cssi/SciSciGPT-SciSciNet huggingface dataset:
Protease-activated receptors: novel central role in modulation of gastric functions

Protease-activated receptors (PARs) are members of a subfamily of G-protein-coupled receptors that regulate diverse cell functions in response to proteolytic cleavage of an anchored peptide domain that acts as a 'tethered' receptor-activating ligand. PAR-1 and PAR-2 in particular are present throughout the gastrointestinal (GI) tract and play prominent roles in the regulation of GI epithelial function, motility, inflammation and nociception. In a recent article in Neurogastroenterology and Motility, Wang et al. demonstrate, for the first time, that PAR-1 and PAR-2 are present on preganglionic parasympathetic neurons within the rat brainstem. As in other cellular systems, proteases such as thrombin and trypsin activate PAR-1 and PAR-2 on neurons of the dorsal motor nucleus of the vagus (DMV), leading to an increase in intracellular calcium levels via signal transduction mechanisms involving activation of phospholipase C and inositol triphosphate (IP3). The authors also report that the level of PAR-1 and PAR-2 transcripts in DMV tissue is increased following experimental colitis, suggesting that inflammatory conditions may modulate neuronal behavior or induce plasticity within central vagal neurocircuits. It seems reasonable to hypothesize, therefore, that the activity and behavior of vagal efferent motoneurons may be modulated directly by local and/or systemic proteases released during inflammation. This, in turn, may contribute to the increased incidence of functional GI disorders, including gastric dysmotility, delayed emptying and gastritis observed in patients with inflammatory bowel diseases.
Meteorological predictions for the Beagle 2 mission to Mars

[1] A general circulation and mesoscale model are used to predict the weather at the Beagle 2 landing site. The afternoon high temperature predicted by the general circulation model varies from 237 to 243 K over the duration of the primary mission. The overnight low temperature is 193 K ± 2 K. Near surface wind speeds remain below 15 ms−1 at all times. The mesoscale model predicts a wind maximum at the top of the ∼4 km deep convective boundary layer. Gravity waves are evident in the free atmosphere above the PBL. The overall weather pattern is dominated by upslope and downslope circulations, but these are modulated by changes in the large-scale circulation.
Nutrient retention in salt marsh plots experimentally fertilized with sewage sludge

Abstract Salt marsh plots 10 m in diameter were fertilized once every two weeks with commercially-available sewage sludge and nutrient losses measured in ebbing tidal water. Principal losses were in the form of ammonium and phosphate and were related principally to dosage applied and height of tide following application. Calculated nitrogen losses varied from 6 to 20% of that applied, phosphate from 6 to 9% during summer when plants were growing. Salt marshes are able to retain substantial amounts of applied nutrients.
Characteristics of Polymerized Pyridoxylated Hemoglobin

Polymerization of SFH-P currently provides the only approach that leads to a hemoglobin solution that approximates the O2 carrying capacity of whole blood and can be infused without altering the COP of plasma. It appears to have an adequate O2 loading and unloading characteristic and a greatly improved intravascular half-life. In addition, stable shelf-life at 4°C of greater than five months, makes it a prime candidate for future pre-clinical and clinical investigations.
High-dose chemotherapy and hematopoietic stem cell rescue for breast cancer: experience in California.

The role of high-dose chemotherapy (HDCT) and autologous hematopoietic stem cell rescue in breast cancer is still controversial. We analyzed the outcomes of 1111 consecutive patients with histologically proven breast cancer who underwent HDCT at 5 major California medical centers. The overall treatment-related mortality (TRM) was 2.3%. TRM was not influenced by disease stage or the HDCT regimen delivered, but it was influenced by hematopoietic graft source. The TRM was 6.1% when bone marrow with or without blood stem cells was used, but only 1.4% when blood stem cells alone were used (P or =10 involved axillary lymph nodes were 67% and 76%, respectively. Patients with metastatic breast cancer (MBC) (median follow-up, 1.9 years [range, 0.03-8.3 years]) achieving a complete response (CR) to conventional-dose chemotherapy or rendered to a "no evidence of disease" status before HDCT had significantly better estimated 5-year EFS and OS (28% and 57%, respectively) than those achieving a partial response before HDCT (19% and 27%, respectively; P < or = .0001). Our data suggest that HDCT with hematopoietic stem cell rescue is safe and can be beneficial to patients with high-risk primary breast cancer and for those with MBC achieving CR/no evidence of disease.
Examining Air Travel Demand Using Time Series Data

One of the most commonly available types of data available to transportaton public and private properties are monthly data on ridership and revenue. A technique, based almost solely on such data, for determining the effects of various factors on ridership and revenue and for making forecasts under various pricing assumptions is presented. The technique is very simple (the analysis on which this paper is based took less than 2 hr without the use of a computer), and the results are easy to present to a non-technically oriented audience. The approach consists of first smoothing the data using running medians, and then examining the smoothed data for patterns, using data for Indian Airlines.
Abstract C199: Coordinate phosphorylation of multiple residues on single AKT1 and AKT2 molecules.

Aberrant AKT activation is prevalent across multiple human cancer lineages providing an important new target for therapy. Twenty-two independent phosphorylation sites have been identified on specific AKT isoforms likely contributing to differential isoform regulation. However, the mechanisms regulating phosphorylation of individual AKT isoform molecules have not been elucidated due to the lack of robust approaches able to assess phosphorylation of multiple sites on a single AKT molecule. Using a nanofluidic proteomic immunoassay (NIA), consisting of isoelectric focusing followed by sensitive chemiluminescence detection, we demonstrate that under basal and ligand-induced conditions that the pattern of phosphorylation events is markedly different between AKT1 and AKT2. Indeed, there are at least 12 AKT1 peaks and at least 5 AKT2 peaks consistent with complex combinations of phosphorylation of different sites on individual AKT molecules. Following insulin stimulation, AKT1 was phosphorylated at Thr308 in the T-loop and Ser473 in the hydrophobic domain. In contrast, AKT2 was only phosphorylated at the equivalent sites (Thr309 and Ser474) at low levels. Further, Thr308 and Ser473 phosphorylation occurred predominantly on the same AKT1 molecules, whereas Thr309 and Ser474 were phosphorylated primarily on different AKT2 molecules. While basal AKT2 phosphorylation was sensitive to inhibition of PI3K, basal AKT1 phosphorylation was essentially resistant. PI3K inhibition decreased pThr451 on AKT2 but not pThr450 on AKT1. Thus NIA technology provides an ability to characterize coordinate phosphorylation of individual AKT molecules providing important information about AKT isoform-specific phosphorylation, which is required for optimal development and implementation of drugs targeting aberrant AKT activation. Citation Information: Mol Cancer Ther 2013;12(11 Suppl):C199. Citation Format: Huifang Guo, Meng Gao, Yiling Lu, Jiyong Liang, Philip L. Lorenzi, Shanshan Bai, David H. Hawke, Jie Li, Turgut Dogruluk, Kenneth L. Scott, Eric Jonasch, Gordon B. Mills, Zhiyong Ding. Coordinate phosphorylation of multiple residues on single AKT1 and AKT2 molecules. [abstract]. In: Proceedings of the AACR-NCI-EORTC International Conference: Molecular Targets and Cancer Therapeutics; 2013 Oct 19-23; Boston, MA. Philadelphia (PA): AACR; Mol Cancer Ther 2013;12(11 Suppl):Abstract nr C199.
Glucose responsive insulin production from human embryonic germ (EG) cell derivatives.

Type 1 diabetes mellitus subjects millions to a daily burden of disease management, life threatening hypoglycemia and long-term complications such as retinopathy, nephropathy, heart disease, and stroke. Cell transplantation therapies providing a glucose-regulated supply of insulin have been implemented clinically, but are limited by safety, efficacy and supply considerations. Stem cells promise a plentiful and flexible source of cells for transplantation therapies. Here, we show that cells derived from human embryonic germ (EG) cells express markers of definitive endoderm, pancreatic and β-cell development, glucose sensing, and production of mature insulin. These cells integrate functions necessary for glucose responsive regulation of preproinsulin mRNA and expression of insulin C-peptide in vitro. Following transplantation into mice, cells become insulin and C-peptide immunoreactive and produce plasma C-peptide in response to glucose. These findings suggest that EG cell derivatives may eventually serve as a source of insulin producing cells for the treatment of diabetes.
Sleep and cognitive function of crewmembers and mission controllers working 24-h shifts during a simulated 105-day spaceflight mission

Abstract The success of long-duration space missions depends on the ability of crewmembers and mission support specialists to be alert and maintain high levels of cognitive function while operating complex, technical equipment. We examined sleep, nocturnal melatonin levels and cognitive function of crewmembers and the sleep and cognitive function of mission controllers who participated in a high-fidelity 105-day simulated spaceflight mission at the Institute of Biomedical Problems (Moscow). Crewmembers were required to perform daily mission duties and work one 24-h extended duration work shift every sixth day. Mission controllers nominally worked 24-h extended duration shifts. Supplemental lighting was provided to crewmembers and mission controllers. Participants' sleep was estimated by wrist-actigraphy recordings. Overall, results show that crewmembers and mission controllers obtained inadequate sleep and exhibited impaired cognitive function, despite countermeasure use, while working extended duration shifts. Crewmembers averaged 7.04±0.92 h (mean±SD) and 6.94±1.08 h (mean±SD) in the two workdays prior to the extended duration shifts, 1.88±0.40 h (mean±SD) during the 24-h work shift, and then slept 10.18±0.96 h (mean±SD) the day after the night shift. Although supplemental light was provided, crewmembers’ average nocturnal melatonin levels remained elevated during extended 24-h work shifts. Naps and caffeine use were reported by crewmembers during ∼86% and 45% of extended night work shifts, respectively. Even with reported use of wake-promoting countermeasures, significant impairments in cognitive function were observed. Mission controllers slept 5.63±0.95 h (mean±SD) the night prior to their extended duration work shift. On an average, 89% of night shifts included naps with mission controllers sleeping an average of 3.4±1.0 h (mean±SD) during the 24-h extended duration work shift. Mission controllers also showed impaired cognitive function during extended duration work shifts. These findings indicate that extended duration work shifts present a significant challenge to crewmembers and mission support specialists during long-duration space mission operations. Future research is needed to evaluate the efficacy of alternative work schedules and the development and implementation of more effective countermeasures will be required to maintain high levels of performance.
Using Clicker 5 to Enhance Emergent Literacy in Young Learners

Best practices in emergent literacy instruction for young children acknowledge and facilitate the smooth progression between children’s early engagement with print materials and subsequent fuller literacy mastery. In so doing, model programs target five key emergent literacy skills. The rapid rise in the breadth and depth of educational technology, including computer software, is offering early childhood education professionals new and powerful tools in teaching early literacy. This paper offers a brief review of best practices in emergent literacy, notes the growth of technology in this instruction, and examines the potential contributions of one specific software program, Clicker 5, in helping diverse emergent literacy learners acquire and practice initial reading and writing skills.
The telecommunications revolution in Korea

From the Publisher: The dynamism of the Republic of Korea's export-led economy and the recent exceptional growth of the Korean electronics industry are renowned worldwide. The communications revolution is even more remarkable: in the 1980s, Korea's basic telecommunications infrastructure grew faster than that of any other country in the world. The Korean people and industry have embraced the information age with extraordinary speed and adaptability. In this first, comprehensive study, James F. Larson analyses the economic, technological, political, and socio-cultural dimensions of the Korean communications phenomenon. He examines the reforms which have fostered greater network access and efficiency, and the role of education in the promotion of new technologies. The author discusses the 1988 Olympic Games in Seoul as a catalyst to progress, and the role of new technologies in Korean reunification. James F. Larson offers original documentary data to the case of Korea, and supports his analysis with interviews with Korean leaders from government, industry, research institutes, and academia.
Characteristics of the hormonal induced cyclic adenosine 3',5'-monophosphate response in the rat and guinea pig lung in vitro.

Abstract The aim of the present study was to investigate the characteristics of the cyclic adenosine 3′,5′-monophosphate (cyclic AMP) response to various hormones in the lung. Slices of rat and guinea pig lung incubated for 6 min in the presence of either epinephrine or histamine yielded 4–6-fold increases in levels of cyclic. AMP and the effect of epinephrine and histamine together was greater than additive. The cyclic AMP response to epinephrine was blocked by propranolol and chlorpromazine in the rat and guinea pig lung while phentolamine was effective in only the guinea pig. The histamine-induced cyclic AMP response was antagonized by chlorpromazine and pyribenzamine in the rat lung only. Adenosine was the only other compound capable of raising cyclic AMP levels and this was restricted to the rat lung. In conclusion it appears that lung cyclic AMP levels may not be associated with bronchiolar relaxation and contraction in that histamine and epinephrine both stimulate cyclic AMP formation and mediate opposite effects on pulmonary smooth muscle. Due to teh many cell types found in lung tissue the possibility exists that these hormones may stimulate cyclic AMP production in cells other than smooth muscle.
The Synergistic Relationship between Soil Moisture and the Low-Level Jet and Its Role on the Prestorm Environment in the Southern Great Plains

Changes in low-level moisture alter the convective parameters [e.g., convective available potential energy (CAPE), lifted index (LI), and convective inhibition (CIN)] as a result of alterations in the latent and sensible heat energy exchange. Two sources for low-level moisture exist in the southern Great Plains: 1) moisture advection by the low-level jet (LLJ) from the Gulf of Mexico and 2) evaporation and transpiration from the soils and vegetation in the region. The primary focus of this study is to examine the spatial distribution of soil moisture on a daily basis and to determine the effect it has on the convective parameters. The secondary objective is to investigate how the relationship between soil moisture and convective parameters is altered by the presence of an LLJ. The soil moisture data were obtained through newly developed procedures and advances in technology aboard the Tropical Rainfall Measuring Mission Microwave Imager. The convective parameter data were obtained through the North American Regional Reanalysis dataset. The study examined seven warm seasons (April‐September) from 1998 to 2004 and found that the convective environment is more unstable (CAPE . 900 J kg 21 ,L I ,2 28C) but more strongly capped (CIN . 70 J kg 21 ) on days with an LLJ present. Spearman’s rank correlation analysis showed a less stable atmosphere with increased soil moisture, after soil moisture reached 5%, on most days. Additional analysis determined that on all synoptic-type days the probability of reaching various thresholds of convective intensity increased as soil moisture values increased. The probabilities were even greater on days with an LLJ present than on the days without an LLJ present. An examination of four days representing each synoptic-type day indicates that on the daily scale the intensity of the convective environment is closely related to the high soil moisture and the presence of an LLJ.
The American Wake of Ireland: Symbolic Death Ritual

Knowledge of a group's death customs can provide insight into their social system. The wake and funeral of nineteenth- and early twentieth-century Ireland have been said to provide the most dramatic revelation of community life during those times. In the early days of Irish emigration when the journey to North America was considered to be a final separation, Irish society developed an institution known as the American wake. Among other things, it provided a mechanism for ventilating the grief associated with this special type of bereavement. This article examines the similarities between the American wake and a wake for the dead and is concerned with how the emigrant wake reflected the Irish view of life and death.
Biocatalytic desulfurization of arylsulfonates

A microbial strain, Klebsiella oxytoca KS3D, has been isolated which is capable of exploiting arylsulfonates as a sole source of sulfur during growth. The desulfurization catalyzed by intact K. oxytoca KS3D results in the conversion of arylsulfonates into the corresponding phenols. Even arylsulfonates carrying substituents which significantly alter steric and electronic characteristics are substrates. Only a single regioisomer is produced from substituted arylsulfonates. Based on the products formed from the biocatalytic desulfurizations and incorporation of isotopic oxygen in phenolic product when the desulfurization is run under 18O-enriched oxygen, hydrolysis mechanisms can be eliminated from consideration. Two reaction types which might mimic the chemistry occurring during microbial desulfurization of arylsulfonates were examined. The first reaction involved conversion of appropriately substituted arylsulfonates into phenols by single electron reduction followed by reaction of the radical anions with molecular oxygen. A second reaction using intramolecular reaction of arylsulfonates and arylsulfones with alkoxy radicals failed to achieve desulfurization. In addition to mechanistic evaluation, desulfurization of arylsulfonates catalyzed by K. oxytoca KS3D is examined from the perspective of its relevance to desulfurization of the organosulfur components of coal and its possible use for industrial manufacture of phenols.
Using Experimental Methods in Higher Education Research

EXPERIMENTAL METHODS have been used extensively for many years to conduct research in education and psychology. However, applications of experiments to investigate technology and other instructional innovations in higher education settings have been relatively limited. The present paper examines ways in which experiments can be used productively by higher education researchers to increase the quality and rigor of studies. Specific topics include types of experiments, common validity threats, advantages and disadvantages of experiments, operational procedures for designing and conducting experiments, and reporting and disseminating results. Emphasis is given to helping prospective researchers evaluate the circumstances that favor or disfavor usage of experimental designs relative to other methods.
Faculty experiences with the National Institutes of Health (NIH) public access policy, compliance issues, and copyright practices

Objectives: The research assessed faculty awareness of the National Institutes of Health (NIH) public access policy and faculty experiences with the copyright terms in their author agreements with publishers.
A Top Down Approach to Enterprise Monitoring Using Change Point Detection

Monitoring is a key aspect of IT service management of any enterprise. Besides providing visibility into the IT infrastructure, it provides information required to manage resources, plan for growth and ensure uptime and availability of applications. At the higher levels of monitoring that are vital to service management, key business and IT processes are constantly monitored to collect valuable data about the performance and availability of the processes. Traditionally, in the bottom-up approach towards monitoring, these IT and business metrics may be defined as an aggregation of multiple lower level metrics which in turn may be defined as an aggregation of other metrics. The complexity of these business and IT processes is captured through modeling (e.g.: CIM) which is both time consuming and requires a high level of skill and understanding of the infrastructure. It requires an in-depth understanding of the various systems that work together to provide the services that need to be monitored. In large enterprises where business and IT change rapidly to adapt to market requirements, configuring a monitoring system to monitor new processes by creating accurate models can be a challenge. Due to the time required to construct these monitoring models, there is a temporal lack of visibility into the behavior of the processes which is a matter of concern to the business and IT teams in the enterprise. In this paper, we present a top-down approach towards monitoring high level business and IT processes. We present a framework that monitors the highest level metrics and detects changes in their behavior without the need for comprehensive modeling, thereby allowing these processes to be quickly and efficiently monitored. We also present examples and results from a deployment of the system in the IT environment of a large telecom company.
Transcription of adenovirus DNA by RNA polymerase III of bovine lymphoid tissue.

Abstract The ability of purified RNA polymerase III (C) of bovine lymphoid tissue to transcribe unnicked, double-stranded viral DNA has been investigated and the RNA product analyzed. RNA polymerase III, one of the enzymes involved in the transcription of adenovirus DNA in infected cells, transcribes native adenovirus DNA in vitro extremely efficiently, in contrast to polymerase I (A) and II (B) which have been previously shown to transcribe native adenovirus DNA poorly. The salt optimum for transcription of viral DNA by polymerase III is lower than the salt optimum for transcription of mammalian DNA by the same enzyme. The unique ability of polymerase III to transcribe intact double-stranded adenovirus DNA efficiently does not appear to result from nucleases in the enzyme preparation or from a dissociable factor which could be used by polymerase I or II. The RNA synthesized enzymically by this enzyme from adenovirus DNA is small (mostly 4–6S) and appears to correspond to about 40% of the DNA sequences. Both “early” and “late” RNA and sequences complementary to “late” RNA are present in the enzymic RNA product. The ability of polymerase III to transcribe a double-stranded viral DNA contrasts with the inability of purified polymerases I and II to transcribe this template. This suggests that purified polymerase III possesses a transcription factor not present in polymerases I and II of comparable purity.
The therapeutic application of melatonin in supportive care and palliative medicine

Melatonin is a hormone produced mainly in the pineal gland. Plasma levels exhibit a circadian variation with the highest concentration occurring at night. The human biologic effects of melatonin depend upon the time of day it is made available. One of these effects is the setting and resetting of circadian clocks (chronobiotic effect). Additionally, it may be a potent antioxidant and immunomodulator and has been shown to have antitumor, anticytokine, anti-insomnia, and anticachexia effects. Melatonin has also been shown to improve survival and performance status in patients with advanced cancer. Objective tumor response occurs with melatonin alone or when combined with interleukin-2 (IL-2). Further, melatonin reduces radiation- and chemotherapeutic-induced toxicity. Symptomatic and circadian disruption is linked to increased cancer risk. The chronobiotic capacity of melatonin to reset circadian clocks may provide a verifiable strategy to reduce cancer risk and enhance quality of life by diminishing cancer-induced circadian disruption.
Chlorinated hydrocarbon insecticides and the world ecosystem

Abstract The chlorinated hydrocarbon insecticides are now among the world's most widely distributed synthetic chemicals, contaminating a substantial part of the biosphere. They are dispersed throughout the environment in currents of air and water. Their movement through an ecosystem is explained by their solubility characteristics and chemical stability, while their broad toxicity indicates a potential for biological effects are presented. The chlorinated hydrocarbons are seriously degrading biotic communities in many parts of the world.
Controlling the growth of constraints in hyperbolic evolution systems

Motivated by the need to control the exponential growth of constraint violations in numerical solutions of the Einstein evolution equations, two methods are studied here for controlling this growth in general hyperbolic evolution systems. The first method adjusts the evolution equations dynamically, by adding multiples of the constraints, in a way designed to minimize this growth. The second method imposes special constraint preserving boundary conditions on the incoming components of the dynamical fields. The efficacy of these methods is tested by using them to control the growth of constraints in fully dynamical 3D numerical solutions of a particular representation of the Maxwell equations that is subject to constraint violations. The constraint preserving boundary conditions are found to be much more effective than active constraint control in the case of this Maxwell system.
Comparison of the reactivity of thiophene, thiophene 1‐oxide, and thiophene 1,1‐dioxide as diene for diels‐alder reactions. An ami semiempirical study

A semiempirical AMI theoretical study was carried out to examine the very low reactivity of thiophene; for example, the high reactivity of thiophene 1-oxide as a diene in the Diels Alder reactions. The reactivities of cyclopentadiene, thiophene, thiophene 1-oxide, and thiophene 1,1-dioxide were studied as dienes in the reaction with ethylene, cyclopropene, and benzoquinone. Ethylene was chosen as a standard, while cyclopropene, with its high strain energy was released in the course of a reaction making it relatively reactive. The benzoquinone has a lower LUMO energy, making it a very reactive dienophile for the Diels-Alder reaction. Frontier molecular orbital energy gap between the reactants was considered, and the disadvantage of this approach in studying the reactivity was demonstrated. For all combinations, the corresponding transition structures are generated and the activation energies are estimated. The estimated activation barrier for sulfur dioxide elimination from the adduct was used to explain the failure to accumulate the cycloadduct in the reaction mixture. The obtained results are compared with experimental data when available. An excellent agreement of theory and experiment was obtained.
Light-induced degradation in a-Si:H and its relation to defect creation

Abstract Light-induced degradation of the photoconductivity of hydrogenated amorphous silicon, a-Si:H, called the Staebler–Wronski effect (SWE) is caused by the creation of defects that act as recombination centers. The creation efficiency as well as its kinetics is essentially the same between 4 and 300 K despite drastic changes in the recombination processes. Defects are created with the same spin signature but with greatly different thermal stability and electron capture cross sections. There appears to be a strong link between the latter two properties. The creation-annealing hystereses of free carrier lifetime and defect concentration are explained. The SWE is reduced in high electric fields at 4.2 K suggesting the possible importance of non-radiative geminate recombinations. The validity of accepted rate equations for the SWE excited by cw and laser pulses is questioned. Evidence for long-lived (∼10 μs) precursors of SWE defect creation is presented. Problems with existing SWE models and understanding of defect capture properties are formulated.
Tumor cell heterogeneity: an overview.

Tumors, particularly malignant tumors, whether primary or metastatic, exhibit considerable heterogeneity in their cellular composition, a phenomenon that has been known for decades. In the past, evidence of cellular heterogeneity was primarily found in the wide variation in morphologic appearance of cells of any given tumor type upon routine histologic examination. During the past lo-15 years, functional and biologic heterogeneity in human or animal neoplasms has been studied extensively through a variety of new and evolving biotechnologies. Among the techniques that have seen wide application recently are: monoclonal antibodies employed in histochemical or flow cytometric systems to detect soluble or surface tumor antigens; DNA/RNA probes used in conjunction with in-situ or in-liquid hybridization assays with or without PCR amplification of key DNA sequences using the polymerase chain reaction (PCR), and high resolution chromosome analyses. Heterogeneity is now recognized as an important aspect of cancer biology with signi~~ant implications for diagnosis and treatment. Neoplasms are known to be composed of cell populations which are heterogeneous with respect to a variety of characteristics e.g. genetic, biochemical, immunologic and other functional properties. Cell diversity is fundamentally an acquired property so that, by the time tumors become clinically overt, their constituent cells are already endowed with diverse biologic characteristics. The origin and significance of such diversity have been the subject of extensive scientific inquiry [1,2]. Experimental and clinical evidence strongly suggest that most neoplasms are clonal in origin i.e. they derive from single cells that have undergone malignant transformation. One might surmise, therefore, that the progeny of such malignant cells might all be alike. This assumption has proven incorrect. A number of
Notch gain of function in mouse periocular mesenchyme downregulates FoxL2 and impairs eyelid levator muscle formation, leading to congenital blepharophimosis.

Notch signaling is pivotal for the morphogenesis and homeostasis of many tissues. We found that aberrant Notch activation in mouse neural-crest-derived periocular mesenchymal cells (POMCs), which contribute to the formation of corneal and eyelid stroma, results in blepharophimosis. Compound transgenic mice overexpressing the Notch1 intracellular domain (N1-ICD) in POMCs (POMCN1-ICD) showed relatively minor effects on the cornea, but increased cell apoptosis and decreased cell proliferation during eyelid morphogenesis. Eyelid closure at E15.5 and eyelid formation at birth were incomplete. In further analyses, overexpression of N1-ICD impaired eyelid levator smooth muscle formation by downregulating the transcription factor FoxL2. This is similar to the effect of haploinsufficiency of FOXL2 in humans, which results in type II BPES (blepharophimosis, ptosis and epicanthus inversus syndrome). In vitro studies showed that FoxL2 expression is augmented by a low dose of N1-ICD but was downregulated by a high dose, depending on the extent of Hes-1 and Hey-1 activation. Moreover, transfection of CMV-FoxL2 enhanced α-SMA promoter activity. These data strongly imply that a physiologically low level of Notch1 is crucial for proper FoxL2 expression in POMCs, which is, in turn, essential for Mueller muscle formation and normal eyelid development.
Ciliary entry of the kinesin-2 motor KIF17 is regulated by importin-beta2 and RanGTP.

How factors are targeted to cilia remains largely unknown. A ciliary localization signal targets the KIF17 motor, important for intraflagellar transport, to cilia through importin-β2 and RanGTP. The biogenesis, maintenance and function of primary cilia are controlled through intraflagellar transport (IFT) driven by two kinesin-2 family members, the heterotrimeric KIF3A/KIF3B/KAP complex and the homodimeric KIF17 motor1,2. How these motors and their cargoes gain access to the ciliary compartment is poorly understood. Here, we identify a ciliary localization signal (CLS) in the KIF17 tail domain that is necessary and sufficient for ciliary targeting. Similarities between the CLS and classic nuclear localization signals (NLSs) suggest that similar mechanisms regulate nuclear and ciliary import. We hypothesize that ciliary targeting of KIF17 is regulated by a ciliary-cytoplasmic gradient of the small GTPase Ran, with high levels of GTP-bound Ran (RanGTP) in the cilium. Consistent with this, cytoplasmic expression of GTP-locked Ran(G19V) disrupts the gradient and abolishes ciliary entry of KIF17. Furthermore, KIF17 interacts with the nuclear import protein importin-β2 in a manner dependent on the CLS and inhibited by RanGTP. We propose that Ran has a global role in regulating cellular compartmentalization by controlling the shuttling of cytoplasmic proteins into nuclear and ciliary compartments.
Analysis of two-sample truncated data using generalized logistic models

Parallel to Cox's [JRSS B34 (1972) 187-230] proportional hazards model, generalized logistic models have been discussed by Anderson [Bull. Int. Statist. Inst. 48 (1979) 35-53] and others. The essential assumption is that the two densities ratio has a known parametric form. A nice property of this model is that it naturally relates to the logistic regression model for categorical data. In astronomic, demographic, epidemiological, and other studies the variable of interest is often truncated by an associated variable. This paper studies generalized logistic models for the two-sample truncated data problem, where the two lifetime densities ratio is assumed to have the form exp{@[email protected](x;@b)}. Here @f is a known function of x and @b, and the baseline density is unspecified. We develop a semiparametric maximum likelihood method for the case where the two samples have a common truncation distribution. It is shown that inferences for @b do not depend the nonparametric components. We also derive an iterative algorithm to maximize the semiparametric likelihood for the general case where different truncation distributions are allowed. We further discuss how to check goodness of fit of the generalized logistic model. The developed methods are illustrated and evaluated using both simulated and real data.
Multitasking Teachers: Mistake or Missing Link?.

Abstract This article presents case studies involving graduate students who exhibited multitasking behaviors during their university courses, and explores how those behaviors functioned in their own classrooms. Though these university students appeared to be inattentive, their multitasking proved to be indicative of creativity and flexibility in their classrooms. Teacher educators should explore the missing link in the evolutionary transition between traditional learning and multitasking classrooms of the future. Findings from classroom observations also revealed possible gender bias.
Single-chain antibodies against DNA aptamers for use as adapter molecules on DNA tile arrays in nanoscale materials organization

Complex DNA nanostructures have been developed as structural components for the construction of nanoscale objects. Recent advances have enabled self-assembly of organized DNA nanolattices and their use in patterning functional bio-macromolecules and other nanomaterials. Adapter molecules that bind specifically to both DNA lattices and nanomaterials would be useful components in a molecular construction kit for patterned nanodevices. Herein we describe the selection from phage display libraries of single-chain antibodies (scFv) for binding to a specific DNA aptamer and their development as adapter molecules for nanoscale construction. We demonstrate the decoration of various DNA tile structures with aptamers and show binding of the selected single-chain antibody as well as the self-assembly of mixed DNA–protein biomolecular lattices.
Do Mothers Know Their Teenagers' Friends? Implications for Individuation in Early Adolescence

This study addresses three issues: (1) Do mothers and teenagers agree less than mothers and children about their friends? (2) Are family and individual characteristics related to agreement? (3) Is agreement related to subsequent substance use? One hundred ten subjects and their mothers provided information on the friendship network at 9 and 13 years, individual and family characteristics at 13 years, and substance use at 15 years. The results indicate little change in the percent of friends the mother knows from middle childhood to early adolescence, although the number of friends the mother does not know does increase significantly. High mother teenager agreement about opposite-sex friends is related to close family relations, social and moral competence, and a lower likelihood of cigarette use. The findings are discussed as they relate to the constructs of individuation in adolescence and parental monitoring.
A Control Oriented SI and HCCI Hybrid Combustion Model for Internal Combustion Engines

The combustion mode transition between SI (spark ignited) and HCCI (Homogeneously Charged Compression Ignition) of an IC (Internal Combustion) engine is challenge due to the thermo inertia of residue gas; and model-based control becomes a necessity. This paper presents a control oriented two-zone model to describe the hybrid combustion that starts with SI combustion and ends with HCCI combustion. The gas respiration dynamics were modeled using mean-value approach and the combustion process was modeled using crank resolved method. The developed model was validated in an HIL (Hardware-In-the-Loop) simulation environment for both steady-state and transient operations in SI, HCCI, and SI-HCCI hybrid combustion modes through the exhaust valve timing control (recompression). Furthermore, cooled external EGR (exhaust gas re-circulation) was used to suppress engine knock and enhance the fuel efficiency. The simulation results also illustrates that the transient control parameters of hybrid combustion is quite different from these in steady state operation, indicating the need of a control oriented SI-HCCI hybrid combustion model for transient combustion control.Copyright © 2010 by ASME
Bubble entrainment by the impact of drops on liquid surfaces

The impact of a drop on the plane surface of the same liquid is studied numerically. The accuracy of the calculation is substantiated by its good agreement with available experimental data. An attempt is made to explain the recent observation that, in a restricted range of drop radii and impact velocities, small air bubbles remain entrained in the liquid. The implications of this process for the underwater sound due to rain are considered. The numerical approach consists of a new formulation of the boundary-element method which is explained in detail. Techniques to stabilize the calculation in the presence of strong surface-tension effects are also described.
Electron-impact ionization of Zn+ and Ga+

Absolute cross sections for electron-impact ionization of ${\mathrm{Zn}}^{+}$ and ${\mathrm{Ga}}^{+}$ have been measured from below threshold to 2 keV with the use of the crossed-charged-beams technique. Excitation autoionization was shown to be of major importance in both ions for the region between 1 and 2 times threshold, leading to enhancement of the cross sections by factors of up to \ensuremath{\sim}2.5. Discrepancies between experiment and the well-known semi-empirical formula of Lotz were up to 70%, but reduction of Lotz's ${a}_{3d}$ coefficient by a factor of 2 leads to satisfactory agreement at high energies. Comparison is also made with scaled-Born-approximation calculations.
Five-year survival after perforation of interventricular septum caused by coronary occlusion: Histologic study of kidneys after 350 injections of mercurial diuretics

Abstract The patient described in this report had coronary occlusion in 1936, at the age of forty-four, and perforation of the ventricular septum through the infarcted area; he lived four years and ten months after this complication occurred. He led a fairly active existence during that time, despite continued congestive heart failure. He received approximately 650 c.c. of mercurial diuretics to control edema. No evidence of renal damage was found at necropsy.
Abstract 742: Up-regulation of histone deacetylases in colon cancer.

Proceedings: AACR 104th Annual Meeting 2013; Apr 6-10, 2013; Washington, DC The reversible acetylation of histones and non-histone proteins by histone acetyltransferases (HATs) and deacetylases (HDACs) play critical roles in transcriptional regulation in eukaryotic cells. Acetylation of histones is commonly associated with transcriptional activation of genes, and is thought to be responsible for the formation of a local “open chromatin” structure. In contrast, removal of acetyl groups by histone deacetylases (HDACs) frequently accompanies suppression of gene activity. Mammalian HDACs are classified into four classes (I, II, III and IV) based on the sequence homology to the yeast histone deacetylases Rpd3 (reduced potassium dependency), Hda1 (histone deacetylase1), and Sir2 (silent information regulator 2), respectively. Although the precise cellular functions of the different HDAC enzymes are still poorly understood, evidence suggests that different members of the HDAC family have distinct functions. It had been shown that overexpression of class I HDACs are more relevant to cancer development in many cancer types. In the absence of class I HDACs, cancer cells arrest either at the G1 phase of the cell cycle or the G2/M transition, resulting in the loss of mitotic cells, cell growth inhibition, and an increase in the percentage of apoptotic cells. Therefore, HDAC inhibitors had been used as a class of chemotherapeutic agents in cancer treatment. However, little is known about factors involved in regulation of class I expression in cancer cells. Our study focuses on the regulation of HDAC1 and 2 expressions in colon cancer cells. We found that compared with normal colon cell lines, both mRNA and protein level of HDAC1 and HDAC2 are higher in colon cancer cells, which suggests that HDAC1/2 is regulated at transcriptional level in colon cancer. HDAC1 and HDAC2 promoters were cloned and the promoter reporter activity was studied. Our result shows that HDAC1 and 2 promoters are highly active in colon cancer cells. Through mutation study on various putative transcription factors binding sites, we found that promoter activity is regulated by transcription factor Sp1/Sp3, which are also elevated in colon cancer cells lines and tissues. Chromatin immunoprecipitation assay also indicate that Sp1/Sp3 is recruited to HDAC1/HDAC2 promoter. Inhibition of Sp1/Sp3 through inhibitor or shRNA decreased HDAC1/2 expression and reduced cell proliferation. These results indicate that Sp1/Sp3 may be major regulators for HDAC1 and HDAC2 overexpression in colon cancer and this finding may shed light on future treatment of colon cancer. Citation Format: Hui Yang, Tal Salz, Maria Zajac-kaye, Daiqing Liao, Suming Huang, Yi Qiu. Up-regulation of histone deacetylases in colon cancer. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 742. doi:10.1158/1538-7445.AM2013-742
Activation of the IκB Kinase Complex by TRAF6 Requires a Dimeric Ubiquitin-Conjugating Enzyme Complex and a Unique Polyubiquitin Chain

TRAF6 is a signal transducer in the NF-kappaB pathway that activates IkappaB kinase (IKK) in response to proinflammatory cytokines. We have purified a heterodimeric protein complex that links TRAF6 to IKK activation. Peptide mass fingerprinting analysis reveals that this complex is composed of the ubiquitin conjugating enzyme Ubc13 and the Ubc-like protein Uev1A. We find that TRAF6, a RING domain protein, functions together with Ubc13/Uev1A to catalyze the synthesis of unique polyubiquitin chains linked through lysine-63 (K63) of ubiquitin. Blockade of this polyubiquitin chain synthesis, but not inhibition of the proteasome, prevents the activation of IKK by TRAF6. These results unveil a new regulatory function for ubiquitin, in which IKK is activated through the assembly of K63-linked polyubiquitin chains.
Hooke's September 1685 Ellipse Vertices Construction and Newton's Instantaneous Impulse Construction☆

Abstract A relatively little-known 1685 manuscript by Robert Hooke provides the occasion for another chapter in the well-known controversy between Hooke and Newton on priority in the field of centripetal force mechanics. This manuscript, with accompanying diagram, was discussed in a 1994 paper by Michael Nauenberg, who claimed that Hooke's manuscript and diagram were “effectively the mathematical formulation of the principles of dynamics which Hooke had been proposing during the past 20 yr.” Our interpretation is very different from Nauenberg's. We conclude that Hooke should be given credit for having hit upon an interesting and ingenious illustration of Newton's instantaneous impulse construction, but that Nauenberg's claim that Hooke, on his own, had developed a quantitative theory of centripetal force motion must be rejected. Un manuscrit de 1685 ecrit par Robert Hooke et relativement peu connu fournit l'occasion pour reevaluer la controverse de priorite bien connue entre Hooke et Newton a propos de la dynamique des forces centripetes. En 1994 Michael Nauenberg a affirme que ce manuscrit et son diagramme accompagnant etaient “effectivement la formulation mathematique des principes de dynamique que Hooke proposait depuis vingt ans.” Nous concluons que Hooke a bien decouvert une illustration interessante et ingenieuse de la construction des impulsions instantanees de Newton, mais que, au contraire de ce que Nauenberg a maintenu, Hooke n'a pas, par lui-meme, developpe une theorie quantitative du mouvement avec force centripete. Ein relativ wenig bekanntes Manuskript von Robert Hooke aus dem Jahre 1685 liefert die Grundlage zu einem weiteren Abschnitt in dem wohlbekannten Streit zwischen Hooke und Newton uber die Prioritat auf dem Gebiet der Zentripetalkraftmechanik. Dieses Manuskript wurde zusammen mit dem beigefugten Diagramm in einer Abhandlung aus dem Jahre 1994 von Michael Nauenberg erortert. Nauenberg behauptete darin, dass Hookes Manuskript und Diagramm “tatsachlich die mathematische Formulierung der Prinzipien der Dynamik sind, die Hooke in den zwanzig Jahren zuvor vorgeschlagen hatte.” Unsere Interpretation ist wesentlich anders als die von Nauenberg. Wir kommen zu dem Ergebnis, dass man Hooke den Ruhm lassen sollte, eine interessante und geistreiche Veranschaulichung von Newtons Konzept eines instantanen Impulses gefunden zu haben, dass aber Nauenbergs Behauptung zuruckzuweisen ist, Hooke habe fur sich eine quantitative Theorie der Zentripetalkraftbewegung entwickelt.