cssi/SciSciGPT-SciSciNet huggingface dataset:
15-Deoxy-Δ12,14-prostaglandin J2 (15d-PGJ2) mediates repression of TNF-α by decreasing levels of acetylated Histone H3 and H4 at its promoter

Prostaglandin metabolite 15-Deoxy-Delta(12,14)-prostaglandin J2 (15d-PGJ2) is known to inhibit a number of pro-inflammatory cytokines as well as being a ligand for nuclear receptor PPARgamma. We investigated the ability of 15d-PGJ2 to inhibit TNF-alpha gene expression through mechanisms that involve histone modification. Pretreatment with 15d-PGJ2 (10 microM) inhibited LPS-stimulated TNF-alpha mRNA in THP-1 monocytes or PMA-differentiated cells to nearly basal levels. A specific PPARgamma ligand, GW1929, failed to inhibit LPS-induced TNF-alpha mRNA expression nor did a PPARgamma antagonist, GW9662, alter the repression of TNF-alpha mRNA in LPS-stimulated cells pretreated with 15d-PGJ2 suggesting a PPARgamma-independent inhibition of TNF-alpha mRNA in THP-1 cells. Transfection studies with a reporter construct and subsequent treatment with 15d-PGJ2 demonstrated a dose-dependent inhibition of the TNF-alpha promoter. Additional studies demonstrated that inhibition of histone deacetylases with trichostatin A (TSA) or overexpression of histone acetyltransferase CBP could overcome 15d-PGJ2-mediated repression of the TNF-alpha promoter, suggesting that an important mechanism whereby 15d-PGJ2 suppresses a cytokine is through factors that regulate histone modifications. To examine the endogenous TNF-alpha promoter, chromatin immunoprecipitations (ChIP) were performed. ChIP assays demonstrated that LPS stimulation induced an increase in histone H3 and H4 acetylation at the TNF-alpha promoter, which was reduced in cells pretreated with 15d-PGJ2. These results highlight the ability of acetylation and deacetylation factors to affect the TNF-alpha promoter and demonstrate that an additional important mechanism whereby 15d-PGJ2 mediates TNF-alpha transcriptional repression by altering levels of acetylated histone H3 and H4 at its promoter.
Electric field directed assembly of high-density microbead arrays

We report a method for rapid, electric field directed assembly of high-density protein-conjugated microbead arrays. Photolithography is used to fabricate an array of micron to sub-micron-scale wells in an epoxy-based photoresist on a silicon wafer coated with a thin gold film, which serves as the primary electrode. A thin gasket is used to form a microfluidic chamber between the wafer and a glass coverslip coated with indium-tin oxide, which serves as the counter electrode. Streptavidin-conjugated microbeads suspended in a low conductance buffer are introduced into the chamber and directed into the wells viaelectrophoresis by applying a series of low voltage electrical pulses across the electrodes. Hundreds of millions of microbeads can be permanently assembled on these arrays in as little as 30 seconds and the process can be monitored in real time using epifluorescence microscopy. The binding of the microbeads to the gold film is robust and occurs through electrochemically induced gold-protein interactions, which allows excess beads to be washed away or recycled. The well and bead sizes are chosen such that only one bead can be captured in each well. Filling efficiencies greater than 99.9% have been demonstrated across wafer-scale arrays with densities as high as 69 million beads per cm2. Potential applications for this technology include the assembly of DNA arrays for high-throughput genome sequencing and antibody arrays for proteomic studies. Following array assembly, this device may also be used to enhance the concentration-dependent processes of various assays through the accelerated transport of molecules using electric fields.
Psychophysiological and Memory Effects of Negative Political ADS: Aversive, Arousing, and Well Remembered

This study examines whether negative political advertisements elicit automatic activation in the aversive motivational system among viewers. A measure is introduced—the eyeblink startle reflex—that provides evidence that negative ads do activate the aversive motivational system. As these participants watched negative political ads, physiological responses indicated that their body was reflexively preparing to move away. Negative ads also elicited more physiological and self-reported arousal than moderate ads. Recognition data show that detailed information from negative ads is better recognized; however, participants were also more likely to incorrectly report that they recognized information from negative ads they did not see.
Modeling Occurrences of Non-VFR Weather: A Case Study for Design of Flight Instruction Programs.

Objective methods in which climatology is considered are needed in the design of flight instruction programs. Weather conditions less than the minimum (LM) thresholds designated for Minimum Instructional Visual Flight Rules (MIVFR) were defined as those with 25 kt. The climatology of the LM conditions for four two-hour flight periods during the spring, fall, and summer semesters at Purdue University was generated. The negative binomial distribution was used to develop the expected LM probability deciles, which, for a fixed level of controllable resources, were used to predict the maximum number of students that should be enrolled in each semester. In the general aviation flight technology program at Purdue University, it was found that with present class enrollments in Visual Flight Rules (VFR) flight training, all students could be expected to complete their scheduled flying hours during a semester, without considerable makeup flight i...
Real-Time Assessment of Secondary Task Intrusiveness upon Real-World Driver Steering Performance using a Fiber-Optic Gyroscope:

Lateral steering stability is a critical parameter of driving performance from both a theoretical as well as applied perspective. The measurement of lateral steering stability in a driving simulation environment is both straightforward and ubiquitous. However, the ability to measure this performance parameter in real-time during real-world driving has typically been fraught with technical challenges. The recent introduction of low cost fiber-optic gyroscope devices appears to have addressed many of the traditional difficulties associated with the real-time measurement of steering performance. State-of-the-art fiber-optic gyroscopes are capable of providing continuous data representing the rate of change in heading angle with a precision of 0.001 deg/sec. The current study evaluated the reliability and potential usefulness of real-time angular heading rate data collected from a instrumented research vehicle fitted with a KVH AutoGyro (fiber-optic laser gyroscope). Data from the fiber-optic gyroscope was co...
Physical mapping of a region in the soybean ( Glycine max ) genome containing duplicated sequences

Pulsed-field gel electrophoresis (PFGE) was used to study a cluster of molecular markers in the soybean genome. There were 550 kb per centimorgan (cM) in the cluster, which is close to the calculated average for the whole genome. The analysis was complicated by the presence of duplicated sequences, and some ambiguities arising from this were resolved by using second-dimension conventional electrophoresis to relate physical maps to the RFLP map of soybean. The results show that there is a high degree of conservation of ‘rare cutter’ sites between homoeologous regions. Finally, PFGE can confirm physical linkage of monomorphic copies of markers, which can aid in the study and comparison of homoeologous regions that are invisible to RFLP analysis.
Genetic modifiers of MeCP2 function in Drosophila.

The levels of methyl-CpG–binding protein 2 (MeCP2) are critical for normal post-natal development and function of the nervous system. Loss of function of MeCP2, a transcriptional regulator involved in chromatin remodeling, causes classic Rett syndrome (RTT) as well as other related conditions characterized by autism, learning disabilities, or mental retardation. Increased dosage of MeCP2 also leads to clinically similar neurological disorders and mental retardation. To identify molecular mechanisms capable of compensating for altered MeCP2 levels, we generated transgenic Drosophila overexpressing human MeCP2. We find that MeCP2 associates with chromatin and is phosphorylated at serine 423 in Drosophila, as is found in mammals. MeCP2 overexpression leads to anatomical (i.e., disorganized eyes, ectopic wing veins) and behavioral (i.e., motor dysfunction) abnormalities. We used a candidate gene approach to identify genes that are able to compensate for abnormal phenotypes caused by MeCP2 increased activity. These genetic modifiers include other chromatin remodeling genes (Additional sex combs, corto, osa, Sex combs on midleg, and trithorax), the kinase tricornered, the UBE3A target pebble, and Drosophila homologues of the MeCP2 physical interactors Sin3a, REST, and N-CoR. These findings demonstrate that anatomical and behavioral phenotypes caused by MeCP2 activity can be ameliorated by altering other factors that might be more amenable to manipulation than MeCP2 itself.
Determination of double bond location in fatty acids by manganese adduction and electron induced dissociation.

Double bond locations in fatty acids can be determined from characteristic charge-remote fragmentation patterns of alkali metal-adducted fatty acids following high energy collision activated dissociation (CAD). With low energy CAD, several chemical derivatization methods, including ozonization, epoxidation, and hydroxylation, have been used to generate characteristic fragments. However, high energy CAD is not universally available and involves a high degree of scattering, causing product ion loss. Further, derivatization reactions involve side reactions and sample loss. Here, we analyzed metal-adducted fatty acids to investigate the utility of electron induced dissociation (EID) for determining double bond location. EID has been proposed to involve both electronic excitation, similar to high energy CAD, and vibrational exciation. Various metals (Li, Zn, Co, Ni, Mg, Ca, Fe, and Mn) were investigated to fix one charge at the carboxylate end of fatty acids to promote charge-remote fragmentation. EID of Mn(II...
Applications of Desensitization Procedures for School-Related Problems; A Review.

A variety of desensitization and counterconditioning procedures have been utilized to deal with school-related problems. These procedures are reviewed with respect to applications for treating school phobia, test anxiety, and other academic anxieties. The case and experimental studies reviewed indicate that desensitization procedures in combination with other techniques are most effective. Guidelines for using these procedures in the schools are suggested.
Age characteristics in a multidecadal Arctic sea ice simulation

[1] Results from adding a tracer for age of sea ice to a sophisticated sea ice model that is widely used for climate studies are presented. The consistent simulation of ice age, dynamics, and thermodynamics in the model shows explicitly that the loss of Arctic perennial ice has accelerated in the past three decades, as has been seen in satellite-derived observations. Our model shows that the September ice age average across the Northern Hemisphere varies from about 5 to 8 years, and the ice is much younger (about 2–3 years) in late winter because of the expansion of first-year ice. We find seasonal ice on average comprises about 5% of the total ice area in September, but as much as 1.34 × 106 km2 survives in some years. Our simulated ice age in the late 1980s and early 1990s declined markedly in agreement with other studies. After this period of decline, the ice age began to recover, but in the final years of the simulation very little young ice remains after the melt season, a strong indication that the age of the pack will again decline in the future as older ice classes fail to be replenished. The Arctic ice pack has fluctuated between older and younger ice types over the past 30 years, while ice area, thickness, and volume all declined over the same period, with an apparent acceleration in the last decade.
Surgery and pancreas divisum: a dwindling role?

Pancreas divisum (PD) was described nearly 300 years ago. 33 Until 2 decades ago, it remained a dormant anatomic entity—an autopsy finding without clinical relevance. In the past 20 years, endoscopic retrograde cholangiopancreatography (ERCP) has found widespread application for patients with abdominal pain or with acute and chronic pancreatitis. 1,7,10,11,12,14,16,18,22,23,24,28,32 As a result, PD has become more than an irrelevant congenital anomaly. Detected in 3% to 10% of the population, PD has been causally related to pancreatitis or abdominal pain. 5,10,11,14,18,35 In the past 2 decades, several articles described the pathophysiology of PD and its anatomic correction by surgical sphincteroplasty of the minor pancreatic duct. 1,5,6,13,14,17,20,26,27,35 The end result after surgery was variable, with the result very dependent on the indication for the procedure, that is, pain or pancreatitis. 4,5,9,29,30,31 After an initial successful surgical correction of PD, there is a common need for reoperation or reintervention because of the return of abdominal pain. 4,9,21,30,31 This has posed a dilemma for surgeons. The guidelines that applied to failed operations for chronic pancreatitis also were applied to these patients, namely, a failed drainage procedure (sphincteroplasty) often was followed by a major pancreatic resection, and a failed resection was followed by a total pancreatectomy. 3,4,19,25,31,36 At the time of repeat surgery, the gland often was found to be minimally diseased and resection commonly was followed by persistent pain and the sequelae of resection—steatorrhea and diabetes. In this issue, Cohen and Siegel (see pages 321–328 and 467–477) summarize the status of PD and the increasing role of endoscopic stenting of the minor pancreatic duct in an attempt to relieve pain, provide long-term drainage of the pancreatic duct, and preserve pancreatic function and delay or prevent diabetes. There are three reasons that patients with PD require interventional therapy: (1) acute pancreatitis, (2) chronic pancreatitis, and (3) pancreatic-type pain.
Analysis of functionally graded plates

Theoretical formulation, Navier's solutions of rectangular plates, and finite element models based on the third-order shear deformation plate theory are presented for the analysis of through-thickness functionally graded plates. The plates are assumed to have isotropic, two-constituent material distribution through the thickness, and the modulus of elasticity of the plate is assumed to vary according to a power-law distribution in terms of the volume fractions of the constituents. The formulation accounts for the thermomechanical coupling, time dependency, and the von Karman-type geometric non-linearity. Numerical results of the linear third-order theory and non-linear first-order theory are presented to show the effect of the material distribution on the deflections and stresses. Copyright © 2000 John Wiley & Sons, Ltd.
Comparison of predictors of heart failure-related hospitalization or death in patients with versus without preserved left ventricular ejection fraction.

Heart failure with preserved ejection fraction (HFpEF) is recognized as a major cause of cardiovascular morbidity and mortality. An ability to identify patients with HFpEF who are at increased risk for adverse outcomes can facilitate their more careful management. We studied the patients having heart failure (HF) using data from the Heart Failure Adherence and Retention Trial (HART). HART enrolled 902 patients in the New York Heart Association (NYHA) class II or III who had been recently hospitalized for HF to study the impact of self-management counseling on the primary outcome of death or HF hospitalization. In HART, 208 patients had HFpEF and 692 had HF with reduced ejection fraction (HFrEF) and were followed for a median of 1,080 days. Two final multivariate models were developed. In patients having HFpEF, predictors of primary outcome were male gender (odds ratio [OR] 3.45, p = 0.004), NYHA class III (OR 3.05, p = 0.008), distance covered on a 6-minute walk test (6-MWT) of 65 years (OR 1.63, p = 0.01). In conclusion, indicators of functional status (6-MWT and NYHA class) were common to both patients with HFpEF and those with HFrEF, whereas gender and adherence to prescribed therapy were unique to patients having HFpEF in predicting death or HF hospitalization.
Mechanisms of disease: mitochondria as new therapeutic targets in diabetic neuropathy.

Diabetic neuropathy is the most common complication of diabetes mellitus, and there are currently no effective treatments for this condition. In this Review, Leinninger et al. discuss the proposed role of mitochondrial degeneration in the pathogenesis of diabetic neuropathy, and highlight potential mitochondrial sites for therapeutic intervention. Diabetic neuropathy (DN) is the most common complication of diabetes mellitus, and it imposes a considerable burden on a patient's quality of life and the health-care system. Despite the prevalence and severity of DN, there are no effective treatments. Pathogenetic evidence suggests that DN is marked by degeneration of dorsal root ganglion (DRG) neurons in peripheral nerves, and that DRG mitochondria are particularly affected. DRG mitochondria are especially vulnerable because they are the origin of reactive oxygen species production in the hyperglycemic neuron. Accumulating evidence indicates that neuronal mitochondria are subject to damage at the level of their DNA, and their outer and inner membranes, and also via deregulation of mitochondrial fission and fusion proteins that control mitochondrial shape and number. This Review will survey the mechanisms of mitochondrial degeneration in the pathogenesis of DN, highlighting potential mitochondrial sites for therapeutic intervention.
Throughput-Optimal Queue Length Based CSMA/CA Algorithm for Cognitive Radio Networks

Cognitive radio networks allow unlicensed users to access licensed spectrum opportunistically without disrupting primary user (PU) communication. Developing a distributed implementation that can fully utilize the spectrum opportunities for secondary users (SUs) has so far remained elusive. Although throughput optimal algorithms based on the well-known maximal weight scheduling (MWS) algorithm exist for cognitive radio networks, they require central processing of network-wide SU information. In this paper, a new distributed algorithm is introduced that asymptotically achieves the capacity region of the cognitive radio systems. The proposed algorithm achieves the full SU capacity region while adapting to the channel availability dynamics caused by unknown primary user activity. Extensive simulation results are provided to illustrate the efficacy of the algorithm.
Clinical Course and Systemic Correlates of Retinopathy of Prematurity in Quintuplets

Purpose/Methods We studied clinical correlates of retinopathy of prematurity in four surviving quintuplets with similar low birth weights and gestational age of 27 weeks. Prospective serial ophthalmoscopic examinations and retrospective chart analysis were used. Results/Conclusions Retinopathy of prematurity varied among the neonates from stage 2 with total regression to threshold progressing to retinal detachment. Severity of eye disease correlated with duration of mechanical ventilation and of parenteral nutrition, as well as frequency of hypoglycemia and of hypercapnia. Poor outcome correlated inversely with weight gain.
Fault Tolerant Computer System for the A129 Helicopter

The A129 integrated multiplex system (IMS) is a highly reliable computer system designed to implement automatic flight control, navigation, system monitoring, and other flight-critical and mission related tasks. The reliability of the IMS has been achieved through the development of hardware-implemented and software implemented fault-tolerance techniques which exploit several unique architectural and hardware characteristics. This paper describes the fault-tolerance design philosophy, the IMS architecture, the fault detection and fault recovery techniques, and the hardware and software structures. Also presented is a Markov reliability analysis which was used to quantify the reliability of the system.
Perfusion imaging of cerebrovascular reserve.

Cerebral infarction results when nutrient supply is unable to meet minimum requirements needed to maintain cellular viability or when nutrient deprivation is sufficient to induce apoptosis. The conditions necessary to produce irreversible damage to the cerebral parenchyma have been studied extensively in experimental models and humans [1]. From these studies we know that cell death is a complex function of the duration of ischemia, the magnitude of ischemia, the nutrient and oxygen content of blood, and the specific cerebral structure involved. At the extreme represented by cessation of blood flow, we know that cell viability may be lost in as little as 20 minutes. For more mild but prolonged hypoperfusion, irreversible injury to gray matter will occur with a cerebral blood flow (CBF) below approximately 20 mL/100 mg/h. In between there is a wide spectrum of infarct-producing factor combinations. In clinical practice, we group this spectrum into several distinct scenarios. These well-known entities include (1) acute ischemia resulting from sudden occlusion of a vessel by thromboembolism, (2) global hypoxic injury resulting from respiratory arrest, and (3) chronic borderline hypoperfusion due to the occlusion or stenosis of large arteries in the neck or circle of Willis. This last scenario is the chief focus of efforts to measure cerebrovascular reactivity or reserve. Here, ischemia is the result of a combination of chronic and acute factors. There is long-standing and often slowly progressive narrowing of the large arteries (eg, internal carotid artery, middle cerebral artery). These stenoses act to decrease local perfusion pressure. The deficit is most marked at the regions farthest from the heart—the arterial border zones. These border zones are the regions at the margins of the territories supplied by the anterior, middle, and posterior cerebral arteries or between the cortical vessels and small penetrating arteries at the base of the brain. The baseline decrease in perfusion pressure makes these areas susceptible to fluctuations in systemic blood pressure, oxygen capacity, and local vascular resistance. When hypoperfusion is brief, transient neurologic deficits may occur. When perfusion pressure falls below critical levels for a sufficient time, infarction will result.
IEEE Std 1149.1: where are we? where from here?

The authors discuss the status and celebrate the success of IEEE Std 1149.1, hoping to motivate discussion and action that will encourage further development of boundary scan-based testing. They offer the insight of experienced implementers of the standard working in competitive business environments. >
Teacher Feedback to Support Oral Language Learning for Young Dual Language Learners.

With the increasing numbers of dual language learners (DLLs) in early childhood programmes, the use of research-based and effective pedagogical strategies to support oral language learning is important. Early childhood classrooms can provide many opportunities to support language learning. Teacher feedback is an intentional teaching strategy to support oral language skills for both English and children's home language. We first present an overview of contexts for language learning in early childhood including a discussion of intentional teaching. Next, we discuss considerations for early childhood teachers’ provision of feedback to children regarding their oral language use. Finally, we present six teacher feedback strategies to foster oral English and/or home language skills for DLLs.
Towards physical object manipulation by small unmanned aerial systems

This paper identifies five human-robot interaction (HRI) challenges for physical object manipulation by small unmanned aerial systems (UAS). A survey of small unmanned aerial vehicles (UAVs) was used to categorize physical interaction into three configurations (ventral, frontal, and dorsal). Following this, anticipated individual and shared responsibilities for physical object manipulation are discussed for two previously established human team roles for small UAS (Pilot and Mission Specialist) using the Shared Roles Model. For each physical interaction configuration, the two human team roles are evaluated to determine: 1) what types of human-robot interactions are likely, 2) how the Pilot and Mission Specialist could interact with existing user interface technology, and 3) what are the perceived consequences of these physical interactions in the context of the human-robot team. The HRI challenges identified through this work suggest that Pilot interfaces will need to support a mixed view (exocentric and egocentric) and that interfaces for both roles will require shared visual common ground.
Endoscopic management of postcholecystectomy bile duct strictures.

Background Review of 1.6 million cholecystectomies, from 1992 to 1999, demonstrated a 0.5% incidence of bile duct injury, despite increasing experience with laparoscopy. The incidence has not decreased after the "learning curve." The management of major bile duct injuries has traditionally been by hepaticojejunostomy. Endoscopy has been increasingly used to treat these injuries. This study reviews the senior author's endoscopic treatment of bile duct injuries. Study Design This is a retrospective study, from 1991 to 2006, examining data on 292 patients who were referred for postcholecystectomy problems; 199 had cholecystectomy-related injuries and 93 had other pathologies. Sixty-seven patients had bile duct injuries (Amsterdam Academic Medical Center Classification, types B, C, and D). Nineteen patients underwent bilioenteric bypass for complete bile duct occlusion or transection. In the remaining 48, endoscopic retrograde cholangiopancreatography (ERCP) evaluation and treatment were possible. Our protocol called for biliary stenting for 11 to 14 months, with stent changes at 3-month intervals. Short- and longterm results were evaluated by clinical, radiologic, and laboratory studies. Results Forty-six patients were selected for endoscopic management by balloon dilation and biliary stent placement. The mean ± SD duration of endoscopic stenting was 12±9.8 months and followup was 30±24 months after stent removal. During the followup period, 10 of 46 patients (22%) had recurrent stricture: 6 (13%) responded to endoscopic biliary stenting and 4 (9%) required hepaticojejunostomy. Complications included pancreatitis (8%). There were no deaths in the endoscopic group. Conclusions ERCP intervention is a safe, effective, minimally invasive treatment for bile duct strictures after cholecystectomy and can be an alternative to hepaticojejunostomy.
Lipopolysaccharide down-regulates inducible nitric oxide synthase expression in swine heart in vivo.

Studies of the regulation of iNOS expression have provided many contradictory results. Comparing iNOS expression profile between cell types or organs of the same animal under the same experimental conditions may provide an explanation for these conflicting results. We have examined iNOS mRNA and protein expression in heart and liver of the same group of pigs. We found that there is a sharp difference in iNOS expression between heart and liver. The iNOS mRNA and protein was constitutively expressed in the heart at high level, but was not detectable in the liver of the same control animal. Lipopolysaccharide (LPS, 100 μg/kg, i.v.) caused a marked iNOS induction in the liver, but significantly down-regulated iNOS expression in the heart. This differential iNOS expression appears to be physiologically relevant, since LPS and the iNOS inhibitor, S-methylisothiourea, exerted different effects on hepatic and myocardial blood flow. Our data demonstrate a fundamental difference in iNOS regulation in the heart and liver of swine, and may explain the contradictory data on the regulation of iNOS expression.
Dispersive hole growth kinetics and fluence broadening of the zero-phonon hole of impurities in amorphous hosts

Abstract A detailed treatment of the relationship between the dispersive growth kinetics of the zero-phonon hole (ZPH) of an impurity molecule in an amorphous host and burn fluence broadening of the ZPH is presented. Focus is on non-photochemical hole burning (NPHB). The equation used for simulations accounts for dispersion due to a distribution of tunneling parameters (λ-distribution), the angle between the laser polarization and the transition dipole (α-distribution), and off-resonant absorption of the zero-phonon line (ω-distribution). Two cases are considered: burned laser linewidth narrow relative to the homogeneous width of the zero-phonon line; and the reverse situation. Results are presented for two model systems whose parameter values are similar to those of aluminum phthalocyanine tetrasulphonate (APT) in hyperquenched glassy water and in hyperquenched glassy ethanol. For comparison, results are presented for the case where the hole growth kinetics are non-dispersive (single-exponential). It is found that at the early stage of burning fluence broadening is considerably more severe for a dispersive system than for a non-dispersive system. A straightforward explanation for this is given. The results are compared with those of earlier works on dispersive hole growth kinetics and fluence broadening. The results reveal the types of experiment needed to understand the aforementioned relationship, a requirement for determination of the homogeneous width of the ZPH that reflects the dynamics of the system.
Operators in a relativistic fock space for fermions

We extend the definition of creation and annihilation operators for a particle in an arbitrary state in Fock space to the relativistic case. We pay special attention to the metric in this space and to the phase convention that leads to anticommutation relations for these operators. The same conventions also apply in the case of several types of fermions.
Abstract 1242: Induction and targeting of polyploid senescent cells in cancer therapeutics

Proceedings: AACR 102nd Annual Meeting 2011‐‐ Apr 2‐6, 2011; Orlando, FL Therapy-induced cellular senescence (TCS), an emerging concept in cancer therapeutics, describes an in vivo response of human tumors to chemotherapy and radiation. These treatments elicit a coordinated response that results in prolonged cell cycle arrest, characteristic senescence morphology and expression of senescence-specific markers. In the past decade, a growing body of evidence has supported the hypothesis that “senescence response occurs in treated human cancers and the response is reversible.” We now present evidence that TCS may be adverse to cancer therapeutics based on a clinicopatholgical study conducted in patients with advanced non-small cell lung cancer following induction therapy prior to surgery. To further define how a subpopulation of senescent cells could escape terminal arrest, our work now implicates a polyploid state through which senescent cells can survive and eventually resume proliferation. In H1299 lung cancer cells, we show that mitotic kinase Cdk1 facilitates endoreplication and formation of polyplid senescent cells (PSCs) following chemotherapy as the genetic modulation of Cdk1 activity profoundly affect the prevalence of these polyploid cells. Importantly, senescence escape occurs from the PSCs at 2.5 times the frequency of escape observed from diploid (2/4n) cells through novel non-canonical cell division mechanisms. Furthermore, we also demonstrate distinct functions of p21 and p27, two members of KIP family in TCS. While both interact with endogenous cyclin B1-Cdk1 complex in senescent cells, only p27 directly inhibits Cdk1 kinase activity and modulates PSC formation, whereas the knockdown of p21 leads to massive apoptosis. Finally, we show that statins, HMG-CoA inhibitors, currently approved for treatment of dyslipidemia down-regulate several key targets of the Cdk1 pathway, including Cdk1 itself, cyclin B1, and survivin, while up-regulating p27. Statins both decrease polyploid cells and abrogate escape of several cancer cell lines from TCS. Altogether, our work here challenges the current cancer treatment paradigm and supports the incorporation of novel strategies to enforce irreversible cell cycle exit in senescent tumor cells following treatment. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 1242. doi:10.1158/1538-7445.AM2011-1242
Fragmentation mechanisms of oligodeoxynucleotides: effects of replacing phosphates with methylphosphonates and thymines with other bases in T-rich sequences.

This article reports another step in an ongoing effort to understand the fragmentation of T-rich oligodeoxynucleotides. We extended an earlier investigation of T-rich 4-mers [1] to T-rich 6-mers, 8-mers and 10-mers by using four different tandem mass spectrometric methods. The methods include low-energy collisionally activated decomposition (CAD) of electrospray ionization (ESI)-produced ions, source-CAD of ESI-produced ions, post-source decay (PSD), and CAD of matrix assisted laser desorption ionization (MALDI)-generated ions. The most abundant fragment ions produced from [M − 2H]2− precursors upon low-energy CAD in an ion trap are the [a − B]− and their complementary w ions. The predominant cleavage sites for T-rich oligodeoxynucleotides are always the 3′ C-O bonds adjoining a non-T nucleobase (i.e., a base with a higher proton affinity (PA) than that of T). The relative abundance of [a − B]− correlates with the PAs of the nucleobases, underscoring the importance of proton transfer to the base. The propensity to form [a − B]− ions falls in the order of G > C ≈ A ≫ T. Structural isomers up to 10-mers can be readily sequenced and distinguished with each of the four tandem mass spectrometric methods applied. The fragmentation of oligodeoxynucleotides in which various phosphates were replaced with methylphosphonate is a measure of the participation of the phosphate proton in the formation of [a − B]− ions. For 4 and 5-mers, transfer of an acidic proton from the 5′-phosphate to the departing base is the initiating step in the formation of [a − B]− ions.
Experienced Teachers' Planning Practices: A US Survey.

Abstract Thirty‐three teachers who taught in a school district that required the use of the Madeline Hunter model of planning were surveyed about their instructional planning practices. The majority of teachers reported using this planning model but in a more flexible manner than prescribed, which allowed for wide ranges in student ability and interruptions in the school schedule. Teachers reported difficulty in integrating the Madeline Hunter model with approaches newly adopted by the district, such as cooperative learning and whole‐language. Other planning dilemmas involved prioritizing content in the mandated curriculum and planning in a flexible manner. Only about half of the teachers made plans from unit notebooks or folders.
First Grade Norms, Factor Analysis and Cross Correlation for Conners, Davids, and Quay-Peterson Behavior Rating Scales

Three behavior rating scales were filled out by teachers for the entire first grades of three public schools, totalling 225 children. Factor analyses on this nonclinical sample yielded different factors from those found previously on clinical samples. The Conners scale showed four factors: hyperkinetic, shy-inept, rebellious-unsocialized, and antisocial-immature. The Quay-Peterson checklist also showed four factors: hyperkinetic, shy-inept, depressed, and dyssocial. The “inattentive” items, which formed a separate factor on older clinical samples, blended into the hyperkinetic factor on this younger normal sample. The whole Davids scale was one clean factor with all loadings above .6 and “impulsiveness” the highest loading. The hyperkinetic factors of both scales correlated highly with each other and with the Davids whole scale. The two shy-inept factors correlated at .82 with each other. Factor analysis of all the items from the 3 scales as if they were one large scale yielded seven factors: hyperkinetic...
Auditory segregation of concurrent signals: an operational definition

Auditory segregation of simultaneous, multiple (quasi-) steady-state acoustic signals which compose an ensemble implies simultaneous resolution along three "cardinal dimensions": vectors of pitch (residue plus timbre), temporal structure, and location. It is proposed that the normalized distance between two, or several, component signals in an ensemble along any of the three dimensions is traded off by differences on the two other dimensions. A psychophysical paradigm is described for objective measurement of auditory segregation and a metric is suggested for the prediction of segregation in the 3D parameter space.
The ABCs of sterol transport.

Mammalian cells have developed various responses to minimize accumulation of unesterified cholesterol, as the latter can result in cell toxicity and death [reviewed in this edition by Bjorkhem (Bjorkhem, I. 2009. Are side-chain oxidized oxysterols regulators also in vivo? J. Lipid Res. In press)]. These responses include esterification to sequester excess sterol in intracellular lipid droplets, repression of both cholesterol synthesis and LDL receptor expression (thus reducing endocytosis of LDL), and induction of a panoply of genes that promote sterol efflux and affect lipid metabolism. The nuclear receptor liver-X-receptor (LXR) functions as a cellular "sterol sensor" and plays a critical role in these latter transcriptional changes [reviewed in this edition by Glass (Shibata, N., and Glass C, K. 2009. Regulation of macrophage function in inflammation and atherosclerosis. J. Lipid Res. In press)]. Activation of LXR by either endogenous oxysterols or synthetic agonists induces the expression of many genes, including those encoding ATP-binding cassette (ABC) transporters ABCA1, ABCG1, ABCG5, and ABCG8. As discussed below, these four proteins function to promote sterol efflux from cells.
R-Ras interacts with filamin a to maintain endothelial barrier function.

The molecular mechanisms regulating vascular barrier integrity remain incompletely elucidated. We have previously reported an association between the GTPase R-Ras and repeat 3 of Filamin A (FLNa). Loss of FLNa has been linked to increased vascular permeability. We sought to determine whether FLNa’s association with R-Ras affects endothelial barrier function. We report that in endothelial cells endogenous R-Ras interacts with endogenous FLNa as determined by co-immunoprecipitations and pulldowns with the FLNa-GST fusion protein repeats 1–10. Deletion of FLNa repeat 3 (FLNa 3) abrogated this interaction. In these cells FLNa and R-Ras co-localize at the plasma membrane. Knockdown of R-Ras and/or FLNa by siRNA promotes vascular permeability, as determined by TransEndothelial Electrical Resistance and FITC-dextran transwell assays. Re-expression of FLNa restored endothelial barrier function in cells lacking FLNa whereas re-expression of FLNaΔ3 did not. Immunostaining for VE-Cadherin in cells with knocked down R-Ras and FLNa demonstrated a disorganization of VE-Cadherin at adherens junctions. Loss of R-Ras and FLNa or blocking R-Ras function via GGTI-2133, a selective R-Ras inhibitor, induced vascular permeability and increased phosphorylation of VE-Cadherin (Y731) and Src (Y416). Expression of dominant negative R-Ras promoted vascular permeability that was blocked by the Src inhibitor PP2. These findings demonstrate that maintaining endothelial barrier function is dependent upon active R-Ras and association between R-Ras and FLNa and that loss of this interaction promotes VE-Cadherin phosphorylation and changes in downstream effectors that lead to endothelial leakiness.
An analysis of the robustness of CMOS delay elements

In this paper, we review three different families of delay elements used in CMOS VLSI design: (1) transmission gate based, (2) cascaded inverter based, and (3) voltage-controlled ones. We compare their effectiveness in terms of yield, which is defined as the number of delay elements that have delays within a specified delay range. The delay variations are obtained through HSpice Monte Carlo simulations and are analyzed using analytical delay expressions. The sensitivity of the delay elements to different process and environmental variations can be studied using the simulation results. This will enable designers to select the best delay element for their design and also do a robust design by taking into account the sensitivities of delay elements to different parameters.
Declining Plasma Progesterone Concentration with Advancing Gestation in Blood From Umbilical and Uterine Veins and Fetal Heart in Monkeys

No fall in maternal progesterone values preceding the onset of labor has been demonstrated in pregnant monkeys in plasma from a peripheral vein, giving rise to the question of how this hormone maintains the uterus in a quiescent state during gestation without blocking parturition. We wondered whether progesterone levels taken from sites more directly related to the uterus would yield different results. Plasma progesterone values were determined during the last half of gestation in pregnant monkeys in samples taken from the uterine veins, the umbilical vein, the fetal heart and a maternal peripheral vein. Peripheral vein levels during this period ranged from 1.3 to 18.0 ng/ml and showed no trend with advancing gestation. Levels in the uterine vein ranged from 2.2 to 150 ng/ml, in the unbilicalvein from 6.9 to 233 ng/ml, and in the fetal heart from 3.8 to 223 ng/ml. In plasma from these 3 sitestherewas a significanttrend toward lower values with advancing gestation. Uterine and umbilical vein progesterone levelsappear more likelyto reflectconditions in the uterus than maternal peripheralvein levels.Their decliningvalues in the latterpart of gestation
Progesterone regulation of endometrial estrogen receptor and cell proliferation during the late proliferative and secretory phase in artificial menstrual cycles in the rhesus monkey.

Progesterone (P) down-regulation of uterine estradiol (E) receptor (ER) appears to be a general mechanism by which P modulates E action in the uterus. Our present studies focus on the regulation of ER by P during the changeover from E to P dominance during artificial menstrual cycles in the rhesus monkey. Because of differential cell-type response and the cellular zonation of the primate uterus, we used immunohistochemical analysis in addition to biochemical assays to study the regulation of ER by P. Ki-67 immunoreactivity was used as an index of endometrial proliferation. We performed our analyses on Days 13 (peak of E), 14 (declining E and rising P), 17 (basal E and rising P), and 21 (basal E and peak P). ER immunoreactivity was present throughout the endometrium in luminal and glandular epithelia and stromal fibroblasts on Day 13. As E was withdrawn and P rose on Day 14 there were few distinct changes in ER staining in stromal and epithelial cells. On Day 17, immunoreactive staining showed a distinct reduction for stromal cells in all zones. Although luminal epithelial cells showed a decrease in immunoreactivity on Day 17, zones II, III, and IV retained positive staining for ER in glandular epithelia. ER staining in stromal cells on Day 21 was similar to the pattern observed on Day 17, whereas epithelial cells in zones I, II, and III showed a reduction in staining. Glandular epithelia in zone IV maintained strong positive staining for ER on Day 21. According to biochemical assays, total and occupied nuclear ER and cytosolic ER were significantly decreased on Day 14 and remained suppressed through Day 21. Endometrial proliferation (Ki-67 immunoreactivity) occurred throughout the endometrium on Day 13, showed little change on Day 14, and was dramatically suppressed in stromal fibroblasts and epithelial cells of zones I, II, and III on Days 17 and 21. Proliferation continued in glandular epithelium of zone IV during the changeover from E to P dominance. Removal of secretory estradiol (all E implants removed on Day 13) did not affect the proliferation pattern in zone IV on Day 21. Therefore, proliferation of glandular epithelial cells in zone IV is not dependent on secretory E. These results describe the temporal changes in ER immunostaining during the onset of P action in artificial menstrual cycles and demonstrate that not only are there zone-dependent differences in response to P but also that the sensitivity of different cell-types within the endometrium is subject to temporal differences in response. The coincident temporal and zone-dependent decrease in proliferation and ER in zones I, II, and III suggests a close relationship between P-dependent down-regulation of ER and endometrial proliferation.
Getting Past the Gatekeepers: Differences Between Access and Cooperation in Public School Research

This article describes differences in access and cooperation in four qualitative research studies in public schools. Gatekeepers grant formal access but withhold cooperation if they think studies threaten them or their schools. Project approval by official gatekeepers does not guarantee cooperation from informal gatekeepers and participants. The author describes gatekeepers’ practices to grant or withhold access and cooperation and the influence of perceived benefits and threats to cooperation. The article concludes with lessons from these research experiences that may lead to more cooperative relationships between researchers and gatekeepers.
Treatment process, alliance and outcome in brief versus extended treatments for marijuana dependence

Aims The Marijuana Treatment Project, a large multi-site randomized clinical trial, compared a delayed treatment control condition with a brief (two-session) and extended (nine-session) multi-component treatment among 450 marijuana-dependent participants. In this report we present treatment process data, including the fidelity of treatment delivery in the three community-based treatment settings as well as the relationships between treatment process and outcome.
The surface and catalytic chemistry of olefin metathesis catalyzed by metallic and oxygen-modified molybdenum

Abstract It is shown that model oxides grown on metallic substrates catalyze propylene metathesis to form ethylene and butene with an activity that mimics that of supported catalysts for reaction below ∼650 K. Another regime is found above ∼650 K where the reaction proceeds with a much higher activation energy of ∼60 kcal/mol. Unfortunately, alkenes do not react to any detectable extent on the model oxide surfaces in ultrahigh vacuum. However, the high-temperature (>650 K) metathesis rate is found to be effected by the presence of oxygen overlayers, which also modify the chemistry of alkenes on Mo(100) in ultrahigh vacuum. Methane is formed in temperature-programmed desorption following adsorption of alkenes (ethylene, propylene and 2-butene) on O/Mo(100). The only other products detected are ascribed to either hydrogenation reactions or to total thermal decomposition into carbon and hydrogen and it is proposed that alkenes dissociate via CC bond cleavage forming carbenes which then hydrogenate to yield methane. This chemistry is in accord with that found catalytically at high temperatures where the product distribution from the reaction of ethylene is well described by a Schulz–Florey distribution and the product distribution from propylene is well described by co-polymerization of carbenes and methyl carbenes. The reaction is also found to proceed in the presence of a carbonaceous layer which appears to consist of both adsorbed hydrocarbons and graphite. The adsorbed hydrocarbons are removed by hydrogen with fairly low activation energy (∼6.5 kcal/mol) and it is also shown that the rate of olefin metathesis is accelerated by the addition of hydrogen to the reaction mixture. Since this reaction does not require hydrogen to proceed, this effect is ascribed to a removal of these strongly bound hydrocarbons which increases the number of reactions sites on the surface.