cssi/SciSciGPT-SciSciNet huggingface dataset:
Upregulated Chemokine and Rho-GTPase Genes Define Immune Cell Emigration into Salivary Glands of Sjögren’s Syndrome-Susceptible C57BL/6.NOD-Aec1Aec2 Mice

The C57BL/6.NOD-Aec1Aec2 mouse is considered a highly appropriate model of Sjogren’s Syndrome (SS), a human systemic autoimmune disease characterized primarily as the loss of lacrimal and salivary gland functions. This mouse model, as well as other mouse models of SS, have shown that B lymphocytes are essential for the development and onset of observed clinical manifestations. More recently, studies carried out in the C57BL/6.IL14α transgenic mouse have indicated that the marginal zone B (MZB) cell population is responsible for development of SS disease, reflecting recent observations that MZB cells are present in the salivary glands of SS patients and most likely initiate the subsequent loss of exocrine functions. Although MZB cells are difficult to study in vivo and in vitro, we have carried out an ex vivo investigation that uses temporal global RNA transcriptomic analyses to profile differentially expressed genes known to be associated with cell migration. Results indicate a temporal upregulation of specific chemokine, chemokine receptor, and Rho-GTPase genes in the salivary glands of C57BL/6.NOD-Aec1Aec2 mice that correlate with the early appearance of periductal lymphocyte infiltrations. Using the power of transcriptomic analyses to better define the genetic profile of lymphocytic emigration into the salivary glands of SS mice, new insights into the underlying mechanisms of SS disease development and onset begin to come into focus, thereby establishing a foundation for further in-depth and novel investigations of the covert and early overt phases of SS disease at the cellular level.
Design, synthesis and analysis of novel sphingosine kinase-1 inhibitors to improve oral bioavailability

Abstract The sphingomyelin pathway is important in cell regulation and determining cellular fate. Inhibition of sphingosine kinase isoform 1 (SK1) within this pathway, leads to a buildup of sphingosine and ceramide, two molecules directly linked to cell apoptosis, while decreasing the intracellular concentration of sphingosine-1-phosphate (S1P), a molecule linked to cellular proliferation. Recently, an inhibitor capable of inhibiting SK1 in vitro was identified, but also shown to be ineffective in vivo. A set of compounds designed to assess the impact of synthetic modifications to the hydroxynaphthalene ring region of the template inhibitor with SK1 to obtain a compound with increased efficacy in vivo. Of these fifteen compounds, 4A was shown to have an IC50 = 6.55 μM with improved solubility and in vivo potential.
Joining the Circle: Native American Philosophy Applied to the Study of Late Archaic Shell Rings of the Southeast United States

Archaeology is in a period of change, a point of inflection in which the discipline strives to reject its colonial roots. Embracing the “ontological turn,” archaeologists are applying diverse worldviews within their interpretations, yet these worldviews continue to reintroduce colonial ideals as they emerge out of Western philosophical schools. Using Native American philosophy, a recent addition to the academy, several key themes are identified and applied to the study of Late Archaic shell rings found along the Southeast United States coastlines. Through these themes, these sites are interpreted as places where Native Americans established communication with non-human forces and eventually socialized the newly formed coastline. The use of Native American philosophy is provided as a counter-balance to the use of Western philosophy as a means of further decolonizing archaeology
A brief history of interdependencies and water on the Colorado plateau

Abstract Over 40 million people in the U.S. Southwest depend on water from the Colorado River. Seven States, Arizona, California, Colorado, Nevada, New Mexico, Utah, and Wyoming, have rights to the river. For millions of years, it has carved its way from high in the western Rocky Mountains south and west, skirting the borders of California, Nevada, and Arizona before giving its water to a delta in Mexico. It rarely makes it to the Gulf of California, its original terminus. The Colorado Plateau encompasses over 150,000 square miles. The plateau includes geologic wonders like the Grand Canyon, Black Canyon of the Gunnison River, Canyon de Chelly on the Navajo Reservation, Canyonlands, Arches, and Rainbow Bridge, among others. The authors recommend that we turn to the past and include the perspectives of diverse communities, who have ties to the region and its waters going back centuries to avoid a water shortage in the future.
Individuals with both perceived ankle instability and mechanical laxity demonstrate dynamic postural stability deficits.

Background Chronic ankle instability is a frequent and serious consequence of lateral ankle sprains. The contribution of perceived instability and potential for mechanical laxity to contribute to the overall deficit in dynamic postural stability is unclear. The purpose was to determine if those with mechanical laxity demonstrated significant differences in dynamic postural stability compared to controls, copers and those with perceived instability. Methods Of 93 participants, 83 recreationally active individuals were divided into 4 groups: controls, copers, those with perceived instability, and those with both perceived instability and mechanical laxity. Injury history and the Cumberland Ankle Instability Tool were collected, and an instrumented arthrometer was applied. Participants completed a single limb jump landing, balancing upon completion. Ground reaction force data were collected, scaled to body mass, and the Dynamic Postural Stability Indices were calculated for anterior–posterior, medial–lateral, vertical and composite. One-way ANOVAs with Tukey post-hoc tests (α < 0.05) were conducted on each of the stability indices among the four groups. Findings The mechanically lax group had significantly greater mean (standard deviation) medial–lateral stability index scores 0.57 (0.62) than the coper group 0.24 (0.20; P = 0.02) and significantly greater composite index scores 0.73 (0.57) than the perceived instability 0.49 (0.09) and coper groups 0.47 (0.12 P = 0.05). No other indices were significantly different among groups. Interpretation Individuals with perceived instability and mechanical laxity exhibited dynamic postural deficits compared to copers and those with perceived instability alone. Mechanical laxity may contribute to the deficits in dynamic postural stability.
Are Higher 529 College Savings Plan Fees Linked to Greater State Tax Incentives

Despite the fact that 529 College Savings Plans have existed for over a decade, there has been limited scholarly attention on investment questions related to this savings vehicle. In some of the first academic literature on this topic, Alexander and Luna (Supplement 2005) identified a surprising relationship between 529 College Savings Plan participation and plan fees. They found a positive relationship between participation rates and fees. While they link this counterintuitive result to plan marketing efforts by brokers, I propose an alternative view. In my data which covers a five year time span, I find no significant relationship between participation rates and fees. However, when investigating the tax incidence with respect to 529 plans, I find a positive relationship between state tax rates and 529 plan fees. This suggests that investment companies could be opportunistically setting fees to usurp the benefits which state governments intended for investors. Since state tax incentives are designed to induce participation and plan fees (by design) are correlated with these incentives, the positive link between plan fees and participation becomes less of a puzzle.
The subunits of human pituitary thyroid-stimulating hormone. Isolation, properties, and composition.

Abstract The subunits, α and β, of human thyroid-stimulating hormone (TSH) from the pituitary have been obtained by the same procedures utilized for the preparation of bovine TSH subunits, namely, dissociation in 1 m propionic acid and separation by gel filtration. The amino acid composition of human TSH-α indicates that this subunit is identical or nearly so with the α subunits of human luteinizing hormone and human chorionic gonadotropin. The NH2-terminal residue is valine and it appears that human TSH-α is shortened at its amino end by 7 residues relative to bovine TSH-α; a similar relationship has been shown by others for human LH-α relative to the ovine or bovine subunit. The β subunit of human TSH differs markedly in amino acid composition from those of the two human gonadotropins, particularly with respect to tyrosine, isoleucine, valine, proline, arginine, and lysine. The carbohydrate analyses for the 2 subunits are given. A major difference between human and bovine TSH is the presence of sialic acid in the former, nearly all in the α subunit. Immunological comparisons by double diffusion show that antisera to the intact hormone or its α subunit cross-react with homologous TSH and with the human gonadotropins but that the antiserum against the β subunit is specific for thyroid-stimulating hormone. The human subunits were shown, by gel electrophoresis and bioassay, to form intra- and interspecies recombinants with complementary subunits from other glycoprotein hormones.
AMPA-receptor trafficking and injury-induced cell death.

AMPA receptors (AMPARs) are critical for synaptic plasticity, and are subject to alterations based on subunit composition and receptor trafficking to and from the plasma membrane. One of the most potent regulators of AMPAR trafficking is the pro-inflammatory cytokine tumor necrosis factor (TNF)α, which is involved in physiological regulation of synaptic strength (Beattie et al., (2002) Science, 295, 2282–2285; Stellwagen and Malenka, (2006) Nature, 440, 1054–1059) and is also present at high concentrations after CNS injury. Here, we review evidence that TNF can rapidly alter the surface expression of AMPARs so that the proportion of Ca++-permeable receptors is increased and that this increase, in combination with increased levels of extracellular glutamate after injury, plays an important role in enhancing excitotoxic cell death after CNS injury. Thus, the pathophysiological hijacking of a critical regulator of synaptic plasticity and homeostasis by the secondary injury cascade may represent a new therapeutic target for neuroprotection.
What's so Great About Constitutionalism?

This paper identifies and then criticizes ten of the leading accounts of constitutionalism: enforcement of a principal-agent relationship; enforcement of societal precommitments; providing a mechanism for checks and balances; protection of minority rights; maintenance of continuity or tradition; symbolizing national unity; serving an educational function; securing finality for disputed issues; providing a rule of recognition for law; satisfying a majoritarian preference for constitutionalism. The bulk of the paper consists of normative and positive criticism of these ten putative justifications for constitutionalism; that is, I argue that they are neither unambiguously attractive, nor do they describe particularly well our own constitutional system. In a brief, second part of the article, I offer what I believe to be a better description of our constitutional system and then assess whether that account is normatively attractive. Boiled down to essentials, my positive account of the American system of judicial review is this: The Supreme Court, in politically unpredictable ways, imposes culturally elite values in marginally countermajoritarian fashion.
Gelfand-Zeitlin Theory from the Perspective of Classical Mechanics. II

Let M(n) be the algebra (both Lie and associative) of n × n matrices over ℂ. Then M(n) inherits a Poisson structure from its dual using the bilinear form (x, y) = −tr xy. The Gl(n) adjoint orbits are the symplectic leaves and the algebra, P(n), of polynomial functions on M(n) is a Poisson algebra. In particular, if f ∈ P(n), then there is a corresponding vector field ξ f on M(n). If m ≤ n, then M(m) embeds as a Lie subalgebra of M(n) (upper left hand block) and P(m) embeds as a Poisson subalgebra of P(n). Then, as an analogue of the Gelfand-Zeitlin algebra in the enveloping algebra of M(n), let J(n) be the subalgebra of P(n) generated by P(m)Gl(m) for m = 1, . . ., n. One observes that $$ J\left( n \right) \cong P\left( 1 \right)^{Gl\left( 1 \right)} \otimes \cdots \otimes P\left( n \right)^{Gl\left( n \right)} $$ . We prove that J(n) is a maximal Poisson commutative subalgebra of P(n) and that for any p ∈ J(n) the holomorphic vector field ξ p is integrable and generates a global one-parameter group σ p(z) of holomorphic transformations of M(n). If d(n) = n(n + 1)/2, then J(n) is a polynomial ring ℂ[p 1, . . ., p d(n)] and the vector fields \( \xi _{p_i } \) , i = 1, . . ., d(n − 1), span a commutative Lie algebra of dimension d(n − 1). Let A be a corresponding simply-connected Lie group so that A ≅ ℂd(n−1). Then A operates on M(n) by an action σ so that if a ∈ A, then $$ \sigma \left( a \right) = \sigma _{p_1 } \left( {z_1 } \right) \cdots \sigma _{pd\left( {n - 1} \right)} \left( {z_{d\left( {n - 1} \right)} } \right) $$ where a is the product of exp z i \( \xi _{p_i } \) for i = 1, . . ., d(n − 1). We prove that the orbits of A are independent of the choice of the generators p i. Furthermore, for any matrix the orbit A · x may be explicitly given in terms of the adjoint action of a n − 1 abelian groups determined by x. In addition we prove the following results about this rather remarkable group action.
Implementing Intensive Vocabulary Instruction for Students at Risk for Reading Disability.

Concerns regarding literacy levels in the United States are long standing. Debates have existed for decades regarding the most effective ways to teach reading, especially the polarizing dilemma of how much to focus on decoding versus code-emphasis and whole language instruction. Fortunately, as a result of concentrated research efforts and analyses of the extant literature on teaching reading, perhaps spurred by these debates, we know more now than we ever have about how to teach basic reading skills. However, there is still much work to be done in order to determine which instructional practices are the most effective ways in which to teach children to read. The need for more research focusing on best instructional practices is exacerbated by the well-documented gap between research. Literacy rates among this nation's students have consistently missed the mark over the years. The 2009 Nation's Report Card shows that 33 percent of students are reading below the basic level of achievement as measured by the National Assessment of Education Progress (NAEP). Likewise, only 33 percent of our nation's fourth graders are achieving at the proficient (25 percent) or advanced (8 percent) levels on the NAEP. Our purpose in this article is to begin to bridge the research-to-practice gap by translating recent research in beginning reading to help teachers to more easily implement effective practices in their classrooms. In particular, our focus is on effective use of vocabulary instruction. Several researchers have begun to examine the important role of vocabulary in beginning reading and to determine the best ways to teach vocabulary to children at risk for reading failure. We begin with an explanation of the role of vocabulary in beginning reading and describe recent intervention research in this area. We conclude with a detailed description of the interventions we used in our research so that teachers may create their own vocabulary lessons that best meet the needs of their students.
cis-element combinations determine phenylalanine ammonia-lyase gene tissue-specific expression patterns.

The bean phenylalanine ammonia-lyase gene 2 (PAL2) is expressed in the early stages of vascular development at the inception of xylem differentiation, associated with the synthesis of lignin precursors. This is part of a complex program of developmental expression regulating the synthesis of functionally diverse phenylpropanoid natural products. Analysis of the expression of PAL2 promoter-P-glucuronidase gene fusions in transgenic tobacco plants showed that functionally redundant cis elements located between nucleotides -289 and -74 relative to the transcription start site were essential for xylem expression, but were not involved in expression in leaf primordia and stem nodes or in establishing tissue specificity in petals. The -135 to -119 region implicated in xylem expression contains a negative element that suppresses the activity of a cryptic cis element for phloem expression located between -480 and -289. The functional properties of each vascular element are conserved in stem, petiole, and root, even though the xylem and phloem are organized in different patterns in these organs. We conclude that the PAL2 promoter has a modular organization and that tissue-specific expression in the vascular system involves a negative combinatorial interaction, modulation of which may provide a flexible mechanism for modification of tissue specificity.
Androgens Modulate Endothelial Function and Endothelial Progenitor Cells in Erectile Physiology

The incidence of erectile dysfunction (ED) increases with age and cardiovascular disease risk factors, such as hypertension, hyperlipidemia, insulin resistance, obesity, and diabetes. These risk factors are thought to contribute to endothelial dysfunction and atherosclerosis, thus contributing to the pathophysiology of ED. The role of the endothelium in regulating erectile physiology is well established. However, the role of androgens in modulating endothelial function and endothelial repair mechanisms subsequent to vascular injury in erectile tissue remains a subject of intensive research. The clinical and preclinical evidence discussed in this review suggests that androgens regulate endothelial function and also play an important role in the development and maturation of endothelial progenitor cells (EPCs), which are thought to play a critical role in repair of endothelial injury in vascular beds. In this review, we discuss the data available on the effects of androgens on endothelial function and EPCs in the repair of vascular injury. Indeed, more research is needed to fully understand the molecular and cellular basis of androgen action in regulating the development, differentiation, maturation, migration, and homing of EPCs to the site of injury. A better understanding of these processes will be critical to the development of new therapeutic approaches to the treatment of vascular ED.
Deformation studies of polymers by time resolved Fourier transform infra-red spectroscopy: 1. Development of the technique

Abstract We have constructed a miniature closed-loop servo-controlled hydraulic tensile tester interfaced to our fast scanning Fourier transform infra-red spectrometer. Macroscopic information in the form of stress-strain curves can be collected along with the microstructural changes in the form of infra-red data. This technique in conjunction with our newly developed time resolved Fourier transform spectroscopy package has been used to follow structural changes in macromolecules.
Cyclopentanoid Terpene Biosynthesis in a Phasmid Insect and in Catmint

The stick insect, Anisomorpha buprestoides, and the catmint, Nepeta cataria, produce closely related cyclopentanoid terpenes, anisomorphal and nepetalactone. Tracer experiments with isotopes indicate that anisomorphal is synthesized by the walking stick from normal terpene precursors (acetate or mevalonate). In the catmint plant, isolated leaf disks synthesized nepetalactone, utilizing the same precursors.
Rational design, synthesis, and biological evaluation of rigid pyrrolidone analogues as potential inhibitors of prostate cancer cell growth

Abstract In view of its role in tumor promotion and signal transduction, protein kinase C (PKC) has proven to be an exciting target for cancer therapy. With the aid of molecular modeling, we rationally designed and stereoselectively synthesized a new class of rigidified pyrrolidone-based PKC activators. Pyrrolidone 15 was found to exhibit reasonable affinity for PKCδ, with lower affinity for the other isozymes tested. Pyrrolidone Figure 1 , Scheme 1 causes the dose-dependent induction of apoptosis in LNCaP prostate cancer cells. This apoptotic effect could be markedly potentiated by the use of LNCaP cells overexpressing the PKCα or δ isozymes.
Proteomic and metabolomic biomarkers for III-V semiconductors: and prospects for application to nano-materials.

There has been an increased appreciation over the last 20 years that chemical agents at very low dose levels can produce biological responses in protein expression patterns (proteomic responses) or alterations in sensitive metabolic pathways (metabolomic responses). Marked improvements in analytical methodologies, such as 2-D gel electrophoresis, matrix-assisted laser desorption-time of flight (MALDI-TOF) and surface enhanced laser desorption-time of flight (SELDI-TOF) technologies are capable of identifying specific protein patterns related to exposure to chemicals either alone or as mixtures. The detection and interpretation of early cellular responses to chemical agents have also made great advances through correlative ultrastructural morphometric and biochemical studies. Similarly, advances in analytical technologies such as HPLC, proton NMR, MALDI-TOF, and SELDI-TOF have permitted early detection of changes in a number of essential metabolic pathways following chemical exposures by measurement of alterations in metabolic products from those pathways. Data from these approaches are increasingly regarded as potentially useful biomarkers of chemical exposure and early cellular responses. Validation and establishment of linkages to biological outcomes are needed in order for biomarkers of effect to be established. This short review will cover a number of the above techniques and report data from chemical exposures to two binary III-V semiconductormore » compounds to illustrate gender differences in proteomic responses. In addition, the use of these methodologies in relation to rapid safety evaluations of nanotechnology products will be discussed. (Supported in part by NIH R01-ES4879)« less
A thermomechanical framework for modeling the compaction of asphalt mixes

Compaction of asphalt mixes is a very important process that is known to influence the performance of these mixes. This study is aimed at developing a nonlinear model for the compaction process within a thermodynamic framework that exploits the notion of a body possessing multiple natural configurations. By specifying the forms for the stored energy, the rate of dissipation, the heat flux vector, etc., for the material, a specific model is developed to describe and study asphalt mix compaction. The phenomenon of compaction requires the development of a compressible viscoelastic material to describe the response of asphalt mixes. A numerical scheme was developed to solve the equations governing compaction and the results were compared with results from experiments that were carried out. The agreement with the experimental results are quite good indicating that this model may be used to predict the compactability of asphalt mixes and in the design of asphalt mixes that can be compacted in the field to achieve desirable performance characteristics.
Reactions against the Mass Society

(1962). Reactions against the Mass Society. The Sociological Quarterly: Vol. 3, No. 4, pp. 316-330.
Investigation of Cavitating Cascades

Experiments on cavitating and noncavitating cascades were carried out in a conventional water tunnel modified for this purpose. The comparison of the experimental results with theory, in both the fully wetted and fully cavitating conditions, was found to be satisfactory.
A split-foundry asynchronous FPGA

We present the first published measurements of a complex digital integrated circuit fabricated in both standard and split-foundry processes. Our 1.3-million-transistor asynchronous FPGA operates at over 300MHz in 130nm. We discuss the challenges inherent in split design and our automated layout tools that address them.
Decoupling the structural modes estimated using recursive lattice filters

The modal amplitudes generated by recursive least square lattice filters are coupled. For the adaptive scheme being developed the modal amplitudes are required to be decoupled. A scheme for transforming the coupled modes into decoupled ones is presented herein and is tested in simulation studies on a free-free beam.
Prostaglandin modulation of development of cell-mediated immunity in culture

Prostaglandins (PGs) have been implicated as possible modulators of the immune response and various inflammatory processes1–4. Various cell components of the immune system are sources of PGs, and mitogen or antigen stimulation of human or murine lymphocytes leads to their enhanced release5–8. They are also released from various human and animal tumours9,10. Thus, as cells of the immune system are both sensitive to and sources of PGs, these factors may be important as physiological immune regulators. For example, PGs of the E series are capable of inhibiting many effector functions9–15. They have also been shown to inhibit the development of the humoral response16,17. Although they inhibit the proliferative response to mitogens18,19, little is known about their effects on the development of the cell-mediated immune response to antigens. The data summarized here implicate PGs, thromboxane A2 (TXA2) and prostacyclin (PGI2) in the regulation of cellular immune responses at the inductive phase. Some of these data have been reported in abstract form20.
Allergen Immunotherapy Extract Treatment Set Preparation: Making a Safer and Higher Quality Product for Patients

The best possible allergen immunotherapy clinical outcomes require the provision of high quality and safe allergen immunotherapy extract preparations. Evolving national guidelines and regulatory bodies have devoted special attention to the safe compounding of sterile products, including allergen extracts. It is incumbent upon allergists preparing extract treatment sets for patients to be familiar with and adopt training, procedures and safety measures that lead to standardized high quality products. Preparers and supervisors must maintain ongoing competency in aseptic technique and prescribing principles, such as probable effective dose ranges, allergen cross-reactivity, and separation of high protease-containing extracts from susceptible extracts. Accordingly, knowledge and application of vial labeling, diluent selection, standard operating procedures, mixing log documentation, and mixing condition principles are a necessity. Although there have been no instances of infectious complications from allergen immunotherapy in a century of clinical practice, continued vigilance in the use of measures that ensure extract sterility is paramount. A review of allergen immunotherapy preparation recommendations and best practices based on published national guidelines is presented. Further study of preparation measures and prescribing principles will continue to advance the practice of allergen immunotherapy and offer opportunities for refinement of current recommendations.
Photonic band structure of fcc colloidal crystals.

Polystyrene colloidal crystals form three dimensional periodic dielectric structures which can be used for photonic band structure measurements in the visible regime. From transmission measurements the photonic band structure of an fcc crystal has been obtained along the directions between the $L$ point and the $W$ point. Kossel line patterns were used for locating the symmetry points of the lattice for exact positioning and orientation of the crystals. In addition, these patterns reveal the underlying photonic band structure of the crystals in a qualitative way.
Positive solutions of quasilinear parabolic systems with nonlinear boundary conditions

Abstract The aim of this paper is to investigate the existence, uniqueness, and asymptotic behavior of solutions for a coupled system of quasilinear parabolic equations under nonlinear boundary conditions, including a system of quasilinear parabolic and ordinary differential equations. Also investigated is the existence of positive maximal and minimal solutions of the corresponding quasilinear elliptic system as well as the uniqueness of a positive steady-state solution. The elliptic operators in both systems are allowed to be degenerate in the sense that the density-dependent diffusion coefficients D i ( u i ) may have the property D i ( 0 ) = 0 for some or all i. Our approach to the problem is by the method of upper and lower solutions and its associated monotone iterations. It is shown that the time-dependent solution converges to the maximal solution for one class of initial functions and it converges to the minimal solution for another class of initial functions; and if the maximal and minimal solutions coincide then the steady-state solution is unique and the time-dependent solution converges to the unique solution. Applications of these results are given to three model problems, including a porous medium type of problem, a heat-transfer problem, and a two-component competition model in ecology. These applications illustrate some very interesting distinctive behavior of the time-dependent solutions between density-independent and density-dependent diffusions.
A precessionally-driven dynamo in a plane layer

A simple model of precessionally-forced flow has been proposed and studied by Mason and Kerswell (Mason, R.M. and Kerswell, R.R., Chaotic dynamics in a strained rotating flow: a precessing plane fluid layer. Geophys. Astrophys. Fluid Dynam., 491, 2002, 71–106). The fluid is viscous and incompressible and occupies a plane layer that spins about its normal that itself precesses about an axis fixed in space. The present article confirms the linear stability results of Mason and Kerswell and investigates in greater detail the complicated bifurcation that arises at the onset of two-dimensional instability. Three-dimensional modes are studied and it is shown that, if the fluid is sufficiently electrically conducting, the motions can, for sufficiently strong precessional forcing, maintain a magnetic field by dynamo action. The Lorentz force is found to reduce the vigor of the motions but to modify them in a way that assists magnetic field generation.
Toosendanin: Synthesis of the AB-ring and Investigations of Its Anti-Botulinum Properties (Part II)

Botulinum neurotoxins (BoNTs) are the etiological agents responsible for botulism, a disease characterized by peripheral neuromuscular blockade and a characteristic flaccid paralysis of humans. The natural product toosendanin, a limonoid, is a traditional Chinese medicine that has reported anti-botulinum properties in animal models. Toosendanin effectively inhibits the biological activity of BoNT/A in neuronal cells at concentrations of 200 nM, and partial inhibition can be observed with concentrations as low as 8 nM. Mechanistically, toosendanin's inhibition is due to prevention of transduction of the BoNT LC through the HC channel. Intriguing questions as to the molecular architecture of toosendanin as related to its anti-botulinum properties have focused our attention on a synthesis of toosendanin's unusual AB-ring, containing a unique bridged hemi-acetal. Within the current work, a synthetic strategy allowing access to the AB-fragment of toosendanin was achieved from a trans-decalin system. In addition, this fragment was examined for its modulation of BoNT/A intoxication in a rat spinal cord cellular assay.
The Effect of an Elemental Diet with and without Gluten on Disease Activity in Dermatitis Herpetiformis

Abstract Elemental diets are reported to decrease disease activity of patients with dermatitis herpetiformis. We tested the hypothesis that gluten, given in addition to an elemental diet, is responsible for the intestinal abnormalities, cutaneous immunoreactant deposition, and skin disease activity in dermatitis herpetiformis. At entry eight patients with dermatitis herpetiformis, who were consuming unrestricted diets, were stabilized on their suppressive medications at dosage levels that allowed individual lesions to erupt. Six patients were then given an elemental diet plus 30 g of gluten for 2 weeks, followed by the elemental diet alone for 2 weeks. Conversely, two patients received an elemental diet alone for 2 weeks followed by an elemental diet plus gluten during the final 2 weeks. Small bowel biopsies, skin biopsies, and clinical assessments were done at 0, 2, and 4 weeks. Suppressive medication dose requirement decreased over the 4 weeks by a mean of 66%. Six of eight subjects significantly improved clinically during the glutenchallenge phase of the elemental diet and all were improved at the end of the study. The amount of IgA in perilesional skin did not change significantly, but the amount of C3 increased in five of seven evaluable subjects after gluten challenge. Circulating anti-gluten and anti-endomysial antibodies were not significantly affected by the diets. All subjects completing evaluable small bowel biopsies (seven of seven) demonstrated worsening of their villus architecture (by scanning electron microscopy and intraepithelial lymphocyte counts) during gluten challenge and improvement (six of six subjects) after 2 weeks of elemental dietary intake. We conclude that 1) there is a significant improvement in clinical disease activity on an elemental diet, independent of gluten administration, 2) small bowel morphology improves rapidly on an elemental diet, and 3) complement deposition but neither IgA deposition nor circulating antibody levels correlate with gluten intake. It seems likely that dietary factors other than gluten are important in the pathogenesis of the skin lesions in dermatitis herpetiformis.
Aqueous Solubility, Polymorphism, and Pseudopolymorphism of meso-1,2,3,4-Butanetetracarboxylic Acid

The solubility of meso-1,2,3,4-butanetetracarboxylic acid (BTCA) in water and the nature of the solid phases in BTCA-water mixtures were studied. The form of BTCA that was isolated after crystallizing from a saturated aqueous solution and remaining in contact with the solution for over 4 years was BTCA.H 2 O. At 25 °C, a saturated aqueous solution of this product contained 6.99% BTCA. Other hydrates of BTCA were isolated after equilibration of BTCA with water at 25 °C for 1 h to 36 days. Thermal analysis identified these products as BTCA.2H 2 O after 1 h, BTCA.4H 2 O or BTCA.2H 2 O after 5 h, and BTCA.H 2 O after 15 and 36 days. The BTCA concentration in the liquid phase decreased from 18.67% after 5 h to 10.32% after 36 days. A saturated solution of BTCA.2H 2 O contained 18.38% BTCA. Several thermograms for BTCA. H 2 O or BTCA.2H 2 O contained endothermic peaks that are attributed to transitions between forms of anhydrous BTCA.
Fibroblast growth factor in the eye and prospects for its therapeutic use

Fibroblast growth factor (FGF) is a monomeric mitogenic protein that exists as an acidic and a basic form and is distributed widely in tissues of the eye. Because FGF interacts with the cells and with the extracellular matrix, it has potential as a therapeutic agent, either alone or in combination with other agents such as epidermal growth factor, in promoting healing of corneal wounds, in restoring corneal endothelial cell loss due to dystrophic, degenerative, and surgical insults, as well as in regenerating lens cells after cataract surgery. Excess FGF probably plays a significant role in the pathogenesis of blinding disorders of the eye such as neovascular glaucoma, age-related macular degeneration, and proliferative diabetic vitreoretinopathy, as well as failure of surgical filtering procedures for glaucoma. The use of transforming growth factor-beta, anti-FGF antibodies, and other blocking agents in the treatment of such diseases seems logical.
Elastic wave scattering in a solid half-space with a circular cylindrical hole using the Distributed Point Source Method

Abstract Ultrasonic wave scattering in a solid half-space containing a circular cylindrical hole is studied. The solid is struck by a bounded ultrasonic beam. Distributed Point Source Method (DPSM) which is a semi-analytical technique is adopted to model the ultrasonic field. A finite size transducer is used to generate the ultrasonic field. The circular hole in the solid is modeled by passive point sources. These point sources along with the point sources placed near the fluid–solid interface contribute to the scattered wave field in the solid. Even though the wave scattering by a circular hole in a solid is a classical problem this is the first time the complete variation of the scattered wave field generated by a bounded ultrasonic beam in a solid half-space with a circular hole is shown. The solution of this problem will help us to understand the distortion of the ultrasonic field in a solid and in the neighboring fluid due to the presence of a cylindrical anomaly which plays an important role in sensitivity analysis and calibration of different non-destructive testing techniques. Numerical examples for 1 MHz and 2.25 MHz transducers are given and scattered wave fields generated by holes of different diameters in an aluminum half-space are compared with the wave fields generated in the defect-free environment.
Treatment of Rhinocerebral Mucormycosis with Intravenous, Interstitial, and Cerebrospinal Fluid Administration of Amphotericin B: Case Report

Importance Rhinocerebral mucormycosis is extremely difficult to treat. Approximately 70% of patients are poorly controlled diabetics, and many of the remainder are immunocompromised as a consequence of cytotoxic drugs, burn injuries, or end-stage renal disease. Despite standard treatment consisting of surgical debridement and the intravenous administration of amphotericin B, rhinocerebral mucormycosis is usually a fatal disease. Clinical presentation We describe the case of a 16-year-old male patient with juvenile onset diabetes mellitus who presented with fever, right-sided hemiparesis, and dysarthria. Axial view computed tomography revealed abscess formation in the left basal ganglia and frontal lobe, which was proven by stereotactic biopsy to contain Rhizopus oryzae. Intervention Intravenous administration of amphotericin B (30-280 mg/dose) was begun on the day of admission. On hospital Day 20, after the occurrence of frank abscess formation, the lesion was aggressively debrided. Despite these therapies, there was neurological deterioration characterized by the development of hemiplegia and aphasia. Sequential computed tomographic scans enhanced with contrast medium demonstrated progressively enlarging lesions. Ommaya reservoirs were placed into the abscess cavity and the frontal horn of the contralateral lateral ventricle. The patient was then treated with intracavitary/interstitial injections of amphotericin B during the course of 80 days and three doses of intraventricular amphotericin B. Clinical and radiographic improvement was achieved after treatment. Two years after the initial diagnosis, magnetic resonance imaging of the brain showed no evidence of disease and an examination revealed a neurologically intact and fully functional patient. Conclusion We conclude that with an infection as morbid as rhinocerebral mucormycosis, it is advisable to use surgical debridement and all available routes for delivering amphotericin B to infected cerebral parenchyma, which include intravenous, intracavitary/interstitial, and cerebrospinal fluid perfusion pathways.
Varieties of Realism: Thucydides and Machiavelli

Realists have dominated the postwar study of international politics, but they have not always taken seriously the problems of realism as a moral theory. One such problem is the difficulty of reconciling realism with devotion to ethics in any sphere, including domestic politics. This problem was taken seriously by two originators of the realist school, Thucydides and Machiavelli. I explore the thought of these two authors with special attention to their views of the relation of international realism to general ethical skepticism and to domestic politics in particular. Examining their respective views of international realism, of the origin of societies, of the overall relation between justice and amoral necessity, I conclude that while for Machiavelli international realism is only a part of a more general ethical skepticism. Thucydides tries to manage a difficult if not tragic tension between the requirements of international realism and domestic morality.
Change in Party Identification: The Role of Prospective Economic Evaluations

In the past few years, a new direction has been taken in the study of economics and politics. Researchers have begun to focus on the role of prospective economic evaluations. The research presented here applies the prospective model to changes in partisanship. Regardless of the time period examined, these prospective economic evaluations exert an important influence on party identification. Individuals change their partisanship in response to their expectations concerning the ability of the parties to provide financial prosperity. These findings indicate that previous examinations of the electorate have understated the rationality of the populace, and, accordingly, previous theories of political behavior are in need of revision.
Evolution of electronic resources support: is virtual reference the answer?

Purpose – The purpose of this paper is to describe the further evolution of electronic resources access support at Texas A&M University Libraries with recommendations for incorporating ER support into a virtual reference (VR) service. In a previous article, the implementation of a two‐tiered electronic resources (ER) HelpDesk service was discussed. While an improvement, that service existed in parallel with the library's VR service, requiring separate staff and expertise. After considerable discussion and exploration, it became apparent that the needs of ER support could be met, with some modification, within the VR service.Design/methodology/approach – A project at the Texas A&M University Libraries sought to utilize an existing VR service, staffed by reference librarians and staff, to expand and improve handling and resolving ER access problems.Findings – VR software is effective for managing an electronic access problem reporting system. Integrating ER support into VR more broadly and equitably distrib...
Roles of electrophilic sulfuric acid ester metabolites in mutagenesis and carcinogenesis by some polynuclear aromatic hydrocarbons

Hydroxylation of meso-methyl groups with subsequent formation of reactive benzylic esters bearing a good leaving group (e.g. sulfate) was proposed as a possible biochemical mechanism of activation and tumorigenicity of methyl-substituted polycyclic aromatic hydrocarbons (PAHs). In support of this postulation, recent studies have demonstrated the formation by rodent hepatic sulfotransferase activity of electrophilic, mutagenic, and carcinogenic sulfuric acid esters of several hydroxymethyl aromatic hydrocarbons including hydroxymethyl derivatives of benz[a]anthracene, 6-hydroxymethylbenzo[a]pyrene, 5-hydroxymethylchrysene, 9-hydroxymethyl-10-methylanthracene, and 1-hydroxymethylpyrene. Besides these hydroxymethyl PAHs containing a primary benzylic alcoholic group, some aromatic hydrocarbons with secondary benzylic hydroxyl functional group(s) are also metabolically activated through sulfuric acid esterification.
Captivate Your Students' Minds: Developing Interactive Tutorials to Support the Teaching of Spreadsheet Modeling Skills

Kolb's experiential theory of learning, later modified by McCarthy to develop the 4MAT model, shows that active experimentation is a large part of learning for all types of learners. We use the 4MAT model as the theoretical underpinning to explore and develop some illustrative interactive tutorials to support the teaching of OR/MS spreadsheet modeling. Due to a much shallower learning curve on the new generation of screen capture technology, the design and creation of such spreadsheet support modules can now realistically be done by individual faculty in a reasonable amount of time. Three levels of interactivity are used in the modules to match the learning stages of the 4MAT model. We discuss implementation issues with current screen capture software and the benefits and limitations of this approach for supporting the teaching of spreadsheet modeling in OR/MS.
Reduced production rates in the economic lot scheduling problem

The economic lot scheduling problem were the item's production rates can be reduced from the current or nominal production rates is considered. Management may be interested in reducing production rates to avoid a rapid accumulation of inventories. The instances of the problem where reducing the production rates leads to a decrease in a sharp lower bound of the average cost are characterized. These instances include problems where the independent solution ( strictly) satisfies the capacity constraint. The independent solution is likely to satisfy the capacity constraint in facilities with nominal production rates that are high relative to the demand rates, or in facilities with small setup times. It is shown that, in minimizing a sharp lower bound on the average cost, it is optimal to reduce the rate of at most one item. A simple test identifies the item, typically the slowest, with potential for production rate reduction. If a reduction is warranted a line search, on the dual variable of the capacity cons...
Asymptotically decoupled systems

In this paper, two linear-quadratic systems are shown to be asymptotically decoupled. We obtain the steady-state term and the first-order transient term of optimal controls. We also obtain an estimate of the rate at which the first-order transient term diminishes and approaches zero.
Escherichia coli RNase T Functions in Vivo as a Dimer Dependent on Cysteine 168

Abstract It was shown that Cys-168 is required for RNase T function and thermostability and that its hydrophobic properties are important for this role (Li, Z., Zhan, L., and Deutscher, M. P.(1996) J. Biol Chem. 271, 1127-1132). To understand the molecular basis for these findings, further studies of Cys-168 and RNase T structure were carried out. Treatment of RNase T with the sulfhydryl-modifying agent 5,5′-dithiobis-(2-nitrobenzoic acid) leads not only to inactivation, but also to monomerization of the protein. Similarly, specifically converting Cys-168 to either serine or asparagine leads to loss of activity and to monomer formation at 37°C. However, at 10°C the serine mutant remains as a dimer and retains full RNase T activity, whereas the asparagine derivative shows only a low level of activity and of dimer formation. These data show a strong correlation between activity and the dimer form of RNase T. The importance of dimer formation was also shown in vivo using genetic studies. An inactive mutant of RNase T, termed HA2, which exists as a dimer at 37°C in vitro, completely suppresses endogenous RNase T activity in vivo and in vitro when introduced into a RNase T cell on a multicopy phagemid, most likely as a consequence of inactive heterodimer formation. Introduction of the HA2 gene on a single-copy plasmid, as expected, leads to a proportionally smaller effect on endogenous activity. The dominant negative effect displayed by the HA2 protein can be relieved by an additional mutation in HA2 RNase T that abolishes its ability to dimerize. An inactive mutant asparagine derivative of Cys-168, which also does not dimerize, also shows little of the dominant negative phenotype. Thus, these data demonstrate that RNase T dimerizes in vivo, that the dimer form is required for RNase T activity, and that Cys-168 is needed for dimerization of the enzyme.