cssi/SciSciGPT-SciSciNet huggingface dataset:
Autoregulation of Musashi1 mRNA Translation During Xenopus Oocyte Maturation

The mRNA translational control protein, Musashi, plays a critical role in cell fate determination through sequence-specific interactions with select target mRNAs. In proliferating stem cells, Musashi exerts repression of target mRNAs to promote cell cycle progression. During stem cell differentiation, Musashi target mRNAs are de-repressed and translated. Recently, we have reported an obligatory requirement for Musashi to direct translational activation of target mRNAs during Xenopus oocyte meiotic cell cycle progression. Despite the importance of Musashi in cell cycle regulation, only a few target mRNAs have been fully characterized. In this study, we report the identification and characterization of a new Musashi target mRNA in Xenopus oocytes. We demonstrate that progesterone-stimulated translational activation of the Xenopus Musashi1 mRNA is regulated through a functional Musashi binding element (MBE) in the Musashi1 mRNA 3' untranslated region (3' UTR). Mutational disruption of the MBE prevented translational activation of Musashi1 mRNA and its interaction with Musashi protein. Further, elimination of Musashi function through microinjection of inhibitory antisense oligonucleotides prevented progesterone-induced polyadenylation and translation of the endogenous Musashi1 mRNA. Thus, Xenopus Musashi proteins regulate translation of the Musashi1 mRNA during oocyte maturation. Our results indicate that the hierarchy of sequential and dependent mRNA translational control programs involved in directing progression through meiosis are reinforced by an intricate series of nested, positive feedback loops, including Musashi mRNA translational autoregulation. These autoregulatory positive feedback loops serve to amplify a weak initiating signal into a robust commitment for the oocyte to progress through the cell cycle and become competent for fertilization.
Comparison of extracardiac Fontan techniques: Pedicled pericardial tunnel versus conduit reconstruction☆☆☆

Abstract Objective: This study was designed to determine whether either of 2 alternative methods of extracardiac Fontan reconstruction provides superior results. Methods: We reviewed 58 consecutive Fontan procedures performed between 1995 and 2001 with a pedicled pericardial tunnel (group P, n=21) or an extracardiac conduit of polytetrafluoroethylene or allograft aorta (group C, n=37). Operations were performed with cardiopulmonary bypass at 32°C; an aortic crossclamp was applied in only 6 patients. All group P patients and 33 (89%) group C patients received fenestrations. Results: The groups were similar in terms of age, weight, anatomy, and preoperative hemodynamics. There were 3 hospital deaths (5%; 70% confidence limit, 2%-30%), all in group C. Median durations of mechanical ventilation (group P, 1 day; group C, 1 day), intensive care unit stay (group P, 3 days; group C, 3 days), chest tube drainage (group P, 8 days; group C, 7 days), and hospitalization (group P, 10 days; group C, 9 days) were not significantly different. There were no late deaths. All patients received warfarin sodium, and there were no late strokes. Before the Fontan procedure, 1 patient in group P and 3 patients in group C required pacemaker implants. Of the 51 surviving patients in sinus rhythm before the Fontan procedure, only 1 patient in group C subsequently required a pacemaker. Conclusions: Extracardiac Fontan procedures with either a pericardial baffle or conduit are associated with low operative mortality and low risks of arrhythmia and late thromboembolic complication. J Thorac Cardiovasc Surg 2003;125:465-71
Gamma knife radiosurgery for trigeminal neuralgia: a study of predictors of success, efficacy, safety, and outcome at LSUHSC.

Abstract Background Trigeminal neuralgia (TN) is a painful condition of controversial origin; however, vascular compression of the root entry zone of the trigeminal nerve is thought to be responsible in some cases. Recently, stereotactic radiosurgery has been established as an alternative treatment for medically intractable TN. Methods Forty patients with medically refractory TN underwent gamma knife surgery for pain control at our institution. Dose planning was based on high-resolution, contrast-enhanced, axial, volume acquisition magnetic resonance images. Images were reviewed to detect vascular compression of the trigeminal nerve at the root entry zone by an observer blinded to the affected side and the outcome. Another observer, blinded to radiologic findings, conducted the patient follow-up. Results were classified as excellent and good (favorable outcomes) and failure (unfavorable) based upon the intensity of pain, frequency of episodes, pain medications, and need for additional interventions after radiosurgery. Results Pain was left-sided in 22 patients and right-sided in 18 patients. Vascular compression of the affected nerve at the root entry zone was demonstrable in 14 patients. Prescription dose ranged from 70 to 90 Gy. At a median follow-up of 14 months (range, 3–31 months), 16 patients (40%) had excellent pain control, 12 (30%) had good control, while 12 (30%) had failed treatment. The Kaplan-Meier actuarial pain control rate at 15 months was 82.25 ± 0.8% (95%CI). Magnetic resonance detectable vascular compression did not affect the outcome (p = 0.6). Increasing marginal dose (≥40Gy) was a significant predictor of favorable outcome (p = 0.015). Conclusions gamma knife surgery is an effective and safe treatment for TN. In our study, we found that vascular compression of the nerve at the root entry zone was not a predictor of the outcome of gamma surgery for TN. The outcome improves with marginal prescription dose of 80 Gy or higher.
A Holistic Approach to Schema Matching

Schema matching, which establishes whether two objects are semantically related, has been a focus of data management research due to its critical role in enterprise information integration. Current schema matching techniques typically tend to exploit only a single method selected from matching schema structure, or syntax, or semantics, or data and probability distributions, which reduces the success of schema matching. An alternative approach to improve the effectiveness of schema matching is to use a holistic approach that integrates and generalizes techniques based on structural and syntactic comparisons, as well as probability distribution and mutual information. This paper describes this holistic approach and its implementation, and presents initial results of comparisons with existing techniques.
Fine-grained activity recognition by aggregating abstract object usage

In this paper we present results related to achieving finegrained activity recognition for context-aware computing applications. We examine the advantages and challenges of reasoning with globally unique object instances detected by an RFID glove. We present a sequence of increasingly powerful probabilistic graphical models for activity recognition. We show the advantages of adding additional complexity and conclude with a model that can reason tractably about aggregated object instances and gracefully generalizes from object instances to their classes by using abstraction smoothing. We apply these models to data collected from a morning household routine.
SMALL EMBEDDINGS OF PARTIAL DIRECTED CYCLE SYSTEMS

In this paper, a generalisation of the Andersen, Hilton, Rodger Theorem for embedding partial idempotent latin squares is proved. This result is then used to prove that a partial directed m-cycle system of order n can be embedded in a directed m-cycle system of order (2n + l)"i if m is odd, of order 2nm if m ^ 8 is even, 12n + 1 if m = 6 and approximately In + \/2n if m = 4.
ASSESSING THE UNIT OF MEASUREMENT FOR SCHOOL CLIMATE THROUGH PSYCHOMETRIC AND OUTCOME ANALYSES OF THE SCHOOL CLIMATE SURVEY

This study examines the appropriate unit of theory of school climate while simultaneously conducting a psychometric analysis of a modification of the School Climate Survey for an elementary school population. A conceptualization of school climate as an individual-level property unique to each school participant is compared to the idea that climate is a characteristic of the school with school participants having the role of informants. These two theories are compared by testing their differing implications. The School Climate Survey is found to have a stable and identical factor structure both within and between schools, ratings by different respondent groups are found to be moderately correlated, and average school climate within each school is found to predict a statistically significant amount of the between-school variation in children’s academic achievement and cognitive functioning. Differences between individual raters within each school are not found to have a meaningful relationship to child outc...
Parental Emotional Support and Subsequent Internalizing and Externalizing Problems Among Children

This study examined the association between early emotional support provided by parents and child internalizing and externalizing problems, using a nationally representative, longitudinal sample of 1361 children. Parental emotional support was assessed using the Home Observation for the Measurement of the Environment, incorporating both parent report and interviewer observation. We found that, controlling for child externalizing problems at age 6 years, parental emotional support at age 6 years was negatively related to child externalizing problems at age 8 years. A developmental model that assessed the timing of the emergence of this relationship was then analyzed by including parental emotional support at ages 2, 4, and 6 years as predictors of child externalizing problems at age 8 years. The developmental model suggested that less parental emotional support as early as age 2 years is associated with later externalizing problems in children. This study discusses the importance of very early parental emotional support in promoting positive child development. J Dev Behav Pediatr 26:267-275, 2005. Index terms: parenting, emotional support, child internalizing, child externalizing.
THE BIOLOGICAL DECOMPOSITION OF PLANT MATERIALS PART VIII. THE AVAILABILITY OF THE NITROGEN OF FUNGAL TISSUES

SUMMARY. 1 Various aspects of the availability of the nitrogen, of fungal tissue to micro-organisms have been investigated, with particular reference to the influence of the C/N ratio of the material. 2 Fungal tissue was found to be as suitable a source of nitrogen as ammonium salts and nitrates for the decomposition of straw both by a mixed soil flora and by pure cultures of certain fungi. 3 The liberation of ammonia in sand culture from fungal tissue by pure cultures of reputedly active ammonifiers was measured. 4 The nitrification in soils of a number of samples of fungus tissue was compared with that of artificial mixtures of equal C/N ratio built up from glucose, cellulose and straw, each with added inorganic nitrogen. 5 A very clear correlation was found between the C/N ratio of the fungal material and the nitrogen nitrified. In one series in hill-side soil nitrification increased from 42 to 80 per cent, in 6 months as the ratio decreased from 15.8 to 5.5; in another, from 20 to 75 per cent, as the ratio decreased from 17 to 7. 6 No evidence was found for the existence of a very resistant and unnitrifiable residue from fungal tissue as claimed by some workers, and incomplete nitrification is probably due to the attainment of biological equilibrium or of a state in which change is very slow.
Tantalum oxide nanoscale resistive switching devices: TEM/EELS study (Presentation Recording)

The field of non-volatile memory devices has been boosted by resistive switching, a reversible change in electrical resistance of a dielectric layer through the application of a voltage potential. Tantalum oxide being one of the leading candidates for the dielectric component of resistance switching devices was investigated in this study. 55nm TaOx devices in all states were compared through cross sectional TEM techniques including HRTEM, EELS, and EFTEM and will be discussed in this presentation. Based on the chemical and physical features found in the cross sectioned nanodevices we will discuss the switching mechanism of these nanoscale devices.
Firm-Specific Triggers of LBO Defaults

This study aims to provide a theoretical framework to explicate the specific attributes of leveraged buyouts, which may alter the probability of default in contrast to non-private-equity-backed firms. The author hereby suggests controlling for the asset liquidation potential as an additional source of cash flow available for servicing debt, the valuation of the investment, the strength of the negotiated covenants, the pressure of the target's refinancing need, and the stage of the fund's life cycle. In addition, the model is augmented by the capital market attractiveness, expressed by the debt capital market liquidity and the risk aversion of bond investors. Finally, industry attractiveness in terms of industry rivalry, volatility of the sector, and the historical sector default rates may provide significant insights into the probability of default.
19.6 voltage-scalable frequency-independent quasi-resonant clocking implementation of a 0.7-to-1.2V DVFS System

Clock power remains a substantial contributor to power dissipation, from ultra-low-power to high-performance systems [1, 2, 3]. Recently, resonant clocking has been shown to achieve power reduction in clock distribution networks [2, 3]. However, the limited voltage-frequency (VF) scalability of resonant clocking implementations remains a key drawback. Continued aggressive use of DVFS will require efficient resonant clocking across the increasingly wider operating range of the system. In this paper, we present a test chip implementing quasi-resonant clocking (QRC), incorporating a voltage-scalable, frequency-independent and DVFS-enabled resonant clock architecture. The test chip achieves a 32-to-47% clock power reduction over a 0.7-to-1.2V supply-voltage range.
Effect of clutter on joint radar-communications system performance inner bounds

We analyze the effects of clutter on inner bounds for the performance of a joint radar-communications system. Radar returns from clutter are often characterized by a randomly fluctuating cross section. Hence, statistical methods must be employed to model the clutter and its cross-section. In this paper we consider two clutter models and analyze their effect on the inner bounds on performance of a joint radar-communications system. Bounds on performance of the joint system are measured in terms of data information rate for communications, and radar estimation information rate for the radar.
The fuzzball

The Fuzzball is an operating system and applications library designed for the PDP11 family of computers. It was intended as a development platform and research pipewrench for the DARPA/NSF Internet, but has occasionally escaped to earn revenue in commercial service. It was designed, implemented and evolved over a seventeen-year era spanning the development of the ARPANET and TCP/IP protocol suites and can today be found at Internet outposts from Hawaii to Italy standing watch for adventurous applications and enduring experiments. This paper describes the Fuzzball and its applications, including a description of its novel congestion avoidance/control and timekeeping mechanisms.
Impact of perceived weight stigma among underserved women on doctor–patient relationships

SummaryObjective The aim of this study was to evaluate how perception of weight stigma among underserved women with obesity impacts doctor–patient relationships. Methods This study consisted of an interviewer-administered survey of 149 women with obesity (body mass index (BMI) > 30 kg m−2) immediately after their physician visit at four Federally Qualified Health Centers. Perceptions of weight stigma and physician empathy were measured using the Stigma Situations in Health Care instrument and Consultation and Relational Empathy (CARE) measure, respectively. Associations of CARE and Stigma scores with BMI and patient characteristics were analysed using Mantel–Haenszel chi-squared test and ordinal logistic regression. Results The mean CARE score was 42.1 (standard deviation 8.4; range 11.0–50.0), and mean stigma score was 4.6 (standard deviation 7.6; range 0–43.0). Each increase in BMI category was associated with almost twofold increased odds of higher perception of stigma (odds ratio, 1.90, 95% confidence interval 1.30–2.78, P = 0.001). BMI was not associated with CARE. However, for each increase in stigma category, the odds of lower CARE score doubled (odds ratio, 0.52, 95% confidence interval 0.36–0.75, P = 0.0005). Conclusions While BMI was not associated with perception of physician empathy, higher frequency of weight stigmatizing situations was negatively associated with perception of physician empathy. Reducing weight stigma in primary care could improve doctor–patient relationships and quality of care in patients with obesity.
Effect of natalizumab on brain atrophy and disability progression in multiple sclerosis patients over 5 years

Background and purpose The long-term benefit of natalizumab on brain atrophy progression in multiple sclerosis (MS) patients is unknown. Our aim was to investigate its effect over 5 years. Methods This prospective study included 60 relapsing MS patients who started natalizumab treatment in years 2006−2007. Results At the 5-year follow-up, 20 patients discontinued natalizumab after an average of 29.5 cycles, 27 continued natalizumab treatment with some periods of honeymoon (average of 38.4 infusions) and 13 never stopped natalizumab (average of 60.6 infusions). In multiple linear regression analysis, adjusted for age, sex and baseline magnetic resonance imaging (MRI) status, the number of natalizumab infusions was associated with decrease of relapse rate (adjusted P = 0.037), but no association was found with the progression of disability, accumulation of lesion burden or brain volume loss. However, only one (8%) patient in the continuous monthly group experienced disability progression compared to 10 (37%) in the non-continuous and seven (35%) in the discontinuation natalizumab groups. At the follow-up, two patients had died [one from a fatal case of progressive multifocal leukoencephalopathy (PML) and one from a car accident] and 15 patients were lost to follow-up. There was another case of non-fatal PML over the follow-up. Conclusions In line with previous reports, MS patients with longer and continuous use of natalizumab had fewer relapses and remained stable in their disability status. No difference in lesion burden accumulation or brain atrophy development was found in relation to the duration of natalizumab use. PML occurred in 2.5% of patients in this small sample cohort. Given the increased risk of PML and uncertain benefit of prolonged natalizumab use on clinical and MRI outcomes of disease progression found in this study, a careful risk−benefit therapeutic assessment is mandatory.
Geographic Distribution of Healthy Resources and Adverse Pregnancy Outcomes

Objective To determine the risk of gestational diabetes (GDM) and preeclampsia associated with various community resources. Methods An ecological study was performed in Los Angeles and Orange counties in California. Fast food restaurants, supermarkets, grocery stores, gyms, health clubs and green space were identified using Google © Maps Extractor and through the Southern California Association of Government. California Birth Certificate data was used to identify cases of GDM and preeclampsia. Unadjusted and adjusted risk ratios were calculated using negative binomial regression. Results There were 9692 cases of GDM and 6288 cases of preeclampsia corresponding to incidences of 2.5 and 1.4 % respectively. The adjusted risk of GDM was reduced in zip codes with greater concentration of grocery stores [relative risk (RR) 0.95, 95 % confidence interval (CI) 0.92-0.99] and supermarkets (RR 0.94, 95 % CI 0.90-0.98). There were no significant relationships between preeclampsia and the concentration of fast food restaurants, grocery store, supermarkets or the amount of green space. Conclusion The distribution of community resources has a significant association with the risk of developing GDM but not preeclampsia.
Additions to the Avifauna of the Adelbert Range, Papua New Guinea

This paper reports previously unrecorded populations of thirty-two species of hill forest and montane birds from the Adelbert Range, Papua New Guinea. Three new subspecies are described: Rallicula forbesi parva, Sericornis nouhuysi adelberti, and Amblyornis macgregoriae amati. The avifauna of this range is impoverished, as are avifaunas of other isolated ranges in New Guinea. Adelbert species show subspecific affinities to populations from the ranges of the Huon Peninsula, or from the Central Ranges, or from both. Montane species may be restricted to only a very small part of the Adelbert Range.
Computer Simulation of Concurrent Bulk- and Surface-Initiated Living Polymerization

We use Monte Carlo simulation implementing the bond fluctuation model formalism in the canonical (NVT) ensemble to study living polymerization initiated concurrently in bulk and on flat substrates. Our results reveal that the molecular weights and molecular weight distributions of both classes of polymers depend on the grafting density of the surface-bound polymers (σ) and the fraction of polymers on the surface (η) relative to that in bulk. In general, polymer grafts on the surface possess lower molecular weight and higher polydispersity index compared to their bulk counterparts. The difference between the molecular weight of the two populations of polymers decreases with decreasing σ and increasing η. Our work provides evidence that the common practice of using the molecular weight of bulk-initiated polymers in estimating the grafting density of polymeric anchors on flat substrates is not generally valid.
A comparison of skin tone discrimination among African American men: 1995 and 2003.

This study investigated perceptions of skin tone discrimination among adult African American men. Research suggests that through negative African American stereotypes, out-group members (Whites) perceive light-skinned African Americans favorably and dark-skinned African Americans unfavorably. However, it is unclear how treatment by in-group members (other African Americans) uniquely affects men. Using data from the 1995 Detroit Area Study and the 2003 National Survey of American Life, we investigated these relationships among African American men representing a wide range of socioeconomic groups. We found that African American men’s perceptions of out-group and in-group treatment, respectively, were similar across time. Light-skinned men perceived the least out-group discrimination while dark-skinned men perceived the most out-group discrimination. In appraisals of skin tone discrimination from in-group members, medium-skinned men perceived the least discrimination while both light- and dark-skinned men perceived more in-group discrimination. Additionally, men of lower social economic groups were more affected by skin tone bias than others. Future research should explore the influence of these out- and in-group experiences of skin tone discrimination on social and psychological functioning of African American men.
Follow Suit or Try Another Way:China’s Approach to Catching up with Japan and the United States

This article argues that it would be more difficult for China’s GDP to catch up with the United States by simply repeating the approach to exceeding Japan in 2010.Based on a comparison of indicators in the context of G-20 countries,including GDP,savings,investment,money supply,credit,labor,and productivity,the article heightens the urgency and feasibility to improve efficiency by pushing forward reform and opening-up policy.Only in this way,can China exceed Japan and the United States in a solid and sustainable manner.
Image quality testing and clinical photographs evaluation of 33 magnetic resonance imaging systems

Objective To evaluate the image qualities of medical magnetic resonance imaging(MRI) equipments in Tianjin. Methods Using a phantom of Magphan 170-type, the signal-to-noise ratios(SNR) and the other seven main performance indexes of 33 MRI equipments were measured. The qualities of the photographs taken by the scanners were assessed. Results According to the standard of Specification of Image Quality Test and Evaluation for Medical Magnetic Resonance Imaging Equipmentin, only 18.2% of the scanners passed the SNR control. However, according to the MRI Quality Control Handbook released by MRI Quality Assurance Committee of American College of Radiology, 100% of the scanners passed the SNR control. For the image uniformity, geometric distortion, slice thickness deviation, slice non-uniformity, highcontrast spatial resolution and aspect ratio, the pass rates was 100%, 96.9%, 96.9%, 87.9%, 97.0% and 96.9%, respectively. The assessments of the photographs were graded A in 6 scanners, B in 22 scanners, and C in 5 scanners. Conclusion The imaging qualities of the 33 MRI devices are overall good, fulfill the basic requirements of national standards. However, the detection method of SNR should be further refined and strengthen the quality control through the daily maintenance and stability testing as well the training for the technical staff to ensure the image quality of MRI equipment.
The Hekaton Memory-Optimized OLTP Engine.

Hekaton is a new OLTP engine optimized for memory resident data and fully integrated into SQL Server; a database can contain both regular disk-based tables and in-memory tables. In-memory (a.k.a.Hekaton) tables are fully durable and accessed using standard T-SQL. A query can reference both Hekaton tables and regular tables and a transaction can update data in both types of tables. T-SQL stored procedures that reference only Hekaton tables are compiled into machine code for further performance improvements. To allow for high concurrency the engine uses latch-free data structures and optimistic, multiversion concurrency control. This paper gives an overview of the design of the Hekaton engine and reports some initial results.
Looking for My Rural Identity, Finding Community and Place

Previously in my academic work I have carefully considered how my identities as white, middle class, and female have impacted the ways in which I prepare teachers who come from similar backgrounds as myself. In this self-study, I intended to examine to what extent my identification as “rural” might contribute to my work with those who experience inequities as a result of their being positioned as rural. The themes of community and place figure prominently in what I learned while on a yearlong sabbatical in Australia. My understanding of my rural identity has been informed by the importance of place in building community and connecting to rural contexts. The chapter concludes with how I applied my findings to my practice in the Rural Teacher Residency program in Chico, California.
Power and Conflict Management: The Joban-God Talk

Sara Cobb begins her book, Speaking of Violence by stating that “stories matter. They have gravitas; they are grave. They have weight. They are concrete. They materialize policies, institutions, relationships, and identities.” [1] Applied to the book of Job 1—2, one can ask, how grave is the story of Job? What conflict does it create? What is at stake in this conflict? What does the story concretize? In this paper I point out that there are two narrative approaches to reading Job's conflict with God. One is that Job does not resist divine power and the other is that he does. If we take it that job does not resist divine power, we implicitly begin fostering stories that can create docility/passivity in the face of imperial power. If we argue that he resists divine power, we create stories that enable people to stand up for their freedoms/rights, hence fostering the idea that conflict cannot be solved by docility but by confronting the powers-that-be, which create conflicts in the first place. In this paper, I argue for the later position. [1] Sara Cobb, Speaking of Violence: The Politics and Poetics of Narrative in Conflict Resolution (Oxford and New York, NY: Oxford University Press, 2013), 3.
SU-F-T-538: CyberKnife with MLC for Treatment of Large Volume Tumors: A Feasibility Study

Purpose: CyberKnife is a well-documented modality for SRS and SBRT treatments. Typical tumors are small and 1–5 fractions are usually used. We determined the feasibility of using CyberKnife, with an InCise multileaf collimator option, for larger tumors undergoing standard dose and fractionation. The intent was to understand the limitation of using this modality for other external beam radiation treatments. Methods: Five tumors from different anatomical sites with volumes from 127.8 cc to 1,320.5 cc were contoured and planned on a Multiplan V5.1 workstation. The target average diameter ranged from 7 cm to 13 cm. The dose fractionation was 1.8–2.0 Gy/fraction and 25–45 fractions for total doses of 45–81 Gy. The sites planned were: pancreas, head and neck, prostate, anal, and esophagus. The plans were optimized to meet conventional dose constraints based on various RTOG protocols for conventional fractionation. Results: The Multiplan treatment planning system successfully generated clinically acceptable plans for all sites studied. The resulting dose distributions achieved reasonable target coverage, all greater than 95%, and satisfactory normal tissue sparing. Treatment times ranged from 9 minutes to 38 minutes, the longest being a head and neck plan with dual targets receiving different doses and with multiple adjacent critical structures. Conclusion: CyberKnife, with the InCise multileaf collimation option, can achieve acceptable dose distributions in large volume tumors treated with conventional dose and fractionation. Although treatment times are greater than conventional accelerator time; target coverage and dose to critical structures can be kept within a clinically acceptable range. While time limitations exist, when necessary CyberKnife can provide an alternative to traditional treatment modalities for large volume tumors.
RNAi-Mediated Gene Silencing in Mammalian Cells

Publisher Summary RNA interference (RNAi) is the sequence-specific silencing of gene expression in response to double-stranded (ds) RNA. Biochemical and genetic studies have begun to provide the molecular details for how dsRNA can lead to the targeted disruption and silencing of gene expression. In the first step of the RNAi pathway, long dsRNA is cleaved into siRNAs. The antisense strand of the siRNA guides the endonuclease activity of RISC to the homologous site on the cognate mRNA, resulting in the cleavage of the mRNA in the center of the siRNA–mRNA recognition site. The binding of long dsRNA leads to the activation of the dsRNA-dependent protein kinase (PKR). The demonstration that chemically or enzymatically synthesized siRNAs are capable of effectively silencing gene expression has led to the rapid development of RNAi-based technologies. These technologies have served to address two limitations inherent in the gene silencing by transfection of synthetic siRNAs, the transient nature of the silencing phenotype and the low efficiency of siRNA transfection in certain cell types, particularly primary cells.
Inquiry and wonder in the university classroom

This session will highlight findings from a case study exploring the use of inquiry and wonder as pedagogical tools essential for meaningful engagement with science. This includes exploring current research findings regarding the powerful connection between emotion and learning in science. Lastly, we will brainstorm ideas for bringing these connections into our current classroom practices.
Initial experience withhirudin andstreptokinase in acute myocardial infarction: Results of the thrombolysis in myocardial infarction (TIMI) 6 trial

Abstract Hirudin is a potent, direct, and highly specific inhibitor of both free and clot-bound thrombin. Previous reports have shown hirudin to be superior to heparin when given with tissue plasminogen activator and aspirin for improving the incidence and rate of reperfusion as well as reducing reocclusion of infarct-related arteries. Patients with acute myocardial infarction were randomized to hirudin versus heparin in conjunction with streptokinase (1.5 × 10 6 U) and aspirin (325 mg/day). Study drug treatment was a 5-day infusion of either heparin, as a 5,000 U bolus, followed by a 1,000 U/hour infusion adjusted to a target activated partial thromboplastin time of 65 to 90 seconds (n = 71), or a constant infusion of hirudin at 1 of 3 doses (dose 1, n = 55: 0.15 mg/kg bolus + 0.05 mg/kg/hour infusion; dose 2, n = 31: 0.3 mg/kg bolus + 0.1 mg/kg/hour infusion; or dose 3, n = 36: 0.6 mg/kg bolus + 0.2 mg/kg/hour infusion). The incidence of major hemorrhage was similar between the heparin group (5.6%) and any of the hirudin dose groups (dose 1 = 5.5%, dose 2 = 6.5%, dose 3 = 5.6%). At hospital discharge the occurrence of death, nonfatal reinfarction, congestive heart failure, or cardiogenic shock was greater in patients receiving the lowest dose of hirudin (21.6%) than in those receiving the higher doses of hirudin (dose 2 = 9.7%, dose 3 = 11.4%). A trend toward a reduction in mortality and nonfatal reinfarction was seen at hospital discharge with the 2 higher doses of hirudin (dose 2 = 9.7%, dose 3 = 5.7%) when compared with the lowest dose of hirudin (13.7%) and at 6 weeks (dose 2 = 9.7%, dose 3 = 5.7% vs dose 1 = 17.6%). In this pilot trial, hirudin appeared to be as safe as heparin when given with streptokinase and aspirin to patients with acute myocardial infarction. Although this study was not prospectively designed to detect a difference in efficacy, a trend toward a lower rate of death, reinfarction, cardiogenic shock, and congestive heart failure was observed with the higher doses of hirudin when compared with the lowest dose.
Localization of transforming growth factor beta 1 (TGFβ1) and Smad-4 in dysplastic human cervix

Proc Amer Assoc Cancer Res, Volume 45, 2004 5272 Abnormal regulation of the TGFβ family of proteins and their Smad mediators has been reported in some reproductive tract tumors including cervical cancer. Smad proteins mediate the action of TGFβs. This mediation involves the binding of Smad-4 with another Smad protein family member. This complex migrates to the cell nucleus where it acts to regulate gene expression. The diversity of Smads and TGFβs allows for multiple biological responses. In this study we compared the distribution TGFβ1 and Smad-4, one of its common mediators, in normal and dysplastic human cervix. Tissue samples from subjects with Papanicoloau smears that indicated mild to moderate dysplasia were examined. Slides were prepared for immunocytochemical localization of TGFβ1 and Smad-4 and H&E staining to grade the dysplasia by the Bethesda system. The primary antibodies were obtained from Santa Cruz Biotechnology (Santa Cruz, CA) and the second antibodies were obtained from Vector Diagnostics (Burlingame, CA). TGFβ1 and Smad-4 levels were graded on a 0-3 scale with 0 indicating staining equal to negative control. Levels 1–3 indicated low, medium and intense staining. Staining intensity was compared to non-immune serum control slides. Dysplastic regions of the cervix were also compared to staining patterns in normal areas of the cervix. The dysplasias varied from mild to severe. In the normal cervical epithelium TGFβ1 was localized most strongly (+2) in the keratinized superficial layers of the cervical epithelium. In dysplastic areas TGFβ1 was at levels below +1 intensity. Smad-4 was expressed more widely in normal cervical epithelia. Intense (+3) Smad-4 staining was found in the nuclei of cervical epithelium at all levels from deep to superficial. In contrast, in dysplastic areas, Smad-4 was reduced. We found nuclear staining only in the basal cell layer. In more apical cells the nuclei were not stained and cytoplasm staining was reduced. Smad proteins are localized to the nuclei when TGFB signaling is active. Nuclear staining did not occur in dysplastic regions. These results suggest active roles for Smad-4 and TGFB1 in differentiation of normal cervical epithelia and their possible deregulation in dysplasia. We chose Smad-4 for our study because this protein is involved in the action of all TGFβs. However, different Smad-4 complexes can have similar or antagonistic actions, and in future studies we will examine the distributions of the other Smad proteins and TGFβs in the cervix. Our goal is to clarify the roles of Smad proteins and TGFβs in normal cervical epithelial differentiation and determine whether these proteins are deregulated in dysplastic tissue.
The Cytotoxicity and Genotoxicity of Particulate and Soluble Cobalt in Human Urothelial Cells

Cobalt use is increasing particularly due to its use as one of the primary metals in cobalt-chromium-molybdenum (CoCrMo) metal-on-metal prosthetics. CoCrMo is a high-strength, wear-resistant alloy with reduced risk for prosthetic loosening and device fracture. More than 500,000 people receive hip implants each year in the USA which puts them at potential risk for exposure to metal ions and particles released by the prosthetic implants. Data show cobalt ions released from prosthetics reach the bloodstream and accumulate in the bladder. As patients with failed hip implants show increased urinary and blood cobalt levels, no studies have considered the effects of cobalt on human urothelial cells. Accordingly, we investigated the cytotoxic and genotoxic effects of particulate and soluble cobalt in urothelial cells. Exposure to both particulate and soluble cobalt resulted in a concentration-dependent increase in cytotoxicity, genotoxicity, and intracellular cobalt ions. Based on intracellular cobalt ion levels, we found, when compared to particulate cobalt, soluble cobalt was more cytotoxic, but induced similar levels of genotoxicity. Interestingly, at similar intracellular cobalt ion concentrations, soluble cobalt induced cell cycle arrest indicated by a lack of metaphases not observed after particulate cobalt treatment. These data indicate that cobalt compounds are cytotoxic and genotoxic to human urothelial cells and solubility may play a key role in cobalt-induced toxicity.
Improving Survival in Patients With Eisenmenger Syndrome: Are We Any Closer?

Article, see p 1432 The population with Eisenmenger syndrome is only 1 of several congenital heart disease (CHD) cohorts that has pulmonary arterial hypertension. Other groups include those with hemodynamically significant left-to-right shunting (both correctable and noncorrectable) where cyanosis is not a feature, those with small cardiac defects (eg, coincidental CHD), those with pulmonary hypertension after successful congenital heart defect repair, and those with left-sided CHD (including left heart obstructive lesions and congenital cardiomyopathies). Even within the simple class of patients with Eisenmenger syndrome, a variety of underlying cardiac defects exist, including simple atrial septal defect, ventricular septal defect, patent ductus arteriosus, and more complex anatomy resulting in a fairly heterogeneous group of patients. Although the underlying pathology in the pulmonary vascular bed may be similar, the pathophysiology is clearly different. Eisenmenger syndrome is a multisystem disorder associated with a multitude of complications and reduced survival. It has generally been accepted that survival prospects of patients with Eisenmenger syndrome are substantially better than other forms of pulmonary arterial hypertension (PAH). Although some patients with Eisenmenger syndrome expire during childhood or young adulthood, a sizable proportion survives to middle and old age despite the degree of pulmonary hypertension, detrimental long-term effects of cyanosis, polycythemia, accompanying renal dysfunction, and poor exercise tolerance. Compared with patients who develop PAH with a structurally normal heart, the population with Eisenmenger syndrome has had their heart defect throughout life, thus potentially facilitating adaptation of the right ventricle to the pressure overload at an early age. Nevertheless, estimating the survival prospects of patients with Eisenmenger syndrome and identifying those at high risk for imminent death is considered important to inform when therapy should be initiation or intensified. The study by Kempny et al1 in this issue …
Examining Trends Over Time in International Law Decisions of the US Courts of Appeals

This paper examines trends in decision-making over time in the US Courts of Appeals in cases involving international law. It argues that given the explosion in the number of cases, as well as in the number of appellate judges, judges in the modern (post-1948) era are more likely to rely on cues from the Executive in decision-making. On the other hand, judges from the early era (1900-1947) had fewer issues to master as well as more personal experience with international law cases, thus it was expected that they would be less likely to rely on Executive position-taking.
Comparison of forced-air and water-circulating warming for prevention of hypothermia during transcatheter aortic valve replacement.

Introduction Transcatheter Aortic Valve Replacement (TAVR) procedures at our institution were complicated by perioperative hypothermia despite use of the standard of care forced-air convective warming device (the BairHugger, Augustine Medical Inc, Eden Prairie, MN, USA). To remedy this problem, we initiated a quality improvement process that investigated the use of a conductive warm water-circulating device (the Allon ThermoWrap, Menen Medical Corporation, Trevose, PA, USA), and hypothesized that it would decrease the incidence of perioperative hypothermia. Methods We compared two different intraoperative warming devices using a historic control. We retrospectively reviewed intraoperative records of 80 TAVRs between 6/2013 and 6/2015, 46 and 34 of which were done with the forced-air and water-circulating devices, respectively. Continuous temperature data obtained from pulmonary artery catheter, temperature upon arrival to cardiothoracic ICU (CTU), age, BSA, height, and BMI were compared. Results Patients warmed with both devices were similar in terms of demographic characteristics. First recorded intraoperative temperature (mean 36.26 ± SD 0.61 vs. 35.95 ± 0.46°C, p = 0.02), lowest intraoperative temperature (36.01 ± 0.58 vs. 34.89 ± 0.76°C, p<0.001), temperature at the end of the procedure (36.47 ± 0.51 vs. 35.17 ± 0.75°C, p<0.001), and temperature upon arrival to the CTU (36.35 ± 0.44 vs. 35.07 ± 0.78°C, p<0.001) were significantly higher in the water-circulating group as compared to the forced-air group. Conclusion A quality improvement process led to selection of a new warming device that virtually eliminated perioperative hypothermia at our institution. Patients warmed with the new device were significantly less likely to experience intraoperative hypothermia and were significantly more likely to be normothermic upon arrival to the CTU.
Neural Correlates of Verbal Episodic Memory and Lexical Retrieval in Logopenic Variant Primary Progressive Aphasia.

Objective: Logopenic variant primary progressive aphasia (lvPPA) is commonly associated with Alzheimer’s disease (AD) pathology. But lvPPA patients display different cognitive and anatomical profile from the common clinical AD patients, whose verbal episodic memory is primarily affected. Reports of verbal episodic memory difficulty in lvPPA are inconsistent, and we hypothesized that their lexical retrieval impairment contributes to verbal episodic memory performance and is associated with left middle temporal gyrus atrophy. Methods: We evaluated patients with lvPPA (n=12) displaying prominent word-finding and repetition difficulties, and a demographically-matched cohort of clinical Alzheimer’s disease (AD, n=26), and healthy seniors (n=16). We assessed lexical retrieval with confrontation naming and verbal episodic memory with delayed free recall. Whole-brain regressions related naming and delayed free recall to gray matter atrophy. Medial temporal lobe (MTL) subfields were examined using high in-plane resolution imaging. Results: lvPPA patients had naming and delayed free recall impairments, but intact recognition memory. In lvPPA, delayed free recall was related to naming; both were associated with left middle temporal gyrus atrophy but not MTL atrophy. Despite cerebrospinal fluid evidence consistent with AD pathology, examination of MTL subfields revealed no atrophy in lvPPA. While AD patients displayed impaired delayed free recall, this deficit did not correlate with naming. Regression analyses related delayed free recall deficits in clinical AD patients to MTL subfield atrophy, and naming to left middle temporal gyrus atrophy. Conclusion: Unlike amnestic AD patients, MTL subfields were not affected in lvPPA patients. Verbal episodic memory deficit observed in lvPPA was unlikely to be due to a hippocamal-medicated mechanism but appeared to be due to poor lexical retrieval. Relative sparing of MTL volume and intact recognition memory are consistent with previous reports of hippocampal-sparing variant cases of AD pathology, where neurofibrillary tangles are disproportionately distributed in cortical areas with relative sparing of the hippocampus. This suggests that AD neuropathology in lvPPA may originate in neuronal networks outside of the MTL, which deviates from the typical Braak staging pattern of spreading pathology in clinical AD.
ANGLE-BOUNDED OPERATORS AND UNIQUENESS OF PERIODIC SOLUTIONS OF CERTAIN ORDINARY DIFFERENTIAL EQUATIONS

Publisher Summary This chapter describes the angle-bounded operators and uniqueness of periodic solutions of certain ordinary differential equations. Angle-bounded linear mappings are like positive symmetric mappings in a Hilbert space to a large extent in the sense that they admit a splitting much in the same way as the square root of a positive symmetric mapping in a Hilbert space. The chapter highlights the usefulness and simplicity of angle-bounded mappings in uniqueness problems. It discusses the uniqueness of periodic solutions of certain ordinary differential equations by highlighting the usage of angle-bounded mappings.