cssi/SciSciGPT-SciSciNet huggingface dataset:
Novel Third-Generation EGFR Tyrosine Kinase Inhibitors and Strategies to Overcome Therapeutic Resistance in Lung Cancer

EGFR-activating mutations are observed in approximately 15% to 20% of patients with non–small cell lung cancer. Tyrosine kinase inhibitors have provided an illustrative example of the successes in targeting oncogene addiction in cancer and the role of tumor-specific adaptations conferring therapeutic resistance. The compound osimertinib is a third-generation tyrosine kinase inhibitor, which was granted full FDA approval in March 2017 based on targeting EGFR T790M resistance. The compound has received additional FDA approval as first-line therapy with improvement in progression-free survival by suppressing the activating mutation and preventing the rise of the dominant resistance clone. Drug development has been breathtaking in this space with other third-generation compounds at various stages of development: rociletinib (CO-1686), olmutinib (HM61713), nazartinib (EGF816), naquotinib (ASP8273), mavelertinib (PF-0647775), and AC0010. However, therapeutic resistance after the administration of third-generation inhibitors is complex and not fully understood, with significant intertumoral and intratumoral heterogeneity. Repeat tissue and plasma analyses on therapy have revealed insights into multiple mechanisms of resistance, including novel second site EGFR mutations, activated bypass pathways such as MET amplification, HER2 amplification, RAS mutations, BRAF mutations, PIK3CA mutations, and novel fusion events. Strategies to understand and predict patterns of mutagenesis are still in their infancy; however, technologies to understand synthetically lethal dependencies and track cancer evolution through therapy are being explored. The expansion of combinatorial therapies is a direction forward targeting minimal residual disease and bypass pathways early based on projected resistance.
Associations between state-level policy liberalism, cannabis use, and cannabis use disorder from 2004 to 2012: Looking beyond medical cannabis law status.

Abstract Background Medical cannabis laws (MCL) have received increased attention as potential drivers of cannabis use (CU), but little work has explored how the broader policy climate, independent of MCL, may impact CU outcomes. We explored the association between state-level policy liberalism and past-year cannabis use (CU) and cannabis use disorder (CUD). Methods We obtained state-level prevalence of past-year CU and CUD among past year cannabis users for ages 12–17, 18–25, and 26+ from the 2004–2006 and 2010–2012 National Surveys on Drug Use and Health. States were categorized as liberal, moderate, or conservative based on state-level policy liberalism rankings in 2005 and 2011. Linear models with random state effects examined the association between policy liberalism and past-year CU and CUD, adjusting for state-level social and economic covariates and medical cannabis laws. Results In adjusted models, liberal states had higher average past-year CU than conservative states for ages 12–17 (+1.58 percentage points; p = 0.03) and 18–25 (+2.96 percentage points; p = 0.01) but not for 26+ (p = 0.19). CUD prevalence among past year users was significantly lower in liberal compared to conservative states for ages 12–17 (−2.87 percentage points; p = 0.045) and marginally lower for ages 26+ (-2.45 percentage points; p = 0.05). Conclusion Liberal states had higher past-year CU, but lower CUD prevalence among users, compared to conservative states. Researchers and policy makers should consider how the broader policy environment, independent of MCL, may contribute to CU outcomes.
Correction of medication nonadherence results in better seizure outcomes than dose escalation in a novel preclinical epilepsy model of adherence.

OBJECTIVE Medication nonadherence directly contributes to poor seizure control. A lack of emphasis on correcting poor adherence and failures in patient adherence can result in unwarranted alterations to a patient's drug regimen. We have modeled nonadherent patients in an animal model of epilepsy to study how alterations to pharmacotherapy, made without consideration of a patient's adherence, result in changes to seizure control. METHODS Newly diagnosed rats with epilepsy were treated with carbamazepine (CBZ) during a 4-week baseline period to establish their baseline seizure rate in the presence of 50% adherence. Next, animals were randomized to one of three treatment interventions and monitored for 6 weeks. Groups included: (1) no change in therapy-rats continued the 50% adherent paradigm; (2) dose escalation-the dose of CBZ was doubled, and the 50% adherent paradigm continued; and (3) nonadherence corrected-rats continued the initial dose of CBZ, but the adherence rate was adjusted to 100% (ie, fully adherent). RESULTS The rats in the no change in therapy arm displayed a 61% increase in seizure burden over the 6-week intervention phase. Similarly, rats in the dose escalation arm had a 66% worsening of their daily seizure burden. In contrast, rats in the nonadherence corrected arm displayed a 33% reduction in their daily seizure burden; a significant improvement when compared to the normalized seizure burden scores of rats in the other two treatment arms (P < 0.01). SIGNIFICANCE We found that failure to correct medication nonadherence resulted in an increase in daily seizure burden in rats, even following dose escalation. In the presence of nonadherence, dose escalation worsened seizure control. In contrast, correcting nonadherence alone resulted in improved seizure control. These findings suggest that improving adherence should be prioritized over dose escalation in the clinical management of uncontrolled epilepsy.
Positron Emission Tomography Molecular Imaging Biomarkers for Amyotrophic Lateral Sclerosis

Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disorder with limited treatment options. Despite decades of therapeutic development, only two modestly efficacious disease-modifying drugs-riluzole and edaravone-are available to ALS patients. Biomarkers that can facilitate ALS diagnosis, aid in prognosis, and measure drug pharmacodynamics are needed to accelerate therapeutic development for patients with ALS. Positron emission tomography (PET) imaging has promise as a biomarker for ALS because it permits visualization of central nervous system (CNS) pathology in individuals living with ALS. The availability of PET radioligands that target a variety of potential pathophysiological mechanisms-including cerebral metabolism, neuroinflammation, neuronal dysfunction, and oxidative stress-has enabled dynamic interrogation of molecular changes in ALS, in both natural history studies and human clinical trials. PET imaging has potential as a diagnostic biomarker that can establish upper motor neuron (UMN) pathology in ALS patients without overt UMN symptoms, as a prognostic biomarker that might help stratify patients for clinical trials, and as a pharmacodynamic biomarker that measures the biological effect of investigational drugs in the brain and spinal cord. In this Review, we discuss progress made with 30 years of PET imaging studies in ALS and consider future research needed to establish PET imaging biomarkers for ALS therapeutic development.
Patient-Derived Organoids from Human Bile: An In Vitro Method to Study Cholangiopathies

Cholangiopathies, including primary sclerosing cholangitis, are a group of heterogeneous diseases characterized by inflammation and fibrosis of the intrahepatic and extrahepatic bile duct epithelium. Studies, especially of primary sclerosing cholangitis, have been hampered by the difficulty in accessing the cholangiocyte, instability of in vitro culture systems, and reliance on (limited) samples from end-stage disease. Here we describe a novel method of culturing biliary cells from bile of primary sclerosing cholangitis patients undergoing endoscopic retrograde cholangiopancreatography for clinical indications. These 3D organoid cultures demonstrate a biliary phenotype, can be maintained in vitro, and biobanked for future analyses. Given the need for diagnostic and therapeutic endoscopic retrograde cholangiopancreatography throughout the disease in many primary sclerosing cholangitis patients, this method can provide longitudinal studies in individual patients, allowing for a correlation of gene expression with disease status. These organoids can react to inflammatory stimuli, resulting in the secretion of chemo/cytokines indicative of the reactive immune phenotype characteristic of primary sclerosing cholangitis. Therefore, bile-derived organoids provide a model to study the pathogenesis and pharmacotherapeutic treatment of cholangiopathies.
Pattern of Postural Sway of Diabetic Peripheral Neuropathy People

Diabetic peripheral neuropathy can cause a loss of sensation in the feet, leading to impaired stability of body balance, and resulting in a risk of falls or slips. In the literature, a considerable number of studies have reported that people with diabetic peripheral neuropathy tend to have trouble keeping posture stable when the equilibrium of body balance is disturbed, even when standing quietly. In general, many studies found differences of postural stability between people with diabetic peripheral neuropathy and without neuropathy. However, little research has been done to find a difference of sway patterns between them. The objective of this study was to characterize the pattern of body sway for finding an effect of peripheral neuropathy on postural control when the stability of posture was disturbed. Pattern of body sway was investigated in terms of placement of center of pressure over the four quadrants during several time intervals such as quiet standing before a perturbation, during the perturbation, and after the perturbation. No significant difference of patterns of body sway was found between diabetic people with and without peripheral neuropathy during quiet standing and for most of considered perturbation directions at low velocity of perturbation. However, when the velocity of perturbation increased, a significant difference of placement of center of pressure was found from the third and fourth quadrants.
Person-First & Identity-First Language: Supporting Students with Disabilities on Campus

ABSTRACTLanguage pertaining to the disability community has changed significantly over the years. Previous identity-first language has recently been replaced with person-first language. Person-firs...
Dynamic Profiling of Antitumor Activity of CAR T Cells Using Micropatterned Tumor Arrays

Cancer immunotherapy based on the engineering of chimeric antigen receptors (CAR) on T cells has emerged as one of the most promising new therapies for patients with B-cell malignancies. Preclinical assessments of essential CAR T cell functions such as trafficking and cytotoxicity are critical for accelerating the development of highly effective therapeutic candidates. However, current tools for evaluating CAR-T functions lack sufficient precision. Here, a micropatterned tumor array (MiTA) is described that enables detailed and dynamic characterization of CAR T cell trafficking toward tumor-cell islands and subsequent killing of tumor cells. It is shown that CAR T cells often merge into large clusters that envelop and kill the tumor cells with high efficiency. Significant differences are also measured between CAR T cells from different donors and between various CAR T cell constructs. Overall, the assay allows for multifaceted, dynamic, high-content evaluation of CAR T trafficking, clustering, and killing and could eventually become a useful tool for immune-oncology research and preclinical assessments of cell-based immunotherapies.
Disruption of Redox Balance Enhances the Effects of BRAF-inhibition in Melanoma Cells

Summary Melanomas harboring BRAF mutations can be treated with BRAF inhibitors (BRAFi), but responses are varied and tumor recurrence is inevitable. Here, using an integrative approach of experimentation and mathematical flux balance analyses in BRAF-mutated melanoma cells, we report that elevated antioxidant capacity is linked to BRAFi sensitivity in melanoma cells. High levels of antioxidant metabolites in cells with reduced BRAFi sensitivity confirm this conclusion. By extending our analyses to other melanoma subtypes in TCGA, we predict that elevated redox capacity is a general feature of melanomas, not previously observed. We propose that redox vulnerabilities could be exploited for therapeutic benefits and identify unsuspected combination targets to enhance the effects of BRAFi in any melanoma, regardless of mutational status.
Coherent Reflections Using Closed-Loop PLL Processing of CYGNSS IF Data

This paper presents a Kalman filter-based closed-loop carrier phase tracking algorithm and results of coherent GNSS-R signal from ocean and land surfaces using CYGNSS raw IF measurements. The carrier phase measurement from coherent GNSS-R signal allows centi-meter level carrier phase altimetry. Closed-loop tracking of coherent reflection GNSS-R signal can provide higher resolution and accuracy estimates of signal parameters for other remote sensing applications, e.g., SNR measurements for land surface monitoring, than non-coherent measurements.
Identifying high‐density regions of pests within an orchard

This paper proposes a statistical method for identifying high‐density regions of pests, so‐called hot spots, within an orchard. Our method uses scanning windows to search for clusters of high counts within the sampled data. The proposed method enables a localized alternative for treatment that could be faster, less costly, and more environmentally friendly. R code that implements the hot spot identification method is provided as online supplementary material. The method is illustrated through simulated examples and a real data on counts of cottony cushion scales from an orchard.
Asymmetrical Paleolithic wooden spear tips: Expediency or design?

Abstract Paleolithic wooden spears provide rare but unique insights into early hunting technology. Examples from Schoningen, Germany indicate that spear tips were sometimes asymmetrical. This asymmetry has previously been interpreted as evidence for planning depth. A more parsimonious explanation, however, is that asymmetrical tips could be more efficiently produced (i.e., took less time to make) than symmetrical ones. Here, we experimentally investigated two different manufacturing processes, producing asymmetrical and symmetrical spear tips, while also testing the influence of biometric factors on spear-tip manufacturing efficiency (measured by time). One group of experimental participants sliced the wooden stave into an asymmetrical shape (slicing on one side of the stave with a steel blade), while the other group created a symmetrical shape (slicing on multiple sides of the stave). Based on time taken, results demonstrated no significant difference in efficiency between symmetrical and asymmetrical spear-tip manufacture. Conversely, some biometric characteristics (specifically pinch strength) present a more dominant influence in explaining time variation. These results demonstrate that the asymmetrical tips at Schoningen were not merely a byproduct of maximizing efficiency during the manufacturing process, but rather are evidence of planning and the associated cognitive capacities of these later Middle Pleistocene hominins.
Book Review: Like a Loaded Weapon: The Rehnquist Court, Indian Rights, and the Legal History of Racism in America, by Robert A. Williams Jr., University of Minnesota Press, 2005

This article is review of "Like a Loaded Weapon: The Rehnquist Court, Indian Rights, and the Legal History of Racism in America", by Robert A. Williams Jr., University of Minnesota Press, 2005.
Conspicuous consumption and peer-group inequality: the role of preferences

We develop a model that predicts changes in household consumption following a mean preserving increase in consumption inequality. The model allows for multiple peer-groups (a high-consumption (HC) group and a low-consumption (LC) group) as well different degrees of conspicuousness between the goods. We find that following a mean preserving increase in consumption inequality, a household with a constant level of income will increase its consumption of the more conspicuous good when it has preferences consistent with (i) ‘keeping up with the Joneses’ and a relatively stronger HC effect or (ii) ‘running away from the Joneses’ and a relatively stronger LC effect. Using U.S. consumer expenditure data from 1986 to 2002, we find tremendous heterogeneity in household preferences. While U.S. households consistently demonstrate ‘keeping up with the Joneses’, the relative strengths of HC and LC effects vary across racial sub-groups as well as across goods. Likewise, while expenditure on clothing, jewelry, personal care, etc., is generally more conspicuous than expenditure on healthcare, home furnishings, vehicle maintenance, etc., among the LC group, it is less conspicuous among the HC group with some heterogeneity by race. We conclude that heterogeneity in preferences is a likely explanation for the differences in the observed relationship between conspicuous spending and peer group inequality.
Analysis of Hip and Knee Reconstruction Questions on the Orthopedic In-Training Examination.

Abstract Background It is vital for orthopedic residents and residency programs to have a current understanding of the materials and resources utilized on the Orthopedic In-Training Examination (OITE) to tailor resident educational curricula accordingly. This study presents an updated analysis of the hip and knee section of the OITE. Methods All OITE questions related to hip and knee reconstruction over six examinations between 2014 and 2019 were analyzed for topic, subtopic, taxonomy, imaging modalities, resident performance, and references. Results There were 166 hip and knee reconstruction questions of 1600 OITE questions (10.4%) over a six-year period. The most commonly tested topics include mechanical properties of total knee and hip implants (10.8%), instability after THA (10.8%), periprosthetic fracture (10.2%), and prosthetic joint infection (10.2%). A total of 362 references were cited from 68 different sources. The most common sources were JOA, JBJS, JAAOS, and CORR, which were collectively responsible for 68% of all citations. There was an average publication lag of 7.1 years, with 75% of all citations falling within 10 years of the question date. Compared with a prior analysis from 2005 and 2009, there were significantly more complex multistep questions regarding treatment and fewer one-step knowledge recall questions (P = .003). Similarly, recent tests had significantly more questions involving interpretation of radiographs (55%, P Conclusions The OITE continues to evolve over time, incorporating recent literature and topics. The current analysis identifies high-yield topics and resources that can guide resident preparation for the OITE hip and knee section.
Intestinal barrier dysfunction as a therapeutic target for cardiovascular disease.

The gut microbiome and intestinal dysfunction have emerged as potential contributors to the development of cardiovascular disease (CVD). Alterations in gut microbiome are well documented in hyperte...
Online Smart Face Morphing Engine with Prior Constraints and Local Geometry Preservation

We present an online system for automatic smart face morphing, which can be accessed at http://facewarping.com. This system morphs the user-uploaded image to “beautify” it by embedding features from a user-selected celebrity. This system consists of three major modules: facial feature point detection, geometry embedding, and image warping. To embed the features of a celebrity face and at the same time preserve the features of the original face, we formulate an optimization problem which we call prior multidimensional scaling (prior MDS). We propose an iterated Levenberg-Marquardt algorithm (ILMA) to efficiently solve prior MDS in the general case. This online system allows the user to configure the morphing parameters, and has been tested under different conditions.
Health Disparities and Their Impact on Community Health

Health disparities are differences in frequency of and impact of health conditions between specific population groups. These groups may be defined in many ways such as gender, ethnicity, age, socioeconomic status, or geographical location. Often, these disparities are the result of social, economic, educational, and occupational disadvantages suffered by one group in comparison to others. Moreover, these disadvantages vary greatly by ethnicity. Currently, there is a growing body of research explaining how these disadvantages impact the health of individuals and communities. Health disparities require complex solutions that are beyond the capacity of just the health care industry to those for community wellness. Therefore, a multidisciplinary approach is required, and stakeholders must form novel community partnerships between disparate industries to achieve health equity. In this chapter, we discuss the concepts of health disparities and health equity, and their role in community health. We discuss the major factors that contribute to health disparities to be addressed for sustainable community health. Lastly, we review approaches to research and address health disparities with a particular focus on community-engaged scholarship for health systems sustainability.
Microbiome diversity declines while distinct expansions of Th17, iNKT, and dendritic cell subpopulations emerge after anastomosis surgery

Background Anastomotic failure causes morbidity and mortality even in technically correct anastomoses. Initial leaks must be prevented by mucosal reapproximation across the anastomosis. Healing is a concerted effort between intestinal epithelial cells (IECs), immune cells, and commensal bacteria. IEC TLR4 activation and signaling is required for mucosal healing, leading to inflammatory factor release that recruits immune cells to limit bacteria invasion. TLR4 absence leads to mucosal damage from loss in epithelial proliferation, attenuated inflammatory response, and bacteria translocation. We hypothesize after anastomosis, an imbalance in microbiota will occur due to a decrease in TLR4 expression and will lead to changes in the immune milieu. Results We isolated fecal content and small intestinal leukocytes from murine, Roux-en-Y and end-to-end anastomoses, to identify microbiome changes and subsequent alterations in the regulatory and pro-inflammatory immune cells 3 days post-operative. TLR4+ IECs were impaired after anastomosis. Microbiome diversity was reduced, with Firmicutes, Bacteroidetes, and Saccharibacteria decreased and Proteobacteria increased. A distinct TCRβhi CD4+ T cells subset after anastomosis was 10-20-fold greater than in control mice. 84% were Th17 IL-17A/F+ IL-22+ and/or TNFα+. iNKT cells were increased and TCRβhi. 75% were iNKT IL-10+ and 13% iNKTh17 IL-22+. Additionally, Treg IL-10+ and IL-22+ cells were increased. A novel dendritic cell subset was identified in anastomotic regions that was CD11bhi CD103mid and was 93% IL-10+. Conclusions This anastomotic study demonstrated a decrease in IEC TLR4 expression and microbiome diversity which then coincided with increased expansion of regulatory and pro-inflammatory immune cells and cytokines. Defining the anastomotic mucosal environment could help inform innovative therapeutics to target excessive pro-inflammatory invasion and microbiome imbalance.
Zhuangzi, Amputees, and Virtue (de)

This chapter offers a new perspective on amputation, bodily integrity, and disability ethics through ancient Chinese philosophy. Through a reading of stories about amputees in the Daoist text Zhuangzi, Singh shows how Daoism, in contrast to Confucianism, refused to view the disabled as social outcasts and, by modifying its view of integrity, presents amputees as exemplars of Daoist virtue (de). For Zhuangzi, Singh argues, the practice of virtue is more important than conventional notions of bodily integrity; and insofar as amputees in the text accept transformation to such a degree that they can even embrace the loss of their feet, they are extraordinary examples of those who abide by his Daoist Way.
Solvation Dynamics and Ultrafast Electron Transfer

Ultrafast fluorescence spectroscopy has been used to study two processes: (i) the transient solvation of electronically excited coumarin probes and (ii) the solvent mediated excited state intramolecular electron (charge) transfer of 9,9′—bianthryl and related compounds. The solvation measurements have been analyzed in terms of contemporary theory to gain insight on the molecular aspects of microscopic motion in polar liquids. The excited state electron transfer (et) examples are well modeled by an electronically adiabatic approach, employing an “outer sphere” generalized Langevin equation description of motion along the et reaction coordinate. The relationship between solvation and electron transfer dynamics is discussed.
Strength, stiffness, resonance and the design of offshore wind turbine monopiles

Abstract A monopile supporting an offshore wind turbine (OWT) is currently designed for both strength and stiffness. Regarding strength, the monopile is designed to have sufficient capacity to withstand demands under both 50-year operational conditions, when the rotor is spinning and blades are oriented to optimize power generation, and 50-year extreme conditions, when the rotor is parked and the blades feathered to minimize aerodynamic loads. Regarding stiffness, the monopile is designed to have sufficient stiffness such that the first structural frequency of the OWT falls between the 1P and 3P frequencies (rotation frequency and blade passing frequency for a three-bladed turbine). For six case studies, including three sites along the U.S. Atlantic coast and two mudline conditions (fixed and compliant), this paper delineates the conditions under which stiffness and strength govern the design of the monopile. This distinction has important implications for the overall risk profile of an OWT, as monopiles controlled by stiffness will have more reserve capacity than monopiles controlled by strength. The six case studies are intended to consider a range of water depths, metocean environments and mudline conditions that is representative of conditions suitable for installing OWTs supported by monopiles along the U.S. Atlantic coast. The monopile designs are controlled by stiffness for two of the six cases studies and, for these two cases, a modest (6–8%) reduction in monopile area (and mass) could be achieved if dynamic design requirements were achieved through means other than increasing monopile stiffness. Monopile designs for the remaining four cases are controlled by operational moment demands.
The nature of controlled respiration and its relationship to protonmotive force and proton conductance in blowfly flight-muscle mitochondria.

1. To determine whether controlled (State 4) pyruvate oxidation can support a high energy state, measurements of the redox span NAD–cytochrome c, phosphorylation potential and protonmotive force (the gradient in electrochemical activity of protons across the mitochondrial inner membrane) were made as indices of energy status. For comparison, these three measurements were also made with glycerol 3-phosphate, an alternative substrate. The two substrates gave essentially identical values for the redox span NAD–cytochrome c in State 4, and the phosphorylation potential was of sufficient magnitude to be considered in equilibrium with the redox span over the first two phosphorylation sites. The magnitude of the protonmotive force in State 4 was much less and the implications of this finding are discussed. 2. Measurements made during the controlled (State 4) to active (State 3) transition indicated that with glycerol 3-phosphate as substrate, both the redox span NAD–cytochrome c and the protonmotive force were diminished; the State 4 → State 3 transition with pyruvate as substrate was accompanied by an increase in the redox span but a decrease in protonmotive force. The contrary behaviour of these two energetic parameters in the presence of pyruvate was ascribed to a transient excess in the flux of protons through the adenosine triphosphatase relative to the protonpumping respiratory chain, in spite of the increased dehydrogenase activity. 3. The lower protonmotive force seen in State 3 relative to State 4 with pyruvate as substrate was due to a diminution of both the electrical (ΔΨ) and the chemical (ΔpH) components; with glycerol 3-phosphate, the magnitude of the decrease in protonmotive force during the State 4 → State 3 transition was similar to that seen with pyruvate, but was due to a large decrease in the electrical component (ΔΨ) and a small rise in the chemical component (ΔpH). The reason for the difference seen in the behaviour of the components of the protonmotive force was investigated but not established. 4. In the presence of oligomycin and ADP, oxidation of pyruvate, but not of glycerol 3-phosphate, supported a greater protonmotive force than in State 4, in keeping with the dehydrogenase activation and increased redox span NAD–cytochrome c found under these conditions. 5. Experiments involving the use of uncoupling agent to stimulate respiration are compared with those in which limiting concentrations of ADP were used. Estimates of the proton conductance of the inner membrane indicate a similar non-linear dependence on uncoupler concentration with the two substrates. 6. A model is proposed as an explanation of the high rates of controlled glycerol 3-phosphate oxidation. The model relies on a high permeability of the inner membrane to protons and other ions being induced by glycerol 3-phosphate oxidation in State 4.
Fibronectin signaling via toll-like receptprs: a novel paradigm for persistent fibrosis in scleroderma

Scleroderma is a systemic autoimmune disease with unknown etiology. Fibrosis, the hallmark of scleroderma, is the transformation of self-limited wound healing into a self-sustaining non-healing process. The factors responsible for maintaining persistent fibroblast activation in scleroderma and other conditions with chronic fibrosis are not well understood. We recently showed that TLR4 and fibronectin extra domain A (Fn EDA ), an endogenous TLR4 ligand, both are markedly elevated in the lesional skin biopsies from scleroderma patients and were shown to be involved in scleroderma disease pathogenesis. Here, we highlight the role of the Fn EDA -TLR4 signaling axis in fibrosis, and the mechanisms involved in driving persistence of fibrosis in scleroderma.
THEORETICAL BASIS AND DESIGN FOR A RESIDENTIAL SIZE SOLAR POWERED AMMONIA/WATER ABSORPTION AIR CONDITIONING SYSTEM

ABSTRACT Coincident with the design and construction of a residential size intermittent ammonia/water absorption air conditioning unit at the University of Florida Solar Research Residence, a project was implemented to design a continuous ammonia/water absorption air conditioning unit. Previous work performed at the University of Florida has yielded valuable heat transfer information which was necessary for pursuing the design of the continuous prototype system. The ammonia/water absorption unit is comprised of components typical of an absorption system; a generator, condenser, evaporator, and an absorber. The design was optimized for compactness, high thermal efficiency and low fabrication cost. This paper describes the anlytical work performed prior to the design of a three-ton capacity prototype unit. The projected thermal efficiency, energy efficiency ratio and cost are presented in the paper.
Electromagnetic response of thin laterally anisotropic conductive sheets

We solve ab initio the boundary value problem of a highly conducting sheet of infinite extent for an exterior source. The sheet is characterized by conductances which may be different in the two principal orthogonal directions. The sources considered are: a vertical magnetic dipole, horizontal line current, and a vertical electric dipole. Among other things, it is shown that the anisotropy of the sheet causes coupling between the TE and the TM waves resulting in depolarization of the radiation fields.
Perceptual Structures and Distributed Motor Control

The sections in this article are: 1 The Place of Brain Theory Within Cybernetics 2 Concepts from Computer Science and Control Theory 2.1 Programs Need Not Be Stereotypes 2.2 State and Feedback in Control Theory 2.3 Serial Order in Behavior Revisited 3 Visuomotor Coordination in Frog and Toad 3.1 Maps as Control Surfaces 3.2 A Model of Frog Snapping 3.3 The Many Visual Systems 3.4 Summary 4 Perceptual and Motor Schemas 4.1 Perceptual Schemas and the Action-Perception Cycle 4.2 Optic Flow and Control of Movement 4.3 Motor Schemas 4.4 Summary 5 Coordinated Control Programs 5.1 Feedforward 5.2 Interwoven Activation of Motor Schemas 5.3 Skill Acquisition 5.4 Summary 6 The Perspective of Artificial Intelligence 6.1 Programs and Planners 6.2 Program Synthesis and Visuomotor Coordination 6.3 Summary 7 Conclusion
9 The Alternative Economy: Resilience in the Face of Complexity from the Eastern Lowlands

The ancient eastern Maya Lowlands are characterized by both small, highly resilient communities and the growth of large regional centers. The smaller communities, separated by 2–5 kilometers and dispersed across the landscape, established a circle of interdependency between one another and a spatial separation from the largest centers. Degrees of sustainability were achieved through time by way of a negotiated settlement and land use balance within the relatively fragile biophysical environment. Because tropical ecosystems are identified by low specific species richness in any one patch or microenvironment, humans tend to mimic this spatial dispersion—a high-density “ruralism.” When assessed by way of high humidity and precipitation, decomposition and disease were significant deranging factors affecting surplus and storage. Roads and navigable canal systems shorten the time necessary for distribution of organics—principally food; and when coupled with routinized scheduling (calendars), time and distance were reduced. Salting and “natural” root crop preservation techniques are discussed. A dual or alternative economy is proposed in the context social complexity.
GEOLOGICAL PROCESSES AND ORCHID BIOGEOGRAPHY WITH APPLICATIONS TO SOUTHEAST CENTRAL AMERICA

This contribution owes its origins to a paper and presentation by Dr. Calloway H. Dodson at the Second International Conference on Neotropical Orchidology held in San Jose, Costa Rica in May of 2003 (Dodson 2003). Dr. Dodson outlined some of the reasons to suspect that regional geological fac- tors may play important roles in orchid speciation and biogeography and gave examples from the northwestern South America. He also suggested that evolutionary change in orchid might occur over fair- ly short time periods, perhaps even as short as decades, centuries or millennia (Dodson 2003, SHK lecture notes).
An Analysis of Customers' E-Complaints for Luxury Resort Properties

Using content analysis, this study examined online comments of six luxury resort properties located in a popular travel destination in the southwestern United States. By categorizing and analyzing the online comments, the study not only revealed customers' online complaint behaviors, but also identified reasons customers post comments online. Suggestions for practitioners are provided for responding to online customer comments.
Local fingerprint image reconstruction based on gabor filtering

In this paper, we propose two solutions for fingerprint local image reconstruction based on Gabor filtering. Gabor filtering is a popular method for fingerprint image enhancement. However, the reliability of the information in the output image suffers, when the input image has a poor quality. This is the result of the spurious estimates of frequency and orientation by classical approaches, particularly in the scratch regions. In both techniques of this paper, the scratch marks are recognized initially using reliability image which is calculated using the gradient images. The first algorithm is based on an inpainting technique and the second method employs two different kernels for the scratch and the non-scratch parts of the image to calculate the gradient images. The simulation results show that both approaches allow the actual information of the image to be preserved while connecting discontinuities correctly by approximating the orientation matrix more genuinely.
Selective Modulation of BV-2 Microglial Activation by Prostaglandin E2 DIFFERENTIAL EFFECTS ON ENDOTOXIN-STIMULATED CYTOKINE INDUCTION

Abstract The influence of prostaglandins on glial functions and, more specifically, on glial activation is not well understood. We report here that prostaglandin E2(PGE2), one of the major prostaglandins produced in the brain, acts as a potent and selective inhibitor of tumor necrosis factor α (TNF-α) production in lipopolysaccharide-stimulated primary microglia and the microglial cell line BV-2. The IC50 for this effect is 1 nm, and 100 nm PGE2 suppresses TNF-α production by >95%. More detailed studies of BV-2 cells show that PGE2also prevents the secretion of interleukin (IL)-6 but does not significantly modify lipopolysaccharide-stimulated expression of cyclooxygenase-2, pro-IL-1β, or inducible nitric oxide synthase. PGE2 appears to act primarily at the level of translation or protein stability, because TNF-α and IL-6 mRNA levels were only modestly decreased at high PGE2 concentrations; concomitantly with this inhibition, PGE2 up-regulated the levels of IL-1β mRNA. The effects of PGE2 could be largely mimicked by 8-bromo-cAMP, suggesting that, as in other cell types, PGE2 action is mediated at least in part by a rise in intracellular cyclic AMP. However, the protein kinase A inhibitor H89 only partially reversed the inhibition of TNF-α production by PGE2, implying that the PGE2 effect in BV-2 cells is mediated through both protein kinase A-dependent and -independent pathways.
Use of a continuously-fed batch reactor for gas-phase mixture with many first-order reactions

Abstract A continuously-fed batch reactor (CFBR) and its use are presented for the kinetic studies of gas-phase mixtures where many species participate in the reactions and yet aggregates of some of the species (lumps) are of interest. Results obtained from a series of CFBR runs can be used to tell whether all the kinetically distinct species have the same order of reaction. For the reaction mixtures with many first-order reactions, a CFBR run results in making the concentration of species to be in the order of decreasing rate constant, a species with the lowest rate constant having the highest concentration regardless of the initial composition of the mixtures. By running the CFBR in batch mode at the end of a CFBR run, initial concentration and rate constant of kinetically distinct species can be determined one species at a time or a group of species at a time. Furthermore, the CFBR run provides conditions that can he used to determine a minimum number of kinetically distinct species for the mixtures.
Microdosimetric-based risk factors for radiation received in space activities during a trip to Mars.

A system for evaluating quality factors, Q, based on the microdosimetric distribution of the radiation field of interest has been set up; it makes use of a specific quality function (SQF) to obtain-given microdosimetric spectra-values for Q. The advantages of a system based on lineal energy are well recognized. Furthermore, recent studies have shown that spectra in 1-μm diameter tissue-equivalent spherical volumes reproduce correctly (in the sense of this formalism) measured RBE values, and thus a proportional counter would be usable as a practical instrument for radiation protection. All specific quality functions, q(y), available to date have been calculated from in vitro cellular data. To extend this approach to radiations of interest in space activities we have recently obtained a new function q(y) for in vivo radiogenic neoplasia using data on the Harderian gland of the mouse. These data were obtained for charged particles and energies relevant to space exposures. Furthermore, we introduce a new procedure that allows one to obtain-here with the use of microdosimetric distributions for the Hiroshima-Nagasaki radiation fields-risk factors scaled from the A-bomb survivorship results. We apply these concepts to particles and energies representing the galactic spectrum. We estimate that for a trip to Mars (450 d) the excess lifetime cancer mortality due to galactic cosmic ray (GCR) radiation is 0.037. This is about 50% lower than the risk coefficient obtained with the aid of standard (LET-based) quality factors.
Big Five trait predictors of differential counterproductive work behavior dimensions

Abstract Counterproductive work behaviors (CWBs) negatively affect the well-being of an organization and/or the performance of its employees. This study compared the predictive validity of the Big Five traits with respect to the one-, two-, and five-dimensional approaches for measuring CWBs. Survey results from employees ( N = 233) confirmed previous relationships with agreeableness predicting a composite measure of CWBs and interpersonally-directed (ID) behaviors, and conscientiousness predicting a composite measure of CWBs and organizationally-directed (OD) behaviors. However, conscientiousness only predicted the OD behaviors of sabotage and theft. Extraversion predicted theft while openness to experience predicted production deviance. Further results and implications are discussed.
The Reverberating Effects of Job Rotation: A Theoretical Exploration of Nonrotaters' Fairness Perceptions

Abstract Human resource researchers have long regarded job rotation as a valuable form of job-based experiential learning. However, given the dearth of prior conceptual work in the collection of rotation research and the sparse attention given to rotation's collateral effects, we pursue two objectives in this article. First, to guide future research we develop a general model of the fairness perceptions and responses related to job rotation decisions. In this effort, we apply organizational justice concepts within a social information-processing framework. Second, we advance specific propositions to address the reverberating effects of job rotation on nonrotating employees. Specific recommendations for future research and implications for practice are also discussed.
The economic implications of using HACCP as a food safety regulatory standard

Abstract This article discusses the nature and role of Hazard Analysis Critical Control Point (HACCP) as a food safety control system and, in particular, its role as an element of public food safety regulation. The notion of efficiency in food safety regulation is discussed and related to the nature of food safety controls. It is suggested that, if appropriately applied, HACCP is a more economically efficient approach to food safety regulation than command and control (CAC) interventions. The economic implications of HACCP are discussed with reference to estimates of the costs and benefits, in particular for the food industry. Finally, the use of HACCP as an international trade standard and the facilitation of trade in processed food products is considered.
Development of low-noise high value chromium silicide resistors for cryogenic detector applications

Extremely high sensitivity detectors, such as silicon bolometers are required in many NASA missions for detection of photons from the x-ray to the far infrared regions. Typically, these detectors are cooled to well below the liquid helium (LHe) temperature (4.2 K) to achieve the maximum detection performance. As photoconductors, they are generally operated with a load resistor and a pre-set bias voltage, which is then coupled to the input gate of a source-follower Field Effect Transistor (FET) circuit. It is imperative that the detector system signal to noise performance be limited by the noise of the detector and not by the noise of the external components. The load resistor value is selected to optimize the detector performance. These two criteria tend to be contradictory in that these detectors require load resistors in the hundreds of megaohms, which leads to a higher Johnson noise. Additionally, the physical size of the resistor must be small for device integration as required by such missions as the NASA High Resolution Airborne Wide-Band Camera (HAWC) instrument and the Submillimeter High Angular Resolution Camera (SHARC) for the Caltech Submillimeter Observatory (CSO). We have designed, fabricated and characterized thin film resistors using a CrSi/TiW/Al metal system on optical quality quartz substrates. The resistor values range from 100 megaohms to over 650 megaohms and are Johnson noise limited at LHe temperatures. The resistor film is sputtered with a sheet resistance ranging from 300 ohms to 1600 ohms and the processing sequence developed for these devices allows for chemically fine tuning the sheet resistance in-situ. The wafer fabrication process was of sufficiently high yield (>80%) providing clusters of good resistors for integrated multiple detector channels, a very important feature in the assembly of these two instruments.
Variations in the mineral content of Myriophyllum heterophyllum Michx related to site and season

Abstract The mineral composition of submersed apical shoots of Myriophyllum heterophyllum Michx from Lees Pond and Lake Winnipesaukee, New Hampshire, U.S.A., was analyzed from 1976 to 1978. Minerals analyzed were P, Na, K, Ca, Mg, Fe, Mn, Zn and Cu, as well as ash. Apical mineral content was influenced by both the seasons and sample site location. Seasonal variations in mineral content were largest for Fe and Mn. A generalized seasonal pattern for Na, K, Ca and Mg was a summer maximum. Fe and Mn had late winter maxima, while ash, P and Zn had no significant seasonal variation. Recurrent seasonal patterns were most pronounced for Fe, Mn and Na. Seasonal maxima in Fe content were greater at tributary sampling sites than at non-tributary sites. The recurrent seasonal variations in mineral content observed in this study suggest that the time of sampling can greatly influence the results and therefore the interpretation of tissue chemistry studies of submersed hydrophytes.
The Effects of Medically Relevant Compounds on the Physical Properties of Biofilms

The adaptation of bacteria to form biofilms has been linked to many problems in the medical field including the rise of drug-resistant superbugs. Exopolymeric substances (EPS), including carbohydrates, proteins, and polysaccharides, secreted by the bacteria provide protection from harmful chemical elements, such as chlorhexidine digluconate, commonly found in medical grade soap. Much is known about the biological and chemical mechanisms of chlorhexidine digluconate as an antiseptic, whereas the physical response of the bacterial biofilm to the chemical is poorly understood. In this investigation, we used force spectroscopy to analyze the physical effects of varied concentrations of chlorhexidine digluconate on a robust biofilm-forming Escherichia coli strain. Preliminary data suggest a correlation between the stiffness (spring constant) of the biofilm and the concentration of chlorhexidine digluconate.