cssi/SciSciGPT-SciSciNet huggingface dataset:
Effective therapy of a vascular tumor of infancy with vincristine

Vascular tumors are common in infancy, affecting as many as 10% of children. These lesions often follow a benign course, with an initial proliferative phase followed by spontaneous involution, and require no therapy. Others manifest explosive early growth and Kasabach-Merritt phenomenon, requiring therapeutic intervention. Occasionally, some bulky tumors threaten life or vision because of mass effect, also mandating intervention. Steroids are the mainstay of therapy, but often are ineffective. Interferon alpha (2a and 2b) has been used as second-line therapy in cases of steroid failure. However, interferon therapy has been associated with a significant incidence of spastic diplegia. The authors present the case of a 3-month-old girl in whom respiratory distress secondary to tracheal compression developed. Magnetic resonance imaging and magnetic resonance angiography showed a large cervicothoracic lesion encasing the great vessels and displacing the airway. She did not display associated Kasabach-Merritt phenomenon. The lesion proved refractory to standard steroid therapy, but responded dramatically to 4 cycles of vincristine (0.05 mg/kg). Although this agent has been used in children with life-threatening Kasabach-Merritt phenomenon, this is the first time it has been described in the setting of compromised vital function. Vinca alkaloids recently have been shown to have potent antiangiogenic activities in experimental models. Given the low predicted incidence of side effects at this dose, vincristine used as an antiangiogenic agent may prove an attractive alternative therapy for patients with life-threatening vascular tumors of infancy.
The Progression of Branching Morphogenesis in the Embryonic Lung Involves Apoptosis •276

Apoptosis is becoming recognized as an important mechanistic process in embryonic structural development. Branching morphogenesis of the embryonic lung involves incompletely characterized complex interactions between the developing epithelium and mesenchyme. The involvement of apoptosis in this process not known. We hypothesized that apoptosis is actively involved in the formation of new buds in the embryonic lung, and that apoptosis is altered by factors which stimulate branching morphogenesis. Day 11.5 Swiss Webster mouse lung explants were cultured for 48 hours in serum free BGJb medium with either DHT, DHT plus a 10fold excess of Flutamide (an androgen receptor blocker), or equal volumes of diluent as control. Branching morphogenesis was evaluated by counting the number of terminal buds of the left lung at 0, 24, and 48 hrs under light microscopy. At 24 and 48 hrs individual lungs were harvested, formalin fixed, embedded in OCT, and sectioned (5 microns). After treatment with Proteinase K, endogenous peroxidase activity was quenched with 2% Hydrogen Peroxide. Apoptosis was evaluated using the ApopTag Detection Kit(Oncor) by direct immunoperoxidase detection of digoxigeninlabeled DNA. DHT(106 and 107M) treatment increased the number of terminal buds after 24 and 48 hrs (DHT 106M: 127±6% of control after 48 hrs, P<0.005). This was blocked by a 10fold excess of Flutamide (DHT 106M Flutamide 105M: 109±6% of control after 48 hrs, P=NS). In control lungs apoptosis was present nearly exclusively in distal new bud structures, where intermittent clusters of mesenchymal cells in the thin septa, and occasional adjacent low cuboidal epithelial cells showed apoptosis. Rare mesenchymal cells in the more central areas were also positive. Columnar and cuboidal cells of established airways were negative. DHTtreated lungs showed a similar restriction of apoptosis to cells of new bud structures, but more new structures, and more cells per structure were positive. We speculate that apoptosis occurs in cells of newly forming terminal buds to facilitate the progressive development of new bud structures. This process is enhanced by a growth factor (DHT) that stimulates branching morphogenesis. (Supported by HL37930)
Coral growth rates and environmental control of density banding

Abstract Linear and mass growth rates are compared for the massive coral species Favia pallida (Dana), Goniastrea retiformis (Lamarck), and Porites lutea Milne Edwards & Haime at Enewetak Atoll. Marshall Islands. Goniastrea retiformis is the densest of the three species and has an intermediate growth rate; Porites lutea grows more rapidly. All three grow indeterminately at a declining rate with increasing depth. The high-density portion of annual band couplets is produced during the late summer and fall when water temperatures are highest and possibly the availability of light is reduced, and the low density portion is formed during periods of seasonally lower water temperatures and possibly higher availability of light. A similar pattern is found in three massive coral species from Belize. The high density portions of annual bands account for a greater proportion of linear and mass growth in deeper water and in corals with relatively slow growth rates. I predict that linear growth rates will be highest where conditions are most favorable for deposition of the low density portion. Geographical patterns of coral density banding based on the literature are discussed and a model is proposed relating the interplay of light availability and water temperature to the production of high and low density skeletal bands.
Modification of the zona‐free hamster ova bioassay of boar sperm fertility and correlation with in vivo fertility

These studies were designed to evaluate the ability of the zona-free hamster ova bioassay to detect differences in fertility of boar sperm. In the first study, sperm from two previously infertile boars were compared to sperm from seven previously fertile boars. The percentage of zona-free hamster ova penetrated by sperm from the previously infertile boars was significantly lower than the percentage of ova penetrated by sperm from previously fertile boars (18% of ova penetrated vs. 83%, P less than .001). In the 14 ejaculates from the previously infertile boars that had ejaculate motilities of 50% or greater, the percentage of zona-free hamster ova penetrated continued to be lower than in ejaculates from the fertile boars. One of the two previously infertile boars consistently had a normal semen analysis. The only two observed manifestations of his reduced fertility were his zero conception rate and the limited ability of his sperm to penetrate zona-free hamster ova. In the second study, females were inseminated with equal numbers of sperm from two previously fertile males and the paternity of offspring determined at birth. The experiment was replicated with four combinations of six boars. A high correlation was observed between the percentage of offspring sired and the ability to penetrate zona-free hamster ova (R = .89). Neither morphology nor the ability of the sperm to undergo an acrosome reaction during in vitro incubation was correlated with fertility in the competitive mating situation. These results suggest the zona-free hamster ova bioassay can improve the in vitro fertility assessment of fresh boar semen.
Phase I trial of diaziquone (AZQ) plus GM-CSF

Diaziquone (AZQ) is a lipid soluble alkylating agent which was designed for increased CNS penetration. Its principle toxicity is myelosuppression. We conducted a phase I trial using AZQ in combination with GM-CSF to determine if the maximal tolerated dose (MTD) of AZQ could be escalated. Using GM-CSF on a standard schedule, we were unable to escalate the previously determined MTD of diaziquone with the use of this colony stimulating factor.
Truncated Egalitarian solutions

A family of solutions to the bargaining problem with a variable population, generalizing the Egalitarian solution, is introduced under the name of Truncated Egalitarian solutions. A Truncated Egalitarian solution solves small problems at thier Egalitarian outcome and larger problems at some fixed and therefore non-optimal point, violations of optimality being more severe for large than for small groups. Any solution satisfying Symmetry, Independence of Irrelevant Alternatives, Continuity and Monotonicity (when the claims of more agents have to be accomodated, all agents should sacrifice) coincides with a Truncated Egalitarian solution except perhaps when only two agents are involved, in which case utility substitutions are possible in some limited range.
Cloning and characterization of a 5.9 kb promoter region of the human pyruvate dehydrogenase α subunit gene

Abstract A human genomic clone containing a 5.9 kb promoter region of the human pyruvate dehydrogenase (E1) α subunit gene (PDHA1) was isolated from a human X-chromosome library. The nucleotide sequence showed two Alu repeats at the −2880 and −2200 bp regions. Comparison between the −1400 bp E1α promoter and the −1241 bp E1β promoter revealed a 57% homology, with a high degree of homology at the putative protein binding regions in these two promoters. Computer-aided transcription factor binding consensus sequence analysis revealed the presence of PPAR, HOXD, MyoD and other tissue-specific transcription factor binding sites. Promoter function analysis using the chloramphenicol acetyltransferase reporter gene indicated that the −2.2 kb/−1.7 kb and −5.9 kb/−5.2 kb regions of the E1α promoter may possess negative regulatory elements which are likely to function in a tissue-specific manner.
Prostaglandin synthesis in homogenates of cultured neuroblastoma cells

Abstract Homogenates of 5 neuroblastoma cell lines were found to produce prostaglandin products from exogenous [ 14 C]arachidonate, with specific enzyme activities ranging from 60 to 365 pmol per min per mg protein. Under identical conditions a glial cell line was much less active. PGF 2α and PGE 2 were the major products from neuroblastoma cells, with PGF 2α predominating in all cases. The prostaglandin synthesizing activity of neuroblastoma extracts was at least an order of magnitude higher than activities reported for endogenous prostaglandin synthesis in brain tissues. The pattern of products was similar to that achieved after incubation of a rat brain microsomal extract with [ [ 14 C]arachidonate, although the enzyme activity of neuroblastoma was about 200-fold higher. The presence of a relatively high prostaglandin cyclooxygenase activity in cultured neuroblastoma cells is of particular interest in that these cells may be useful model systems for studies of some aspects of neuronal prostaglandin synthesis.
COGNITIVE COMPLEXITY AND THE LEARNING CONGREGATION

Abstract Do congregations that become learning congregations require a certain level of cognition? Members and leaders of learning congregations know themselves to be co-creators of the congregation's culture and shapers of its decisions and life, engaging in and reflecting on the shared practice of ministry. These congregations find that education occurs when problems are identified and solved, assumptions are examined, and mental maps are clarified. Cognitive theory would assume that a complex level of cognition is required of persons who make up such a congregation. This article challenges this assumption, suggesting that cognitive complexity is not necessary for the membership as a whole and suggesting ways congregations may carry out fourth order structuring for conventional thinkers while inviting and nurturing movement toward this complex level of cognition.
Chemokine receptor expression and in vivo signaling pathways in the joints of rats with adjuvant-induced arthritis.

Objective This study was undertaken to characterize the role of CC chemokines and their receptors in rat adjuvant-induced arthritis (AIA), a model for rheumatoid arthritis (RA). Furthermore, we investigated the signaling pathways associated with CC receptors as well as the cell type distribution of the receptors. Methods Using TaqMan real-time reverse transcription–polymerase chain reaction, Western blot analysis, and immunohistochemistry, we defined chemokine and chemokine receptor messenger RNA (mRNA) expression, CC chemokine receptor (CCR) protein activation during the disease course, CCR-associated signaling pathways, and immunopositive CCR5, phosphorylated signal transducer and activator of transcription 1 (p-STAT-1), and p-STAT-3 cells in rat AIA versus control joints. Results We showed significant up-regulation of CCR1, CCR2, CCR5, and macrophage inflammatory protein 1β/CCL4 mRNA in AIA on post–adjuvant injection day 18, coincident with peak inflammation. Additionally, increases in tyrosine phosphorylation of CCR1 (days 14, 18, 21, and 24), CCR2 (days 14 and 18), and CCR5 (days 14, 18, and 21) were detected in AIA rats compared with control (nonarthritic) rats. JAK-1, STAT-1, and STAT-3 were associated with CCR1 and were highly tyrosine phosphorylated on days 14 and 18. Moreover, CCR2 was associated with JAK-2, STAT-1, and STAT-3 on day 18. The association of STAT-1 and STAT-3 with CCR5 on days 18 and 21 correlated with JAK-1 phosphorylation and binding on day 18. However, the activation of JNK was not associated with CCR5 activation in rat AIA. Immunohistochemical analysis demonstrated that the expression of CCR5, p-STAT-1, and p-STAT-3 was detected on synovial lining cells, macrophages, and endothelial cells in arthritic rat ankles on post–adjuvant injection day 18. While the majority of the CCR5 and p-STAT-1 immunostaining was on synovial lining cells and macrophages, p-STAT-3 was predominantly expressed on endothelial cells. Conclusion CCR1, CCR2, and CCR5 mRNA expression and tyrosine phosphorylation increased with peak inflammation in the AIA model. CCR1, CCR2, and CCR5 tyrosine phosphorylation are associated with the JAK/STAT-1/STAT-3 pathway at different stages of rat AIA, as well as with macrophage and endothelial cell infiltration. However, their signaling activation overlaps with peak inflammation. Up-regulation and activation of CCRs may play a role in macrophage and endothelial cell infiltration in rat AIA joints in addition to activating the associated signaling pathways. The downstream intermediate signaling proteins associated with CC receptors may be used as potential tools to control inflammation in RA.
VHL loss in renal cell carcinoma leads to up-regulation of CUB domain-containing protein 1 to stimulate PKCδ-driven migration

A common genetic mutation found in clear cell renal cell carcinoma (CC-RCC) is the loss of the von Hippel-Lindau (VHL) gene, which results in stabilization of hypoxia-inducible factors (HIFs), and contributes to cancer progression and metastasis. CUB-domain-containing protein 1 (CDCP1) was shown to promote metastasis in scirrhous and lung adenocarcinomas as well as in prostate cancer. In this study, we established a molecular mechanism linking VHL loss to induction of the CDCP1 gene through the HIF-1/2 pathway in renal cancer. Also, we report that Fyn, which forms a complex with CDCP1 and mediates its signaling to PKCδ, is a HIF-1 target gene. Mechanistically, we found that CDCP1 specifically regulates phosphorylation of PKCδ, but not of focal adhesion kinase or Crk-associated substrate. Signal transduction from CDCP1 to PKCδ leads to its activation, increasing migration of CC-RCC. Furthermore, patient survival can be stratified by CDCP1 expression at the cell surface of the tumor. Taken together, our data indicates that CDCP1 protein might serve as a therapeutic target for CC-RCC.
Pharmacologic Inhibition of CXCL10 in Combination with Anti-malarial Therapy Eliminates Mortality Associated with Murine Model of Cerebral Malaria

Despite appropriate anti-malarial treatment, cerebral malaria (CM)-associated mortalities remain as high as 30%. Thus, adjunctive therapies are urgently needed to prevent or reduce such mortalities. Overproduction of CXCL10 in a subset of CM patients has been shown to be tightly associated with fatal human CM. Mice with deleted CXCL10 gene are partially protected against experimental cerebral malaria (ECM) mortality indicating the importance of CXCL10 in the pathogenesis of CM. However, the direct effect of increased CXCL10 production on brain cells is unknown. We assessed apoptotic effects of CXCL10 on human brain microvascular endothelial cells (HBVECs) and neuroglia cells in vitro. We tested the hypothesis that reducing overexpression of CXCL10 with a synthetic drug during CM pathogenesis will increase survival and reduce mortality. We utilized atorvastatin, a widely used synthetic blood cholesterol-lowering drug that specifically targets and reduces plasma CXCL10 levels in humans, to determine the effects of atorvastatin and artemether combination therapy on murine ECM outcome. We assessed effects of atorvastatin treatment on immune determinants of severity, survival, and parasitemia in ECM mice receiving a combination therapy from onset of ECM (day 6 through 9 post-infection) and compared results with controls. The results indicate that CXCL10 induces apoptosis in HBVECs and neuroglia cells in a dose-dependent manner suggesting that increased levels of CXCL10 in CM patients may play a role in vasculopathy, neuropathogenesis, and brain injury during CM pathogenesis. Treatment of ECM in mice with atorvastatin significantly reduced systemic and brain inflammation by reducing the levels of the anti-angiogenic and apoptotic factor (CXCL10) and increasing angiogenic factor (VEGF) production. Treatment with a combination of atorvastatin and artemether improved survival (100%) when compared with artemether monotherapy (70%), p<0.05. Thus, adjunctively reducing CXCL10 levels and inflammation by atorvastatin treatment during anti-malarial therapy may represent a novel approach to treating CM patients.
Adolescents' disclosure to best and good friends: The effects of gender and topic intimacy

The disclosure of 227 7th- through 12th-grade adolescents to four other persons – their closest same- and cross-sex best friends, and lesser-but-good same- and cross-sex friends – about 40 topics varying widely in intimacy was examined; in addition, each subject rated every topic's intimacy. A (2) gender × (2) friend's gender × (2) closeness × (3) age × (3) intimacy level ANOVA yielded two large main effects (partial ω2 > .15), closeness and topic intimacy. Three large interaction effects – gender by friend's gender, friend's gender by intimacy, and gender by closeness by intimacy – were also found, as was a moderate-sized closeness by gender by friend's gender interaction (partial co2= .08). A number of other effects were statistically significant but of only small magnitude. The perceived intimacy of 6 of the studied topics varied across age groups, and one topic, “your weight” was rated differently by males and females. The data are discussed in relation to previous research on adolescent gender differences in friendship and disclosure.
Monte Carlo Method for Magnetic Impurities in Metals

The paper discusses a Monte Carlo algorithm to study properties of dilute magnetic alloys; the method can treat a small number of magnetic impurities interacting wiith the conduction electrons in a metal. Results for the susceptibility of a single Anderson impurity in the symmetric case show the expected universal behavior at low temperatures. Some results for two Anderson impurities are also discussed.
Long step homogeneous interior point algorithm for the p* nonlinear complementarity problems

A P * . -Nonlinear Complementarity Problem as a generalization of the P * -Linear Complementarity Problem is considered. We show that the long-step version of the homogeneous self-dual interior-point algorithm could be used to solve such a problem. The algorithm achieves linear global convergence and quadratic local convergence under the following assumptions: the function satisfies a modified scaled Lipschitz condition, the problem has a strictly complementary solution, and certain submatrix of the Jacobian is nonsingular on some compact set.
Diurnal variations in brain serotonin are driven by the photic cycle and are not circadian in nature.

In an effort to determine the driving force of the diurnal variation of serotonin (5-HT) in the brain, over 500 Syrian hamsters were exposed to long photoperiods (LD17:7; LD), short photoperiods (LD8:16; SD), constant dark (DD) or constant light (LL) for 12 weeks. Hamsters exposed to LD or SD were sacrificed at 3 h intervals; those in constant conditions were sacrificed around the clock. The circadian time (CT) of tissue collection, in the animals in constant conditions, was determined from the onset of locomotor activity (defined as CT12; the beginning of the subjective night). Serotonin content was determined by HPLC with electrochemical detection in the medial basal hypothalamus (MBH); anterior hypothalamus (AH) and olfactory bulbs (OB). In LD and SD, 5-HT levels displayed significant diurnal variation in the MBH, AH and OB (ANOVA; P less than 0.001). The sine waves of the 5-HT rhythm in these conditions were similar in amplitude and phase with relation to lights on (i.e. high 5-HT content during the day and low content at night, with a sharp rise occurring just after lights on). This variation, however, was not apparent in animals exposed to DD or LL; 5-HT content did not display a significant diurnal oscillation. Since 5-HT failed to oscillate in the absence of environmental time cues, the rhythm is likely driven by the environment and not an internal circadian clock.
Effect of Environmental Stilbestrol in Shortening Prolonged Gestation in the Lactating Rat

ConclusionsSmall amounts of diethylstilbestrol scattered about the cages of inseminated lactating rats suckling 9 young brings about implantation at the normal time (day 6) rather than around the 1...
Mechanics of the avian propatagium: flexion-extension mechanism of the avian wing

The supporting elements of the avian propatagium were examined in intact birds and as isolated components, using static force-length measurements, calculated models, and airflow observations. The propatagial surface supported between Lig. propatagiale (LP) and brachium-antebrachium is equally resistant to distortion over the range of wing extension used in flight. The lengths LP assumes in flight occur across a nearly linear, low-stiffness portion of the force-length curve of its extensible pars elastica. In an artificial airflow, intact wings automatically extend; their degree of extension is roughly correlated with the airflow velocity. Comparisons between geometric models of the wing and the passive force-length properties of LPs suggest that the stress along LP blances the drag forces acting to extend the elbow. The mechanical properties (stiffness) of the LP vary and appear to be tuned for flight-type characteristics, e.g., changes in wing extension during flight and drag. Lig. limitants cubiti and LP combine to limit elbow extension at its maximum, a safety device in flight preventing hyperextension of the elbow and reduction of the propatagium's cambered flight surface. Calculations using muscle and ligament lengths suggest that M. deltoideus, pars propatagialis, via its insertions onto both the propatagial ligaments, controls and coordinates propatagial deployment, leading edge tenseness, and elbow/wing extension across the range of wing extensions used in flight. The propatagial ligaments and M. deltoideus, pars propatagialis, along with skeleto-ligamentous elbow/carpus apparatus, are integral components of the wing's extension control mechanism. © 1995 Wiley-Liss, Inc.
Analysis methodology for a piezoelectric-driven optical tracker for ground-based interferometry

We present our analysis methodology for a 20.3 cm prototype optical tracker to determine why instabilities occur below 50 Hz and suggest improvements. The Navy Precision Optical Interferometer makes use of six small optical telescope stations spaced along a Y-array to synthesize an equivalent single larger telescope. Piezoelectric-driven optical trackers steer 12.5 cm output beams from each station to an optics laboratory up to 700 m distant. A percentage of this starlight is split off and used in a closed-loop feedback to update the pointing of the telescope and steering of the tracker. Steering stabilizes atmospheric induced beam trajectory deviations, required for fringe generation. Because of closedloop feedback, we require all fundamental frequencies to be at least 3 times the desired operational frequency, or 150 Hz. These trackers are modified commercial aluminum gimbal mounts with flex-pivot axles and very small damping ratio. Steering is tip/tilt mirror rotation by push-only actuators and a return spring. It is critical contact be maintained between actuator, mirror mount and return spring. From our dynamic analysis, the 122 N return spring is 2.9 times that required, and has a natural frequency equal to 238 Hz. The range of steering, 140 microradian, is double that required and the 0.077 microradian precision is 2.6 times that required. The natural frequency of the tracker is 66 Hz and the tuned closed-loop operational frequency is only 22 Hz. We conclude the low fundamental frequency of the mount limits its performance below 50 Hz and stiffening the structure is required.
Bessel capacities and rectangular differentiation in Besov spaces

We consider the differentiation of integrals of functions in Besov spaces with respect to the basis of arbitrarily oriented rectangular parallelepipeds in Rn. We study almost everywhere convergence with respect to Bessel capacities. These outer measures are more sensitive than n-dimensional Lebesgue measure, and therefore we improve the positive results in [H. Aimar, L. Forzani, V. Naibo, Rectangular differentiation of integrals of Besov functions, Math. Res. Lett. 9 (2–3) (2002) 173–189].
Neochloris oleoabundans grown on anaerobically digested dairy manure for concomitant nutrient removal and biodiesel feedstock production

Microalgae have been investigated as a promising biodiesel feedstock; however, large-scale production is not currently cost-competitive with petroleum diesel, and its environmental impacts have received little attention. Using wastewater to supply nutrients for algal growth obviates synthetic fertilizer use, provides on-site nutrient removal, and reduces greenhouse gas emissions. In this work, anaerobically digested dairy manure was used to grow the oleaginous green alga Neochloris oleoabundans. In batch culture experiments with both synthetic media and anaerobic digester effluent, N. oleoabundans assimilated 90–95% of the initial nitrate and ammonium after 6 d and yielded 10–30% fatty acid methyl esters on a dry weight basis. Cellular lipid content and the N concentration in the growth media were inversely correlated. In addition, the proportion of polyunsaturated fatty acids (i.e. C16:3, C18:2, and C18:3) decreased with N concentration over time while the proportion of C18:1 fatty acid increased. Although N deficiency is likely the primary driver behind lipid accumulation, the influence of culture pH confounded results and requires further study. Other living microorganisms in the digester effluent were not observed to affect algal growth and lipid productivity, though the breakdown of organic nitrogen may have hindered lipid accumulation traditionally achieved through the manipulation of synthetic media. This work highlights the potential for waste-grown mono-algal cultures to produce high quality biodiesel while accomplishing simultaneous wastewater treatment.
Mock trials and role-playing in computer ethics courses

Mock trials are an effective and fun way of eliciting thoughtful dialogue from students, and encouraging them to produce incisive analyses of current ethical dilemmas related to computers and society. This paper describes our experience using mock trials in two computer ethics courses. Each trial was centered on a specificcontroversial and ethically or legally ambiguous topic related to current computer usage in society. Students participated in a series of mock trials during the term, alternating their role in each trial between jury, proponent, and opponent. Class participation was nearly 100% for every trial, with many students electing todefine their own sub-role within their assigned major role. The logistics of the trials were initially difficult to administer and monitor; however, they quickly became manageable as we gained more experience with the opportunities and pitfalls associated with the mock-trial system, and as students volunteered suggestions for improvements.
STIM1 signalling controls store-operated calcium entry required for development and contractile function in skeletal muscle

It is now well established that stromal interaction molecule 1 (STIM1) is the calcium sensor of endoplasmic reticulum stores required to activate store-operated calcium entry (SOC) channels at the surface of non-excitable cells. However, little is known about STIM1 in excitable cells, such as striated muscle, where the complement of calcium regulatory molecules is rather disparate from that of non-excitable cells. Here, we show that STIM1 is expressed in both myotubes and adult skeletal muscle. Myotubes lacking functional STIM1 fail to show SOC and fatigue rapidly. Moreover, mice lacking functional STIM1 die perinatally from a skeletal myopathy. In addition, STIM1 haploinsufficiency confers a contractile defect only under conditions where rapid refilling of stores would be needed. These findings provide insight into the role of STIM1 in skeletal muscle and suggest that STIM1 has a universal role as an ER/SR calcium sensor in both excitable and non-excitable cells.
An experimental investigation of multidimensional quenching of a simulated core debris bed

Abstract Quenching by bottom flooding of a particulate bed simulating core debris has been experimentally studied in this work. In the experiments 6.4 mm diameter apriori oxidized stainless steel particles were placed in a basket up to a height of 28 cm from the bottom. These particles were topped with a 27 cm deep layer of 4.8 mm diameter particles. An annular passage 1.45 cm in width existed between the basket containing the particles and the test chamber. Fresh Zircaloy was distributed uniformly in the central portion of the particulate bed. The initial average temperature of the particles varied from 889 to 979°C. During flooding, though the system pressure varied, the pressure difference across the particulate layer was held constant. The experiments were carried out to determine the effect on the quenching process of the magnitude of the pressure difference across the particulate bed, the amount of Zircaloy, and the initial temperature distribution. From experiments it is found that increased pressure drop across the bed increases the multidimensional effects and reduces the quenching time. The presence of Zircaloy leads to increased local temperatures and delays complete quenching of the particulate layer. The initial temperature distribution can affect the shape of the quench front, the hydrogen production rate and the total time to quench.
Accelerated motion of a spherical particle

The force components on an oscillating sphere in a fluid medium were studied by experimental means. These force components on the oscillating sphere were separated into the inertial effective force and the dissipative (shear) force. In order to accomplish this experimental program, the writer assumed that the sphere motion was approximately simple harmonic motion, and he analyzed the data as if the motion were exactly simple harmonic motion. The experimental results were applied to an allied problem of a sphere in an oscillating fluid. The experimental results, as applied to this problem, were found to compare with the data of an experiment performed in Germany in about 1920. Extending the analysis further, the writer presents a simple analysis of the diffusion characteristics of suspended sediment in water.
Time-dependent changes in transcriptional profiles within five rat brain regions in response to nicotine treatment

Many years of behavioral and neurobiology studies have demonstrated broad physiological and pharmacological effects of nicotine on the central nervous system (CNS). However, the gene expression profiles associated with these effects are largely unknown. In this study, we characterized gene expression profiles in the prefrontal cortex, striatum, hypothalamus, amygdala and ventral tegmental area of the rat brain in response to subacute and chronic systemic nicotine administration using a pathway-focused microarray developed in this laboratory that contains 638 sequence-verified genes representing broad, yet targeted, biological functions. By comparing the regional effects of nicotine treatment on gene expression levels, we derived the expression profiles of targeted genes and gene families responding to the new environment created by nicotine throughout the complex connections of the CNS. While the expression of many genes was modulated by nicotine in several regions, only a few were co-modulated in multiple brain regions, suggesting region-specific transcriptional responses. Cluster analysis of significantly altered genes within each brain region over the course of nicotine treatment indicated the genes could be grouped into clusters. Subsequent ANOVA analysis demonstrated these clusters within each brain region to be significantly different at most time points. The clusters were comprised of broad functional groups, such as signaling, neurotransmission and protein modifications, demonstrating unique expression patterns within each region. Using a systematic approach to compare the different regional responses to nicotine administration will eventually provide a better understanding of how the different brain regions responding to this drug.
High-speed optoelectronic pulse generation and sampling system

A very-high-frequency (>100-GHz) optoelectronic pulsing and sampling system is presented. This system is used for the characterization of high-speed electronic devices and transmission line structures, and for the study of electronic transport phenomena at picosecond time scales. The signal-to-noise ratio obtained in this system is greater than 50 dB, the sensitivity limit is approximately 1 mu V/Hz/sup 1/2/, and the temporal resolution can be less than 1 ps, thereby permitting studies of very fast low-level signals. >
Innateness as an explanatory concept

Although many of the issues surrounding innateness have received a good deal of attention lately, the basic concept of token innateness has been largely ignored. In the present paper, I try to correct this imbalance by offering an account of the innateness of token traits. I begin by explaining Stephen Stich's account of token innateness and offering a counterexample to that account. I then clarify why the contemporary biological approaches to innateness will not be able to resolve the problems that beset Stich's account. From there, I develop an alternative understanding of the innateness of token traits, what I call a ‘causal/explanatory’ account. The argument to be made is that token innateness is both a causal, and an explanatory, concept. After clarifying this understanding of innateness, and showing how it handles several counterexamples to other accounts, I end with some comments on what the causal/explanatory account suggests for our understanding of innateness in general.
Pregnancy-linked suppression of TcR signaling pathways by a circulating factor absent in recurrent spontaneous pregnancy loss (RPL)

Evidence suggests that maternal cell-mediated immunity is suppressed during pregnancy and that failure to suppress immune responses can result in partial or total rejection of the fetus. The molecular events associated with suppression of maternal T-cell activation mediated by circulating pregnancy-associated 14 kDa zeta inhibitor protein (ZIP) were defined in women with and without histories of recurrent pregnancy loss (RPL). Using cDNA microarray analysis, ZIP modulations of specific genes associated with T-cell activation signaling were defined. Alterations of defined components were confirmed at the protein level using chromatographically purified ZIP from normal pregnancies versus analogous material from women experiencing RPL. Based on microarray analyses, ZIP from normal pregnancies induced an increase (> or =2-fold) in the expression of 19 genes and a decrease (> or =2-fold) in 15 genes, when incubated with cultured T-cells. In contrast, when T-cells were incubated with analogous material from RPL or non-pregnant controls, no significant differences were observed in the expression of these genes. At the protein level, ZIP from normal pregnancies induced decreases in CD3-zeta (2.36-fold), JAK3 (2.41-fold), STAT5 (1.85-fold), and NF-kappaB (4.24-fold) and a 2.05-fold increase in SOCS2 (all at p<0.001 compared to RPL and non-pregnant controls). The suppressive effects of Zip can lead to the failure of T-cell production of Th1 cytokines, such as IL-2. The 14 kDa circulating ZIP from normal pregnancies suppressed components within the JAK/STAT pathway and induced suppressors of cytokine stimulation, SOCS2.
Colliding Worlds: Practical and Political Tensions of Prekindergarten Implementation in Public Schools

This chapter examines how the previously distinct worlds of early childhood education (ECE) and K-12 public school education are being drawn together through the recent and rapid advances of prekindergarten programming in the United States. Tensions around teaching philosophies, teacher qualifications, and financing are presented to illustrate the complexities involved in bridging the ECE and K-12 worlds. Common theories from the Politics of Education, including Policy Innovation Diffusion Theory, Institutional Theory, and Micropolitics are used to further understand current trends and issues around prekindergarten implementation, as well as to identify areas for future investigation. Despite the inherent tensions, prekindergarten has the potential to serve as a bridge between these two historically distinct systems, resulting in a better overall education system for young children.
Scalability, fidelity, and containment in the potemkin virtual honeyfarm

The rapid evolution of large-scale worms, viruses and bot-nets have made Internet malware a pressing concern. Such infections are at the root of modern scourges including DDoS extortion, on-line identity theft, SPAM, phishing, and piracy. However, the most widely used tools for gathering intelligence on new malware -- network honeypots -- have forced investigators to choose between monitoring activity at a large scale or capturing behavior with high fidelity. In this paper, we describe an approach to minimize this tension and improve honeypot scalability by up to six orders of magnitude while still closely emulating the execution behavior of individual Internet hosts. We have built a prototype honeyfarm system, called Potemkin, that exploits virtual machines, aggressive memory sharing, and late binding of resources to achieve this goal. While still an immature implementation, Potemkin has emulated over 64,000 Internet honeypots in live test runs, using only a handful of physical servers.
Framework for net-zero and net-positive building water cycle management

Consumption of limited energy, water and material resources within the building sector drives the need for integrated building management strategies that alleviate the pressure placed on the environment. Net-zero buildings balance the inputs with outputs in order to offset negative external impacts associated with structure operations. Historically the net-zero concept has been applied to the building energy budget; however, the popularity of achieving net-zero compliance has expanded to carbon emissions, waste generation and water consumption. Concordant to the building energy subsystem, the water subsystem consists of multiple demands and sources that dynamically interact. The resultant building water cycle is unique to each building; and thus a generic strategy toward net-zero water compliance does not apply. Distinct differences between energy and water infrastructure components result in variant management strategies for net-zero or regenerative achievement. The application of net-zero concepts to th...
Invasive rats and recent colonist birds partially compensate for the loss of endemic New Zealand pollinators

Reported declines of pollinator populations around the world have led to increasing concerns about the consequences for pollination as a critical ecosystem function and service. Pollination could be maintained through compensation if remaining pollinators increase their contribution or if novel species are recruited as pollinators, but empirical evidence of this compensation is so far lacking. Using a natural experiment in New Zealand where endemic vertebrate pollinators still occur on one offshore island reserve despite their local extinction on the adjacent North Island, we investigated whether compensation could maintain pollination in the face of pollinator extinctions. We show that two recently arrived species in New Zealand, the invasive ship rat (Rattus rattus) and the recent colonist silvereye (Zosterops lateralis; a passerine bird), at least partly maintain pollination for three forest plant species in northern New Zealand, and without this compensation, these plants would be significantly more pollen-limited. This study provides empirical evidence that widespread non-native species can play an important role in maintaining ecosystem functions, a role that needs to be assessed when planning invasive species control or eradication programmes.
Sociologists, Economists, and Opportunism

The markets and hierarchies paradigm holds out the promise of a general theory of the conditions under which organizations come into existence. This paper argues that the two most influential statements of the paradigm (Williamson's and Ouchi's) rest on different—indeed competing—assumptions regarding human motivation. A viable program of research requires that the differences and their implications be carefully spelled out and confronted empirically.
A global router for sea-of-gates circuits

Describes a new global routing algorithm designed specifically for sea-of-gates circuits. The algorithm has been generalized to handle gate array and standard cell circuits. The main features of the algorithm are: (1) interconnection length minimization using a new Steiner tree generation method, (2) a two-stage coarse global routing method which seeks to even congestion, (3) a maze routing procedure which removes overflows and reduces the congestion, (4) vertical track assignment, and (5) congestion evening at the detailed global routing level. In tests on the MCNC benchmark circuits, the algorithm produced layouts with an average of 11% fewer routing tracks than the other algorithms. In tests on gate array benchmark circuits, the algorithm not only achieved uniform channel densities, but the maximum channel densities it produced are the lowest values that have ever been reported. >
Neoadjuvant strategies for the treatment of locally advanced esophageal cancer

Patients with locally advanced esophageal carcinoma have consistently poor survival following surgery with associated high systemic and local-regional failure rates. Neoadjuvant therapeutic strategies have been employed in an attempt to improve outcome with variable success. Randomized trials of either neoadjuvant chemotherapy or chemoradiotherapy have shown conflicting results regarding survival and local-regional control. Future efforts should focus on identifying novel agents and targets to improve therapeutic efficacy.
Time-varying interval volumes

In this paper, we study the interval segmentation and direct rendering of time-varying volumetric data to provide a more effective and interactive volume rendering of time-varying structured and unstructured grids. Our segmentation is based upon intervals within the scalar field between time steps, producing a set of geometrically defined time-varying interval volumes. To construct the time-varying interval volumes, we cast the problem one dimension higher, using a five-dimensional iso-contour construction for interactive computation or segmentation. The key point of this paper is how to render the time-varying interval volumes directly. We directly render the 4D interval volumes by projecting the 4D simplices onto 3D, decomposing the projected 4-simplices to 3-simplices and then rendering them using a modified hardware-implemented projected tetrahedron method. In this way, we can see how interval volumes change with the time in one view. The algorithm is independent of the topology of the polyhedral cells comprising the grid, and thus offers an excellent enhancement to the volume rendering of time-varying unstructured grids. Another advantage of this algorithm is that various volumetric and surface boundaries can be embedded into the time-varying interval volumes.
Dynamic modeling and system identification of a tubular solid oxide fuel cell (TSOFC)

Solid Oxide Fuel Cells (SOFCs) are high temperature fuel cells with a strong potential for stationary power house applications. However, considerable challenges are to be overcome to connect these cells to the power grid. The cells have to satisfy the changing demand of the grid without sacrificing their efficiencies and without causing any structural or material damage. Such an operation, coupled with fast and highly nonlinear transients of the transport variables, leads to a very challenging control problem. This requires an efficient and robust controller. For synthesizing such a controller, a well-validated dynamic model is essential. In this work, a dynamic model is validated by using experimental data from an industrial cell. The data are generated over a broad range of cell temperatures, reactant flow rates, DC polarizations, and amplitudes of step. In the process of validation, it is identified that the Knudsen diffusion and an extended active area for the electrochemical reactions play key roles in determining the current transients of the cell. The dynamic model is used for identification of reduced order models that can be solved in real time for implementation in the MPC framework. Several linear and nonlinear models are considered and the best model is chosen according to the AIC values of the models. Both SISO and MIMO models are identified. For the MIMO model, voltage and H2 flow are considered as inputs. Power and utilization factors are considered as outputs. A linear model such as ARX model is found to be satisfactory for most SISO cases. However, a nonlinear model such as NAARX model with more cross terms is found to improve the model performance significantly for the MIMO case. All through this work, efforts have been made to synthesize the simplest, yet representative model that can be used for real-time applications.
Drosophila Lin-52 Acts in Opposition to Repressive Components of the Myb-MuvB/dREAM Complex

The Drosophila melanogaster Myb-MuvB/dREAM complex (MMB/dREAM) participates in both the activation and repression of developmentally regulated genes and origins of DNA replication. Mutants in MMB subunits exhibit diverse phenotypes, including lethality, eye defects, reduced fecundity, and sterility. Here, we used P-element excision to generate mutations in lin-52, which encodes the smallest subunit of the MMB/dREAM complex. lin-52 is required for viability, as null mutants die prior to pupariation. The generation of somatic and germ line mutant clones indicates that lin-52 is required for adult eye development and for early embryogenesis via maternal effects. Interestingly, the maternal-effect embryonic lethality, larval lethality, and adult eye defects could be suppressed by mutations in other subunits of the MMB/dREAM complex. These results suggest that a partial MMB/dREAM complex is responsible for the lethality and eye defects of lin-52 mutants. Furthermore, these findings support a model in which the Lin-52 and Myb proteins counteract the repressive activities of the other members of the MMB/dREAM complex at specific genomic loci in a developmentally controlled manner.