cssi/SciSciGPT-SciSciNet huggingface dataset:
DNA methylation evidence against the accelerated aging hypothesis of schizophrenia

The accelerated aging hypothesis of schizophrenia posits that physiological changes throughout the body that are associated with normal aging occur at an earlier age in individuals with schizophrenia. Testing this hypothesis has been limited by problems measuring biological age. Recently, a method using DNA methylation levels at 353 genomic sites to produce “DNA methylation age”, an estimate of tissue biological age, was described and validated. We used this method to test the hypothesis in the postmortem superior temporal gyrus of 22 non-psychiatric control and 22 schizophrenia subjects. DNA methylation age correlated with chronological age in both non-psychiatric control (r = 0.95, p < 0.0001) and schizophrenia subjects (r = 0.96, p < 0.0001). Age acceleration did not differ between non-psychiatric control and schizophrenia subjects (t = 1.27, p = 0.21). Our findings suggest there is no acceleration of brain aging in schizophrenia. Larger studies using samples from multiple brain regions and homogenous cell populations will be necessary to confirm these findings.
Modeling chloride ingress in concrete with thermodynamically calculated chemical binding

An alternative approach is developed to incorporate chloride binding/release processes during modeling of ingress of external chlorides in concrete through the use of thermodynamic modeling of chemical reactions. Transport of chloride in concrete is modeled through transient finite element analysis. At each time marching step, the chloride binding/release reactions are modeled using thermodynamic calculations. For this purpose, an open-source thermodynamic modeling software is used to model all possible reactions within the cementitious matrix including the reactions of chlorides with unhydrated and hydrated cementitious materials. The predictive ability of thermodynamic calculations is presented by comparing them with experimental data. The proposed and traditional modeling approaches for chloride transport with binding are compared. Finally, a parametric investigation is presented to demonstrate some of the strengths of the proposed approach using thermodynamic calculations over the traditional approach using binding isotherms to simulate chloride ingress in concrete.
Abstract P47: Predicting Death and Stroke After Carotid Endarterectomy in Asymptomatic Patients: A Clinical Prediction Model

Background and Purpose: National AHA guidelines on carotid endarterectomy (CEA) for asymptomatic patients (Pts) stipulate that the long term benefit of surgery is dependent on having a ≤ 3% risk of perioperative death or stroke (D/S) due to the procedure. We developed and validated a multivariate model of risk of D/S within 30 days of CEA for asymptomatic disease and a clinical prediction rule based on the final model. Methods: We analyzed data from 6553 asymptomatic cases in the New York Carotid Artery Surgery (NYCAS) study, a population-based cohort of all Medicare beneficiaries having CEA in NY State from 1/98 to 6/99. Medical records were abstracted for: sociodemographics, neurological history, carotid imaging data, comorbidities, and D/S within 30 days. All events were adjudicated. Multivariate logistic regression with GEE was used to identify independent predictors of combined D/S. The final model was cross-validated with100 random splits. A CEA-8 Clinical Risk Score assigned 1 point to each risk factor except for disability which got 2 points. Results: The 6553 CEAs were performed by 435 surgeons in 157 hospitals. Mean age was 74 years, 3655 were male, 4152 had coronary artery disease (CAD), 873 valvular disease, 611 congestive heart failure (CHF), 1453 history of distant stroke or TIA, and 93 severe disability. Nearly all (6413) had 70-90% ipsilateral stenosis, and 2469 had ≥ 50% contralateral stenosis. The combined 30 day D/S rate was 3.0% (198 of 6553). Multivariable predictors of perioperative D/S were: female (OR, 1.5; 95% CI, 1.1-1.9), non-white (OR, 1.8; 1.1-2.9), severe disability (OR, 3.7; 1.8-7.7), CHF (OR, 1.6; 1.1-2.4), CAD (OR, 1.6; 1.2- 2.2), valvular heart disease (OR, 1.5; 1.1-2.3), distant history of stroke/TIA (OR, 1.5; 1.1- 2.0), and non-operated stenosis ≥50% (OR, 1.8; 1.3-2.3). The CEA-8 Risk Score stratified Pts from a D/S rate of 0.6% (3 of 509) to 10% (16 of 159). Conclusions: Several sociodemographic, neuroseverity, and comorbidity factors predicted risk of D/S in asymptomatic patients having CEA. A CEA-8 Risk Score of ≥ 4 identifies high risk Pts (predicted D/S rate of >7.5%) with 2.5 times the AHA guideline acceptable complication risk in asymptomatic Pts (≤ 3%).
Association of Changes in Neighborhood-Level Racial Residential Segregation With Changes in Blood Pressure Among Black Adults: The CARDIA Study.

Importance Despite cross-sectional evidence linking racial residential segregation to hypertension prevalence among non-Hispanic blacks, it remains unclear how changes in exposure to neighborhood segregation may be associated with changes in blood pressure. Objective To examine the association of changes in neighborhood-level racial residential segregation with changes in systolic and diastolic blood pressure over a 25-year period. Design, Setting, and Participants This observational study examined longitudinal data of 2280 black participants of the Coronary Artery Risk Development in Young Adults (CARDIA) study, a prospective investigation of adults aged 18 to 30 years who underwent baseline examinations in field centers in 4 US locations from March 25, 1985, to June 7, 1986, and then were re-examined for the next 25 years. Racial residential segregation was assessed using the Getis-Ord G i * statistic, a measure of SD between the neighborhood’s racial composition (ie, percentage of black residents) and the surrounding area’s racial composition. Segregation was categorized as high (G i * >1.96), medium (G i * 0-1.96), and low (G i * Main Outcomes and Measures Within-person changes in systolic and diastolic blood pressure across 6 examinations over 25 years. Results Of the 2280 participants at baseline, 974 (42.7%) were men and 1306 (57.3%) were women. Of these, 1861 (81.6%) were living in a high-segregation neighborhood; 278 (12.2%), a medium-segregation neighborhood; and 141 (6.2%), a low-segregation neighborhood. Systolic blood pressure increased by a mean of 0.16 (95% CI, 0.06-0.26) mm Hg with each 1-SD increase in segregation score after adjusting for interactions of time with age, sex, and field center. Of the 1861 participants (81.6%) who lived in high-segregation neighborhoods at baseline, reductions in exposure to segregation were associated with reductions in systolic blood pressure. Mean differences in systolic blood pressure were −1.33 (95% CI, −2.26 to −0.40) mm Hg when comparing high-segregation with medium-segregation neighborhoods and −1.19 (95% CI, −2.08 to −0.31) mm Hg when comparing high-segregation with low-segregation neighborhoods after adjustment for time and interactions of time with baseline age, sex, and field center. Changes in segregation were not associated with changes in diastolic blood pressure. Conclusions and Relevance Decreases in exposure to racial residential segregation are associated with reductions in systolic blood pressure. This study adds to the small but growing body of evidence that policies that reduce segregation may have meaningful health benefits.
Species abundance plays a dominant role in local and regional extinctions in freshwater communities and allows the identification of selective extinctions

Recent declines in global biodiversity emphasize that understanding the factors that determine extinction risk should be a priority for ecologists and conservation biologists. A key question is whether extinctions are nonrandom and selective, in which case knowledge of selectivity may help predict and prevent future extinction. We suggest, however, that a premature focus on the identification of selective, trait-based determinants of extinctions risk is problematic if the potential importance of stochastic extinction processes are not first considered. Within this context we aimed to determine the roles that stochastic extinction and species abundance play in extinction risk by applying a rarefaction-based null model approach to analyzing biodiversity declines and extinctions in an experimental system. We focused on aquatic macroinvertebrate declines and extinction caused by predation by fish (Lepomis cyanellus) in semi-natural freshwater mesocosms. We found that null-predicted local extirpations based on the random loss of individuals were a significant predictor of observed local extirpations, and that the majority of observed extinctions were consistent with stochastic mechanisms of extinction, as predicted by a rarefaction model. We were able to identify a number of selective extinctions that were not predicted by the rarefaction model, and while these were relatively rare, they contributed to greater-than-expected loss of diversity at both local (mesocosm) and regional (whole experiment) spatial scales. Our results confirm that species abundance and occupancy are among the most important factors in identifying extinction risk in response to a disturbance. Moreover, owing to our use of a stochastic null model, we also conclude that measures of abundance are important indicators of extinction probability because they are operated on by the random loss of individuals, suggesting that stochastic extinction is an important process in this system and in biodiversity loss in general.
Fractal modes and multi-beam generation from hybrid microlaser resonators.

Fractals are ubiquitous in nature, and prominent examples include snowflakes and neurons. Although it has long been known that intricate optical fractal patterns can be realized with components such as gratings and reflecting spheres, generating fractal transverse modes from a laser has proven to be elusive. By introducing a 2D network of microspheres into a Fabry-Perot cavity bounding a gain medium, we demonstrate a hybrid optical resonator in which the spheres enable the simultaneous generation of arrays of conventional (Gaussian) and fractal laser modes. Within the interstices of the microsphere crystal, several distinct fractal modes are observed, two of which resemble the Sierpinski Triangle. Coupling between adjacent fractal modes is evident, and fractal modes may be synthesized through design of the microsphere network. Owing to a unique synergy between the gain medium and the resonator, this optical platform is able to emit hundreds of microlaser beams and probe live motile cells.
Characteristics of proliferative cells from young, old, and transformed WI 38 cultures.

An important, perhaps central event in the aging of human fibroblasts in vitro is a decline in proliferative capacity exhibited by cell populations as they are carried in serial passage (1–3). In characterizing this aging process at the cell, rather than at the population level, Cristofalo and Sharf (4) have reported that there is a progressive loss by individual cells of the capacity to synthesize DNA and to complete the division cycle. Changes in size of this non-dividing subpopulation may be monitored by autoradiographic techniques, and these data have predictive value in assessing the amount of potential lifespan completed by a particular cell population during its sojourn in culture.
Spontaneous movement of an intracranial missile.

This case report illustrates the unusual path of a bullet in the brain during a period of three years and its final successful removal from the floor of the fourth ventricle. — Since metallic foreign bodies may move within the brain, a surgically inaccessible fragment may later migrate and become accessible for surgical removal. Serial radiographs in varying projections and positions of the patient may thus provide valuable information.
REGULATION OF HUMAN ACETYLCHOLINESTERASE GENE EXPRESSION

Acetylcholinesterase (AChE) in human cells is encoded by a single gene, ACHE, located on chromosome 7q22. We have investigated the transcriptional regulation of ACHE by defining the mRNA cap sites and characterizing essential promoter and enhancer elements. We find putative promoter elements reside immediately upstream of the first untranslated exon, and are characterized by GC rich sequences containing consensus binding sites for transcription factors SP1, EGR-1 and AP-2. In vitro transcription studies and RNase protection of mRNA from human NT2/D1 teratocarcinoma cells reveal two closely spaced transcription cap sites. Both cap sites are located at a consensus initiator element similar to the terminal transferase gene initiator element. Transient transfection experiments show removal of three bases of this initiator sequence reduce promoter activity 98% in NT2/D1 cells. In vitro transcription and transient transfection of a series of ACHE promoter 5’ deletion mutants linked to a luciferase reporter show one SP1 site at −70 is essential for promoter activity. Purified recombinant SP1 protein protects this site in DNase footprinting experiments. Footprinting also shows purified recombinant transcription factor AP-2 binds 17 base pairs upstream of the initiator element. In vitro transcription studies with AP-2 protein and transient co-transfection of wild type AP-2 cDNA with ACHE promoter-luciferase reporter constructs show AP-2 functions as a repressor of A CHE transcription. Retinoic acid treatment of NT2/D1 cells induces AChE enzyme activity greater than 30 fold and mRNA levels 50 fold, while the rate of gene transcription remains unchanged. These data indicate ACHE transcription is activated by SP1 or similar factors, AP-2 represses ACHE transcription in vitro, and mRNA levels are controlled by changes in mRNA stability. (Supported by USPHS GM18360).
The Functional Morphologists

During the 1830’s developments in organic and physiological chemistry were taking place which considerably altered perceptions of some of the central issues in previous debates over biological organization. As we have seen, teleomechanists had two principal lines of argument to offer in defense of i their holist approach to physiology. On the one hand it had been argued by no less a figure than Johannes Muller that in vivo experimentation could not yield reliable results. Intervention supposedly disrupted the systematic interconnection with the whole of the organ under study, and its normal functioning depended essentially upon this vital connection. The most convincing support in defense of this position, however, concerned the damage inflicted to the organism through the crudeness of surgical technique and instrumentation. Although success in this area was limited, improvements had definitely been registered, particularly by the French.1 Magendie’s classic work on absorption, his investigation of the lacteal and lymphatic vessels were noteable demonstrations of how in vivo experiments could resolve questions of organ function.2 In the early 1840s further advances in surgical technique, such as the fistula developed by Beaumont and Blondlot, which was exploited by Claude Bernard as early as 1843 in his own investigations of digestion, provided further evidence that through refinement of technique valid inferences concerning physiologic processes could be made through direct experiments within living animals.
Regarding: "Insurance Reimbursement for Complementary Healthcare Services".

In the article, “Insurance Reimbursement for Complementary Healthcare Services,” we reported that the likelihood of reimbursement for complementary health care services in New Hampshire was significantly lower as compared with services of primary care physicians. The relatively low likelihood of reimbursement for integrative health care suggests that many patients who want such services must pay for them out of pocket. Affordable access to these services may be similarly limited in other states; certainly the utilization of integrative health care services varies significantly across the US states, and such variation may be tied to likelihood of reimbursement. Unwarranted geographic variation in reimbursement for integrative health care services is likely to compound inequities in access to health care in general, particularly for people of lower socioeconomic status. The aspirational value of Health Justice asserts the obligation of societies to attend to the basic health needs of all, with particular at...
An Application of Network Science to Phonological Sequence Learning in Children with Developmental Language Disorder.

Purpose Network science has been a valuable tool in language research for investigating relationships between complex linguistic elements but has not yet been applied to sound sequencing in product...
Open image in new windowGrowth and Growth Form

Growth form, that is, the shape and mode of construction of an organism, together with size sets fundamental opportunities as well as limits on the biology of living things. We consider here the case that organisms can be viewed as either basically unitary or modular in construction. This division pertains broadly to whether or not the life cycle consists essentially of repeated ontogenies at multiple levels. Being designed according to one plan or the other carries numerous implications, the most important of which are evolutionary consequences pertaining to fecundity and the transfer and expression of genetic variation. Further, it is argued that at least some microorganisms, notably the bacteria and fungi, are inherently modular in construction and share with macroorganisms the ecological properties that emerge from this design. Thus, the ecology and evolutionary biology of modular macroorganisms should be instructive to microbial ecologists. Conversely, experiments with the relevant microorganisms into the theoretical predictions of modularity may inform plant and animal ecologists.
The WikiLeaks Cables: How the United States Exploits the World, in Detail, from an Internal Perspective, 2001–2010

The disclosure of more than 250,000 American diplomatic cables by the dissident media organisation WikiLeaks in 2010–2011 gained much attention in the American mass media but generated little inter...
Self-Pacing with Constraints— A Modular Approach to the Teaching of Precalculus Mathematics

OVER the years, demands have been made on the mathematics department at Brigham Young University to develop several tracks of precalculus mathematics. Each mathematical consumer (mathe matics majors, engineers, physical sci entists, biological scientists, behavioral and management scientists, technicians, etc.) felt that a "special course" for them was necessary to satisfy the special needs of their discipline. This eventually involved six separate tracks in the usual college algebra-trigonometry-elementary func tions sequence. To be sure, each had its own flavor and particular combination of topics. However, the instruction from the various departments was the same?teach them the necessary mathematics. Seeking a method to combine many tracks while meeting the special demands of each consumer discipline and satisfying stu dent needs, the mathematics department decided that some type of modularization would be needed. The following characteristics were deemed important:
Protozoan Parasite Babesia microti Subverts Adaptive Immunity and Enhances Lyme Disease Severity

Lyme disease is the most prominent tick-borne disease in the United States. Co-infections with the tick-transmitted pathogens Babesia microti and Borrelia burgdorferi sensu stricto are becoming a serious health problem. B. burgdorferi is an extracellular spirochete that causes Lyme disease while B. microti is a protozoan that infects erythrocytes and causes babesiosis. Testing of donated blood for Babesia species is not currently mandatory due to unavailability of an FDA approved test. Transmission of this protozoan by blood transfusion often results in high morbidity and mortality in recipients. Infection of C3H/HeJ mice with B. burgdorferi and B. microti individually results in inflammatory Lyme disease and display of human babesiosis-like symptoms, respectively. Here we use this mouse model to provide a detailed investigation of the reciprocal influence of the two pathogens on each other during co-infection. We show that B. burgdorferi infection attenuates parasitemia in mice while B. microti subverts the splenic immune response, such that a marked decrease in splenic B and T cells, reduction in antibody levels and diminished functional humoral immunity, as determined by spirochete opsonophagocytosis, are observed in co-infected mice compared to only B. burgdorferi infected mice. Furthermore, immunosuppression by B. microti in co-infected mice showed an association with enhanced Lyme disease manifestations. This study demonstrates the effect of only simultaneous infection by B. burgdorferi and B. microti on each pathogen, immune response and on disease manifestations with respect to infection by the spirochete and the parasite. In our future studies, we will examine the overall effects of sequential infection by these pathogens on host immune responses and disease outcomes.
A multi-modal approach for natural human-robot interaction

We present a robot that is able to interact with people in a natural, multi-modal way by using both speech and gesture. The robot is able to track people, process speech and understand language. To track people and recognize gestures, the robot uses an RGB-D sensor (e.g., a Microsoft Kinect). To recognize speech, the robot uses a cloud-based service. To understand language, the robot uses a probabilistic graphical model to infer the meaning of a natural language query. We have evaluated our system in two domains. The first domain is a robot receptionist (roboceptionist); we show that the roboceptionist is able to interact successfully with people 77% of the time when people are primed with the capabilities of the robot compared to 57% when people are not primed with its capabilities. The second domain is a mobile service robot, which is able to interact with people via natural language.
A Reconsideration of Sexual Violence in German Colonial and Nazi Ideology and Its Representation in Holocaust Texts

This chapter examines the genocide the Germans committed in their colony in Africa between 1904 and 1907 and the ways in which this genocide functioned as a precursor to the Holocaust. Colonial discourse was made familiar to citizens of the Fatherland through newspaper accounts, debates in the Reichstag, and self-congratulatory books published by Schutztruppe, the colonial military. Yet scant attention has been given to the discourse about gender in Germany’s colonies and its subsequent impact on aspects of Nazi rule, including the Nuremberg Laws, regulations regarding prostitution, and the prevalence of sexual violence in the Third Reich. This chapter introduces texts by two survivors: Liana Millu, and Nanda Herbermann. The representation of rape, brothels located in lagers, and other forms of sexual violence echo colonial practice and perspectives.
Exploring the human-nature dynamics of Hunga Tonga Hunga Ha'apai, Earth's newest landmass

Abstract This paper examines the human-nature dynamics of volcanic eruptions through a multidisciplinary exploration of the recently-formed Hunga Tonga Hunga Ha‘apai (HTHH) landmass in the Kingdom of Tonga. HTHH was formed in early 2015 in the Ha‘apai island group in southwestern Tonga. This landmass has persisted longer than expected, providing a rare opportunity to examine pathways of erosion and biological colonization, and offering a glimpse into the cultural dynamics of a continuously changing Polynesian seascape. In 2018 and 2019, a collaborative partnership between the Kingdom of Tonga, Sea Education Association (SEA), and the United States National Aeronautics and Space Administration (NASA) ran expeditions to HTHH to calibrate satellite observations via field, ship, and drone-based measurements. In accessing HTHH via SEA's sailing school vessel (SSV) the Robert C. Seamans, a team of scientists and students combined fieldwork in anthropology, oceanography, and physical volcanology to study micro- and macro-scale dynamics of this classical surtseyan eruption site. In this pathfinding paper, we discuss the value of involving students in the process of real-time scientific discovery with on-the-fly adaptive hypothesis testing; this collaborative project provided mutual benefit to initiatives in science and education by offering robust data collection, while expanding environmental and cultural literacy. Additionally, we integrate collaborative research on HTHH with ethnographic research to understand how this ever changing “sea of islands” or intimately interconnected island spaces impact social-cultural relations within Oceania. We emphasize the importance of such multidisciplinary research in understanding the complexity of human-nature relations in a rapidly changing world.
Taxation of asset income in the presence of a world securities market

Abstract This paper examines a CAPM model of world security prices in which governments recognize their ability to influence international security prices via their tax treatment of foreign and domestic investors. In this model, governments have the incentive to set tax rates such that investors tend to specialize in domestic securities, and to restrict net capital flows between countries. Each country does this to increase the utility of domestic residents, taking as given the tax policies of other governments, but the net outcome is a reduction in world efficiency and likely a reduction in the utility of all investors.
Altered Resting-State Neural Oscillations and Spectral Power in Children with Fetal Alcohol Spectrum Disorder

Background Consumption of alcohol during pregnancy impacts fetal development and may lead to a variety of physical, cognitive, and behavioral abnormalities in childhood collectively known as fetal alcohol spectrum disorder (FASD). The FASD spectrum includes children with fetal alcohol syndrome (FAS), partial fetal alcohol syndrome (pFAS), and alcohol-related neurodevelopmental disorder (ARND). Children with a FASD or prenatal alcohol exposure (PAE) have impaired white matter, reduced structural volumes, impaired resting-state functional connectivity when measured with fMRI, and spectral hypersynchrony as infants. Magnetoencephalography (MEG) provides high temporal resolution and good spatial precision for examining spectral power and connectivity patterns unique from fMRI. The impact of PAE on MEG resting-state spectral power in children remains unknown. Methods We collected 2 minutes of eyes-open and eyes-closed resting-state data in 51 children (8 to 12 years of age) with 3 subgroups included: 10 ARND/PAE, 15 FAS/pFAS, and 26 controls (TDC). MEG data were collected on the Elekta Neuromag system. The following spectral metrics were compared between subgroups: power, normalized power, half power, 95% power, and Shannon spectral entropy (SSE). MEG spectral data were correlated with behavioral measures. Results Our results indicate children with FAS/pFAS had reduced spectral power and normalized power, particularly within the alpha frequency band in sensor parietal and source superior parietal and lateral occipital regions, along with elevated half power, 95% power, and SSE. We also found select hemisphere specific effects further indicating reduced corpus callosum connectivity in children with a FASD. Interestingly, while the ARND/PAE subgroup had significant differences from the FAS/pFAS subgroup, in many cases spectral data were not significantly different from TDC. Conclusions Our results were consistent with previous studies and provide new insight into resting-state oscillatory differences both between children with FAS and TDC, and within FASD subgroups. Further understanding of these resting-state variations and their impact on cognitive function may help provide early targets for intervention and enhance outcomes for individuals with a FASD.
Light, nitrogen supply, and neighboring plants dictate costs and benefits of nitrogen fixation for seedlings of a tropical nitrogen-fixing tree.

▪The ability to fix nitrogen may confer a competitive advantage or disadvantage to symbiotic nitrogen-fixing plants depending on the availability of soil nitrogen and energy to fuel fixation. Understanding these costs and benefits of nitrogen fixation is critical to predicting ecosystem dynamics and nutrient cycling. ▪We grew inoculated (with symbiotic bacteria) and uninoculated seedlings of Pentaclethra macroloba (a nitrogen-fixing tree species) both in isolation and with Virola koschnyi (a non-fixing species) under gradients of light and soil nitrogen to assess how the ability to fix nitrogen and fixation activity affect growth, biomass allocation, and responses to neighboring plants. ▪Inoculation itself did not provide a growth advantage to nitrogen fixers, regardless of nitrogen limitation status. Higher nitrogen fixation rates increased biomass growth similarly for nitrogen-limited and nitrogen-saturated fixers. Nodule production was offset by reduced fine-root biomass for inoculated nitrogen fixers, resulting in no change in total belowground allocation associated with nitrogen fixation. Under nitrogen-limited conditions, inoculated nitrogen fixers partially down-regulated fixation in the presence of a non-fixing neighbor. ▪These results suggest that nitrogen fixation can provide a growth advantage, even under nitrogen-saturated conditions, and that nitrogen fixers may reduce fixation rates to minimize facilitation of neighbors.
PDK1 as a preferred target for sensitizing breast cancer cells to gemcitabine

3857 3-Phosphoinositide-dependent protein kinase-1 (PDK1) is a 63-kDa serine/threonine protein kinase, which serves as an important mediator of multiple signaling pathways coupled to growth factor receptor activation in human cancers. Specifically, PDK1 functions at an important bifurcation point in the phosphoinositide 3-kinase (PI3-K) signaling, phosphorylating multiple downstream targets, including Akt, FRAP/mTOR, p70S6 kinase, p90S6 kinase and most PKC isoforms. Gemcitabine is currently being evaluated in clinical trials as a first-line drug candidate for metastatic breast cancer. To evaluate potential roles of PDK1 and Akt1 expression in mediating resistance of breast cancer cells to gemcitabine, we first compared the cellular sensitivity to gemcitabine of a mouse mammary epithelial cell line (COMMA-1D) infected with a recombinant retrovirus containing the human PDK1 or Akt1 cDNA. Compared with control vector infected COMMA-1D cells, we found that enforced expression of high levels of PDK1, but not high levels of Akt1, showed increased resistance to gemcitabine as measured by both MTT cell proliferation assay and apoptosis ELISA assay. Further studies were carried out in four established breast cancer cell lines. MDA453 and SKBR3 cells express high levels of PDK1 (total and Ser-241 phosphorylated PDK1) but low levels of Ser-473 phosphorylated Akt1. In contrast, MDA231 and MDA468 cells express high levels of Ser-473 phosphorylated Akt1 but low levels of Ser-241 phosphorylated PDK1. We found that MDA453 and SKBR3 cells are much more resistant than MDA231 and MDA468 cells to gemcitabine-induced cytotoxicity with the IC50 of gemcitabine being at least two-log scales higher in MDA453 and SKBR3 compared with MDA231 and MDA468. To determine whether PDK1 plays a greater role than Akt1 in conferring cellular resistance to gemcitabine in breast cancer cells, we chose MCF7 cells, which express high levels of both PDK1 and Akt1, to selectively knockdown PDK1 or Akt1 with small interfering RNA oligonucleotides (siRNA). We found that knockdown in the level of PDK1 markedly sensitized MCF7 to gemcitabine-induced apoptosis, whereas knockdown in the level of Akt1 had much less effect on sensitizing the cells to gemcitabine-induced apoptosis. Our data suggest that PDK1 is a preferred molecular target for sensitizing breast cancer cells to gemcitabine, and thereby justify the development of novel PDK1 inhibitors to enhance the efficacy of gemcitabine (Supported in part by Eli Lilly & Co.).
Type-based derivational morphology

Approaches to morphology typically account for regular, completely productive affixation, while ignoring subregular and semiproductive schemata. The alternative approach to derivational morphology presented here relates exceptions and subregularities to productive rules. It accounts for the contribution lexicalized words make to the rule and for the fact that not all new formations follow the 'rules'. It also captures linguistically relevant generalizations that cannot be expressed in other theories. The approach is formalized in terms of complex recursive schemata structured in a multiple inheritance hierarchy, without positing lexical rules or lexical entries for affixes. These schemata structure the existing lexicon, reducing redundancy, and at the same time serve as the basis for productive word formation. The approach handles zero-derivation and other nonconcatenative morphology straightforwardly.
Investigation of human sewage pollution and pathogen analysis at Florida Gulf coast Beaches

Aims: Water quality at two Florida beaches was compared using faecal indicator bacteria measurements, microbial source tracking (MST) methods for detecting human source pollution and the assessment of pathogen presence. These values were also compared before and after remediation of wastewater infrastructure at one beach. Methods and Results: Faecal coliforms, Escherichia coli and enterococci were enumerated in estuarine water and sediment samples. PCR assays for the human-associated esp gene of Enterococcus faecium and human polyomaviruses (HPyVs) were used to detect human sewage. Culturable Salmonella and enteric viruses were also analysed. MST identified human sewage contamination at one beach, leading to repair of a sewer main and relocation of portable restrooms. Exceedances of Florida recreational water regulatory standards were significantly reduced after remediation (by 52% for faecal coliforms and 39% for enterococci), and the frequency of detection of MST markers decreased. Coxsackie virus B4 and HPyVs were codetected following a major sewage spill, but Salmonella was not detected during the study. Conclusions: These data indicate that infrastructure remediation significantly reduced pollution from human sewage at the impacted beach. Significance and Impact of the Study: A comprehensive microbial water quality study that can identify contamination sources through the use of MST markers and close collaboration with local/and state agencies can result in tangible actions to improve recreational water quality and safety.
EReX: A Conceptual Model for XML

In the last few years, XML has been widely used as a logical data model, and several database applications are modeled in XML. To model a database application in XML, we should first come up with a conceptual design for representing the application requirements, and then translate this conceptual design to XML. Existing conceptual models like the ER (Entity Relationship) model, UML and ORM do not have modeling capabilities to represent main features provided by XML, such as union types. In this work, we extend the ER model with additional features; we call our conceptual model as EReX (ER extended for XML). Translating an EReX design to XML enables us to make use of the different features provided by XML. Our approach further enables us to study a fundamental problem facing XML database community today: what structural and constraint specification should be provided in XML so that any generic database application can be modeled in XML.
Surface Diffusion-Controlled Neck Growth Kinetics in Early Stage Sintering of Zirconia, with and without Applied DC Electrical Field

We report on the measurements of neck growth in early stage sintering of yttria-stabilized zirconia powders with and without the application of electrical fields. It is concluded that surface diffusion kinetics are not influenced by the application of DC electrical fields and currents. These measurements are in contrast to the influence of electrical fields on grain growth, where weak applied fields have been shown to significantly retard grain growth. The activation energy for surface diffusivity obtained in this way is in the range that is expected from literature values. Together, these results provide further insights into relationships between electrical fields and interfacial phenomena in the sintering and grain growth of ceramic materials.
Redesigning the Medical Office for Improved Efficiency: An Object-Oriented Event-Driven Messaging System

Medical practitioners are under ever increasing pressure to maximize patient care, while minimizing costs. One productivity area that has not previously undergone thorough investigation is the efficient utilization of time for intra-office communication. Medical office personnel typically need to communicate patient information and resource requests, as well as personal messages. An intra-office communication system is designed that reduces time-waste typically incurred in medical office environments. Redesigning medical offices with intra-office communication systems provides time savings of several man hours per day. The subsequent increase in time efficiency enables higher quality of patient care and larger patient loads to be managed by existing medical staff.
On Virtual Worlds: Copyright and Contract at the Dawn of the Virtual Age

This Article argues that copyright law can and should apply to artistic and literary creations occurring entirely in virtual worlds. First, the Article introduces the concept of virtual worlds as places millions of people visit not only for entertainment but also for life and work. Second, the Article reviews the philosophical justifications for copyright, examines objections to applying copyright to virtual, rather than real, creative works, and concludes that neither precludes copyright for virtual creations. Third, the Article articulates how copyright law would function within virtual spaces and reviews copyrightable creations from the perspective of both game developers and players. The Article also examines the validity of licensing agreements requiring players to waive their intellectual property rights as a condition of access to virtual spaces. Finally, the Article demonstrates that because virtual worlds are more than just games, courts and legislators will have to apply laws to virtual worlds as to protect the interests of developers and players alike.
Association of inflammatory bowel disease and large vascular lesions.

Abstract A case of inflammatory bowel disease with associated multiple large vessel vascular lesions similar to that seen in Takayasu's arteritis is described in a 15-year-old female. It is suggested that this type of vascular lesion may represent another rare systemic manifestation of inflammatory bowel disease.
Plantarflexion opening wedge medial cuneiform osteotomy for correction of fixed forefoot varus associated with flatfoot deformity.

Background: Flatfoot presents as a wide spectrum of foot deformities that include varying degrees of hindfoot valgus, forefoot abduction, and forefoot varus. Medial displacement calcaneal osteotomy, lateral column lengthening, and subtalar fusion can correct heel valgus, but may not adequately correct the fixed forefoot varus component. The purpose of this study was to determine the effectiveness of plantarflexion opening wedge medial cuneiform (Cotton) osteotomy in the correction of forefoot varus. Methods: Sixteen feet (15 patients) had plantarflexion opening wedge medial cuneiform osteotomies to correct forefoot varus associated with flatfoot deformities from several etiologies, including congenital flatfoot (six feet, average age 37 years), tarsal coalition (five feet, average age 15 years), overcorrected clubfoot deformity (two feet, ages 17 years and 18 years), skewfoot (one foot, age 15 years), chronic posterior tibial tendon insufficiency (one foot, 41 years), and rheumatoid arthritis (one foot, a...
Empirical method for the estimation of electron affinities

Abstract AM1 calculations were made to obtain the Mulliken population analysis charges for selected oxy anions. It is shown that the charges may be correlated with the experimental electron affinities of the associated oxy radicals, and that the resulting correlation may then be used to predict the electron affinities of other oxy radicals. The above correlation suggests that the ability of an oxy radical to accept an electron is dependent on the ability of the oxy anion to delocalize the charge through either the σ or π framework of the molecule (via induction or resonance). Comparisons are also made between this work and recent work by others on the acidity of alcohols and carboxylic acids. Finally, it is demonstrated that the calculated electron affinities of selected oxy radicals can be used along with calculated O-H bond dissociation energies of the corresponding alcohols to determine gas phase acidities of certain alcohols, which in turn can be used to calculate the heats of formation of oxy anions.
Spatial policy and the behavior of fishermen

Abstract Fishery policy makers would often benefit from information on how a policy might change fishermen behavior before the policy is implemented. This paper contributes to the literature by comparing simulated behavioral response with actual response to a spatial policy using a discrete choice model of fishing location choice. The results point to the inherent problem of the simulation's inability to capture the fundamental change in the nature of the choice problem that occurs with the change in policy. Addressing this problem will be important as these models continue to be used to inform policy makers.
Therapeutic suppression of tau kinases in the CNS with antisense oligonucleotides

to target pathogenic tau in 4-, 8-, and 18-month-old P301L tau transgenic mice, a model of AD and FTD, that have an onset of NFT pathology at 6 months of age. After up to 10 months of treatment, the degree of NFT pathology was determined by histological analysis. Results:All age groups, NFT pathology was significantly reduced in treated compared to non-immunized mice. Similarly, phosphorylation of tau at pathological sites was reduced. In addition, increased astrocytosis was found in the oldest treated group. Conclusions: Our data suggests that tau-targeted immunization slows the progression of NFT pathology in a mouse model of tau pathology.
The link between dispositional pride and creative thinking depends on current mood

Abstract Pride has long been considered a characteristic of creative geniuses, but the link between pride and creative thinking has yet to be systematically examined. In Study 1, we found that authentic pride related positively, whereas hubristic pride related negatively to creative thinking, assessed using the Unusual Uses Task, a behavioral measure of creative thinking. In Study 2, we found that the relation between pride and creativity depends on current mood. Specifically, authentic pride was most strongly related to creativity in the happiness condition, whereas hubristic pride was most strongly related to creativity in the anger condition. We discuss implications for understanding the affective processes underlying creativity and the adaptive and maladaptive consequences of pride.
TREATMENT OF IDIOPATHIC ORTHOSTATIC HYPOTENSION (SHY-DRAGER SYNDROME) WITH INDOMETHACIN

Four patients with idiopathic orthostatic hypotension (I.O.H.) and one with postural hypotension and diabetes were studied. Plasma-renin activity (P.R.A.) was low and did not rise appropriately with salt restriction and diuretic stimulation. Aldosterone levels were normal and rose with diuretic therapy. Plasma-volume, plasma dopamine beta-hydroxylase, urinary catecholamines, metanephrines, and vanillyl mandelic acid (V.M.A) were normal. Treatment with indomethacin (75-150 mg/day) raised the upright blood-pressure (B.P.) by an average of 20-30 mm Hg diastolic and allowed the four patients with I.O.H. to walk about without orthostatic symptoms but it had no effect in the fifth patient. When indomethacin was discontinued in one patient who had been taking it for 9 months with symptomatic relief, the B.P. fell to pretreatment levels within 48 h. When indomethacin was reinstituted the B.P. rose again. Indomethacin was more effective in these patients than either propranolol or fludrocortisone. There may be an absolute or relative excess of certain vasodepressor prostaglandins in the peripheral vessels which results in pooling of blood and orthostatic hypotension. If this is the case indomethacin might improve the orthostatic symptoms of I.O.H. by its inhibitory effect on prostaglandin synthesis, but its mechanism of action remains to be determined.
Adaptive multidimensional modulation and multiplexing for next generation optical networks

The overall spectral efficiency in optical transmission systems needs to be enhanced by employment of advanced modulation, multiplexing, and coding schemes, as well as the advanced detection techniques. In parallel, novel networking concepts with the griddles and elastic bandwidth allocation are needed to increase the network dynamics and flexibility. In this paper we discuss multidimensional modulation, multiplexing, and coding schemes, which are enablers not only of the information capacity increase, but also for the next generation elastic high-speed optical networking and outline possible future directions and application scenario in different networking segments.
The N-terminal membrane anchor domain of the membrane-bound prostacyclin synthase involved in the substrate presentation of the coupling reaction with cyclooxygenase

Abstract To mimic the native conditions, the cyclooxygenase (COX)/prostaglandin I 2 synthase (PGIS) coupling reaction system was used to determine the coordination of PGIS with COX for the biosynthesis of prostacyclin (PGI 2 ) using arachidonic acid (AA) as a substrate in a membrane-bound environment. The membrane-bound PGIS exhibited a faster isomerization of PGH 2 produced by COX to PGI 2 than the detergent-solubilized PGIS. To determine whether the N-terminal domain of PGIS responds to the facilitation of PGH 2 movement (presentation) from COX to the active site of PGIS, the first 20 residues of PGIS (Δ20-PGIS) were deleted and expressed in COS-7 cells. Δ20-PGIS retained membrane-bound properties and exhibited a slower substrate presentation property. Furthermore, a chimeric molecule (PGIS/TXAS 8–27 ) with the replacement of the first 20 residues of PGIS by the corresponding membrane anchor region (residues 8–27) of thromboxane A 2 synthase was created to evaluate the mechanism influencing the biosynthesis of PGI 2 in coordination with COX. The chimera revealed a multiple fold delay in the PGH 2 presentation in low range concentrations of AA (0.3–3 μM) at 30 s reactions. However, the delay could be recovered by a longer incubation time in high range concentrations of AA (>10 μM), but not in low range concentrations of AA. These results demonstrated that the N-terminal domain of PGIS plays a role in the facilitation of the substrate presentation to the PGIS active site in low concentrations of AA, which may be a physiological condition. The TXAS N-terminal domain could not replace the function of the corresponding domain of PGIS, indicating that the facilitation of the substrate presentation is specific.
The effects of mevinolin and neomycin alone and in combination on plasma lipid and lipoprotein concentrations in type II hyperlipoproteinemia

Abstract The reduction of elevated low density lipoprotein (LDL) cholesterol concentrations in patients with Type II hyperlipoproteinemia leads to improved cardiovascular morbidity and mortality. Two agents which may be of value in treating hypercholesterolemia are mevinolin and neomycin. Since these drugs lower cholesterol levels through complementary mechanisms, we evaluated the effects of mevinolin and combined mevinolin-neomycin treatment on plasma lipoprotein concentrations in 21 type II hyperlipoproteinemic patients. Mevinolin reduced total and LDL cholesterol concentrations by 24% and 31% respectively ( P P
CONTINUOUS TISSUE pH MONITORING USING A DISPOSABLE, NONGLASS ELECTORODE IN CRITICALLY ILL NEONATES

CONTINUOUS TISSUE pH MONITORING USING A DISPOSABLE, NONGLASS ELECTORODE IN CRITICALLY ILL NEONATES