cssi/SciSciGPT-SciSciNet huggingface dataset:
The retail inventory method: The third major costing system

Abstract An organization that has but a single product would be a rarity in the United States today. While single-product firms and tools such as break-even analysis may have been in vogue at the turn of the century, today jointness pervades the scene. The bank that issues a mortgage to a customer also may have managed his or her checking account or granted a student loan to his or her daughter. The department store that sold a suit one week earlier may have attracted the customer with its furniture, toys, and cosmetics. The hospital whose obstetrical team delivered the baby may have been chosen because its excellent orthopedics department set the husband's broken leg three years prior. The sporting goods manufacturer may sell its golf clubs because of its reknown for skis and tennis rackets. It makes no difference whether it is products or services or departments; all share equipment, time, and reputation. The list goes on forever; jointness is the rule, not the exception. Management can pretend that there is only one product and attempt to isolate its effects, as if it were in a vacuum. However, pretending does not eliminate jointness and the purifying assumption is apt to mislead analysis. So how should jointness be treated? Other than the mathematical programming models of the last forty years, only one model for dealing with jointness has been widely adopted for most of the twentieth century; that model is the retail inventory method. The retail system typically is used by department stores to control inventories that consist of 100,000 or more items. The retail system recognizes costs and prices, inflation and obsolescence, mistakes and successes. It tracks purchases and sales, deals with discounts and transfers, and controls investment while providing an estimate of ending inventory. Fortunately, the retail system, the favorite of the department store and the boutique, could be used in the factory as well as in a variety of service and nonprofit organizations. This article briefly reviews the retail method and then uses linear programming (LP) and postoptimality analysis to modernize the traditional conceptions—to attempt to make a good system even better. Many constraints are studied including overlapping seasons, sales quotas, target inventories, product life cycles, and spatial and monetary limitations, among others. In the process, one comes to appreciate the size of the inventories being controlled, the human and departmental interactions, and the usefulness of the LP-retail system (“knotty retail” is perhaps an appropriate name) not only to generate cash budget estimates and to manage stock levels, but also to select the most satisfying alterations of managerial policy. The article concludes by discussing further constraints and other types of organizations that might benefit from adapting the retail system.
Data cleansing as a transient service

There is often a transient need within enterprises for data cleansing which can be satisfied by offering data cleansing as a transient service. Every time a data cleansing need arises it should be possible to provision hardware, software and staff for accomplishing the task and then dismantling the set up. In this paper we present such a system that uses virtualized hardware and software for data cleansing. We share actual experiences gained from building such a system.We use a cloud infrastructure to offer virtualized data cleansing instances that can be accessed as a service. We build a system that is scalable, elastic and configurable. Each enterprise has unique needs which makes it necessary to customize both the infrastructure and the cleansing algorithms to address these needs. In this paper we will present a system that is easily configurable to suit the data cleansing needs of an enterprise.
Application of the IS-MP-IA Model and the Taylor Rule to Croatia: Policy Implications for Economic Integration

Applying the IS-MP-IA model and the Taylor rule, this study finds that a lower expected inflation rate, real appreciation, a lower federal funds rate, and more world output would help increase the Croatian output. The insignificance of government deficit spending suggests that the Ricardian-equivalence hypothesis may be applicable to Croatia. The conventional wisdom to pursue currency devaluation to stimulate the economy may not work for Croatia.
Tadpole Conformation of Gradient Polymer Brushes

Cylindrical molecular brushes, each with a gradient of grafting density along the backbone, demonstrated a transition from rodlike to tadpole conformations. Using atomic force microscopy (AFM), a coexistence of two conformational phases was observed within individual molecules adsorbed on a mica substrate. These observations were made by compressing monolayers on the surface of water and then transferring a sample of this monolayer to a mica substrate for AFM studies. Upon compression, the rod−globule transition occurs at the end where the brush is densely grafted, leaving a molecule with a globular “head” and an extended “tail”a so-called tadpole conformation. This research demonstrates the asymmetric changes in the molecular conformation, which is one of the prerequisites for directed motion.
Sudakov form factor in a massive vector field theory

The leading-logarithm approximation for the Sudakov form factor is examined in a theory containing massive fermion and massive neutral vector meson fields. In the on-shell case, where there is only one mass scale (the meson mass), the Sudakov form factor in this model agrees with the result in QED. In the off-shell case, however, with two different mass scales (the meson mass and the off-shell mass of the fermion), the Sudakov form factor differs from the QED result.
Reactive oxygen species contribute to neuropathic pain by reducing spinal GABA release

Although both a loss of spinal inhibitory neurotransmission and the involvement of oxidative stress have been regarded as important mechanisms in the pathogenesis of pain, the relationship between these 2 mechanisms has not been studied. To determine whether reactive oxygen species (ROS) involvement in pain mechanisms is related to the diminished inhibitory transmission in the substantia gelatinosa (SG) of the spinal dorsal horn, behavioral studies and whole-cell recordings were performed in FVB/NJ mice. Neuropathic pain was induced by a tight ligation of the L5 spinal nerve (SNL). Pain behaviors in the affected foot were assessed by behavioral testing for mechanical hyperalgesia. Pain behaviors developed by 3 days and lasted more than 8 weeks. Both systemic and intrathecal administration of an ROS scavenger, phenyl-N-tert-butylnitrone (PBN), temporarily reversed mechanical hyperalgesia up to 2 hours, 1 week after SNL. In nonligated mice, an intrathecal injection of an ROS donor, tert-butyl hydroperoxide (t-BOOH), dose-dependently induced mechanical hyperalgesia for 1.5 hours. In whole-cell voltage clamp recordings of SG neurons, perfusion with t-BOOH significantly decreased the frequency of mIPSCs, and this effect was reversed by PBN. Furthermore, t-BOOH decreased the frequency of GABA(A) receptor-mediated mIPSCs without altering their amplitudes but did not affect glycine receptor-mediated mIPSCs. In SNL mice, mIPSC frequency in SG neurons was significantly reduced as compared with that of normal mice, which was restored by PBN. The antihyperalgesic effect of PBN on mechanical hyperalgesia was attenuated by intrathecal bicuculline, a GABA(A) receptor blocker. Our results indicate that the increased ROS in spinal cord may induce pain by reducing GABA inhibitory influence on SG neurons that are involved in pain transmission.
Modelling Alternative Subsistence Strategies for the Middle Snake River

This article models acquisition costs and nutritional returns for Late Archaic (post-A.D. 1200) peoples of the Middle Snake River. It is an attempt to demonstrate probable deficiencies in the ethno...
Widespread projections from subgriseal neurons (layer VII) to layer I in adult rat cortex.

Theories of information processing and plasticity in mammalian cortex often rely on knowledge of intracortical networks studied in rodent cortex. Accordingly, the contribution of all cells involved in this circuitry is potentially significant, including connections from a subset of neurons that persist from the developmental subplate, called subgriseal neurons in the present study. Ascending corticocortical connections from subgriseal neurons were identified by using in vivo transport of fluorescent retrograde tracers from discrete applications confined to cortical layer I (approximately 1 mm2) or from injections placed into superficial cortical layers. Applications restricted to cortical layer I can be identified by a subsequent retrograde labeling pattern that includes neurons in layers II/III and V but not those in layer IV. In contrast, when retrograde tracer is deposited in layers II/III, layer IV cells are also labeled. By using this identification technique in juvenile and adult rats, widespread interareal projections to superficial layers, including unequivocal connections to cortical layer I, were found to originate from a tangential band of neurons directly below the conventionally identified gray matter (i.e., subgriseal) and from a smaller number of cells in the white matter (WM) proper. Subgriseal and WM neurons were labeled below application and injection sites in somatosensory, auditory, visual, motor, frontal, and adjacent areas at distances of more than 4 mm. However, the subgriseal-to-superficial pathway was not sensitive to nonfluorescent retrograde tracers including horseradish peroxidase. Because neurons in the deeper cortical layers can be strongly influenced through input to their apical dendritic extensions in cortical layer I, the widespread connections described in the present study indicate that the ascending subgriseal projections should be considered in models of mature cortical function. J. Comp. Neurol. 407:275–286, 1999. © 1999 Wiley-Liss, Inc.
Biphasicity of the incubation curve

Two experiments were performed using a one-trial passive-avoidance task. In Experiment 1, different groups of mice were retested at different times after training. In Experiment 2, different groups were administered a footshock outside the conditioning apparatus and then were given the step-through experience at different times after the footshock. The time-response curve was found to be triphasic only in Experiment 1, while it produced a monotonie incubation curve in Experiment 2.
On the Influences of Boundary Reflections and Piezoelectric Sensors to the Characteristics of Elastic Waves for Pattern Recognition Methods

In this study, the influences of boundary reflections and piezoelectric sensors on the detection of propagating elastic waves emitted from newly formed damage surfaces are demonstrated using numerical and experimental models. The concepts of the displacement-based, time-domain equations of non-splitting perfectly matched layer (PML) and spectral finite elements are utilized to facilitate computationally efficient modeling for high frequency wave propagation in large scale structures. The PML is an artificial layer, which provides an exponential decay regardless of frequency or angle of incidence and does not produce any reflection from the interface. The numerical result under ball drop impact excitation is validated with experimental measurements. The boundary reflections within small scale-coupon specimens modify the received wave characteristics such a way that transferring the laboratory scale data to other geometries for pattern recognition methods becomes a challenge. The features used in the pattern recognition algorithms cannot be scaled up to large-scale structures unless the experimental geometry is designed through considering the target wavelength, and the waveform record-window is limited to prevent the influence of reflected waves as well as the transfer function of piezoelectric sensor is taken into account. A model based on selecting the sample size as a function of wavelength is developed. The influence of piezoelectric sensors to the output signals is demonstrated such that the selected piezoelectric sensor controls the waveform features, which further limits the test repeatability under different conditions.
MHD stability of Spheromak

The 'Spheromak', an optimal force-free spherical plasma configuration, is analysed for its MHD stability properties. It is shown that flattened ellipse (oblimak) with = k (k independent of ) should be stable against all magnetically driven MHD and resistive tearing modes if surrounded by a conducting wall at about rw/r0 = 1.15. β's of at least 2% can be stably confined, equivalent to 20% in tokamaks.
Oxazine dyes. 3. Simultaneous nuclear and cytoplasmic staining from single solutions.

Of 84 dyes tested, 26 were found to give a stable solution with celestine blue B dispersions which simultaneously stained nuclei and cytoplasm. The cytoplasmic dye is dissolved in celestine blue B dispersion prepared by the method of Cray et al. (1956). Croceine scarlet (C.I. 286), in the proportion of 0.38 gm to 114 ml of celestine blue B dispersion, gives results strikingly similar to hematoxylin-eosin when used for 2 min on a wide variety of tissues. No differentiation, other than that which occurs during dehydration, is necessary.
Squalene, Olive Oil, and Cancer Risk: Review and Hypothesis

Epidemioiogical studies of breast and pancreatic cancer in several Mediterranean populations have demonstrated that increased dietary intake of olive oil is associated with a small decreased risk or no increased risk of cancer, despite a higjier proportion of overall lipid intake. Experimental animal model studies of high dietary fat and cancer also indicate that olive oil has either no effect or a protective effect on the prevention of a variety of chemically induced tumors. As a working hypothesis, it is proposed that the high squalene content of olive oil, as compared to other human foods, is a major factor in the cancer risk-reducing effect of olive oil. Experiments in vitro and in animal models suggest a tumor-inhibiting role for squalene. A mechanism is proposed for the tumor-inhibitory activity of squalene based on its known strong inhibitory activity of �3-hydroxy-fi-methylg1utarylCoA reductase catalytic activity in vivo, thus reducing farnesyl pyrophosphate availability for prenylation of the ras oncogene, which relocates this oncogene to cell membranes and is required for the signal-transducing
A novel probe drug interaction study to investigate the effect of selected antiretroviral combinations on the pharmacokinetics of a single oral dose of maraviroc in HIV-positive subjects

AIMS Maraviroc (UK-427 857), an antagonist of the CCR5 receptor with potent anti-HIV activity, was recently approved for use in treatment-experienced patients infected with CCR5-tropic HIV-1. The aim of this study was to evaluate the effect of selected commonly used antiretroviral therapy (ART) combinations on the pharmacokinetics of a single oral dose of maraviroc 300 mg in HIV-positive subjects compared with historical controls. METHODS In this study, four cohorts of HIV-positive patients (n = 8 each) receiving one of the following combination therapies were recruited: cohort 1 – efavirenz + Combivir® (lamivudine/zidovudine); cohort 2 – efavirenz + didanosine + tenofovir; cohort 3 – nevirapine + lamivudine + tenofovir; cohort 4 – Kaletra® (lopinavir/ritonavir) + stavudine + lamivudine. Subjects continued on their prescribed ART and also received a single oral dose of maraviroc 300 mg. Serial blood samples and urine for determination of maraviroc pharmacokinetics were collected over 12 h postdose. Plasma pharmacokinetic parameters from this study were compared with historical data generated in HIV-positive subjects receiving maraviroc monotherapy in a Phase IIa study. RESULTS A total of 29 subjects were recruited (eight each in cohorts 1–3, and five in cohort 4). The geometric mean ratios for AUC12 and Cmax for each treatment group compared with maraviroc monotherapy were: 47% and 67% (cohort 1); 48% and 76% (cohort 2); 101% and 154% (cohort 3); and 265% and 180% (cohort 4), respectively. Tmax was similar in all treatment groups. Mean values for renal clearance ranged from 8.2 l h−1 (cohort 1) to 13.2 l h−1 (cohort 4). There were no renal clearance data collected in the comparator study. CONCLUSIONS The results of this study support those previously seen in healthy volunteer studies that showed that efavirenz reduces maraviroc exposure, whereas lopinavir/ritonavir increases maraviroc exposure. These data also suggest that nevirapine does not lead to a clinically significant effect on maraviroc pharmacokinetics.
The opportunity cost of mean–variance choice under estimation risk

Abstract Mean–variance portfolio choice is often criticized as sub-optimal in the more general expected utility framework. It is argued that the expected utility framework takes into consideration higher moments ignored by mean variance analysis. A body of research suggests that mean–variance choice, though arguably sub-optimal, provides very close-to-expected utility maximizing portfolios and their expected utilities, basing its evaluation on in-sample analysis where mean–variance choice is sub-optimal by definition. In order to clarify this existing research, this study provides a framework that allows comparing in-sample and out-of-sample performance of the mean variance portfolios against expected utility maximizing portfolios. Our in-sample results confirm the results of earlier studies. On the other hand, our out-of-sample results show that the expected utility model performs worse. The out-of-sample inferiority of the expected utility model is more pronounced for preferences and constraints under which in-sample mean variance approximations are weakest. We argue that, in addition to its elegance and simplicity, the mean–variance model extracts more information from sample data because it uses the covariance matrix of returns. The expected utility model may reach its optimal solution without using information from the covariance matrix.
Characterization of serotonin binding sites on human platelets.

A high affinity, saturable 3H-spiroperidol binding site was identified for the first time on the intact human platelet, with drug affinities comparable to the serotonin-2 (S-2) receptor in human frontal cortex. The site was characterized by a KD of 2.7 ± 0.3nM and a Bmax of 1.4 ± 0.2 pmoles/108 platelets. A 3H-serotonin binding site was also found, with a KD of 42 ± 8 nM, which appeared to represent the serotonin uptake site. No 3H-serotonin binding site with features of the serotonin-1 (S-1) receptor in brain was found on the platelet. Assay of 3H-spiroperidol binding to platelets may serve as an easily applied model for studying S-2 receptor function in man, and its relationship to age, hormonal, drug, and disease effects.
THE RADIATIVE PROPERTIES OF LONG-RANGE MOLECULES

$^{1}$See e.g., W. C. Stwalley, ``Atom-Atom Interactions from Spectroscopy"", in D. W. Smith and W. B. McRae, Editors, Energy, Structure, and Reactivity (Wiley, New York, 1973), p. 259. Acknowledgment is made to the Donors of the Petroleum Research Fund, administered by the American Chemical Society, and to the National Science Foundation for support of this work. Temporary address of William C. Stwalley: Chemistry Division, National Science Foundation, Washington, D. C., 2055 (8/1/75 - 7/31/76).
Interferometric detection of ultrafast thermoelastic transients in thin films:theory with supporting experiment

The thermoelastic generation and interferometric detection of ultrafast thermal and acoustic transients in a 300-nm-thick tungsten film are theoretically predicted and supported through experiment. Detection of these picosecond transients is obtained with a time-resolved spectroscopy scheme that uses a rotated cube, common path, self-stabilized Michelson interferometer and subpicosecond laser pulses from a mode-locked laser. These observations are theoretically described by the superposition of changes in the complex index of refraction and displacements over the absorption volume. Data analysis is completed in both time and frequency domains to support the validity of the classical assumptions involved in the theoretical derivation.
Changing the Receptor Specificity of Anthrax Toxin

The actions of many bacterial toxins depend on their ability to bind to one or more cell-surface receptors. Anthrax toxin acts by a sequence of events that begins when the protective-antigen (PA) moiety of the toxin binds to either one of two cell-surface proteins, ANTXR1 and ANTXR2, and is proteolytically activated. The activated PA self-associates to form oligo- meric pore precursors, which, in turn, bind the enzymatic moieties of the toxin and transport them to the cytosol. We intro- duced a double mutation into domain 4 of PA to ablate its native receptor-binding function and fused epidermal growth factor (EGF) to the C terminus of the mutated protein. The resulting fusion protein transported enzymatic effector proteins into a cell line that expressed the EGF receptor (A431 cells), but not into a line lacking this receptor (CHO-K1 cells). Addition of excess free EGF blocked transport of effector proteins into A431 cells via the fusion protein, but not via native PA. We also showed that fus- ing the diphtheria toxin receptor-binding domain to the C terminus of the mutated PA channeled effector-protein transport through the diphtheria toxin receptor. PA fusion proteins with altered receptor specificity may be useful in biological research and could have practical applications, including ablation or perturbation of selected populations of cells in vivo. IMPORTANCE Bacterial toxins that act within mammalian cells have receptor-dependent mechanisms to transport their enzy- matic components to the cytoplasmic compartment. By inactivating or otherwise modifying their respective intracellular targets, these intracellular effectors disrupt metabolic pathways and in some cases cause death of the cell. Our results show that the re- ceptor specificity of the transport protein of anthrax toxin may be readily changed, raising the possibility that receptor- redirected forms of protective antigen (PA) and PA homologs may be useful for research and medical applications requiring modification or ablation of designated populations of cells.
Pulmonary function, bronchial reactivity, and epithelial permeability are response phenotypes to ozone and develop differentially in healthy humans

Effect of laboratory exposure to O3 (220 ppb) and filtered air (FA) on respiratory physiology were evaluated at two time points (acute and 1 day postexposure) in healthy cohort (n = 138, 18–35 yr, ...
The practice of Interventional Cardiovascular Medicine: “Evidence‐based” or “Judgment‐based”?

Evidence-based medicine has emerged in response to empiric clinical decision-making with the quest of infusing more “science” into the process of caring for the sick. Yet, evidence-based medicine today is being applied to clinical practice in a rigid and, paradoxically, unscientific manner. The perception that evidence-based medicine is the “ultimate and unquestionable biologic truth” that should supersede all other components of clinical decision-making at the individual patient level needs to be critically reexamined. The practice of Interventional Cardiovascular Medicine should represent a bottom-up approach that integrates the best external evidence—that has been critically analyzed—with individual clinical expertise and patient choice; it cannot result in cookbook approaches to patient care. External clinical evidence should inform, not replace, individual clinical expertise, and it is this expertise that decides whether the external evidence applies to the individual patient at all and, if so, how it should be integrated into a clinical decision. © 2008 Wiley-Liss, Inc.
Availability of Nutrition Information from Chain Restaurants in the United States

Background Although obesity and poor dietary habits are complex multifactorial problems, away-from-home food has been identified as one likely and important contributor. Restaurants provide a growing and substantial portion of the average American's diet, yet the Nutrition Labeling and Education Act (NLEA), which went into effect in 1994, explicitly exempts restaurants from most labeling requirements. Thus, this study examined the availability of nutrition information from the largest chain restaurants in the United States. Methods Between January and August 2004, we surveyed the 300 largest chain restaurants by telephone, e-mail, or examining company websites (response rate was 96%). The top chains, as ranked by revenue, were selected based on 2002 ratings in Restaurants and Institutions . Results Fifty-four percent of the 287 largest chain restaurants made some nutrition information available. Forty-four percent had nutrition information for the majority of their standard menu items. We found no significant differences in the availability of nutrition information based on the size of the restaurant chain. Of those restaurants with nutrition information, 86% provided information on the company website. Conclusions The number of restaurants providing nutrition information has increased over the last 10 years. However, making informed and healthful food choices is hampered by the absence of nutrition information at many restaurants. Given the growing and significant role that away-from-home foods play in Americans' diets, the Surgeon General and the National Academies' Institute of Medicine recommend that nutrition information be available to customers at restaurants, and state legislatures and the U.S. Congress are beginning to address the issue.
TAXONOMY, DISTRIBUTION, AND CHARACTERS OF PRE-OLIGOCENE MEMBERS OF THE CANTHARUS GROUP OF PISANIINAE (NEOGASTROPODA: BUCCINOIDEA)

This paper presents a review of Cretaceous to Eocene genera and species of the Cantharus group of the buccinoidean neogastropod subfamily Pisaniinae, the description of two new genera and one new species, and a nonphylogenetic discussion of character evolution in this group. The new genus Ickarus is introduced for Tritonidea ickei Martin, 1914, from the Nanggulan beds (middle Eocene) of Java, Indonesia. Editharus (type species: Fusus polygonus Lamarck, 1803, middle Eocene of the Paris Basin, France) is a new genus with seven to nine species ranging from the early to late Eocene of Europe. Editharus is unusual in having a labral tooth formed at the angular junction between the adapical and abapical sectors of the outer lip. Editharus angulilabris from the Marinesian (early late Eocene) is a new species from the Paris Basin closely related to E. polygonus. The incidence and expression of several characters has sharply increased in the Cantharus group from the Paleogene to the Neogene. These characters include the presence of lirae (spiral ridges) on the inner side of the outer lip, the presence of a parietal tooth at the adapical end of the inner lip, and determinate growth (as inferred from a unique adult varix). These trends are also exhibited by other Cenozoic gastropod clades.
Metallocycles as Intermediates in Organotransition-Metal Reactions

Metallocycles have been proposed as intermediates in a number of transition metal catalyzed reactions of organic compounds.1,2,3 In most cases it is difficult to distinguish between a non-concerted, stepwise reaction proceeding through a metallocyclic intermediate and a concerted “symmetry controlled” reaction.2,3,4,5 Consequently, stable tetramethylene metallocycles have been prepared and their structure and reactivities have been examined. These compounds should provide models for reactions which may involve metallocycles. Evidence for metallocycles in transition metal catalyzed olefin reactions, especially in the olefin metathesis reaction, has also been sought.
It Is Not Just About Testosterone: Physiological Mediators and Moderators of Testosterone’s Behavioral Effects

The inclusion of hormones in social and personality psychology research offers researchers a powerful methodological tool, although careful consideration must be paid to the complex and dynamic biological systems that connect hormones to behavior. Testosterone has been clearly established as a biological fuel for dominance, although behavioral findings have been inconsistent and weak. We suggest a number of physiological systems that affect the influence of testosterone on behavior. Vasopressin synthesis and the aromatization into estradiol both serve to facilitate testosterone’s effects. Testosterone’s behavioral responses to threats are suppressed by basal cortisol and moderated by allele length on the serotonin transporter gene. Variation in the expression of monoamine oxidase A regulates the levels of neurotransmitters responsible for impulse control, potentially suppressing testosterone’s influence over behavior. We argue that researchers must consider these dynamic relationships between hormones and other biological systems when engaging in future social endocrinology research.
Crystallization and preliminary X-ray analysis of a native human tRNA synthetase whose allelic variants are associated with Charcot-Marie-Tooth disease.

Glycyl-tRNA synthetase (GlyRS) is one of a group of enzymes that catalyze the synthesis of aminoacyl-tRNAs for translation. Mutations of human and mouse GlyRSs are causally associated with Charcot–Marie–Tooth disease, the most common genetic disorder of the peripheral nervous system. As the first step towards a structure–function analysis of this disease, native human GlyRS was expressed, purified and crystallized. The crystal belonged to space group P43212 or its enantiomorphic space group P41212, with unit-cell parameters a = b = 91.74, c = 247.18 A, and diffracted X-rays to 3.0 A resolution. The asymmetric unit contained one GlyRS molecule and had a solvent content of 69%.
Cytokine-dependent and-independent gene expression changes and cell cycle block revealed in Trypanosoma cruzi-infected host cells by comparative mRNA profiling.

The requirements for growth and survival of the intracellular pathogen Trypanosoma cruzi within mammalian host cells are poorly understood. Transcriptional profiling of the host cell response to infection serves as a rapid read-out for perturbation of host physiology that, in part, reflects adaptation to the infective process. Using Affymetrix oligonucleotide array analysis we identified common and disparate host cell responses triggered by T. cruzi infection of phenotypically diverse human cell types. We report significant changes in transcript abundance in T. cruzi-infected fibroblasts, endothelial cells and smooth muscle cells (2852, 2155 and 531 genes respectively; fold-change ≥ 2, p-value < 0.01) 24 hours post-invasion. A prominent type I interferon response was observed in each cell type, reflecting a secondary response to secreted cytokine in infected cultures. To identify a core cytokine-independent response in T. cruzi-infected fibroblasts and endothelial cells transwell plates were used to distinguish cytokine-dependent and -independent gene expression profiles. This approach revealed the induction of metabolic and signaling pathways involved in cell proliferation, amino acid catabolism and response to wounding as common themes in T. cruzi-infected cells. In addition, the downregulation of genes involved in mitotic cell cycle and cell division predicted that T. cruzi infection may impede host cell cycle progression. The observation of impaired cytokinesis in T. cruzi-infected cells, following nuclear replication, confirmed this prediction. Metabolic pathways and cellular processes were identified as significantly altered at the transcriptional level in response to T. cruzi infection in a cytokine-independent manner. Several of these alterations are supported by previous studies of T. cruzi metabolic requirements or effects on the host. However, our methods also revealed a T. cruzi-dependent block in the host cell cycle, at the level of cytokinesis, previously unrecognized for this pathogen-host cell interaction.
Coherent anti-Stokes Raman spectra of oxygen atoms in flames.

Coherent anti-Stokes Raman spectroscopy (CARS) was used to detect oxygen atoms (electronic Raman scattering) and oxygen molecules (rotational Raman scattering) in both hydrogen–oxygen and methane–oxygen flames. The high spectral resolution of CARS is useful for distinguishing the oxygen-atom signals from larger nearby rotational Raman signals. Saturation of the molecular CARS signal that is due to stimulated Raman scattering was observed. This effect limits the sensitivity of the CARS method.
Mechanisms of action and efficacy of nitrates in heart failure

Abstract Nitrates exert hemodynamic and possibly nonhemodynamic effects that result in reduced cardiac filling pressures, increased cardiac output, reduced pulmonary vascular pressures, and improvement in symptoms and exercise tolerance in patients with heart failure. Combined with hydralazine, chronic oral administration of isosorbide dinitrate has been demonstrated to improve survival when added to digoxin and diuretic therapy. A long-term improvement in left ventricular ejection fraction in these clinical studies has raised the possibility that the nitrates may be acting at least in part by inhibiting left ventricular remodeling. The precise rote of nitrates and the optimal dosing regimen in the therapeutic armamentarium for heart failure, particularly in patients already treated with a converting enzyme inhibitor, remains to be established.
CHANCE OF MISCLASSIFICATION IN THE CASE OF SEVERAL NORMAL POPULATIONS

SUMMARY When a new observation is to be classified into one of several multivariate normal populations with different means and the same covariance matrix, by Rao's method of scoring, the chance of misclassification is expressed as a multiple integral. This paper gives a practical method of obtaining reasonable approximations to this integral by using tables prepared by Gibbons, Olkin & Sobel (1977) for a different task.
Is Microglia the New Target for the Treatment of Resistant Hypertension

See related article, pp 309–316 Despite a large array of drugs available, the number of patients with uncontrolled hypertension or drug-resistant hypertension keeps increasing. With it, also rises the risk of end-organ damage, such as stroke, chronic kidney disease, heart failure, and vascular pathologies, leading to increased morbidity and mortality. A common denominator to resistant hypertension is an increase in sympathetic activity. Initial drugs targeting the enhanced sympathetic activity (eg, reserpine, α-methyl Dopa, clonidine) came with significant adverse effects, leading to a lack of compliance and the progressive disregard for this class of medications. Following was the development of other classes of drugs, able to preserve various organs function, but most of them unable to cross the blood brain barrier and therefore with limited impact on the sympathetic nervous system. The targeted scope of these medications resulted in combination therapies which ultimately are failing to achieve blood pressure control. In the past 15 years, a major role for the immune system has been rediscovered in the development and maintenance of resistant hypertension. Beyond the obvious role of tumor necrosis factor-α, cytokines and other mediators of inflammation, immune-competent cells have been highlighted as pivotal players in hypertension.1,2 It is now well recognized that in peripheral organs and tissues (eg, …
Tensegrity II. How structural networks influence cellular information processing networks

The major challenge in biology today is biocomplexity: the need to explain how cell and tissue behaviors emerge from collective interactions within complex molecular networks. Part I of this two-part article, described a mechanical model of cell structure based on tensegrity architecture that explains how the mechanical behavior of the cell emerges from physical interactions among the different molecular filament systems that form the cytoskeleton. Recent work shows that the cytoskeleton also orients much of the cell's metabolic and signal transduction machinery and that mechanical distortion of cells and the cytoskeleton through cell surface integrin receptors can profoundly affect cell behavior. In particular, gradual variations in this single physical control parameter (cell shape distortion) can switch cells between distinct gene programs (e.g. growth, differentiation and apoptosis), and this process can be viewed as a biological phase transition. Part II of this article covers how combined use of tensegrity and solid-state mechanochemistry by cells may mediate mechanotransduction and facilitate integration of chemical and physical signals that are responsible for control of cell behavior. In addition, it examines how cell structural networks affect gene and protein signaling networks to produce characteristic phenotypes and cell fate transitions during tissue development.
A Phase I Study of Pemetrexed, Carboplatin, and Concurrent Radiotherapy in Patients with Locally Advanced or Metastatic Non–Small Cell Lung or Esophageal Cancer

Purpose: The primary objective of this phase I study was to determine the maximum tolerated dose for pemetrexed, alone and in combination with carboplatin, with concurrent radiotherapy. Experimental Design: Patients with locally advanced or metastatic non–small cell lung cancer (NSCLC) or esophageal cancer were treated every 21 days for two cycles. Regimen 1 was pemetrexed (200-600 mg/m 2 ); regimen 2 was pemetrexed (500 mg/m 2 ) with escalating carboplatin doses (AUC = 4-6). Both regimens included concurrent radiation (40-66 Gy; palliative-intent doses were lower). Results: Thirty patients (18 locally advanced and 12 metastatic with dominant local symptoms) were enrolled, with an Eastern Cooperative Oncology Group performance status of 0/1/2 ( n = 8/21/1). All dose levels were tolerable for regimen 1 ( n = 18: 15 NSCLC and 3 esophageal cancers) and regimen 2 ( n = 12: all NSCLC). In regimen 1, one dose-limiting toxicity (grade 4 esophagitis/anorexia) occurred (500 mg/m 2 ). Grade 3 neutropenia (3 of 18 patients) was the main hematologic toxicity. In regimen 2, one dose-limiting toxicity (grade 3 esophagitis) occurred (500 mg/m 2 ; AUC = 6); grade 3/4 leukopenia (4 of 12 patients) was the main hematologic toxicity. Four complete responses (2 pathology proven) and eight partial responses were observed. When systemically active chemotherapy doses were reached, further dose escalation was discontinued, and a phase II dose-range was established (pemetrexed 500 mg/m 2 and carboplatin AUC = 5-6). Conclusions: The combination of pemetrexed (500 mg/m 2 ) and carboplatin (AUC = 5 or 6) with concurrent radiation is well tolerated, allows for the administration of systemically active chemotherapy doses, and shows signs of activity. To further determine efficacy, safety profile, and optimal dosing, the Cancer and Leukemia Group B study 30407 is currently evaluating this regimen in patients with unresectable stage III NSCLC.
Can Endothelial Progenitor Cells Treat Patients With Refractory Angina

Refractory angina continues to pose a therapeutic challenge for patients and clinicians because treatment options including medication and surgery are limited.1 Therefore, the idea that cell-based therapy could offer a new therapeutic opportunity continues to raise enthusiasm.2 With this regard, circulating endothelial progenitor cells (EPCs) have gained significant attention because of their participation in neovascularization and re-endovascularization.3 EPCs are a specific population of progenitor cells—expressing CD133, CD34, and kinase insert domain receptor, KDR (also known as vascular endothelial growth factor 2, VEGFR-2, and fetal liver kinase 1, FLK1) cell-surface markers—that differentiate into endothelial cells, thereby lining blood vessels and playing a critical role in angiogenesis and vasculogenesis.3 EPCs incorporate into both new and injured vessels, and release proangiogenic and immunomodulatory factors,3 making them an ideal candidate for treating patients with ischemic heart diseases like refractory angina.4 Article, see p 950 Although cell-based therapy is exciting, it remains to be established which EPC cell population best targets refractory angina: CD34+ or CD133+ EPCs. Both CD34+ and CD133+ are endogenous cell-surface markers expressed on EPCs that originate from bone marrow and are mobilized into peripheral blood in response to cytokine signaling and injury.5 During the past decade, it has become possible to purify EPCs by mobilizing them into peripheral blood using granulocyte colony-stimulating factor. Endogenous granulocyte colony-stimulating factor is synthesized by the endothelium, macrophages, and immune cells, and it acts as a cytokine that stimulates bone marrow to produce granulocytes and stem cells and then release them into the bloodstream.6 Therefore, granulocyte colony-stimulating factor is used pharmacologically to enhance the number of EPCs obtained from patients undergoing cell therapy.7 Specifically, patients are given granulocyte colony-stimulating factor treatment for 4 to 5 days to mobilize EPCs, which is immediately followed …
Erratum for “Effective Saturated Hydraulic Conductivity of an Infiltration-Based Stormwater Control Measure” by Peter T. Weiss and John S. Gulliver

Site Type of SCM n Average ψ (cm) Average Δθ Arithmetic mean Ksat (cm=h) Geometric mean Ksat (cm=h) Best effective Kbest-fit (cm=h) Cottage Grove Bioinfiltration 20 19.5 0.20 18.5 16.0 16.9 Burnsville Bioinfiltration 20 26.0 0.20 13.2 9.6 11.4 UM-St. Paul Bioinfiltration 37 97.1 0.21 2.9 0.9 1.5 UM-Duluth Bioinfiltration 18 36.7 0.17 9.2 1.7 4.3 Infiltration Basin Infiltration basin 33 29.0 0.11 14.1 6.8 8.3 HWY 51 North Swale 18 2.0 0.29 14.5 6.5 10.6 HWY 51 Center Swale 18 11.4 0.25 6.57 2.97 4.07 HWY 51 South Swale 21 40.9 0.23 6.38 1.99 2.27 HWY 47 Swale 21 20.7 0.21 20.6 11.5 14.2 HWY 212 East Swale 21 26.7 0.20 4.65 1.18 1.73 HWY 212 Center Swale 21 32.8 0.20 2.50 0.44 0.78 HWY 212 West Swale 20 1.71 0.18 25.8 8.32 15.5
Two Cyanobacterial Photoreceptors Regulate Photosynthetic Light Harvesting by Sensing Teal, Green, Yellow, and Red Light

ABSTRACT The genomes of many photosynthetic and nonphotosynthetic bacteria encode numerous phytochrome superfamily photoreceptors whose functions and interactions are largely unknown. Cyanobacterial genomes encode particularly large numbers of phytochrome superfamily members called cyanobacteriochromes. These have diverse light color-sensing abilities, and their functions and interactions are just beginning to be understood. One of the best characterized of these functions is the regulation of photosynthetic light-harvesting antenna composition in the cyanobacterium Fremyella diplosiphon by the cyanobacteriochrome RcaE in response to red and green light, a process known as chromatic acclimation. We have identified a new cyanobacteriochrome named DpxA that maximally senses teal (absorption maximum, 494 nm) and yellow (absorption maximum, 568 nm) light and represses the accumulation of a key light-harvesting protein called phycoerythrin, which is also regulated by RcaE during chromatic acclimation. Like RcaE, DpxA is a two-component system kinase, although these two photoreceptors can influence phycoerythrin expression through different signaling pathways. The peak responsiveness of DpxA to teal and yellow light provides highly refined color discrimination in the green spectral region, which provides important wavelengths for photosynthetic light harvesting in cyanobacteria. These results redefine chromatic acclimation in cyanobacteria and demonstrate that cyanobacteriochromes can coordinately impart sophisticated light color sensing across the visible spectrum to regulate important photosynthetic acclimation processes. IMPORTANCE The large number of cyanobacteriochrome photoreceptors encoded by cyanobacterial genomes suggests that these organisms are capable of extremely complex light color sensing and responsiveness, yet little is known about their functions and interactions. Our work uncovers previously undescribed cooperation between two photoreceptors with very different light color-sensing capabilities that coregulate an important photosynthetic light-harvesting protein in response to teal, green, yellow, and red light. Other cyanobacteriochromes that have been shown to interact functionally sense wavelengths of light that are close to each other, which makes it difficult to clearly identify their physiological roles in the cell. Our finding of two photoreceptors with broad light color-sensing capabilities and clearly defined physiological roles provides new insights into complex light color sensing and its regulation.
Options and Choices in the Disposition of Excess Weapon Plutonium

More than 50 tons of weapon-related plutonium (WPu) is expected to become excess and available for disposition by the year 2003 in Russia and a similar amount in the United States. Per two reports from the Committee on International Security and Arms Control of the National Academy of Sciences (1994 1 and 1995 2), the hazard of theft and incorporation into nuclear weapons impels us to guard this Pu carefully and as soon as possible to transform it into a form less accessible for use in nuclear weapons. To this end, CISAC adopted the “Spent Fuel Standard” for the disposed WPu, which, if met, renders the WPu no greater hazard per kg than the much larger amount of reactor Pu in the form of spent fuel, since CISAC finds that separated RPu can be used for nuclear weapons with little additional difficulty beyond that posed by separated WPu. Many disposition routes can be eliminated on the basis of cost or other metric. The two principal survivors (of about equal cost and difficulty for the United States) are the partial burning of WPu as MOX and the direct vitrification of WPu (as oxide) with high-level “defense wastes”. Both these approaches should be pursued urgently, with experiments to qualify the processes, until one is selected on the basis of hard evidence. Either approach would cost about $1 B, within a factor two, to dispose of 50 tons of excess WPu. The CISAC analysis will be presented, with comments on utility of RPu in weapons, on the DOE Plutonium Disposition Study, and on “explosive criticality” in the repository.
Structure and Dynamics of the HIV-1 Frameshift Element RNA

The HIV-1 ribosomal frameshift element is highly structured, regulates translation of all virally encoded enzymes, and is a promising therapeutic target. The prior model for this motif contains two helices separated by a three-nucleotide bulge. Modifications to this model were suggested by SHAPE chemical probing of an entire HIV-1 RNA genome. Novel features of the SHAPE-directed model include alternate helical conformations and a larger, more complex structure. These structural elements also support the presence of a secondary frameshift site within the frameshift domain. Here, we use oligonucleotide-directed structure perturbation, probing in the presence of formamide, and in-virion experiments to examine these models. Our data support a model in which the frameshift domain is anchored by a stable helix outside the conventional domain. Less stable helices within the domain can switch from the SHAPE-predicted to the two-helix conformation. Translational frameshifting assays with frameshift domain mutants support a functional role for the interactions predicted by and specific to the SHAPE-directed model. These results reveal that the HIV-1 frameshift domain is a complex, dynamic structure and underscore the importance of analyzing folding in the context of full-length RNAs.