cssi/SciSciGPT-SciSciNet huggingface dataset:
Does the evidence for spinal manipulation translate into better outcomes in routine clinical care for patients with occupational low back pain? A case-control study

Abstract Background context Previous research has identified clinical characteristics of patients who are likely to respond favorably to thrust manipulation. The application of this evidence and its effect on clinical outcomes among patients with occupational low back pain has not been examined. Purpose Examine patients treated in physical therapy with occupational low back pain who fit a subgroup likely to respond to thrust manipulation. Study design/setting Retrospective review of clinical database. Patient sample Patients with low back pain of less than 16 days duration with no symptoms distal to the knee or signs of nerve root compression receiving workers' compensation and referred to physical therapy were included. Outcome measures Self-report measures: numeric pain rating and Oswestry disability questionnaire. Functional measures Number of visits, duration, and costs of physical therapy. Methods Physical therapy notes for the first two sessions were examined. Patients were categorized as having received thrust manipulation, nonthrust manipulation, or no manipulation. Pain intensity and disability were recorded at initial and final sessions. The number of sessions, length of stay, and costs of physical therapy were recorded. Comparisons were made between patients receiving manipulation versus no manipulation, and between those receiving thrust versus nonthrust manipulation. Results Two hundred fifteen patients were included (mean age 35.9 [±10.1] years, 67.9% male). Thrust manipulation was received by 107 (49.8%) patients; 36 (16.7%) received nonthrust manipulation and 72 (33.5%) received no manipulation. Patients receiving manipulation (thrust or nonthrust) experienced greater reductions in pain and disability with treatment. Patients receiving thrust manipulation had fewer sessions, a shorter length of stay, and lower costs in physical therapy than patients receiving nonthrust manipulation. Conclusions The evidence supporting superior clinical outcomes with the use of manipulation for a subgroup of patients was corroborated by this retrospective review of patients with occupational low back pain. The use of thrust manipulation appeared to be more efficient than the use of nonthrust manipulation for these patients.
Sectoral shocks, human capital, and displaced workers

Abstract This paper extends the Lucas–Prescott island economy to allow for finite lived agents and sector specific human capital. Unlike the Lucas–Prescott model in which workers who leave declining sectors find employment in expanding sectors, this models predicts that workers who leave declining sectors may simply become non-employed, whereas increased employment in expanding sectors is accomplished by increasing the rate at which new entrants enter the sector.
Nanoscale architectural control and macromolecular engineering of nonlinear optical dendrimers and polymers for electro-optics

Recent progress in developing highly efficient nonlinear optical dendrimers and polymers for high-performance electro-optic (EO) devices has been reviewed. Our efforts are focused on using nanoscal...
Abstract C61: GRP78 as a regulator of liver steatosis and cancer progression mediated by loss of the tumor suppressor PTEN

Glucose-regulated protein 78 (GRP78), a molecular chaperone widely elevated in human cancers, is critical for endoplasmic reticulum (ER) protein folding, stress signaling, and PI3K/AKT activation. Genetic knockout models of GRP78 revealed that GRP78 maintains homeostasis of metabolic organs, including liver, pancreas, and adipose tissues. Hepatocellular carcinoma (HCC) and cholangiocarcinoma (CC) are the most common liver cancers. There is a lack of effective therapeutics for HCC and CC, highlighting the need to further understand liver tumorigenic mechanisms. Phosphatase and tensin homolog (PTEN), a tumor suppressor that antagonizes the PI3K/AKT pathway, is inactivated in a wide range of tumors, including 40-50% of human liver cancers. To elucidate the role of GRP78 in liver cancer, we created a mouse model with biallelic liver-specific deletion of Pten and Grp78 mediated by Albumin-Cre-recombinase (cPf/f78f/f). Interestingly, in contrast to PTEN, deletion of GRP78 was progressive but incomplete. At 3 months cPf/f78f/f livers showed hepatomegaly, activation of lipogenic genes, exacerbated steatosis, and liver injury, implying that GRP78 protects the liver against PTEN-null mediated pathogenesis. Furthermore, in response to liver injury, we observed increased proliferation and expansion of bile duct and liver progenitor cells in cPf/f78f/f livers. Strikingly, bile duct cells in cPf/f78f/f livers maintained wild-type GRP78 level while adjacent areas showed GRP78 reduction. Analysis of signaling pathways revealed selective c-Jun N-terminal protein kinase activation, β-catenin downregulation, along with platelet-derived growth factor receptor α upregulation, which was unique to cPf/f78f/f livers at 6 months. Development of both HCC and CC were accelerated and evident in cPf/f78f/f livers at 8-9 months, coinciding with intense GRP78 expression in the cancer lesions, and GRP78 expression in adjacent normal areas reverted back to the WT level. In contrast, livers of Albumin-Cre; Grp78f/f (c78f/f) mice showed no malignancy even at 14 months. These studies reveal GRP78 is a novel regulator for PTEN-loss mediated liver injury and cancer progression. Citation Format: Wan-Ting Chen, Genyuan Zhu, Kyle Pfaffenbach, Gary Kanel, Bangyan Stiles, Amy S. Lee. GRP78 as a regulator of liver steatosis and cancer progression mediated by loss of the tumor suppressor PTEN. [abstract]. In: Proceedings of the Third AACR International Conference on Frontiers in Basic Cancer Research; Sep 18-22, 2013; National Harbor, MD. Philadelphia (PA): AACR; Cancer Res 2013;73(19 Suppl):Abstract nr C61.
Resource-Constrained Assignment Problems with Shared Resource Consumption and Flexible Demand

This paper considers a very general class of customer-to-resource assignment problems relevant to a variety of manufacturing contexts. This problem class addresses settings in which subsets of customer types share resource capacities as well as a fixed amount of capacity consumption, independent of production volume. More broadly, our model addresses cross-facility production limits and shared capacity consumption within each customer type. To solve these large-scale optimization problems, we apply a branch-and-price solution approach. This approach relies on an effective solution method for a novel class of nonlinear knapsack pricing problems. As our computational results demonstrate, despite the fact that the resulting master problem is not a simple set-partitioning problem, the problem's relaxation is sufficiently tight to produce an algorithm that significantly outperforms CPLEX for a wide range of problem parameter settings.
A dynamic nonisothermal model for triphase catalysis in organic synthesis

Phase-transfer catalysis has been in use for over 3 decades, but triphase catalysis, where the phase-transfer catalyst is immobilized on a solid support, is of much more recent origin. Despite its significant advantages over soluble phase-transfer catalysts, triphase catalysis has not attracted industrial attention. One of the main reasons for this lack of industrial interest is the insufficient understanding of the complex diffusion-reaction processes involved. Significant insights into this problem can be gained by mathematical modeling of these reaction systems. Unfortunately, while a few studies have been reported on the mathematical modeling of triphase catalysis, none of them address the important problem of nonisothermal effects. In the present paper we develop a dynamic model for triphase catalytic systems that includes intraparticle heat-transfer effects. An important conclusion is that the catalyst exhibits maximum effectiveness (with an effectiveness factor greater than 1) at a particular reaction time and that it can be tailored to physically realize this enhanced conversion.
Effect of growth parameters on step structure and ordering in GaInP

Abstract Ga 0.52 In 0.48 P layers have been grown by organometallic vapor phase epitaxy using various values of substrate temperature, tertiarybutylphosphine (TBP) flow rate, and growth rate on singular (0 0 1) GaAs substrates. The surface structure, measured using high resolution atomic force microscopy, consists of small islands surrounded by either monolayer or bilayer steps. An increase in the TBP flow rate at 670°C leads to a change in the step structure from mainly monolayer steps at low flow rates to predominantly bilayer steps at high flow rates. The increased TBP flow rate also results in an increase in the degree of order in the epitaxial layers. Changing the growth rate over a limited range for a constant TBP flow rate gives no change in either the step structure or the degree of order of the epitaxial layer. This preliminary data suggests that, contrary to previous reports, a change in growth rate in the range 0.25–0.5 μm/h has no inherent effect on the ordering process. The step structure also changes from predominately monolayer to bilayer as the growth temperature increases from 520 to 700°C. A possible kinetic model is proposed for this process. Again, the most highly ordered layers are those with the highest fraction of bilayer steps on the surface during growth. Together, these data appear to suggest the importance of bilayer steps in the ordering process, although it is difficult to separate the effects of the step structure from those associated with the changes in surface reconstruction caused by the variations in temperature and P partial pressure.
Coronal holes, solar wind streams, and geomagnetic activity during the new sunspot cycle

We have extended our previous study of coronal holes, solar wind streams, and geomagnetic disturbances from the declining phase (1973–1975) of sunspot cycle 20 through sunspot minimum (1976) into the rising phase (1977) of cycle 21. Using daily He I 10830 A spectroheliograms and photospheric magnetograms, we found the following results: An updated Bartels display of the occurrence of holes, wind speed, and geomagnetic activity summarizes the evolution of their characteristics and interrelations as the sunspot cycle has progressed. Long-lived, low-latitude holes have become rare but remain terrestrially effective. The more common high-latitude holes are effective only when the Earth lies at a relatively high heliographic latitude in the same solar hemisphere.
Characteristics of Patients Receiving or Forgoing Resuscitation at the Time of Cardiopulmonary Arrest

OBJECTIVE: To compare clinical, functional and social characteristics of DNR patients at the time of their cardiopulmonary arrest with characteristics of patients who receive cardiopulmonary resuscitation. DESIGN: Retrospective chart review of all 261 patients who had a cardiopulmonary arrest during a 6-month period in an academic institution. SETTING: Teaching Veterans Affairs Medical Center serving a large metropolitan area. MEASUREMENTS: Demographic characteristics, medical diagnoses, and measures of functional status were collected when DNR orders were initiated and at the time of cardiopulmonary arrest. RESULTS: The mean age of the studied group was 62 years. Ninety-nine percent were males, and the majority were non- Hispanic white men. One hundred ninety-eight (76%) patients/proxies elected for limiting treatment. Most (85%) elected a DNR order only. Patients were the most frequently documented participants in advance directive decisions in the DNR group. At the time of cardiopulmonary arrest, a higher proportion of the CPR group had coronary artery disease or chronic renal failure, and a higher proportion of the DNR group had cancer or AIDS. The functional status of the DNR group deteriorated from the time of DNR order to death. At the time of cardiopulmonary arrest, the majority of both groups were dependent in all functional domains, and 70% of the DNR group were stuporous or comatose compared with 47% of the CPR group (P =.05). DNR patients were hospitalized for an average of 13.7 ± 29.5 days after a DNR order was initiated. Six of the 81 patients who received CPR (7.4%) were alive at discharge. CONCLUSIONS: Patients and physicians deciding to implement a DNR order may be overly focused on medical diagnoses and less so on functional status. A significant proportion of patients with clinical characteristics associated with poor CPR outcome are electing for CPR.
Seeing asymptotic freedom in an exact correlator of a large-$N$ matrix field theory

Exact expressions for correlation functions are known for the large-$N$ (planar) limit of the $(1+1)$-dimensional $\mathrm{SU}(N)\ifmmode\times\else\texttimes\fi{}\mathrm{SU}(N)$ principal chiral sigma model. These were obtained with the form-factor bootstrap, an entirely nonperturbative method. The large-$N$ solution of this asymptotically free model is far less trivial than that of the $\mathrm{O}(N)$ sigma model (or other isovector models). Here we study the Euclidean two-point correlation function ${N}^{\ensuremath{-}1}⟨\mathrm{Tr}\mathrm{\ensuremath{\Phi}}(0{)}^{\ifmmode\dagger\else\textdagger\fi{}}\mathrm{\ensuremath{\Phi}}(x)⟩$, where $\mathrm{\ensuremath{\Phi}}(x)\ensuremath{\sim}{Z}^{\ensuremath{-}1/2}U(x)$ is the scaling field and $U(x)\ensuremath{\in}\mathrm{SU}(N)$ is the bare field. We express the two-point function in terms of the spectrum of the operator $\sqrt{\ensuremath{-}{d}^{2}/d{u}^{2}}$, where $u\ensuremath{\in}(\ensuremath{-}1,1)$. At short distances, this expression perfectly matches the result from the perturbative renormalization group.
Structure-activity relationship of ligands of dihydrouracil dehydrogenase from mouse liver.

Abstract One hundred and five nucleobase analogues were screened as inhibitors of dihydrouracil dehydrogenase (DHUDase, EC 1.3.1.2) from mouse liver. 5-Benzyloxybenzyluracil, 1-deazauracil (2,6-pyridinediol), 3-deazauracil (2,4-pyridinediol), 5-benzyluracil, 5-nitrobarbituric acid and 5,6-dioxyuracil (alloxan) were identified as potent inhibitors of this activity, with apparent Ki values of 0.2, 0.5, 2.1, 3.4, 3.8 and 6.6 μM respectively. Both 5-benzyloxybenzyluracil and 1-deazauracil were also potent inhibitors of DHUDase from human livers. These findings along with an extensive review of literature allowed the formulation of a structure-activity relationship. The binding to DHUDase required intact C2 and C4 oxo groups. Replacement of N1 or N3 by an endocyclic carbon enhanced binding. In contrast, replacement of C5 or C6 by an endocyclic nitrogen abolished binding. Addition of a charged group to C5 and/or C6, and of a hydrophobic group to C5 but not C6 improved the binding.
Effect of continuous tolazoline infusion on cardiopulmonary response to dopamine in unanesthetized newborn lambs.

We evaluated the cardiopulmonary interaction of tolazoline and low-, medium-, and high-dose dopamine infusion (2.7, 27, and 270 μg/kg/min) in 11 normal, chronically instrumented, unsedated neonatal lambs. Concomitant tolazoline and dopamine infusions caused tachycardia at all dopamine doses and blocked alpha-adrenergic-mediated increases in systemic resistance and left atrial pressure caused by medium and high doses of dopamine. Moderate doses of dopamine alone increased cardiac output. During simultaneous tolazoline infusion, dopamine increased cardiac output at both moderate and high doses. The effect of dopamine on pulmonary artery pressure was not modified by tolazoline; pulmonary pressure increased similarly with dopamine alone and with dopamine plus tolazoline. Calculated pulmonary vascular resistance rose with dopamine alone, but not with infusion of tolazoline and dopamine, because pulmonary blood flow rose in proportion to pulmonary artery pressure.
Rossby wave packets in baroclinic mean currents

Abstract A WKB description of the propagation of Rossby wave packets in a shallow water model of the tropical oceans indicates that the presence of the baroclinic mean currents can modify the characteristics of wave propagation significantly. For currents with weak latitudinal shear the effect of the current itself is less important than the effect of the associated variations in the depth of the thermocline, except near critical layers where waves are absorbed. For example, a westward current, and the associated shoaling of the thermocline towards the equator, can cause the speed of the long Rossby waves to decrease with decreasing latitude. (The speed increases towards the equator in the absence of mean currents.) Westward currents inhibit meridional propagation, but eastward currents enhance it. The amplification and decay of a wave packet as it propagates through a mean current are described in terms of these conservation of wave action. Implications of these results for the propagation of Rossby waves in the real ocean are discussed.
Optical Reflectance of Polymeric Sulfur Nitride Films from the Ultraviolet to the Infrared

We report the first synthesis of chemically pure polymeric sulfur nitride [${(\mathrm{SN})}_{x}$]. The optical reflectance of well-characterized films of this polymeric solid has been measured from the near ultraviolet (30 000 ${\mathrm{cm}}^{\ensuremath{-}1}$) to the far infrared (500 ${\mathrm{cm}}^{\ensuremath{-}1}$). Metallike reflectance is observed in the infrared through the visible region with a well-defined plasma minimum near 22 000 ${\mathrm{cm}}^{\ensuremath{-}1}$, corresponding to light polarized parallel to the polymer chain axis. The Drude-Lorentz model is used to analyze the data, and the physical implications of the resultant parameters are discussed.
Local Harmonic Estimation in Musical Sound Signals

Statistical modeling and analysis have been applied to different music-related fields, including sound synthesis and analysis. Sound can be represented as a real-valued function of time. This function can be sampled at a sufficiently small rate such that the resulting discrete version is a good approximation of the continuous version, thus enabling the study of musical sounds as a discrete time series, an entity for which many statistical techniques are available. Physical modeling suggests that many musical instruments' sounds may be characterized by a deterministic periodic and stochastic signal model. In this article the interest is in separating these two elements of the sound and finding parametric representations with musical meaning. To do so, a local harmonic model that tracks changes in pitch and in the amplitudes of the harmonics is fitted. Deterministic changes in the signal, such as pitch change, suggest that different temporal window sizes should be considered. Ways to choose appropriate wind...
Transthyretin-Derived Peptides as β-Amyloid Inhibitors

Self-association of β-amyloid (Aβ) into soluble oligomers and fibrillar aggregates is associated with Alzheimer's disease pathology, motivating the search for compounds that selectively bind to and inhibit Aβ oligomerization and/or neurotoxicity. Numerous small-molecule inhibitors of Aβ aggregation or toxicity have been reported in the literature. However, because of their greater size and complexity, peptides and peptidomimetics may afford improved specificity and affinity as Aβ aggregation modulators compared to small molecules. Two divergent strategies have been employed in the search for peptides that bind Aβ: (i) using recognition domains corresponding to sequences in Aβ itself (such as KLVFF) and (ii) screening random peptide-based libraries. In this study, we propose a third strategy, specifically, designing peptides that mimic binding domains of Aβ-binding proteins. Transthyretin, a plasma transport protein that is also relatively abundant in cerebrospinal fluid, has been shown to bind to Aβ, inhibit aggregation, and reduce its toxicity. Previously, we identified strand G of transthyretin as a specific Aβ binding domain. In this work we further explore and define the necessary features of this binding domain. We demonstrate that peptides derived from transthyretin bind Aβ and inhibit its toxicity. We also show that, although both transthyretin and transthyretin-derived peptides bind Aβ and inhibit toxicity, they differ significantly in their effect on Aβ aggregation.
Stability of internally pressurized conical shells under torsion

E = modulus of elasticity h — thickness of shell I = slant length of cone n = number of circumferential waves p = internal hydrostatic pressure pe = critical external hydrostatic pressure denned by Eq. (2) Ri = radius of small end of truncated cone R2 = radius of large end of truncated cone T = torque Z = curvature parameter for cylinder (1 — )/(L a. = semivertex angle of the cone v = Poisson's ratio pav = mean radius of curvature = (Ri + Rz)/2 cos a T = maximum torsional stress = (T/2wRih) Tcr = critical torsional stress given by Eq. (1)
The Virtual Worlds Exploratorium: Using Large-Scale Data and Computational Techniques for Communication Research

The Virtual Worlds Exploratorium is a multidisciplinary project dedicated to the study of communication-related behaviors using data from massively multiplayer online games (MMOs). In a partnership with a corporation that hosts an MMO, a 20-person team of scholars is engaged in the study of behavior within a game and also game activities that parallel those in “real life” (e.g., economic activity, social networking, group processes). A key aspect of our approach is a unique multidisciplinary collaboration of social and computational scientists to help advance the state of the research. This article discusses the methodological, measurement and organizational challenges of the project, the game, the data, and several representative research streams. It also articulates several measurement issues that the research team has faced in order to provide best practices and lessons learned for others considering similar investigations.
The reported evaluation of alcoholism treatments, 1968-1971: a methodological review.

Abstract The state of the art in the evaluation of alcoholism treatment programs for the years 1968–1971 was surveyed by reviewing journal articles reporting treatment evaluations. A comprehensive computer-based search of the literature yielded 40 such studies. These were analyzed along 10 methodological dimensions. Serious inadequacies in evaluation methodology were revealed in a large proportion of the studies. Comparisons with two previous comprehensive reviews of program evaluations indicate modest improvements in description and methodology. These include greater use of control groups and random assignment of subjects; the use of multiple criteria of success and more adequate descriptions of follow-up techniques.
Control of Fungus Growth on Fish Eggs by Asellus militaris and Gammarus pseudolimnaeus

Abstract A test was conducted to evaluate the effect of two invertebrates, Asellus militaris Hay and Gammarus pseudolimnaeus Bousfield, on the growth of fungus, Saprolegnia sp., on walleye eggs, Stizostedion vitreum vitreum (Mitchill). In a second test the effect of the two invertelbrates on mortality of white sucker fry, Catostomus commersonnii commersonnii (Lacepede), was ascertained. Egg mortality was 100% where fungus was not controlled. Both Asellus and Gammarus eliminated fungus-related mortality. Gammarus caused about 15% mortality for both eggs and fry. Asellus did not cause mortality for either stage.
Reliability and Validity of the Speed of Thinking Test

The Speed of Thinking Test (STT) has been developed as a measure of cognitive speed. Individuals must decide quickly whether pairs of letters, such as Ab or aA, have the same name. A group of 129 college students were administered this measure plus the Nelson-Denny Reading Test (NDRT), the Accuracy Level Test (ALT), and the Rate Level Test (RLT). The reliability coefficient for the STT was .80, which was higher than the reliability coefficient for the Comprehension score on the Nelson Denny Reading Test, .68. The SPT correlated .26 with the Rate score on the NDRT, and .60 with the RLT. The STT appears to provide a reasonably reliable and valid method for measuring cognitive speed that may be used to diagnose whether individuals are reading at a rate commensurate with their thinking rate.
Center-of-mass corrections to overlap factors for two-nucleon transfer

Abstract The following simple recipe is presented for making c.m. corrections to the overlap factors involved in two-nucleon transfer: Expand the shell-model overlap in products of harmonic oscillator wave functions of the relative and c.m. coordinates of the two nucleons. Change the oscillator ν-value to Aν (A + 2) in the c.m. functions, and multiply each term in the sum by [ (A + 2) A ] 1 2 N , where N is the energy quantum number associated with the c.m. state of that term. The recipe depends on the value of ν used in the expansion. The proper choice of ν is discussed, and numerical examples are presented which indicate the magnitude of the correction. The zero-range form factor for two-neutron stripping on 16O is increased by a factor of about two, or more, in the surface region, resulting in a factor of about five in the cross section. The correction is greater at larger distances, implying that heavy-ion reactions will be effected more than light ion reactions.
Integration of object-oriented programming languages and database systems in KOPERNIK

Abstract KOPERNIK is an object-oriented database system, that allows uniform specification of database requests and application programs. The user interface is based on Smalltalk, and the object-oriented data model is represented in terms of classes and messages. Techniques are discussed for implementing such a model on top of an underlying relational database system. Those parts of application programs that cannot be translated into a relational language are handled by a Smalltalk processor. The semantics of the database requests is defined in terms of a meta-model and meta-messages, using an object-oriented approach. Hence we derive rules for translation of database requests into SQL queries over a binary relational view, introduced as an intermediate level between the underlying database and our conceptual view.
Uniform Exponential Stability and Approximation in Control of a Thermoelastic System

This paper has two objectives. First, necessary and sufficient conditions are given to characterize the uniform exponential stability of a sequence of $c_0$-semigroups $T_{n}(t)$ on Hilbert space $H_n$. Secondly, approximation in control of a one-dimensional thermoelastic system, subject to Dirichlet-Dirichlet as well as Dirichlet-Neumann boundary conditions, is considered. The uniform exponential stability and strong convergence of corresponding semigroups associated with approximate scheme are proved. Numerical experimental results are also presented.
Pulsed Feedback Defers Cellular Differentiation

Environmental signals induce diverse cellular differentiation programs. In certain systems, cells defer differentiation for extended time periods after the signal appears, proliferating through multiple rounds of cell division before committing to a new fate. How can cells set a deferral time much longer than the cell cycle? Here we study Bacillus subtilis cells that respond to sudden nutrient limitation with multiple rounds of growth and division before differentiating into spores. A well-characterized genetic circuit controls the concentration and phosphorylation of the master regulator Spo0A, which rises to a critical concentration to initiate sporulation. However, it remains unclear how this circuit enables cells to defer sporulation for multiple cell cycles. Using quantitative time-lapse fluorescence microscopy of Spo0A dynamics in individual cells, we observed pulses of Spo0A phosphorylation at a characteristic cell cycle phase. Pulse amplitudes grew systematically and cell-autonomously over multiple cell cycles leading up to sporulation. This pulse growth required a key positive feedback loop involving the sporulation kinases, without which the deferral of sporulation became ultrasensitive to kinase expression. Thus, deferral is controlled by a pulsed positive feedback loop in which kinase expression is activated by pulses of Spo0A phosphorylation. This pulsed positive feedback architecture provides a more robust mechanism for setting deferral times than constitutive kinase expression. Finally, using mathematical modeling, we show how pulsing and time delays together enable “polyphasic” positive feedback, in which different parts of a feedback loop are active at different times. Polyphasic feedback can enable more accurate tuning of long deferral times. Together, these results suggest that Bacillus subtilis uses a pulsed positive feedback loop to implement a “timer” that operates over timescales much longer than a cell cycle.
1,3-Bisalkylcarbonyl- and 3-Alkylcarbonyl-5-fluorouracil Prodrugs: Syntheses, Thermal, and Hydrolytic Stability

AbstractFour homologous 1,3-bisalkylcarbonyl and the corresponding 3-alkylcarbonyl derivatives of 5-fluorouracil (1, 5-FU) have been synthesized and characterized by 1H nuclear magnetic resonance, and infrared and ultraviolet spectroscopy. The 1,3-bisacetyl derivative hydrolyzed rapidly in pH 7.1 buffer at 32°C (t1/2 =0.8 min) to give the 3-acetyl derivative. The hydrolyses of 3-acetyl-, 6, and 3-propionyl-5-FU, 7, were much slower (t1/2 = 200 and 300 min, respectively) and they were biexponential. Both the 1,3- and the 3-derivatives hydrolyzed in the presence of formaldehyde to give significant, and approximately equal amounts of 1- and 3-alkylcarbonyloxymethyl-5-FU derivatives, in addition to 5-FU, which suggested that for both types of derivatives the hydrolyses of the 3-alkylcarbonyl group went through a symmetrical O2-alkylcarbonyl intermediate. The 1,3-derivatives were thermally unstable above about 110°C, giving up to about 20% of the corresponding 1-alkylcarbonyl derivatives at 140°C. On the other...
Force Spectroscopy in the Bloodstream of Live Embryonic Zebrafish with Optical Tweezers

Fluid forces in vivo are difficult to measure and key to understanding the mechano-biology of cardiovascular development. Optical tweezers force spectroscopy has been implemented in live zebrafish embryos during the first stages of blood circulation.
DRUG USE AND EXPERIENCE IN AN URBAN COLLEGE POPULATION

Report of a pilot effort to determine the prevalence of certain drug usage (without medical prescription) among seniors in a New York City college. About 7% admitted to some degree of drug experience, but only about 1% could be classified as frequent users. Marijuana was by far the focal “popular” drug in campus use.
How Applicable is the Dominant Firm Model of Price Leadership

In this paper, we examine the usefulness of the dominant firm model of price leadership to serve as a benchmark for organizing behavior in laboratory markets. This well established model, whose origins can be traced back over a hundred years, has been recently applied to such landmark antitrust cases as Standard Oil and Alcoa and more recently to the analysis of deregulated markets for electric power. Our results indicate that in posted offer markets the dominant firm quite often produces more than the model's benchmark and sometimes at much greater prices. With sealed offer auction rules and a low elasticity of fringe supply, the dominant firm produces the theoretical output at a price greater than the prediction. However, with a high elasticity of fringe supply, the dominant firm produces more output over a wide range of prices that includes the predicted price.
Reaction of ethylene with the unsaturated cluster complex H2Os3 (CO)10

Abstract Treatment of H 2 Os 3 (CO) 10 with excess ethylene forms ethane and a hydridovinyl cluster complex HOs 3 (CO) 10 (CHCH 2 ), which rearranges in refluxing octane to the vinylidene complex H 2 Os 3 (CO) 9 (CCH 2 ).
Clarence Ayres, technology, pragmatism and progress

This paper explores the origins and continued relevance of Clarence Ayres' definition of technology as a process involving both physical tools and a scientific method of reasoning, where science is understood to achieve cross-cultural explanatory power by virtue of technological validation. Ayres' concept of technology derived from his training as a Pragmatist and was primarily philosophical rather than descriptive, but is congruent with the work of modern historians of technology and remains useful in addressing a variety of concerns about both the promise and dangers of technological change. Copyright The Author 2009. Published by Oxford University Press on behalf of the Cambridge Political Economy Society. All rights reserved., Oxford University Press.
Characterization of dip1p reveals a switch in Arp2/3-dependent actin assembly for fission yeast endocytosis

Summary Background During endocytosis in yeast, a choreographed series of discrete local events at the plasma membrane lead to a rapid burst of actin polymerization and the subsequent internalization of an endocytic vesicle. What initiates Arp2/3-dependent actin polymerization in this process is not well understood. Results The Schizosaccharomyces pombe WISH/DIP/SPIN90 ortholog dip1p is an actin-patch protein that regulates the temporal sequence of endocytic events. dip1Δ mutants exhibit a novel phenotype in which early events such as WASp localization occur normally but arrival of Arp2/3, actin polymerization, and subsequent steps are delayed and occur with apparently random timing. In studying this mutant, we demonstrate that positive feedback loops of WASp, rapid actin assembly, and Arp2/3 contribute to switch-like behavior that initiates actin polymerization. In the absence of dip1p, a subset of patches is activated concurrently with the "touch" of a neighboring endocytic vesicle. Conclusions These studies reveal a switch-like mechanism responsible for the initiation of actin assembly during endocytosis. This switch may be activated in at least two ways, through a dip1p-dependent mechanism and through contact with another endocytic vesicle.
Computational Model of Erratic Arrhythmias in a Cardiac Cell Network: The Role of Gap Junctions

Cardiac morbidity and mortality increases with the population age. To investigate the underlying pathological mechanisms, and suggest new ways to reduce clinical risks, computational approaches complementing experimental and clinical investigations are becoming more and more important. Here we explore the possible processes leading to the occasional onset and termination of the (usually) non-fatal arrhythmias widely observed in the heart. Using a computational model of a two-dimensional network of cardiac cells, we tested the hypothesis that an ischemia alters the properties of the gap junctions inside the ischemic area. In particular, in agreement with experimental findings, we assumed that an ischemic episode can alter the gap junctions of the affected cells by reducing their average conductance. We extended these changes to include random fluctuations with time, and modifications in the gap junction rectifying conductive properties of cells along the edges of the ischemic area. The results demonstrate how these alterations can qualitatively give an account of all the main types of non-fatal arrhythmia observed experimentally, and suggest how premature beats can be eliminated in three different ways: a) with a relatively small surgical procedure, b) with a pharmacological reduction of the rectifying conductive properties of the gap-junctions, and c) by pharmacologically decreasing the gap junction conductance. In conclusion, our model strongly supports the hypothesis that non-fatal arrhythmias can develop from post-ischemic alteration of the electrical connectivity in a relatively small area of the cardiac cell network, and suggests experimentally testable predictions on their possible treatments.
Targeted chemotherapy with cytotoxic bombesin analogue AN-215 inhibits growth of experimental human prostate cancers.

We developed a powerful cytotoxic analogue of bombesin AN-215, in which the bombesin (BN)-like carrier peptide is conjugated to 2-pyrrolino doxorubicin (AN-201). Human prostate cancers express high levels of receptors for BN/gastrin releasing peptide (GRP) that can be used for targeted chemotherapy. The effects of targeted chemotherapy with cytotoxic BN analogue AN-215 were evaluated in nude mice bearing subcutaneous xenografts of DU-145, LuCaP-35, MDA-PCa-2b and intraosseous implants of C4-2 human prostate cancers. Intraosseous growth of C4-2 tumors was monitored by serum PSA. BN/GRP receptors were evaluated by 125I-[Tyr4]BN binding assays and RT-PCR. The effects of AN-215 on apoptosis and cell proliferation were followed by histology, and the expression of Bcl-2 and Bax protein was determined by Western blot analysis. Targeted analog AN-215 significantly inhibited growth of subcutaneously implanted DU-145, LuCaP-35 and MDA-PCa-2b prostate cancers by 81% to 91% compared to controls, while cytotoxic radical AN-201 was less effective and more toxic. Serum PSA levels of mice bearing intraosseous C4-2 prostate tumors were significantly reduced. In LuCaP-35 tumors administration of BN antagonist RC-3095 prior to AN-215 blocked the receptors for BN/GRP and inhibited the effects of AN-215. High affinity receptors for BN/GRP and their m-RNA were detected on membranes of all 4 tumor models. Therapy with AN-215, but not with AN-201, decreased the ratio of Bcl-2/Bax in DU-145 and the expression of antiapoptotic Bcl-2 in LuCaP-35 tumors. The presence of BN/GRP receptors on primary and metastatic prostate cancers makes possible targeted chemotherapy with AN-215 for the treatment of this malignancy. © 2005 Wiley-Liss, Inc.
Trimethylsilyl Derivatives of Organic Compounds in Source Samples and in Atmospheric Fine Particulate Matter

Source sample extracts of vegetative detritus, motor vehicle exhaust, tire dust, paved road dust, and cigarette smoke have been silylated and analyzed by GC−MS to identify polar organic compounds that may serve as tracers for those specific emission sources of atmospheric fine particulate matter. Candidate molecular tracers were also identified in atmospheric fine particle samples collected in the San Joaquin Valley of California. A series of normal primary alkanols, dominated by even carbon-numbered homologues from C_(26) to C_(32), the secondary alcohol 10-nonacosanol, and some phytosterols are prominent polar compounds in the vegetative detritus source sample. No new polar organic compounds are found in the motor vehicle exhaust samples. Several hydrogenated resin acids are present in the tire dust sample, which might serve as useful tracers for those sources in areas that are heavily impacted by motor vehicle traffic. Finally, the alcohol and sterol emission profiles developed for all the source samples examined in this project are scaled according to the ambient fine particle mass concentrations attributed to those sources by a chemical mass balance receptor model that was previously applied to the San Joaquin Valley to compute the predicted atmospheric concentrations of individual alcohols and sterols. The resulting underprediction of alkanol concentrations at the urban sites suggests that alkanols may be more sensitive tracers for natural background from vegetative emissions (i.e., waxes) than the high molecular weight alkanes, which have been the best previously available tracers for that source.
Meeting Synopsis: Advances in Skeletal Muscle Biology in Health and Disease (Gainesville, Florida, February 22nd to 24th 2012) – Day 1: “Cell Signaling Mechanisms Mediating Muscle Atrophy and Hypertrophy” and “muscle Force, Calcium Handling, and Stress Response”

The “Advances in Skeletal Muscle Biology in Health and Disease” conference was held in Gainesville, Florida February 22nd to 24th 2012. The primary purpose of this meeting was to facilitate advances in adult skeletal muscle biology and physiology. There were 210 registered participants from 64 different institutions and 4 pharmaceutical companies, including participants from 10 different countries. Approximately 40% of the attendees and one-third of the symposium speakers were women. The meeting began with a grant writing workshop that included an overview of training grants, R01 grant structure, and grants scoring and interpreting reviewer comments given by Drs. Tom Clanton, Denis Guttridge, Marcas Bamman, and Sue Bodine. This workshop was followed by a poster session that included 65 outstanding posters presented by faculty, postdoctoral fellows, and graduate students. The symposium consisted of 28 total speakers across four main sessions. In this two part synopsis we outline some of the main findings, current paradigms, and future directions presented in each of these sessions. In Part 1, we outline Day 1 of the symposium which consisted of sessions on “Cell signaling mechanisms mediating muscle atrophy and hypertrophy” and “Muscle force, calcium handling, and stress response.” In Part 2, we outline Day 2 of the symposium which consisted of sessions on “Muscle diseases and regeneration” and “Clinical/translational research.”
Spatially resolved temperature measurement in microchannels

Non-intrusive local temperature measurement in convective microchannel flows using infrared (IR) thermography is presented. This technique can be used to determine local temperatures of the visualized channel wall or liquid temperature near this wall in IR-transparent heat sinks. The technique is demonstrated on water flow through a silicon (Si) microchannel. A high value of a combined liquid emissivity and substrate overall transmittance coupled with a low uncertainty in estimating this factor is important for quantitative temperature measurement using IR thermography. The test section design, and experimental and data analysis procedures that provide increased sensitivity of the detected intensity to the desired temperature are discussed. Experiments are performed on a 13-mm long, 50 μm wide by 135 μm deep Si microchannel at a constant heat input to the heat sink surface for flow rates between 0.6 and 1.2 g min−1. Uncertainty in fluid temperature varies from a minimum of 0.60°C for a Reynolds number (Re) of 297 to a maximum of 1.33°C for a Re of 251.
Imaging of mandibular trauma: ROC analysis.

OBJECTIVES To compare the diagnostic efficacies of panoramic radiographs, mandibular trauma series, and digitized radiographs for detection of fractures of the mandible. METHODS Fractures were induced using blunt trauma in 25 cadaver mandibles. Panoramic radiographs, digitized radiographs, and mandibular series comprising an anteroposterior view, two lateral oblique, and a reverse Towne's were used. Six observers recorded their diagnoses using a five-point confidence rating scale. The data were analyzed using receiver operating characteristic (ROC) curve analysis. RESULTS Significant differences based on imaging modalities were found (p < 0.0015) in the area under the curves (A(z)): panoramic radiograph, 0.8762; mandibular series, 0.7521; panoramic plus anteroposterior radiographs combination, 0.8886; and digitized mandibular series, 0.7723. No observer-based differences were noted. Condylar and coronoid fractures were difficult to detect than those in other areas of the mandible (p < 0.033). Intra- and inter-observer agreements were high (kappa(w) = 0.81 and 0.76, respectively). CONCLUSIONS Panoramic radiographs are adequate for detection of mandibular fractures. Addition of an anteroposterior view augments diagnostic accuracy.
Expression of Ia-like antigens on the vasculature of human kidney.

Abstract The distribution of Ia-like antigens in human kidney has been investigated by indirect immunofluorescence staining of frozen sections with monoclonal antibodies to framework determinants of Ia-like antigens. These antigens are localized by patchy and interrupted linear fluorescence along the endothelium of glomerular efferent arterioles and capillaries, intertubular cortical and medullary capillaries as well as the vasa recta. Ia-like antigens are undetectable, however, on the endothelia of arcuate and interlobular arteries and on tubular epithelial cells. The expression of Ia-like antigens on kidney endothelial cells may account for the role of Ia-like antigens in kidney allograft rejection.
Tooth mobility and periodontal therapy

Data collected as part of an 8-year longitudinal study on periodontal therapy involving 82 patients and 1974 teeth were analyzed to determine if tooth mobility influenced the result of treatment. For each patient, pocket depth, attachment level and tooth mobility were scored clinically at the initial appointment, and once a year for 8 years following periodontal therapy. The treatment consisted of scaling, oral hygiene instruction, occlusal adjustment, periodontal surgery (curettage, modified Widman or pocket elimination), followed by recall prophylaxes every 3 months. Tooth mobility data on a scale of 0--3 were related to changes in attachment levels for three grades of severity of periodontal disease, based on initial pocket depth (1--3 mm, 4--6 mm, and 7 + mm). Mean patient attachment changes were calculated from teeth in the same severity category for each patient. The data were analyzed by one-way analysis of variance and Scheffe's multiple comparison procedure to test the hypothesis of equal effects of tooth mobility on the results of the treatment for the three severity groups over 8 years. The results indicate that there is a statistically significant relationship between original tooth mobility and the change in level of attachment following treatment. Pockets of clinically mobile teeth do not respond as well to periodontal treatment as do those of firm teeth exhibiting the same initial disease severity.
On the extraction of channel networks from digital elevation data

Channel networks with artibtrary drainage density or resolution can be extracted from digital elevation data. However, for digital elevation data derived networks to be useful they have to be extracted at the correct length scale or drainage density. Here we suggest a criterion for determining the appropriate drainage density at which to extract networks from digital elevation data. The criterion is basically to extract the highest resolution (highest drainage density) network that satisfies scaling laws that have traditionally been found to hold for channel networks. Procedures that use this criterion are presented and tested on 21 digital elevation data sets well distributed throughout the U.S.
Inhibition of Na+K+ATPase Activity in Membranes of Sindbis Virus-Infected Chick Cells

Abstract Alterations in intracellular concentrations of Na + and K + in Sindbis virus-infected cells result largely from inhibition of ouabain-sensitive Na + K + ATPase (Na + pump) activity. Here we report that membrane preparations derived from Sindbis virus-infected chick cells exhibit reduced Na + K + ATPase activity, indicating that limitation of cellular factors is not responsible for inhibition of ion transport. In vitro phosphorylation of the Na + K + ATPase by [ 32 P]orthophosphate or [γ- 32 P]ATP is unaltered in membranes of Sindbis virus-infected cells, indicating that a loss of specific enzymatic functions unrelated to formation of Na + pump phosphoenzyme intermediates occurs during the course of viral infection. However, phosphoenzyme intermediates of the Na + K + ATPase prepared from membranes of Sindbis virus-infected cells are inherently less stable than those prepared with membranes of uninfected cells. The instability of these intermediates in vitro is correlated with an altered capacity of the Na + pump to transport monovalent cations into virus-infected cells. 22 Na + transport studies reveal enhanced ouabain-sensitive Na + uptake by Sindbis virus-infected cells, suggesting that the Na + pump may catalyze enhanced Na + -Na + exchange in the infected cells. These results indicate that the capacity of the Na + K + ATPase to discriminate between binding of extracellular Na + and K + is specifically altered during the course of infection by Sindbis virus.