cssi/SciSciGPT-SciSciNet huggingface dataset:
Topological signatures of species interactions in metabolic networks.

The topology of metabolic networks can provide insight not only into the metabolic processes that occur within each species, but also into interactions between different species. Here, we introduce a novel pair-wise, topology-based measure of biosynthetic support, reflecting the extent to which the nutritional requirements of one species could be satisfied by the biosynthetic capacity of another. To evaluate the biosynthetic support for a given pair of species, we use a graph-based algorithm to identify the set of exogenously acquired compounds in the metabolic network of the first species, and calculate the fraction of this set that occurs in the metabolic network of the second species. Reconstructing the metabolic network of 569 bacterial species and several eukaryotes, and calculating the biosynthetic support score for all bacterial-eukaryotic pairs, we show that this measure indeed reflects host-parasite interactions and facilitates a successful prediction of such interactions on a large-scale. Integr...
Induction of tumor cell resistance to macrophage-mediated lysis by preexposure to non-activated macrophages

Abstract Thioglycollate-elicited peritoneal exudate (non-activated) macrophages do not lyse tumor cells and in contrast to activated macrophages bind less target cells. However, a non-lethal encounter of tumor cells with non-activated macrophages resulted in a pronounced effect on the subsequent tumor cell binding to and lysis by activated macrophages. Our results have shown that binding of tumor cells by non-activated macrophages (a) was Ca 2+ and temperature dependent; (b) had a requirement for a Pronase-sensitive structure on macrophage surface membranes; (c) was saturable; and (d) was 2–3× less than that observed for activated macrophages. Experiments were conducted in which syngeneic tumor cells were incubated with a monolayer of non-activated macrophages and then assayed for selective binding and sensitivity to lysis. The important observations were that as a result of a 3-hr incubation with non-activated macrophages at an EC: TC ratio of 5:1 there was (a) an increase in the number of tumor cells that bound to both activated and non-activated macrophages; (b) a loss of selective binding in which the ratio of tumor cells bound to activated/non-activated macrophages (normally greater than 2) was lowered to 1.0; and (c) a concomitant decrease in the susceptibility of tumor cells to macrophage-mediated cytolysis. The induction of tumor cell resistance to macrophage kill required an exposure to an excess number of non-activated macrophages, was reversible upon culturing with or without macrophages for 24 hr and required cell-cell contact. Our results reinforce the importance of selective binding between tumor cells and activated macrophages as an initial phase in tumor cell killing and also illustrates an active role for non-activated macrophages in vivo in allowing tumor cells to escape the immune surveillance by activated macrophages.
Controls on the Activation and Strength of a High-Latitude Convective Cloud Feedback

Previous work has shown that a convective cloud feedback can greatly increase high-latitude surface temperature upon the removal of sea ice and can keep sea ice from forming throughout polar night. This feedback activates at increased greenhouse gas concentrations. It may help to explain the warm ‘‘equable climates’’ of the late Cretaceous and early Paleogene eras (;100 to ;35 million years ago) and may be relevant for future climate under global warming. Here, the factors that determine the critical threshold CO2 concentration at which this feedback is active and the magnitude of the warming caused by the feedback are analyzed using both a highly idealized model and NCAR’s single-column atmospheric model (SCAM) run under Arctic-like conditions. The critical CO2 is particularly important because it helps to establish the relevance of the feedback for past and future climates. Both models agree that increased heat flux into the high latitudes at low altitudes generally decreases the critical CO2. Increases in oceanic heat transport and in solar radiation absorbed during the summer should cause a sharp decrease in the critical CO2, but the effect of increases in atmospheric heat transport depends on its vertical distribution. It is furthermore found (i) that if the onset of convection produces more clouds and moisture, the critical CO2 should decrease, and the maximum temperature increase caused by the convective cloud feedback should increase and (ii) that reducing the depth of convection reduces the critical CO2 but has little effect on the maximum temperature increase caused by the convective cloud feedback. These results should help with interpretation of the strength and onset of the convective cloud feedback as found, for example, in Intergovernmental Panel on Climate Change (IPCC) coupled ocean‐atmosphere models with different cloud and convection schemes.
What are the latest pharmacotherapy options for small bowel adenocarcinoma

Incidence of small bowel adenocarcinoma is slowly but steadily increasing. As we gain more knowledge of the molecular basis of this disease, we may be able to approach it via using novel biologic or targeted therapies with or without traditional chemotherapy agents. In the meantime, early diagnosis is still best as it prompts early surgical resection and offers potential cure. The role of adjuvant and neoadjuvant therapy is currently being explored in clinical trials. Several clinical trials have suggested that first-line chemotherapy for patients with metastatic disease should consist of either 5-fluorouracil-leucovorin-oxalipatin or capecitabine-oxaliplatin, while 5-fluorouracil-leucovorin-irinotecan can be reserved for second-line treatment. However, we realize the limitations of these studies, given their small sample size and/or retrospective nature. Single-agent 5-fluorouracil/capecitabine should be considered in patients who are either intolerant to or experience significant side effects with oxaliplatin or irinotecan. We believe that cancers originating in the ampulla of Vater probably deserve a prospective randomized trial of cisplatin-gemcitabine, the current standard of therapy for advanced biliary malignancies.
LORETA Neurofeedback for Addiction and the Possible Neurophysiology of Psychological Processes Influenced: A Case Study and Region of Interest Analysis of LORETA Neurofeedback in Right Anterior Cingulate Cortex

ABSTRACT Introduction. This case study explores the efficacy of low-resolution electromagnetic tomographic (LORETA) neurofeedback (LNFB) in the right anterior cingulate cortex (ACC) as a method for addiction treatment and examines the frequency specific effects of this training in eight other regions of the cortex identified as playing an important role in substance use disorders. Methods. This case study was completed with one right-handed, 28-year-old female participant with 3 years of continuous abstinence from polysubstance abuse; her drugs of choice were heroin and alcohol, and she reported an 8-year history of alcohol abuse and a 4-year history of heroin use (IV). She completed 25 sessions of LNFB training in which she increased 14–18 Hz activity in the right ACC. We utilized electrophysiological measures to assess the increase or decrease in eight regions of interest (ROI): the right hippocampus, the right amygdaloid complex, the right orbitofrontal cortex (OFC), the right occipital lobe, the right...
The Werner Syndrome Protein Stimulates DNA Polymerase β Strand Displacement Synthesis via Its Helicase Activity

Werner syndrome is a hereditary premature aging disorder characterized by genomic instability. Genetic analysis and protein interaction studies indicate that the defective gene product (WRN) may play an important role in DNA replication, recombination, and repair. DNA polymerase β (pol β) is a central participant in both short and long-patch base excision repair (BER) pathways, which function to process most spontaneous, alkylated, and oxidative DNA damage. We report here a physical interaction between WRN and pol β, and using purified proteins reconstitute of a portion of the long-patch BER pathway to examine a potential role for WRN in this repair response. We demonstrate that WRN stimulates pol β strand displacement DNA synthesis and that this stimulation is dependent on the helicase activity of WRN. In addition, a truncated WRN protein, containing primarily the helicase domain, retains helicase activity and is sufficient to mediate the stimulation of pol β. The WRN helicase also unwinds a BER substrate, providing evidence that WRN plays a role in unwinding DNA repair intermediates. Based on these findings, we propose a novel mechanism by which WRN may mediate pol β-directed long-patch BER.
On Communicating Pride, Crying in Movies, and Recruiting Innocent Bystanders: The Effect of Sex on Communication Schemas Activated with Gay and Heterosexual Targets

Invoking social identity theory as an interpretive frame, a previous content analysis of heterosexuals' representations of imagined conversations with gay men revealed a number of communication schemas for talk with the latter (e.g., homonegativity and offense avoidance). This study explores the role of participant sex in determining the prevalence of such schemas, comparatively incorporating representations of conversations with a heterosexual target. Two hundred American undergraduates imagined a conversation with a gay or heterosexual male target. Male participants' imagined conversations with a gay target were rated more negative, indicated less evidence of relational development, and included more gay stereotyping than did females' imagined dialogues.
Interactions between dissimilar surfaces in high ionic strength solutions as determined by atomic force microscopy

Abstract The recent non-equilibrium electrophoretic mobility measurements by laser-Doppler electrophoresis coupled with the stability and prevalence of collector colloids in soluble salt flotation systems suggest that the selective flotation of alkali halides is due to the adsorption of oppositely charged collector colloids by heterocoagulation. Previously reported flotation results confirm this surface charge/collector colloid adsorption model. However, the nature of the interparticle forces responsible for heterocoagulation of such oppositely charged particles at high ionic strengths remains to be determined. In this regard, atomic force microscopy was used for interparticle force measurements at high ionic strengths. Model systems such as polystyrene/quartz and silica/sapphire were studied to measure the particle interaction forces prevalent at high ionic strengths. Results from this study indicate that while repulsive hydration forces exist between similarly charged hydrophilic particles, attractive forces exist between oppositely charged particles in high ionic strength solutions. The repulsive forces between similarly charged hydrophilic surfaces at high ionic strengths (2–4 m ) are described by a double exponential function with decay lengths of 0.17 and 1.4 nm, depending upon the surfaces involved. On the other hand, attractive forces were observed between oppositely charged hydrophilic surfaces at high ionic strengths (2–4 m ) and were described by a single exponential function with decay lengths of up to 9 nm, depending upon the surfaces involved.
Predicting college success: the importance of ability and non-cognitive variables

Abstract This chapter introduces a study which focuses on predicting college success as measured by students’ grade point averages (GPAs). The chapter also reviews prior research related to various types of predictors. Specifically, two categories of predictors are identified: ability measures and non-cognitive variables. Finally, an overview of the study is presented.
Nonlinear power dependence for efficient THz generation from InGaN/GaN multiple quantum wells

In this work, we present our new findings following our studies of the THz generation from InGaN/GaN multiple quantum wells (MQW's), pumped by a frequency-doubled sub-picosecond Ti:sapphire amplifier at the output wavelength of 395 nm. For the pump power of 320 mW, an average output power of 32 nW was measured in the frequency range of 300 GHz - 4.28 THz. Based on the photo luminescence (PL) spectra measured on these InGaN/GaN MQW's, quantum dots (QD's) were formed.
Network-aware, energy-conscious, fair service for real-time applications on multiprocessor SoC

We consider systems consisting of wireless nodes that execute CPU intensive applications on multiprocessor systemon- a-chip (MPSoC) and must transmit packets over the network in a timely manner. Existing methods do not consider packet deadlines in conjunction with energy and real-time task performance, making it hard to predict system behavior. We present an energy-aware adaptive CPU scheduling algorithm to maximize the number of packet deadlines met in a fair manner and discuss future work.
Efficiency of some sampling designs for spatially clustered populations

The efficiencies of two sampling designs for estimating the mean of a fixed, finite population are considered. The first is adaptive cluster sampling (ASRS; Thompson, 1990 Journal of the American Statistical Association) which is designed to adaptively increase sampling effort in the neighbourhood of units whose observed value meets some predefined condition. The other is Balanced Sampling Excluding Contiguous Units (BSEC) (Hedayat, Rao and Stufken, 1988, Journal of Statistical Planning and Inference), a conventional design in which neighbouring units are deliberately excluded from being sampled under the idea that they provide little new information to the sampling effort. We consider the effect of type of neighbourhood, initial sample size, condition for adaptively sampling neighbours, and degree and extent of clustering in the population on the efficiency of ASRS relative to BSEC and simple random sampling. Populations having different degrees of clustering are simulated using a modified Neyman–Scott process. We compare the design-based variances of two estimators, a Horvitz–Thompson-type estimator and a Hansen–Hurwitz-type estimator. While the Horvitz–Thompson-type estimator can have the lowest variance under some of the situations explored, it is also the most sensitive to changes in the conditions. The efficiency of the estimator often comes at the cost of a large effective sample size. In general, ASRS is more efficient when the population elements are rare and highly clustered although BSEC designs are generally more efficient for a wider array of combinations of conditions. © 1997 John Wiley & Sons, Ltd.
Not by search alone: how recommendations complement search results

This paper presents a novel approach to combining search and recommendations methods into one integrated system to satisfy user information seeking needs. It is shown theoretically and experimentally using simulations that the proposed combined approach outperforms "pure" search and "pure" recommendations in those cases when search is hindered by the user's inability to come up with a complete set of search criteria, and recommendation engine produces mediocre results.
Effects of psychotropic drugs on second messenger signaling and preference for nicotine in juvenile male mice

A common treatment strategy for pediatric attention deficit/hyperactivity disorder (ADHD) and major depressive disorder (MDD) is combined methylphenidate (MPH) and fluoxetine (FLX). This has raised concerns because MPH + FLX treatment may have pharmacodynamic properties similar to cocaine, potentially increasing drug abuse liability. To examine the short- and long-term consequences of repeated vehicle, MPH, FLX, MPH + FLX, and cocaine treatment on gene expression in juvenile (postnatal days [PD] 20–34) and adult (PD 70–84) male mice. We further assessed whether juvenile drug treatment influenced subsequent sensitivity for nicotine in adulthood. Juvenile and adult C57BL/6J mice received vehicle, MPH, FLX, MPH + FLX, or cocaine twice-daily for 15 consecutive days. Mice were sacrificed 24 h or 2 months after the last drug injection to assess drug-induced effects on the extracellular signal-regulated protein kinase-1/2 (ERK) pathway within the ventral tegmental area. Subsequent sensitivity for nicotine (0.05, 0.07, and 0.09 mg/kg) was measured using the place-conditioning paradigm (CPP) 24 h and 2 months after juvenile drug exposure. MPH + FLX, or cocaine exposure in juvenile mice increased mRNA expression of ERK2 and its downstream targets (CREB, cFos, and Zif268), and increased protein phosphorylation of ERK2 and CREB 2 months after drug exposure. Similar mRNA findings were observed in the adult-treated mice. Findings on gene expression 24 h following drug treatment were variable. Juvenile drug exposure increased preference for nicotine when tested in adulthood. Early-life MPH + FLX, or cocaine exposure similarly disrupts the ERK pathway, a signaling cascade implicated in motivation and mood regulation, and increases sensitivity for nicotine in adulthood.
The plasma pump — A new magnetic mirror plasma confinement scheme

Abstract A method of using rf to produce an asymmetric mirror is described, and its theory developed. Suggestions for using this asymmetric mirror in multiple mirror confinement systems are presented.
The effect of N-methyl-N'-nitro-N-nitrosoguanidine (MNNG) on cultured dog pancreatic duct epithelial cells.

To study the morphologic and genetic events associated with the carcinogenic process in the pancreas, we have isolated and cultured a cell line of dog pancreatic duct epithelial cells and treated these cells with a carcinogen. The pancreatic duct epithelial cells were plated onto Vitrogen-coated Transwell inserts suspended above a feeder layer of human gallbladder myofibroblasts. The epithelial cells grew steadily into polarized monolayers, could be passaged repeatedly, and demonstrated the typical morphologic, immunohistochemical, and flow cytometric profile of normal well-differentiated columnar pancreatic epithelial cells. After being treated with 10 -5 M N-methyl-N'-nitro-N-nitrosoguanidine (MNNG) for 48 h, the treated cells grew on plastic surfaces. When grown in organotypic culture, the MNNG-treated cells were cuboidal with a multilayered, pseudostratified architecture. Flow cytometry demonstrated aneuploidy and a high percentage of the cells in S phase after reaching confluency, in sharp contrast to untreated cells. Cytogenetic analysis of the MNNG-treated cells revealed frequent chromosomal trisomy and tetrasomy. The secretion of mucin was also different in the MNNG-treated cells versus the untreated cells. The cultured pancreatic epithelial cells may be useful as an assay system to study the genotoxicity of known and potential carcinogens.
New design for a rotatory joint actuator made with shape memory alloy contractile wire

A design approach for a rotatory joint actuator using a contractile shape memory alloy (SMA) wire is presented and an example design is followed. In this example, the output torque of the actuator is 18 Newton-meters, and its angular range is 30 degrees. Compared with a SMA spring type actuating component, a SMA wire type actuating component uses less SMA material and uses less electrical energy when it is electrically powered. On the other hand, a SMA wire type actuating component must have a large SMA wire length to produce a required amount of angular rotation of the joint. When pulleys are used to arrange a lengthy SMA wire in a small space, the friction between pulleys and pins is introduced and the performance of the joint actuator is degenerated to some degree. The investigated joint actuator provides a good chance for developing powered orthoses with SMA actuators for disabled individuals. It can relieve the weight concern with hydraulic and motor-powered orthoses and the safety concern with motor-powered orthoses. When electrically powered, a SMA actuator has the disadvantage of low energy efficiency.© (1996) COPYRIGHT SPIE--The International Society for Optical Engineering. Downloading of the abstract is permitted for personal use only.
Centroid-moment tensor solutions for July–September 1988

Abstract Centroid-moment tensor solutions are presented for 247 earthquakes that occurred during the third quarter of 1988. The solutions are obtained using corrections for aspherical Earth structure.
Chyluria after radiofrequency ablation of renal tumors.

Abstract Purpose To assess the incidence of chyluria after radiofrequency (RF) ablation of renal tumors and attempt to identify predictors of this phenomenon. Materials and Methods Over a 3-year period, 62 consecutive patients with renal tumors were treated by percutaneous computed tomography (CT)–guided or laparoscopic RF ablation, of which 41 underwent at least three posttreatment CT studies and were evaluated in this study. Three radiologists reviewed the pretreatment and posttreatment CT images for the presence or absence of fat-fluid levels in the bladder, the location of the tumor, and the size of the postablation defect. A logistic regression model was used to assess whether ablation defect size or tumor location predicted chyluria. Results Chyluria was detected at a mean time of 44.5 weeks in 17 (41%) of 41 patients with renal tumors treated by RF ablation. A pretreatment biopsy specimen showed renal cell carcinoma in 74%. Mean tumor size was 2.77 cm, and mean initial ablation size was 4.2 cm. Chyluria persisted in seven patients. Zone of ablation defect size and tumor location were not significant predictors of chyluria ( P = .64 and P = .42). Mean follow-up was 77 weeks. Conclusions Chyluria is a common and asymptomatic finding in a significant proportion of patients undergoing RF ablation for renal tumors. Tumor location and zone of ablation defect size were not predictors of chyluria. The presence of a fat-fluid level should not be mistaken for an air-fluid level.
Peroxo−Iron Mediated Deformylation in Sterol 14α-Demethylase Catalysis

The mechanisms of cytochrome P450 (CYP) catalyzed C−C bond cleavage have been strongly debated and difficult to unravel. Herein, deformylation mechanisms of the sterol 14α-demethylase (CYP51) from Mycobacterium tuberculosis are elucidated using molecular dynamics simulation, density functional theory, and hybrid quantum mechanics/molecular mechanics methods. These results provide strong theoretical support for the operation of the peroxo intermediate in CYP-catalyzed deformylation. Molecular dynamics simulations support the lanosterol carboxaldehyde intermediate diverts the hydrogen-bonded network of water putatively involved in proton delivery to peroxo and compound 0 (Cmpd 0) away from the O2 ligand. In the presence of the aldehyde substrate, the peroxo intermediate is trapped as the peroxohemiacetal without an apparent barrier, which may then be protonated in the active site. The unprotonated peroxohemiacetal provides a branch point for a concerted deformylation mechanism; however, a stepwise mechanism...
The nature of the Si-O-Si bond angle distribution in vitreous silica

Abstract Experimental and modelling studies from the literature on vitreous silica have shown anomalous differences in the position of the maximum in the Si-O-Si bond angle distribution. A careful review of a purported refinement of experimental data indicates that the maximum at α=144° reported by Mozzi and Warren (1969) is, in fact, relatively insensitive to various analytical treatments. The original experimental bond angle distribution is, in turn, in reasonable agreement with Gaskell and Tarrant's computer-relaxed version of the Bell and Dean model (Gaskell and Tarrant 1980, Bell and Dean 1972).
CyberKnife frameless single-fraction stereotactic radiosurgery for tumors of the sacrum.

Object. The role of stereotactic radiosurgery for the treatment of intracranial lesions is well established. The experience with radiosurgery for the treatment of spinal and sacral lesions is more limited. Sacral lesions should be amenable to radiosurgical treatment similar to that used for their intracranial counterparts. The authors evaluated a single-fraction radiosurgical technique performed using the CyberKnife Real-Time Image-Guided Radiosurgery System for the treatment of the sacral lesion. Methods. The CyberKnife is a frameless radiosurgery system based on the coupling of an orthogonal pair of x-ray cameras to a dynamically manipulated robot-mounted linear accelerator possessing six degrees of freedom, which guides the therapy beam to the intended target without the need for frame-based fixation. All sacral lesions were located and tracked for radiation delivery relative to fiducial bone markers placed percutaneously. Eighteen patients were treated with single-fraction radiosurgery. Tumor histology included one benign and 17 malignant tumors. Dose plans were calculated based on computerized tomography scans acquired using 1.25-mm slices. Planning treatment volume was defined as the radiographically documented tumor volume with no margin. Tumor dose was maintained at 12 to 20 Gy to the 80% isodose line (mean 15 Gy). Tumor volume ranged from 23.6 to 187.4 ml (mean 90 ml). The volume of the cauda equina receiving greater than 8 Gy ranged from 0 to 1 ml (mean 0.1 ml). All patients underwent the procedure in an outpatient setting. No acute radiation toxicity or new neurological deficits occurred during the mean follow-up period of 6 months. Pain improved in all 13 patients who were symptomatic prior to treatment. No tumor progression has been documented on follow-up imaging. Conclusions. Stereotactic radiosurgery was found to be feasible, safe, and effective for the treatment of both benign and malignant sacral lesions. The major potential benefits of radiosurgical ablation of sacral lesions are relatively short treatment time in an outpatient setting and minimal or no side effects. This new technique offers a new and important therapeutic modality for the primary treatment of a variety of sacral tumors or for lesions not amenable to open surgical techniques.
Natural killer cell activity in reticulum-cell sarcomas of SJL/J mice. III. Characterization of the effector cells within RCS that mediate NK lysis.

Various cell depletion techniques were employed to identify the cells responsible for the natural killer (NK) activity against YAC-1 targets that is present in lymphoid tissues of SJL/J mice bearing transplantable reticulum-cell sarcomas (RCS). The NK-activating potential of irradiated RCS cells (X-RCS) allowed a comparison of three NK-cell activities in this model system: conventional, induced and RCS-cell-mediated cytotoxicity, represented by effector cells derived from lymphoid tissues of normal, X-RCS-injected and RCS-bearing donors, respectively. Both the conventional and induced NK cells were resistant to pretreatment with anti-la serum and C, whereas RCS-mediated NK activity was significantly reduced by similar antiserum treatment. The cytotoxicity expressed by both conventional and induced NK cells was moderately radiosensitive, however, 5- to 10-fold higher doses of irradiation were required to effect an equivalent reduction of RCS-mediated NK activity. To further characterize the effector cells that mediated RCS-associated NK activity, viable RCS tumor cells were injected into SJL F1 hybrids that either supported (SJL × C57EL/6 and SJL × A.TH) or did not support [SJL × B10.S(7R)] RCS growth. After pretreatment of RCS cell preparations taken from these F1 mice with alloantisera directed against the non-SJL parental H-2 haplotype, to remove F1 host cells (F1-purified RCS), >75% of NK activity was recovered in the RCS-injected SJL × C57BL/6 and SJL × A.TH F1 hybrids; however, <15% of NK activity was apparent in RCS-injected SJL × B10.S(7R) F1 recipients. 89Sr treatment of SJL mice abrogated their ability to show increased (induced) NK activity following injection of X-RCS. In contrast, viable, F1-purified RCS cells demonstrated both growth and NK activity in 89Sr-treated SJL mice that was comparable to that seen in normal controls. Treatment of effector cells with three different NK-reactive antisera (αLy-11.2, αNK-1.2 and αasialo-GM1) effectively depleted conventional and induced NK activities, but had a minimal effect on RCS-cell-mediated NK cytotoxicity. These data support the conclusion that RCS tumor cells of SJL/J origin possess NK cytotoxic function and that, by virtue of their pre-B-cell characteristics, they may represent a unique class of NK effectors.
Sanctius' Minerva of 1562 and the Evolution of His Linguistic Theory

The 1587 edition of Sanctius' Minerva was not the first edition: a 1562 version has recently been discovered. This paper outlines Sanctius' linguistic theory as it is advanced in the earlier version and traces its evolution. Some aspects of Sanctius' system are briefly considered with relation to his immediate predecessors Linacre, Scaliger, and Ramus. I attempt to show that the basic tenets of his theory are already present in the early work: his conception of grammar, the importance of his logical rules (rationes), and his abstract notion of ellipsis as an essential mechanism for positing underlying structures and general rules, as well as for explaining obscure syntactic constructions. His views on the noun and the constructio of nouns, on verbs and the constructio of verbs are presented in an effort to show his evolution towards a more simple and general system of language. No attempt is made to cover those aspects of his theory which appear only in the later Minerva.
Evolving novel anti-HER2 strategies

Summary The approval of trastuzumab for use in metastatic breast cancer marked a breakthrough in the understanding of the biology of the disease. However, like most cancer therapies, the disease finds a way to advance despite the treatments developed to eradicate it. Although trastuzumab has had a large effect on the treatment of early and advanced-stage disease, a substantial proportion of patients with HER2-positive breast cancer still progress after receiving the drug. Potential mechanisms of resistance to trastuzumab include bypass mechanisms, mutations of the HER2 target, masking of HER2 proteins, inhibition of insulin-like growth factor, and phosphatase and tensin homologue (PTEN) deficiency. Many therapies are being developed to target these mechanisms in patients with HER2-positive, trastuzumab-resistant breast cancer. Additionally, treatment strategies other than trastuzumab with unique mechanisms of action are being assessed in this specific group of patients. In this review, we discuss the emerging data assessing therapeutic approaches in the management of trastuzumab-resistant HER2-positive disease.
Comparative QSAR and radical toxicology: the aromatic CH2OH moiety

Evidence is summarized to show via quantitative structure–activity relationships (QSAR) that the aromatic CH2OH group when conjugated with electron-releasing substituents displays toxic effects that suggest a radical reaction mechanism. The evidence can be used to explain the inhibitory action of lucanthone toward schistosomiasis. That is, lucanthone per se is not active, but its metabolite in which a methyl group has been converted to CH2OH is. This calls to mind the activity of chloramphenicol, which was a very effective anti-bacterial agent, but also caused serious blood dyscrasias in some patients. Presumably this could have been due to the toxic action of radicals.
Al2O3-mediated deacetylation of CpFe(ethyl-2-phenylacetoacetate) hexafluorophosphate

Abstract Passage of the title compound through a short column of Al 2 O 3 induces deacetylation to form CpFe(ethyl-2-phenylacetate) hexafluorophosphate. This compound is shown to react with base to generate the stabilized enolate, which is dideuteriated or dimethylated upon quenching with excess D 2 O or CH 3 I.
Who's afraid of absolute space?

(1970). Who's afraid of absolute space? Australasian Journal of Philosophy: Vol. 48, No. 3, pp. 287-319.
Just-in-time annotation of clusters, outliers, and trends in point-based data visualizations

We introduce the concept of just-in-time descriptive analytics as a novel application of computational and statistical techniques performed at interaction-time to help users easily understand the structure of data as seen in visualizations. Fundamental to just-intime descriptive analytics is (a) identifying visual features, such as clusters, outliers, and trends, user might observe in visualizations automatically, (b) determining the semantics of such features by performing statistical analysis as the user is interacting, and (c) enriching visualizations with annotations that not only describe semantics of visual features but also facilitate interaction to support high-level understanding of data. In this paper, we demonstrate just-in-time descriptive analytics applied to a point-based multi-dimensional visualization technique to identify and describe clusters, outliers, and trends. We argue that it provides a novel user experience of computational techniques working alongside of users allowing them to build faster qualitative mental models of data by demonstrating its application on a few use-cases. Techniques used to facilitate just-in-time descriptive analytics are described in detail along with their runtime performance characteristics. We believe this is just a starting point and much remains to be researched, as we discuss open issues and opportunities in improving accessibility and collaboration.
Taking on the World: The International Activities of American State Legislatures

State legislatures in the United States engage in a substantial amount of international activity. In the 2001-2002 legislative sessions, some 886 bills and resolutions with significant international implications were introduced. Approximately 306 of these were adopted. This level of international activity has increased substantially since 1991, and the substantive focus has changed over time. In addition, about half of all state legislatures received at least one foreign delegation and sent at least one delegation of members abroad in the last session. As in most areas of state policy, there is considerable interstate variation in legislatures' international activities. Some states had virtually no international legislative activity, whereas others were very active. The principal factors explaining this variation were the degree of state involvement in the international economy, as measured by the level of state exports, and party control of the legislature. Copyright 2004, Oxford University Press.
Ion Temperature Variations in the Daytime High-Latitude F Region

The Schunk and Sojka (1981a, b) high latitude ionospheric model is improved through the inclusion of thermal conduction and diffusion terms in the ion energy equation, permitting the study of daytime, high latitude F layer temperature variations in a region poleward of the auroral oval. It is found that ion temperature variation with solar cycle, season and geomagnetic activity closely follows the neutral atomic oxygen variation, and that meridional electric fields of more than 40 mV/m can cause larger ion temperature changes than those due to solar cycle, seasonal or geomagnetic activity variations. In the presence of meridional electric fields, there is an upward flow of heat from the lower ionosphere that also acts to raise ion temperatures at high altitudes. Zonal electric fields affect ion temperature indirectly, through electron density changes.
Performance measurements of Web applications

The goal of this research is to produce objective data comparing the performance of the most widely utilized Web application classes in an invariant laboratory environment. Efficient Web applications lead to faster response to user requests and to more efficient utilization of server resources. Commercial tests utilize aggregated load-test benchmarks to obtain outcomes usually intended to promote proprietary products. In this research, various Web applications are tested on the same system with homogeneous page requests having known content that produces a known response from the application. The laboratory LAN environment ensures repeatability of test conditions and avoids problems such as multipath effects on the Internet. The test environment and testing protocol are described. Results of the first round of performance testing are summarized.
Computer‐Based Voice Recognition: Characteristics, Applications, and Guidelines for Use

The use of various computer interfaces has evolved from the exclusive use of teletype terminals and keypunch cards to the use of specialized hardware devices designed for specific applications or environments. One of the most recent additions to this growing list of interface options is voice recognition technology, generally defined as the ability to control a computer system through voice input from the operator. Although still somewhat in its infancy, this technology is becoming more commonplace in situations where traditional input devices cannot be used, such as hands–busy operations or with physically disabled users. This paper provides a description of this technology, information about several applications in industry and education where it has been utilized, and a number of guidelines for its implementation and use.
Corporate authority, exchange, and personal opposition in Bobo marriages

This article explores the bases of corporate authority and personal autonomy in marriage decisions among the Bobo, a West African people with a double-descent system. Elder men and women allocate young women within the uterine descent group, thereby constraining the choices of partners and creating patterns that are consistent with the desire to maintain control over dependents. These practices, however, are continuously challenged by young people who advocate divergent perspectives and whose opposition is facilitated by the support of other types of kin. The emergence of wealth differences and the effect of administration and missionary activity contributed to dissension against the men and women who have positions of authority within lineage segments, at the same time as it reduced the solidarity among them. [kinship, social organization, double descent, rural transformation, West Africa]
An interdomain binding site on HIV-1 Nef interacts with PACS-1 and PACS-2 on endosomes to down-regulate MHC-I

The human immunodeficiency virus type 1 (HIV-1) accessory protein Nef directs virus escape from immune surveillance by subverting host cell intracellular signaling and membrane traffic to down-regulate cell-surface major histocompatibility complex class I (MHC-I). The interaction of Nef with the sorting proteins PACS-1 and PACS-2 mediates key signaling and trafficking steps required for Nef-mediated MHC-I down-regulation. Little is known, however, about the molecular basis underlying the Nef–PACS interaction. Here we identify the sites on Nef and the PACS proteins required for their interaction and describe the consequences of disrupting this interaction for Nef action. A previously unidentified cargo subsite on PACS-1 and PACS-2 interacted with a bipartite site on Nef formed by the EEEE65 acidic cluster on the N-terminal domain and W113 in the core domain. Mutation of these sites prevented the interaction between Nef and the PACS proteins on Rab5 (PACS-2 and PACS-1)- or Rab7 (PACS-1)-positive endosomes as determined by bimolecular fluorescence complementation and caused a Nef mutant defective in PACS binding to localize to distorted endosomal compartments. Consequently, disruption of the Nef–PACS interaction repressed Nef-induced MHC-I down-regulation in peripheral blood mononuclear cells. Our results provide insight into the molecular basis of Nef action and suggest new strategies to combat HIV-1.
Labile anticoagulant in a patient with lymphoma

A patient with diffuse lymphocytic lymphoma and monoclonal IgM kappa immunoglobulin was found to have an unstable circulating anticoagulant. The anticoagulant inhibited phospholipid-dependent plasma coagulation reactions. Unlike previously described anticoagulants of this type, this plasma inhibitor was neutralized in vitro by products of platelet lysis but not by exogenous addition of other phospholipids or by intact platelets. Inhibitory activity seemed dependent on the monoclonal immunoglobulin, but isolated immunoglobulin fractions lacked anticoagulant activity, suggesting that the inhibitory function was dependent on an easily disrupted macromolecular aggregate. Recognition and characterization of other similar anticoagulants may provide a means of studying the role of phospholipids in normal hemostasis.
MULTIPLE SCLEROSIS AND EXPERIMENTAL ALLERGIC ENCEPHALOMYELITIS: SPECIFIC DEMYELINATION OF CNS IN CULTURE

Multiple sclerosis and experimental allergic encephalomyelitis: specific demyelination of CNS in culture Cultures of mouse spinal cord tissue coupled to dorsal root ganglia, in which both CNS and PNS myelin develop, have been exposed for various periods of time to sera from patients with multiple sclerosis (MS) and animals with experimental allergic encephalomyelitis (EAE) induced by inoculation with whole CNS tissue in complete Freund's adjuvant. In both instances (MS and EAE), there was a selective depletion of CNS myelin with no adverse effect visible on PNS myelin in the same cultures. Prolonged exposure to demyelinating sera led to a sclerotic appearance in the CNS portion of cultures while PNS myelination progressed unimpeded. The results lend weight to the hypothesis that MS results from an immunological mechanism directed specifically against the CNS.
Soft tissue sarcomas in the African hedgehog (Atelerix albiventris): microscopic and immunohistologic study of three cases.

Three soft tissue tumors from 2 female hedgehogs were examined microscopically and immunohistochemically. Two tumors involved haired skin and the third one was vaginal. Microscopically, the cutaneous tumors had features of malignant peripheral nerve sheath tumor (MPNST), whereas the vaginal tumor was classified only as a spindle cell sarcoma. Immunohistochemically, all 3 tumors were strongly positive for vimentin and strongly to moderately positive for CD10 and neuron-specific enolase but did not stain with antibody to S100 protein, an antigen typically present in human MPNST. The cutaneous tumor from hedgehog no. 1 was examined ultrastructurally and the neoplastic cells resembled fibroblasts. Hedgehog no. 1 was euthanized at the time of the biopsy. The outcome of the other hedgehog was unknown.
Organoboranes for synthesis. 12. The reaction of organoboranes with nitrogen trichloride. A convenient procedure for the conversion of alkenes into alkyl chloridesvia hydroborationi

Abstract Trialkylboranes are readily converted to the corresponding alkyl chlorides by a free radical reaction with nitrogen trichloride (NCl 3 ). Compared to many other chlorinating agents examined, NC1 3 is a superior reagent for the effective conversion of organoboranes into alkyl chlorides. Combined with the high regioselectivity inherent in the hydroboration reaction, the treatment with NC1 3 allows alkenes to be transformed into pure alkyl chlorides of predictable structure. This process constitutes a valuable method for the anti-Markovnikov hydrochlorination of alkenes in 66–94% yield. Experimental evidence indicates that this reaction proceeds via free radical intermediates. The reaction of organoboranes with NC1 3 is comparable to or better than other methods, such as those requiring refluxing aqueous cupric or ferric chloride, or those producing hydrogen chloride as a by-product. Consequently, this procedure could be very useful for the conversion of acid-sensitive ( e.g. , certain bicyclic) alkenes into alkyl chlorides where extensive skeletal rearrangements occur in hydrogen chloride additions.
Force, Mathematics, and Physics in Newton's Principia: A New Approach to Enduring Issues

ArgumentThis paper investigates the conceptual treatment and mathematical modeling of force in Newton's Principia. It argues that, contrary to currently dominant views, Newton's concept of force is best understood as a physico-mathematical construct with theoretical underpinnings rather than a “mathematical construct” or an ontologically “neutral” concept. It uses various philosophical and historical frameworks to clarify interdisciplinary issues in the history of science and draws upon the distinction between axiomatic systems in mathematics and physics, as well as discovery patterns in science. It also dwells on Newton's “philosophy” of mathematics, described here in terms of mathematical naturalism. This philosophy considers mathematical quantities to be physically significant quantities whose motions are best mapped by geometry. It then shows that to understand the epistemic status of force in the Principia, it is important to scrutinize both Newton's mathematical justificatory strategies and his background assumptions about force – without constructing, however, an overarching metaphysical framework for his science. Finally, the paper studies scientific attempts to redefine or eliminate force from science during the period between Newton and Laplace. From a philosophical standpoint, the paper implicitly suggests that questions about the reality of force be distinguished from questions about the validity of force, and that both sets of questions be distinguished from questions about the utility of the concept of force in science.
Drospirenone and estradiol: a new option for the postmenopausal woman

The efficacy of estrogen with or without a progestogen as hormone replacement therapy (HRT) for menopausal symptoms is well-established. Recent large-scale randomized studies with combined estrogen/progestogen therapy (EPT) have raised a number of safety issues, specifically the potential risk for coronary heart disease. Subsequent analyses and other studies have indicated that HRT may be cardioprotective in younger postmenopausal women. A new continuous EPT combines natural 17beta-estradiol (E2) 1 mg with the novel progestin, drospirenone (DRSP) either 0.5 or 2 mg. DRSP has a physiological profile closer to that of natural progesterone than any other synthetic progestin. This paper reviews recent clinical trial data demonstrating the efficacy and safety of combined DRSP/E2 therapy as EPT in postmenopausal women. DRSP/E2 provides symptomatic relief of vasomotor symptoms and improvement in genitourinary atrophy. DRSP/E2 protects against endometrial hyperplasia and reduces the risk of osteoporosis. Combined DRSP/E2 therapy has a favorable impact on cholesterol and triglyceride levels, and decreases blood pressure in women with elevated blood pressure. The favorable efficacy and safety profile of DRSP/E2, and potential for long-term health benefits, represents a new option for the effective management of menopause and its clinical sequelae.
Molecular dynamics studies of brittle fracture in vitreous silica : Review and recent progress

Abstract The dynamics of brittle fracture in vitreous silica has been a subject of many molecular dynamics (MD) simulations and experiments. A striking similarity between both simulations and experiments is the observation of nanoscale voids that eventually coalesce leading to failure. In this work, we review the above MD simulations and carry out further MD investigations using two variations of classical 2-body potentials. We study the effect of charge-transfer, an important aspect neglected by previous simulations. Further, we examine the growth of ‘critical’ voids and characterize regions surrounding the voids.
Distinguishing the Trees from the Forest: Applying Cluster Analysis to Thematic Qualitative Data

Qualitative data analysis requires organizing and synthesizing often large quantities of text. In many cases, this analysis entails negotiating the interplay between raw data, semantic themes or co...