cssi/SciSciGPT-SciSciNet huggingface dataset:
A nonpeptidyl thrombopoietin receptor agonist SB559457, induces apoptosis in primary human myeloid leukemia cells.

2392 The treatment of autoimmune, or iatrogenic thrombocytopenia remains problematic. When stimulation of endogenous megakaryocyte (MEG) development with thrombopoietin (Tpo), the natural ligand of the thrombopoietin receptor (TpoR) failed as a treatment strategy, the development of small molecule TpoR agonists (TpoRA) was stimulated. In the course of investigating the biological effects, and mechanism of action, of SB559457 (a nonpeptidyl, hydrazone class, TpoRA supplied by GlaxoSmithKline (GSK), Collegeville, PA) we found that the molecule robustly stimulated human megakaryocytopoiesis in vitro In anticipation of TpoRA use in the treatment of patients with hematologic malignancies, we also evaluated SB559457’s effect on human leukemia cell (HLC) growth in vitro since it is known that HLCs may express TpoR Surprisingly, SB559457 not only failed to stimulate HLC growth, it proved toxic to primary acute myelogenous leukemia (AML) cells Specifically, we examined the effects of SB559457 on samples obtained from 21 patients with AML, 7 with ALL, and 5 with CML In 20 of 21 primary AML samples exposed to SB559457 (5μM) a large fraction (70-90%) of cells died between days 3 and 6 of culture, while untreated control cells survived No significant effects on cell growth or viability were observed in the ALL or CML patient samples To investigate the mechanism(s) of AML cell killing, we examined signaling cascades initiated by SB559457 compared to recombinant human Tpo (rhTpo) Initially, we employed N2C-Tpo cells (a Tpo dependent megakaryoblastic cell line that express TpoR) and focused on kinases known to be phosphorylated after TpoR activation; STAT5, ERK, p70S6, and ribosomal kinase S6 When N2C-Tpo cells were stimulated with rhTpo (2 8μM, 30min) all these kinases were highly phosphorylated In contrast, none were phosphorylated in SB559457 (5μM, 30min) stimulated cells Normal human CD34+ marrow cells were next examined using same conditions like for N2C-Tpo cells In contrast to N2C-Tpo cells, ERK, and p70S6 kinases were both phosphorylated after exposure to SB559457 but STAT5 remained unphosphorylated Since AML cells may require STAT5 activation for growth, we hypothesized that perturbation of STAT5 activation might be involved in the apoptotic mechanism The molecular consequences of differential signaling were pursued by Affymetrix GeneChip analysis in 5 separate primary AML cell samples stimulated for 6 hours with either Tpo or SB559457 Remarkably, statistically significant difference in expression was found in only 2 of 22000 genes represented on the chips: GAPDH and Redd1 - both genes are induced in stressed cells undergoing apoptosis We therefore hypothesize that inability of SB559457 to phosphorylate STAT5, and associated induction of GAPDH and Redd1 provide clues to its ability to induce leukemic cell death
Connexin 43 gap junctional intercellular communication inhibits evx1 expression and joint formation in regenerating fins.

The gap junction protein Connexin 43 (Cx43) contributes to cell fate decisions that determine the location of fin ray joints during regeneration. Here, we provide insights into how Cx43, expressed medially, influences changes in gene expression in lateral skeletal precursor cells. Using the Gap27 peptide inhibitor specific to Cx43, we show that Cx43-gap junctional intercellular communication (GJIC) influences Cx43-dependent skeletal phenotypes, including segment length. We also demonstrate that Cx43-GJIC influences the expression of the Smp/β-catenin pathway in the lateral skeletal precursor cells, and does not influence the Sema3d pathway. Moreover, we show that the cx43lh10 allele, which has increased Cx43 protein levels, exhibits increased regenerate length and segment length. These phenotypes are rescued by Gap27, suggesting that increased Cx43 is responsible for the observed Cx43 phenotypes. Finally, our findings suggest that inhibition of Cx43 hemichannel activity does not influence Cx43-dependent skeletal phenotypes. These data provide evidence that Cx43-GJIC is responsible for regulating cell fate decisions associated with appropriate joint formation in the regenerating fin.
Nutrient requirements of walleyes (Stizostedion vitreum vitreum)

Two experiments were conducted to determine the crude protein requirement and the effect of dietary protein on body composition of fingerling walleyes. In the first experiment, quadruplicate lots of 55 fish (x = 8 g) were housed in 130-liter flow-through tanks and fed one of six isocaloric (3720 kcal/kg ME) diets ranging from 37 to 57% protein. In the second experiment, quadruplicate lots of four fish (x = 50 g) housed in 18-liter cylindrical tanks were fed one of six isocaloric diets (3470 kcal/kg ME) ranging from 32 to 52% protein. Anchovy meal was the primary protein source, and synthetic amino acids were supplemented to match the amino acid profile of the unfertilized walleye egg. Tanks were supplied with 3 liters of 21 C water per minute. Photoperiod was automatically controlled providing 12 hours of light and simulated dawndusk periods. Fish were collected at the beginning and end of each experiment for body composition analysis. Three mathematical models were fit to the data. The best fitting model, as determined by the lowest residual sum of squares, was used to estimate the protein requirement. Weight gain increased quadratically with increasing dietary protein to a breakpoint at 50% protein (p<.05) in the first experiment and 42% (p<.10) in the second experiment. The grams of carcass protein, ash and moisture gained increased linearly and carcass fat quadratically with increased dietary protein in both experiments. Maximum fat gain was predicted to occur at 48 and 42% protein in experiments one and two, respectively. Carcass condition factor was optimized at 43% protein (p<.05) in
Microencapsulation of hemp seed oil by pea protein isolate−sugar beet pectin complex coacervation: Influence of coacervation pH and wall/core ratio

Abstract The objective of this study was to investigate the impact of coacervation formation pH (3.5 and 2.5) and wall/core ratio (1:1, 2:1 and 4:1) on physicochemical properties of spray-dried hemp seed oil (HSO) microcapsules by means of pea protein isolate (PPI)–sugar beet pectin (SBP) complex coacervates. In general, both phase behaviors and viscoelastic properties of PPI−SBP coacervates were affected by the wall/core ratio. The coacervates structures were highly dependent on the coacervation formation pH, which greatly impacted the spray drying efficiency (PY), encapsulation efficiency (EE), oil distributions in microcapsules and oxidative stability of HSO. At the pHopt (3.5), PPI−SBP complex coacervates possess denser structure owing to the greater electrostatic interaction, whereas softer structure was formed at pH 2.5 as evidenced by rheological properties and FTIR. Because of the homogeneous large pore size and smooth inner surface of liquid coacervates formed at pH 2.5, spray-dried microcapsules had a remarkable higher EE than that formed at pH 3.5. However, the oxidative stability of HSO in PPI−SBP microcapsules prepared at pH 2.5 was significantly shortened due to the weaker electrostatic interaction strength between PPI−SBP, resulting in the partially broken PPI−SBP network caused by the spray drying process. As such, some hollow particle and incomplete particle shape was observed in SEM and CLSM image, which promoted the lipid oxidation of encapsulated HSO. In terms of wall/core ratio, the lower wall/core ratio had lower EE, higher percentage of surface oil on microcapsules, and lower oxidative stability of HSO.
Factors Associated with Early versus Delayed Expansion of Acute Subdural Hematomas Initially Managed Conservatively.

Acute subdural hematomas (ASDHs) are highly morbid and increasingly common. Hematoma expansion is a potentially fatal complication, and few studies have examined whether factors associated with hem...
Response: Dempster and Corkill's “Interference and Inhibition in Cognition and Behavior: Unifying Themes for Educational Psychology”

Dempster and Corkill present a persuasive case for the utility of the concepts of interference and inhibition in their review, “Interference and Inhibition in Cognition and Behavior: Unifying Themes for Educational Psychology.” We were especially attracted to their drawing attention to the role of inhibition in learning and to the argument that closer links of educational psychology to neuroscience are needed. At a general level of analysis, we agreed that the concepts of interference and inhibition can provide a unifying framework for describing phenomena in several areas of inquiry, but these concepts seemed to us to be less useful for understanding structured, meaningful learning in instructional domains. Overall, we viewed Dempster and Corkill's review as a creative effort that usefully redirects our attention to neglected basic learning processes.
Measuring Target Predictability for Optimal Environment Design

Motivated by the study of deceptive strategies, this paper considers the problems of detecting an agent's objective from its partial path and determining an optimal environment to enable such detection. We focus on a scenario where the agent's objective is to reach a particular target state from a set of potential targets, while an observer seeks to correctly identify such a state prior to the agent reaching it. In order to quantify the predictability of the agent's target given the observed path, we introduce the notion of target entropy, where higher entropy implies lower target predictability. The problem of optimal environment design, i.e., optimal target placement, then becomes a minimax problem with target entropy as an objective function. Under the assumption that the agent chooses its path towards its target maximally unpredictably, we consider models of the agent's motion on both discrete and continuous state spaces. Using dynamic programming, we establish a simple way of computing target entropy for the discrete state space. In a continuous state space, we obtain a formula for target entropy by employing geometrical arguments on volumes of hypersimplices. Additionally, we provide an algorithm yielding an optimal environment in a discrete state space, discuss its computational complexity, and provide a computationally simpler approximation that yields a locally optimal environment. We validate our results on a previously developed model of deceptive agent motion.
Improving Weibull distribution estimation for generalized Type I censored data using modified SMOTE

Abstract In reliability analysis, lifetime data may be heavily censored and this censoring can have an adverse effect on parameter estimates. Using maximum-likelihood estimation (MLE) to estimate the parameters of reliability functions is common in practice especially with (right) censored observations. However, estimating parameters using MLE introduces an inherent bias which tends to increase as the number of observations decreases and/or the censoring proportion increases. Reliability demonstration tests (RDT) typically use a Type I or Type II censoring mechanism; however, in many real-life applications a generalized Type I censoring mechanism, where each observation has its own censoring times, is often more applicable. These examples occur in structural risk analyses, obsolescence predictions, and medical studies where items under study may have different introduction dates but have lifetimes from the same probability distribution. This research improves Weibull distribution parameter estimates by combining a modified MLE and an oversampling method. Empirical results are presented with recommendations for preferred oversampling sizes, dependent upon the sample size and censoring proportion, using the Kullback–Leibler divergence to measure the difference between the known distribution and estimated distributions. A case study is provided to highlight the method’s use in an obsolescence prediction application.
Rapid Rise of Pediatric Telehealth During COVID-19 in a Large Multispecialty Health System.

Background: Before the COVID-19 pandemic, telemedicine use for outpatient pediatric specialty care was low. Stay-at-home orders (SHO) prompted rapid upscaling of telemedicine capabilities and upski...
A Comparison of Sustainability and Sustainable Value in Three Industries: Chemical, Pharmaceutical and Food.

The future and value of firms, their industries and the economy may well hinge in the long run on the outcome of sustainability efforts across a multitude of industries on a global basis. The authors have previously reported on the sustainability programs and sustainable value in the Food and Beverage industry using twenty of the Top 100 Food and Beverage Firms as a surrogate for the industry’s status in this regard. The objective of the current research is to compare the results from the study of the Food Industry to that of the Chemical and Pharmaceutical industries. The comparison will be made using sustainability program category as defined by the authors, ratings based on the rubric developed by the authors and the overall sustainability score for each firm. These results will be contrasted with each firm’s revenue and income over a five-year period from 2013 through 2017. An in depth analysis and critique will be presented with the objective of identifying the effect of financials on sustainability and sustainability on financial performance.
Characteristics of infective endocarditis in a cancer population.

Background Infective endocarditis (IE) is more common in patients with cancer as compared with the general population. Due to an immunocompromised state, the need for invasive procedures, hypercoagulability and the presence of indwelling catheters, patients with cancer are particularly predisposed to the development of IE. Objectives Limited information exists about IE in patients with cancer. We aimed to evaluate the characteristics of patients with cancer and IE at our tertiary care centre, including a comparison of the microorganisms implicated and their association with mortality. Methods A retrospective chart review of patients with cancer who had echocardiography for suspicion of endocarditis was conducted. A total of 56 patients with a confirmed diagnosis of cancer and endocarditis, based on the modified Duke criteria, were included in the study. Baseline demographics, risk factors for developing IE, echocardiography findings, microbiology and mortality data were analysed. Results Following the findings of vegetations by echocardiography, the median survival time was 8.5 months. Staphylococcus aureus was the most common organism identified as causing endocarditis. The mitral and aortic valves were the most commonly involved sites of endocarditis. Patients with S. aureus endocarditis (SAE) had a significantly poorer survival when compared with patients without SAE (p=0.0217) over the 12-month period from diagnosis of endocarditis. Conclusions Overall survival of patients with cancer and endocarditis is poor, with a worse outcome in patients with SAE.
Rhetoric and Composition: An Introduction

Rhetoric and composition is an academic discipline that informs all other fields in teaching students how to communicate their ideas and construct their arguments. It has grown dramatically to become a cornerstone of many undergraduate courses and curricula, and it is a particularly dynamic field for scholarly research. This book offers an accessible introduction to teaching and studying rhetoric and composition. By combining the history of rhetoric, explorations of its underlying theories, and a survey of current research (with practical examples and advice), Steven Lynn offers a solid foundation for further study in the field. Readers will find useful information on how students have been taught to invent and organize materials, to express themselves correctly and effectively, and how the ancient study of memory and delivery illuminates discourse and pedagogy today. This concise book thus provides a starting point for learning about the discipline that engages writing, thinking, and argument.
Paradigm shifts in neural induction.

La «molecularisation» de la biologie du developpement a d'abord ete consideree comme une menace pour la discipline. Cependant, des apercus nouveaux, issus de l'analyse de l'expression des genes transformerent bientot le domaine d'une anatomie experimentale en celui de l'expression des genes. Un des principaux domaines a etre transforme, d'une etude anatomique en une etude moleculaire, fut celui de l' « induction embryonnaire primaire ». Les analyses moleculaires montraient que certains concepts fondamentaux tires d'une approche de l'induction embryonnaire primaire par l'embryologie experimentale se revelaient faux. Tout d'abord, le destin neural des cellules n'etait pas induit. Ce qui etait induit etait le destin epidermique. L'etat neural etait le destin defaillant et non induit des tissus ectodermiques. En second lieu, l'induction embryonnaire primaire n'etait pas reservee uniquement aux vertebres. La corde neurale ventrale des insectes est formee en utilisant les memes mecanismes que ceux employes par le tube neural dorsal des vertebres. En troisieme lieu, la formation du cerveau est une affaire distincte, differente de celle de la colonne vertebrale. En depit de ces differences, il existe une continuite claire et forte entre la tradition de l'embryologie experimentale et celle de la genetique moleculaire; ces donnees nouvelles sont considerees par de nombreux geneticiens du developpement comme un renforcement plutot qu'une destruction de la science anterieure.
Gen2: eIF2α protein kinase (S. cerevisiae)

Gcn2 regulates protein synthesis at the initiation step by phosphorylating the α subunit of eIF2 on Ser51. Activation of the wild-type enzyme in response to amino acid starvation produces a low level of eIF2a phosphorylation that stimulates the translation of GCN4 mRNA by a unique reinitiation mechanism. Because Gcn4 is a transcriptional activator of amino acid biosynthetic genes, Gcn2 is required for growth when amino acids are limiting. Mutationally activated forms of Gcn2 produce a high level of eIF2α phosphorylation that inhibits total protein synthesis, similar to what occurs in mammalian cells upon activation of the eIF2α kinases PKR or HRI. The only known substrate for Gcn2 is eIF2α. A sequence of 18 amino acids (NIEGMILLSELSRRRIRSI) surrounding S51 is identical between yeast and human eIF2α, and Gcn2 phosphorylates rabbit eIF2α in vitro. These considerations make it likely that Gcn2 closely resembles the mammalian kinases regarding specificity determinants.
Formal education about medication errors in internal medicine clerkships.

tion in recognition, identification, and prevention of such events in US undergraduate internal medicine clerkships has not been recently studied. We studied existing curricula about adverse drug reactions and interactions in US internal medicine clerkship programs. Methods. We conducted a survey of all US undergraduate internal medicine clerkship programs in the spring of 2000. A 2-page, 1-stage survey instrument was sent to all internal medicine clerkship directors (N=105) identified by using the Clerkship Directory in Internal Medicine (CDIM) membership directory. Repeat surveys were sent to nonresponders. We chose internal medicine clerkship programs because, based on national averages, medical students spend an average of 12 weeks in this rotation, the most of any required clinical experience. 3 Also, the discipline of internal medicine trains future physicians to care for patients with complex medical problems that frequently require multiple medications, which may place patients at an increased risk of experiencing an adverse drug reaction. 4 The survey questions addressed adverse event curricula and learning experiences. We specifically asked about total lecture hours, rotations with formal adverse drug event instruction, clerkship directors’ content knowledge of the Institute of Medicine report 1 on medical errors, and clerkship directors’ willingness to add adverse drug reaction/interaction educational modules. Descriptive statistics were computed for each survey question. Questions were asked with 1 to 5 Likert scale responses in which response 3 was used as the midline “undecided” anchor. Results. Of the program directors surveyed, 79 (75%) responded. The mean average of total formal lectures on all topics was 32 (range, 0-160) hours. Sixteen percent of internal medicine clerkships had formal lectures on adverse drug reactions/ interactions. Sixty-five percent of the programs surveyed responded that they would incorporate 1 or 2 (mean average, range 1-10) hours of educational material on adverse drug reactions/interactions, if educational modules were available. Interestingly, 35% of clerkship directors had little or no familiarity with the Institute of Medicine report on medical errors, even though this survey was performed during a period
Audio Production and Critical Listening: Technical Ear Training

Introduction 1 Listening 1.1 Everyday Listening 1.2 What is Technical Ear Training? 1.3 What is Timbre? 1.4 Shaping Sounds 1.5 Sound Reproduction System Configurations 1.6 The Listening Environment 2 Spectral Balance and Equalization 2.1 Types of Filters and Equalizers 2.2 Practice 2.3 Exercises 3 Spatial Attributes 3.1 Time Delay 3.2 Reverberation 3.3 Delay and Comb Filtering 3.4 Reverberation in Multichannel Audio 3.5 Description of the Software Training Module 3.6 Mid-Side Matrixing, Stereo Shuffling, and Polarity Reversal 3.7 Summary 4 Dynamic Range and Levels 4.1 Level Changes 4.2 Compressors and Limiters 4.3 Expanders and Gates 5 Distortion and Noise 5.1 Clipping and Overdrive 5.2 Noise, Hum and Buzz 5.3 Quantization Distortion: Bit Rate Reduction 6 Amplitude Envelope 6.1 Digital Audio Editing: The Source-Destination Technique 6.2 Software Exercise Module 6.3 Focus of the Exercise 6.4 Conclusions 7 Analysis of Sound 7.1 Analysis of Sound from Electroacoustic Sources 7.2 Graphical Analysis of Sound 7.3 Multichannel Audio 7.4 Selecting Listening Material 7.5 Analysis Examples 7.6 Sound Enhancers on Media Players 7.7 Analysis of Sound from Acoustic Sources 7.8 Conclusions A About the software practice modules Bibliography
Implementing a Quantum Algorithm with Exchange-Coupled Quantum Dots: A Feasibility Study

We present Monte Carlo wavefunction simulations for quantum computations employing an exchange-coupled array of quantum dots. Employing a combination of experimentally and theoretically available parameters, we find that gate fidelities greater than 98% may be obtained with current experimental and technological capabilities. Application to an encoded 3 qubit (nine physical qubits) Deutsch-Josza computation indicates that the algorithmic fidelity is more a question of the total time to implement the gates than of the physical complexity of those gates. PACS: 81.07.Ta, 02.70.Ss, 03.67.Lx, 03.65.Yz
Julian English Outside of Samarra

F ALL THE MEMORABLEcharacters in John O'Hara's fiction, surely none is as intriguing as Julian English, the protagonist of Appointment in Samarra. The events of the three days surrounding Christmas 1930 which culminate in Julian's suicide in his garage by his Cadillac motor car continue to have a grip­ ping effect on readers. Part of the staying power of Appointment in Samarra lies in the tantalizing question of the motivations for Julian's suicide. On the book's publication in 1934, reviewers questioned these motives, and they have been the subject of ongoing critical debate ever since. 1 O'Hara's Pennsylvania novels and stories can be examined together as an attempt to create a larger fictional landscape. Other chroniclers of fictional re­ gions such as William Faulkner have made use of the same characters across several books. Similarly, O'Hara incorporates many of his principal Gibbsville characters as minor figures in much of the fiction set in what he called "my Pennsylvania protectorate," even though he made no attempt to integrate his works into a comprehensive story. Careful readers of the O'Hara canon will be aware ofthe fact that Julian English makes cameo appearances, or is the subject of discussion, in other O'Hara novels and stories. If we accept the notion that 0'Hara has created a distinct and coherent fictional landscape that extends over numerous novels, novellas, and short stories, it then seems useful to examine his treatment of Julian English in these other works in order to see what addi­ tionallight, if any, can be shed on the somewhat enigmatic portrait we have of him in Appointmentin Samarra. Julian makes his first appearance outside of Appointment in Samarra in A Rage to Live, the 1949 novel that marked O'Hara's return to life in Pennsylva­ nia as a source for his fiction. Near the end of the book, Grace Caldwell Tate, now a widow, visits Gibbsville to attend the SummerAssembly at the Lantenengo Country Club. The year is 1920. Julian English is a twenty year old college student who meets, dances, and flirts with the thirty-seven year old Grace. This brief encounter with Grace Tate reinforces much of what we know about Julian from Appointment in Samarra. First, he has had too much to drink. Further­ more, it is also painfully evident that his relationship with his parents, espe
Adjuvant chemotherapy for the "oldest old" ovarian cancer patients: can we anticipate toxicity-related treatment failure in a vulnerable population?

BACKGROUND: Patients aged ≥80 years who are diagnosed with advanced ovarian cancer (OC) have been reported to have a poor prognosis. In the current study, chemotherapy‒related toxicity data were evaluated between patients aged ≥80 years and those aged <80 years. METHODS: Patients with OC who underwent cytoreductive surgery with chemotherapy were included. Self-reported toxicity data were obtained from National Cancer Institute Common Toxicity Criteria (CTC) forms. Objective indicators of status including albumin level, weight, and creatinine clearance were abstracted both before and after therapy. Data were compared between patients by decade of age. RESULTS: A total of 246 patients were included. A presenting Karnofsky performance status >2 was recorded in 17% of patients aged ≥80 years versus 0% to 4% of patients aged 90% versus 69% in those aged ≥80 years (P < .0001). Standard‒dose combination therapy was used in 72% to 86% of patients aged <80 years versus 28% of patients aged ≥80 years (P < .0001). Patients aged ≥80 years completed ≥6 cycles of therapy approximately 57% of the time versus 84% to 97% of the time for those aged <80 years (P = .0001). CTC forms identified no self-reported toxicities to be more common among patients aged ≥80 years. Multivariate logistic regression identified creatinine clearance <65 mL/minute (odds ratio [OR] of 4.6), 5% weight loss (OR of 2.5), prechemotherapy albumin level of <2 g/dL (OR of 3.65), and initiation of therapy with a single agent (OR of 3.9) as independent predictors of failure to complete chemotherapy. CONCLUSIONS: Despite initial treatment modifications as well as toxicity assessment, only 57% of patients aged ≥80 years completed planned chemotherapy. It was confirmed that further studies into the pharmacokinetics of chemotherapy in the elderly and more sensitive assessment of therapy‒related toxicity are required. Cancer 2009. © 2009 American Cancer Society.
At What Cost?: Blind Testing, Eyewitness Identification, and the Question of What Can and Cannot Be Counted as a Cost of Reducing Information Available for Decision

One theme of the conference for which this piece was written is “When does less information result in better decisions?” In keeping with that theme, I am taking up an issue which raises a central question concerning what we mean by “information,” and what counts as “less information” and “better decisions.” In what follows, I will dissent, at least in part, from the position of the prominent eyewitness identification researcher Steven Clark, set forth in a recent article in the journal Perspectives on Psychological Science, who appears to hold that in evaluating reforms in eyewitness identification procedures, all losses of selections that are in fact true perpetrator selections must be counted as costs of the proposed reform in evaluating the wisdom of the reform. I will take the position that this is clearly not true in regard to the administration of such line-ups “double blind,” that is, their administration in such a way that the person conducting the procedure has no knowledge of the target of the lineup (or at least of the target’s position in the lineup array), and therefore cannot cue the witness, consciously or unconsciously, about the hoped-for selection. Ultimately, however, I will support Professor Clark’s position that losses of accurate identifications may properly be counted as costs in evaluating some other proposed reforms of eyewitness identification procedures, particularly sequential presentation, but I will conclude that in that case, based on the knowledge currently available, that the epistemic and moral benefits of sequential presentation outweigh such costs.
Holocene fire activity as a record of past environmental change

Publisher Summary This chapter discusses some of the recent advances, including efforts to better understand the processes that introduce charcoal into lakes and wetlands; refine the methods to interpret these deposits; and evaluate the response of fire to climate and vegetation controls operating on different time scales based on paleoecological evidence, paleoclimate simulations, and modern assessments. High-resolution charcoal records, obtained from the sediments of lakes and wetlands, are available from several sites in North America and provide information on changes in fire regime occurring on annual-to-millennial time scales during the Holocene. When charcoal time series are decomposed, it is possible to distinguish between a slowly varying component that represents variation in fuel composition and hydrology and charcoal peaks that signify fire episodes. The influence of large-scale controls of climate on fire patterns, including variations in summer insolation during the Holocene, is evident in the temporal and spatial variations in fire reconstructions in western and northeastern North America and from an analysis of atmospheric circulation features that give rise to fires.
Heavy truck trajectory matching and simulation with VDANL

In this paper, a driver model is designed and developed including steering control loop and speed control loop for heavy truck trajectory matching problem. The objective is to match the simulation results with a set of data from field test, (e.g. trajectory, yaw rate, velocity, lateral acceleration), and to validate truck simulation model for the heavy truck simulation model for the heavy truck system for further vehicle maneuvering study. To this aim, a good driver model which can best interpret driver maneuver from the field test data and keep the vehicle moving according to the maneuver stably is important. Based on previous work, a two-loop look-ahead yaw rate feedback perception and PI compensation steering strategy is developed and achieved very good matching results. Stability is proved and comparison with other kind of driver model is given. Simulations are done in VDANL.
The challenge of intelligent sensing of monitoring and control

Intelligent sensors offer new capabilities in process measurement. Traditional control and system theory models do not adequately consider the measurement uncertainty information and the nonperiodic sampling possible from intelligent sensors. A new modeling framework for systems exhibiting these irregular observations is introduced. The framework uses linear constraints and a variation of descriptor system models to represent relational dynamics and set-valued observation information. The use of the model framework for set-valued state estimation is illustrated. >
Structure of a RING E3 Trapped in Action Reveals Ligation Mechanism for the Ubiquitin-like Protein NEDD8

Most E3 ligases use a RING domain to activate a thioester-linked E2∼ubiquitin-like protein (UBL) intermediate and promote UBL transfer to a remotely bound target protein. Nonetheless, RING E3 mechanisms matching a specific UBL and acceptor lysine remain elusive, including for RBX1, which mediates NEDD8 ligation to cullins and >10% of all ubiquitination. We report the structure of a trapped RING E3-E2∼UBL-target intermediate representing RBX1-UBC12∼NEDD8-CUL1-DCN1, which reveals the mechanism of NEDD8 ligation and how a particular UBL and acceptor lysine are matched by a multifunctional RING E3. Numerous mechanisms specify cullin neddylation while preventing noncognate ubiquitin ligation. Notably, E2-E3-target and RING-E2∼UBL modules are not optimized to function independently, but instead require integration by the UBL and target for maximal reactivity. The UBL and target regulate the catalytic machinery by positioning the RING-E2∼UBL catalytic center, licensing the acceptor lysine, and influencing E2 reactivity, thereby driving their specific coupling by a multifunctional RING E3.
Magnetic Resonance Imaging-Guided Catheter Interventions in Congenital Heart Disease

Magnetic resonance imaging (MRI) has long been recognized as a useful technique for guiding diagnostic and therapeutic procedures. Biopsies have been guided by MRI since the 1980s1; neurosurgery followed soon thereafter.2 Excellent soft tissue contrast and accurate spatial localization and display in 3 dimensions were particular advantages of MRI over other modalities in neurological and body imaging. The application of MRI to cardiovascular interventions, however, has been much slower because of the technical challenges related mainly to cardiac motion. More recently, experimental work in animal models of acquired and congenital heart disease has demonstrated the feasibility of MRI-guided interventional cardiac catheterization.3–5 In 2003, Razavi et al6 published the first clinical experience with cardiac catheterization aided by MRI in 16 children and adults with congenital heart disease. In this issue of Circulation , Krueger and colleagues7 report on extending this concept to another clinical application: MRI-guided balloon angioplasty of aortic coarctation. Using commercially available catheters filled with a diluted solution of iron oxide particles, a homemade nonmetallic guidewire, and passive catheter tracking, the procedure was judged technically successful in all of the 5 patients in whom it was attempted. Article p 1093 The experience reported by Krueger et al7 highlights a familiar reality for pediatric cardiologists. Because most equipment is designed for adults, pediatric cardiologists frequently operate in a world of imperfect tools, bedside modifications of equipment, and off-label use of devices and diagnostic techniques. Most of the tools used to perform the procedure described in this report were not designed for …
Overexpression of 12/15-lipoxygenase increases anxiety behavior in female mice

The 12/15-lipoxygenase (12/15-LO) is an enzyme widely distributed in the central nervous system, and it has been involved in the neurobiology of Alzheimer's disease. However, whether this pathway is also involved in neuropsychiatry disorders including anxiety remain to be investigated. In this study we investigated whether genetic over-expression of 12/15-LO (H12/15-LO) modulates some elevated plus maze and Y-maze behaviors. While we observed that H12/15LO mice at the age of 12 months did not differ from wild type in the elevated plus maze paradigm, when they reached the age of 15 months, they manifested an increased anxiety-like behavior compared with controls. By contrast, no differences between the 2 groups at both ages when they were tested for working memory in the Y-maze paradigm. Additionally, we found that the change in anxiety was associated with a reduction in phosphorylation of the transcription factor CREB (cAMP response element-binding protein), and a significant increase in the synaptic protein synaptophysin. Taken together our findings suggest a novel role for 12/15-LO in the pathogenesis of anxiety-like behavior.
Optimizing Information Flow in Small Genetic Networks. II. Feed-forward Interactions

Central to the functioning of a living cell is its ability to control the readout or expression of information encoded in the genome. In many cases, a single transcription factor protein activates or represses the expression of many genes. As the concentration of the transcription factor varies, the target genes thus undergo correlated changes, and this redundancy limits the ability of the cell to transmit information about input signals. We explore how interactions among the target genes can reduce this redundancy and optimize information transmission. Our discussion builds on recent work [Tka\ifmmode \check{c}\else \v{c}\fi{}ik et al., Phys. Rev. E 80, 031920 (2009)], and there are connections to much earlier work on the role of lateral inhibition in enhancing the efficiency of information transmission in neural circuits; for simplicity we consider here the case where the interactions have a feed forward structure, with no loops. Even with this limitation, the networks that optimize information transmission have a structure reminiscent of the networks found in real biological systems.
Nonpharmacological treatment of tics in Tourette syndrome adding videotape training to self-hypnosis.

Objective This case series examines the practicality of using a standardized method of training children in self-hypnosis (SH) methods to explore its efficiency and short-term efficacy in treating tics in patients with Tourette syndrome. Methods The files of 37 children and adolescents with Tourette syndrome referred for SH training were reviewed, yielding 33 patients for analysis. As part of a protocol for SH training, all viewed a videotape series of a boy undergoing SH training for tic control. Improvement in tic control was abstracted from subjective patient report. Results Seventy-nine percent of the patients trained in this technique experienced short-term clinical response, defined as control over the average 6-week follow-up period. Of the responders, 46% achieved tic control with SH after only 2 sessions and 96% after 3 visits. One patient required 4 visits. Conclusions Instruction in SH, aided by the use of videotape training, augments a protocol and probably shortens the time of training in this technique. If SH is made more accessible in this way, it will be a valuable addition to multi-disciplinary management of tic disorders in Tourette syndrome.
The General Law of Fall of a Small Spherical Body through a Gas, and its Bearing upon the Nature of Molecular Reflection from Surfaces

Law of fall of a small spherical body through a gas at any pressure.—(1) Theoretical derivation. When the ratio of free path to radius of droplet, l / a, is small, the resistance to motion is due entirely to viscosity and is proportional to a, while when l / a is large the resistance is due entirely to the inertia of the molecules hit and is proportional to a^2. The equation: F=6 pi eta av [1+A'l / a]-1 satisfies both these theoretical conditions. From Kinetic theory, however, it has been shown that A' is not constant but varies from a lower theoretical limit of.7004 (diffuse reflection) for l / a small, to 1.164 for l / a large. We therefore put A'=A+B epsilon -ca / l and write the complete equation: F=6 pi eta av [1+(A+B epsilon -ca / l)l / a]-1. (2) Experimental verification. By the oil drop method, values of A' have been determined for a wide range of values of l / a, from 0.5 to 134, for oil drops in air. These results are found to agree within the experimental error of ±2 per cent or less with the theoretical equation, and give A=.864, B=0.290, c=1.25. A discussion of results obtained with other drops indicates that while A varies with the nature of the gas and even more with the material of the droplet, (A+B) is within two or three per cent the same for most sorts of particles which might settle through the atmosphere. (3) Differentiation between diffuse reflection, specular reflection, radial reflection, and condensation and re-evaporation of molecules. Radial reflection is shown to be thermodynamically and dynamically impossible; condensation and re-evaporation to be inconsistent with the observed value of (A+B). This observed value is satisfied only by a combination of about 1/10 of specular reflection with 9/10 of diffuse reflection, this last being defined as a reemission from each element of surface and in such directions as to satisfy the Maxwell distribution law, of all molecules which impinge upon that element. The agreement adds new evidence for the existence of specular reflection of molecules since 1/10 had also been indicated by the values of A previously obtained for oil-drops in air. (4) Effects of mechanical roughness of the surface. The apparent discrepancies between the author's results and those of Knudsen and Gaede, which seemed to indicate complete diffuse reflection, are explained by the effects of minute mechanical proturberances which are thought to have existed on the insides of these authors' capillary tubes.
Opening up new fronts in the fight against cholesterol

An unexpected connection between a secretory protein called PCSK9 and Sec24A, a well known protein-transport protein, could lead to the development of novel treatments for patients with high levels of low-density lipoproteins in their blood.
Δ1-11-oxa-11-deoxycortisol: A new antiglucocorticoid with activity in vivo

Abstract A new steroid-like compound, Δ 1 -11-oxa-11-deoxycortisol, was tested in a one-week growth suppression, thymus suppression and adrenal weight suppression bioassay for possible glucocorticoid antagonist activity in vivo . We hypothesized that this compound would have antiglucocorticoid activity based on previous studies of 11-deoxycortisol and Δ 1,9 (11) -11-deoxycortisol, which were optimal glucocorticoid antagonists in vivo in adrenalectomized rats, but which lost antiglucocorticoid activity in intact animals, apparently due to adrenal 11β-hydroxylation. Thus, Δ 1 -11-oxa-11-deoxycortisol, a compound which cannot undergo llβ-hydroxylation, was synthesized and tested as an antiglucocorticoid. This analog had an affinity for the rat thymus glucocorticoid receptor similar to that of its parent compounds (Ki 0.9-3.1×10 −7 M). A dose of 1 mg rat antagonized the effect of 15μg of dexamethasone in the growth suppression assay (p 1 -11-oxa-11-deoxycortisol did not exhibit glucocorticoid activity in any of the three assays. These data suggest that Δ 1 -11-oxa-11-deoxycortisol may be a pure competitive antagonist of dexamethasone.
Human cytomegalovirus DNA: BamHI, EcoRI and PstI restriction endonuclease cleavage maps

The cloned HindIII fragments of human cytomegalovirus (HCMV) strain AD169 DNA were mapped with respect to the BamHI, EcoRI and PstI restriction endonuclease cleavage sites. Composite restriction endonuclease cleavage maps for the entire virus genome were constructed using the previously established linkages between the HindIII fragments.
Health Technology Assessment Implementation The Politics of Ethics

Using a 2009 American debate on a federal public health recommendation on mammography screening for women under the age of 50 as a case study, it is argued that public acceptance of health technology assessment (HTA) depends on the ethical acceptability of its recommendations. At the same time, that acceptability cannot be separated from the politics and values of the health care system of which it is part. In the United States, those values display a sharp ideological split between a conservative individual-based ethic and a liberal community-oriented ethic. A clash of this kind cannot be solved by invocation of ethical principles when it is those principles themselves that are in conflict. Inevitably HTA acceptance is threatened by this conflict as is the fate of health care reform.
Isolation of a Lipopolysaccharide Mutant of Neisseria gonorrhoeae: An Analysis of the Antigenic and Biologic Differences

Analysis of the surface constituents of a pyocin 611 131-resistant variant of strain no. JW-31 of Neisseria gonorrhoeae revealed substantial differences in the lipopolysaccharide (LPS) but not changes in the auxotype or outer-membrane proteins. Immunodiffusion and an enzyme-linked immunosorbent assay showed that the variant strain (no. JW-31R) lost both the LPS serotype and the variable antigens while retaining at least a portion of the common determinant. The use of monoclonal antibody indicated that LPSs from strain no. JW-31R and pyocin 611 131-resistant strains of other LPS serotypes lack a D-galactosaminyl-D-galactopyranosyl-D-glucose moiety. The LPS-derived polysaccharide from strain no. JW-31 binds to wheat-germ lectin in precipitin and inhibition systems, whereas the JW-31R polysaccharide exhibits a markedly reduced affinity. In the presence of normal human serum, 99% of strain no. JW-31R was killed within 20 min and strain no. JW-31 was not.
Osseous metaplasia in ovarian papillary serous cystadenocarcinoma

The finding of osseous metaplasia within an ovarian papillary serous cystadenocarcinoma is very rare. A review of the medical literature reveals only two previously published cases where mature bone was found in an ovarian serous cystadenocarcinoma. This report presents an additional case of this unusual phenomenon whose clinical significance remains uncertain.
Metal binding and substrate positioning by evolutionarily invariant U6 sequences in catalytically active protein-free snRNAs

We have previously shown that a base-paired complex formed by two of the spliceosomal RNA components, U6 and U2 small nuclear RNAs (snRNAs), can catalyze a two-step splicing reaction that depended on an evolutionarily invariant region in U6, the ACAGAGA box. Here we further analyze this RNA-catalyzed reaction and show that while the 5′ and 3′ splice site substrates are juxtaposed and positioned near the ACAGAGA sequence in U6, the role of the snRNAs in the reaction is beyond mere juxtaposition of the substrates and likely involves the formation of a sophisticated active site. Interestingly, the snRNA-catalyzed reaction is metal dependent, as is the case with other known splicing RNA enzymes, and terbium(III) cleavage reactions indicate metal binding by the U6/U2 complex within the evolutionarily conserved regions of U6. The above results, combined with the structural similarities between U6 and catalytically critical domains in group II self-splicing introns, suggest that the base-paired complex of U6 and U2 snRNAs is a vestigial ribozyme and a likely descendant of a group II-like self-splicing intron.
The use of crown ethers to access new M[Al2R6X] species. Synthesis and crystal structure of [K · dibenzo-18-crown-6] [Al2Me6Cl] · 2 C6H6

Potassium chloride does not react with trimethylaluminium in benzene in the absence of a crown ether. With the addition of dibenzo-18-crown-6, a normal liquid clathrate ensues. The composition of the parent compound has been established by a single crystal X-ray diffraction study. The space group is monoclinicP21/c with unit cell dimensionsa=21.319(8),b=9.512(4),c=21.081(8) A, β=93.79(3)°, andρcalc1.15 g cm−3 forZ=4. Refinement led to a final conventionalR value of 0.049 for 2224 observed reflections. The anion has the expected angular geometry (Al−Cl−Al=120.0(1)°). There are two different types of benzene in the crystalline solid. One is associated with the K+ ion, while the other exists in layers normal to thea axis.