cssi/SciSciGPT-SciSciNet huggingface dataset:
Using massively parallel simulation and Markovian models to study protein folding: examining the dynamics of the villin headpiece.

We report on the use of large-scale distributed computing simulation and novel analysis techniques for examining the dynamics of a small protein. Matters addressed include folding rate, very long time scale kinetics, ensemble properties, and interaction with water. The target system for the study, the villin headpiece, has been of great interest to experimentalists and theorists both. Sampling totaled nearly 500μs—the most extensive published to date for a system of villin’s size in explicit solvent with all atom detail—and was in the form of tens of thousands of independent molecular dynamics trajectories, each several tens of nanoseconds in length. We report on kinetics sensitivity analyses that, using a set of short simulations, probed the role of water in villin’s folding and sensitivity to the simulation’s electrostatics treatment. By constructing Markovian state models (MSMs) from the collected data, we were able to propagate dynamics to times far beyond those directly simulated and to rapidly compu...
Functional identification of spike-processing neural circuits

We introduce a novel approach for a complete functional identification of biophysical spike-processing neural circuits. The circuits considered accept multidimensional spike trains as their input and comprise a multitude of temporal receptive fields and conductance-based models of action potential generation. Each temporal receptive field describes the spatiotemporal contribution of all synapses between any two neurons and incorporates the passive processing carried out by the dendritic tree. The aggregate dendritic current produced by a multitude of temporal receptive fields is encoded into a sequence of action potentials by a spike generator modeled as a nonlinear dynamical system. Our approach builds on the observation that during any experiment, an entire neural circuit, including its receptive fields and biophysical spike generators, is projected onto the space of stimuli used to identify the circuit. Employing the reproducing kernel Hilbert space RKHS of trigonometric polynomials to describe input stimuli, we quantitatively describe the relationship between underlying circuit parameters and their projections. We also derive experimental conditions under which these projections converge to the true parameters. In doing so, we achieve the mathematical tractability needed to characterize the biophysical spike generator and identify the multitude of receptive fields. The algorithms obviate the need to repeat experiments in order to compute the neurons' rate of response, rendering our methodology of interest to both experimental and theoretical neuroscientists.
The Dynamics of Odd Sawtooth Functions

This note considers a family of piece-wise linear functions that can be used in the classroom to illustrate various concepts involved in iteration theory such as periodicity. These functions require minimal background on the part of the student.
MADD Massachusetts Versus Senator Burke: A Media Advocacy Case Study:

In 1991, the Massachusetts legislature considered a bill that would have allowed a drunk driving defendant's refusal to take a breathalyzer test to be admitted as evidence in a criminal trial. After the measure passed in both houses, a state senator used a parliamentary maneuver to prevent it from being prepared for the governor's signature. Mothers Against Drunk Driving (MADD) employed media advocacy techniques to alert the public, but the senator was unyielding and the legislative calendar ran out with the bill unsigned. Because of MADD's efforts, however, the senate president put the bill on a "fast track" the following year. The news media's focused attention on MADD's protests exposed deep schisms among its volunteer leadership regarding the nature and purpose of the organization and the appropriateness of using confrontational media strategies to advance its agenda. Paralyzed by the lack of consensus, MADD Massachusetts was rendered a far less effective advocate for policy change.
Airway management in neurological emergencies and neuroanesthesia

Summary Airway management in the neurosurgical patient with a multitude of medical problems connotes a difficult task with the various physiological ramifications. In this article, we reviewed some specific clinical situations frequently encountered in clinical neuroanesthesia practice. Focus was placed on the specific disease processes of these patients, airway requirements as they relate to the patient positioning, stereotactic neurosurgery, and conscious sedation techniques. Although there are many alternative airway devices, it is imperative that proper planning and advance preparation be at hand before approaching any of these scenarios. A conservative approach to the airway management is recommended, with awake approach a primary thought if there is any doubt regarding the safety of laryngoscopy in the asleep patient. We would like to emphasize that for any awake approach to be optimal and successful, optimal topicalization needs to be performed. Expertise in the techniques of securing the airway along with an understanding of the patient's physiological requirements, plus a knowledge of the surgical requirements, are critical to meet the demands for airway management in neuroanesthesia.
The Constitution as Instrument and as Symbol.

On an early page of his celebrated Constitutional Limitations , Judge Cooley defines “constitution” in the following curt terms: “That body of rules and maxims in accordance with which the powers of sovereignty are habitually exercised.” Returning later to the subject, he quotes with approval a more elaborate conception, couched in these words: “What is a constitution, and what are its objects? It is easier to tell what it is not than what it is. It is not the beginning of a community, nor the origin of private rights; it is not the fountain of law, nor the incipient state of government; it is not the cause, but consequence, of personal and political freedom; it grants no rights to the people , but is the creature of their power, the instrument of their convenience. Designed for their protection in the enjoyment of the rights and powers which they possessed before the constitution was made, it is but the framework of the political government, and necessarily based upon the preexisting condition of laws, rights, habits, and modes of thought. There is nothing primitive in it, it is all derived from a known source. It presupposes an organized society, law, order, property, personal freedom , a love of political liberty, and enough of cultivated intelligence to know how to guard it against the encroachments of tyranny. A written constitution is in every instance a limitation upon the powers of government in the hands of agents ; for there never was a written republican constitution which delegated to functionaries all the latent powers which lie dormant in every nation, and are boundless in extent, and incapable of definition.”
Educating for a “Spirituality of Dialogue”: Theological Foundations, Hermeneutical Invitations, and Pedagogical Directions

Abstract To be truly effective, dialogue in communities of faith must be more than tactics or strategies for community management. Fostering a “spirituality of dialogue” is a unique contribution that Religious Education can offer faith communities, providing a concrete locus for the interplay and mutual enrichment of theological inquiry and Religious Education. This article explores Trinitarian and hermeneutical aspects of dialogue as it looks to the question, “How might we educate toward a spirituality of dialogue” that will support effective conversation within faith communities … and beyond?
Enhanced Photocatalytic Activity by Aligned WO3/TiO2 Two-Layer Nanorod Arrays

The photocatalytic and structural properties of TiO2/WO3 two-layer nanostructures made by electron beam deposition were studied and compared with single-layer TiO2 nanostructures. Three different two-layer structures, thin film, tilted nanorods, and vertical nanorods, were fabricated by a normal deposition, oblique angle deposition, and glancing angle deposition. The as-deposited and annealed samples at Ta = 300 °C and Ta = 400 °C, respectively, were studied by SEM, XRD, Raman spectroscopy, and UV−vis spectrophotometry. The photocatalytic properties of those samples were investigated and found to be improved significantly by increasing the surface and interfacial area, annealing at a proper temperature, the enhanced charge separation due to the WO3−TiO2 coupling, and the arrangement of the two layers. The optimal structure was found to be the two-layer vertical TiO2/WO3 nanorods after annealing at Ta = 300 °C, which had a photodegradation rate about 10 times higher than a single-layer TiO2 vertical nanoro...
Characteristics of intermittent fuel sprays

Abstract The spray-tip penetrations and the drop sizes of intermittent fuel sprays were measured by using a modified pulsed optical spray sizer. The average spray tip speeds were determined from simultaneously recorded needle lift signals and obscuration traces. The speeds of a sequence of fuel pulses injected at ∼ 10 3 Hz were analyzed to elucidate penetration mechanisms. A correlation that relates penetration distance to time, pressure drop across the nozzle, fuel density, and ambient gas density was obtained. The temporal variations of drop size in penetrating pulses of sprays were measured. The concentration of drops were calculated by combining drop size and obscuration data. The Sauter mean diameter of penetrating fuel drops increased with an increase of the chamber pressure and decreased with an increase of the injection pressure.
Repopulation of rat liver by fetal hepatoblasts and adult hepatocytes transduced ex vivo with lentiviral vectors

Recent studies have shown that nondividing primary cells, such as hepatocytes, can be efficiently transduced in vitro by human immunodeficiency virus-based lentivirus vectors. Other studies have reported that, under certain conditions, the liver can be repopulated with transplanted hepatocytes. In the present study, we combined these procedures to develop a model system for ex vivo gene therapy by repopulating rat livers with hepatocytes and hepatoblasts transduced with a lentivirus vector expressing a reporter gene, green fluorescent protein (GFP). Long-term GFP expression in vivo (up to 4 months) was achieved when the transgene was driven by the liver-specific albumin enhancer/promoter but was silenced when the cytomegalovirus (CMV) enhancer/promoter was used. Transplanted cells were massively amplified (∼10 cell doublings) under the influence of retrorsine/partial hepatectomy, and both repopulation and continued transgene expression in individual cells were documented by dual expression of a cell transplantation marker, dipeptidyl peptidase IV (DPPIV), and GFP. In this system, maintenance or expansion of the transplanted cells did not depend on expression of the transgene, establishing that positive selection is not required to maintain transgene expression following multiple divisions of transplanted, lentivirus-transduced hepatic cells. In conclusion, fetal hepatoblasts (liver stem/progenitor cells) can serve as efficient vehicles for ex vivo gene therapy and suggest that liver-based genetic disorders that do not shorten hepatocyte longevity or cause liver damage, such as phenylketonuria, hyperbilirubinemias, familial hypercholesterolemia, primary oxalosis, and factor IX deficiency, among others, might be amenable to treatment by this approach.
Optimal schedule for cancer chemotherapy

In this paper we consider the problems of modeling the tumor growth and optimize the chemotherapy treatment. A biologically based model is used with the goal of solving an optimization problem involving discrete delivery of antineoplastic drugs. Our model is formulated via compartmental analysis in order to take into account the cell cycle. The cost functional measures not only the final size of the tumor but also the total amount of drug delivered. We propose an algorithm based on the discrete maximum principle to solve the optimal drug schedule problem. Our numerical results show nice interpretations from the medical point of view.
Combined optimal price and optimal inventory replenishment policies when a sale results in increase in demand

Abstract When a supplier reduces the price of a product temporarily a buyer might place a large order and offer a sale on these units to its customers. In most cases a price discount results in an increase in demand. In this paper we relax the constant demand assumption made in most studies of inventory systems with price changes. We analyze the options available to a buyer and develop profit functions for different combinations of sales period and replenishment time and present optimal ordering policies. The paper also presents a procedure to include any relationship between price and demand to determine the combined optimal price and optimal order quantity.
Relative effects of streptomycin on motor nerve terminal and endplate

Abstract Using standard microphysiologic recording techniques, the effects of streptomycin on nerve terminal and endplates were evaluated using the isolated frog satorius muscle. Twitch tension studies were performed on the sciatic nerve sartorius muscle preparation. In low concentrations the agent increased mepp frequency and twitch strength and caused antidromic firing from the nerve terminal. In the concentration range causing inhibition of muscle twitch, nerve terminal activity remained elevated. In this range mepp amplitude and endplate sensitivity were markedly reduced. At high doses streptomycin finally inhibited nerve terminal function. The reduction in twitch height was explained by blockade of the post-junction membrane. It is postulated that streptomycin has three effects on the myoneural junction: (1) stimulation of the nerve terminal at low doses; (2) reduction of the endplate sensitivity to acetylcholine concomitant with a reduction in the twitch height at higher doses and (3) inhibition of nerve terminal function at the highest doses studied.
Ultrafast Excited State Dynamics of Oxidized Flavins: Direct Observations of Quenching by Purines

We have measured the excited-state dynamics and spectral evolution of oxidized flavin−adenine dinucleotide (FADox) and flavin mononucleotide (FMNox) in simple solvents with subpicosecond time resolution by one-color and white-light continuum transient absorption spectroscopy. In water, the FADox transient shows significant quenching of the excited state with a lifetime of ∼4 ps while for FMNox this component is of much lower amplitude. However, when caffeine is added to the FMN solution the amplitude of the fast component is recovered. Additionally, the excited-state dynamics of FAD in neat formamide, a solvent that breaks up stacking interactions in FAD, is similar to that obtained for FMN in water. These measurements provide conclusive evidence that the excited-state quenching observed in FAD or flavin−purine complexes occurs in less than 5 ps. The observed spectral evolution shows that internal conversion from S2 to S1 occurs in less than 100 fs.
Static electric dipole polarizabilities of An5+/6+ and AnO2+/2+ (An = U, Np, and Pu) ions

The parallel components of static electric dipole polarizabilities have been calculated for the lowest lying spin-orbit states of the penta- and hexavalent oxidation states of the actinides (An) U, Np, and Pu, in both their atomic and molecular diyl ion forms (An5+/6+ and AnO2+/2+) using the numerical finite-field technique within a four-component relativistic framework. The four-component Dirac-Hartree-Fock method formed the reference for MP2 and CCSD(T) calculations, while multireference Fock space coupled-cluster (FSCC), intermediate Hamiltonian Fock space coupled-cluster (IH-FSCC) and Kramers restricted configuration interaction (KRCI) methods were used to incorporate additional electron correlation. It is observed that electron correlation has significant (∼5 a.u.3) impact upon the parallel component of the polarizabilities of the diyls. To the best of our knowledge, these quantities have not been previously reported and they can serve as reference values in the determination of various electronic and response properties (for example intermolecular forces, optical properties, etc.) relevant to the nuclear fuel cycle and material science applications. The highest quality numbers for the parallel components (αzz) of the polarizability for the lowest Ω levels corresponding to the ground electronic states are (in a.u.3) 44.15 and 41.17 for UO2+ and UO22+, respectively, 45.64 and 41.42 for NpO2+ and NpO22+, respectively, and 47.15 for the PuO2+ ion.
Context-sensitive in-the-world interfaces for mobile manipulation robots

We present an interface that allows users to direct a mobile manipulation robot in tabletop pick-and-place tasks using only their head motions and a single button. The system uses an estimate of the user's head pose and a 3d world model maintained by the robot to determine where the user is pointing their head. We give the results of some preliminary evaluations of our system, which suggest that it is both intuitive and effective. We also describe an example trash-sorting application where the user directs a PR2 robot sort objects in to “trash” and “recycle” piles.
Characterization of rat liver microsomal metabolites of AM-630, a potent cannabinoid receptor antagonist, by high-performance liquid chromatography/electrospray ionization tandem mass spectrometry

The in vitro metabolism of AM-630 was studied by high-performance liquid chromatography coupled with tandem mass spectrometry. AM-630 is an aminoalkylindole analogue that behaves primarily as a potent CB2-selective antagonist. In this study, 17 metabolic products were identified that resulted from the incubation of AM-630 in rat liver microsome preparations. Six metabolic pathways were proposed to account for all detected metabolites: (1) o-demethylation of the methoxyphenyl group, (2) morpholinyl ring opening, (3) hydroxylation on the methoxy/hydroxyl phenyl ring, (4) hydroxylation on the indole ring, (5) hydroxylation on the morpholine ring and (6) loss of the morpholine ring leading to metabolites containing either a hydroxylated or a carboxylated alkyl terminal. Three metabolites were identified as morpholinyl ring-opening products: M1, M6 and M13. Six metabolites (M2-M5, M7 and M8) were proposed to be the products of o-demethylation, hydroxylation on the methoxyphenyl group or the morpholinyl ring, dehydration following morpholinyl ring monohydroxylation, or a combination of the above metabolic pathways. The remaining eight metabolites were attributed to a pathway involving the loss of the morpholine ring at various points during the metabolic processes.
Fracture-surface energy of rocks

Abstract Effective fracture-surface energies γ eff , as determined from stable tensile-fracture tests on a variety of rock types, are of the order of 10 4 ergs/cm 2 in contrast to values for constituent crystals which are 10 2 –10 3 ergs/cm 2 . The major source of discrepancy has been ascribed to improperly accounting for the entire new surface created by the propagation of fractures through granular media. One aspect of our continuing investigation of residual elastic strain in rocks has been the assessment of the contribution of such strain to the process of fracturing. Although the work is incomplete, it has confirmed this reason for these order-of-magnitude differences in single-crystal and rock values. From X-ray diffraction studies of changes in residual strain adjacent to tensile fractures in sandstone and also from thin-section studies of stained specimens, we conclude that intergranular displacements take place in a region as much as 5 mm wide on each side of the fractures. When the total surface area of the grains within this region is equated to the total effective area of fracture created, γ eff is reduced to the same order as that for single crystals.
Multiple-site concerted proton-electron transfer reactions of hydrogen-bonded phenols are nonadiabatic and well described by semiclassical Marcus theory.

Photo-oxidations of hydrogen-bonded phenols using excited-state polyarenes are described to derive fundamental understanding of multiple-site concerted proton–electron transfer reactions (MS-CPET). Experiments have examined phenol bases having −CPh2NH2, −Py, and −CH2Py groups ortho to the phenol hydroxyl group and tert-butyl groups in the 4,6-positions for stability (HOAr-NH2, HOAr-Py, and HOAr-CH2Py, respectively; Py = pyridyl; Ph = phenyl). The photo-oxidations proceed by intramolecular proton transfer from the phenol to the pendent base concerted with electron transfer to the excited polyarene. For comparison, 2,4,6-tBu3C6H2OH, a phenol without a pendent base and tert-butyl groups in the 2,4,6-positions, has also been examined. Many of these bimolecular reactions are fast, with rate constants near the diffusion limit. Combining the photochemical kCPET values with those from prior thermal stopped-flow kinetic studies gives data sets for the oxidations of HOAr-NH2 and HOAr-CH2Py that span over 107 in kCP...
Build it, and they will Come Narcotics and Money Laundering in the Leeward Islands

This article concentrates on three Leeward Island nations in the Caribbean that lie between the Anegada Passage on the northwest and the Guadeloupe Passage on the southeast. The islands are St. Martin, which is divided into a French side and a Dutch side, and two formerly British ones—St. Kitts and Antigua. With regard to St. Martin, only the Dutch half, St. Maarten, shall be discussed. Each has been involved in the illicit drug industry, especially in money-laundering activities. This article will discuss a number of themes, including the interplay between casino culture and narcotics trafficking, as well as the economy of each island nation. By focusing on these three island nations, a template can be formed for understanding the contemporary criminal justice problems throughout the Caribbean region.
The lingula is an appropriate site for lung biopsy.

Abstract Background . Lung biopsy is commonly performed for diagnosis of diffuse pulmonary disease. The lingula offers technical advantages for biopsy, however the quality of tissue obtained by lingula biopsy has been questioned. We sought to determine whether lingula biopsy was a satisfactory site for biopsy in terms of diagnostic yield, therapeutic interventions, and survival results. Methods . All diagnostic lung biopsies performed for diffuse lung disease at 3 university affiliated hospitals between July 1, 1992 and December 31, 1998 were retrospectively reviewed. Patients were divided into 2 groups, depending upon site of biopsy: patients with lingula biopsy only and those with biopsies from other sites. Results . There were 75 patients; 20 underwent biopsy of the lingula alone, 48 had biopsy of other sites with or without biopsy of the lingula, and location of biopsy was unknown in 7 patients. Histologic diagnosis was achieved in all patients. Significant beneficial therapeutic changes were made in 14 lingula patients, and consisted of immunosuppression in 12 cases. Three patients died in the hospital or within 30 days. Fourteen patients survived 1 year. There was no significant difference between patients that had biopsy of the lingula alone and those that had biopsies from other sites in urgency, technique, histologic diagnosis, rate of therapeutic interventions, hospital mortality, or 1 year survival. Conclusions . Lung biopsy of the lingula compared to other anatomic sites has equivalent diagnostic yield, therapeutic significance, and survival. Given the technical ease of biopsy, when disease is present radiographically it is the preferred site for lung biopsy.
SU‐FF‐J‐80: Implementation of On‐Board Imager for Daily Image‐Guided Radiation Therapy in a Multi Vendor Environment

Purpose: To report our initial experience of using Varian On‐Board Imager (OBI) image‐guidedradiation therapy(IGRT), on a prostate patient with implanted fiducials. Varian's OBI‐IGRT system enables clinicians to obtain high‐quality daily kV images of the patient in treatment position. An attempt has been made to implement and evaluate various possible workflow issues, when using the Varian OBI system in a multi vendor environment. Method and Materials: Daily shifts based on OBI images were made on an implanted fiducial prostate patient who underwent treatment on a Varian Trilogy Clinac. Using Varian's OBI 2D/2D matching software, orthogonal kV images were compared to Pinnacle3 (Philips) DRR's generated from the planning CT, to determine and correct for any daily target shifts. The kV images were transferred to our record and verification system IMPAC MultiAccess (Elekta), for physician review. The shifts predicted by the Varian software using manual matching, was compared daily, with the shifts predicted by the Acculoc software (Medtec), based on three implanted fiducials. In addition, cone beam CT(CBCT) scans were acquired once a week, to predict shifts using our in‐house developed 3D/3D‐ matching software. Results: Daily shifts predicted by the Varian OBI 2D/2D software, matched daily shifts predicted by the Acculoc fiducial alignment software to within 1 mm during the entire treatment course. The weekly CBCT scans also confirmed that these shifts were within 1 mm on the same treatment days. Various software issues were discovered and workarounds were proposed using in‐house solutions. For example, the electronic graticule could not be transferred to ACCESS from the OBI software, etc. Conclusions: In‐house validations and implementations were needed to make all pieces of equipment work together correctly. Once the workflow was established, we demonstrated that OBI based IGRT solutions was consistent and clinically acceptable across different vendor's solutions.
The Alpha-1D Is the Predominant Alpha-1-Adrenergic Receptor Subtype in Human Epicardial Coronary Arteries

Objectives The goal was to identify alpha-1-adrenergic receptor (AR) subtypes in human coronary arteries. Background The α1-ARs regulate human coronary blood flow. The α1-ARs exist as 3 molecular subtypes, α1A, α1B, and α1D, and the α1D subtype mediates coronary vasoconstriction in the mouse. However, the α1A is thought to be the only subtype in human coronary arteries. Methods We obtained human epicardial coronary arteries and left ventricular (LV) myocardium from 19 transplant recipients and 6 unused donors (age 19 to 70 years; 68% male; 32% with coronary artery disease). We cultured coronary rings and human coronary smooth muscle cells. We assayed α1- and β-AR subtype messenger ribonucleic acid (mRNA) by quantitative real-time reverse transcription polymerase chain reaction and subtype proteins by radioligand binding and extracellular signal-regulated kinase (ERK) activation. Results The α1D subtype was 85% of total coronary α1-AR mRNA and 75% of total α1-AR protein, and α1D stimulation activated ERK. In contrast, the α1D was low in LV myocardium. Total coronary α1-AR levels were one-third of β-ARs, which were 99% the β2 subtype. Conclusions The α1D subtype is predominant and functional in human epicardial coronary arteries, whereas the α1A and α1B are present at very low levels. This distribution is similar to the mouse, where myocardial α1A- and α1B-ARs mediate beneficial functional responses and coronary α1Ds mediate vasoconstriction. Thus, α1D-selective antagonists might mediate coronary vasodilation, without the negative cardiac effects of nonselective α1-AR antagonists in current use. Furthermore, it could be possible to selectively activate beneficial myocardial α1A- and/or α1B-AR signaling without causing coronary vasoconstriction.
Anatomy of a Concretion: Life, Death, and Burial in the Western Interior Seaway

Concretions are the most characteristic mode of fossil occurrence in the Upper Cretaceous Western Interior of the United States. An in-depth analysis of a single concretion from the upper Campanian Pierre Shale, South Dakota, drawing upon sedimentology, paleontology, shell preservation, degree of encrustation, and geochemistry allows us to determine a time frame for the accumulation and burial of the organisms and the process of cementation and diagenesis of the concretion. The concretion is very fossiliferous and dominated by mollusks. Large ammonites are commonly broken up with pieces missing from the adapical end of the body chamber. This breakage pattern is widely interpreted as evidence of lethal damage, implying introduction into the burial site via predation. In contrast, smaller ammonites are nearly complete and may have died due to smothering in resuspended sediment produced by bottom currents. The concretion is rich in cephalopod jaws, which mostly appear as isolated occurrences, usually deformed, with the calcite covering (aptychus) missing. The preservation of jaws suggests that the organic debris did not remain in the taphonomically active zone for more than a few years. The concretion, thus, represents a time-averaged deposit of organisms derived from the local community. In contrast, host sediments contain fewer fossils, most of which are crushed. Oxygen and carbon isotopic composition of samples in the concretion and the host sediments reveals a two-stage diagenetic history of the concretion. First, cementation probably occurred at shallow burial depths in early diagenesis in association with the decomposition of organic matter and the oxidation of methane. Second, alteration of the shelly material and the formation of calcite crystals filling the empty chambers of ammonites probably occurred during later diagenesis in contact with meteoric water.
Designing enterprise applications that connect employees on the go

This paper describes the process of designing an enterprise application that connects employees, the unique interface challenges, research activities, and subsequent changes to the design. The user-centered design process was driven by three research activities that informed the design in stages. Focus group sessions enabled us to understand requirements, wireframe usability evaluations helped us to validate macro level design decisions, and live prototype testing provided feedback that helped refine the design and validate the interactions. The collective research activities contributed to improved usability for navigation, actions, search, and a hierarchical organization chart. In addition, social networking within the work context was better understood and important concerns were identified. Key changes to the design included a streamlined three-level organization chart, the reduction of icons, and a new layout for search.
TEL-AML1 fusion precedes differentiation to pre-B cells in childhood acute lymphoblastic leukemia

The TEL-AML1 gene fusion results from a karyotypically cryptic t(12;21) translocation, the most common genetic abnormality in pediatric acute lymphoblastic leukemia (ALL). The presence of the TEL-AML1 fusion in utero, its protracted latency to overt leukemia, and secondary loss of the untranslocated TEL suggest it is an initiating event. Sequences of the TEL-AML1 genomic breakpoint and the immunoglobulin heavy chain (IgH) and/or T-cell receptor (TCR) gene rearrangements were characterized in four pediatric pre-B ALL patients. Analysis of these markers in relapsed patients revealed that immunophenotypically and cytogenetically distinct, and clonally unrelated antigen receptor leukemic cell populations harbored the same initiating TEL-AML1 molecular abnormality. Furthermore, TEL-AML1-positive cells persisted during remission even in the absence of detectable clone-specific IgH and TCR markers. We demonstrate that the TEL-AML1 translocation can occur in vivo during B-cell development before rearrangement of the IgH and TCR genes. We propose, in some cases, that the TEL-AML1 translocation occurs in a stem or B progenitor cell, and that recurrent TEL-AML1-positive pre-B ALL represents a de novo-transformed population that retains the same diagnostic initiating event.
The Biggest Problem in Diabetes

An assessment of the big gest problem in diabetes care from the viewpoint of 115 health care profes sionals and 428 diabetic patients was obtained. There was substantial agreement by health pro fes...
CAROTENOID PIGMENTS IN A MUTANT CARDINAL: IMPLICATIONS FOR THE GENETIC AND ENZYMATIC CONTROL MECHANISMS OF CAROTENOID METABOLISM IN BIRDS

Abstract Birds that use carotenoids to color their feathers must ultimately obtain these pigments from the diet, but they are also capable of metabolically transforming dietary carotenoids into alternate forms that they use as plumage colorants. The genetic and enzymatic control mechanisms underlying carotenoid metabolism are poorly understood. We investigated carotenoid pigments present in the feathers of an aberrantly colored yellow Northern Cardinal (Cardinalis cardinalis) to determine how metabolic pathways may have been altered. Normal red cardinals display four primary keto-carotenoids in plumage that are endogenously derived from a series of common food carotenoids. We found that the yellow feathers of this mutant lacked all four of the typical red pigments, and instead contained a yellow dietary carotenoid (lutein) and three yellow metabolic derivatives (3′-dehydrolutein and canary-xanthophylls A and B). Because yellow metabolites appear to be manufactured via a different metabolic process (dehydr...
Johne's Disease in a Free-Ranging White-tailed Deer from Virginia and Subsequent Surveillance for Mycobacterium avium subspecies paratuberculosis

Johne's disease (paratuberculosis) was diagnosed in a 2-yr-old, male, free-ranging white-tailed deer (Odocoileus virginianus) from Fauquier County, Virginia, USA, based on histopathology and culture for Mycobacterium avium subspecies paratuberculosis. Clinical and pathologic findings included emaciation; loss of body fat; chronic diarrhea; severe, chronic, diffuse granulomatous colitis with intrahistiocytic acid-fast bacilli; moderate, chronic granulomatous lymphadenitis with intrahistiocytic acid-fast bacilli; as well as moderate chronic, multifocal, lymphoplasmacytic hepatitis. These findings are consistent with previous reports of Johne's disease in cervids. Subsequent targeted surveillance of 10 emaciated deer with diarrhea, as well as sampling of 72 asymptomatic deer for M. avium subsp. paratuberculosis using culture of multiple tissue types, as well as serology using an enzyme-linked immunosorbent assay (ELISA) optimized for cervid antibody detection, did not reveal any additional cases of infection in this geographic region. To date, this appears to be an isolated case of Johne's disease in a free-ranging white-tailed deer, and infection with the causative agent for Johne's disease appears to be an infrequent occurrence in deer from this region. The origin of infection was most likely domestic ruminants. This is the first report of clinical Johne's disease in a free-ranging white-tailed deer outside of the Florida Keys, USA. Stressors, such as high deer population density and low selenium levels, may have contributed to the development of clinical disease in this case and warrant further investigation.
Mechanical strain regulates syndecan-4 expression and shedding in smooth muscle cells through differential activation of MAP kinase signaling pathways

Syndecan-4 (S4) belongs to a family of transmembrane proteoglycans, acts as a coreceptor for growth factor binding as well as cell-matrix and cell-cell interactions, and is induced in neointimal sm...
An Evaluation of the Effectiveness of Measurement-based Anomaly Detection Techniques

A number of recent studies have proposed measurement based approaches to network traffic analysis. These techniques treat traffic volume and traffic header data as signals or images in order to make analysis feasible. We use trace-driven experiments and compare the performance of different strategies. Our evaluations on real traces reveal differences in the effectiveness of different traffic header data as potential signals for traffic analysis in terms of their detection rates and false alarm rates. Our results show that address distributions and number of flows are better signals than traffic volume for anomaly detection.
In silico analyses of substrate interactions with human serum paraoxonase 1.

Abstract : Human paraoxonase (HuPON1) is a serum enzyme that exhibits a broad spectrum of hydrolytic activities including the hydrolysis of various organophosphates esters, and recently identified lactone substrates. Despite intensive site-directed mutagenesis and other biological studies, the structural basis for the specificity of substrate interactions of HuPON1 remains elusive. In this study, we apply homology modeling, docking, and molecular dynamic (MD) simulations to probe the binding interactions of HuPON1 with representative substrates. The results suggest that the active site of HuPON1 is characterized by two distinct binding regions: the hydrophobic binding site for arylesters/ lactones, and the paraoxon binding site for phosphotriesters. The unique binding modes proposed for each type of substrate reveal a number of key residues governing substrate specificity. The polymorphic residue R/Q192 interacts with the leaving group of paraoxon, suggesting it plays an important role in the proper positioning of this substrate in the active site. MD simulations of the optimal binding complexes show that residue Y71 undergoes an open-closed conformational change upon ligand binding, and forms strong interactions with substrates. Further binding free energy calculations and residual decomposition give a more refined molecular view of the energetics and origin of HuPON1/ substrate interactions. These studies provide a theoretical model of substrate binding and specificity associated with wild type and mutant forms of HuPON1, which can be applied in the rational design of HuPON1 variants as bioscavengers with enhanced catalytic activity.
Differential adaptations in GABAergic and glutamatergic systems during ethanol withdrawal in male and female rats.

Background: There are significant and consistent sex differences in recovery from ethanol withdrawal in our animal model of ethanol dependence. We have also observed significant and varied sex differences in subunit protein levels of γ-aminobutyric acid A (GABAA) and the N-metheyl-D-aspartate subtype of glutamate receptors occurring with ethanol dependence and withdrawal. Considering the major role of these two systems as targets of ethanol, we wanted to explore additional possible mechanisms underlying changes in GABAergic and glutamatergic responses after chronic ethanol exposure. Therefore, the objective of the present study was to examine GABAergic- and glutamatergic-associated proteins at three days of ethanol withdrawal, when female rats appear to have largely recovered but male rats still display robust signs of withdrawal. Methods: Male and female rats were fed 6% ethanol in a nutritionally complete liquid diet for 14 days according to a pair-fed design; withdrawal was initiated by replacement of the diet with chow. At three days of withdrawal, the cerebral cortex and hippocampus were dissected for use in Western blot analysis. The paired design was maintained throughout all experimental procedures. Results: At three days of ethanol withdrawal, we found region-specific and sex-selective alterations in levels of GAD (glutamic acid decarboxylase, GABA synthetic enzyme), GABA and glutamate transporters, and the synapse-associated proteins HSP70, PSD-95, and synaptophysin. There were also several significant differences in transporter function at this time that varied between males and females. Conclusions: Taken together, these findings show differential adaptations of GABAergic and glutamatergic neurotransmission between female and male rats that are associated with withdrawal recovery. This suggests that selective withdrawal-induced neuroadaptations in regulation of these systems’ activities underlie, at least in part, sex differences in withdrawal recovery between male and female rats.
Synthesis and evaluation of a new fluorine-18 labeled rotenoid as a potential PET probe of mitochondrial complex I activity

Fluorine-18 labeled (6aS, 12aS, 5′R)-12-deoxo-6′,7′-dihydro-7′-fluororotenone (F-DDRT), a new potential PET probe of mitochondrial complex I activity, was synthesized. [18F]-DDRT was prepared with good specific activity by nucleophilic displacement with an overall radiochemical yield of 25% (EOB). The uptake of [18F]-DHRT in rat brain and heart was compared with the uptake of another fluorine-18 labeled rotenoid: [18F]-DHRT. In comparison to [18F]-DHRT, the brain and heart retention of [18F]-DDRT were both lower at any point of the study (respectively 0.49 and 2.82 dose/g vs 0.34 and 1.24% dose/g at 60 min post injection). Copyright © 1999 John Wiley & Sons, Ltd.
Planktonic Foraminiferal Indices Common to Lower Pliocene of Southern California and Italy: ABSTRACT

Five planktonic foraminiferal relations common to the lower Pliocene marine record of Italy and southern California are: (1) "Sphaeroidinellopsis" has an upper limit within or near the top of the lower Pliocene; (2) "Sphaeroidinella dehiscens" (Parker and Jones) makes its first appearance within or at the base of the lower Pliocene; (3) Globigerina woodi decoraperta Takayanagi and Saito extends through the lower Pliocene into the middle Pliocene; (4) rare specimens referable to Turborotalia globorotaloidea (Colom), a typical upper Miocene species, continue to occur in the lower Pliocene; and (5) Turborotalia puncticulata (d'Orbigny) appears to be restricted to the lower Pliocene in both areas. End_Page 465------------------------------ Differences between the lower Pliocene planktonic foraminiferal ranges of Italy and southern California include: (1) appearance of Globorotalia crassaformis Galloway and Wissler in the lower Pliocene of California whereas it does not appear until the middle Pliocene in Italy; (2) Turborotalia inflata (d'Orbigny) first appears as a rare member of T. puncticulata populations in the lower Pliocene of southern California whereas it first appears in the upper Pliocene of Italy; and (3) Globigerina pachyderma (Ehrenberg) occurs in the lower Pliocene of both areas; it is dextrally coiled in southern California and probably is dextral in Italy as well. End_of_Article - Last_Page 466------------
Tuning Gene Expression in Yarrowia lipolytica by a Hybrid Promoter Approach

The development of strong and tunable promoter elements is necessary to enable metabolic and pathway engineering applications for any host organism. Here, we have expanded and generalized a hybrid promoter approach to produce libraries of high-expressing, tunable promoters in the nonconventional yeast Yarrowia lipolytica. These synthetic promoters are comprised of two modular components: the enhancer element and the core promoter element. By exploiting this basic promoter architecture, we have overcome native expression limitations and provided a strategy for both increasing the native promoter capacity and producing libraries for tunable gene expression in a cellular system with ill-defined genetic tools. In doing so, this work has created the strongest promoters ever reported for Y. lipolytica. Furthermore, we have characterized these promoters at the single-cell level through the use of a developed fluorescence-based assay as well as at the transcriptional and whole-cell levels. The resulting promoter libraries exhibited a range of more than 400-fold in terms of mRNA levels, and the strongest promoters in this set had 8-fold-higher fluorescence levels than those of typically used endogenous promoters. These results suggest that promoters in Y. lipolytica are enhancer limited and that this limitation can be partially or fully alleviated through the addition of tandem copies of upstream activation sequences (UASs). Finally, this work illustrates that tandem copies of UAS regions can serve as synthetic transcriptional amplifiers that may be generically used to increase the expression levels of promoters.
Characterization of betidamino acid- containing somatostatin and gonadotropin-releasing hormone analogs with electrospray mass spectrometry and tandem mass spectrometry

We report the electrospray mass spectra and tandem mass (MS/MS) spectra of a series of chemically-stable somatostatin (SRIF) and gonadotropin-releasing hormone (GnRH) analogs which incorporate acylated or alkylated/acylated aminoglycine residues (betidamino acids) into their structure. In the case of SRIF, we compare the betidamino acid-containing analogs with the equivalent peptide without the betide-type linkage. We observe significant differences in the fragmentation patterns of each class of compound. We extend this study by comparing a variety of different betidamino acid-containing GnRH analogs to investigate the effects of different acyl groups, chirality and methylation of the side-chain nitrogen of amino glycine on the gas-phase stability of these protonated peptide molecules.
Research and the Doctor of Nursing Practice A Cause for Consternation

This column concerns itself with the issue of research and the doctor of nursing practice. The reports of the Institute of Medicine about patient safety, quality in healthcare, and the restructuring of education of healthcare providers are reviewed. The reasons for the creation of the doctor of nursing practice are illuminated along with the essentials of educating nurses for the role and the position statement on nursing research by the American Association of Colleges of Nursing. Finally, the impact that those with a doctor of nursing practice who conduct nursing research may have on the discipline of nursing is considered.
Selecting Null Distributions When Calculating rwg A Tutorial and Review

rwg is a common metric used to quantify interrater agreement in the organizational sciences. Finn developed rwg but based it on the assumption that raters’ deviations from their true perceptions ar...
Interindividual and Intraindividual Variability in Labetalol Pharmacokinetics

The between-subject and within-subject variability in the pharmacokinetics of labetalol at steady state were determined. Sixteen nonobese normal volunteers (mean age, 27 years) received five different formulations of labetalol orally on five different occasions every 12 hours for five doses. A 7-day washout separated each administration phase. Plasma concentration-time data for labetalol were obtained over the 24-hour period after the fifth dose in each phase. Labetalol concentrations in plasma were measured using high-performance liquid chromatography (HPLC). Pharmacokinetic parameters for each subject after each study phase were estimated. The mean V beta/F, Vdss/F, TBC/F, t1/2 beta, and AUC tau 0 for each subject ranged between 18.1 and 161.9 L/kg, 7.1 and 53.9 L/kg, 1.3 and 5.72 L/hr/kg, 6.9 and 11.0 hours, and 154 and 520 micrograms.hr/L, respectively, indicating large interindividual variability. Considerable intraindividual variability in each of the pharmacokinetic parameters was also observed. These data indicate that a larger number of subjects will be required to detect "significant" differences in the disposition of labetalol.
Medication Errors in Family Practice, in Hospitals and After Discharge from the Hospital An Ethical Analysis

Thousands of medical errors are occurring daily in physician's offices, in hospitals, and even upon discharge from the hospital, leading to unnecessary injury and death and costing billions of dollars. We have a systems approach that has been proven to be tried and true in aviation, nuclear energy and many other industrial settings. Being honest when medical mistakes occur, reporting them to national clearing house, objectively searching for root causes, avoiding the fixing of arbitrary blame, and then, where possible, implementing safeguards to minimize the occurrence of future mistakes, is the best way to enhance patient safety. But until the medical establishment takes medical errors and patient safety more seriously, and until the general public rises up in protest, it is up to the state and federal governments to take the lead in protecting the lives of innocent Americans by creating a public policy.