cssi/SciSciGPT-SciSciNet huggingface dataset:
A prospective outcomes study of four-corner wrist arthrodesis using a circular limited wrist fusion plate for stage II scapholunate advanced collapse wrist deformity.

Background: Scapholunate advanced collapse wrist deformity is a common pattern of degenerative arthrosis of the wrist. This study prospectively evaluated a series of patients who underwent four-corner fusion using a circular plate internal fixation technique. Methods: Patients with symptomatic stage II scapholunate advanced collapse wrist deformity were treated with scaphoid excision and four-corner fusion using the Spider Limited Wrist Fusion Plate (KMI, San Diego, Calif.). Patients were prospectively evaluated at 6 months and 1 year using a standard study protocol with radiographs, functional tests, and an outcomes questionnaire. Outcomes were compared with those of historical series from the literature. Results: Eleven patients were enrolled and 10 patients completed their 1-year follow-up. Grip strength, lateral pinch strength, and Jebsen-Taylor test scores at 1 year were not significantly different from preoperative values. Mean active range of motion was 87 degrees preoperatively and 74 degrees at 1-year follow-up (p = 0.19). The Michigan Hand Outcomes Questionnaire showed no significant improvement in function, activities of daily living, work, pain, or patient satisfaction. The mean pain scores decreased from 54 preoperatively to 42 1–year postoperatively (p = 0.30), indicating persistent wrist discomfort. Three patients had broken screws: one was asymptomatic, one required 3 months of strict wrist immobilization, and one was reoperated for symptomatic nonunion. Conclusions: Four-corner fusion using the first-generation Spider plate technique has the advantage of earlier mobility and more patient comfort from absence of protruding Kirschner wires; however, patients continued to have disabling pain, functional limitations, work impairment, and low satisfaction scores postoperatively. Although limited by a small patient sample, this series presents outcomes data that may be useful in counseling patients who are contemplating four-corner fusion using this internal fixation device. Further investigation is necessary to evaluate the biomechanical properties of the Spider plate. The data suggest that better implants should be designed to avoid implant failure, which occurred in three of the 11 patients in this series.
Automated Simplification of Full Chemical Mechanisms

A code has been developed to automatically simplify full chemical mechanisms. The method employed is based on the Intrinsic Low Dimensional Manifold (ILDM) method of Maas and Pope. The ILDM method is a dynamical systems approach to the simplification of large chemical kinetic mechanisms. By identifying low-dimensional attracting manifolds, the method allows complex full mechanisms to be parameterized by just a few variables; in effect, generating reduced chemical mechanisms by an automatic procedure. These resulting mechanisms however, still retain all the species used in the full mechanism. Full and skeletal mechanisms for various fuels are simplified to a two dimensional manifold, and the resulting mechanisms are found to compare well with the full mechanisms, and show significant improvement over global one step mechanisms, such as those by Westbrook and Dryer. In addition, by using an ILDM reaction mechanism in a CID code, a considerable improvement in turn-around time can be achieved.
Pyrolysis oil substituted epoxy resin: Improved ratio optimization and crosslinking efficiency

The objective of this study was to determine the compatibility of whole pyrolysis oil (PO) of pine as a substitute for the phenolic component of epoxy resins (ER). Pyrolysis oil-based epoxy resin (POBER) was synthesized by modification of EPON828 ER with PO at various mixing ratios (1 : 3–1 : 8, PO:EPON828, w/w). Acetone extraction determined that a ratio of 1 : 7–1 : 8 resulted in a fully reacted thermoset, leaving neither PO nor EPON828 in a significantly unreacted state. Dynamic mechanical analysis (DMA) revealed that a ratio of 1 : 8 produced the highest storage modulus (E’); in addition, it was determined that this ratio provided a superior glass transition temperature (Tg) of 120°C and crosslinking density of 1891 mol/m3. FTIR spectra concluded that the reaction between the EPON828 and PO was complete at the 1 : 8 ratio, citing the removal of hydroxyl and epoxide peaks within the cured product. © 2015 Wiley Periodicals, Inc. J. Appl. Polym. Sci. 2015, 132, 42239.
Deep-water microbialites of the Mesoproterozoic Dismal Lakes Group: microbial growth, lithification, and implications for coniform stromatolites

Offshore facies of the Mesoproterozoic Sulky Formation, Dismal Lakes Group, arctic Canada, preserve microbialites with unusual morphology. These microbialites grew in water depths greater than several tens of meters and correlate with high-relief conical stromatolites of the more proximal September Lake reef complex. The gross morphology of these microbial facies consists of ridge-like vertical supports draped by concave-upward, subhorizontal elements, resulting in tent-shaped cuspate microbialites with substantial primary void space. Morphological and petrographic analyses suggest a model wherein penecontemporaneous upward growth of ridge elements and development of subhorizontal draping elements initially resulted in a buoyantly supported, unlithified microbial form. Lithification began via precipitation within organic elements during microbialite growth. Mineralization either stabilized or facilitated collapse of initially neutrally buoyant microbialite forms. Microbial structures and breccias were then further stabilized by precipitation of marine herringbone cement. During late-stage diagenesis, remaining void space was occluded by ferroan dolomite cement. Cuspate microbialites are most similar to those found in offshore facies of Neoarchean carbonate platforms and to unlithified, buoyantly supported microbial mats in modern ice-covered Antarctic lakes. We suggest that such unusual microbialite morphologies are a product of the interaction between motile and non-motile communities under nutrient-limiting conditions, followed by early lithification, which served to preserve the resultant microbial form. The presence of marine herringbone cement, commonly associated with high dissolved inorganic carbon (DIC), low O2 conditions, also suggests growth in association with reducing environments at or near the seafloor or in conjunction with a geochemical interface. Predominance of coniform stromatolite forms in the Proterozoic—across a variety of depositional environments—may thus reflect a combination of heterogeneous nutrient distribution, potentially driven by variable redox conditions, and an elevated carbonate saturation state, which permits preservation of these unusual microbialite forms.
RNA directed therapeutics: mechanisms and status

Progress in antisense technology has identified multiple post hybridization mechanisms that have been successfully exploited to produce pharmacological effects in cells, animals and humans. Advances in understanding the pharmacokinetics and toxicological properties of various types of oligoneucleotides have also been reported. Together these data support optimism that RNA-based therapeutics may bring value. In this very brief review, I focus on the advances in understanding the molecular mechanisms by which antisense drugs work with particular focus on RNase H1 and RISC mediated target reduction.
Rho-family GTPases: it's not only Rac and Rho (and I like it).

The Rho-family proteins make up a major branch of the Ras superfamily of small GTPases. To date, 22 human genes encoding at least 25 proteins have been described. The best known `classical9 members are RhoA, Rac1 and Cdc42. Highly related isoforms of these three proteins have not been studied as intensively, in part because it has been assumed that they are functionally identical to their better-studied counterparts. This now appears not to be the case. Variations in C-terminal-signaled modifications and subcellular targeting cause otherwise highly biochemically related isoforms (e.g. RhoA, RhoB and RhoC) to exhibit surprisingly divergent biological activities. Whereas the classical Rho GTPases are regulated by GDP/GTP cycling, other Rho GTPases are also regulated by other mechanisms, particularly by transcriptional regulation. Newer members of the family possess additional sequence elements beyond the GTPase domain, which suggests they exhibit yet other mechanisms of regulation.
Computer Literacy Preparation

This paper addresses three sets of perplexing factors of conundrums - ambivalence, ambiguity, and alienation - associated with computerization in the human services that have copmlicated and confounded the task of computer literacy perparation. The primary focus is on dilemmas encountered, and at times generated, by educators in social work programs, particularly masters level training. Recommendations for constructive approaches to ameliorating these dilemmas and to anticipating future needs are detailed.
Partitioning polyhedral objects into nonintersecting parts

An algorithm is described for partitioning intersecting polyhedrons into disjoint pieces and, more generally, removing intersections from sets of planar polygons embedded in three space. Polygons, or faces, need not be convex and may contain multiple holes. Intersections are removed by considering pairs of faces and slicing the faces apart along their regions of intersection. To reduce the number of face pairs examined, bounding boxes around groups of faces are checked for overlap. The intersection algorithm also computes set-theoretic operations on polyhedrons. Information gathered during face cutting is used to determine which portions of the original boundaries may be present in the result of an intersection, a union, or a difference of solids. The method includes provisions to detect and in some cases overcome, the effects of numerical inaccuracy on the topological decisions that the algorithm must make. The regions in which ambiguous results are possible are flagged so that the user can take appropriate action. >
The Relationship Between Intimal Tears During Coronary Angioplasty and Fibrinopeptide A

Arterial injury during routine percutaneous trans-luminal coronary angioplasty (PTCA) may stimulate clotting mechanisms. Excessive (i.e., angiographically visible) arterial trauma might accordingly predispose to a greater tendency for thrombosis. This study evaluates whether arterial trauma (i.e., angiographically visible intimal tears and arterial dissections) is related to evidence of active thrombosis. Fibrinopeptide A (FPA), a sensitive marker of thrombin activity, was measured in 79 patients undergoing elective PTCA immediately following angioplasty, as well as prior to hospital discharge (mean 2 days post-PTCA). Levels > 2.0 ng/mL were considered elevated. Intimal tears were visualized in 41 patients. Of these 41, 31 had elevated FPA levels (sensitivity = 0.76). This association between FPA elevation and intimal tears was significant (P = 0.033). Of the remaining 38 patients without intimal tears, 20 had elevated FPA levels (specificity = 0.47). Concomitant arterial dissection, as well as an intimal tear, was found in four patients with elevated FPA and in one patient with normal FPA. Conclusion. Arterial trauma during PTCA is accompanied by a greater degree of ongoing thrombosis. Although FPA elevation was not specific for intimal tears, a highly significant association with intimal tears was observed. Further study may yield even more specific hematologic parameters on ongoing early thrombosis following PTCA, particularly in patients with intimal tears. (J Interven Cardiol 1989:2:3)
An efficient hierarchical generalized linear mixed model for pathway analysis of genome-wide association studies

Motivation: In genome-wide association studies (GWAS) of complex diseases, genetic variants having real but weak associations often fail to be detected at the stringent genome-wide significance level. Pathway analysis, which tests disease association with combined association signals from a group of variants in the same pathway, has become increasingly popular. However, because of the complexities in genetic data and the large sample sizes in typical GWAS, pathway analysis remains to be challenging. We propose a new statistical model for pathway analysis of GWAS. This model includes a fixed effects component that models mean disease association for a group of genes, and a random effects component that models how each gene's association with disease varies about the gene group mean, thus belongs to the class of mixed effects models. Results: The proposed model is computationally efficient and uses only summary statistics. In addition, it corrects for the presence of overlapping genes and linkage disequilibrium (LD). Via simulated and real GWAS data, we showed our model improved power over currently available pathway analysis methods while preserving type I error rate. Furthermore, using the WTCCC Type 1 Diabetes (T1D) dataset, we demonstrated mixed model analysis identified meaningful biological processes that agreed well with previous reports on T1D. Therefore, the proposed methodology provides an efficient statistical modeling framework for systems analysis of GWAS. Availability: The software code for mixed models analysis is freely available at http://biostat.mc.vanderbilt.edu/LilyWang. Contact:lily.wang@vanderbilt.edu; zhongming.zhao@vanderbilt.edu Supplementary information:Supplementary data are available at Bioinformatics online.
Printer and Scribe: Caxton, the Polychronicon, and the Brut

On June 10, 1480, William Caxton issued his edition of the Chronicles of England, based on the Middle English prose Brut. On August 18 of the same year he issued the Description of Britain, a short work adapted from John Trevisa's translation of Ranulph Higden's Polychronicon. Two years later, at some point between July 2 and November 20, 1482, Caxton published his full edition of Trevisa's Polychronicon, and on October 8 of the same year he issued a second edition of the Chronicles of England.' Caxton's choice of texts shows his usual sound business sense, giving the public popular works in printed form for which it had already shown a taste in manuscript form.2 Among secular works the Brut was unsurpassed in popularity in England; there survive at least 170 manuscripts in English, 50 in Anglo-Norman, and 15 in Latin. After its appearance in print the work sustained its popularity and appeared in thirteen editions between 1480 and 1528.3 Higden's Latin Polychronicon survives in at least 118 manuscripts and
FIT HARRT Plus: A Study of Participant Informed Text Messages to Promote Physical Activity in Adolescent and Young Adult African American Women

project began in June 2012. The intervention involved screening each adolescent woman on initial entry to the juvenile detention center for the date of her last sexual encounter using a new emergency contraception screening form approved by medical administrators. Physician notification took place if the last reported sexual encounter occurred within five days prior to arrival. All eligible patients presented to the medical clinic for counseling the same day of admission or the following day for overnight admissions. When feasible, physicians offered and prescribed emergency contraception immediately. Medical staff and physicians documented screening, counseling, offering of EC and acceptance or refusal of EC in the patient’s medical record. We calculated a sample size of 42 in the pre and post-intervention groups to achieve 90% power, alpha 0.05. We performed statistical analysis using 2 x 2 contingency tables and Fisher’s exact test. Results: The population consisted of young women aged 11 e 17 years seen in the medical department at the juvenile detention center from November 2010 to July 2013. The pre-intervention group included charts reviewed prior to June 2012 (n1⁄4 49) and the post-intervention group included charts reviewed from June 2012 to July 2013 (n 1⁄4 104). Of those encounters, 14 and 27 adolescents, in the pre and post intervention groups respectively, were eligible to receive emergency contraception by reporting sexual activity within the five days prior to admission. With the addition of the emergency contraception screening form, the number of youth screened for EC eligibility increased significantly from 55% preintervention to 80% post-intervention (p < .05). The number of eligible young women offered EC also increased from 21% preintervention to 96% post-intervention (p < .05). While not statistically significant, the number of eligible young women taking EC likewise increased from 14% pre-intervention to 41% postintervention. The majority of post-intervention eligible patients declined EC for the following reasons: desired pregnancy, “If I am pregnant, then I am,” and “I don’t want to take it.” Conclusions: Applying a universal and standardized screening and counseling procedure results in increased EC awareness and utilization among detained young women. Timely access to EC may result in decreased unintended pregnancies among these especially high risk teens. Preventing teen pregnancies reduces abortions, miscarriages, teen parenting and its consequences. Sources of Support: None.
Paleolimnology of Lake Tanganyika, East Africa, over the past 100 k yr

New sediment core data from a unique slow-sedimentation rate site in Lake Tanganyika contain a much longer and continuous record of limnological response to climate change than have been previously observed in equatorial regions of central Africa. The new core site was first located through an extensive seismic reflection survey over the Kavala Island Ridge (KIR), a sedimented basement high that separates the Kigoma and Kalemie Basins in Lake Tanganyika. Proxy analyses of paleoclimate response carried out on core T97-52V include paleomagnetic and index properties, TOC and isotopic analyses of organic carbon, and diatom and biogenic silica analyses. A robust age model based on 11 radiocarbon (AMS) dates indicates a linear, continuous sedimentation rate nearly an order of magnitude slower here compared to other core sites around the lake. This age model indicates continuous sedimentation over the past 79 k yr, and a basal age in excess of 100 k yr. The results of the proxy analyses for the past ~ 20 k yr are comparable to previous studies focused on that interval in Lake Tanganyika, and show that the lake was about 350 m lower than present at the Last Glacial Maximum (LGM). Repetitive peaks in TOC and corresponding drops in δ 13 C over the past 79 k yr indicate periods of high productivity and mixing above the T97-52V core site, probably due to cooler and perhaps windier conditions. From ~ 80 through ~ 58 k yr the δ 13 C values are relatively negative (–26 to –28‰) suggesting predominance of algal contributions to bottom sediments at this site during this time. Following this interval there is a shift to higher values of δ 13 C, indicating a possible shift to C-4 pathway-dominated grassland-type vegetation in the catchment, and indicating cooler, dryer conditions from ~ 55 k yr through the LGM. Two seismic sequence boundaries are observed at shallow stratigraphic levels in the seismic reflection data, and the upper boundary correlates to a major discontinuity near the base of T97-52V. We interpret these discontinuities to reflect major, prolonged drops in lake level below the core site (393 m), with the lower boundary correlating to marine oxygen isotope Stage 6. This suggests that the previous glacial period was considerably cooler and more arid in the equatorial tropics than was the last glacial period.
16-channel oversampled analog-to-digital converter

Oversampled analog-to-digital conversion has been demonstrated to be an effective technique for high resolution analog-to-digital (A/D) conversion that is tolerant to process imperfections. The area and power budget of conventionally designed oversampled analog-to-digital converters has precluded their application from areas where a large number of low frequency signals need to be converted simultaneously. A new oversampled A/D design methodology is proposed to cut the area and power budget per channel of an oversampled analog-to-digital converter. The design and implementation of a 16-channel oversampled analog-to-digital converter is presented which can be used as the core of the multichannel data acquisition system. The prototype achieved 80 dB of signal-to-noise-plus-distortion over 1 kHz, -80 dB of crosstalk and used less than 20 mW of power excluding clock generation. >
Hyperthermia and Surface Morphology of P388 Ascites Tumour Cells: Effects of Membrane Modifications

SummaryThe quantitative distribution of cell surface alterations of heated P388 ascites tumour cells was determined by scanning electron microscopy. Cells harvested from host animals maintained on a standard rodent chow diet or one high in saturated fatty acids responded differently, to identical hyperthermic treatment in vitro, to cells obtained from animals on a highly unsaturated diet. The morphological response of cells from chow fed animals was modified by addition to the incubation medium, of procaine, a membrane-active drug. The pattern of response observed after these cells were heated in the presence of procaine resembled that seen following heat treatment of ascites cells obtained from animals fed diet high in unsaturated fatty acids. These data are consistent with the hypothesis that a cell's response to hyperthermic insult is related to its membrane fluidity at the time of treatment.
Cognitive therapy with couples

Although behavior therapists who treat distressed marriages traditionally have acknowledged that spouses’ cognitive appraisals of each other’s behavior play a role in relationship dysfunction, interventions focusing on cognitive components of relationship problems clearly have played a secondary or even a minor role in formal behavioral approaches. However, due to the influence of a general growth of interest in cognitive variables in behavioral models and to the recognition that spouses’ negative beliefs and attitudes easily can undermine even the best conceived behavior-change programs (Jacobson & Margolin, 1979), significant attention now is being paid to the development of assessment and treatment procedures for cognitive factors. In the general cognitive model, an individual’s emotional and behavioral responses to a stimulus (internal or external) are mediated by his or her perception and interpretation of the stimulus rather than elicited directly by objective characteristics of the stimulus (Beck, 1976; Meichenbaum, 1977). In an interpersonal system such as a marriage, the members of the relationship continuously provide stimuli for each other and actively construe the behaviors they exchange. Because marital satisfaction is a subjective state that is related to proportions of idiosyncratically defined pleasing and displeasing behaviors exchanged by spouses (Jacobson & Margolin, 1979; Weiss, 1978), understanding and changing a distressed relationship necessitates attention to cognitive events in the marriage.
Rites of passage through puberty: A complex genetic ensemble

Worldwide, puberty is recognized by various cultures and celebrated as a rite of passage into adulthood. The methodical drumbeat of these religious and social ceremonies foreshadows the rhythm of reproduction that, in many ways, marks the final stage of development. Despite its social and physiological significance, including perpetuation of the species, the pathways that regulate the onset of puberty have evaded traditional physiological inquiries. No clear hormonal or metabolic trigger has been identified as a switch that activates the hypothalamic gonadotropin-releasing hormone (GnRH) pulse generator (1). Instead, geneticabnormalities that preclude puberty have provided the major insights into the pathways that are critical for the development and maturation of the reproductive axis (2, 3). Perhaps the best candidate for regulating the onset of puberty is kisspeptin, the ligand for the receptor encoded by GPR54, a gene identified as a cause of recessive hypogonadotropic hypogonadism (4, 5). The report by Pitteloud et al. (6) in this issue of PNAS identifies loss-of-function mutations in the prokineticin 2 (PROK2) gene, which encodes a secreted peptide that regulates the development and migration of the olfactory tract and GnRH neuron progenitors. The PROK2 mutations caused hypogonadotropic hypogonadism in both males and females. Using Prok2 −/− knockout mice, the GnRH neuron progenitors were shown to cross the cribriform plate but fail to migrate into and populate the hypothalamus. Interestingly, olfactory tract development in humans with PROK2 mutations was variable, resulting in both nonanosmic and anosmic forms of hypogonadotropic hypogonadism. This report highlights the role of genetics as a means to unravel complex developmental processes and helps explain why anosmia is a frequent, but variable, feature of inherited forms of hypogonadotropic hypogonadism.
Demonstration of narrowband notch and multi-notch filters

ABSTRACT Narrow notch and multi-notch thin-film filters have applications in many fields. Raman spectroscopy and laser-based fluorescence instruments both desire filters that can remove one or more narrow spectral bands while maintaining high transmittance for light at adjacent wavelengths. Key figures of merit for notch filters include the width of the notch as a fraction of the blocked wavelength (narrower is better), the degree of suppression, and the overall transmittance of the filter. Design approaches for narrowband notch and multi-notch filters are well-known, and include rugate or quasi-rugate designs. The manufacturing of these filters has proven to be challenging. The filters have to be very thick to achieve high suppression, and typically involve the deposition of gradient index layers or many very thin, discrete layers. Accurate spectral placement of the notches often requires extreme process control or post-deposition tuning of the filter. JDSU has recently developed a design and manufacturing capability for single and multi-notch filters in the visible wavelength region where the notch width is less than 2% and the blocking levels are greater than OD 6. Designs for these types of filters can be 20  60 µm thick and consist of more than 1,000 layers. Our Ucp-1 high-rate magnetron sputtering platform with load-lock provides an inherently stable deposition process. This enables us to coat these challenging designs. In this paper, we present examples of both single and multi-notch filters that have 612 to 4410 layers and are 31 to 127 µm thick. Keywords: rugate filter, notch filter, multi-notch filter, magnetron sputtering, optical thin-film coating, laser line suppression, optical density
Impact of a pediatric asthma clinical pathway on hospital cost and length of stay.

This study sought to determine if a clinical pathway developed and executed by specialists in pediatric asthma would reduce hospital costs and length of stay (LOS). The study design was a retrospective, nonrandomized, controlled trial. Subjects were children aged 2-18 years (N = 1,004) with a history of recurrent wheezing, hospitalized with a diagnosis of acute asthma exacerbation between 1995-1998 at the New York Hospital-Weill Cornell Medical Center and treated via the pathway, as well as a control group of 206 children ages 2-18 hospitalized for acute asthma exacerbation in 1994, the year prior to pathway implementation. Patients were treated via the pathway under the supervision of an asthma specialist. The pathway provided guidelines for: 1) frequency of patient assessment; 2) bronchodilator usage; 3) corticosteroid use; 4) laboratory evaluation; 5) vital signs, oxygen saturation, and peak flow measurements; 6) chest x-rays; 7) social work intervention; and 8) discharge planning. The main outcome measures were hospital length of stay, cost per hospitalization, nursing, medication, laboratory and radiology costs, and relapse rate. Total charges for admission and average LOS for 1995-1998 were calculated, and compared with 1994, the year preceding implementation of the pathway. LOS decreased from 4.2 days to 2.7 days (P < 0.0001). The annual total charges for pediatric asthma admissions decreased from 2 million dollars to 1.4 million dollars (P < 0.005). Nursing and laboratory costs showed a statistically significant decrease. Follow-up study at 8 months showed a readmission rate of 0.02%. The implementation of a pediatric asthma clinical pathway, directed by specialists, resulted in significantly decreased length of stay and overall cost, without an increased rate of readmission.
The San Francisco MSM Epidemic: A Retrospective Analysis

We investigate various scenarios for ending the San Francisco MSM (men having sex with men) HIV/AIDS epidemic (1978–1984). We use our previously developed model and explore changes due to prevention strategies such as testing, treatment and reduction of the number of contacts. Here we consider a “what-if” scenario, by comparing different treatment strategies, to determine which factor has the greatest impact on reducing the HIV/AIDS epidemic. The factor determining the future of the epidemic is the reproduction number R0; if R0 < 1, the epidemic is stopped. We show that treatment significantly reduces the total number of infected people. We also investigate the effect a reduction in the number of contacts after seven years, when the HIV/AIDS threat became known, would have had in the population. Both reduction of contacts and treatment alone, however, would not have been enough to bring R0 below one; but when combined, we show that the effective R0 becomes less than one, and therefore the epidemic would have been eradicated.
Lambda Red-mediated Recombineering in the Attaching and Effacing Pathogen Escherichia albertii

The ability to introduce site-specific mutations in bacterial pathogens is essential towards understanding their molecular mechanisms of pathogenicity. This has been greatly facilitated by the genetic engineering technique of recombineering. In recombineering, linear double- or single-stranded DNA molecules with two terminal homology arms are electroporated into hyperrecombinogenic bacteria that express a phage-encoded recombinase. The recombinase catalyzes the replacement of the endogenous allele with the exogenous allele to generate selectable or screenable recombinants. In particular, lambda red recombinase has been instrumental in engineering mutations to characterize the virulence arsenal of the attaching and effacing (A/E) pathogens enteropathogenic Escherichia coli (EPEC), enterohemorrhagic E. coli (EHEC), and Citrobacter rodentium. Escherichia albertii is another member of this taxon; however, the virulence of E. albertii remains cryptic despite accumulating evidence that E. albertii is an emerging pathogen. Multiple retrospective studies have reported that a substantial number of EPEC and EHEC isolates (~15 %) that were previously incriminated in human outbreaks actually belong to the E. albertii lineage. Thus, there is increased urgency to reliably identify and rapidly engineer mutations in E. albertii to systematically characterize its virulence determinants. To the best of our knowledge not a single chromosomal gene has been altered by targeted mutagenesis in E. albertii since it was first isolated almost 25 years ago. This is disconcerting because an E. albertii outbreak could cause significant morbidity and mortality owing to our inadequate understanding of its virulence program. In this report we describe a modified lambda red recombineering protocol to mutagenize E. albertii. As proof of principle, we successfully deleted three distinct virulence-associated genetic loci – ler, grlRA, and hfq – and replaced each wild type allele by a mutant allele with an encodable drug resistance cassette bracketed by FRT sites. Subsequently, the FRT-site flanked drug resistance marker was evicted by FLP-dependent site-specific recombination to generate excisants containing a solitary FRT site. Our protocol will enable researchers to construct marked and unmarked genome-wide mutations in E. albertii, which, in turn, will illuminate its molecular mechanisms of pathogenicity and aid in developing appropriate preventative and therapeutic approaches to combat E. albertii outbreaks.
Discovery of a Small Molecule MDM2 Inhibitor (AMG 232) for Treating Cancer

We recently reported the discovery of AMG 232 (1), a potent and selective piperidinone inhibitor of the MDM2-p53 protein–protein interaction. Compound 1 is currently being evaluated in human clinical trials for the treatment of cancer. This article provides an overview of its discovery from the de novo design of the piperidinone series to the structure–activity studies leading to the identification of 1. In addition, this article also describes the preclinical pharmacology and pharmacokinetics of 1, along with its drug metabolism and safety assessment.
BAZ1B in Nucleus Accumbens Regulates Reward-Related Behaviors in Response to Distinct Emotional Stimuli

ATP-dependent chromatin remodeling proteins are being implicated increasingly in the regulation of complex behaviors, including models of several psychiatric disorders. Here, we demonstrate that Baz1b , an accessory subunit of the ISWI family of chromatin remodeling complexes, is upregulated in the nucleus accumbens (NAc), a key brain reward region, in both chronic cocaine-treated mice and mice that are resilient to chronic social defeat stress. In contrast, no regulation is seen in mice that are susceptible to this chronic stress. Viral-mediated overexpression of Baz1b , along with its associated subunit Smarca5 , in mouse NAc is sufficient to potentiate both rewarding responses to cocaine, including cocaine self-administration, and resilience to chronic social defeat stress. However, despite these similar, proreward behavioral effects, genome-wide mapping of BAZ1B in NAc revealed mostly distinct subsets of genes regulated by these chromatin remodeling proteins after chronic exposure to either cocaine or social stress. Together, these findings suggest important roles for BAZ1B and its associated chromatin remodeling complexes in NAc in the regulation of reward behaviors to distinct emotional stimuli and highlight the stimulus-specific nature of the actions of these regulatory proteins. SIGNIFICANCE STATEMENT We show that BAZ1B, a component of chromatin remodeling complexes, in the nucleus accumbens regulates reward-related behaviors in response to chronic exposure to both rewarding and aversive stimuli by regulating largely distinct subsets of genes.
Association between Lifetime Exposure to Inorganic Arsenic in Drinking Water and Coronary Heart Disease in Colorado Residents

Background: Chronic diseases, including coronary heart disease (CHD), have been associated with ingestion of drinking water with high levels of inorganic arsenic (> 1,000 μg/L). However, associatio...
Human lymphocyte antibody-dependent cell-mediated cytotoxicity (ADCC) toward human red blood cells.

Previous investigations involving mononuclear cell antibody-dependent cell-mediated cytotoxicity (ADCC) toward human red cell (RBC) targets indicated that monocytes but not lymphocytes are able to produce erythrocyte lysis. We reexamined this reported insensitivity of human RBC to lymphocyte cytotoxicity using a variety of human RBC targets and a wide range of antisera to various erythrocyte antigens. We observed, as did other investigators, that normal O+ red cells (R1R2-CDē/ c ¯ DE) pretreated with small amounts of typical anti-D serum were quite susceptible to monocyte lysis but were completely resistant to lymphocyte ADCC. However, four other human RBC-antibody combinations were found to mediate striking lymphocyte and monocyte cytotoxicity. These included (1) -D-cells plus typical anti-D, (2) normal O+ cells (R1R2) plus Ripley anti-CD, (3) papa in-pre treated normal O+ cells plus small amounts of anti-D and (4) normal 0+ cells plus very large amounts of anti-D. These findings show that human RBC are not uniquely resistant to lymphocyte ADCC and that antibody density and/or distribution on the target cell surface may be very important to cytotoxicity by leukocytes. The basic characteristics of lymphocyte ADCC toward human RBC are similar to those reported for nucleated targets. Cytolysis is temperature-dependent and rapid, with nearly all erythrocyte lysis occurring in the first 4 hr of incubation. Extent of target cell destruction is positively related to the effector/target ratio and the amount of antibody bound to the erythrocyte surface. Further evidence showing the antibody-dependent cell contact-mediated nature of the cytolytic event includes inhibition of ADCC with nonspecific immunoglobulin and data obtained from “innocent bystander” studies.
The effect of political factors on sovereign default

ABSTRACTThis aricle examines the effect of political factors on sovereign default. Using a theoretical model, we find that political instability increases the likelihood of default. To test this theoretical implication, we use a panel logit model to estimate the effect of long- and short-run political factors, along with other macroeconomic variables, on the probability of default. Data from 68 developed and developing countries between 1970 and 2010 is used to conduct the study. Our findings suggest that a country is more likely to default when (i) it has a relatively younger political regime in place; (ii) it faces a higher chance of political turnover; and (iii) it has a less democratic political system. Economic factors are also vital; a country with stronger growth and less external debt is less likely to experience sovereign default. Robustness tests using alternative measures of political risk, trade balance and EMBI sovereign bond spreads also support the baseline findings.
Brain Potentials and Prediction of Performance

To test an idea, use it to predict something. Only when we try to predict can we discover that we are wrong and the possibility of disproof is the principal distinction between scientific and theological concepts. One has almost to begin a paper on the use of brain potentials to measure IQ with such an apology. An applied goal often suggests commercial exploitation and extravagant claims. I hope to illustrate that an applied goal such as this has theoretical as well as practical merit, that prediction of performance from brain potentials is a real possibility, and that some novel approaches are waiting for exploitation.
CD19 Targeted Cord Blood Derived T Cells for Cancer Immunotherapy.

Abstract 3767 Transplantation of unrelated umbilical cord blood (CB) derived stem cells is often used to treat adult patients with B-cell acute lymphoblastic leukemia (B-ALL). However, many patients relapse and overall prognosis is poor. We hypothesize that additional therapy involving adoptive transfer of CB derived T cells modified to express a CD19-specific chimeric antigen receptor (CAR) could improve patient outcome following allogeneic CB transplant. To this end, we have previously demonstrated that human T cells which express the anti-CD19 19–28ζ CAR, containing the signaling domains of the co-stimulatory CD28 receptor and CD3ζ chain, effectively eradicate CD19 + tumors both in vitro as well as in vivo in SCID-Beige mice. Herein, we demonstrate the ability to effectively isolate and expand T cells from CB samples using magnetic beads coated with agonistic CD3 and CD28 antibodies (Invitrogen) and comparing subsequent T cell expansions in in vitro cultures with varying additions of exogenous stimulatory cytokines, including IL-2, a combination of IL-2 and IL-7, IL-12 or IL-15. We demonstrate that in vitro culture in the context of exogenous IL-12 (10 ng/ml) resulted in optimal expansion of CB T cells (150-fold). In addition, expansion of T cells in the context of exogenous IL-12 resulted in a favorable phenotype for adoptive cell transfer, with T cells expressing high levels of Granzyme B and Perforin while retaining a “memory” phenotype as assessed by persistent expression of CD62L. This combination of cytotoxic and memory phenotype is optimal for adoptive cell therapy. T cells expanded in this manner were subsequently efficiently retrovirally transduced to express the 19–28ζ CAR. The resulting CD19-specific CB derived T cells were able to specifically lyse CD19 + tumor targets as assessed by standard 51 Cr release cytotoxicity assays. We are currently investigating the in vivo anti-tumor function of these modified cells in our previously established preclinical SCID-Beige mouse tumor model and ultimately plan to conduct a Phase 1 clinical trial with these modified T cells in patients with B-ALL undergoing CB transplant. Disclosures: No relevant conflicts of interest to declare.
Frege’s Prison of Functions

Masterful piano players captivate audiences not only with sound, but with the spectacle of their movements, which also influence the quality of the sound. Many interesting gestures involve rotations in space. We can use a formula to describe a rotation, but the formula denies us the understanding of its essence. Mathematical abstraction neglects the gestural aspect; it takes away from the preceding gestural essence, hiding its nature of movement that connects points in spaces. The whole movement is hidden at the very least, or destroyed at the worst. We should be able to understand a formula via its unfolding in gestures, as in the case of rotation. Several important mathematical topics can be re-thought under the light of gestures. Complex numbers can also be seen as the result of the gestural action of rotation. We will use the imagery of mirrors and vampires to help us understand. We end the chapter with the distinction between imaginary time and real time, the two components of the complex time.
Analytical solutions to the finite-pulse Bloch model for multidimensional coherent spectroscopy

We present perturbative analytical solutions to the optical Bloch equations at third order, with finite duration Gaussian pulse envelopes. We find that a given double-sided Feynman diagram in this approximation can be conveniently described in the frequency domain as a product of the expression in the impulsive limit and a finite-pulse factor. Finite-pulse effects are Feynman-diagram-dependent, however, and include nontrivial phase corrections that can occur even in the case of transform-limited pulses. The results constitute a practical framework for modeling phenomena in multidimensional coherent spectroscopy that cannot easily be captured in the impulsive limit, including the roles of bandwidth, resonance, and pulse chirp.
Edgeways as a theoretical extension: connecting crime pattern theory and New Urbanism

Recently, scholars have examined the criminological implications of the growing trend of new urban design. Building on recent research (Cozens in Urban Policy Res 26(4):429–444, 2008) and past theoretical works (Brantingham and Brantingham in J Environ Psychol 13(1):3–28, 1993; Eur J Crim Policy Res 3(3):5–26, 1995), the current project suggests crime pattern theory requires new conceptual terms to understand and investigate the implications of crime clustering in new urban areas. It is argued in the current project that “edgeways”—or edges that become simultaneous paths—are prevalent in new urban space due to an array of combining features such as crowd generation, alleyways and parking difficulties, incomplete implementation of new urban principles, and the density paradox. The current paper entails a theoretical discussion of the problem and potential policy implications.
Entwicklung über die Lebensspanne

Das Leben ist eine Reise, vom Bauch bis zur Bahre. Das gilt fur mich ebenso wie fur Sie. Unsere Geschichten begannen jeweils mit einem Mann und einer Frau, die mehr als 20.000 Gene zu einer Eizelle zusammenbrachten, die schlieslich zu einem einzigartigen Menschen heranwuchs.
Genome Sequences of 34 Shiga Toxin-Producing Escherichia coli Isolates from Swine and Other Sources.

ABSTRACT Shiga toxin-producing Escherichia coli (STEC) bacteria are foodborne pathogens that can be carried by various animals. The swine STEC population is partially composed of host-specific strains that are often not well characterized. In this work, the genome sequences of a number of swine STEC strains are presented.
Tracing Times in Place

Describes how this important and diverse commercial centre once worked as a social space and its transformation into a site of concrete division. An exploration of praxis, it describes shopkeepers’ memories of everyday life in the city’s main marketplace in the 1950s, through its transformation into a no-man’s land in 1974. This chapter renders visible previously unrecorded memories that have been overshadowed or obscured by official narratives of the contested past in Cyprus. The main conclusions of the chapter affirm that memories about place are able to reveal apparently ‘forgotten’ histories, and that the process of visual inquiry and mapping work allowed individuals access to memories that they had been encouraged to forget.
Imagining Disaster in the Eco-Thriller

This chapter discusses the origins and characteristics of the eco-thriller as a subset of the American thriller as groundwork for analysis of two films: The Happening and The Bay . Both films address environmental issues from different perspectives; what they have in common, however, is the portrayal of the environment as the central antagonist against which humans must fight for survival. In both films, the environment is violent and seeking revenge against humans for the ecological harm they have caused. A central focus of the chapter is to discern why the environment is so vengeful. Are its concerns clearly stated, or is the audience left to guess? The chapter places the films in environmental context, including overconsumption and pollution (The Happening) and pollution in Chesapeake Bay (The Bay).
Employee Ability to Innovate: How Can Organizations Recognize It

Abstract Searching through the relevant literature, this paper identifies and explains the process behind many of the available instruments that may predict one’s personality for producing innovation. Based on the research and scholarly journal entries, the types of personalities that are more prone to be innovative are also introduced. The qualities of an innovative person are then compared with the results from these various tests so that the foundational question of this paper is answered: what type of person is most innovative? In the end, while the merit and certitude of these tests will be called into question, this paper, at the very least, explains the current rationale and processes behind assessing which type of personality is best suitable for innovation.
Does Vasopressin Exacerbate Cerebral Edema in Patients with Severe Traumatic Brain Injury

Arginine vasopressin (AVP) is often used as an alternative pressor to catecholamines (CATs). However, unlike CATs, AVP is a powerful antidiuretic that could promote edema. We tested the hypothesis that AVP promoted cerebral edema and/or increased requirements for osmotherapy, relative to those who received CATs, for cerebral perfusion pressure (CPP) management after traumatic brain injury (TBI). This is a retrospective review of 286 consecutive TBI patients with intracranial pressure monitoring at a single institution from September 2008 to January 2015. Cerebral edema was quantitated using CT attenuation in prespecified areas of gray and white matter. RESULTS To maintain CPP >60 mm Hg, 205 patients required no vasopressors, 41 received a single CAT, 12 received AVP, and 28 required both. Those who required no pressors were generally less injured; required less hyperosmolar therapy and less total fluid; and had lower plasma Na, lower intracranial pressure, less edema, and lower mortality (all P < 0.05). Edema; daily mean, minimum, and maximum Na levels; and mortality were similar with AVP versus CATs, but the daily requirement of mannitol and 3 per cent NaCl were reduced by 45 and 35 per cent (both P < 0.05). In patients with TBI who required CPP therapy, AVP reduced the requirements for hyperosmolar therapy and did not delay resolution or increase cerebral edema compared with CATs.