cssi/SciSciGPT-SciSciNet huggingface dataset:
High Initial Dosing of Olanzapine for Stabilization of Acute Agitation : A Retrospective Case Series

Background:There are several possible dosing strategies for the use of atypical antipsychotics for acute agitation, such as the rapid initial dose escalation protocol (olanzapine) or starting at the maximum recommended dose (aripiprazole). There can be challenges to dose escalation as compared with “loading” patients with an atypical antipsychotic.Objective:To describe an effective loading dose protocol for olanzapine used to enhance control of acute psychotic and manic symptoms.Methods:A retrospective case series was constructed from the records of inpatients treated on an acute psychiatry unit. Records from 8 patients who were diagnosed with bipolar disorder or schizophrenia and who received an initial dose of olanzapine 40 mg for 2 days, 30 mg for 2 days, and 20 mg for 2 days were retrieved and examined. Scores on the Brief Psychiatric Rating Scale (BPRS) and the Young Mania Rating Scale (YMRS) were assigned retrospectively on the basis of chart review.Results:The dosing regimen was associated with ave...
Elastosis of the lamina cribrosa in pseudoexfoliation syndrome with glaucoma.

Background: Pseudoexfoliation syndrome is characterized by the presence of glycoprotein fibers in ocular and extraocular tissues, and often is associated with glaucoma. Pseudoexfoliation material may be associated closely with elastic microfibrillar-associated glycoprotein as well as elastin. Methods: Four optic nerve heads of two patients with pseudoexfoliation syndrome and glaucoma were examined using electron microscopy and immunogold detection of elastin. Optic nerve heads from healthy age-matched individuals and patients with primary open-angle glaucoma were used for comparisons. Results: In all eyes with pseudoexfoliation and glaucoma, there was marked and widespread elastosis in the connective tissue of the lamina cribrosa. Elastotic fibers appeared as large and irregular aggregates of electron-dense material labeled with antielastin antibody. Abundant microfibrils were interspersed in the elastotic aggregates, whereas no typical pseudoexfoliation fibers were observed. In contrast, there were less elastotic fibers in the lamina cribrosa from patients with primary open-angle glaucoma compared with pseudoexfoliation glaucoma. Other changes of extracellular matrix were similar to those observed in primary open-angle glaucoma: decreases in collagen fiber density, presence of basement membranes not associated with cell surfaces, and abundant bundles of microfibrils not labeled with elastin antibody. The elastic fibers appeared normal in other locations within the optic nerves of patients with pseudoexfoliation glaucoma, including in the pial septa and blood vessels of the retrolaminar myelinated optic nerve. Conclusion: The authors' findings demonstrate marked and site-specific elastosis in the lamina cribrosa of patients with pseudoexfoliation syndrome with glaucoma, suggesting an abnormal regulation of elastin synthesis and/or degradation in the optic nerve of patients with this disease.
The Interactive Framing of Play in Adult Conversations.

Drawing upon the theory (developed by Bateson and by Goffman) of play as a metacommunicative frame created interactively, this study examined how adults frame play through their messages and behaviors. Interactants signalled play through such messages as overt invitations, nonverbal cues, abrupt topic changes, and outrageous or put‐on utterances. The nature of these messages led to different types of episodes labelled as play with a partner, play for a partner, and play at a partner. Often the signalling of play is incomplete, or “taken‐for‐granted” by participants. Implications for future research on play, metacommunication, and interpersonal interactions are discussed.
Ultrasound-Assisted Lumbar Puncture in Obese Patients

The use of ultrasound to mark landmarks for diagnostic lumbar puncture has been described in emergency medicine as well as in the anesthesia literature. One of the most difficult scenarios arises when obese patients with a body mass index (BMI) of greater than 30 present to an acute care setting, such as the emergency department or intensive care unit and require diagnostic LP. This article discusses lumbar puncture in patients with a high BMI.
PHENOMENON OF LOCAL SKIN REACTIVITY TO BACTERIAL FILTRATES: FORMATION OF REACTING FACTORS IN VIVO

In this paper there is described a new method for the demonstration of antigen-antibody combination, as follows: A rabbit sensitized a week previously to some animal protein receives a skin-preparatory injection of a potent bacterial filtrate. 24 hours after the skin preparation the rabbit is injected intravenously with the same animal protein. From 4 to 5 hours later there appears severe hemorrhagic necrosis at the prepared skin site. The incidence of positive results is high. A single sensitizing injection and 1 week incubation period are sufficient. The test is highly specific unless repeated sensitizing injections of large doses of antigen are made. The necessary sensitization can be elicited with minute quantities of animal proteins. It is also possible to elicit severe reactions in the prepared skin sites of non-sensitized rabbits upon separate intravenous injections of non-bacterial and bacterial antigens and homologous antibodies (i.e., passive transfer). The relation of the phenomenon of local skin reactivity to bacterial filtrates to various fields of immunology is discussed in the light of the above observations.
“Mrs. His Name”: Women's Preferences For Married Names

Psychologists have long acknowledged the link between names and identity, but little research has studied women's choices about their married names. This study examines the descriptive characteristics of women who plan different choices and women's reasoning behind their choices in a sample of undergraduate women. Women who wish to keep or hyphenate their names have more feminist attitudes, score higher on instrumentality/agency, and are more likely to be immigrants and/or women of color. Content coding of open-ended responses on reasons for name choices showed those who want their husbands' names for themselves and their children most often cited tradition, a denial that names were linked with identity, and union within marriage. Women who want to keep or hyphenate their names mentioned the link between names and identity, professional reasons, and also union within marriage. The two groups often used similar language to explain different choices.
In Situ Processing and Properties of SiC/MoSi2 Nanocomposites

A novel concept for in situ processing of SiC/MoSi2 nanocomposites has been developed that combines the pyrolysis of MoSi2 particles coated with polycarbosilane and subsequent densification by hot pressing. After densification, a uniform dispersion of SiC particles is obtained in the MoSi2 matrix. The strength at both room and elevated temperature is dramatically improved by the processing protocol employed. The average room-temperature flexural strength measured for the SiC/MoSi2 nanocomposite was 760 versus 150 MPa for unreinforced MoSi2. The average 1250°C flexural strength measured for the SiC/MoSi2 nanocomposite was 606 versus 77 MPa for unreinforced MoSi2.
The spacing effect: Consolidation or differential encoding?

Theoretical explanations of the spacing effect fall into two classes: those that attribute the advantage of two spaced presentations over two massed presentations to better consolidation of the first presentation, and those that attribute the advantage to better encoding of the second presentation. This paper reports an experimental test of the two classes of theory. Rather than manipulate spacing, the experiment varied the information processing difficulty of the activity interpolated between two presentations of an item. Consolidation-type theories imply decreasing consolidation with increasing difficulty of the interpolated activity. In fact, recall performance following two presentations separated by a difficult task was found to be slightly but consistently better than performance following two presentations separated by an easy task. The outcome thus favors encoding-type theories.
RADIATION SCATTER AND ITS ATTRIBUTES IN THE CARDIAC CATHETERIZATION LABORATORY

Radiation scatter (RS) in the catheterization laboratory is a function of beam angulation, among other factors. RS is an important determinant of total radiation dose, although has undergone limited clinical study. To model radiation dosimetry during diagnostic catheterization (DC) and percutaneous
5 -dihydroprogesterone influence on ovulation of prepuberal rats.

Administration of 5-alpha-dihydroprogesterone DHP to 30-day-old prepuberal rats 24 or 48 hours after administration of pregnant mares serum gonadotropin (PMSG) stimulated ovulation. When 5-alpha-DHP was administered 51 hours after PMSG stimulation of ovulation was inhibited. This is similar to the action of progesterone. 5-alpha-DHP may have interfered with the release of ovulating hormone (OH) resulting in newer eggs at 72 hours.(Authors modified)
Abstract 223: High-throughput drug discovery against breast cancer stem cells

Proceedings: AACR Annual Meeting 2014; April 5-9, 2014; San Diego, CA The cancer stem cell (CSC) hypothesis postulates that tumors are maintained by a self-renewing CSC population that is also capable of differentiating into non-self renewing cell populations that constitute the bulk of the tumor. Clinically, CSCs are predicted to mediate tumor recurrence after chemotherapy and radiotherapy due to the relative inability of these modalities to effectively target CSCs. Therefore, new therapies that target CSC must be developed and combined with standard therapy to achieve a true cure. Targeting breast CSC represents an attractive avenue for developing therapeutics; however, there are multiple pools of breast CSCs utilizing distinct signaling pathways, such as Wnt/β-catenin & NF-κB. These breast CSC pools are identified using flow cytometry as cells with high expression of aldehyde dehydrogenase (ALDH), CD44+CD24-, or CD90+. We have developed a high-throughput flow cytometry based screen against CD90+ breast CSCs. We screened ∼18,500 small molecules for inhibitors of CD90+ frequency and identified 19 compounds. Here, we will present data examining this compounds against ALDH+, and CD44+CD24- breast CSCs. By identifying compounds with that target multiple pools of breast CSCs, these compounds might be exploited in future drug development endeavors. Citation Format: Sean P. McDermott, Fatou Ndaw, Alexandra Fox, Steve R. Vander Roest, Martha J. Larsen, Max S. Wicha. High-throughput drug discovery against breast cancer stem cells. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 223. doi:10.1158/1538-7445.AM2014-223
Optimal design of electrostatic lenses using integral equation field methods

The integral method of solving Laplace's or Poisson's equation results in a formulation for solution which is suitable for directly calculating the change in the domain potentials due to displacing the domain boundaries. Specifically, the order and locations remain the same for the matrix ∂Φ/∂x i.e., the change in potential per boundary change, which is required for the optimum design problem.
Changing Interracial Evaluations and Behavior: The Effects of a Common Group Identity:

Two studies examined whether developing a common ingroup identity among Blacks and Whites can improve Whites’ interracial evaluations. In Study 1, White participants interacted with a Black or White confederate under conditions designed to produce cognitive representations as fellow group members or as separate individuals. Consistent with the Common Ingroup Identity Model, Whites evaluated Blacks more favorably when they interacted with them as members of the same group than as separate individuals. Study 2, conducted as fans entered a football stadium, revealed that Whites complied more frequently with a Black interviewer’s request to interview them when they shared common university affiliation, relative to when the Black interviewer was affiliated with the opposing team.
Social capital, social currency, and portable assets: The impact of residential mobility on exchanges of social support

We examined the impact of physical distance on mobilized social capital resources. Social capital theory assumes that physical proximity and residential stability are prerequisites to social capital assets. We tested these assumptions using a two-wave panel sample from the National Survey of Families and Households consisting of respondents who experienced residential moves between waves. We found local duration since the last move to be beneficial for involvement in social exchanges. Mobility distance was related to deficits for some exchanges but not for others. Rather than a simple dichotomy between material resources that require proximity and nonmaterial resources that do not, we found that emotional and financial support are not affected by mobility distance but that tangible favors and companionship are affected negatively. Although kin exchanges are negatively affected by distant and recent mobility, nonkin exchanges are more extensive for respondents whose kin ties are more distant, suggesting a process of substitutability whereby nonkin may replace kin in the network. Our findings confirm the assumption of social capital theory about distance. They also point to the importance of adding the dimension of distance to exchange theory. Our study demonstrates that place has not lost all relevance in our highly technological postmodern society.
The viscosity of superheated steam up to 270°C

Abstract The paper describes a series of measurements on the viscosity of superheated steam obtained with the aid of an oscillating-disk viscometer. Measurements were made along the following four approximate isotherms: 136 ° C, 168 ° C, 198 ° C and 234 ° C, made about atmospheric to saturation pressure. It is considered that the results are accurate to ± 0.5%. The measurements show excellent agreement with an earlier series obtained by J. R. Moszynski and the combined results were used to provide a tabulation for superheated steam up to 270 ° C. The extrapolated results for 1 atm show good agreement with the recent measurements due to A. S. Shifrin. The results presented in the paper reveal an anomaly in that the pressure coefficient of viscosity is negative, decreasing with increasing temperature down to zero at 270 ° C.
Biophysical synaptic dynamics in an analog VLSI network of hodgkin-huxley neurons

We study synaptic dynamics in a biophysical network of four coupled spiking neurons implemented in an analog VLSI silicon microchip. The four neurons implement a generalized Hodgkin-Huxley model with individually configurable rate-based kinetics of opening and closing of Na+ and K+ ion channels. The twelve synapses implement a rate-based first-order kinetic model of neurotransmitter and receptor dynamics, accounting for NMDA and non-NMDA type chemical synapses. The implemented models on the chip are fully configurable by 384 parameters accounting for conductances, reversal potentials, and pre/post-synaptic voltage-dependence of the channel kinetics. We describe the models and present experimental results from the chip characterizing single neuron dynamics, single synapse dynamics, and multi-neuron network dynamics showing phase-locking behavior as a function of synaptic coupling strength. The 3mm × 3mm microchip consumes 1.29 mW power making it promising for applications including neuromorphic modeling and neural prostheses.
Hemispheric differences in the interference among components of compound gratings

The relationship between local/global and high/low spatial-frequency processing in hemispheric asymmetries was explored. Subjects were required to judge the orientation of a high- or low-spatial-frequency component of a compound grating presented in the left visual field (LVF) or right visual field (RVF). In Experiment 1, attention was focused on one or the other component. A signal detection analysis indicated that sensitivity (d′) to the high-spatial-frequency target was reduced more by the presence of the low-spatial-frequency component when both were presented in the LVF rather than in the RVF. In Experiment 2, subjects determined whether a target orientation was present, independent of spatial frequency at only a single level (i.e., at the high- or low-spatial-frequency level), as opposed to both or neither level. An RVF/LH (left hemisphere) advantage was found when the decision was based on the orientation of the high-frequency component. The asymmetrical influence of visual field of presentation and spatial frequency upon sensitivity is discussed in terms of hemispheric differences in the magnitude of inhibition between spatial-frequency channels and in the role of transient channel activity to capture and direct higher order attentional processes.
Aqueous quenched asymmetric polysulfone hollow fibers prepared by dry/wet phase separation

Abstract A dry/wet phase separation process has been applied to a dry/wet spinning process to prepare asymmetric polysulfone hollow fibers for gas separations. A spinning solution consisting of tetrahydrofuran as a volatile solvent, dimethylacetamide as a less volatile solvent, and ethanol as a nonsolvent was used to induce phase separation in nascent hollow fiber membranes prior to their coagulation in water. Statistical experimental designs were used to optimize the permeation properties of these fibers which showed essentially defect-free selective skin layers with thicknesses of t 1,200 A (αO2/N2=5.8, (P/L)O2=8.8 GPU, o.d.=580 μm). Scanning electron photomicrographs revealed many noncircular distortions in the hollow fiber lumens which appeared more prevalent at low draw ratios and when higher “water-activity” bore fluids were used. The influence of water activity in the bore fluid was investigated in detail with both salt/water and solvent/water mixtures.
1-Soliton solution of the generalized Zakharov equation in plasmas by He's variational principle

This paper obtains the 1-soliton solution to Zakharov equation with power law and dual-power law nonlinearities. The He's variational principle is used to carry out the integration of this equation.
Like subject verbs and causal clauses in English

Perlmutter claimed (Perlmutter, 1968) that the like subject constraint in English is a deep structure constraint. Apart from being a contribution to a theory of filtering devices in natural languages, this claim is of interest because it is based on the assignment of abstract deep structures containing causal clauses which do not appear in surface structure. For example, Perlmutter proposed deriving the sentence: (1) ( = (7)) I tried to be arrested. from the deep structures: rather than from the more conservative: (3) ( = (9)) I tried [Pro arrest I] Like other proposed abstract deep structures, (2) brings out the meaning of the sentence; it predicts paraphrase relations between (1) and the sentences: Perlmutter presented independent evidence for this analysis, but he also used it to explain away what would otherwise have been counterexample to the claim that the like subject constraint holds over deep structures (the ‘deep subject hypothesis’).
Epilepsy associated with supratentorial brain tumors under 3 years of life.

Summary Objective To investigate the clinical features and outcome of epilepsy in children under 3 years of age with supratentorial brain tumors. Methods Patients under 3 years with primary supratentorial hemispheric brain tumors were collected during a 10-year period through a database including demographic and clinical features, neuroimaging, tumor location, developmental outcome, pharmacological and surgical treatment, and tumor histology. Postoperative outcome was assessed according to Engel classification. Results Among 28 children evaluated, twenty (71.4%) suffered from epilepsy. Mean age at seizure onset was 18.7 months (range: 1–60). In fifteen (75%) children, epilepsy was an early manifestation or the presenting symptom of the tumor; seizures were focal in 8 (53.3%) and generalized in 7 (46.7%) individuals. Three (15%) children presented with an epileptic encephalopathy and continuous spike-waves during sleep. Of the five children with epilepsy onset after surgery, four had focal seizures. Post-surgical follow-up ranged from 4 to 10 years (mean: 7.6±3.74). The outcome of epilepsy was generally good, with most children (76.4%) being seizure free (Engel I) or showing >90% improvement in seizure frequency (Engel II) after surgery. However, in about 20% of the cases, epilepsy persisted despite surgery and different AEDs regimen. Best epilepsy outcome was observed in patients with low-grade tumors ( p p Conclusions Epilepsy is a common and early symptom in infants with brain tumors. Its outcome is negatively influenced by high tumor malignancy and by the persistence of neurological deficits after surgery. Treatment of these patients needs a multidisciplinary approach.
How apoptosis got the immune system in shape

The discovery that apoptosis is an integral component of normal development has facilitated the widespread recognition that cell death is not at all inimical to life. For much of our lifetime the body maintains a cellular homeostasis persisting until, ultimately, it is broken during the aging process. However, unlike the body as a whole, fluctuations at any age in this cellular balance are frequent in the immune system, which responds to infections via massive clonal expansions and elimination of reactive T and B cells. Moreover, cell death also plays a key, and essential, role in the education of immune cells in the thymus and the bone marrow, where autoreactive cells are eliminated, thereby establishing tolerance to self tissues. Furthermore, the mechanism by which cytotoxic T and NK cells kill virus infected or transformed target cells is by inducing apoptotic cell death. Thus, cell death, and in particular apoptosis, is an integral facet of almost all aspects of immune function. Failure to execute apoptosis appropriately has dire consequences leading to the development of autoimmune disease and malignant growth. This narration provides a historical overview of the impact that the discovery of apoptosis had on the understanding of the function of the immune system.
After the child dies.

The parents of a child who dies feel the emotions of shock, mourning, and confusion as they slowly come to accept the finality of the child's death. In contemporary America they frequently feel isolated and abandoned. The individuals and institutions that were sources of emotional support in the period immediately after the child's death are no longer available after a few weeks or months. This is due to several factors: (1) American society is very mobile and the nuclear family often does not have the emotional support of the stable, extended family. (2) Children die less frequently today than they did in the past. In fact, it is almost a unique event. As a consequence, the parents of the dead child have less opportunity to share their feelings with other adults and the community at large. (3) There appears to be a misconception held by the general population that the mourning process and emotional confusion terminate after an interval of a few weeks or months. These factors were influential in motivating a number of parents who had lost children to organize a group which meets bi-monthly. The group is openended and nothing said is out of place. The parents have been very helpful to each other in diminishing feelings of isolation, concerns about “strange” thoughts, and feelings of hopeless depression. Requests for information on how to form such a group have come from a number of communities in various parts of the country.
Preparation of phosphorus oxynitride glasses

Abstract The preparation of oxynitride glass by melting sodium metaphosphate in anhydrous ammonia is described. Glasses containing up to ≈ 12 wt% nitrogen were prepared with the nitrogen content depending upon the melting temperature, time, and ammonia flow rate through the furnace. Nitriding the NaPO 3 starting glass decreased the dissolution rate in water and thermal expansion coefficient while increasing the dilatometric softening temperature, glass transition temperature, refractive index, and microhardness. Oxynitride glasses were considerably more difficult to crystallize than the starting NaPO 3 glass. Models for nitrogen dissolution are used to calculate the glass composition from the measured weight loss and analyzed nitrogen content.
Gauge-independent thermal β function in Yang-Mills theory via the pinch technique

Abstract It is proposed to use the pinch technique to obtain the gauge-independent thermal β function β T in a hot Yang-Mills gas. Calculations of β T are shown detail at one-loop level in two different gauges, (i) the background field method with an arbitrary gauge parameter and (ii) the Coulomb gauge. When the pinch contributions to the gluon self-energy are included, the same result is derived for β T in both cases.
Use of solid-state 13C NMR in structural studies of humic acids and humin from Holocene sediments☆

Abstract 13C NMR spectra of solid humic substances in Holocene sediments have been obtained using cross polarization with magic-angle sample spinning techniques. The results demonstrate that this technique holds great promise for structural characterizations of complex macromolecular substances such as humin and humic acids. Quantifiable distinctions can be made between structural features of aquatic and terrestrial humic substances. The aliphatic carbons of the humic substances are dominant components suggestive of input from lipid-like materials. An interesting resemblance is also noted between terrestrial humic acid and humin spectra.
BCS theory of superconductivity: it is time to question its validity

The time-tested Bardeen–Cooper–Schrieffer (BCS) theory of superconductivity is generally accepted to be the correct theory of conventional superconductivity by physicists and, by extension, by the world at large. There are, however, an increasing number of 'red flags' that strongly suggest the possibility that BCS theory may be fundamentally flawed. An ever-growing number of superconductors are being classified as 'unconventional', not described by the conventional BCS theory and each requiring a different physical mechanism. In addition, I argue that BCS theory is unable to explain the Meissner effect, the most fundamental property of superconductors. There are several other phenomena in superconductors for which BCS theory provides no explanation. Furthermore, BCS theory has proven unable to predict any new superconducting compounds. This paper suggests the possibility that BCS theory itself as the theory of 'conventional' superconductivity may require a fundamental overhaul. I outline an alternative to conventional BCS theory proposed to apply to all superconductors, 'conventional' as well as 'unconventional', that offers an explanation for the Meissner effect as well as for other puzzles and provides clear guidelines in the search for new high temperature superconductors.
The Dielectric Function of Silver Nanoparticle Langmuir Monolayers Compressed through the Metal Insulator Transition

Algorithms and experimental techniques for extracting the complex dielectric function of thin films (monolayers and bilayers) of quantum dots are developed. The algorithms are based on a combination of the so-called Newton−Raphson method, used in conjunction with a Kramers−Kronig analysis, and are used to analyze normal-incidence reflectance and transmission measurements of organically passivated silver quantum dot Langmuir monolayers. Single, unambiguous solutions to the dielectric function were determined for several particle monolayers and at various stages of compression. A transition of the quantum dot superlattice from the insulating to a metallic state was observed. When a monolayer of 6-nm-diameter Ag nanocrystals is compressed to an interparticle separation distance of ∼8−9 A, a negative-valued featureless component of the real part of the dielectric function is detected. This indicates the onset of Drude-like behavior that is characteristic of a metallic film. The impact of superlattice disorder...
Monotone versus positive

In connection with the least fixed point operator the following question was raised: Suppose that a first-order formula P(P) is (semantically) monotone in a predicate symbol P on finite structures. Is P(P) necessarily equivalent on finite structures to a first-order formula with only positive occurrences of P? In this paper, this question is answered negatively. Moreover, the counterexample naturally gives a uniform sequence of constant-depth, polynomial-size, monotone Boolean circuits that is not equivalent to any (however nonuniform) sequence of constant-depth, polynomial-size, positive Boolean circuits.
Use of the concentration gradient diffusion assay (Etest) for susceptibility testing of anaerobes, fungi, and Mycobacterium spp.

Abstract The concentration gradient diffusion assay (Etest) is an alternative to agar disk diffusion and broth dilution methods for performing in vitro susceptibility testing of bacterial and fungal isolates. Since its introduction in 1988, many clinical microbiology laboratories have chosen this method as their primary susceptibility testing method for organisms such as Streptococcus pneumoniae , other more fastidious isolates, or those that require limited drug testing. A sizable literature has accumulated about the use of the concentration diffusion method for susceptibility testing anaerobic bacteria, Mycobacterium spp., and fungi. The Etest is also a less laborious method than broth microdilution for obtaining MIC values. These applications will be addressed and references given to provide the reader with information on additional uses of this method.
Economic Implications of Adding One Therapist to a Practice

Comparisons of time, productivity, revenue, costs, and income for a dentist working with two chairside assistants, or a dentist working with one therapist and three chairside assistants were made in this analysis of a surrogate private practice. Computations show that a team composed of a dentist, a therapist, and three chairside assistants can produce 26% more services than a dentist and two chairside assistants can provide. The income of a dentist grossing more than $120,000 can be increased by 37% if one therapist and one chairside assistant are added to the staff and sufficient patient demand exists.
Allosteric Regulation of Protein Kinase Enzymes via an Electrostatic Switch that Modulates Active Site Dynamics

Protein kinase (PK) enzymes are a large family of signaling proteins that play a central role in signal transduction pathways. Robust regulation of their catalytic activity is critical, and many oncogenes harbor mutations that result in misregulated PK activity. The chemical basis for how some PK regulatory factors ultimately affect the rate of chemistry is still not completely understood. We have identified a long-range electrostatic switch that we believe is used by allosteric PK regulatory factors to modulate the rate of chemistry by tuning active-site dynamics.We applied a combination of crystallography, kinetics, and molecular dynamics to determine the chemical kinetic basis for how this electrostatic switch, toggled by regulatory subunit binding, affects each step of catalysis by CDK2 kinase. We engineered point mutants to deconstruct the kinetic, dynamic, and thermodynamic consequences of the switch. We also evaluated other PKs and find that, although it has evolved to be triggered in different ways by diverse PK regulatory factors, the mechanics of this switch can be conserved.We demonstrate that a key component of the switch is that it affects a significant change in the electrostatic potential within the ATP∗Mg binding site of the enzyme. This electrostatic effect is propagated through the low-dielectric protein interior and directly affects the two dominant rate-determining steps of catalysis: attenuating both the recruitment of catalytically essential Mg cofactors (affecting both kcat and KM) as well as the release of the ADP product.Conclusion: We present a chemical hypothesis that provides a mechanistic explanation for one way that a large-scale conformation transition, observed in diverse PK family members, is able to significantly affect the rate of chemistry by acting at a distance from the active site.
Neurofilament phosphorylation in the axonless horizontal cells of rat retina

Axonless horizontal cells in the outer plexiform layer of rat retina were studied with 19 monoclonal antibodies reacting with phosphorylated and non-phosphorylated epitopes of the two high molecular weight neurofilament proteins (NF 150K and NF 200K). With 6 antibodies, immunoreactivity was confined to the nerve fiber layer on the inner surface of the retina. Horizontal cells were not stained. Four antibodies in this group were axon-specific, while the remaining two stained motor and sensory neuron perikarya in rat spinal cord and dorsal root ganglia, respectively. Of the 13 antibodies which stained horizontal cells, 11 reacted with phosphorylated epitopes and failed to decorate motor neuron perikarya in the spinal cord, while in dorsal root ganglia, they stained a subpopulation of sensory neurons.
Empennage/afterbody integration for single and twin-engine fighter aircraft

An extensive experimental program to determine the effects of empennage surfaces on single and twin-engine afterbody/nozzle drag has been conducted by the Propulsion Aerodynamics Branch at the NASA Langley Research Center. Empennage interference drag was obtained by using experimental values of afterbody/nozzle drag and computed values of empennage drag. The effects of tail location, span, number (single versus twin), toe angle, cant angle, camber and root chord length are discussed. The magnitude of empennage interference drag on single and twin engine configurations is examined.
Optimal design of LAN-WAN internetworks: an approach using simulated annealing

This paper addresses the problem of designing LAN-WAN (Local Area Network, Wide Area Network) computer networks with transparent bridges. Bridges are high performance devices that are used to interconnect LANs at the MAC (Medium Access Control) level in the protocol hierarchy. LANs in remote areas are connected by leased telecommunications lines such as T1 and DDS. A requirement of transparent bridges is that networks must be configured in a spanning tree topology. We have developed mathematical models of LAN-WAN networks and formulated an optimization problem. This problem is a nonconvex, nonlinear, mixed integer program. A simulated annealing algorithm is proposed. The algorithm generates sequences of neighboring spanning trees and evaluates design constraints based on maximum flow, bridge capacity, and end-to-end delay. As the annealing temperature parameter is lowered the algorithm moves towards the global optimal solution. Experimental results have shown that LAN-WAN designs using simulated annealing are better than 99.99% of all feasible designs.
Role of Interleukin-6 in Mortality from and Physiologic Response to Sepsis

Previous studies have suggested that interleukin-6 (IL-6) serves as both a marker and a mediator for the severity of sepsis. We tested whether interleukin 6 knockout (IL-6KO) mice were more susceptible to sepsis mortality induced by cecal ligation and puncture. IL-6KO and wild-type (WT) mice were subjected to increasing degrees of sepsis severity. Physiologic support was given with fluids and appropriate antibiotics. Plasma IL-6 levels were determined 6 h after the onset of sepsis, and a complete hematologic profile was performed on day 2. As expected, increasing sepsis severity resulted in greater and more rapid mortality. However, the mortality was nearly identical in the IL-6KO and WT mice. All WT septic mice had high plasma levels of IL-6 6 h after the onset of sepsis, while IL-6KO were near or below the lower limit of detection. Among the WT mice, mortality was significantly higher in mice with plasma IL-6 >3,000 pg/ml. Both IL-6KO and WT mice destined to die in the early stages of sepsis had substantial and nearly identical weight gain in the first 24 h. However, at later stages the WT mice had significantly greater weight loss than the KO mice. The KO mice failed to develop the characteristic hypothermia within the first 24 h of severe sepsis routinely observed in the WT mice. These data demonstrate that IL-6 serves as a marker of disease severity in sepsis and does modulate some physiologic responses, but complete lack of IL-6 does not does not alter mortality due to sepsis.
“—ing” Project: Encouraging Cohesion in Small Groups

Objective: To encourage cohesiveness in small groups at the beginning of the semester Course: Small Group or other courses with a group component
An Educational Interactive Program to Illustrate Equipotential Nlumerical Solution Procedures

An interactive and graphical computer program implemented in a personal computer environment is discussed. It is designed to allow students to conveniently study the electrical equipotential lines of various types of geometries found in high-voltage installations. The program uses an interactive, graphical user interface to allow students to draw the geometries to be studied directly on the display; the same display is then used to provide a visual output for the equipotential lines as computed by the program. The numerical solution procedures implemented in the program as well as the user interfaces are reviewed. A computational example is discussed along with the required hardware and software environments. >
Evaluation of vancomycin and daptomycin against methicillin-resistant Staphylococcus aureus and heterogeneously vancomycin-intermediate S. aureus in an in vitro pharmacokinetic/pharmacodynamic model with simulated endocardial vegetations

Objectives: Glycopeptides have historically been the drugs of choice for the treatment of infections caused by methicillin-resistant Staphylococcus aureus (MRSA). However, the continued selective pressure has led to the emergence of non-susceptible strains including heterogeneously vancomycin-intermediate S. aureus (hVISA). Infections with hVISA have been associated with poor outcomes including vancomycin treatment failures. The objective of this study was to evaluate vancomycin and daptomycin against vancomycin-susceptible MRSA and hVISA in a pharmacokinetic/pharmacodynamic (PK/PD) model with simulated endocardial vegetations. Methods: Six clinical isolates obtained from patients at the Detroit Medical Center were used: MRSA 494, MRSA 67, hVISA R1720, hVISS R2295, hVISA R3640 and hVISA R1629. All heteroresistant strains were confirmed by a population analysis profile ratio, with Mu3 as a control strain. Vancomycin regimens of 1 g every 12 h and 2 g every 12 h and daptomycin regimens of 6, 10 and 12 mg/kg daily were utilized in a PK/PD model over 72 h. Results: Against MRSA isolates, vancomycin displayed minimal activity and minimal-to-no activity against hVISA. In general, the use of high dose vancomycin over standard dose vancomycin did not improve activity except against one of six isolates (MRSA 494). Daptomycin was bactericidal against both MRSA and hVISA isolates, although the rate of kill was slower against hVISA. Conclusions: Overall, daptomycin achieved rapid and effective kill against both MRSA and hVISA while vancomycin displayed slow and minimal kill against MRSA and minimal-to-no activity against hVISA, regardless of high dose exposure.
A choice theory analysis of similarity judgments.

The selection of one of several stimuli as most similar to a reference stimulus is assumed to satisfy a choice axiom that permits assigning ratio scale values to each variable-reference stimuli pair. The logarithm of this scale is treated as a distance measure, leading to the following testable conclusions about the pairwise choice probabilities as the reference stimulus is varied. First, the plot is a symmetrically truncated ogive with horizontal tails. Second, if two pairs of choice stimuli have the same midpoint, the ogive of one pair is part of the ogive of the other. In terms of this model, the hysteresis and midpoint displacement effects in the method of bisection are discussed, and relations with Coombs' unfolding techniques are explored.
Changing relative roles of hepatitis B and C viruses in the aetiology of hepatocellular carcinoma in Greece. Epidemiological and clinical observations

Chronic infection with hepatitis B virus (HBV) has been reported in two-thirds of cases of hepatocellular carcinoma (HCC) in Greece from 1973 to 1995, while chronic hepatitis C virus (HCV) infection in 10% of them. We studied the roles of HBV and HCV in HCC in Greece between 1996 and 2000 compared with the past, and possible differences in clinical and laboratory characteristics of HBV- and HCV-related HCC. Complete clinical and laboratory data from 306 patients with HCC, diagnosed from January 1996 to December 2000, were analyzed. Chronic HBV and HCV infection were detected in 52.3 and 21.6% of the patients, respectively. The ratio of HBV- to HCV-related HCC was 2.42. Compared with the data prior to 1996, there was a 101.8% increase in the relative frequency of HCV (P < 0.0001) and an 11.8% decrease in that of HBV (P = 0.033), with a -56.3% change in the ratio of HBV- to HCV-related HCC cases. Statistically significant differences in the male/female ratio, median age and frequency of multifocal lesions were found in HBV- vs HCV-related HCC. Although HBV still represents the major aetiological factor of HCC in Greece, its role has significantly decreased in the last 5 years, while a more significant increase has occurred in HCV-related HCC. The two aetiological types of HCC differ in Greece in demographic, epidemiological and other features.
Ermüdungsprobleme geschweißter Verbindungen

Ausgehend vom gegenwartigen Stand der Technik werden die fur das Ermudungsverhalten von Schweisverbindungen masgebenden Faktoren zusammengefast. Dann wird diskutiert, wie sich die Verbindungen in Guteklassen oder Qualitatsstufen unterteilen lassen. Die Bedeutung der Schweisfehler fur die Ermudungsfestigkeit wird erlautert. Die Fehler werden unterteilt, und es wird gezeigt, wie man unter Verwendung der Bruchmechanik eine Verallgemeinerung der Versuchsresultate zu erreichen versucht. Auf diesem Wege ist es evtl. moglich, mit der Zeit objektive Beurteilungskriterien abzuleiten.
Characterization of nirV and a gene encoding a novel pseudoazurin in Rhodobacter sphaeroides 2.4.3.

Sequencing of the region flanking nirK, the gene encoding the copper-containing nitrite reductase in Rhodobacter sphaeroides 2.4.3, has identified two genes whose products could potentially be involved in nitrite reductase expression and activity. One of the genes has been designated nirV. Putative nirV orthologues are found in other denitrifiers, where they are also located downstream of the structural gene for nitrite reductase. The nirV in 2.4.3 is apparently cotranscribed with nirK. Inactivation of nirV had no effect on cell growth, or on nitrite reductase expression or activity. Downstream of nirV and divergently transcribed is a gene, designated ppaZ, encoding a protein with significant similarity to pseudoazurins from other denitrifiers. However, three of the four residues required for binding of the type I copper centre are not conserved in the deduced sequence of the protein in 2.4.3. ppaZ is expressed only when oxygen becomes limiting. ppaZ expression is dependent on both FnrL and NnrR, and a putative binding site for these proteins has been identified. Expression of ppaZ is also dependent on the two-component PrrB/PrrA system. Inactivation of ppaZ had no significant effect on cell growth or on nitrite reductase expression or activity. Expression of a maltose-binding protein–PpaZ fusion indicated that the protein could not bind copper. Examination of the genome of the related bacterium R. sphaeroides 2.4.1 revealed that it encodes ppaZ but not nirV and evidence is presented suggesting that a common ancestor of 2.4.3 and 2.4.1 had both nitrite and nitric oxide reductase activity but as the strains diverged 2.4.1 lost nirK and nirV, making it incapable of nitrite reduction.
Methods for optimizing statistical analyses in pharmacogenomics research

Pharmacogenomics is a rapidly developing sector of human genetics research with arguably the highest potential for immediate benefit. There is a considerable body of evidence demonstrating that variability in drug-treatment response can be explained in part by genetic variation. Subsequently, much research has ensued and is ongoing to identify genetic variants associated with drug-response phenotypes. To reap the full benefits of the data we collect we must give careful consideration to the study population under investigation, the phenotype being examined and the statistical methodology used in data analysis. Here, we discuss principles of study design and optimizing statistical methods for pharmacogenomic studies when the outcome of interest is a continuous measure. We review traditional hypothesis testing procedures, as well as novel approaches that may be capable of accounting for more variance in a quantitative pharmacogenomic trait. We give examples of studies that have employed the analytical metho...
Temporal and Spatial Interpolation of the Standardized Precipitation Index for Computational Efficiency in the Dynamic Drought Index Tool

AbstractThe feasibility of interpolating gamma-distribution parameters between different precipitation accumulation intervals (durations) is statistically evaluated. The interpolation of these parameters for a specific accumulation interval, but ending on different dates, is similarly assessed. Such interpolation increases the computational efficiency of drought-monitoring tools that require calculation of the standardized precipitation index (SPI) for any user-specified accumulation period on any given day. Spatial interpolation of the distribution parameters is also assessed. Given a 60-yr period of record, few statistically significant differences were found between gamma-distribution percentiles interpolated between fixed base durations and those computed directly. Shorter interpolation intervals (generally 30 days) were required for the shortest (e.g., 30 days) durations, whereas interpolation over periods of as long as 180 days could be used for the longest (between 360 and 720 days) durations. Inte...
Pseudolymphoma with mycosis fungoides manifestations, hyperresponsiveness to diphenylhydantoin, and lymphocyte disregulation

Three patients receiving diphenylhydantoin (DPH) were seen with a reversible process suggesting mycosis fungoides. Clinical and laboratory manifestations included generalized pruritic exfoliative erythroderma, eosinophilia, lymphadenopathy, hepatosplenomegaly, circulating Sezary cells, epidermal Pautrier's microabscesses on skin biopsy, and moderate liver dysfunction. Studies of the distribution and function of the various lymphocyte subpopulations from these patients showed: (1) an increase in the relative and absolute number of T lymphocytes (85--92%); (2) significant stimulation of lymphocyte-blastic transformation by DPH and low response to pokeweed mitogen stimulation; (3) the impaired ability of T gamma lymphocytes to suppress B-cell differentiation and immunoglobulin production. With only one exception, 15 symptom-free patients on DPH showed none of these abnormalities. The clinical manifestations and immunologic abnormalities of patients with this pseudo mycosis fungoides syndrome remitted three to four weeks after DPH administration was discontinued. The proliferation of T lymphocytes and the inhibition of the function of T gamma-suppressor lymphocytes noted in these patients may be significant to the development of other types of pseudolymphoma and to that of true lymphoma.