cssi/SciSciGPT-SciSciNet huggingface dataset:
Breast cancer: HER2--a good addiction.

Recent neoadjuvant studies have examined the effects of adding single or dual agents targeting HER2 to chemotherapy, finding unanimously that dual HER2 targeting markedly improves pathologic response. These findings have significant implications for future trial designs, particularly if the impact on pathologic response is accompanied by improved disease-free survival or overall survival.
Immunomodulation of natural killer activity by polyribonucleotides.

Several synthetic polyribonucleotides have been examined for the ability to augment natural killer (NK) activity and induce interferon (IFN) production. The results demonstrate that the complex of polyinosinic-polycytidylic acid and poly-L-lysine, which has been stabilized in carboxymethylcellulose [poly(I,C)-LC], polyadenylic-polyuridylic acid [poly(A).poly(U)], and a labile poly (I,C) compound with mismatched bases, designated poly(I).poly(C12U), all augment NK activity. However, poly(A).poly(U) and poly(I).poly(C12U) are less efficient augmentors of NK activity on a milligram per kilogram basis, than is poly(I,C)-LC. Similarly, poly(I,C)-LC induces more serum IFN following administration of 1, 10, or 100 micrograms/mouse (1,000-10,000 U/ml) than does either poly(A).poly(U) (0-25 U/ml) or poly(I).poly(C12U) (0-250 U/ml) at the same doses. Further studies with poly(I,C)-LC demonstrated that this molecule is an excellent augmentor of liver-associated NK activity. In fact, administration of poly(I,C)-LC resulted in higher NK levels in lever (63% lysis) than in spleen (44%) or blood (36%), and the augmented NK response was maintained in the liver for up to 13 days, whereas levels of NK activity in both blood and spleen returned to normal by days 3-6.
Microstructures of High Dielectric Constant Materials

A brief overview is given of the important microstructural characteristics of several classes of high dielectric constant ceramics. Attention is focussed on the understanding of ferroelectric domain structures in BaTiO3, the effect of grain size on the dielectric constant in BaTiO3, and the microstructure and microchemistry of so-called “relaxor” ferroelectrics. The relaxor families discussed in particular are Pb(Sc1/2Ta1/2)O3,Pb(Mg1/3Nb2/3)O3 and Pb(Zn-1/3Nb2/3)O3. The nature of the B-site cation ordering and the ferroelectric domain structures of these materials are discussed in some detail.
Patients With Multiple Myeloma Have More Complications After Surgical Treatment of Hip Fracture

Objectives:Bone lesions from multiple myeloma may lead to pathological fracture of the proximal femur, requiring either fixation or arthroplasty. Little is known about the impact of multiple myelom...
Teaching Policy Analysis Through Animated Films: A Mickey Mouse Assignment?

To conduct a policy analysis, students must master foundational concepts and apply them using critical and evaluative thinking. A film-based assignment allows students to practice the steps of policy analysis in a low-stakes setting that requires a limited investment of time. Ideally, the assignment is used as an initial practice exercise before engaging in applied projects later in the semester. The applied projects are enhanced because students already have used the steps of policy analysis and been given feedback in a sheltered setting. We suggest using animated films for this assignment because they force students to define problems, solutions, and criteria without reference to existing practices or dominant perspectives. Therefore, student time and instructor feedback is devoted to developing what Bardach termed “first-rate thinking.” Concentrating attention on logical thought processes builds a strong foundation for further training in policy analysis.
Warm antibody autoimmune hemolytic anemia

Autoimmune hemolytic anemia (AIHA) is a rare and heterogeneous disease that affects 1 to 3/100 000 patients per year. AIHA caused by warm autoantibodies (w-AIHA), ie, antibodies that react with their antigens on the red blood cell optimally at 37°C, is the most common type, comprising ∼70% to 80% of all adult cases and ∼50% of pediatric cases. About half of the w-AIHA cases are called primary because no specific etiology can be found, whereas the rest are secondary to other recognizable underlying disorders. This review will focus on the postulated immunopathogenetic mechanisms in idiopathic and secondary w-AIHA and report on the rare cases of direct antiglobulin test-negative AIHA, which are even more likely to be fatal because of inherent characteristics of the causative antibodies, as well as because of delays in diagnosis and initiation of appropriate treatment. Then, the characteristics of w-AIHA associated with genetically defined immune dysregulation disorders and special considerations on its management will be discussed. Finally, the standard treatment options and newer therapeutic approaches for this chronic autoimmune blood disorder will be reviewed.
Thioredoxin-dependent disulfide bond reduction is required for protamine eviction from sperm chromatin

Cysteine oxidation in protamines leads to their oligomerization and contributes to sperm chromatin compaction. Here we identify the Drosophila thioredoxin Deadhead (DHD) as the factor responsible for the reduction of intermolecular disulfide bonds in protamines and their eviction from sperm during fertilization. Protamine chaperone TAP/p32 dissociates DNA-protamine complexes in vitro only when protamine oligomers are first converted to monomers by DHD. dhd-null embryos cannot decondense sperm chromatin and terminate development after the first pronuclear division. Therefore, the thioredoxin DHD plays a critical role in early development to facilitate the switch from protamine-based sperm chromatin structures to the somatic nucleosomal chromatin.
Resonance Raman Investigation of the Interaction between Aromatic Dithiocarbamate Ligands and CdSe Quantum Dots

Ligand exchange with phenyl dithiocarbamates is known to significantly red-shift the lowest excitonic transition of CdSe quantum dots. Here we show that the resonance Raman spectra of CdSe quantum dots treated with p-methoxyphenyldithiocarbamate are nearly identical to those of CdSe quantum dots to which thin CdS shells have been added by standard synthetic methods. We conclude that the dithiocarbamate ligands decompose and react with Cd2+ not fully removed following the synthesis to form CdS on the surface of the quantum dots. This red-shifts the absorption spectrum primarily by delocalizing the electron into the CdS shell. These results are consistent with the common use of aliphatic dithiocarbamates as single-source precursors for adding ZnS or CdS shells to CdSe quantum dots and with the recent demonstration through NMR that phenyldithiocarbamate ligands decompose during nanocrystal ligand exchange.
Local Immune Responsiveness of Mice Bearing Premalignant Oral Lesions to PD-1 Antibody Treatment.

A carcinogen-induced premalignant oral lesion model that progresses to oral cancer was used to examine the immunological impact of a 5-week treatment regimen to block programmed cell death protein 1 (PD-1). PD-1 antibody treatment resulted in concurrent, but transient, increases in interleukin (IL)-2, IFN-γ and IL-17, and delayed increases in IL-6 and IL-10 within the lesion-bearing tongue epithelium. In contrast, cytokine secretion by lymph node cells of PD-1 antibody-treated mice was lower than for mice treated with control antibodies, with the exception of interferon (IFN)-γ, whose secretion increased late in the treatment period. This delayed secretion of IFN-γ coincided with an increase in CD4+ lymph node cells expressing IFN-γ. Lymph node cells of PD-1 antibody-treated mice reacted to a challenge with lysates of lesions or cancer by early production of IFN-γ, but this rapidly subsided. There also was increased production IL-17 and tumor necrosis factor (TNF)-α in response to the challenge, but the response was greatest by cells of control lesion-bearing mice. Clinical assessment showed an early but transient, stabilization of disease in mice treated with PD-1 antibody. These results show an early beneficial, but time-limited, response to PD-1 antibody treatment, which then fails with continued lesion progression.
From Plate Tectonics to Global Domain Tectonics

The assessment of crust/mantle recycling processes requires a detailed knowledge of the time-dependent, three-dimensional dynamic behavior of the earth as a whole system including physical and chemical properties of the components involved. Unfortunately, plate tectonics has so far failed to provide us with such a dynamic picture. Plate tectonics may be described as a kinematical description of the thin spherical outer shell of the earth. Even the driving mechanism of the plates still remains an unanswered question. As repeatedly pointed out, plate tectonics also cannot satisfactorily account for continental deformation.
The Academic-Publication Racket: Whatever Happened to Authors’ Rights?

Academic publishing has become big business; and as a result both readers’ access and authors’ rights are under serious threat. This impedes communication and undermines academics’ incentive to do the best work they can. I begin by disentangling some of the many factors that have created this disastrous situation—focusing primarily on publishing in philosophy, though I suspect that things are equally bad across the humanities, and beyond. Then I describe some of the ways I have tried to make my work widely available and to maintain control of its re-use; and how, despite my best efforts, this has gotten harder and harder as academic publishing has grown more and more inhospitable to authors’ interests. Of course, simply writing about what a mess academic publishing has become won’t, by itself, improve things. But my hope is that, by articulating what’s gone so wrong, I can reassure readers that their frustration isn’t unique, and perhaps persuade them to fight back in some of the ways I will suggest in my concluding pages, and in other ways they can see that I haven’t thought of. And perhaps, if more of us turn our minds to thinking about what might help change the situation, and join in the effort, things might gradually get better.
IQC-Based Robustness Analysis with Time-Varying Multipliers

This work deals with the use of time-varying integral quadratic constraint (IQC) multipliers when conducting robustness analysis. The main result enables robustness analysis of interconnections where the nominal plant and the IQC multiplier are general time-varying linear systems. When the nominal plant and the IQC multiplier are eventually periodic (not necessarily of the same period), robustness analysis can be accomplished by solving a finite-dimensional semidefinite program. Time-varying IQC multipliers are beneficial in analysis because they (1) provide the possibility of reducing conservatism and (2) are capable of expressing uncertainties which have unique characteristics in the time domain.
Abstract 370: A Novel Algorithm for the Collective Integration of Single Cell Rna-seq During Embryogenesis

Background: Single cell RNA-seq (scRNA-seq) over specified time periods has been widely used to dissect the cell populations during mammalian embryogenesis. Integrating such scRNA-seq data from dif...
Um olhar sobre os dispositivos de governança

O texto busca problematizar a governanca na escala territorial, considerando as iniciativas de desenvolvimento territorial em andamento no Brasil. Esta dividido em tres partes: inicialmente traca uma rapida panorâmica das correntes do pensamento em ciencia politica, que contribuem na analise e discussao do tema da governanca, depois elege sete pontos centrais do tema, relacionados as estrategias de apoio ao desenvolvimento territorial, sobre os quais se problematiza a governanca. Na terceira parte sao tecidas algumas consideracoes finais.
CONNECTIVE TISSUE GROWTH FACTOR

Connective tissue growth factor (CTGF) is a peptide growth factor that is upregulated during fibrogenesis. CTGF was originally found to promote fibroblast proliferation, migration, adhesion, and extracellular matrix formation, and subsequently has been implicated in fibrogenesis, wound healing, chondrogenesis, angiogenesis, transdifferentiation, and tumor growth. CTGF has numerous cellular profibrotic activities, which include increasing synthesis of fibrillar collagen and fibronectin, enhancing secretion of factors that impede matrix degradation, and stimulating the transformation of fibroblasts into the more fibrogenic myofibroblast phenotype. Increased CTGF expression is observed during lung fibrogenesis in animal models, as well as in diseases that cause lung fibrosis in humans. Overexpression of CTGF has been reported to cause lung fibrosis in rats, as well as to render lung fibrosis-resistant mouse strains more susceptible to fibrogenic agents. These observations have raised interest in developing CTGF inhibitors for employment in trials to arrest lung fibrogenesis in humans.
Statistical machine learning model to predict Oncotype DX risk category in women over age 50.

524Background: The 21-gene Oncotype DX Breast Recurrence Score multigene assay (RS) identifies women with ER positive, HER negative, axillary node-negative breast cancer (BC) for whom chemotherapy ...
Automated knowledge extraction from polymer literature using natural language processing

Summary Materials science literature has grown exponentially in recent years making it difficult for individuals to master all of this information. This constrains the formulation of new hypotheses that scientists can come up with. In this work, we explore whether materials science knowledge can be automatically inferred from textual information contained in journal papers. Using a data set of 0.5 million polymer papers, we show, using natural language processing methods that vector representations trained for every word in our corpus can indeed capture this knowledge in a completely unsupervised manner. We perform time-based studies through which we track popularity of various polymers for different applications and predict new polymers for novel applications based solely on the domain knowledge contained in our data set. Using co-relations detected automatically from literature in this manner thus, opens up a new paradigm for materials discovery.
Microbiome-specific T follicular helper cells drive tertiary lymphoid structures and anti-tumor immunity against colorectal cancer

Colorectal cancer (CRC) is a common and deadly disease, and patients with metastatic tumors often fail to respond to therapy. While select members of the microbiome are associated with improved anti-tumor immunity, mechanistic understanding of how the microbiome provides a benefit is lacking. We show that modification of the CRC-associated microbiome with a single immunogenic commensal bacteria can alter T cell differentiation, inhibit tumor growth, and increase survival. Microbiome-driven control of CRC required the formation of colonic tertiary lymphoid structures (TLS) and increased infiltration of the tumor with cytotoxic immune cells. In the context of CRC, CD4+ T cells specific to the newly introduced commensals differentiated into T follicular helper cells and were necessary for the formation of TLS, immune infiltration of the tumor, and control over CRC. Thus, modification of the intestinal T cell response by the microbiome can be used to augment anti-tumor immunity in colorectal cancer.
Early Stress-Response Gene REDD1 Controls Oxazolone-Induced Allergic Contact Dermatitis

REDD1 is an energy sensor and stress-induced mTOR inhibitor. Recently, its novel role in linking metabolism and inflammation/immune responses has emerged. In this study, we assessed the role of REDD1 in murine oxazolone-induced allergic contact dermatitis (ACD), a T cell-dependent model with features of human ACD. A variety of immune indices, including edema, cellular infiltration, inflammatory gene expression, and glucocorticoid response, were compared in Redd1 knockout (KO) and isogenic (C57BL/6 × 129)F1 wild-type mice after sensitization and subsequent ear challenge with oxazolone. Despite relatively normal thymic profiles and similar T cell populations in the lymph nodes of naive Redd1 KO mice, early T cell expansion and cytokine production were profoundly impaired after sensitization. Surprisingly, higher steady-state populations of CD4+ and CD8+ T cells, as well as macrophages (CD45+/Ly-6G-/CD11b+), dendritic cells (CD45+/Ly-6G-/CD11c+), neutrophils (CD45+/Ly-6G+/CD11b+), and innate lymphoid cells (CD45+/Lineage-/IL-7Ra+/ST2+/c-Kit+), were observed in the ears of naive Redd1 KO mice. Upon challenge, ear edema, T cell, macrophage, neutrophil, and dendritic cell infiltration into the ear was significantly reduced in Redd1 KO animals. Accordingly, we observed significantly lower induction of IFN-γ, IL-4, and other cytokines as well as proinflammatory factors, including TSLP, IL-33, IL-1β, IL-6, and TNF-α, in challenged ears of Redd1 KO mice. The response to glucocorticoid treatment was also diminished. Taken together, these data establish REDD1 as an essential immune modulator that influences both the initiation of ACD disease, by driving naive T cell activation, and the effector phase, by promoting immune cell trafficking in T cell-mediated skin inflammation.
Erythrocyte-Associated Transients in Capillary PO2 in the Rat Spinotrapezius Muscle During Hemodilution with Hespan and a Hemoglobin-Based Oxygen Carrier

ERYTHROCYTE-ASSOCIATED TRANSIENTS IN CAPILLARY PO2 IN THE RAT SPINOTRAPEZIUS MUSCLE DURING HEMODILUTION WITH HESPAN AND A HEMOGLOBIN-BASED OXYGEN CARRIER By Matthew C. Barker A thesis submitted in partial fulfillment of the requirements for the degree of Master of Science at Virginia Commonwealth University Virginia Commonwealth University, 2005 Advisor: Roland N. Pittman, Ph.D. Department of Physiology Hemoglobin-based oxygen carriers for use as transfusion fluids have emerged as a leading technology directed at stemming shortages of a safe blood supply and providing a readily available resuscitation fluid in various trauma situations. The purpose of this investigation was to determine the effects of isovolemic hernodilution with Hespan and a hemoglobin-based oxygen carrier (HBOC) on erythrocyte-associated transients (EATs) in capillary PO2. The particulate nature of blood flow in capillaries, when observed from a stationary observation point, results in fluctuations of PO2 as alternating red blood cells and plasma gaps move through the detection region. Therefore, through experimental methods which provided the necessary temporal and spatial resolution required to make such measurements, EATs can be observed and corresponding PO2 fluctuations can be determined. The spinotrapezius muscle in sixteen Sprague-Dawley rats was exteriorized for intravital microscopy measurements in capillaries. Capillary PO2 was measured using Pd-porphyrin phosphorescence quenching microcopy. The hemodiluents used in isovolemic hemodilution included Hespan, a non-oxygen carrying plasma expander, and OxyglobinB, a HBOC. Two isovolemic hemodilution steps were performed, reducing the systemic hematocrit to an average of 27.5% after the first step and 13.5% after the second step. Results showed that erythrocyte-associated transients in PO2 can be observed in the rat spinotrapezius with significant differences occurring between red blood cell and plasma gap PO2 under control conditions, isovolemic hemodilution with Oxyglobin after step one, and isovolemic hemodilution with Hespan after step two. This study concludes that EATs are observable and POz transients relating to EATs can be measured in the rat spinotrapezius muscle. Furthermore, it can be concluded that the HBOC Oxyglobin caused a decrease in erythrocyte-associated capillary POz transients, as well as a general decrease in capillary PO2. In addition, this study concludes that erythrocyte-associated capillary PO2 transients can best be observed under control conditions and after step two of isovolemic hemodilution with Hespan.
The Electrocatalytic Hydrogenation of Glucose: I . Kinetics of Hydrogen Evolution and Glucose Hydrogenation on Raney Nickel Powder

The kinetics of H[sub 2] evolution and glucose reduction to sorbitol was investigated using a batch slurry reactor containing Raney nickel powder catalyst. In the presence and absence of glucose, hydrogen evolution proceeds via a Volmer-Heyrovsky mechanism, with both steps simultaneously rate controlling at low overpotentials and the Volmer reaction rate limiting at high cathodic overvoltages. A kinetic model for the electrocatalytic hydrogenation of glucose with simultaneous H[sub 2] generation was developed and tested. The model contains rate equations for the individual Volmer, Heyrovsky, and glucose hydrogenation steps, a Langmuir adsorption isotherm for glucose, an equation describing the shift in open-circuit potential due to glucose adsorption on the nickel catalyst, and steady-state atomic hydrogen and charge balance relationships. The theory accurately predicted potentiostatic polarization data and glucose hydrogenation rates. The results indicate that the mechanism for sorbitol formation with electrogenerated atomic hydrogen on Raney nickel is the same as that for the high temperature and pressure chemical catalytic hydrogenation process.
Context based mixture model for cell phase identification in automated fluorescence microscopy

Automated identification of cell cycle phases of individual live cells in a large population captured via automated fluorescence microscopy technique is important for cancer drug discovery and cell cycle studies. Time-lapse fluorescence microscopy images provide an important method to study the cell cycle process under different conditions of perturbation. Existing methods are limited in dealing with such time-lapse data sets while manual analysis is not feasible. This paper presents statistical data analysis and statistical pattern recognition to perform this task. The data is generated from Hela H2B GFP cells imaged during a 2-day period with images acquired 15 minutes apart using an automated time-lapse fluorescence microscopy. The patterns are described with four kinds of features, including twelve general features, Haralick texture features, Zernike moment features, and wavelet features. To generate a new set of features with more discriminate power, the commonly used feature reduction techniques are used, which include Principle Component Analysis (PCA), Linear Discriminant Analysis (LDA), Maximum Margin Criterion (MMC), Stepwise Discriminate Analysis based Feature Selection (SDAFS), and Genetic Algorithm based Feature Selection (GAFS). Then, we propose a Context Based Mixture Model (CBMM) for dealing with the time-series cell sequence information and compare it to other traditional classifiers: Support Vector Machine (SVM), Neural Network (NN), and K-Nearest Neighbor (KNN). Being a standard practice in machine learning, we systematically compare the performance of a number of common feature reduction techniques and classifiers to select an optimal combination of a feature reduction technique and a classifier. A cellular database containing 100 manually labelled subsequence is built for evaluating the performance of the classifiers. The generalization error is estimated using the cross validation technique. The experimental results show that CBMM outperforms all other classifies in identifying prophase and has the best overall performance. The application of feature reduction techniques can improve the prediction accuracy significantly. CBMM can effectively utilize the contextual information and has the best overall performance when combined with any of the previously mentioned feature reduction techniques.
Millennial mind-set: Pursuing the next generation of consumers

TINA WELLS There is no globally accepted definition of the millennial generation, but most observers think of them as the group of people born sometime between 1980 and the early 2000s. Regardless of the exact years you use to define the demographic, there is little doubt that this generation of Americans has a unique mind-set when it comes to their expectations in the marketplace, and part of my job is to advise companies and businesses on how best to approach them. The rest of the economy is already wrestling with how to adjust their business models to appeal to this new generation of consumers, and there is little doubt that the medical world will have to make a similar adjustment in the coming years. My company, Buzz Marketing Group, has been studying the millennial generation in detail for several years, and I believe that there are 10 major trends that businesses, including your own, will have to be cognizant of in the years to come.
Information retrieval in systematic reviews: challenges in the public health arena.

Abstract Background: Information retrieval for systematic reviews in occupational injuries and other public health areas is much more elusive than retrieval for reviews in clinical medicine, due to the interdisciplinary nature of the field and the lack of a significant body of evaluative literature. Objective: The objective of this study is to provide information about challenges and methodology in relevant literature retrieval for systematic reviews in the effectiveness of strategies to prevent occupational injury. Methods: Participants from Injury Control Research Centers and Agricultural Health and Safety Centers identified 12 areas of occupational injury and evaluated the effectiveness of interventions in each area. A systematic review of the literature was conducted, and results were critically reviewed and summarized. Results: The search strategy captured 41,871 abstracts or titles across all research topics. After screening, 1356 documents were identified as being potentially eligible studies. Relevant articles were also identified through gleaning references and contact with professionals in the field. Conclusions: Literature reviews in the field of occupational injury cannot be limited to database searches. Much of the literature is not well-indexed, and librarians must employ information retrieval methods other than database searching to retrieve relevant literature in the field.
Two-photon absorption based optical limiting and stabilization in organic molecule-doped solid materials

Abstract Optical limiting and stabilization via two-photon absorption (TPA) in organic molecule-doped solid materials have been investigated. The nonlinear materials are epoxy rod and a composite glass rod doped with the same organic dopant (2,5-benzothiazole 3,4-didecyloxy thiophene). An ultrashort laser source with 0.5 ps pulsewidth and 602 nm wavelength was employed. The transmissivity of these two materials has been measured as a function of the input beam intensity. The measured results can be well fitted based on the assumption that TPA is the predominant mechanism producing the observed optical limiting behavior. Also, optical stabilization behavior is observed, and, at ∼930 MW/cm 2 input intensity level, the output intensity fluctuation is three times less than the input intensity fluctuation.
Protective Effects of Standardized Pomegranate (Punica granatum L.) Polyphenolic Extract in Ultraviolet-Irradiated Human Skin Fibroblasts

Exposure to ultraviolet (UV) radiation has been associated with several acute and chronic conditions, including sunburn, edema, hyperplasia, immunosuppression, photoaging, and skin cancer. The role of naturally occurring phytochemicals in the prevention of such UV-related conditions has captured increased interest. Pomegranate (Punica granatum L.) is a rich source of polyphenolics, which have been shown to exert anti-inflammatory, antioxidant, and anticarcinogenic activity in numerous in vivo and in vitro studies. This work investigated potential protective effects of a pomegranate fruit extract standardized to punicalagins against UVA- and UVB-induced damage in SKU-1064 human skin fibroblast cells. Pomegranate extract (PE), in a range from 5 to 60 mg/L, was effective at protecting human skin fibroblasts from cell death following UV exposure, likely related to a reduced activation of the pro-inflammatory transcription factor NF-κB, a downregulation of proapoptotic caspase-3, and an increased G0/G1 phase, ...
Docosahexaenoic acid biosynthesis and dietary contingency: Encephalization without aquatic constraint

Reconstructing evolutionary processes in the distant past is necessarily an inductive endeavor, typically appealing to numerous considerations thought to be relevant to the veracity of a particular conclusion. In this respect, it is essential that the considerations invoked to support hypotheses are in turn well-established truths. It is with these concerns that we sought to examine the nutritional, physiological, and archeological premises underlying the perspective that access to an aquatic diet rich in docosahexaenoic acid (DHA, 22:6n-3) was critical to human brain evolution (Carlson and Kingston [2007]: Am J Hum Biol 19:132–141). In our report investigating links between omega-3 (n-3) fatty acids and hominin encephalization, we concluded that the regular consumption of aquatic resources rich in preformed DHA may not have been essential given a varied diet of wild terrestrial foods (Carlson and Kingston [2007]). This assessment was based primarily on evidence of potential physiological adaptations in modern humans to ensure sufficient availability of DHA during critical periods of brain growth. While modern human physiology provides critical information regarding DHA as a constraint in evolving a large brain, it is also important to consistently contextualize interpretations within a framework of eclectic foraging diets rather than nutritionally limited modern agricultural populations or even modern foragers. We contend that current interpretations of Pleistocene hominin nutritional ecology do not uniquely support a shore-based foraging niche as claimed by Cunnane et al. ([2007]: Am J Hum Biol, 19:578–581). Specific issues raised in response to our article by Cunnane et al. and Joordens et al. ([2007]: Am J Hum Biol, 19:582–584) are addressed here. Am. J. Hum. Biol. 19:585–588, 2007. © 2007 Wiley-Liss, Inc.
Alterations in nuclear scaffold constituents during carbon tetrachloride-induced liver regeneration.

Liver regeneration was induced in rats by treatment with CCl4, which results in substantial regenerative activity with a sharp mitotic response 2 days after intoxication. Closely paralleling the mitotic index, we observed fourfold increases in nuclear scaffold nucleoside triphosphatase, an activity thought to participate in nucleocytoplasmic RNA transport and in the 46 kD putative enzyme and its selective photolabeling. Because previous work has indicated that the 46 kD protein may be proteolytically derived from lamins A/C by cleavage at a tyrosine residue at aa376, we investigated the response of lamin A/C transcripts during this regeneration. Surprisingly, Northern blot analyses after CCl4 administration showed low levels of lamin A/C transcripts (which appeared to be predominantly poly[A]-), and we found a decrease in immunoprecipitable lamins A/C from in vitro translation of poly(A)-selected RNA. To circumvent potential problems with such analyses, we used reverse transcription/polymerase chain reaction amplification of lamin A/C transcripts from total cytoplasmic RNA. These assays showed a transient, comparatively minor increase in lamin A/C transcripts 1 day after treatment, but levels rapidly declined from 1 to 3 days and were decreased at 3 to 5 days. However, nuclear scaffold protease activity, which shows a considerable selectivity for lamins A/C and may be involved in derivation of the 46 kD protein, increased in parallel to the mitotic response and increases in nucleoside triphosphatase, as assessed using a nonspecific (Azocoll) protease assay. Assays with a specific tyrosine-containing substrate (Z-Y-Sbenzyl) showed an increase that mirrored that observed with the nonspecific substrate. Our results suggest that the increases in nuclear scaffold nucleoside triphosphatase activity attendant to nuclear replication appear to result, in large part, from activation of nuclear scaffold proteases. Furthermore, one third to one half of hepatocytes apparently regenerate without any major increase in synthesis of lamins A/C, the major structural proteins of the nuclear scaffold. (HEPATOLOGY 1991;13:515–522.)
The effects of central injections of adenosine analogs on blood pressure and heart rate in the rat.

Abstract Rats were implanted with chronic indwelling cannulae into the lateral cerebral ventricle. After recovery from surgery, acute experiments on blood pressure were conducted under methoxyflurane/nitrous oxide anesthesia. Rats were injected intracerebroventricularly with two adenosine analogs, 5'- N -ethylcarboxaminidoadenosine (NECA) and (−)- N -(1-methyl-2-phenylethyl)adenosine( l -phenylisopropyladenosine) ( l -PIA), and the effects on blood pressure and heart rate recorded. Both analogs produced dose-related reductions in blood pressure and heart rate with l -PIA producing a more potent depression of heart rate than NECA. These effects on blood pressure and heart rate were antagonized by parenteral injections of caffeine. In separate experiments, the responses of blood pressure and heart rate to microinjection of NECA into the brainstem of rats anaesthetized with methoxyflurane/nitrous oxide were also examined. Microinjection of 2.7 nmol kg into the fourth ventricle in the region of the area postrema produced a profound and long-lasting depression of blood pressure and heart rate. These results show that central injections of analogs of adenosine can influence the areas of the central nervous system involved in the control of cardiovascular function.
The participation of water in the Nef reaction of aci-nitro compounds

Abstract A kinetic study of the effect of water content on the hydrolysis of three nitro aliphatic compounds in methanol, ethanol and dioxan solutions reveals the existence of two reaction pathways for the Nef reaction. The experimental results are shown to follow the rate law: where HA represents the aci-nitro compound. The constants ka and kb are evaluated and a reaction mechanism consistent with all available experimental evidence is presented.
Development of a bead-based immunoassay to routinely measure vimentin autoantibodies in the clinical setting.

Abstract Introduction Vimentin is an intermediate filament protein generally expressed in the cytosol of many adult cell types, including leukocytes, fibroblasts and endothelial cells. Several tissue and/or injury-specific isoforms of vimentin are known to exist that may trigger autoimmune responses due to aberrant structural or conformational variations. Such scenarios include allograft rejection and certain autoimmune diseases, such as rheumatoid arthritis. The primary objective for this study was to develop a Luminex immunobead assay to quantitate circulating levels of vimentin antibodies and, secondarily, to appraise the feasibility of these autoantibodies as a biomarker for clinical diagnosis. Methods Recombinant human vimentin was conjugated to MagPlex® beads using standard carbodiimide/NHS chemistry and coupling efficiency tested and assay parameters determined using a commercial anti-vimentin polyclonal antibody. A limited number of serum samples (n = 71) were then tested to evaluate the diagnostic value for future biomarker development efforts. Results Findings from repeated testing of three distinct batches of assays provide assay range parameters of 0.18–15 μg/mL, median inter-assay recovery parameter within 1% of completion, and inter-assay variation (%CV) at 7%. The assay was found to be stable at several conditions with less than 5% loss in a month. Preliminary evaluation of the assay demonstrates significantly (p = 0.022) higher circulating levels of anti-vimentin antibodies in 51 cases of renal allograft rejection relative to 20 cases of age-matched controls. Conclusion A direct capture assay for vimentin autoantibodies was developed and analytically validated. Preliminary evaluation of this assay against patient materials was promising and justifies additional testing with larger cohorts in future studies.
Silicic acid uptake by natural populations of marine phytoplankton

Abstract The response of silicic acid uptake by phytoplankton populations to varyingsilicic acid concentrations has been investigated using a newly developed Si stable isotope tracer technique in the Peru upwelling region. Since silicic acid uptake follows the Michaelis-Menten expression for enzyme kinetics, a hyperbola describes the relationship between concentration and uptake. The half saturation constant ( K τ ) for uptake and the maximum uptake ( V max ) were 2·93 μg atoms Si. 1. −1 and 0·075 hr −1 , respectively. The uptake is light-dependent and this relation is also described by the Michaelis-Menten equation. Since uptake is both light- and silicic acid concentration-dependent, vertical profiles of it obtained with the Si isotope tracer technique can be interpreted from the interaction of light and silicic acid concentrations at different depths. The uptake of silicic acid by natural phytoplankton populations had diel periodicity, with a maximum about noon and significant nearly uniform rate at night. Nitrate reductase activity and 15 N-nitrate and 15 N-ammonium uptake had a similar diel periodicity.
Effects of Network Pattern and Status Congruence on Computer-Mediated Group Decision Making:

Classic experimental studies on restrictive communication networks concluded that network patterns and status congruency affect efficiency, satisfaction, and leadership of group decision making. This experiment had a two-fold purpose: (1) to determine if computer-mediated communication would effect the results of these studies; and (2) to assess centrality of network position as a context cue of social status. The results suggested that network pattern retained its influence in computer-mediated groups, while influence of status congruence was weakened by the equalization effects of the computer media. The results also indicated that a center position in the computer network did serve a social-context cue of status: a high-status person exerted status influence only occupying the hub position. Thus, assignment of group members to network positions of equal or different centrality can be used as means of controlling influence of status and authority in computer-mediated groups.
Cross-correlation of common lines: A novel approach for single-particle reconstruction of a structure containing a flexible domain

We describe a novel approach to sorting class averages of a structure in multiple conformational states in order to generate 3D reconstructions that account for conformational variability present in the sample. The method assumes that the relative Euler angles between class averages are known, then uses a common lines approach to match any given class against a set of distinct conformations from a selected view of the structure. We show the effectiveness of the method both on model data and on an experimental dataset for which the conformational variability is limited to a defined region within the structure. During our studies of hepatitis C virus (HCV) internal ribosome entry site (IRES) interaction with the human translation initiation factor eIF3, we observed that the IRES RNA included a flexible region holding multiple conformations. While current classification methods were used to produce two-dimensional averages of the complex showing these different conformations, no method existed for relating these averages in three dimensions. Our approach overcame these limitations, giving us structural insight that was previously not possible.
Modeling discharge and charge characteristics of nickel-metal hydride batteries

Abstract A combined numerical and experimental study of the discharge and charge of nickel–metal hydride (Ni–MH) batteries has been performed. Numerical simulations were based on a previously developed micro–macroscopic coupled model which includes both the proton diffusion in the nickel active material and the hydrogen diffusion in metal-hydride particles. Oxygen generation and recombination, a principal mechanism to ensure safe operation of Ni–MH cells during overcharge, is also accounted for. A sealed Ni–MH cell (AA size, 1 Ah capacity) was prepared and discharge experiments were conducted at various rates. These experimental data along with other discharge and charge data available in the literature were used to validate the present model. Numerical results were presented to show the effects of oxygen evolution on battery performance, particularly on the charge acceptance, cell pressure build-up and self-discharge. This combined experimental and numerical study yields a computer-aided tool for the design and optimization of Ni–MH batteries.
Customer satisfaction, customer retention, and market share

Abstract We provide a mathematical framework for assessing the value of customer satisfaction. The framework enables managers to determine which customer satisfaction elements have the greatest impact, and how much money should be spent to improve particular customer satisfaction elements. This makes it possible to hold customer satisfaction programs accountable, in the way that other business programs are held accountable, by forcing them to demonstrate their benefits with respect to bottom-line profitability. We use an individual-level model of loyalty and retention, and then build up to market share by aggregation. We demonstrate the application of our approach in a pilot study of a city's retail banking market.
Unipolar depression/bipolar depression: connections and controversies.

The modern dichotomous divide between unipolar and bipolar depressive disorders derives from several monographs that appeared in the mid-twentieth century. Studies of illness course and differing symptomatic profiles in unipolar and bipolar illness support this interpretation, but more recent descriptions of ‘bipolar spectrum disorders’ and genetic findings suggest otherwise. Whether these illnesses represent categories or points on a continuum remains an unresolved question.
Effect of beta blockers alone, of angiotensin-converting enzyme inhibitors alone, and of beta blockers plus angiotensin-converting enzyme inhibitors on new coronary events and on congestive heart failure in older persons with healed myocardial infarcts and asymptomatic left ventricular systolic dysfunction.

Persons with asymptomatic left ventricular (LV) systolic dysfunction after myocardial infarction treated with blockers 1,2 or with angiotensin-converting enzyme (ACE) inhibitors 3,4 have a significant reduction in cardiovascular morbidity and mortality. The combined use of blockers plus ACE inhibitors in these persons causes a significantly greater reduction in cardiovascular morbidity and mortality. 5,6 We are reporting data from an observational study investigating the effects of the use of blockers alone, ACE inhibitors alone, and of combined blockers plus ACE inhibitors on the incidences of new coronary events and of congestive heart failure (CHF) in older asymptomatic persons with prior myocardial infarction and LV ejection fraction 40%. One hundred ninety-six men and 281 women, mean age 79 8 years (range 60 to 96), with prior myocardial infarction and asymptomatic LV systolic dysfunction with a LV ejection fraction 40% were followed prospectively in a long-term health care facility for the incidences of new coronary events and CHF. The full-time staff physicians taking care of the 477 persons treated 107 of them (22%) with blockers alone, 89 (19%) with ACE inhibitors alone, 132 (28%) with both blockers plus ACE inhibitors, and 149 (31%) with no blocker or ACE inhibitor. Physician use of drugs determined whether blockers, ACE inhibitors, blockers plus ACE inhibitors, or no blockers or ACE inhibitors were administered. Persons were considered to have prior myocardial infarction if they had a documented clinical history of myocardial infarction or electrocardiographic evidence of Q-wave myocardial infarction. New coronary events were diagnosed if the person developed nonfatal or fatal myocardial infarction 7 or sudden coronary death 8 as previously described.
A PRICING OPERATOR‐BASED TESTING FOUNDATION FOR A CLASS OF FACTOR PRICING MODELS

This paper develops a cross-market version of factor pricing models. It is shown that exact factor pricing holds across two submarkets with respect to their common factors if and only if the unique pricing operator for the first submarket is equal to that for the other submarket with probability 1. We define an APT measure as the squared distance between the two pricing operators. Then, testing whether this measure is zero is equivalent to testing exact factor pricing across the two submarkets. Since the estimation of this measure does not require parameterizing and extracting the underlying factors, one can test factor pricing models without knowing any factors. In addition, we present a randomization procedure so that one can use it to conduct a more comprehensive investigation on the empirical robustness of factor pricing models.
Core Values Are the Bedrock of a Culture of Compliance in Health Care Agencies

Core values should be reexamined periodically in every health care agency to ensure that they are still the bedrock of its compliance culture. A health care agency culture is partially the outward demonstration of the core values underlying the ethical framework that dictates decision making. The question that must be asked is whether these existing core values are creating the culture of compliance that your agency desires. This article explores essential core values that are the bedrock of health care agencies and establishes the ingredients for developing a culture of compliance.
Removal of Polysialylated Neural Cell Adhesion Molecule Increases Morphine Analgesia and Interferes with Tolerance in Mice

Neurons that express high levels of polysialylated neural cell adhesion molecule (PSA-NCAM) in adult spinal substantia gelatinosa also express the μ-opioid receptor. While PSA removal from NCAM by spinal intrathecal injection of endoneuraminidase-N (endo-N) did not detectably change opioid receptor expression, morphine-induced analgesia was significantly increased. This analgesic strengthening was detected as early as 15 min after endo-N treatment and persisted for at least 7 days. In addition, the tolerance that develops with chronic morphine treatment was overcome in the absence of PSA. Interestingly, the same effects on analgesia and tolerance were also produced by selective deletion of the NCAM-180 isoform.
Strategies for selective priming of memory B cells.

Abstract Long-term humoral immunity elicited by pathogens and vaccines alike relies upon the generation of both memory B cells (B mem ) and long-lived plasma cells (PCs). Virtually all vaccine formulations induce the concomitant emergence of both B mem and PCs, suggesting that the emergence of these two differentiated B cells subsets is commonly controlled. Evidence presented shows specific Toll-like receptor (TLR) agonists coupled with soluble protein antigen (sAg) can selectively induce the expansion of antigen specific B mem in the absence of PC generation. The co-administration of either TLR 3 or 9 agonists with sAg induced germinal centre (GC) formation, antigen-specific B mem , but failed to substantively induce the generation of long-lived bone marrow (BM) PCs. Upon re-challenge, high levels of PCs were induced with concomitant high titres of antigen-specific serum IgG. Hence, vaccines can be developed that can prime and protect the host to subsequent infectious agents without initial, high levels of antibody production. Furthermore, these studies suggest that the signals that govern the expansion and differentiation of B mem can be uncoupled from those that induce long-lived BM PCs.