cssi/SciSciGPT-SciSciNet huggingface dataset:
Phase I trial to evaluate the addition of alisertib to fulvestrant in women with endocrine-resistant, ER+ metastatic breast cancer.

In estrogen receptor-positive (ER+) breast cancer models, activation of Aurora A kinase (AURKA) is associated with downregulation of ERα expression and resistance to endocrine therapy. Alisertib is an oral selective inhibitor of AURKA. The primary objectives of this phase I trial were to determine the recommended phase II dose (RP2D) and evaluate the toxicities and clinical activity of alisertib combined with fulvestrant in patients with ER+ metastatic breast cancer (MBC). In this standard 3 + 3 dose-escalation phase I study, postmenopausal patients with endocrine-resistant, ER+ MBC previously treated with endocrine therapy were assigned to one of two dose levels of alisertib (40 or 50 mg) in combination with fixed-dose fulvestrant. Ten patients enrolled, of which nine were evaluable for the primary endpoint. The median patient age was 59. All patients had secondary (acquired) endocrine resistance, and all had received prior aromatase inhibitor. Six had experienced disease progression on fulvestrant. There were no severe (grade 3+) toxicities reported during cycle 1 at either dose level. The median progression-free survival time was 12.4 months (95% CI 5.3–not met), and the 6-month clinical benefit rate was 77.8% (95% CI 40.0–87.2%). In patients with endocrine-resistant, ER+ MBC, alisertib in combination with fulvestrant was well tolerated. A favorable safety profile was observed. The RP2D is 50 mg twice daily on days 1–3, 8–10, and 15–17 of a 28-day cycle with standard dose fulvestrant. Promising antitumor activity was observed, including activity among patients with prior progression on fulvestrant.
Family Disorganization: A Sociological Perspective:

Criteria for defining child neglect are, to some extent, culturally determined and may or may not be related to social class and family malfunction
Searching for Meaghan (Morris)

I am delighted to be here celebrating the unique career of Meaghan Morris, who is, after all, not just a precious intellectual partner (and sometimes mentor) but also a deeply valued friend.1 As it turned out, the invitation to speak at an event honouring Meaghan on the occasion of her retirement provided the pressure I needed to write something I have been trying to write—and postponing—for decades. Why try for so long? Because she is, in my opinion, one of the most original and dedicated practitioners of cultural studies. Why try for so long? Because I could never find a comfortable way of doing it. I would try identifying some representative sample, some set of exemplary texts, that would enable me to make visible the commonalities and diversities that define the singularity of her analytic practice, the contextuality of her political thematic and the trajectory of her career. Every time I thought I had settled on the texts, I would remember another of my favourites, or Meaghan would send me a new one, inevitably shattering my selection and the comfortable assumptions I had made about how to ‘read’ them.
Evans Syndrome: Background, Clinical Presentation, Pathophysiology, and Management

Evans syndrome (ES) is a descriptive diagnostic term encompassing autoimmune disorders which affect two or more blood cell lines, resulting most commonly in autoimmune hemolytic anemia (AIHA) and immune thrombocytopenia (ITP) but also autoimmune neutropenia (AIN) in some cases. Since Evans and colleagues first described this phenomenon in the 1940s, classically defined ES has expanded to include the occurrence of multilineage autoimmune cytopenias either concurrently or sequentially. Furthermore, advances in the understanding of disease pathogenesis have uncovered many of the underlying etiologies responsible for the autoimmune cytopenias which define this syndrome, such that “idiopathic” is no longer a defining feature of the syndrome. Some of the most common pathologies now known to drive ES include autoimmune lymphoproliferative syndrome (ALPS), common variable immunodeficiency (CVID), and other systemic autoimmune diseases, all with the commonality of a dysregulated immune system in which autoreactive lymphocytes are poorly controlled, ultimately predisposing to autoimmunity. The recent advances in understanding of the pathologies driving ES have allowed for improved insight into optimal diagnostic and management strategies, although work is ongoing in the quest for continued improvement in understanding of disease pathogenesis and better outcomes for patients with ES.
MOORE - CLOSED AND LOCALLY MOORE - CLOSED SPACES

Publisher Summary This chapter discusses Moore-closed and locally Moore-closed spaces. Every Moore-closed space is separable and a completely regular Moore space is Moore-closed if it is pseudocompact. A Moore space not having infinitely many isolated points is compact if there is a development G such that (*) if H is a development, there is an increasing sequence of positive integers such that for each i, Gn. refines Hi. One may easily verify that a Moore space is Moore - closed iff it is closed in each Moore space in which it is densely embedded. An analogous statement is true of P-closed spaces for many other properties P. In order that a Moore space S be densely embedded in a Moore-closed space, it is sufficient that there exist a nested development G having property B such that if H is a nested development for S having property B, then every H nest meets some G-nest.
Risk of waterborne illness via drinking water in the United States.

The quality of drinking water in the United States is among the best in the world; however, waterborne disease outbreaks continue to occur, and many more cases of endemic illness are estimated. Documented waterborne disease outbreaks are primarily the result of technological failures or failure to treat the water (Craun et al. 2006). Current federal regulations require that all surface waters used for a drinking water supply be treated to reduce the level of pathogens so as to reduce the risk of infection to 1:10,000 per year (Regli et al. 1991). To achieve this goal, water treatment must, at a minimum, reduce infectious viruses by 99.99% and protozoan parasites by 99.9% (Regli et al. 2003). If Cryptosporidium concentrations exceed a certain level in the source water, additional reductions are required. This degree of treatment is usually achieved by a combination of physical processes (coagulation, sedimentation, and filtration) and disinfection (chlorination, ozonation). Filtration is essential for the removal of protozoan parasites due to their resistance to chlorination and ozonation at doses normally used in drinking water treatment (Barbeau et al. 2000; Korich et al. 1990; Rennecker et al. 1999). A variance from filtration is allowed in some cases if the watershed is protected and carefully monitored for protozoan pathogens.
The van der Waerden Permanent Conjecture

A short history of the van der Waerden permanent conjecture, and versions of Falikman’s and Egoryĉev’s proofs of the conjecture, are presented.
Testing the 2-3 Shear Strength of Unidirectional Composite

In this study, the objective was to measure the “out-of-plane” 2-3 shear strength of unidirectional composite, working within constraints in supplied material geometry. Unidirectional carbon/epoxy composite material was tested using a sandwich-type beam specimen under 3-point bending with a low span-to-thickness ratio to achieve failure under 2-3 shear. Specimens were carefully designed to deliberately cause shear failure near the midplane, avoiding other possible failure mechanisms. A photoelastic coating and post-mortem microscopy were used to verify failures. Results were compared with a simple analytical description of failure and found to have good agreement. Notably, this approach was able to accommodate the limitations of the supplied material (thin sheets) while still providing an accurate means of obtaining the F23 shear strength of the material. The results also imply the possibility of testing the transverse tensile strength (F2t) in lieu of performing a shear test, which is far simpler, and inferring the out-of-plane shear strength F23.
Kinetic Enhancement of Direct Hydrogenation of MgB2 to Mg(BH4)2 upon Mechanical Milling with THF, MgH2, and/or Mg

Modification of magnesium diboride, MgB2 , by mechanical milling with THF, MgH2 , and/or Mg results in a lowering of the conditions required for its direct, bulk hydrogenation to magnesium borohydride, Mg(BH4 )2 , by 300 bar and 100 °C. Following mechanical milling with MgH2 or THF and Mg, MgB2 can be hydrogenated to Mg(BH4 )2 at 300 °C under 700 bar of H2 while achieving ∼54-71 % conversion to the borohydride. The discovery of a means of dramatically lowering the conditions required for the hydrogenation of MgB2 is an important step towards the development of a practical onboard hydrogen storage system based on hydrogen cycling between Mg(BH4 )2 and MgB2 . We suggest that mechano-milling with THF, Mg, and/or MgH2 may possibly introduce defects in the MgB2 structure which enhance hydrogenation. The ability to activate the MgB2 through the introduction of structural defects transcends its relevance to hydrogen storage, as a method of overcoming its chemical inertness provides the key to harnessing other interesting properties of this material.
Social-medication in bees: the line between individual and social regulation

We use the term social-medication to describe the deliberate consumption or use of plant compounds by social insects that are detrimental to a pathogen or parasite at the colony level, result in increased inclusive fitness to the colony, and have potential costs either at the individual or colony level in the absence of parasite infection. These criteria for social-medication differ from those for self-medication in that inclusive fitness costs and benefits are distinguished from individual costs and benefits. The consumption of pollen and nectar may be considered a form of social immunity if they help fight infection, resulting in a demonstrated increase in colony health and survival. However, the dietary use of pollen and nectar per se is likely not a form of social-medication unless there is a detriment or cost to their consumption in the absence of parasite infection, such as when they contain phytochemicals that are toxic at certain doses. We provide examples among social bees (bumblebees, stingless bees and honey bees) in which the consumption or use of plant compounds have a demonstrated role in parasite defense and health of the colony. We indicate where more work is needed to distinguish between prophylactic and therapeutic effects of these compounds, and whether the effects are observed at the individual or colony level.
The inter-ligand Overhauser effect: a powerful new NMR approach for mapping structural relationships of macromolecular ligands.

NMR experiments that transfer conformational information from the bound to the uncomplexed state via exchange have been utilized for many years. It is demonstrated here that inter-ligand NOEs (‘ILOEs’), which exist in ternary complexes with enzymes or other macromolecular receptors, can be transferred via exchange to pairs of uncomplexed ligands. This approach is illustrated by studies of glycolate + NAD+ in the presence of porcine heart lactate dehydrogenase, and by glucose-6-phosphate + NADPH in the presence of L. mesenteroides glucose-6-phosphate dehydrogenase. This strategy opens up a general methodology for exploring the active sites of enzymes and for the development of artificial ligands which can function as inhibitors, or more generally as modifiers of protein function.
Reducing the Biological and Psychological Toxicity of Poverty-related Stress: Initial Efficacy of the BaSICS Intervention for Early Adolescents.

This proof-of-concept study tests the initial efficacy of the Building a Strong Identity and Coping Skills (BaSICS) intervention, a selective prevention of internalizing problems program for early adolescents exposed to high levels of poverty-related stress. Eighty-four early adolescents (Mage = 11.36 years) residing in very low-income neighborhoods were randomized to receive the 16-session intervention (n = 44) or to an assessment-only control condition (n = 40). BaSICS teaches coping skills, social identity development, and collective social action to empower youth with the ability to connect with members of their communities and cope with poverty-related stress in positive and collaborative ways. Pretest-posttest analyses showed that intervention adolescents acquired problem-solving and cognitive-restructuring skills and reduced their reliance on avoidant coping. In addition, HPA reactivity was significantly reduced in the intervention youth, but not controls. Finally, intervention youth's internalizing and somatic symptoms as reported by both youth and their parents, showed significant reductions over time, whereas control youth had no such changes. Results provide strong support for this approach to strength-building and symptom reduction in a population of early adolescents exposed to poverty-related stress.
Pseudo-Haptic Display of Mass and Mass Distribution During Object Rotation in Virtual Reality

We propose and evaluate novel pseudo-haptic techniques to display mass and mass distribution for proxy-based object manipulation in virtual reality. These techniques are specifically designed to generate haptic effects during the object's rotation. They rely on manipulating the mapping between visual cues of motion and kinesthetic cues of force to generate a sense of heaviness, which alters the perception of the object's mass-related properties without changing the physical proxy. First we present a technique to display an object's mass by scaling its rotational motion relative to its mass. A psycho-physical experiment demonstrates that this technique effectively generates correct perceptions of relative mass between two virtual objects. We then present two pseudo-haptic techniques designed to display an object's mass distribution. One of them relies on manipulating the pivot point of rotation, while the other adjusts rotational motion based on the real-time dynamics of the moving object. An empirical study shows that both techniques can influence perception of mass distribution, with the second technique being significantly more effective.
An Ultraefficient DC Hybrid Circuit Breaker Architecture Based on Transient Commutation Current Injection

Protection against circuit faults represents a major technical challenge in the emerging dc transmission and distribution power networks. A popular prior-art dc hybrid circuit breaker (HCB) using a series load commutation switch (LCS) offers an excellent solution with arcless operation but suffers from a high conduction power loss associated with the LCS. This article proposes a new HCB architecture that relies on a switching-mode transient commutation current injector (TCCI) circuit instead of the LCS. The TCCI in the electronic path remains in a standby mode with near-zero power loss under normal conditions, but can rapidly generate a pulse current matching the fault current, and therefore facilitate current commutation from the mechanical to the electronic path. It completely eliminates the conduction power loss associated with the LCS, and delivers ultrahigh transmission efficiency. The TCCI circuit provides a near-zero voltage and a small high-frequency ac ripple current condition for the mechanical contacts to separate arclessly. A 600-V/20-A HCB prototype based on a two-phase current source buck converter topology and a high-voltage vacuum relay has experimentally validated the HCB concept, and demonstrated a mechanical to electronic commutation time of $7.2~\mu \text{s}$ , a total active response time of $310~\mu \text{s}$ , and a peak interrupted fault current of 89 A at a dc bus voltage of 400 V. The new HCB architecture can be applicable in medium voltage direct current (MVDC) (>5 kV) and high voltage direct current (HVDC) (>100 kV) applications as well.
The Effect of Molecular Weight on Association in Anionic Polymerization

The effect of molecular weight on the equilibrium between the tetrameric and dimeric associates of the active chain-ends in the polymerization of isoprene by lithium based initiators has been studied by UV spectroscopy. This equilibrium is equivalent to the association of two polymer chains linked by active groups centrally placed on the chains where large changes of equilibrium constant are found in going from low molecular analogs to polymers in other systems. Large effects are found in this case also in both cyclohexane and benzene solution. The dissociation constant in benzene solution with high molecular weight species is sufficiently high that it modifies the kinetics of the propagation reaction. The kinetic order changes from one quarter to one half with dilution to follow the change in equilibrium, with parallel changes in activation energy. Also the propagation rate differs for very low molecular weight species.
Effect of Random Nanostructured Metallic Environments on Spontaneous Emission of HITC Dye.

We have studied emission kinetics of HITC laser dye on top of glass, smooth Au films, and randomly structured porous Au nanofoams. The observed concentration quenching of luminescence of highly concentrated dye on top of glass (energy transfer to acceptors) and the inhibition of the concentration quenching in vicinity of smooth Au films were in accord with our recent findings. Intriguingly, the emission kinetics recorded in different local spots of the Au nanofoam samples had a spread of the decay rates, which was large at low dye concentrations and became narrower with increase of the dye concentration. We infer that in different subvolumes of Au nanofoams, HITC molecules are coupled to the nanofoams weaker or stronger. The inhibition of the concentration quenching in Au nanofoams was stronger than on top of smooth Au films. This was true for all weakly and strongly coupled subvolumes contributing to the spread of the emission kinetics. The experimental observations were explained using theoretical model accounting for change in the Forster radius caused by the strong energy transfer to metal.
Asparagine Endopeptidase (δ Secretase), an Enzyme Implicated in Alzheimer's Disease Pathology, Is an Inhibitor of Axon Regeneration in Peripheral Nerves.

Asparagine endopeptidase (AEP) is a lysosomal protease implicated in the pathology of Alzheimer’s disease (AD). It is known to cleave the axonal microtubule associated protein, Tau, and amyloid precursor protein (APP), both of which might impede axon regeneration following peripheral nerve injury. Active AEP, AEP-cleaved fragments of Tau (Tau N368), and APP (APP N585) were found in injured peripheral nerves. In AEP null mice, elongation of regenerating axons after sciatic nerve transection and repair was increased relative to wild type (WT) controls. Compound muscle action potentials (M responses) were restored in reinnervated muscles twice as fast after injury in AEP knockout mice as WT controls. Neurite elongation in cultures of adult dorsal root ganglion neurons derived from AEP knockout mice was increased significantly relative to cultures from wild type controls. In AEP knockout mice exposed to one hour of 20 Hz electrical stimulation at the time of nerve injury, no further enhancement of axon regeneration was observed. These findings support inhibition of AEP as a therapeutic target to enhance axon regeneration after peripheral nerve injury. Significance Statement Axons in injured peripheral nerves can regenerate, but recovery from such injuries is poor. Asparagine endopeptidase (AEP) is an enzyme linked to the major pathological features of Alzheimer’s disease. We show here that it is highly expressed in injured peripheral nerves and both reduces the microtubule stabilizing effect of Tau on axons and degrades amyloid precursor protein in a manner that hinders any axon pathfinding role. Removing AEP by gene knockout enhanced the elongation of regenerating axons in cut nerves and promoted an accelerated restoration of neuromuscular function. Inhibition of AEP is thus a target for development of novel strategies to treat peripheral nerve injuries.
Peyronie's disease - outcomes of collagenase clostridium histolyticum injection: A systematic review.

Objective To review recent literature pertaining to collagenase clostridium histolyticum (CCh)and other intralesional (IL) therapies for the treatment of Peyronie's disease (PD). Methods A systematic search of literature was performed using MEDLINE and PubMed.'Peyronie's Disease Clostridium Histolyticum', 'Peyronie's Disease Intralesional', 'Peyronie'sDisease Causes', and 'Atypical Peyronie's Disease' were used as query entries. Inclusion criteriarequired English text from 1980 onwards and have a full text available. Records were reviewed for study power, accuracy, and relevance to our research topic. The review was conducted using the Preferred Reporting Items for Systematic Reviews and Meta-Analyses criteria. Results Recent literature supports the notion that CCh is the most effective IL treatment forpatients with typical and atypical PD. The capstone CCh study was the IMPRESS trial thatshowed a 34% reduction in curvature with a mean (SD) - 17.0 (14.8)° reduction with IL CCh,while men in the placebo saw an average 18.2% decrease in penile bend with a mean (SD) - 9.3 (13.6)° per person (P < 0.001). A shortened protocol for IL CCh treatment offered a 31.4%reduction in curvature, while decreasing cost and office visits, potentially increasing patientcompliance. Lastly, literature shows CCh is used most in atypical cases, with ~64.8% of patients being treated with CCh, probably because of the high efficacy and safetyprofile that it offers. Serious complications associated with CCh include urethralinjury, corporal rupture, and penile fracture. Conclusion Since the approval of CCh by the United States Food and Drug Administration in2013, it has been a staple in the treatment of PD, and here we report the continuedsuperiority of this therapy. CCh is an effective, minimally invasive option in most PDpopulations; however, recent changes have made CCh unavailable for commercial use outside the United States, impacting many patients who have previously benefited.
Color is necessary for specialized face learning in the Northern paper wasp, Polistes fuscatus

Visual individual recognition requires animals to distinguish among conspecifics based on appearance. Though visual individual recognition has been reported in a range of taxa, the features that animals rely on to discriminate between individuals are often not well understood. Northern paper wasp females, Polistes fuscatus, possess individually distinctive color patterns on their faces, which mediate individual recognition. It is currently unclear what facial features P. fuscatus use to distinguish individuals. The anterior optic tubercle, a chromatic processing brain region, is especially sensitive to social experience during development, suggesting that color may be important for recognition in this species. We sought to test the roles of color in wasp facial recognition. Color may be important simply because it creates a pattern. If this is the case, then wasps should perform similarly when discriminating color or grayscale images of the same faces. Alternatively, color itself may be important for recognition, which would predict poorer performance on grayscale image discrimination relative to color images. We found wasps trained on grayscale faces, unlike those trained on color images, did not perform better than chance. Suggesting that color is necessary for the recognition of an image as a face by the wasp visual system.
Charge Carriers in Semiconductors

The semi-conductors have a distinctive property of having small band gaps that separate the valence and conduction bands. In these materials, a relatively small number of electrons are excited thermally from the valence band into the conduction band creating electron-hole pairs that can conduct a current. The density of free electrons and holes can be modified by adding impurities to the crystal. A semiconductor having impurities that contribute electrons to the conduction band is said to be n-doped or to have donor atoms; a semiconductor having impurities that contribute holes to the valence band is said to be p-doped or to have acceptor atoms. A p-n junction is formed by depositing a material with either donors or acceptors upon another material with the opposite kind of doping. Interfaces produced in this way have a preferred direction of current and can be used to produce rectifiers. The amplification of a signal by a transistor depends upon the fact that the voltage across two terminals (emitter and collector), which serve as the output terminals, is very sensitive to the voltage across two other terminals (base and emitter), which serve as the input terminals.
Preexisting atrial fibrillation and cardiac complications after liver transplantation.

Atrial fibrillation (AF) is the most common cardiac arrhythmia, and it is associated with increased cardiovascular morbidity and all-cause mortality. Our aim was to determine the impact of preexisting AF on patients undergoing liver transplantation (LT). A retrospective case-control study was performed. Records from patients who underwent LT between January 2005 and December 2008 at Mayo Clinic Florida were reviewed. Patients with preexisting AF were identified and matched to patients who did not have a diagnosis of AF. Thirty-two of 717 LT recipients (4.5%) had AF before LT. These patients were compared to a control group of 63 LT recipients. Pre-LT left ventricular hypertrophy (P = 0.03), a history of congestive heart failure (P = 0.04), and a history of stroke or transient ischemic attack (P = 0.03) were significantly more prevalent in patients with AF versus controls. Intraoperative adverse cardiac events (P = 0.02) and AF-related adverse postoperative events (P < 0.001) were more common in the recipients with known AF. Six patients with paroxysmal AF (19%) developed chronic/persistent AF postoperatively. Graft survival and patient survival were similar in the groups. Although patients with AF had a higher incidence of intraoperative cardiac events, a higher cardiovascular morbidity rate, and a complicated postoperative course, this did not affect overall graft and patient survival. Liver Transpl 21:314–320, 2015. © 2014 AASLD.
Effects of female sex hormones in whole embryo culture.

Abstract Much work has been done in vivo on the effects of sex steroids on the developing foetus. Many genital anomalies have been reported; defects of other organ systems have been suggested. Synthetic oestrogens are considered to be developmental toxicants in vivo, while natural oestrogens are thought to present little or no risk. A small selection of hormones (17β-oestradiol, 17α-ethynyloestradiol, diethylstilboestrol and progesterone) was tested using the rat whole embryo culture technique to see whether this difference could also be confirmed in vitro. Dysmorphogenic embryotoxic effects were evident with both natural and synthetic oestrogens, but at much higher concentrations than would be expected to circulate in humans after therapeutic use.
Efficiency of Estimating Vaccine Efficacy for Susceptibility and Infectiousness: Randomization by Individual Versus Household

In designing vaccine efficacy studies based on the secondary attack rate (SAR) or transmission probability in which both vaccine efficacy for susceptibility, VE(S), and vaccine efficacy for infectiousness, VE(I), are estimated, the allocation of vaccine and placebo within transmission units has an important influence on the efficiency of the study. We compared the following randomization schemes that result in different allocations of vaccine and placebo within two-member households: (1) randomization by individual for a mixed allocation, (2) randomization by transmission unit for concordant allocation, and (3) randomization of only one individual in each transmission unit to either vaccine or placebo. There is a complex interaction among the VE(S), VE(I), and the SAR that determines which allocation of vaccine and placebo within households provides the most information. In general, individual randomization with a mixed allocation of vaccine and placebo is better for estimating both VE(S) and VE(I) than is randomizing by household. However, for estimation of VE(I), at very low SARs and low VE(S), randomization by household is slightly more efficient than randomization by individual.
SNAG: using social networking games to increase student retention in computer science

One of the primary goals of attending academic conferences is professional networking, yet even though this interaction can increase one's feeling of community within a field, conference attendees are not interacting as much as they could be. Similarly, it's known that students who do not feel as if they are part of a larger academic community are less likely to participate in extracurricular activities and organizations, lowering retention rates. To combat both of these problems, we present SNAG (Social Networking and Games). SNAG is a suite of mobile and Internet games which aim to facilitate social networking between members of a group, and can be used in either a conference setting or within a university. This paper focuses on one specific game, Snag'em, and discusses our evaluation for our SNAG games.
Isoprenylation of proteins in the protozoan Giardia lamblia.

Abstract We report the ability of Giardia lamblia to modify several of its cellular proteins by isoprenylation. Trophozoites cultured in the presence of [ 3 H]mevalonate synthesized radiolabeled proteins of approx. 50 and 21–26 kDa. Chemical analysis indicated that farnesyl and geranylgeranyl isoprenoids comprised the majority of the radiolabel covalently associated with trophozoite proteins. In addition, antibodies to human p21 ras immunoprecipitated mevalonate-labelled species of approx. 21 kDa. Inhibitors of several enzymatic steps of the mevalonate pathway dramatically affected Giardia metabolism. Protein isoprenylation and cell growth were blocked by compactin and mevinolin, competitive inhibitors of HMG-CoA reductase, the rate-limiting enzyme in isoprenoid biosynthesis. In the presence of these inhibitors, Giardia growth was restored by the addition of mevalonate to the culture medium. In contrast, cell growth was blocked irreversibly by inhibitors of subsequent steps in the protein isoprenylation pathway. Trophozoite growth inhibition by limonene, perillic acid, perillyl alcohol and N -acetyl- S -farnesyl- l -cysteine was not reversed after the addition of mevalonate, dolichol, ubiquinone or cholesterol to the medium. These observations constitute the first description of protein isoprenylation in any protozoan and indicate that this post-translational modification is an important step in the regulation of the growth of this primitive eukaryote.
Sorbitol accumulation is altered in type 1 (insulin-dependent) diabetes mellitus.

Intracellular sorbitol accumulation has been implicated as an aetiological factor for many of the complications of diabetes mellitus. Erythrocyte sorbitol is found in higher concentration in Type 1 (insulin-dependent) diabetic patients than in normal subjects. When sorbitol accumulation is corrected for its immediate prescursor glucose (sorbitol/glucose ratio), the polyol accumulation remains significantly greater in erythrocytes from the Type 1 diabetic. Erythrocytes from Type 1 diabetic patients exposed to normal extracellular glucose concentrations for 3 h in vitro, accumulate more sorbitol and fructose than normal cells in the same incubation system. Near-normalization of plasma glucose in Type 1 diabetic patients for 12 h did not result in normal erythrocyte sorbitol levels. The increased sorbitol accumulation in erythrocytes from Type 1 diabetic subjects may reflect similar activity in the lens and nerve in long-standing diabetes. This increased sorbitol production was found in most, but not all, individuals with diabetes and appears to be an acquired characteristic. Those factors influencing enhanced tissue sorbitol accumulation may be important in the aetiology of diabetes-associated complications.
A LIM-homeodomain combinatorial code for motor-neuron pathway selection

Different classes of vertebrate motor neuron that innervate distinct muscle targets express unique combinations of LIM-homeodomain transcription factors, suggesting that a combinatorial code of LIM-homeodomain proteins may underlie the control of motor-neuron pathway selection. Studies of LIM-homeodomain genes in mouse, Drosophila melanogaster and Caenorhabditis elegans have revealed functions of these genes in neuronal survival, axon guidance, neurotransmitter expression and neuronal function, but, to our knowledge, none of these studies have addressed the issue of a functional code. Here we study two members of this gene family in Drosophila, namely lim3, the homologue of the vertebrate Lhx3 and Lhx4 genes, and islet, the homologue of the vertebrate Isl1 and Is12 genes. We show that Drosophila lim3 is expressed by a specific subset of islet-expressing motor neurons and that mutating or misexpressing lim3 switches motor-neuron projections predictably. Our results provide evidence that lim3 and islet constitute a combinatorial code that generates distinct motor-neuron identities.
Baldwin vs. Edward VIII: A case study in kategoria and apologia

The theory of kategoria and apologia as a rhetorical speech set is applied to Stanley Baldwin vs. King Edward VIII. The author revises received opinion concerning these two famous speeches.
Optimization of detector pixel size for interventional X-ray fluoroscopy

Visualization of guide-wires and stents is of great interest in x-ray fluoroscopy. Detector pixels need to be small to limit partial-area effects with pixel-thin guide-wires. However, as pixels become smaller, the number of x-ray photons per pixel and the pixel signal-to-noise-ratio (SNR) decrease. Hence, there is a trade-off between resolution and SNR that will affect visualization. For imaging interventional devices, we determined the optimum detector pixel size using human observer detection experiments and modeling. Contrast sensitivities for guide-wire detection were determined for an idealized digital detector with pixels of 100, 200, 300 and 500 micrometers and for a guide-wire diameter of 400 micrometers . Results indicate that the optimal pixel size is around 200 micrometers at fluoroscopic exposures. At higher exposures, a smaller detector pixel is desirable. With large pixels, detection was degraded significantly due to contrast-dilution from partial-area effects. A human observer model predicted results. Having established the model for an idealized situation, we then use it to predict the effect of physical detector parameters like MTF, NPS and fill-factor on image quality. The model is a very promising tool for designing detectors for dose-efficient x-ray systems.
Three-dimensional echocardiographic volume computation: in vitro comparison to standard two-dimensional echocardiography.

Two-dimensional (2D) echocardiographic methods for quantitative left ventricular volume computation have been shown to have a low predictive accuracy and reproducibility. To address the problem of geometric assumptions and image plane positioning errors inherent in 2D echocardiography, three-dimensional (3D) echocardiographic systems have been constructed that provide spatial registration and display of transducer-image position and orientation. Although 3D echocardiography has been shown to accurately measure volume in vitro and in vivo, only preliminary data exist demonstrating its superiority over standard 2D echocardiography. We calculated the volume of 30 water-filled latex balloon phantoms of varying size (40 to 200 ml) and shape using each method. Fifteen phantoms were nondistorted (ellipsoid or pear shaped); 15 were symmetrically distorted (dumbbell shaped). Although both 2D and 3D echocardiography showed an excellent correlation to the true volume 2.650 ± 1.90, respectively). We conclude that 3D echocardiography with guided image plane positioning and a novel algorithm for volume computation (polyhedral surface reconstruction) achieves s' ' cantly more accurate and reproducible results than conventional 2D echocardiography with the modified Simpson's rule. 3D echocardiography therefore has the potential for becoming a more exact and reproducible method for serial quantitative volume determination.
Measurement of water pressure and deformation with time domain reflectometry cables

Time domain reflectometry (TDR) techniques can be deployed to measure water pressures and relative dam abutment displacement with an array of coaxial cables either drilled and grouted or retrofitted through existing passages. Application of TDR to dam monitoring requires determination of appropriate cable types and methods to install these cables in existing dams or during new construction. This paper briefly discusses currently applied and developing TDR techniques and describes initial design considerations for TDR-based dam instrumentation. Water pressure at the base of or within the dam can be determined by measuring the water level within a hollow or air-filled coaxial cable. The ability to retrofit existing porous stone-tipped piezometers is an attractive attribute of the TDR system. Measurement of relative lateral movement can be accomplished by monitoring local shearing of a solid polyethylene-filled coaxial cable at the interface of the dam base and foundation materials or along adversely oriented joints. Uplift can be recorded by measuring cable extension as the dam displaces upward off its foundation. Since each monitoring technique requires measurements with different types of coaxial cables, a variety may be installed within the array. Multiplexing of these cables will allow monitoring from a single pulser, and measurements can be recorded on site or remotely via a modem at any time.© (1995) COPYRIGHT SPIE--The International Society for Optical Engineering. Downloading of the abstract is permitted for personal use only.
Statistical properties of shocks in Burgers turbulence. II. Tail probabilities for velocities, shock-strengths and rarefaction intervals

This paper studies the structure of the random “sawtooth” profile corresponding to the solution of the inviscid Burgers equation with white-noise initial data. This function consists of a countable sequence of rarefaction waves separated by shocks. We are concerned here with calculating the probabilities of rare events associated with the occurrence of very large values of the normalized velocity, shock-strength and rarefaction intervals. We find that these quantities have tail probabilities of the form exp{−Cx 3},x≫1. This “cubic exponential” decay of probabilities was conjectured in the companion paper [1]. The calculations are done using a representation of the shock-strength and length of rarefaction intervals in terms of the statistics of certain conditional diffusion processes.
INTRACELLULAR SITE OF SYNTHESIS OF SOLUBLE BLOOD GROUP SUBSTANCE.

Abstract The intracellular distribution of soluble blood group substance in hog gastric mucosa was investigated. The microsomal fraction contains 1–3% of the total intracellular blood group substance. Labeling experiments in vivo show this small pool to be newly synthesized material and the precursor of other intracellular pools. Attempts to detect a nucleotide-linked, fucose-containing oligosaccharide intermediate in the synthesis of the heterosaccharide chains of blood group substance were unsuccessful.
An integral equation theory for the structure of water around globular solutes

Abstract An integral equation theory for water around globular solutes is described that gives the pair distribution function with spatial and orientational dependence, g ( r ,Ω). After a decomposition of the position and orientation dependence, an HNC-OZ theory is used for the position-dependent part and a probability function approximation for the orientation-dependent part. For a model system of water around frozen water clusters, the theory yields results in good agreement with those from Monte Carlo computer simulations for the dipolar hard-sphere plus sticky potential model for water by Bratko, Blum and Luzar. Extensions to other water models are also described.
ERα regulates lipid metabolism in bone through ATGL and perilipin

A decrease in bone mineral density during menopause is accompanied by an increase in adipocytes in the bone marrow space. Ovariectomy also leads to accumulation of fat in the bone marrow. Herein we show increased lipid accumulation in bone marrow from estrogen receptor alpha (ERα) knockout (ERαKO) mice compared to wild-type (WT) mice or estrogen receptor beta (ERβ) knockout (ERβKO) mice. Similarly, bone marrow cells from ERαKO mice differentiated to adipocytes in culture also have increased lipid accumulation compared to cells from WT mice or ERβKO mice. Analysis of individual adipocytes shows that WT mice have fewer, but larger, lipid droplets per cell than adipocytes from ERαKO or ERβKO animals. Furthermore, higher levels of adipose triglyceride lipase (ATGL) protein in WT adipocytes correlate with increased lipolysis and fewer lipid droplets per cell and treatment with 17β-estradiol (E2) potentiates this response. In contrast, cells from ERαKO mice display higher perilipin protein levels, promoting lipogenesis. Together these results demonstrate that E2 signals via ERα to regulate lipid droplet size and total lipid accumulation in the bone marrow space in vivo.
Cyberspaces of Their Own: Female Fandoms Online, by Rhiannon Bury. New York: Peter Lang Publishing, 2005. x+ 242 pp. $29.95 paper. ISBN 0-8204-7118-6

Rhiannon Bury provides an engaging ethnography of two elite female online fandom spaces. Participants are members of the David Duchovny Estrogen Brigade Research Project (DDEBRP), arising from the ...
Regulation of valve endothelial cell vasculogenic network architectures with ROCK and Rac inhibitors

Abstract Objective The age- and disease-dependent presence of microvessels within heart valves is an understudied characteristic of these tissues. Neovascularization involves endothelial cell (EC) migration and cytoskeletal reorientation, which are heavily regulated by the Rho family of GTPases. Given that valve ECs demonstrate unique mesenchymal transdifferentiation and cytoskeletal mechanoresponsiveness, compared to vascular ECs, this study quantified the effect of inhibiting two members of the Rho family on vasculogenic network formation by valve ECs. Approach and results A tubule-like structure vasculogenesis assay (assessing lacunarity, junction density, and vessel density) was performed with porcine aortic valve ECs treated with small molecule inhibitors of Rho-associated serine-threonine protein kinase (ROCK), Y-27632, or the Rac1 inhibitor, NSC-23766. Actin coordination, cell number, and cell migration were assessed through immunocytochemistry, MTT assay, and scratch wound healing assay. ROCK inhibition reduced network lacunarity and interrupted proper cell–cell adhesion and actin coordination. Rac1 inhibition increased lacunarity and delayed actin-mediated network formation. ROCK inhibition alone significantly inhibited migration, whereas both ROCK and Rac1 inhibition significantly reduced cell number over time compared to controls. Compared to a vascular EC line, the valve ECs generated a network with larger total vessel length, but a less smooth appearance. Conclusions Both ROCK and Rac1 inhibition interfered with key processes in vascular network formation by valve ECs. This is the first report of manipulation of valve EC vasculogenic organization in response to small molecule inhibitors. Further study is warranted to comprehend this facet of valvular cell biology and pathology and how it differs from vascular biology.
Infrared studies of chain folding in polymers. VIII. Metastable conformations in amylose

Abstract Two infrared bands occurring at 790 and 1256 cm−1 can be assigned to conformations within a metastable noncrystalline state of amylose. This metastable conformation can be transformed to a crystallizable conformation with heat or time. Both bands occur in amorphous and V-complex preparations of amylose. These two infrared bands have not been previously reported for amylose.
Superenantioselective Chiral Surface Explosions

Chiral inorganic materials predated life on Earth, and their enantiospecific surface chemistry may have played a role in the origins of biomolecular homochirality. However, enantiospecific differences in the interaction energies of chiral molecules with chiral surfaces are small and typically lead to modest enantioselectivities in adsorption, catalysis, and chemistry on chiral surfaces. To yield high enantioselectivities, small energy differences must be amplified by reaction mechanisms such as autocatalytic surface explosions which have nonlinear kinetics. Herein, we report the first observations of superenantiospecificity resulting from an autocatalytic surface explosion reaction of a chiral molecule on a naturally chiral surface. R,R- and S,S-tartaric acid decompose via a vacancy-mediated surface explosion mechanism on Cu single crystal surfaces. When coupled with surface chirality, this leads to decomposition rates that exhibit extraordinarily high enantiospecificity. On the enantiomorphs of naturally...
Reduction of postsynaptic inhibition tolerated before seizure initiation: Brain stem

The reduction of GABA-mediated postsynaptic inhibition tolerated before seizure initiation was assessed using the GABA-mediated, disynaptic, inhibitory pathway from the ipsilateral vestibular nerve to trochlear motoneurons in pentobarbital-anesthetized cats. The amplitude of intracellularly recorded IPSPs or the corresponding extracellular field potential was monitored while incremental doses of the specific GABA antagonist, bicuculline, were injected intravenously. Cortical seizures (measured by ECoG activity) and spontaneous trochlear motoneuron bursting occurred at bicuculline doses which reduced inhibitory vestibular-trochlear field potentials by 10% or less. After midbrain transection trochlear motoneurons no longer participated in the cortical seizures. Rather, a widespread, paroxysmal increase of intrinsic brain stem activity, including motoneuron bursting, occurred after injection of additional bicuculline sufficient to reduce the vestibular-trochlear inhibition to 25% of control or less. Thus, postsynaptic inhibition could be virtually eliminated before intrinsic brain stem seizures were triggered, but the brain stem could participate in cortical seizures in spite of the integrity of inhibitory brain stem pathways. Because the cortex seized when inhibitory potentials were only slightly reduced in the brain stem, we suggest that factors such as different GABA receptor properties or altered membrane properties may contribute to the greater sensitivity of cortex to bicuculline.
Trophic status of Iowa Lakes in relation to origin and glacial geology

Natural and artificial lakes in the most recently glaciated portions of Iowa have significantly greater total ion concentrations than those in other areas of the state. A similar distribution was found for total nitrogen concentrations. Lake origin seems of greater importance than location in determining trophic state. As a group, the artificial lakes have lower concentrations of total phosphorus, total chlorophyll, and greater Secchi disk transparency than do the natural lakes. This seems related to differences in the dynamics of the phosphorus cycles in these lake types.
Service excellence in electronic channels

Significant research and managerial attention has been devoted to service excellence over the last 20 years. We now need to focus some of that attention on service delivery through electronic channels. Evidence indicates that service is critical to online customers and that it is generally poor. The premise of this article is that we must understand how the customer evaluates electronic service quality as a foundation for improving delivery. This article discusses the definition, conceptualization and measurement of electronic service quality, then offers some ideas for future research.