cssi/SciSciGPT-SciSciNet huggingface dataset:
Abstract 4347: Epigenetic targeting of DNMT1 in adipocytes inhibits high-grade serous ovarian cancer cell migration and invasion through TIMP3 upregulation

Ovarian cancer frequently metastasizes to the omentum and adipocytes play a significant role in tumor progression. As methylation levels in obese adipose tissue are increased due to increased DNMT1 levels and activity, it was of interest to test the hypothesis that inhibiting DNMT1 would reverse adipocyte methylation, alter adipokine secretion, and decrease migration and invasion of ovarian cancer cells towards adipocytes. Human adipocytes were seeded in a 24-well plate and treated with low-dose guadecitabine (100nM daily for 3 days). Ovarian cancer cells (SKOV3, Kuramochi, OVCAR4, OVCAR8) were seeded in the Boyden chamber and allowed to migrate or invade toward adipocytes for 8 and 16h, respectively. Expression of epithelial-mesenchymal transiton (EMT) markers (SLUG, FN1, TWIST1) were assessed by qRT-PCR. Adipocyte-conditioned media was used to culture ovarian cancer cells in clonogenicity assay and a human adipokine array (RD verified by qRT-PCR). Treatment with recombinant TIMP3 (50nM) decreased invasion of OVCAR8 (63%, P 10; FDR 1.5; FDR Citation Format: Jessica Tang, Fang Fang, Aaron Buechlein, Pietro Taverna, Kenneth P. Nephew. Epigenetic targeting of DNMT1 in adipocytes inhibits high-grade serous ovarian cancer cell migration and invasion through TIMP3 upregulation [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2017; 2017 Apr 1-5; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2017;77(13 Suppl):Abstract nr 4347. doi:10.1158/1538-7445.AM2017-4347
Characterization of terrestrial hydrothermal alteration products with mars analog instrumentation: implications for current and future rover investigations

Abstract Interpretation of Martian geology relies heavily on our understanding of terrestrial analog deposits and our ability to obtain comprehensive and accurate mineralogical compositions. Many previous studies of terrestrial hydrothermal deposits relied on limited datasets and/or did not use instruments analogous to those deployed on Mars. We analyzed 100 hydrothermally altered basalts from Costa Rica, Nicaragua, and Iceland with Mars analog Visible to Short Wave Infrared (VSWIR) spectroscopy, X-ray Diffraction (XRD), and Raman laser spectrometry. Alteration mineralogy consisted of amorphous and crystalline SiO2 (cristobalite, tridymite, quartz), Ca/Al/Fe/Mg-sulfates (gypsum, anhydrite, alunite, jarosite, hexahydrite, alunogen), Fe-, Ti-, and Mg-oxides/hydroxides (hematite, goethite, anatase/brookite, brucite), elemental sulfur, and phyllosilicates (montmorillonite, kaolinite). Results indicate VSWIR is best suited for identification of X-ray amorphous materials such as hydrated SiO2 and phyllosilicates, while XRD is best utilized for highly ordered crystalline materials such as sulfates, crystalline SiO2 polymorphs, elemental sulfur, and Mg-hydroxides identification. Surprisingly, XRD had the lowest identification rates for Fe-oxides/hydroxides (42% compared to 61% and 75% for VNIR and Raman, respectively), and nearly equal identification rates as VSWIR for kaolinite (76% for VSWIR, 71% for XRD). Identification of phyllosilicates in XRD, while possible, is not as effective as VSWIR without extensive sample preparation. Our observed identification rates may be attributed to the relative abundance of materials—Fe-oxides/hydroxides being present as surface coatings, the presence of large amounts of kaolinite in some samples, and an increased particle size for kaolinite relative to other clays. Elemental sulfur and Fe- and Ti-oxides/hydroxides were more readily identified with Raman. With NASA's current focus on habitability, hydrothermally altered areas—which we know to host a wide range of microbial life here on Earth—are of high interest and it is likely that future rovers will encounter similar mineral assemblages. Therefore, future rovers would benefit from using a combination of these methods and expanding the VSWIR sampling range to the full 300–2500 nm to conduct a comprehensive mineralogical investigation.
Markets and Violence: Qualitative Research and the Neoliberal Future:

Neoliberal epistemologies are grounded in a temporal paradox. To prosper, you have to know how actions taken now will pay off in the future. But you can’t know that—the future is uncertain and unknowable. In this context, qualitative inquiry becomes less a matter of explanation or interpretation than of feeding information into efforts to collapse the temporal horizon and format the future in a form that you can dominate. This article examines manifestations of this approach in the qualitative research practices of two key institutional sectors of neoliberalism: the corporate and military.
Severe Hemolytic Disease of the Newborn due to Anti-Jsb

Anti-Js(b) has not been reported to cause severe hemolytic disease of the newborn requiring intrauterine evaluation and treatment. We now report on such a patient with high-titered anti-Js(b) causing fetal hydrops with demise in one pregnancy, followed by a pregnancy treated with multiple intrauterine fetal transfusions.
Filifactor alocis modulates human neutrophil antimicrobial functional responses.

Filifactor alocis is a newly appreciated pathogen in periodontal diseases. Neutrophils are the predominant innate immune cell in the gingival crevice. In this study, we examined modulation of human neutrophil antimicrobial functions by F. alocis. Both non-opsonised and serum-opsonised F. alocis were engulfed by neutrophils but were not efficiently eliminated. Challenge of neutrophils with either non-opsonised or serum-opsonised F. alocis induced a minimal intracellular as well as extracellular respiratory burst response compared to opsonised Staphylococcus aureus and fMLF, respectively. However, pretreatment or simultaneous challenge of neutrophils with F. alocis did not affect the subsequent oxidative response to a particulate stimulus, suggesting that the inability to trigger the respiratory response was only localised to F. alocis phagosomes. In addition, although neutrophils engulfed live or heat-killed F. alocis with the same efficiency, heat-killed F. alocis elicited a higher intracellular respiratory burst response compared to viable organisms, along with decreased surface expression of CD35, a marker of secretory vesicles. F. alocis phagosomes remained immature by delayed and reduced recruitment of specific and azurophil granules, respectively. These results suggest that F. alocis withstands neutrophil antimicrobial responses by preventing intracellular ROS production, along with specific and azurophil granule recruitment to the bacterial phagosome.
Local Immunosuppression: The Lung

Lung transplantation represents an unusual situation in solid organ transplantation in that the graft is accessible to the external environment. In this situation aerosolized pharmacologic agents have direct access to the donor graft, and the technology for delivering medication by the inhalational route is well developed for other pulmonary disorders. In 1988, a team of investigators at the University of Pittsburgh made the decision to pursue aerosolized immunosuppression for lung transplant recipients based upon the belief that other limited models of localized immunosuppression have been successful, and the current pharmacologic regimen was not adequate for managing lung transplant rejection.
Concepts on the Role of Epoxy Carotenoids in Plants

Carotenoids in photosynthetic organisms are known to function in at least two ways; namely, as accessory light-harvesting pigments and as protective agents against lethal photo-oxidations (LUMRY et al. 1954, KRINSKY 1968). The fact that epoxy carotenoids are present only in photosynthetic 02 evolving organisms and undergo 1ight-induced changes suggests that they could have a different function in such organisms.
Concerted Actions of Octopamine and Dopamine Receptors Drive Olfactory Learning

Aminergic signaling modulates associative learning and memory. Substantial advance has been made in Drosophila on the dopamine receptors and circuits mediating olfactory learning; however, our knowledge of other aminergic modulation lags behind. To address this knowledge gap, we investigated the role of octopamine in olfactory conditioning. Here, we report that octopamine activity through the β-adrenergic-like receptor Octβ1R drives aversive and appetitive learning: Octβ1R in the mushroom body αβ neurons processes aversive learning, whereas Octβ1R in the projection neurons mediates appetitive learning. Our genetic interaction and imaging studies pinpoint cAMP signaling as a key downstream effector for Octβ1R function. The rutabaga-adenylyl cyclase synthesizes cAMP in a Ca2+/calmodulin-dependent manner, serving as a coincidence detector for associative learning and likely representing a downstream target for Octβ1R. Supporting this notion, the double heterozygous rutabaga/+;octβ1r/+ flies perform poorly in both aversive and appetitive conditioning, while individual heterozygous rutabaga/+ and octβ1r/+ flies behave like the wild-type control. Consistently, the mushroom body and projection neurons in the octβ1r brain exhibit blunted responses to octopamine when cAMP levels are monitored through the cAMP sensor. We previously demonstrated the pivotal functions of the D1 receptor dDA1 in aversive and appetitive learning, and the α1 adrenergic-like receptor OAMB in appetitive learning. As expected, octβ1r genetically interacts with dumb (dDA1 mutant) in aversive and appetitive learning, but it interacts with oamb only in appetitive learning. This study uncovers the indispensable contributions of dopamine and octopamine signaling to aversive and appetitive learning. All experiments were performed on mixed sex unless otherwise noted.SIGNIFICANCE STATEMENT Animals make flexible behavioral choices that are constantly shaped by experience. This plasticity is vital for animals to appropriately respond to the cues predicting benefit or harm. In Drosophila, dopamine is known to mediate both reward-based and punishment-based learning while octopamine function is important only for reward. Here, we demonstrate that the octopamine-Octβ1R-cAMP pathway processes both aversive and appetitive learning in distinct neural sites of the olfactory circuit. Furthermore, we show that the octopamine-Octβ1R and dopamine-dDA1 signals together drive both aversive and appetitive learning, whereas the octopamine-Octβ1R and octopamine-OAMB pathways jointly facilitate appetitive, but not aversive, learning. This study identifies the cognate actions of octopamine and dopamine signaling as a key neural mechanism for associative learning.
Finite Element Modeling of Longitudinal Field-Cast Connections Between Precast Deck Bulb-T Bridge Girders

An alternative mix design using polypropylene fiber-reinforced high early strength concrete was proposed by the Idaho Transportation Department for the longitudinal connections between deck bulb-T ...
Multi-wavelength polarimetry and variability study of the M87 jet

We present a high resolution polarimetry and variability study of the M87 jet using VLA and HST data taken during 2002 to 2008. Both data-sets have an angular resolution as high as 0.06”, which is 2-3 times better than previous observations. New morphological details are revealed in both the optical and radio, which can help to reveal the energetic and magnetic field structure of the jet. By comparing the data with previously published HST and VLA observations, we show that the jet's morphology in total and polarized light is changing significantly on timescales of ~1 decade. We compare the evolution of the inner jet (particularly the nucleus and knot HST-1), when our observations overlap with the multi-wavelength monitoring campaigns conducted with HST and Chandra. We use these data to comment on particle acceleration and main emission processes.
Incidence and predictors of comorbid insomnia in a sleep surgery clinic.

Study Objectives:The objective was to determine the prevalence and predictors of comorbid insomnia in patients presenting for sleep surgery evaluation. The insomnia severity index (ISI) was utilize...
Fidelity of a Traffic Safety Education Intervention for Combat Veterans.

Equipoise, feasibility, and fidelity were studied for the control condition of an occupational therapy driving intervention in a randomized controlled trial. We ranked equipoise and feasibility of ...
Colorimetric quantification of linking in thermoreversible nanocrystal gel assemblies

Nanocrystal gel networks can be responsive, tunable materials, but deliberately designing their structure and controlling their properties have been challenging. By employing reversibly bonded molecular linkers, gelation can be realized under conditions predicted by thermodynamics. But, simulations have offered the only microscopic insights, with no experimental means to monitor linking leading to gelation. Here, we introduce a metal coordination linkage with a distinct optical signature allowing us to quantify linking in situ and establish the structural and thermodynamic basis for assembly. Due to coupling between linked indium tin oxide nanocrystals, their infrared absorption shifts abruptly at a chemically tunable gelation temperature. We quantify bonding spectroscopically and use molecular dynamics simulations to understand bonding motifs as a function of temperature, revealing that gel formation is governed by reaching a critical number of effective links that extend the nanocrystal network. Microscopic insights from our colorimetric linking chemistry enable switchable gels based on equilibrium thermodynamic principles, opening the door to rational design of programmable nanocrystal net-work assemblies.
Mitochondrial complex I as a therapeutic target for Alzheimer’s disease

Abstract Alzheimer’s disease (AD), the most prominent form of dementia in the elderly, has no cure. Strategies focused on the reduction of amyloid beta or hyperphosphorylated Tau protein have largely failed in clinical trials. Novel therapeutic targets and strategies are urgently needed. Emerging data suggest that in response to environmental stress, mitochondria initiate an integrated stress response (ISR) shown to be beneficial for healthy aging and neuroprotection. Here, we review data that implicate mitochondrial electron transport complexes involved in oxidative phosphorylation as a hub for small molecule-targeted therapeutics that could induce beneficial mitochondrial ISR. Specifically, partial inhibition of mitochondrial complex I has been exploited as a novel strategy for multiple human conditions, including AD, with several small molecules being tested in clinical trials. We discuss current understanding of the molecular mechanisms involved in this counterintuitive approach. Since this strategy has also been shown to enhance health and life span, the development of safe and efficacious complex I inhibitors could promote healthy aging, delaying the onset of age-related neurodegenerative diseases.
Giant Cell-Rich Lesions

Although the vast majority of bone/joint tumors contain giant cells, this discussion of giant cell–rich lesions is limited to entities in which the giant cells are an essential lesional component: chief among these are giant cell tumors of bone, giant cell reparative granuloma, and aneurysmal bone cysts. Giant cell reparative granuloma was first described as a nonneoplastic lesion of gnathic bones in children and young adults. Thereafter, the concept of giant cell reparative granuloma of extragnathic sites (also known as giant cell reaction) has been widely recognized. Given the significant histologic overlap, many practitioners have merged giant cell reparative granuloma of extragnathic sites with the solid variant of aneurysmal bone cysts, and the neoplastic nature of these interchangeably termed entities has been supported by the identification of various translocations.
Abstract 4327: Mitochondrial reprogramming in triple negative breast cancer progression

Unlike other subgroups of patients with breast cancer (BCa), for triple negative (TN) BCa, there is a current lack of understanding of driver pathways and hence are often managed using more generic therapies. Thus, it is important to identify the underlying mechanisms of triple negative breast cancer progression and its racial disparity. Mitochondria-nuclear crosstalk is a bidirectional pathway of communication between mitochondria and nucleus that influences many cellular and organismal activities. This crosstalk can regulate several oncogenic pathways that regulate cellular tumor characteristics. With the advent of transmitochondrial cybrid (cybrid) technology, it is now possible to examine the specific contribution of tumor-associated mitochondria in neoplastic growth and development under a defined common nuclear background. We used this model system to identify mitochondria regulated pathways in TN BCa. Among different oncogenic pathways, Src pathway is frequently over-expressed in TN BCa and Src inhibitors are proposed as one of their current treatments of choice. However, single drug therapy with Src inhibitors failed to control metastatic TN BCa in recent Phase-II trials. These highlight an important question on the mechanism behind the regulation of Src oncogenic signature in TN BCa. Using cybrid technology, we have discovered critical role of cancer mitochondria in the post-translational modification of Src oncogenic pathway. Interestingly we discovered that the Src autophosphorylation, which activate Src-mediated oncogenic pathway, depends on mitochondrial tumor characteristics. Specifically, our strong preliminary data suggest that mitochondrial reprogramming is a critical step in the autophosphorylation and activation of Src pathway in metastatic TN BCa cells. Our findings suggest mitochondria targeted drugs as promising combination therapy for the management of Src positive TN BCa. Citation Format: Junhyoung Park, Kavisha Arora, Sajna A. Vithayathil, Taraka R. Donti, Chad Creighton, Michael T. Lewis, Arun Sreekumar, Lee-Jun Wong, Benny A. Kaipparettu. Mitochondrial reprogramming in triple negative breast cancer progression. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 4327. doi:10.1158/1538-7445.AM2014-4327
Robotic totally endoscopic coronary artery bypass grafting for spontaneous coronary artery dissection.

Background Patients with spontaneous coronary artery dissection may require surgical revascularization. Reports on the surgical management of this pathology are primarily limited to classic coronary artery bypass grafting via sternotomy on cardiopulmonary bypass, although a limited number of reports of alternatives also exist. Methods We describe a case of robotic completely endoscopic coronary surgery using the daVinci® Si™ system in a patient with spontaneous coronary artery dissection. Results Robotically assisted single left internal mammary artery grafting to the left coronary artery system was carried out successfully in a completely endoscopic fashion. Conclusions Selected patients with spontaneous coronary artery dissection may benefit from a totally endoscopic approach to surgical coronary revascularization. Copyright © 2012 John Wiley & Sons, Ltd.
Understanding VOT Variation in Spontaneous Speech

This paper reports a corpus study on the variation of VOT in voiceless stops in spontaneous speech. Two speakers’ data from the Buckeye corpus are used: one is an older female speaker with a low speaking rate while the other is a younger male speaker with an extremely high speaking rate. Linear regression analysis shows that place of articulation, word frequency, phonetic context, speech rate and utterance position all have an effect on the length of VOT. However, altogether less than 20% of the variation is explained in both speakers, which suggests that pronunciation variation in spontaneous speech is a highly complicated phenomenon which might need more sophisticated modeling. Our results also show a great deal of individual differences.
A Reply to Szabó’s “Descriptions and Uniqueness”

Szabo (2000) follows Heim (1982,1983) in viewing familiarity, rather thanuniqueness, as the essence of the definitearticle, but attempts to derive bothfamiliarity and uniqueness implicationspragmatically, assigning a single semanticinterpretation to both the definite andindefinite articles. I argue that if there isno semantic (conventional) distinction betweenthe articles, then there is no way to derivethese differences between them pragmatically.
Priority Controlled Incremental Attribute Evaluation in Attributed Graph Grammars

We show how incremental attribute change propagation can be efficiently done on Graph Grammars. The order of evaluation is controlled by priority numbers assigned to each attribute vertex. The priority numbers are assigned in linear time as directed by static grammar analysis. We also develop a powerful set-theoretic based embedding description format, and introduce the idea of roles as a mechanism to aid in graph grammar engineering. Roles are also a powerful aid to static analysis of grammar properties. A key to our approach is the uniformity gained by collapsing the substrate (structure) graph and the attribute dependency graph into a single directed graph structure. Related groups of attributes are simultaneously replaced by cluster rewrites.
Wave reflection and quasiresonance

Wave reflection by smooth media and resonance of systems with radiation damping are instructive examples of a failure of the standard approach to asymptotics. They are also good examples of a type of exponential asymptotics needed for the sciences. Successful modifications of conventional, singular-perturbation theory have been found for them and show some of the principles promising wider usefulness. They have led to recent developments in WKB-connection theory, which are also reported briefly.
Practical applications for natural language processing in clinical research

Display Omitted Capstone shared task for 8years of i2b2 challenges. Co-organized with UTHealth.Four tracks: de-identification, risk factor extraction, software usability, and novel data use.Participation from around the world, from academia and industry.Data sets available for research beyond the lifetime of i2b2, at i2b2.org/NLP.
Punishment and Cooperation

Data from economic games show that the effectiveness of punishment in fostering cooperation varies greatly from society to society.
Abstract 7: Dose Response Relationship in Transcranial Direct Current Stimulation Stroke Motor Recovery Studies

Background: Dozens of clinical trials investigated the potential efficacy of transcranial direct current stimulation (tDCS) in post-stroke motor recovery. Various current levels, pad size, number of sessions were used in different studies with mixed results in motor outcomes. We aimed to investigate a dose/current-response relationship by pooling published studies. Methods: We identified relevant studies in Pubmed, EMBASE and clinicaltrials.gov from January 1990 to June 2014. We included sham-controlled randomized or quasi-randomized studies with ≥5 tDCS sessions and derived percent improvement in primary endpoint (percent improvement in treatment group - percent improvement in sham group) from each study. We plotted current, current density, charge per session, charge density per session, total charge and charge density with percent improvement. To assess the dose-response relationship, we conducted regression analyses where studies were weighed by the number of participants (sample size). Results: We id...
A high performance BiCMOS technology using 0.25 mu m CMOS and double poly 47 GHz bipolar

In this technology, first the CMOS is defined and a major part of the heat cycle is carried out. Then, the bipolar is fabricated by the rest of the CMOS. Patterned subcollector definition and epitaxial silicon growth are followed by the deep and shallow trench isolation processes. Next are the npn collector reach-through and anneal, CMOS well and threshold implants, gate oxidation and poly deposition. CMOS gate definition, reoxidation, and nMOS n/sup +/ implant. Electron-beam lithography is used to pattern the gate level in order to achieve a minimum gate poly width of 0.3 mu m. Next, the CMOS region is protected, while fabricating the bipolar. The annealing cycles for base and emitter during the process are compatible with the CMOS requirements. The minimum final emitter size is 0.5 mu m. CMOS ring oscillators with 50-ps delay per stage at 2.5-V supply, ECL ring oscillator delays of 48 ps at 1.2 mA, and fast loaded BiNMOS gate delays have been achieved. >
DEUS CARITAS EST: THE SOCIAL MESSAGE OF POPE BENEDICT XVI

The first encyclical letter of Pope Benedict XVI contains many surprises, not least among which are observations about the nature of justice, the limits of the state, and the purpose and character of charitable organisations. This article analyses the encyclical by highlighting some of its underlying theological and philosophical influences as well as its practical implications for how Christians think about approaching poverty and the political order.
Expansion of Intestinal Epithelial Stem Cells during Murine Development

Murine small intestinal crypt development is initiated during the first postnatal week. Soon after formation, overall increases in the number of crypts occurs through a bifurcating process called crypt fission, which is believed to be driven by developmental increases in the number of intestinal stem cells (ISCs). Recent evidence suggests that a heterogeneous population of ISCs exists within the adult intestine. Actively cycling ISCs are labeled by Lgr5, Ascl2 and Olfm4; whereas slowly cycling or quiescent ISC are marked by Bmi1 and mTert. The goal of this study was to correlate the expression of these markers with indirect measures of ISC expansion during development, including quantification of crypt fission and side population (SP) sorting. Significant changes were observed in the percent of crypt fission and SP cells consistent with ISC expansion between postnatal day 14 and 21. Quantitative real-time polymerase chain reaction (RT-PCR) for the various ISC marker mRNAs demonstrated divergent patterns of expression. mTert surged earliest, during the first week of life as crypts are initially being formed, whereas Lgr5 and Bmi1 peaked on day 14. Olfm4 and Ascl2 had variable expression patterns. To assess the number and location of Lgr5-expressing cells during this period, histologic sections from intestines of Lgr5-EGFP mice were subjected to quantitative analysis. There was attenuated Lgr5-EGFP expression at birth and through the first week of life. Once crypts were formed, the overall number and percent of Lgr5-EGFP positive cells per crypt remain stable throughout development and into adulthood. These data were supported by Lgr5 in situ hybridization in wild-type mice. We conclude that heterogeneous populations of ISCs are expanding as measured by SP sorting and mRNA expression at distinct developmental time points.
Incontinentia pigmenti: pigmentary changes independent of incontinence.

Incontinentia pigmenti is characterized by swirled hyper-pigmentation associated with incontinence of pigment. A different pattern may be seen on the legs with light-colored atrophic scarred areas admixed with patches of normal but darker skin. Histologic examination confirms that the darker skin is normal without incontinence of pigment, while the light-colored skin lacks melanocytes and appendages but has dermal fibrosis.
Turn Plant Closings and Layoffs into Economic Development

Private equity firms are sometimes obliged to trim payrolls. When they do, there are ways to turn these events into positive local economic development opportunities. Entrepreneurs can be discovered and nurtured to create new businesses, thus creating a win–win situation for communities and investors.
Wear Behavior of Flat and Graded Profile Boron-Implanted Beryllium

Pin-on-disk tests were performed for comparative friction and wear behavior on flat and graded profile boron implanted beryllium samples. Peak, intended boron concentrations of 10, 20, 30 and 40 atom percent were investigated. Auger Electron Spectroscopy was used to determine the boron concentration as a function of depth. Preliminary work was performed to study the effects of (1) a low temperature (450°C, 1–1/2 hours) heat treatment of the implanted specimens and (2) a change in the pin material. All of the boron implanted beryllium samples showed significant improvement versus unimplanted beryllium and an anodized beryllium surface. Graded samples showed comparable friction coefficients but inferior wear resistance with respect to the flat profile samples.
Cdc48pNpl4p/Ufd1p Binds and Segregates Membrane-Anchored/Tethered Complexes via a Polyubiquitin Signal Present on the Anchors

Summary Cdc48p is an abundant and conserved member of the AAA ATPase family of molecular chaperones. Cdc48p performs ubiquitin-selective functions, which are mediated by numerous ubiquitin binding adaptors, including the Npl4p-Ufd1p complex. Previous studies suggest that Cdc48p-containing complexes carry out many biochemical activities, including ubiquitination, deubiquitination, protein complex segregation, and targeting of ubiquitinated substrates to the proteasome. The molecular mechanisms by which Cdc48p-containing complexes participate in these processes remain poorly defined. We show here by using physiologically relevant Cdc48p substrates (i.e., endoplasmic membrane-associated/tethered dimers of Mga2p and Spt23p) and in vitro systems with purified proteins that Cdc48p Npl4p/Ufd1p binds to and promotes segregation of the tethered proteins via a polyubiquitin signal present on the membrane-bound proteins. Mobilization does not involve retrotranslocation of the associated anchors. These results provide biochemical evidence that Cdc48p Npl4p/Ufd1p functions as a polyubiquitin-selective segregase and that a polyubiquitin-Cdc48p pathway modulates protein interactions at cell membranes.
Arachidonate synthesis and uptake in isolated guinea-pig megakaryocytes and platelets.

Abstract Arachidonic acid (20:4) synthesis and uptake were studied in guinea-pig megakaryocytes and platelets. Isolated megakaryocytes and platelets were incubated with ( 3 H]20:4, 8,11,14-[ 14 C]eicosatrienoic acid (γ-20:3) and [ 14 C]linoleic acid (18:2) and their lipids were analyzed for radioactivity. The study showed that there was 0.153 μM of unesterified 20:3 and 0.237 μM of 20:4 in guinea-pig plasma in nonfasting animals. At these concentrations, 42.6 pmol of γ-20:3 and 53.3 pmol of 20:4 were taken up per h per 10 5 megakaryocytes in vitro. Megakaryocytes desaturated 27% of the γ-20:3 to 20:4 but could not desaturate 18:2. Platelets could not desaturate γ-20:3 or 18:2. In megakaryocytes, the distribution of 20:4 synthesized by the desaturation of γ-20:3 and 20:4 taken up reflected the endogenous distribution of 20:4 in megakaryocyte phospholipids and 20:4 was predominantly incorporated into phosphatidylethanolamine (PE). In contrast, the distribution of [ 3 H]20:4 taken up into platelets did not reflect the endogenous distribution. 20:4 was primarily incorporated into platelet phosphatidylcholine and phosphatidylinositol. The study showed that megakaryocytes but not platelets possess a Δ 5 desaturase and can synthesize 20:4 from γ-20:3. Neither cell was shown to have a Δ 6 desaturase. Megakaryocytes appear to have the capacity to determine the composition of all pools of platelet 20:4 either by uptake or synthesis of 20:4. Platelets, most likely, have a limited capacity to alter structural pools of 20:4 contained primarily in PE and phosphatidylserine (PS).
Economics and financing of vaccines for diarrheal diseases

The considerable burden of infectious disease-caused diarrhea around the world has motivated the continuing development of a number of vaccine candidates over the past several decades with some reaching the market. As with all major public health interventions, understanding the economics and financing of vaccines against diarrheal diseases is essential to their development and implementation. This review focuses on each of the major infectious pathogens that commonly cause diarrhea, the current understanding of their economic burden, the status of vaccine development, and existing economic evaluations of the vaccines. While the literature on the economics and financing of vaccines against diarrhea diseases is growing, there is considerable room for more inquiry. Substantial gaps exist for many pathogens, circumstances, and effects. Economics and financing studies are integral to vaccine development and implementation.
Massive Vitreous Hemorrhage and Senile Macular Choroidal Degeneration

In the elderly patient with a massive vitreous hemorrhage in one eye and senile macular choroidal degenerative changes in the fellow eye, a hemorrhagic disciform detachment causing this massive vitreous hemorrhage must be considered in the differential diagnosis. Ultrasonography selectively combined with radioactive phosphorus (32P) testing differentiates between a hemorrhagic disciform detachment or disciform scar and a malignant melanoma of the choroid. The ultrasonographic findings of a hemorrhagic disciform detachment may vary, but usually the posterior pole lesion is relatively flat and broad-based with a fairly homogeneous pattern without choroidal excavation. Posterior polar lesions secondary to senile macular choroidal degeneration do not grow. The vitreous hemorrhage clears in about three fourths of the patients, eventually allowing visualization of the posterior pole and ophthalmoscopic confirmation of a disciform scar. Almost one half of the eyes may be expected to lose all light perception because of the development of an initially hemorrhagic retinal detachment.
Plaque formation in vitro on wires by gram-negative oral microorganisms (Veillonella).

Abstract Primary plaque was formed on nichrome steel wires suspended in sucrose media inoculated with Gram-positive filamentous diphtheroids, previously shown to have plaque forming ability. The plaques were then transferred into a Veillonella inoculated lactate medium which supported growth of Veillonella but retarded that of the diphtheroid. Transfer to lactate medium inoculated with Veillonella resulted in considerable increase in the size of the plaque, usually 2–3 grades over that obtained with the diphtheroid alone. Controls consisting of primary plaque incubated in diphtheroid inoculated, as well as uninoculated, lactate media showed no increase in size. In addition, no primary plaque formation was observed with the Veillonella alone. Gram stains of the outer surface of the secondary plaque revealed essentially Gram-negative diplococci. Optical microscopy of toluidine blue stained thick sections of Epon embedded primary plus secondary plaque specimens showed that the plaque was composed of two morphologically distinct types of bacteria. The diplococci appeared to form microcolonies within, as well as around, the matrix formed by the diphtheroid. Electron microscopy supported this finding.
Laparoscopic Ovariectomy Diminishes Estrus-Associated Behavioral Problems in Mares

Abstract Synthetic progestins, including altrenogest, are employed to modify undesirable estrus-related behavior or poor performance in mares. Bilateral laparoscopic ovariectomy (BLO) is another means of management. Our objective was to compare the perceived improvement in mares with estrus-related problems administered altrenogest to BLO. Owners of mares with estrus-related problem(s) that had undergone BLO after altrenogest treatment completed a telephone survey. They rated the behavioral or performance improvements with altrenogest and after BLO on a Likert scale (1 = no response; 5 = complete resolution). They also compared improvement with altrenogest and following BLO (1 = better response with altrenogest; 2 = comparable responses; 3 = better response with BLO). Likert scores for the two treatments were compared using the Wilcoxon signed rank test. The association between altrenogest and BLO scores was compared using Spearman rank-order correlation. Owners or trainers identified a variety of estrus-related problems in 20 mares meeting the inclusion criteria. Median scores for BLO were significantly higher than those for altrenogest (P = .008). The association of the perceived response to altrenogest and BLO was positive but relatively weak (ρ = 0.288). In a substantial proportion of mares with estrus-related problems, a salutary response to altrenogest was associated with a favorable response to BLO; however, some mares showing limited improvement with the progestagen still responded favorably to BLO. In this series, BLO was perceived by owners or trainers to be at least as effective as altrenogest administration as a means of diminishing a number of estrus-related behavioral and performance problems.
A Theoretical Framework for the Interactions among Models in the Integrated Transportation and Land-Use Package

The framework developed in this paper describes the interactions among the components models in the integrated transportation and land-use package, ITLUP, developed by Putman. A partial solution for employment and residential location patterns can be found with matrix inversion. The existence, uniqueness, and positivity of these solutions is demonstrated. The interactions between the location models are interpreted as a special type of multiplier effect. Also, in the analysis several new functionally equivalent ITLUP algorithms are identified.
A computational analysis of the deformation mechanisms of a nanocrystal–metallic glass composite

Abstract Simulations of a monatomic model amorphous matrix embedded with approximately 37% of a body-centered cubic phase demonstrate mechanisms by which nanocrystallites can alter the mechanical response of metallic glass. Three effects affect the resulting ductility: (i) the presence of weak amorphous–crystalline interfaces, (ii) the fraction of nanocrystallites oriented to prevent twinning relative to the loading stress, and (iii) the shear-induced growth and dissolution of the nanocrystallites when they are impinged by shear bands. While the first effect dominates in these simulations due to system size limitations, the third effect appears to be crucial for understanding the ductility of experimental samples. These simulations indicate that shear-induced growth of existing nanocrystallites, rather than nucleation of new crystalline regions, may account for the observed enhancement in ductility.
Semi-insulating crystalline silicon formed by oxygen doping during low-temperature chemical vapor deposition

In this letter we demonstrate the use of oxygen as a dopant in silicon to create semi‐insulating, crystalline silicon films grown by chemical vapor deposition. The films contain oxygen concentrations that exceed the peak solid solubility of oxygen in silicon by several orders of magnitude, yet they remain crystalline. The resistivities of these films reach levels of 106 Ω cm at room temperature and the electronic properties of the films exhibit classical characteristics of space‐charge‐limited current associated with insulators containing trap states within the band gap. We then demonstrate that metal‐oxide‐semiconductor transistors with bulk‐like mobilities can be fabricated in crystalline silicon layers grown without oxygen on top of the semi‐insulating films.
Wireless location privacy protection

After more than two decades of hype, computing and communication technologies are finally converging. Java-enabled cell phones run a host of powerful applications including mobile Internet access, while many notebook computers offer high-speed wireless connectivity as a standard feature. The big decision when purchasing a PDA is whether to get integrated cellular service or Wi-Fi capability. Location-based services are emerging as the next killer app in personal wireless devices, but there are few safeguards on location privacy. In fact, the demand for improved public safety is pushing regulation in the opposite direction. Today, when a person reports an emergency from a landline phone by dialing 911 in the United States or 112 in Europe, the system displays the caller's phone number and address to the dispatcher. The US Federal Communications Commission has mandated that, by December 2005, all cellular carriers be able to identify the location of emergency callers using mobile phones to within 50 to 100 meters. However, how cellular carriers and other businesses will use this capability remains open to question. The article looks at some of the areas this capability affects, including: privacy risks; economic damages; location-based spam; intermittent connectivity; user interfaces; network privacy; and privacy protection.
Changes in intact membrane lipid content of archaeal cells as an indication of metabolic status

Archaea build their cellular membrane with glycerol dialkyl glycerol tetraether (GDGT) core lipids, bound to polar head groups to form intact GDGTs. These lipids are commonly used as indicators of archaeal biomass in the environment. Here, we measured both intact and core GDGTs and archaeal 16S rRNA gene copies (a proxy for cell abundance) in order to determine cellular GDGT content in a coastal fjord at different locations, seasons and depths. We found that the abundance of both intact and core GDGTs relative to 16S rRNA gene copy numbers varied by two orders of magnitude, were generally higher in surface than deeper water and were elevated during periods associated with seasonal phytoplankton blooms. Core and intact GDGTs followed similar trends, but the ratio of core GDGT/16S rRNA gene copy number reached a maximum in October, following a peak in the ratio of intact GDGT/16S rRNA gene copy number that occurred in August. Our data suggest that spatial and temporal variability in these ratios must be considered when attempting to quantify cell numbers in the environment using either GDGTs or 16S rRNA genes. We used optimized extraction methods for both GDGTs and DNA. However, there is still potential for bias in qPCR methodology that could influence the GDGT/16S rRNA gene copy ratio. The apparent variability in cellular membrane lipid concentration could serve to evaluate the status of archaeal populations as it relates to: (i) varying cell size resulting from changes in either community structure or nutritional status, (ii) population turnover times and (iii) changing environmental factors that affect the lifetime of intact GDGTs after cell death.
Assembly of single wall carbon nanotube-metal nanohybrids using biomolecular components

Biomaterials such as nucleic acids and proteins can be exploited to create higher order structures. The biomolecular components such as DNA and peptides have been used to assemble nanoparticles with high fidelity. Here, we use DNA and peptides, and their preferential interaction with inorganic and carbon nanomaterials to form homogeneous hybrids. The enhanced binding of Pt ions to both DNA and peptide functionalized nanoparticles mediates the assembly of carbon nanotubes functionalized with DNA with peptide coated gold nanoparticles.
THE EFFECT OF THE GUIDE TREE ON MULTIPLE SEQUENCE ALIGNMENTS AND SUBSEQUENT PHYLOGENETIC ANALYSES

Many multiple sequence alignment methods (MSAs) use guide trees in conjunction with a progressive alignment technique to generate a multiple sequence alignment but use differing techniques to produce the guide tree and to perform the progressive alignment. In this paper we explore the consequences of changing the guide tree used for the alignment routine. We evaluate four leading MSA methods (ProbCons, MAFFT, Muscle, and ClustalW) as well as a new MSA method (FTA, for "Fixed Tree Alignment") which we have developed, on a wide range of simulated datasets. Although improvements in alignment accuracy can be obtained by providing better guide trees, in general there is little effect on the "accuracy" (measured using the SP-score) of the alignment by improving the guide tree. However, RAxML-based phylogenetic analyses of alignments based upon better guide trees tend to be much more accurate. This impact is particularly significant for ProbCons, one of the best MSA methods currently available, and our method, FTA. Finally, for very good guide trees, phylogenies based upon FTA alignments are more accurate than phylogenies based upon ProbCons alignments, suggesting that further improvements in phylogenetic accuracy may be obtained through algorithms of this type.
On Overfitting in Analysis of Symmetrically Predicted Endogenous Subgroups from Randomized Experimental Samples: Part Three of a Method Note in Three Parts.

Using exogenous characteristics to identify endogenous subgroups, the approach discussed in this method note creates symmetric subsets within treatment and control groups, allowing the analysis to take advantage of an experimental design. In order to maintain treatment–control symmetry, however, prior work has posited that it is necessary to use a prediction subsample, separate from the subsample used for impact estimation in order to prevent overfitting from affecting impact estimates. Doing so diminishes sample size—both for prediction and analysis—and so has costs. This article delves into this topic to consider the conditions under which overfitting occurs and to characterize the effects of overfitting in terms of bias and variance. It suggests a strategy for preserving the full sample size in all phases of the analysis. The research uses Monte Carlo simulation to directly measure overfitting, identify the circumstances that should concern us, and to explore possible recommended practices and future r...
Bayesian Proteoform Modeling Improves Protein Quantification of Global Proteomic Measurements

As the capability of mass spectrometry-based proteomics has matured, tens of thousands of peptides can be measured simultaneously, which has the benefit of offering a systems view of protein expression. However, a major challenge is that with an increase in throughput, protein quantification estimation from the native measured peptides has become a computational task. A limitation to existing computationally-driven protein quantification methods is that most ignore protein variation, such as alternate splicing of the RNA transcript and post-translational modifications or other possible proteoforms, which will affect a significant fraction of the proteome. The consequence of this assumption is that statistical inference at the protein level, and consequently downstream analyses, such as network and pathway modeling, have only limited power for biomarker discovery. Here, we describe a Bayesian model (BP-Quant) that uses statistically derived peptides signatures to identify peptides that are outside the dominant pattern, or the existence of multiple over-expressed patterns to improve relative protein abundance estimates. It is a research-driven approach that utilizes the objectives of the experiment, defined in the context of a standard statistical hypothesis, to identify a set of peptides exhibiting similar statistical behavior relating to a protein. This approach infers that changes in relative protein abundance can be used as a surrogate for changes in function, without necessarily taking into account the effect of differential post-translational modifications, processing, or splicing in altering protein function. We verify the approach using a dilution study from mouse plasma samples and demonstrate that BP-Quant achieves similar accuracy as the current state-of-the-art methods at proteoform identification with significantly better specificity. BP-Quant is available as a MatLab ® and R packages at https://github.com/PNNL-Comp-Mass-Spec/BP-Quant.