unifying purpose. Hence other concepts such as innovation, creativity are not only impacting modern societies considerably, but are addressing vital economic issues such as employment – through the generation of entrepreneurs and programs which also give consideration to matters of immense social importance – namely sustainable development and the need to address climate change. This phenomenal revolution in the acknowledgement of the potential of sustainability and sustainable development, its potential for innovative partnerships and growth of entrepreneurs is evidenced across many areas which are bounded by the Atlantic and Indian oceans. Such evidence and innovative partnerships and collaborations is exemplified through programs such as “Debt for Nature” and “Debt for Dolphins and Marine Conservation” Swaps.
Living with Autonomy: Public Perceptions of an AI-Mediated Future:

The arrival of autonomous systems powered by artificial intelligence (AI) offers new possibilities for life, yet the focus tends to be more on the technology than the people it serves. Planners sho...
Defining the Variance: The Current State of Female and URM Concordance of Urology Resident Workforce to the General U.S. Population

Abstract Objective To compare the current representation of women and underrepresented minorities in medicine (URM) of the urologic resident workforce to the general U.S. population. Materials and Methods Data on current gender and racial distribution of U.S. urology residents was obtained from the 2019-2020 ACGME Data Resource Book and compared to the projected 2019 U.S. population as reported in the U.S. Census data. In this study, URM status included Black/African American, Hispanic/Latino, Native American/Alaskan, Native Hawaiian or Pacific Islander and Other. For each gender and race/ethnicity, the percent differences in representation were calculated by subtracting the frequency in the general U.S. population from that of the urology resident workforce and two sample z-tests were performed. Results 1734 urology residents were identified in 2019-2020, of which 471 (27.2%) were female and 258 (14.9%) were URM. Two sample z-tests revealed a significantly lower representation in urologic residency programs for women (-23.6%, P-value Conclusion Women and URMs continue to be significantly underrepresented in urology residency relative to the general U.S. population. Further study should better understand barriers to entering the urologic workforce and identify strategies to encourage interest in urology among female and URM prospective trainees.
Light sets the brain’s daily clock by regional quickening and slowing of the molecular clockworks at dawn and dusk

Abstract How daily clocks in the brain are set by light to local environmental time and encode the seasons is not fully understood. The suprachiasmatic nucleus (SCN) is a central circadian clock that orchestrates physiology and behavior in tune with daily and seasonal light cycles. Here we have found that optogenetically simulated light input to explanted SCN changes the waveform of the molecular clockworks from sinusoidal in free-running conditions to highly asymmetrical shapes with accelerated synthetic (rising) phases and extended degradative (falling) phases marking clock advances and delays at simulated dawn and dusk. Daily waveform changes are sufficient to entrain to simulated winter and summer photoperiods, and to non-24h periods. SCN imaging further reveals that acute waveform shifts are greatest in the ventrolateral SCN, while period effects are greatest in the dorsomedial SCN. Thus, circadian entrainment is encoded by SCN clock gene waveform changes that arise from spatiotemporally distinct intrinsic responses within the SCN neural network.
3-D Super-Resolution Ultrasound Imaging for Monitoring Early Changes in Breast Cancer after Treatment with a Vascular-Disrupting Agent

The purpose of this research project was to evaluate the use of 3-dimensional (3-D) super-resolution ultrasound (SR-US) imaging to assess any early changes in breast cancer after treatment with a vascular-disrupting agent (VDA). A Vevo 3100 ultrasound system (FUJIFILM VisualSonics Inc) equipped with an MX 201 transducer was used for image acquisition. A total of $2.5\times 10^{7}$ microbubbles (MBs) were injected into the tail vein of anesthetized breast cancer-bearing mice using repeat bolus injections every 5 min. A total of 10 stacks of ultrasound images were collected as the transducer was mechanically moved across the tumor at 0.6 mm intervals yielding a 6-mm thick volume. At each tumor location, a stack contained $1\ \times\ 10^{4}$ frames of ultrasound data that were acquired at 463 frames/sec and stored as in-phase/quadrature (IQ) format. After motion correction, each temporal stack of ultrasound images was processed separately for clutter signal removal, which was followed by MB localization and enumeration before generation of the final SR-US image. After reconstruction of the 3-D SR-US volume dataset, the tumor microvasculature was enhanced using a multiscale vessel enhancement filter. Vessels from the resultant microvascular network were then segmented using an adaptive thresholding method. Finally, mean microvascular density (MVD) measurements from each tumor volume were computed as a summarizing statistic. While no differences were found between baseline SR-US image-derived measures of MVD ( $p=0.76$ ), these same measurements were significantly lower at 24 $h$ after VDA treatment ( $p ). Overall, 3-D SR-US imaging detected early tumor changes following treatment with a vascular-targeted drug.
Three essays on welfare implications of R&D policies in the presence of spillovers

This dissertation consists of three essays investigating welfare implications of RDThe first essay examines the policy implications of a research joint venture (RJV) while introducing endogenous spillovers and costly RJV. The research joint venture is costly in the sense that the firms incur two kinds of costs when they join in an RJV: RJV formation costs and spillover costs. RJV formation costs are modeled as fixed while spillover costs increase with the amounts of information sharing within an RJV. We derive the condition under which firms do not have an incentive to form an RJV, and identify when firms within an RJV share information completely. This essay also finds that private interests with an RJV are not consistent with public interests for a wide range of RJV formation costs, which suggests the potential need for active government intervention with respect to RJV formation.;The second essay investigates the welfare effects of intellectual property rights (IPR) protection in terms of north-south trade. It asks which southern countries, if any, should provide more IPR protection, assuming that the differentiated IPR protection among southern countries can be made through a WTO (World Trade Organization) agreement. Only the northern country innovates, and n-1 southern countries have different capacities to absorb knowledge from the northern innovations. The outcome of innovations reduces the unit production cost of the northern firm, and also provides benefits to the southern firms through spillovers. This essay shows that the southern countries can be classified into three groups in terms of the welfare effects of spillovers. The countries in the first group are better off from relaxed IPR protection both in their own countries and in the other countries. The countries in the second group are better off from spillovers in their country, but worse off from spillovers in the other group. The third group suffers from welfare loss whenever IPR protection is relaxed in any southern country. The northern country is worse off by relaxed IPR protection in any southern country for wide ranges of RDThe last essay combines the analysis of the R&D cooperation with the strategic trade policy theory. Endogenizing spillovers (information sharing) within an RJV, it identifies when the RJV works as a tool of strategic trade policy, and provides its welfare implications. Many results obtained in the third market structure become reversed in the integrated market structure. In the situation where only the home country allows an RJV formation while the foreign country does not, allowing an RJV benefits the home country in the third market structure, but it hurts the home country in the case of integrated market structure if spillover costs are sufficiently high. We also identify the Nash equilibria of the policy game in which both the home and the foreign countries simultaneously decide whether to allow an RJV or not, and investigate the welfare implications when both the home and the foreign countries allow an RJV formation in each country. (Abstract shortened by UMI.)
Are Epistemic Concepts Reducible to Ethical Concepts

When discussing problems in theory of knowledge we often find ourselves using a terminology that is characteristically ethical. We may ask what it is that distinguishes a good hypothesis or explanation from a bad one. We may affirm or deny that mere simplicity can sometimes make one hypothesis preferable to another. We may say that we ought to trust our memories to the extent that they cohere with one another. We may decide that this or that kind of inference to theoretical entities ispermissible. We may wonder if we could ever have the right to accept a theory if we knew of an equally plausible, but incompatible, alternative. And so forth. Facts of this kind suggest that epistemological questions are a species of ethical questions, and that epistemic concepts are reducible to ethical concepts to whatever extent this entails.
Does a Seller Really Want Another Bidder

Jeremy I. Bulow and Paul D. Klemperer (AER, 1996) argue that the usual concerns of auction design miss the big picture, and show that a simple English auction without a reserve price and N +1 bidders attains expected revenue in excess of any auction with N bidders. The issue of how this additional bidder might be attracted is not treated in their model. In fact, that an auction can convince another bidder it is worth his while to compete carries a critical message about expected revenue. In those many markets where potential bidders decide whether to compete in an auction based on the expected pro…tability of bidding, Bulow and Klemperer’s conclusion is shown here to be overturned. I explore the symmetric equilibrium of a model where potential bidders …rst decide whether to participate in an auction, and then participants select bidding strategies. Expected revenue is increased by some degree of bidder discouragement, in that it is never optimal to have all N potential bidders participate with probability one, even for very small N. D44; D82; C72; Keywords: a¢ liated-values auctions, auction revenue, number of bidders, increased competition, endegenous bidder participation
Local lithospheric relief associated with fracture zones and ponded plume material

[1] Buoyant plume material ponds at the base of oceanic lithosphere. It is a natural probe for the relief on the base of the lithosphere owing to plate age because it flows laterally along an upside-down drainage pattern. Geomorphic and geochemical studies of near-ridge and on-ridge hot spots indicate, as expected, that the oceanic lithosphere thickens as it ages. Corridors of thin lithosphere channel plume material along the axis, while the thick lithosphere at the end of ridge segments dams this along-axis flow. Channel hot spots extend from plumes toward ridge axes. However, a good correlation between local lithospheric thickness and local age is not evident at fracture zones within the old ocean basins. Such a correlation would be expected if the lithosphere cooled only by conduction. Then pressure-release melting and volcanoes would occur preferentially near fracture zones where plume material cascades from thick old to thin young lithosphere. This concentration of volcanic edifices does not occur. This lack of correlation between lithosphere thickness and plate age is an expected consequence of small-scale convection at the base of the lithosphere. Scaling relationships and numerical models indicate that modestly vigorous convection of several milliwatt per meter squared is sufficient to perturb local lithospheric relief beneath fracture zones without changing the gross correlation of lithospheric thickness with plate age. Typically, the step in lithospheric thickness moves toward the old side of the fracture zone.
Regulation and role of heme oxygenase in oxidative injury.

Summary The HO-1 isoenzyme is an early stress response gene regulated by many forms of oxidative stress. The HO-2 isoenzyme is predominantly a constitutive enzyme, which may serve to sequester hemo as well as degrade it. All HO enzyme activity results in the degradation of heme and the production of antioxidant bile pigments, which would favor an antioxidant role for the enzyme. In fact, in oxidative stress in vitro , HO-1 is protective (91–94) but within a narrow threshold of overexpression (93,94) in some models, since iron released in the HO reaction may obviate any cytoprotective effect (Fig. 3). So far, HO-2 appears to be beneficial in oxygen toxicity in vivo , but the consequences of HO-2 overexpression have not yet been tested. It will be important to better define the role of each HO isoenzyme in oxidative stress so as to determine whether enhancing these complex systems could alleviate some of the cellular changes seen as a result of oxidative injury. Furthermore, prior to considering therapeutic maneuvers to enhance HO, a complete understanding of the physiologic consequences of HO-1 induction and associated reactions, in each particular setting, will be crucial.
Earnings Response Coefficient and Persistence: New Evidence Using Tobin's q as a Proxy for Persistence:

Prior studies have documented that the earnings response coefficient is positively related to persistence and growth and negatively related to beta and the risk-free rate. Although these studies pr...
Expression and phosphorylation of insulin receptor substrate 1 during rat liver regeneration

Insulin has been shown to be important for normal liver regeneration to occur. The mechanisms whereby insulin may exert its effects on hepatocyte growth, however, are still unknown. The rat and human insulin receptor substrate 1 (IRS-1) is a specific target molecule for the insulin receptor beta subunit kinase and will bind to signal transducing molecules containing Src homology 2 domains through its multiple tyrosyl phosphorylation (TP) sites. This investigation examined how IRS-1 may be involved in insulin action during hepatocyte growth induced by two-thirds partial hepatectomy. The TP of IRS-1 was strikingly enhanced prior to the major wave of hepatocyte DNA synthesis at 24 h; IRS-1 protein and mRNA expression increased in parallel to a lesser extent after partial hepatectomy. TP of insulin receptor beta subunit, which enhances its kinase activity toward IRS-1, was increased in association with TP of IRS-1. Finally, phosphatidylinositol 3-kinase, one of signal transducing molecules containing Src homology 2 domains, was associated with IRS-1 following TP in vivo. These observations suggest that IRS-1 protein may play an important role in transmitting the insulin signal to intracellular regulators involved in hepatocyte growth.
Crystalline inclusions in the rabbit blastocyst: Evidence for microtubular aggregates

Abstract Rod-shaped, membrane-bounded crystalline inclusions present in rabbit blastocysts were examined using electron microscopy and gel electrophoresis. Ultrastructural analysis reveals that the inclusions contain tubular elements which have the characteristics of microtubules including a wall composed of 13 subunits, or protofilaments. Unusual features of individual microtubules seen in negatively stained preparations are described. SDS polyacrylamide gel electrophoresis of inclusion-enriched fractions from blastocyst homogenates reveals a prominent band having a mobility identical with purified tubulin. The microtubules within the inclusions are considerably more stable than are cytoplasmic microtubules with respect to cold treatment and incubation in colchicine-containing solutions. The possibility that these inclusions might serve as a reservoir of microtubular protein for utilization in blastocyst growth and ovo-implantation is discussed.
Testing for HPV as an objective measure for quality assurance in gynecologic cytology: positive rates in equivocal and abnormal specimens and comparison with the ASCUS to SIL ratio.

BACKGROUND Inappropriate use of the category of atypical squamous cells of undetermined significance (ASCUS) can result in overtreatment or undertreatment of patients, which may decrease the cost effectiveness of screening. Quality assurance tools, such as the ASCUS to squamous intraepithelial lesion ratio (ASCUS:SIL) and case review, are imperfect. High-risk HPV (hrHPV) testing is an objective test for a known viral carcinogen, and hrHPV may be more useful in monitoring the quality of ASCUS interpretations. METHODS hrHPV rates for cytologic diagnoses and patient age groups were calculated for a 2-year period. All hrHPV results for ASCUS and SIL over a 17-month period were analyzed by patient age group, over time, and by individual cytopathologist to compare hrHPV rates with the corresponding ASCUS:SIL. RESULTS The hrHPV positive rate for SIL was >90%, and it was 32.6% for ASCUS. Stratification by patient age showed that approximately 50% of patients younger than 30 years and older than 70 years of age were hrHPV positive, whereas other patients had a lower rate ranging from 14% to 34%. The overall ASCUS:SIL was 1.42, and the overall hrHPV positive rate was 39.9%. Over time and by individual cytopathologist, the hrHPV rate performed similarly to the ASCUS:SIL. The analysis by patient age showed a high statistical correlation (R2 = 0.9772) between the 2 methods. CONCLUSIONS Despite differences between these techniques, the hrHPV rate closely recapitulates the ASCUS:SIL. When used together, the 2 methods can complement each other. The desirable hrHPV-positive range appears to be 40% to 50%; however, this may vary based on the patient population. The hrHPV rate is as quick and cost effective as determining the ASCUS:SIL. Cancer (Cancer Cytopathol). 2007. © 2007 American Cancer Society.
Older Women/Younger Men

Abstract This study provides insight into the lives of eight married couples involved in an age-heterogamous relationship where the wife is ten or more years older than her husband. While there is a lot of information in the literature about men who date and marry younger women, the research on this subject is very limited or outdated. This exploratory study provides valuable information in several areas about couples in woman-older marriages. The interviews were conducted with each participant separately and explored three major topics of interest: The impact the age difference has on the relationship, the issues that arise for the couple, and any difference in husbands and wives experience. Implications for professionals working with such couples, as well as for further research, are discussed.
Content-based image retrieval by scale-space object boundary shape representation

Shape is a popular feature used for content-based image retrieval. In this paper we propose a new method for image retrieval using a shape boundary represented in scale-space. The proposed method is suggested by the notion of 'dynamic shape' where all 2D boundary representations evolve from a single, primeval, featureless shape - a circle. Shape is represented by linearizing the boundary based on the polar coordinates of boundary points relative to the object's centroid. Points on the shape boundary are mapped to a primeval circle, and two functions are defined, the Radius Difference Function and the Angle Difference Function,and smoothed through scale-space to devolve the shape. Maxima and minima of the Radius Difference Function are extracted and used to calculate similarity between objects. Similarity is calculated using Euclidean distance. Other scale-space approaches to shape representation use various techniques to maintain constant boundary arc length, that any otherwise change in non-intuitive ways over scale. We introduce the contour stability over scale property stating that the perceived boundary length should not change significantly over scale. Experiments show that significant similarity computation may be saved by using coarser scales without effectively reducing retrieval performance.
Poly(glycoamidoamine)s for gene delivery. structural effects on cellular internalization, buffering capacity, and gene expression.

The study of polymeric nucleic acid delivery vehicles has recently grown because of their promise for many biomedical applications. In an effort to understand how the chemical traits of polymers affect the biological mechanisms of nucleic acid delivery, we have calculated the buffering capacity in the physiological pH range of a series of 10 poly(glycoamidoamine)s with systematic structural variations in the amine stoichiometry (from 1 to 4), carbohydrate moiety (d-glucarate or l-tartarate), and amine spacer (ethylene or butylene) within their repeat units. In addition, we have compared the buffering capacity of these polymeric vectors to their polyplex (polymer−DNA complex) stability, cellular internalization, and gene expression profiles to understand the parameters that are important for increasing gene delivery efficiency. The results indicate that the buffering capacity is not always the primary characteristic that determines the gene delivery efficiency for all the poly(glycoamidoamine)s. We have fo...