cssi/SciSciGPT-SciSciNet huggingface dataset:
CETP polymorphisms associate with brain structure, atrophy rate, and Alzheimer’s disease risk in an APOE-dependent manner

Two alleles in cholesteryl ester transfer protein (CETP) gene polymorphisms have been disputably linked to enhanced cognition and decreased risk of Alzheimer’s disease (AD): the V and A alleles of I405V and C-629A. This study investigates whether these polymorphisms affect brain structure in 188 elderly controls and 318 AD or mild cognitive impairment (MCI) subjects from the Alzheimer’s Disease Neuroimaging Initiative cohort. Nominally signficant associations were dependent on APOE e4 carrier status. In APOE e4 carriers, the V and A alleles, both of which decrease CETP and increase HDL, associated with greater baseline cortical thickness and less 12-month atrophy in the medial temporal lobe. Conversely, in APOE e4 non-carriers, the I allele, which increases CETP and decreases HDL, associated with greater baseline thickness, less atrophy and lower risk of dementia. These results suggest CETP may contribute to the genetic variability of brain structure and dementia susceptibility in an APOE-dependent manner.
Computational modeling of azotobactin-goethite/diaspore interactions: Applications to molecular force measurements and siderophore-mineral reactivity

Abstract Empirical force field and quantum mechanical calculations were completed to investigate the interaction between azotobactin and iron/aluminum oxide surfaces, and to further evaluate force measurements made on the same systems using an atomic force microscope (AFM). The increased force affinity for goethite over diaspore, characteristic of the experimental force signatures, was also observed in the simulated siderophore interaction with these minerals. Ab initio calculations on siderophore fragment analogs confirm previous findings and suggest that the iron affinity can, in part, be attributed to greater electron density associated with the Fe–O bond compared to the Al–O bond. This observation correlates with iron's larger electronegativity compared to aluminum leading to a more covalent Fe goethite –O siderophore bond. Calculations with hydrated fragment analog Al 3+ /Fe 3+ complexes suggest the lowered siderophore force affinity observed experimentally for diaspore could also reflect the extra energy required to remove water coordinated to the Al in the surface. In the molecular mechanics simulations, chelating ligand pairs, which consisted of both backbone and amino acid side chain oxygen atoms, coordinated with neighboring iron and aluminum atoms to form a binuclear geometry. Upon retraction of azotobactin from each surface, simulated Fe–O siderophore bonds persisted into a higher force regime than Al–O siderophore bonds, and surface metals were removed from both minerals. Extrapolation of the model to more realistic hydrated conditions using a polarizable continuum model (PCM) (e.g., solvent is modeled as a continuum of uniform dielectric constant) and water coordination shells in quantum mechanical calculations and water clusters in the molecular mechanics model demonstrated that the presence of water energetically favors and enhances metal extraction. In this way, our system may be a good model to understand the forces of the azotobactin–mineral interaction and how they relate to siderophore-mediated dissolution of Fe from goethite in a natural system.
Radar signatures of the urban effect on precipitation distribution : A case study for Atlanta, Georgia

[1] Ground-based weather radar from Peachtree City, GA, is used to examine the distribution of summer precipitation in northern Georgia, including metropolitan Atlanta, during June-August of 2002-2006. The study included 194 "synoptically benign" days with a maritime tropical air mass type. Areas in eastern metropolitan Atlanta are shown to have 30% more rainfall during these days than areas west of the city. Both precipitation amount and frequency were enhanced up to 80 km to the east of the urban core of Atlanta. A precipitation maxima northeast of Atlanta occurs near a precipitation anomaly and lightning flash density anomaly identified in previous studies. An hourly analysis of precipitation data demonstrates that the enhanced precipitation on the periphery of the urban core is most evident from 00-05 UTC (19-00 LST). This study is the first to use ground-based radar precipitation estimates in an attempt to quantify the impact of urbanization on precipitation.
An Investigation into the Variability of Heating in a Solar Active Region

Previous studies have indicated that both steady and impulsive heating mechanisms play a role in active region heating. In this paper, we present a study of 20 hours of soft X-ray and EUVobservations of solar active region NOAA AR 8731. We examine the evolution of six representative loop structures that brighten and fade first from X-ray images and subsequently from the EUV images. We determine their lifetime and the delay between their appearance in the different filters. We find that the lifetime in the EUV filters is much longer than expected for a single cooling loop. We also notice that the delay in the loops’ appearance in the X-ray and EUV filters is proportionaltothelooplength.Wemodeloneoftheloopsusingahydrodynamicmodelwithbothimpulsiveandquasisteady heating functions and find that neither of these simple heating functions can well reproduce the observed loop characteristics in both the X-ray and EUVimages. Hence, although this active region is dominated by variable emission and the characteristics oftheobservedloopsarequalitatively consistentwith acooling loop, the timescale of the heating in this active region remains unknown. Subject headingg Sun: corona Online material: mpeg animations
Genetically modified PC12 brain grafts: survivability and inducible nerve growth factor expression

Neural transplantation of genetically modified cells has been successfully employed to reverse functional deficits in animal models of neurodegenerative disorders, including Parkinson's disease. While implanted PC12 cells secrete dopamine in vivo and can ameliorate dopamine deficiency in parkinsonian rat model systems, these cells either degenerate within 2-3 wk postimplantation (presumably due to the lack of neural trophic factor support at the site of implantation), or in some cases, form a tumor mass leading to the death of the host animal. To address these limitations, we have developed a genetically modified PC12 cell line that can synthesize nerve growth factor (NGF) under the control of a zinc-inducible metallothionein promoter. When implanted in the rat striatum and under in vivo zinc stimulation, these cells will neuro-differentiate, express tyrosine hydroxylase, and will undergo survival through potential autocrine trophic support. This regulatable cell line and general approach may provide additional insight on the potential utilization of cell transplants for treatment of Parkinson's disease and other neurodegenerative disorders.
Binding Energy of Metal Oxide Nanoparticles

Current models for the binding energy of nanoparticles generally predict a linear dependence on the inverse particle diameter for spherical clusters or, equivalently, on the inverse of the cube root of the number of particles in the cluster. We have tested this assumption on the simple oxides MgO, CuO, and TiO2 and for the complex oxide FeTiO3. We find that a linear dependence is not observed for these materials despite the fact that it generally occurs for simple metals. Instead, using first principles, density functional theory calculations to calculate the binding energy of these materials, we find an approximately quadratic dependence on the inverse of the particle size, in direct contradiction to current assumptions. This nonlinear dependence of the binding energy has substantial implications on physical properties that depend on the cohesive energy, particularly in the small particle regime.
Evaluation of the genotoxicity of cresols using sister-chromatid exchange (SCE).

o-, m- and p-Cresols were evaluated in both an in vitro and in vivo SCE assay. Dose-dependent SCE increases were not observed in cultured human fibroblasts with any of the isomers at concentrations up to 8 mM. There was a small but significant increase in SCE frequency compared to control at 8 mM o-cresol. A significant decrease in cell-cycle progression as measured by average generation time (AGT), was seen for all isomers at a concentration of 8 mM. Furthermore, no increase in SCE frequencies was observed in bone marrow, alveolar macrophages, and regenerating liver cells of male DBA/2 mice treated with a single i.p. injection of either o-cresol (200 mg/kg), m-cresol (200 mg/kg), or p-cresol (75 mg/kg) 21.5 h prior to sacrifice.
Depression of ventilation by dopamine in goats — effects of carotid body excision

Dopamine (DA) given IV by bolus injection (5, 10, 20 micrograms/kg) and by slow IV infusion (20 micrograms . kg . min) depressed VE significantly in awake normoxic goats. These responses were attenuated but not eliminated during hypoxia (FIO2 = 0.14) and hyperoxia (FIO2 = 1.0). After administering haloperidol (0.3 mg/kg) or removing the carotid bodies (CBE) there was greater attenuation of the response to DA. In normal goats haloperidol also caused a significant increase in ventilatory response to acute hypoxia and exaggerated depression of VE after 3--5 breaths O2 during steady-state hypoxia. After CBE haloperidol caused mild hypoventilation (delta PaCO2 = +2.5 Torr). CBE induced hypoventilation in goats (delta PaCO2 = +7.8 Torr) and reduced, but did not totally eliminate, peripheral chemoreceptor responses to acute stimuli (NaCN injection, transient N2 and transient O2 breathing). Attempted aortic body denervation did not eliminate these residual responses. We conclude: (1) DA may function as a modulator of carotid body (CB) function in the goat, (2) there may be central excitatory DA receptors in the goat, (3) the CB is important in regulating resting ventilation in the goat.
Laparoscopic intestinal stomas.

PURPOSE: We report our early experiences with laparoscopic intestinal stomas, describing the indications, the surgical techniques, and the complications of this new procedure. METHODS: The medical records of the 17 patients who had successfully undergone laparoscopic intestinal diversion at The University of Texas M. D. Anderson Cancer Center were reviewed. RESULTS: The mean follow-up of this group has been 24.3 (range, 3–61) weeks. Seven patients had their stomas created as part of a laparoscopic abdominoperineal resection, six patients underwent palliative laparoscopic colostomy for an obstructing tumor of the rectum, or a colorectal-genitourinary fistula, and four patients treated by local excision of a rectal cancer were believed to require proximal protecting fecal diversion. All six patients treated with palliative intent experienced successful relief from their obstruction or fistula, and were able to resume enteral nutrition. Complications included prolapse in one patient and paracolostomy hernia in another. Neither complication required furthur operative correction. Pneumoperitoneum was established in all patients using an open technique. CONCLUSIONS: Laparoscopy is a well-tolerated and effective method of creating intestinal stomas for a variety of indications. As more experience is gained with this procedure, we anticipate that laparoscopy will become the preferred method of establishing intestinal diversion.
Eating disorders in men: update

Abstract Men with anorexia and bulimia nervosa account for 10% of people with this condition and for binge eating disorder they account for as many as 25%. Risk factors in men include athletics, sexuality, psychiatric co-morbidity and negative life experiences. Differences in eating disorders exist between men and women relating to behavior and psychological symptoms. Men are much more likely than women to underestimate body size and desire a more muscular body. Men are less likely than women to engage in typical compensatory behaviors such as vomiting and more likely to engage in activities such as excessive exercise to attempt to lose weight or counteract the effects of eating. Men are more likely than women to binge rather than restrict due to negative body image. Studies show that men with eating disorders are less likely to seek treatment than women are. Obstacles to treatment include cultural biases toward eating disorders because they are considered to be female disorders, a lack of trained professionals and a lack of treatment setting that specifically deals with male eating disorders patients. Finally, even with little research to guide treatment of eating disorders, the outcome seems to be similar for men and women.
Photochemical bonding of skin with 1,8-naphthalimide dyes

Our ongoing studies out to one year postoperatively of healing in sheep menisci and condylar articular cartilage prompt the study of photochemical bonding of other connective tissues with our 1,8-naphthalimide dyes. Here we report our ex-vivo experiments in photochemical bonding of the dermis of rabbit dorsal skin with 1,8-naphthalimide dyes, in which effects of varying the externally applied pressure during the welding and of the addition of an albumin-collagen protein filler are studied.
Autophagy in the heart and liver during normal aging and calorie restriction.

Autophagy is a highly regulated intracellular process for the degradation of cellular constituents and essential for the maintenance of a healthy cell. We evaluated the effects of age and life-long...
Comparative Shell Microstructure of Two Species of Tropical Laternulid Bivalves from Kungkrabaen Bay, Thailand with After-Thoughts on Laternulid Taxonomy

Abstract: The anomalodesmatan family Laternulidae represents a group of bivalves with a very few well-known taxa and many more poorly known taxa. Laternula rostrata (G. B. Sowerby, 1839) and L. anatina (Linnaeus, 1758) occur in close proximity to each other in and along the margins of mangroves of Kungkrabaen Bay, Thailand. Laternula rostrata resides in soft to sandy sediments often within the interstices of mangrove roots located in more open portions of the mangrove mud flat. Laternula anatina lives deeper in the mangrove in more protected environs. Laternula anatina is a smaller bivalve that has a variable shell outline, sometimes a wrinkled shell appearance, thicker periostracum, and frequently extensive umbonal erosion. Both species have high concentrations of external shell spinules anteriorly and closer to the umbos (i.e., in juvenile shell) reflecting functionality in retaining an infaunal position. The larger L. rostrata is thinner shelled and more fragile; has more distinct and longer shell spin...
Profiling of Anode Surface Cycled in LiBOB-based Electrolyte of Li Ion Batteries

As the youngest battery chemistry, Li ion technology was made possible by the formation of stable electrode/electrolyte interfaces. The correlation between the electrochemistry and the surface profile of the graphitic anode was studied in this work with a new salt lithium bis (oxalate) borate (LiBOB). In an attempt to depict a dynamic picture of the formation of graphite/electrolyte interface during the initial forming cycle, we employed X-ray photoelectron spectroscopy in combination with the “pre-formation” technique to establish the dependence of the surface chemistry on the forming potential of the anode. A progressive transition in the 1s electron binding energies of the major elements was observed as the lithiation proceeds; however, the surface chemical species as well as their abundances seemed to stabilize around 0.55 V and remained constant during the subsequent delithiation process, indicating that a stable solid electrolyte interface (SEI) exists thereafter. Integrating the information revealed by different analyses, we believe that the reductive decomposition of BOB -anion starts at ca. 1.00 V, while the effective protection of graphene surface by SEI is available after the anode is lithiated below the potential of 0.55 V.
Predictors of microinvasion and its prognostic role in ductal carcinoma in situ

Background We sought to determine factors predicting microinvasion and the prognostic role it plays in patients with ductal carcinoma in situ (DCIS). Methods A retrospective cohort study of 205 consecutive patients presenting to the Yale Breast Center, New Haven, CT, was performed. Results Fifty-one (24.9%) patients had microinvasion on pathology. Patients with microinvasion had larger areas of DCIS and were more likely to have high-grade DCIS of the comedo and solid type associated with necrosis and microcalcifications. On multivariate analysis, none of these factors were independent predictors of microinvasion. With a median follow-up of 8.5 years, there was no difference in the recurrence rate or 5-year actuarial survival between those with microinvasion vs those with pure DCIS. Conclusions Microinvasion was associated with more extensive DCIS, higher grade, comedo or solid histology, necrosis, and microcalcifications although none of these were found to be an independent predictor of microinvasion. Furthermore, the presence of microinvasion does not seem to significantly increase the risk of recurrence or decrease survival.
Estimating effects of processing conditions and variable properties upon pool shape, cooling rates, and absorption coefficient in laser welding

This paper examines the role of traverse speed, Beer–Lambert absorption coefficient β, surface reflectivity, and changing liquid thermal conductivity upon the shape of the melt pool and the cooling rates that occur. The dependence of β upon processing conditions is also examined. A three‐dimensional variable property, moving heat source, quasi‐steady‐state, finite difference model for heat conduction into the substrate during laser welding is used. With an increase in traverse speed, the pool flattens out and is swept back, and cooling rates increase. An increase in β sharply decreases the depth of penetration. With the onset of melting, changes in reflectivity did not change pool shape significantly. An increase in effective liquid metal thermal conductivity increases melt pool aspect ratio. Cooling rates increased as the energy density in the pool decreased. A dimensionless melt front velocity Φ is defined such that cooling rates exceed 1000 K/s as Φ approaches unity. The product βz, where z is the depth of penetration, is shown to vary linearly with the natural logarithm of Φ. These results imply that β affects depth of penetration more than the width, that an upper bound for β may be deduced from Φ, that variations in surface reflectivity are less critical in laser welding, that the maximum thickness that can be welded in a single pass decreases as fluid flow becomes more dominant in the melt pool, and that cooling rates increase as pool energy density decreases, especially for values of Φ<100.
Using formal methods to enable more secure vehicles: DARPA's HACMS program

Networked embedded systems are ubiquitous in modern society. Examples include SCADA systems that manage physical infrastructure, medical devices such as pacemakers and insulin pumps, and vehicles such as airplanes and automobiles. Such devices are connected to networks for a variety of compelling reasons, including the ability to access diagnostic information conveniently, perform software updates, provide innovative features, and lower costs. Researchers and hackers have shown that these kinds of networked embedded systems are vulnerable to remote attacks and that such attacks can cause physical damage and can be hidden from monitors [1, 4]. DARPA launched the HACMS program to create technology to make such systems dramatically harder to attack successfully. Specifically, HACMS is pursuing a clean-slate, formal methods-based approach to the creation of high-assurance vehicles, where high assurance is defined to mean functionally correct and satisfying appropriate safety and security properties. Specific technologies include program synthesis, domain-specific languages, and theorem provers used as program development environments. Targeted software includes operating system components such as hypervisors, microkernels, file systems, and device drivers as well as control systems such as autopilots and adaptive cruise controls. Program researchers are leveraging existing high-assurance software including NICTA's seL4 microkernel and INRIA's CompCert compiler. Although the HACMS project is less than halfway done, the program has already achieved some remarkable success. At program kick-off, a Red Team easily hijacked the baseline open-source quadcopter that HACMS researchers are using as a research platform. At the end of eighteen months, the Red Team was not able to hijack the newly-minted "SMACCMCopter" running high-assurance HACMS code, despite being given six weeks and full access to the source code of the copter. An expert in penetration testing called the SMACCMCopter "the most secure UAV on the planet." In this talk, I will describe the HACMS program: its motivation, the underlying technologies, current results, and future directions.
Coping with plagiarism

Abstract The development of research and reporting skills is recognized as an important function of accounting instruction, but the problems associated with such development have not been widely discussed in the accounting literature. One of these problems, that of plagiarism, is examined. The concept of plagiarism is discussed and an evaluative model is described.
Successful culture of rat embryos on human serum: use in the detection of teratogens

Growth of head-fold-stage rat embryos cultured with human serum for 48 hours was enhanced by supplementation with glucose. Embryo growth (protein and DNA contents) varied with the source of the serum. Serum from 16 of 19 untreated subjects produced normal embryos. Serum from five subjects undergoing cancer chemotherapy and six subjects receiving anticonvulsants was either lethal or teratogenic.
The effect of inorganic additives on the formation, composition, and combustion of cellulosic char

At temperature above 300°C the glycosyl units of cellulose are simultaneously depolymerized to a tar and decomposed to a char by evolution of H2O, CO, and CO2. When the glycosyl units are depleted, a stable char is formed containing about 30% aliphatic and 70% aromatic components. The aliphatic component is formed first, but on further heating is converted to polycyclic aromatic structures. The chars formed at lower temperatures are more combustible because the aliphatic component of the char is highly pyrophoric and is oxidized almost at the same temperature at which it is formed (∼360°C). The aromatic component, however, is less reactive and is oxidized at ∼520°C. Consequently, the chars formed at higher temperatures are less combustible. It has been shown that (NH4)2HPO4, which is a well-known flame retardant and smoldering inhibitor, lowers the pyrolysis temperature and increases the char yield by accelerating the decomposition reactions. This affects the composition of the intermediate chars but the final products have about the same composition irrespective of additives. (NH4)2HPO4 also lowers the rate of oxidation of the aromatic component and the corresponding heat release. NaCl, which is an enhancer of smoldering combustion, has a slight stabilizing effect on pyrolysis of cellulose. It lowers the oxidation temperature of the aromatic component and dramatically increases its rate. The corresponding heat release is also increased due to complete oxidation to CO2. The rate of oxidation calculated from the dynamic thermal analysis data is more than tripled by NaCl and significantly reduced by (NH4)2HPO4.
Relativistic nonlinear optics: from the atomic to the quark structure of matter

Summary form only given. Today laser optics is standing on the threshold of new physics frontiers. Until recently, traditional optics and nonlinear optics have addressed phenomena in the eV regime, focusing essentially on the study of the atomic structure of matter. It is today possible to produce intensities in the range of 10/sup 18/-10/sup 22/ W/cm/sup 2/, that is 10/sup 4/-10/sup 6/ higher than was possible only few years ago. These intensities could even reach in the future values as high as 10/sup 29/ W/cm/sup 2/. After a discussion of the laser intensity upper limit, we give an overview of the field of relativistic optics that could be considered as the second wind of nonlinear optics. In particular we give examples of applications to, fusion energy, astrophysics, nuclear physics, high energy physics and gravitational physics.
Charge control for direct injection spark ignition engines with EGR

Modern automotive engines rely increasingly on high performance estimation and control algorithms to deliver the expected performance benefits. This paper discusses a number of control problems and issues that arise in the design of a charge controller for a lean-burn direct injection spark ignition engine with exhaust gas recirculation (EGR). To deal with uncertainties and parameter variations that can significantly affect the engine performance, the use of feedback and adaptive controllers is shown to be essential.
Effects of timber harvest within streamside management zones on salamander populations in ephemeral streams of southeastern Kentucky

Abstract Timber harvest is an important extractive, economic activity to many human economies, but it can be detrimental to ecosystem function and species viability therein by degrading and fragmenting forest habitat. Salamanders comprise a significant amount of forest community biomass, and given their sensitivity to environmental stressors, including those caused by timber harvest, they often serve as important indicators of declines in forest ecosystem function. Several studies have focused on the impacts of timber harvest on salamanders inhabiting perennial and intermittent streams, the findings of which have helped inform best management practices for timber harvest in the U.S. Ephemeral headwater streams and associated riparia account for a small fraction of the total landscape, yet these features are critical to the functioning of forested ecosystems; however, few studies have examined how timber harvest impacts salamanders in or near these areas. Our objective was to investigate the effects of three different silvicultural treatments, each involving different streamside management zone (SMZ) characteristics, on salamander communities in southeastern Kentucky hardwood forest ephemeral streams. Data were collected by regular checks of pitfall traps, coverboards, and transect searches. Using both pre- and post-harvest data, abundance estimates were acquired using binomial mixture models. Declines in some species of terrestrial and stream-breeding salamanders were detected, and were shown to be likely related to characteristics of the corresponding silvicultural treatment. We suggest that application of modest SMZ regulations to ephemeral streams would likely reduce or alleviate salamander declines in these important headwater areas.
New Aspects of Neotropical Polycystic (Echinococcus vogeli) and Unicystic (Echinococcus oligarthrus) Echinococcosis

SUMMARY Of the four species of the genus Echinococcus (Cestoda) distinguished by biological and morphological characteristics, two species, E. vogeli and E. oligarthrus, occur widely in the Neotropics. Approximately 200 cases of polycystic echinococcosis (PE) have been recorded from 12 countries in South America. Following early proliferation of E. vogeli in the human host, typically in the liver, the metacestode usually spreads in the peritoneal and pleural cavities, and numerous organs may be invaded. The clinical characteristics of PE in 81 patients with sufficient information are reviewed. Type I disease consists of polycysts in the liver and abdominal cavity (37% of the patients had this characteristic); type II is similar to type I but also includes hepatic insufficiency (26%); type III consists of cysts in liver and chest (14%); type IV consists of cysts only in the mesenteries (16%); and type V consists of cysts calcified in liver and lung (4%). The percentage of patients with polycysts in the liver was 81%, and the percentage of patients with polycysts in the chest was 14%. PE is most ready diagnosed by geographic origin of the patient and by means of ultrasound or computerized tomography scanning showing cysts and calcifications. The highest mortality was for patients with type II disease, due to hepatic failure and its complications. There were five patients who died due to surgical accidents, whereas 35 cases had uncomplicated surgery. Twenty-three patients died of PE, making the total mortality 29% (23 of 78 cases). None of the 13 patients treated only with albendazole, the most efficacious treatment, was completely cured. PE represents a severe medical problem in South America. A reevaluation of the characteristics of the metacestode of E. oligarthrus indicated that it is unicystic. Only three human cases are known (two with infection in the orbit and one with infection in the heart). The metacestode of E. oligarthrus, in contrast with that of E. vogeli, consists of a spherical, fluid-filled vesicle that enlarges concentrically and is not known to undergo exogenous proliferation.
Computational Irreducibility and the Predictability of Complex Physical Systems

Using elementary cellular automata (CA) as an example, we show how to coarse grain CA in all classes of Wolfram's classification. We find that computationally irreducible physical processes can be predictable and even computationally reducible at a coarse-grained level of description. The resulting coarse-grained CA which we construct emulate the large-scale behavior of the original systems without accounting for small-scale details. At least one of the CA that can be coarse grained is irreducible and known to be a universal Turing machine.
Rates of Retinal Nerve Fiber Layer Thinning in Glaucoma Suspect Eyes

Purpose To compare the rates of retinal nerve fiber layer (RNFL) loss in patients suspected of having glaucoma who developed visual field damage (VFD) with those who did not develop VFD and to determine whether the rate of RNFL loss can be used to predict the development of VFD. Design Prospective, observational cohort study. Participants Glaucoma suspects, defined as having glaucomatous optic neuropathy or ocular hypertension (intraocular pressure, >21 mmHg) without repeatable VFD at baseline, from the Diagnostic Innovations in Glaucoma Study and the African Descent and Glaucoma Evaluation Study. Methods Global and quadrant RNFL thickness (RNFLT) were measured with the Spectralis spectral-domain optical coherence tomography (SD-OCT; Spectralis HRA+OCT [Heidelberg Engineering, Heidelberg, Germany]). Visual field damage was defined as having 3 consecutive abnormal visual fields. The rate of RNFL loss in eyes developing VFD was compared to eyes not developing VFD using multivariate linear mixed-effects models. A joint longitudinal survival model used the estimated RNFLT slope to predict the risk of developing VFD, while adjusting for potential confounding variables. Main Outcome Measures The rate of RNFL thinning and the probability of developing VFD. Results Four hundred fifty-four eyes of 294 glaucoma suspects were included. The average number of SD-OCT examinations was 4.6 (range, 2–9), with median follow-up of 2.2 years (0.4–4.1 years). Forty eyes (8.8%) developed VFD. The estimated mean rate of global RNFL loss was significantly faster in eyes that developed VFD compared with eyes that did not develop VFD (−2.02 μm/year vs. −0.82 μm/year; P P = 0.017). Conclusions The rate of global RNFL loss was more than twice as fast in eyes that developed VFD compared with eyes that did not develop VFD. A joint longitudinal survival model showed that a 1-μm/year faster rate of RNFLT loss corresponded to a 2.05-times higher risk of developing VFD. These results suggest that measuring the rate of SD-OCT RNFL loss may be a useful tool to help identify patients who are at a high risk of developing visual field loss.
Design of software to interpret and display data from continuous glucose monitors

The Diabetes Technology Program (DTP) at the University of Virginia is dedicated to improving diabetes management. The DTP has developed measures, indices, and graphs to help patients and medical professionals identify and assess trends related to diabetes. Based on these efforts, the project team designed and developed software that displays continuous glucose monitor (CGM) data and their related statistics. The result is a human-centered software prototype which uploads, stores, and visualizes multi-trial, multi-patient CGM data. The prototype allows users to easily and quantitatively compare treatment regimes. Quantitative comparison will enable physicians to tailor treatments to patients and eventually alleviate the severity of diabetes symptoms. The project produced a human-centered software prototype that has the potential to contribute to the field of diabetes management.
Adverse childhood experiences and the association with ever using alcohol and initiating alcohol use during adolescence

Abstract Purpose Alcohol is the most common and frequently used drug and has the potential to cause multiple deleterious effects throughout the lifespan. Because early age at initiation of alcohol use increases this potential and programs and laws are in place to attempt to delay the onset of alcohol use, we studied the relationship between multiple adverse childhood experiences (ACEs) and both the likelihood of ever drinking and the age at initiating alcohol use. Methods This was a retrospective cohort study of 8417 adult health maintenance organization (HMO) members in California who completed a survey about ACEs, which included childhood abuse and neglect, growing up with various forms of household dysfunction and alcohol use in adolescence and adulthood. The main outcomes measured were ever drinking and age at initiating alcohol use among ever-drinkers for four age categories: ≤ 14 years (early adolescence), 15 to 17 years (mid adolescence), and 18 to 20 years (late adolescence); age ≥ 21 years was the referent. The relationship between the total number of adverse childhood experiences (ACE score) and early initiation of alcohol use (≤14 years) among four birth cohorts dating back to 1900 was also examined. Results Eighty-nine percent of the cohort reported ever drinking; all individual ACEs except physical neglect increased the risk of ever using alcohol ( p p p Conclusions Adverse childhood experiences are strongly related to ever drinking alcohol and to alcohol initiation in early and mid adolescence, and the ACE score had a graded or "dose-response" relationship to these alcohol use behaviors. The persistent graded relationship between the ACE score and initiation of alcohol use by age 14 for four successive birth cohorts dating back to 1900 suggests that the stressful effects of ACEs transcend secular changes, including the increased availability of alcohol, alcohol advertising, and the recent campaigns and health education programs to prevent alcohol use. These findings strongly suggest that efforts to delay the age of onset of drinking must recognize the contribution of multiple traumatic and stressful events to alcohol-seeking behavior among children and adolescents.
Patient Adherence and Efficacy of Certolizumab Pegol in the Management of Crohn's Disease:

Treatment with Anti-Tumor Necrosis Factor (anti-TNF) therapy has become a mainstay of therapy for patients with CD who are unresponsive to conventional medical management. Currently there are three anti-TNF antibodies that have been approved by the US Food and Drug Administration for the treatment of CD, namely infliximab, adalimumab and certolizumab pegol (CZP). Several double blind placebo controlled trials determined that CZP is effective as induction and maintenance treatment in adult patients with CD regardless of their prior exposure to other anti-TNF antibodies. This review discusses the efficacy of CZP and adherence to therapy with anti-TNF antibodies in patients with CD.
Physicochemical and Electrochemical Properties of Ionic Liquids Containing Aprotic Heterocyclic Anions Doped With Lithium Salts

Ionic liquids (ILs) have been received significant attention in recent years due to their outstanding properties, such as negligibly small vapor pressure, high thermal stability, relatively high conductivity and wide electrochemical windows. [1-3] Especially in the electrochemical field, ILs have been intensively investigated as alternatives for common flammable and volatile organic solvents. [4] A series of novel ionic liquids based on N,N′dialkyimidazolium, alkylphosphonium and N,N′dialkylpyrrolidinium cations paired with two aprotic heterocyclic anions (AHAs) were synthesized in the present study. In addition, their corresponding lithium salts were prepared. Physicochemical and electrochemical properties of the neat ILs and their lithium salt mixtures at various concentrations were measured from 283.15K to 343.15K at atmosphere pressure. Properties investigated include density (ρ), viscosity (η), electrical conductivity (σ), melting point (Tm), and thermal decomposition temperature (Td). Generally, the densities of all the neat ILs and their mixtures with the corresponding lithium salts follow a linear relationship with temperature and decrease with increasing temperature. The densities of all the IL mixtures with lithium salts increased with increasing lithium salt concentrations. The temperature dependence of the viscosity and the electrochemical conductivity were investigated for all neat ILs and lithium salt doped ILs. The empirical Vogel-Fulcher-Tammann (VFT) equation was used to analyze the viscosity and the electrical conductivity experimental results, which gave excellent fits over the temperature range studied.
Reversible Inactivation of Protein-tyrosine Phosphatase 1B in A431 Cells Stimulated with Epidermal Growth Factor

Stimulation of various cells with growth factors results in a transient increase in the intracellular concentration of H2O2 that is required for growth factor-induced protein tyrosine phosphorylation. The effect of H2O2 produced in response to epidermal growth factor (EGF) on the activity of protein-tyrosine phosphatase 1B (PTP1B) was investigated in A431 human epidermoid carcinoma cells. H2O2 inactivated recombinant PTP1B in vitro by oxidizing its catalytic site cysteine, most likely to sulfenic acid. The oxidized enzyme was reactivated more effectively by thioredoxin than by glutaredoxin or glutathione at their physiological concentrations. Oxidation by H2O2 prevented modification of the catalytic cysteine of PTP1B by iodoacetic acid, suggesting that it should be possible to monitor the oxidation state of PTP1B in cells by measuring the incorporation of radioactivity into the enzyme after lysis of the cells in the presence of radiolabeled iodoacetic acid. The amount of such radioactivity associated with PTP1B immunoprecipitated from A431 cells that had been stimulated with EGF for 10 min was 27% less than that associated with PTP1B from unstimulated cells. The amount of iodoacetic acid-derived radioactivity associated with PTP1B reached a minimum 10 min after stimulation of cells with EGF and returned to base line values by 40 min, suggesting that the oxidation of PTP1B is reversible in cells. These results indicate that the activation of a receptor tyrosine kinase by binding of the corresponding growth factor may not be sufficient to increase the steady state level of protein tyrosine phosphorylation in cells and that concurrent inhibition of protein-tyrosine phosphatases by H2O2 might also be required.
Regenerative potential of platelet-rich plasma added to xenogenic bone grafts in peri-implant defects: a histomorphometric analysis in dogs.

Background: The purpose of this investigation was to evaluate the regenerative influence of platelet-rich plasma (PRP) added to xenogenic bone grafts on bone histomorphometric parameters in a dog model. Methods: Ninety endosseous dental implants were inserted in the mandibles of nine hound dogs. Mesial and distal 3-wall peri-implant defects were surgically created adjacent to the implants. Defects were randomly assigned to three groups: demineralized freeze dried bone with platelet-rich plasma (DFDB + PRP), DFDB alone, and no treatment (NT). Animals were sacrificed at 1, 2, and 3 months according to a previously established randomization schedule, and specimens were subjected to histomorphometric analysis. Percentages of bone area inside the implant threads (BiIT), bone-to-implant contact (BIC), and bone area outside implant threads (BoIT) were recorded. Treatment effects were evaluated using analysis of variance models. Results: The effect of the three treatments on the outcome measures did not differ significantly by healing time (P >0.05 for the healing time by treatment interaction). However, the average (standard deviation) percentage of BIC and BoIT was significantly different between the treatment groups. In particular, the average percentage of BIC differed between peri-implant defects treated with DFDB + PRP (33.8% [11.0]) and those treated with DFDB alone (28.5% [10.8]; P = 0.042), as well as those in the NT group (27.9% [11.0]; P = 0.024). Furthermore, the average percentage of BoIT differed significantly between defects treated with DFDB + PRP compared to defects in the NT group (51.6% [12.2] versus 43.3% [10.3]; P = 0.005). There was borderline evidence to suggest that the average percentage of BiIT and BIC was significantly different depending on the length of the healing time (P = 0.054 and P = 0.085, respectively). Conclusion: This study found that the addition of PRP to xenogenic bone grafts demonstrated a low regenerative potential in this animal model.
The effect of varying frequency and intensity of transcutaneous electrical nerve stimulation on secondary mechanical hyperalgesia in an animal model of inflammation

For years, transcutaneous electrical nerve stimulation (TENS) has been used clinically for the treatment of many types of pain. Although there have been many studies conducted on the efficacy of TENS in the clinical setting, the results are conflicting. The purpose of our investigation was to determine the effect of varying frequency and intensity of TENS on secondary mechanical hyperalgesia induced by acute joint inflammation. Male Sprague-Dawley rats were injected with a mixture of 3% carrageenan and 3% kaolin (100 microL in 0.9% sterile saline) into the joint cavity of one knee. The response threshold to mechanical stimuli was determined before inflammation of the knee joint; 4 hours after inflammation; immediately after the administration of TENS (approximately 5 hours after inflammation); and at 8, 12, and 24 hours after inflammation. TENS was applied to the inflamed knee joint at either high (100 Hz) or low (4 Hz) frequency and at either sensory or motor intensity. Sensory intensity was just below the threshold for motor contraction, and motor intensity was 2 x threshold for motor contraction. Either low- or high-frequency TENS is equally successful in reducing secondary mechanical hyperalgesia. Similarly, either sensory- or motor-intensity TENS equally reduces secondary mechanical hyperalgesia. Thus, selection of TENS should be based on patient comfort and symptoms for relief of secondary mechanical hyperalgesia.
Swarm: An Object Oriented Simulation Platform Applied to Markets and Organizations

Swarm is a library of software components developed by the Santa Fe Institute which allow researchers to construct discrete event simulations of complex systems with heterogeneous elements or agents. These libraries provide reusable objects for analyzing, displaying and controlling simulation experiments. Swarm is not based on any assumptions about the system that is being simulated, and is currently being used by a wide variety of researchers in the social and natural sciences. We present examples of economic models which have been implemented in Swarm and discuss the advantages of the Object-Oriented simulation approach.
Fluorescence from Diffusing Single Molecules Illuminates Biomolecular Structure and Dynamics

This review provides an account of single-molecule fluorescence methodologies for freely diffusing molecules applied to a diverse array of biological problems pertaining to biomolecular folding and assembly. We describe the principles of confocal fluorescence microscopy to detect and analyze fluorescence bursts from diffusing single molecules. These methods including single-molecule fluorescence resonance energy transfer, coincidence, correlations and polarization offer a powerful means to uncover hidden information about conformational sub-populations and interconversion dynamics of biomolecular systems in a wide range of timescales. We offer several key examples to illustrate how these methodologies have been extremely useful in teasing out structural and dynamical aspects of many important biomolecular systems.
Comparison of Correspondence Analysis Methods for Synonymous Codon Usage in Bacteria

Synonymous codon usage varies both between organisms and among genes within a genome, and arises due to differences in G + C content, replication strand skew, or gene expression levels. Correspondence analysis (CA) is widely used to identify major sources of variation in synonymous codon usage among genes and provides a way to identify horizontally transferred or highly expressed genes. Four methods of CA have been developed based on three kinds of input data: absolute codon frequency, relative codon frequency, and relative synonymous codon usage (RSCU) as well as within-group CA (WCA). Although different CA methods have been used in the past, no comprehensive comparative study has been performed to evaluate their effectiveness. Here, the four CA methods were evaluated by applying them to 241 bacterial genome sequences. The results indicate that WCA is more effective than the other three methods in generating axes that reflect variations in synonymous codon usage. Furthermore, WCA reveals sources that were previously unnoticed in some genomes; e.g. synonymous codon usage related to replication strand skew was detected in Rickettsia prowazekii. Though CA based on RSCU is widely used, our evaluation indicates that this method does not perform as well as WCA.
Magnetic properties of Co/sub 2/Y-type hexaferrite particles oriented in a rotating field

Cobalt Y-type hexaferrites are of interest as high permeability /spl mu/ materials in the miniaturization of integrated circuits. We oriented particles of sintered Co/sub 2/Y-type hexaferrite with c-axis normal to the slab plane. We measured the magnetic properties of Co substituted Y-type hexaferrites (Co/sub 0.25/Zn/sub 1.75/Y and Mn/sub 0.25/Co/sub 0.75/Zn/sub 1.0/), where the substitutions included Mn and Zn. The uniaxial magnetic anisotropy field, H/sub A/, decreased from 42 to 14.5 kOe as Zn substitution increased at the expense of Co. The ferromagnetic resonance linewidth exhibited similar dependence on Zn substitution varying from 1500 to 200 Oe at 28 GHz. For all the Zn or Mn substitutions, the saturation magnetization was relatively constant at 2000 G.