cssi/SciSciGPT-SciSciNet huggingface dataset:
Human Laboratory Paradigms in Alcohol Research

Human laboratory studies have a long and rich history in the field of alcoholism. Human laboratory studies have allowed for advances in alcohol research in a variety of ways, including elucidating of the neurobehavioral mechanisms of risk, identifying phenotypically distinct sub-types of alcohol users, investigating of candidate genes underlying experimental phenotypes for alcoholism, and testing mechanisms of action of alcoholism pharmacotherapies on clinically-relevant translational phenotypes, such as persons exhibiting positive-like alcohol effects or alcohol craving. Importantly, the field of human laboratory studies in addiction has progressed rapidly over the past decade and has built upon earlier findings of alcohol's neuropharmacological effects to advancing translational research on alcoholism etiology and treatment. To that end, the new generation of human laboratory studies has focused on applying new methodologies, further refining alcoholism phenotypes, and translating these findings to studies of alcoholism genetics, medication development, and pharmacogenetics. The combination of experimental laboratory approaches with recent developments in neuroscience and pharmacology has been particularly fruitful in furthering our understanding of the impact of individual differences in alcoholism risk and in treatment response. This review of the literature focuses on human laboratory studies of subjective intoxication, alcohol craving, anxiety, and behavioral economics. Each section discusses opportunities for phenotype refinement under laboratory conditions, as well as its application to translational science of alcoholism. A summary and recommendations for future research are also provided.
Birdshot retinochoroidopathy associated with HLA-A29 antigen and immune responsiveness to retinal S-antigen.

Abstract Antigen HLA-A29 was present in 16 of 20 patients (80%) with birdshot retinochoroidopathy, but only in 31 of 418 controls (7.4%) (P
Formal anonymity models for efficient privacy-preserving joins

Organizations, such as federally-funded medical research centers, must share de-identified data on their consumers to publicly accessible repositories to adhere to regulatory requirements. Many repositories are managed by third-parties and it is often unknown if records received from disparate organizations correspond to the same individual. Failure to resolve this issue can lead to biased (e.g., double counting of identical records) and underpowered (e.g., unlinked records of different data types) investigations. In this paper, we present a secure multiparty computation protocol that enables record joins via consumers' encrypted identifiers. Our solution is more practical than prior secure join models in that data holders need to interact with the third party one time per data submission. Though technically feasible, the speed of the basic protocol scales quadratically with the number of records. Thus, we introduce an extended version of our protocol in which data holders append k-anonymous features of their consumers to their encrypted submissions. These features facilitate a more efficient join computation, while providing a formal guarantee that each record is linkable to no less than k individuals in the union of all organizations' consumers. Beyond a theoretical treatment of the problem, we provide an extensive experimental investigation with data derived from the US Census to illustrate the significant gains in efficiency such an approach can achieve.
THE X-RAY PROPERTIES OF NORMAL GALAXIES.

X-ray observations with the Einstein satellite have shown that normal galaxies of all morphological types are spatially extended sources of X-ray emission with luminosities in the range of L(x) of about 10 to the 39th to 10 to the 41st erg/s. Although this is only a small fraction of the total energy output of a normal galaxy, X-ray observations are uniquely suited to study phenomena that are otherwise elusive. In X-rays one can study directly the end products of stellar evolution (SNRs and compact remnants). X-ray observations have led to the discovery of gaseous outflows linked to starburst nuclear activity in spiral galaxies and to the detection of a hot interstellar medium in early-type galaxies. Through X-ray observations it is possible to set constraints on structural galaxy parameters, such as the mass of elliptical galaxies, and perhaps get new insight on the origin of cosmic rays and the properties of the magnetic fields of spiral galaxies.
Chlorpromazine in pediatric surgery

Summary Chlorpromazine was administered as part of the preoperative medication given to one hundred children. Apprehension was markedly reduced and induction of anesthesia was easier in all cases. Furthermore, less anesthetic was required to produce adequate relaxation. There was some diminution of salivary secretions, and repeated blood pressure determinations revealed no hypotensive reactions in the group. Bleeding during surgery was reduced. Postoperative nausea and vomiting were almost completely eradicated, and the recovery period was calmer. In the seventy-five tonsillectomy and adenoidectomy operations included there was almost complete elimination of the restlessness and apprehension usually following such surgery.
Computed tomography (CT) of fractures of the ankle and foot: correlating fracture patterns with the presence of tenosynovial fat: Tenosynovial fat in ankle and foot fractures

Abstract Purpose To correlate ankle and foot fracture patterns with the presence of tenosynovial fat on computed tomography (CT). Materials and Methods In this retrospective, cross-sectional, observation study, two blinded musculoskeletal radiologists independently reviewed 89 CT scans of patients with ankle or foot fractures and recorded the presence of fat about Henry’s knot, tibialis posterior tendon, and peroneus longus tendon. Results The agreement between the two readers ranged from excellent to substantial. Sixteen to 23 percent of fractures were associated with tenosynovial fat. Conclusions The finding of tenosynovial fat following ankle or foot trauma warrants a closer search for a fracture.
A projection operator technique for determining selection rules

Abstract A projection operator method is described for obtaining selection rules. Explicit use is made of the representing matrices of the irreducible representations. Except for the one dimensional irreducible representations, this method provides for a more detailed examination of the selection rules than is provided via the character system. The method is of particular importance for investigating localized electronic energy levels in solids.
Composing a peaceful classroom through poetry writing

Poetry writing as an authentic means of composing a peaceful classroom is the focus of this article. Formula poems are described, illustrated, and discussed. Promoting peace through poetry writing in the classroom is one of the ways teachers can have a positive lifelong impact on students.
Harsanyi’s critical rule utilitarianism

In his recent book,Rational Behaviour and Bargaining Equilibrium In Games and Social Situations, John C. Harsanyi devotes a chapter to his new theory of morality, which he calls ‘Critical Rule Utilitarianism’, and which contains his solution to the problem of the interpersonal comparison of utility. After a detailed exposition of his theory, arguments will be presented to show that: (i) there are certain formal difficulties in the solution that he offers which leads to a rejection of the axiom that there is to be agreement between an individualj’s personal preferences and individuali’s (i ≠j) extended utility function out of which the social welfare function is to be constructed; and (ii) Harsanyi’s theory of critical rule utilitarianism cannot be accepted as a theory of morality because it presupposes a more fundamental theory in its actual construction.
Modelling and state estimation for a two‐dimensional moving boundary problem

The five-spot waterflooding problem has been modelled as a two-dimensional moving boundary problem with a sharp interface separating the water and oil regions. The Galerkin method was used to solve for the shape and movement of the interface, as well as for the pressures in the reservoir. Having obtained a working model, the extended Kalman filter was then used to estimate the interfacial position when using corrupted pressure measurements from a single sensor in the field.
Threshold effects in gene regulation: When some is not enough

Understanding a complex system requires more than assembling a parts list and wiring the parts together. We also need to understand the functional consequences of the connections, the biochemical properties of the parts and their interactions, the timing of events in a dynamic circuit, and the response of the system to stimuli if we hope to predict systems behavior and the consequences of changes in the system. In a recent issue of PNAS, Kobiler et al. (1) took an important step in this direction for one of the best-understood model gene regulatory circuits, that of bacteriophage λ. For decades, studies on λ have pioneered this progression toward a systems-level description of a complex regulatory circuit (2, 3). At the same time, since the early days of λ biology, outsiders have been bewildered by the tendency of λ workers to use an apparently endless stream of mutations and multiple-mutant combinations to prove their points. Kobiler et al. (1) offer a relatively mild dose of this treatment, but an introduction to the λ life cycle, the players, and their interactions is helpful. An Escherichia coli cell infected with λ can follow either of two alternative pathways (Fig. 1 A ). The choice between these is termed the lysis–lysogeny decision (4, 5). In the lytic pathway (blue in Fig. 1 A ), the cell executes a pattern of viral gene expression (Fig. 1 B ), replicates the viral DNA, makes ≈100 new virions, and finally lyses. In the lysogenic pathway (green in Fig. 1 A ), by contrast, the viral genome sets up housekeeping in the host; the lytic genes are repressed by CI repressor, and the viral DNA is physically integrated into the host genome. Once established, the lysogenic state is extremely stable; CI can repress the lytic genes indefinitely. However, this state can switch to …
Ocean climate change fingerprints attenuated by salt fingering

[1] Intensified double diffusive mixing may attenuate changes in ocean temperature and salinity patterns from global-warming induced increases in the Earth's hydrological cycle. Increasingly fresher Antarctic Intermediate Water and saltier subtropical waters would tend to increase destabilizing vertical salinity stratification compared to the stabilizing temperature stratification. Destabilization would increase salinity (and temperature) fluxes through double-diffusive salt fingering. These fluxes could in turn act to reduce widely recognized climate change fingerprints, potentially leading to underestimates of ocean changes in climate studies that do not account for double-diffusive mixing. Data from a subtropical trans-Indian Ocean survey occupied in 1987, 1995, 2002, and 2009 are used to investigate temperature-salinity changes and to estimate the variations of double diffusive mixing driven by these changes.
The role of CYP1A inhibition in the embryotoxic interactions between hypoxia and polycyclic aromatic hydrocarbons (PAHs) and PAH mixtures in zebrafish ( Danio rerio )

Polycyclic aromatic hydrocarbons (PAHs) are ubiquitous environmental pollutants with elevated concentrations in waters that may also experience hypoxia. Previous research has shown interactions between hypoxia and some PAHs (fluoranthene, α-naphthoflavone) but no interaction with others (benzo[a]pyrene (BaP), β-naphthoflavone). Here we examine how hypoxia (7.4% oxygen, ~35% of normoxia) affects the embryotoxicity of PAHs that act through different mechanisms and the role that CYP1A inhibition may play in these interactions. About 500 μg/l BaP and 1–200 μg/l benzo[k]fluoranthene (BkF) interacted synergistically with hypoxia to induce pericardial edema in developing zebrafish (Danio rerio). Hypoxia protected from the embryotoxicity of pyrene (PY) and had no effect on the toxicity of polychlorinated biphenyl-126. Despite previous reports of other CYP1A inhibitors interacting with hypoxia, up to 2,000 μg/l dibenzothiophene, 2-aminoanthracene (AA), and carbazole (CB) all failed to induce embryotoxicity under normoxic or hypoxic conditions. The toxicity of PAH mixtures—including binary mixtures of BaP/AA and BaP/CB and two environmentally relevant, complex mixtures—were exacerbated severely by hypoxia to induce or worsen pericardial edema and cause mortality. The interactions between hypoxia and BkF and PY were closely mimicked by morpholino knockdown of CYP1A, indicating a potential role for metabolism of these compounds in their toxicity. Our results indicate that various PAHs may exhibit synergistic, antagonistic or additive toxicity with hypoxia. The enhanced toxicity of environmental mixtures of PAHs under hypoxia suggests that risk assessments that do not take into account potential interactions with hypoxia may underestimate the threat of PAHs to fish in contaminated sites.
Deoxycoformycin: neurological toxicity.

Deoxycoformycin (DCF) is a tight-binding inhibitor of adenosine deaminase (ADA) currently undergoing phase I–II evaluation. Neurological toxicity has been a frequent and occasionally severe complication of treatment with this drug. A T-cell leukemia patient with an Ommaya reservoir was treated with DCF, and the pharmacokinetics of the drug in the cerebrospinal fluid and plasma were studied. DCF penetrates the cerebrospinal fluid and achieves levels as high as 1/10 the concurrent plasma levels. The accumulation of adenosine and deoxyadenosine in plasma, cerebrospinal fluid, and urine was monitored; the neuropharmacological effect of these metabolites is discussed.
Adenylate cyclase from various dopaminergic areas of the brain and the action of antipsychotic drugs

Abstract The present report is a comparative study of adenylate cyclase activity in various areas of the brain identified as dopaminergic. Low levels of dopamine were found to stimulate adenylate cyclase from the striatum, median eminence, olfactory tubercle, nucleus accumbens and amygdala. Apomorphine, known to mimic the pharmacological and physiological effects of dopamine, stimulated adenylate cyclase from the median eminence. Several different classes of drugs effective in the treatment of schizophrenia were potent inhibitors of the stimulation by dopamine of the enzyme from these various regions. The drugs studied included representatives of the phenothiazine, butyrophenone, dibenzodiazepine and dibenzoxazepine classes. The inhibition by the dibenzoxazepine, loxapine, which is structurally very similar to the dibenzodiazepine, clozapine, was competitive with respect to dopamine. The calculated inhibition constant (Ki) for loxapine of about 15 nM was similar to that observed for some of the more potent phenothiazines. The results, considered together with previously published data, support the possibility that the therapeutic effects, as well as the extrapyramidal and endocrinological side effects, of these antipsychotic agents may be attributable to their ability to block the activation of adenylate cyclase in various select areas of the brain.
An Experimental Investigation of the Effect of an Active Magnetic Damper on Reducing Subsynchronous Vibrations in Rotating Machinery

Presented here are results from an experimental study investigating the reduction of subsynchronous vibrations in rotating machinery by adding a single active magnetic bearing actuator to a flexible rotor-bearing system. In this scenario, the Active Magnetic Bearing (AMB) actuator is used as an Active Magnetic Damper (AMD) and is not utilized for rotor support. The AMD can be used to increase stability margins by adding more damping in strategic locations on a rotor allowing for increased tolerance to instability mechanisms and enabling increased performance and efficiency in turbomachinery. Results from an experimental 3-mass test rig supported in fluid-film bushings are presented here. The study shows that subsynchronous vibrations are reducible with an AMD located near the mid-span of the rotor and up to a 98% reduction in the amplitude of subsynchronous vibrations is demonstrated. The overall results from this work demonstrate that reduction in subsynchronous response is feasible and that full rotor dynamic analysis and design is critical for the successful application of this approach as critical speed locations can be altered.Copyright © 2005 by ASME
Identification of the blood component responsible for increased susceptibility to gut-derived infection

It has previously been reported that the transfusion of allogeneic whole blood increases sepsis-related mortality and decreases the ability of the host to kill bacteria that have translocated from the intestinal tract. To determine which blood component contributes to this adverse effect, the impact of the transfusion of white cells (WBCs), red cells (RBCs), and plasma on microbial translocation, bacteria killing, and mortality rate was studied. Blood from C3H/HeJ mice was separated into WBCs, RBCs, and plasma, and these fractions were transfused to Balb/c mice. Controls received sterile saline. Five days after transfusion, all Balb/c mice underwent a 20-percent burn and gavage with 1 x 10(10) Escherichia coli labeled with 14C-glucose. Mortality was observed for 10 days. Four additional groups, receiving the same treatment as above, were sacrificed 4 hours after the burn, and mesenteric lymph nodes, liver, kidney, and blood were harvested aseptically. For each tissue, quantitative colony counts, radionuclide counts, and percentage of translocated bacteria that remained alive were calculated. By radionuclide counts, no difference was observed in the degree of 14C E. coli translocation among the groups. In contrast, the percentage of viable bacteria and the mortality rate were significantly higher in the group receiving allogeneic WBCs than in all other groups (p < 0.05). It is concluded that WBCs are the component in transfused blood that has an adverse effect on host resistance to gut-derived infection.
A simplified approach to force control for electro-hydraulic systems☆

Abstract In this paper, a Lyapunov-based control algorithm is developed for force tracking control of an electro-hydraulic actuator. The developed controller relies on an accurate model of the system. To compensate for the parametric uncertainties, a Lyapunov-based parameter adaptation is applied. The adaptation uses a variable structure approach to account for asymmetries present in the system. The coupled control law and the adaptation scheme are applied to an experimental valve-controlled cylinder. Friction modeling and compensation are also discussed. The experimental results show that the nonlinear control algorithm, together with the adaptation scheme, gives a good performance for the specified tracking task. The original adaptive control law is then simplified in several stages with an examination of the output tracking at each stage of simplification. It is shown that the original algorithm can be significantly simplified without too significant a loss of performance. The simplest algorithm corresponds to an adaptive velocity feedback term coupled with a simple force error feedback.
Mechanism of Action of Thioureylene Antithyroid Drugs in the Rat: Possible Inactivation of Thyroid Peroxidase by Propylthiouracil*

We have previously shown that the thioureylene antithyroid drugs 6-propyl-2-thiouracil (PTU) and 1-methyl-2-mercaptoimidazole (MMI) can inactivate thyroid peroxidase (TPO) in a model iodination system containing relatively high concentrations of iodide. The purpose of the present study was to determine whether these drugs may also inactivate TPO in vivo in rats. Assays for total TPO activity after injection of PTU or MMI did not prove to be a valid approach. As TPO inactivation might be expected to result in a relatively prolonged inhibition of enzyme activity, most of our experiments involved measurement of the duration of the inhibitory effect of a single injection of drug. Young rats were injected with low doses of PTU or MMI, and the effect on thyroidal organic iodine formation was determined at intervals after injection, either by 1-h pulse labeling with 131I- in vivo or by incubation of excised thyroid lobes in a medium containing 131I-. Results of both types of experiment demonstrated that the inhibitory effect of a small dose of PTU (1 mumol/100 g BW) was still very marked 17-18 h after injection. Moreover, an inhibitory effect of this small dose of PTU on the metabolism of [35S]MMI could also be demonstrated. Administration of MMI to rats, on the other hand, did not show the prolonged inhibitory effect observed with PTU. This is most likely attributable to the much lower thyroidal uptake of MMI than of PTU in rats. Intrathyroidal metabolism of [35S]PTU and [35S]MMI was also investigated. In contrast to the rapid disappearance of 35S from plasma, both drugs showed accumulation and retention of 35S in the thyroid. However, we obtained no evidence that thyroidal accumulation of PTU or one of its metabolites could explain the prolonged inhibitory effect of this drug. It seemed more likely that this was attributable to TPO inactivation. The clinical implications of our findings are discussed with relation to the dosage schedule commonly employed in the treatment of Graves' disease with antithyroid drugs.
On-line accuracy assessment for the dual six-port ANA: Extension to nonmating connectors

A technique is described for calibrating a dual six-port or four-port automatic network analyzer (ANA) so that the scattering parameters of two-port devices having any combination of connectors can be measured. The technique is a generalization of the “thru-reflect-line” (TRL) calibration technique in which the thru is replaced with a second length of precision transmission line. Expressions for errors associated with the second line are derived.
Effect of void location on segregation patterns in microgravity solidification

Three recent microgravity experiments have been hampered by convection caused by unwanted voids and/or bubbles in the melt. In this work, we present a numerical study to describe how thermocapillary convection generated by a void or bubble can affect a typical microgravity solidification process. A detailed numerical model for the Bridgman solidification of a doped single crystal from its dilute binary melt is developed which solves the quasi-steady Navier Stokes equations together with the conservation equations for transport of energy and species. The complicating effects of thermocapillary convection generated by the void and solutal rejection at the melt-solid interface are included. Numerical simulations indicate that void-generated thermocapillary convection can affect segregation patterns drastically, especially, if the thermocapillary vortex penetrates the solutal boundary layer at the growth interface. Two lateral void positions are considered with the void placed either in the center of the ampoule or on the side wall. From a transport point of view, three different segregation regimes are identified for each lateral void location based on the distance between the void and the growth interface. These range from a diffusion-controlled regime where most of the radial nonuniformity in the interfacial composition is due to the interface curvature with minimal convective effects to a fully mixed regime where the penetration of the solutal boundary layer by the thermocapillary vortex tends to homogenize the interfacial compositions drastically. Naturally, the extent of each of these regions will not only depend on the size and lateral position of the void but also on the material and growth properties of the system under consideration.
Vitamin D and asthma.

Purpose of review asthma is a disease that continues to carry a significant health burden on humanity. Vitamin D is thought to play a role in many chronic diseases as it may possess immunomodulatory properties. This article will review the role of vitamin D regulation on the immune system and its potential implication in the pathophysiology of asthma. Recent findings vitamin D receptors are present on many cells in the body, specifically peripheral blood mononuclear cells. Vitamin D has been shown to regulate the balance of several pro-inflammatory and anti-inflammatory responses in the immune system. Studies have suggested that prenatal vitamin D intake has an effect on childhood wheezing and asthma. Additionally, vitamin D may play a role in asthma exacerbations, and recent evidence also suggests its importance in steroid resistant asthma. Summary vitamin D has a complex role on the immune system and its regulation of various aspects of immunity has allowed speculation on its potential role in asthma. However, the net effect of vitamin D on the immune system and its role in asthma still remains unanswered. More research needs to address the diagnostic and therapeutic implications vitamin D may have in the future of asthma management.
Raising the Institutional Research Profile: Assessing the Context and Expanding the Use of Organizational Frames.

It is not uncommon to hear institutional researchers, both those new to an institutional research leadership position and veterans, lamenting their absence from the decision-making table. How can institutional research professionals develop strategies that get us to the table?
The Study of Thermal Properties and Micro Structures of YSZ

Thermal barrier coatings (TBCs) are used in gas turbine engines to achieve a better efficiency by allowing increased turbine inlet temperature and decreasing the amount of cooling air used. Plasma spraying is one of the most reliable methods to produce TBCs, which are generally comprised of a top coating of ceramic and a bond-coat of metal. Usually, the top coating is Yttria-Stabilized-Zirconia (YSZ), providing the thermal barrier effect. The bond-coat is typically a layer of M-Cr-Al-Y (where “M” stands for “metal”), employed to improve the attachment between the ceramic top-coat and the substrate. Due to the extreme temperature gradient presented in the plasma jet and the wide particle size distribution, during the coating process, injected ceramic powders may experience a significantly different heating process. Different heating history, coupled with the substrate preheating temperature, may affect the thermal properties of the YSZ layers. In this paper, four sets of mol 8% YSZ disks are fabricated under controlled temperatures of 1100°C, 1200°C, 1400°C and 1600°C. Subsequently the thermal properties and the microstructures of these YSZ disks are studied. The results indicate a strong microstructure change at a temperature slightly below 1400°C. For a high sintering temperature, a dense YSZ layer can be formed, which is good for gas tight operation; At low sintering temperature, say 1200°C, a porous YSZ layer is formed, which has the advantage of low thermal conductivity. For gas turbine TBC applications, a robust low thermal conductivity YSZ layer is desirable, while for Solid Oxide Fuel Cells, a gas-tight YSZ film must be formed. This study offers a general guideline on how to prepare YSZ layers, mainly by controlling the heating process, to form microstructures with desired properties.Copyright © 2007 by ASME
A Phantom Burden for Current Transformer Calibration

A technique is presented for applying a burden to a current transf ormer being calibrated in which the power and reactive volt-amperes are returned to the supply rather than being absorbed in a passive network. The transfer is accomplished either by the magnetic shield if a compensated current comparator is used as the ratio standard, or by an auxiliary current transformer in circuits which employ other standards. Electronic circuitry provides the necessary volt-amperes for exciting the magnetic shield of the current comparator or the auxiliary current transformer, and the current transformer being calibrated, to produce the desired power transfer. The circuit requirements are analyzed and equipment which can develop burdens with both in-phase and quadrature components up to 10 ohms, at secondary currents up to 10 amperes, and for a 0.6 percent accuracy class current transformer or better, is described. The burden setting, which is independent of current, may be made by in-phase and quadrature dials to an accuracy of about one percent of full scale.
Aerostructural safety factor criteria

The present modification of the conventional safety factor method for aircraft structures evaluation involves the expression of deterministic safety factors in probabilistic tolerance limit ratios; these are found to involve a total of three factors that control the interference of applied and resistive stress distributions. The deterministic expression is extended so that it may furnish a 'relative ultimate safety' index that encompasses all three distribution factors. Operational reliability is developed on the basis of the applied and the yield stress distribution interferences. Industry standards are suggested to be derivable from factor selections that are based on the consequences of failure.
SUCCESSIVE ACQUISITIONS AND EXTINCTIONS WITH GOLDFISH (CARASSIUS AURATUS) IN A SWIMWAY SITUATION

Goldfish were trained in a successive acquisition and extinction shuttle-swimway situation. Groups of 12 fish experienced alternating days of acquisition and extinction, extinction following immedi...
Angular correlations for the C13(He3, αγ)C12 reaction

Abstract The angular correlations between the first-excited-state alpha particles from the C 13 (He 3 , α) C 12 reaction and the subsequent 4.43 MeV gamma rays have been studied as functions of the angle of emission of the gamma rays for alpha particles emitted at laboratory angles of 10°, 25°, 40°, 90° and 128° at a bombarding energy of 4.50 MeV. The correlation functions have been fitted with an expression of the form W ( θ γ ) = 1 + b 2 cos 2( θ γ − θ 2 ) + b 4 cos 4( θ γ − θ 4 ). The cos 4 θ term dominates the correlation function at low angles and the θ 4 phase angle remains constant, while the θ 2 phase angle behaves similar to the recoil axis at low angles. The behaviour of the cos 4 θ term is inconsistent with a pickup model for the reaction. Other possible direct-exchange interaction models are discussed.
Triggerable liposomal fusion by enzyme cleavage of a novel peptide–lipid conjugate

A novel peptide–lipid sensitive to enzyme cleavage was designed to generate liposomes that could be triggered to fuse by enzymatic activation. Covalent linkage of dioleoyl phosphatidylethanolamine (DOPE) to an elastase substrate, N-acetyl-ala–ala-, resulted in a cleavable peptide–lipid (N-Ac-AA-DOPE) with no intrinsic fusogenic activity. Cleavage of N-Ac-AA-DOPE and concomitant conversion to the fusogenic lipid DOPE could be detected after treatment with human leukocyte elastase or proteinase K, two proteases with similar substrate specificities. A strategy to utilize this cleavage to trigger fusogenicity was tested by modeling the fusion of liposomes containing the expected product of complete cleavage. Based on these results liposomes were designed to contain N-Ac-AA-DOPE, DOTAP, and PE in the ratio of 15/15/70. These liposomes exhibited lipid mixing with acceptor liposomes after elastase or proteinase K protease treatment. Activation of fusion, as monitored by a lipid mixing assay, appeared to be dependent on protease activity, as (1) heat inactivated enzyme did not activate liposomal fusion, and (2) the time and concentration dependence of proteinase K mediated cleavage of N-Ac-AA-DOPE correlated with membrane mixing. Liposomes could also be formulated that exhibited lipid mixing and transfer of aqueous fluorescent probe with erythrocyte ghosts. These observations demonstrate fusogenic lipids conjugated to enzyme substrates serve as triggerable fusion systems that may be useful for gene and drug delivery.
Stereotyped Traits and Sex Roles in Humorous Drawings

Cartoons are used as indicators of the social meanings, especially personality traits and emotional states, typically assigned to men and women. Single-frame cartoons relevant to sex roles were randomly sampled at five-year intervals, beginning in 1952, from Saturday Evening Post, Saturday Review, and Playboy. Statistical trend analysis on 430 cartoon people in 195 cartoons reveals more trait stereotyping for females than for males. Five dominant, general stereotypes were found: the seductive female, the sexually assertive male, the disconsolate man, the incompetent woman, and the angry woman. There has been a decline in the occurrence of the angry woman stereotype and reciprocal sex role conflict in humorus drawings over the past two decades.
From Nomos to Anomia in Thucydides' History : The moral and political context

Etude de la necessite d'un fondement moral ferme du systeme politique chez Thucydide, a travers l'analyse de l'epidemie de peste et de la chute d'Athenes developpee dans son «Histoire». resumant la psychologie de la revolution, Thucydide decrit le passage de la loi (nomos) a l'anarchie (anomia) comme le resultat d'une derive des valeurs morales
A stream chip-multiprocessor for bioinformatics

Bioinformatics applications such as gene and protein sequence matching algorithms are characterized by the need to process large amounts of data. While uni-processor performance growth is slowing due to an increasing gap between processor and memory speeds and a saturation of processor clock frequencies, Genbank data is doubling every 15 months. With the advent of chip multiprocessor systems, great improvements in processor performance could potentially be achieved by taking advantage of the high interprocessor communication bandwidth and new models of programming. We propose a stream chip multiprocessor micro- architecture customized for bioinformatics applications that takes advantage of the memory bandwidth available in chip multiprocessors by exploiting the data parallelism available in bioinformatics applications. The proposed stream chip multiprocessor micro architecture, on a Xilinx Virtex-5 FPGA with 60 customized MicroBlaze soft processor cores running at 80 MHz with a PCI- bus limited main memory bandwidth of 0.12 GB/s, would achieve a speed-up of 68% for the Smith-Waterman sequence matching algorithm compared to a 2.4 GHz AMD Opteron 250. An extrapolated 60 long stream CMP running at 1 GHz with a memory access rate of 2.7 GB/s would run 41.7 times faster than the 1.2 GHz Sun Niagara processor, 16.5 times faster than the 2.4 GHz AMD Opteron 250 and 12.3 times faster than the 2.4 GHz Intel Xeon processor.
Benefits of early feeding and early hospital discharge in elderly patients undergoing open colon resection

BACKGROUND: Recent studies have demonstrated a reduction in hospital stay and postoperative complications in elderly patients undergoing laparoscopy-assisted colectomy, and have attributed the shorter stays and reduced morbidity to the laparoscopic approach. We questioned whether the improved outcomes in these studies were a result of the laparoscopic procedure alone or a result of early postoperative feeding and early hospital discharge. We hypothesized that early feeding in elderly patients undergoing open colorectal resection results in a short hospital stay and favorably affects postoperative morbidity. STUDY DESIGN: Patients aged 70 years and older who were undergoing elective open colon resection were placed on an early postoperative feeding protocol. The early feeding protocol consisted of clear liquids on postoperative day 2, regular diet on postoperative day 3, and discharge to home as tolerated. The main outcomes measurements included early feeding tolerance, hospital stay, postoperative morbidity, and requirement for postoperative assisted care. RESULTS: There were 87 study patients (42 men and 45 women, mean age 77 years). The most common operation was right hemicolectomy (53%). Overall 78 of 87 patients (89.6%) tolerated early feeding. Five patients (5.7%) initially tolerated a diet but required readmission for ileus. Nine patients (10.4%) did not tolerate early feeding initially. The mean hospital stay for all patients was 3.9 days. There were 15 postoperative complications in 13 patients (14.9%), the most common of which was urinary retention. There were no deaths, anastomotic leaks, abscesses, or pneumonia. Only 3 of 86 patients (3.5%) who were previously independent required assisted care after colectomy. CONCLUSIONS: In elderly patients undergoing elective open colon resection, early feeding results in a short hospital stay and low postoperative morbidity. These results are comparable to those reported for laparoscopy-assisted colectomy.
Action of miracil d and related compounds on dna and rna synthesis in regenerating liver and hepatomas

Miracil D (1-diethylaminoethylamino-4-methyl-10-thiaxanthenone) caused a large and prolonged inhibition of thymidine-3H incorporation into DNA of regenerating rat liver. A similar effect was observed with hycanthone and a desethyl derivative of Miracil D, which also complexes with DNA, but not with a noncomplexing congener bearing a methyl substituent on the proximal nitrogen of the dialkylaminoalkylamino side chain. Miracil D caused a less marked inhibition of orotate-3H incorporation into RNA at 6 and 24 h after partial hepatectomy. Administration of Miracil D 16 h before measurement of DNA synthesis had a marked inhibitory effect on three slowly growing hepatomas (9618A, 47C and 7787) but had little or no effect on three rapidly growing hepatomas (3924A, 5123tc and 7777). RNA synthesis was not inhibited in hepatoma 7777 under these conditions, but a small, though significant, inhibition of tumor DNA synthesis was observed in rats subjected to partial hepatectomy. The data suggested that sensitivity of nucleic acid synthesis to Miracil D may be lost with a decrease in the differentiation of hepatic tissues.
The Staff Ride: Developing Historical Sense in Army Leaders

In the current essay, the author draws on his experience as a serving member of the Armed Forces to discuss the problem of developing military leaders capable of mitigating the disruptive nature of war. Specifically, it discusses the staff ride, a comprehensive analysis of historical events conducted through observation, reflection, and discussion, to develop in leaders an understanding that nothing ever works out the way a leader intends or expects. For the military leader facing the uncertainty and ambiguity of modern combat, this lesson from history is arguably the most essential.
Surgical Lesions and Related Medical Problems Among Narcotic Addicts

A series of unusual lesions of surgical interest among narcotic addicts was presented, their associated problems in surgery briefly discussed, and the surgical management of narcotic addicts commented on.
Relationships between composition and pulmonary toxicity of prototype particles from coal combustion and pyrolysis

The hypothesis that health effects associated with coal combustion fly-ash particles are exacerbated by the simultaneous presence of iron and soot was tested through two sets of experiments. The first set created prototype particles from complete and partial combustion, or oxygen free pyrolysis of a high iron Illinois bituminous coal in an externally heated drop-tube furnace. The second experiment created prototype particles consisting of iron and soot in various concentrations from doped ethylene Burke–Schumann flames. Size-classified samples from the coal tests were separated into coarse (>2.5 lm), fine (0.5–2.5 lm) and ultrafine (<0.5 lm) fractions, and analyzed for total carbon, elemental composition, and detailed iron and sulfur speciation. In a similar manner, ultrafine particles from the ethylene flame tests were also analyzed for total carbon and elemental composition. Pulmonary inflammatory responses were determined after intratracheal aspiration of 100 lg samples in female CD1 mice. IL-6 and neutrophil responses were monitored as markers of inflammation. With carbon present, the coal data suggested that the ultrafine particles containing soot were more toxic than fine or coarse particles containing char, even though the iron and sulfur speciation varied only slightly with particle size. Iron and sulfur chemistry were, however, dependent on the extent of carbon burnout achieved. In the absence of carbon, ultrafine particles (high in bisulfates and semi-volatile alkali metals) were less toxic than the fine fraction (high in oxidized iron and sulfates). Iron-soot particles created from ethylene flames were more toxic than an equivalent physical mixture of
Adaptive Value of Nanitic Workers in Newly Founded Red Imported Fire Ant Colonies (Hymenoptera: Formicidae)

Founding fire ant colonies, Solenopsis invicta Buren, with nanitic workers produced 17% more brood than experimentally modified colonies containing equal weights of normal-sized minor workers. As predicted, the number of workers in our founding colonies, not worker size, was the principal factor influencing brood production. These results provide the first empirical evidence substantiating the hypothesis that nanitic workers are indeed adaptive.
First passage times and asymmetry of DNA translocation.

Motivated by experiments in which single-stranded DNA with a short hairpin loop at one end undergoes unforced diffusion through a narrow pore, we study the first passage times for a particle, executing one-dimensional Brownian motion in an asymmetric sawtooth potential, to exit one of the boundaries. We consider the first passage times for the case of classical diffusion, characterized by a mean-square displacement of the form $⟨{(\ensuremath{\Delta}x)}^{2}⟩\ensuremath{\sim}t$, and for the case of anomalous diffusion or subdiffusion, characterized by a mean-square displacement of the form $⟨{(\ensuremath{\Delta}x)}^{2}⟩\ensuremath{\sim}{t}^{\ensuremath{\gamma}}$ with $0l\ensuremath{\gamma}l1$. In the context of classical diffusion, we obtain an expression for the mean first passage time and show that this quantity changes when the direction of the sawtooth is reversed or, equivalently, when the reflecting and absorbing boundaries are exchanged. We discuss at which numbers of ``teeth'' $N$ (or number of DNA nucleotides) and at which heights of the sawtooth potential this difference becomes significant. For large $N$, it is well known that the mean first passage time scales as ${N}^{2}$. In the context of subdiffusion, the mean first passage time does not exist. Therefore, we obtain instead the distribution of first passage times in the limit of long times. We show that the prefactor in the power relation for this distribution is simply the expression for the mean first passage time in classical diffusion. We also describe a hypothetical experiment to calculate the average of the first passage times for a fraction of passage events that each end within some time ${t}^{*}$. We show that this average first passage time scales as ${N}^{2∕\ensuremath{\gamma}}$ in subdiffusion.
Spherical-Homoscedastic Shapes

Shape analysis requires invariance under translation, scale and rotation. Translation and scale invariance can be realized by normalizing shape vectors with respect to their mean and norm. This maps the shape feature vectors onto the surface of a hypersphere. After normalization, the shape vectors can be made rotational invariant by modelling the resulting data using complex scalar rotation invariant distributions defined on the complex hypersphere, e.g., using the complex Bingham distribution. However, the use of these distributions is hampered by the difficulty in estimating their parameters, which is shown to be very costly or impossible in most cases. The purpose of this paper is twofold. First, we show under which conditions the classification results obtained with complex Binghams are identical to those obtained with the easy-to-estimate complex Normal distribution. Second, we derive a kernel function which (intrinsically) maps the data into a space where the above conditions are satisfied and, hence, where the normal model can be successfully used. This results in a simple, low-cost algorithm for representing and classifying shapes. We demonstrate the use of this technique in several experimental results for object and face recognition. Comparisons to other statistical shape representation/classification approaches demonstrate the superiority of the proposed algorithms in classification accuracy and computational time.
Hierarchical motion history images for recognizing human motion

There has been increasing interest in computer analysis and recognition of human motion. Previously we presented an efficient real-time approach for representing human motion using a compact "motion history image" (MHI). Recognition was achieved by statistically matching moment-based features. To address previous problems related to global analysis and limited recognition, we present a hierarchical extension to the original MHI framework to compute dense (local) motion flow directly from the MHI. A hierarchical partitioning of motions by speed in an MHI pyramid enables efficient calculation of image motions using fixed-size gradient operators. To characterize the resulting motion field, a polar histogram of motion orientations is described. The hierarchical MHI approach remains a computationally inexpensive method for analysis of human motions.
The cytochrome ba3 oxygen reductase from Thermus thermophilus uses a single input channel for proton delivery to the active site and for proton pumping

The heme-copper oxygen reductases are redox-driven proton pumps that generate a proton motive force in both prokaryotes and mitochondria. These enzymes have been divided into 3 evolutionarily related groups: the A-, B- and C-families. Most experimental work on proton-pumping mechanisms has been performed with members of the A-family. These enzymes require 2 proton input pathways (D- and K-channels) to transfer protons used for oxygen reduction chemistry and for proton pumping, with the D-channel transporting all pumped protons. In this work we use site-directed mutagenesis to demonstrate that the ba3 oxygen reductase from Thermus thermophilus, a representative of the B-family, does not contain a D-channel. Rather, it utilizes only 1 proton input channel, analogous to that of the A-family K-channel, and it delivers protons to the active site for both O2 chemistry and proton pumping. Comparison of available subunit I sequences reveals that the only structural elements conserved within the oxygen reductase families that could perform these functions are active-site components, namely the covalently linked histidine-tyrosine, the CuB and its ligands, and the active-site heme and its ligands. Therefore, our data suggest that all oxygen reductases perform the same chemical reactions for oxygen reduction and comprise the essential elements of the proton-pumping mechanism (e.g., the proton-loading and kinetic-gating sites). These sites, however, cannot be located within the D-channel. These results along with structural considerations point to the A-propionate region of the active-site heme and surrounding water molecules as the proton-loading site.
Sequential circuit test generation using dynamic state traversal

This research was supported in part by the Semiconductor Research Corporation under contract SRC 96-DP-109, in part by ARPA under contract DABT63-95-C-0069, and by Hewlett-Packard under an equipment grant. A new method for state justification is proposed for sequential circuit test generation. The linear list of states dynamically obtained during the derivation of test vectors is used to guide the search during state justification. State-transfer sequences may already be known that drive the circuit from the current state to the target state. Otherwise, genetic engineering of existing state-transfer sequences is required. In both cases, genetic-algorithm-based techniques are used to generate valid state justification sequences for the circuit in the presence of the target fault. This approach achieves extremely high fault coverages and thus outperforms previous deterministic and simulation-based techniques.