Retrieval cues fail to influence contextualized evaluations.

Initial evaluations generalise to new contexts, whereas counter-attitudinal evaluations are context-specific. Counter-attitudinal information may not change evaluations in new contexts because perceivers fail to retrieve counter-attitudinal cue-evaluation associations from memory outside the counter-attitudinal learning context. The current work examines whether an additional, counter-attitudinal retrieval cue can enhance the generalizability of counter-attitudinal evaluations. In four experiments, participants learned positive information about a target person, Bob, in one context, and then learned negative information about Bob in a different context. While learning the negative information, participants wore a wristband as a retrieval cue for counter-attitudinal Bob-negative associations. Participants then made speeded as well as deliberate evaluations of Bob while wearing or not wearing the wristband. Internal meta-analysis failed to find a reliable effect of the counter-attitudinal retrieval cue on speeded or deliberate evaluations, whereas the context cues influenced speeded and deliberate evaluations. Counter to predictions, counter-attitudinal retrieval cues did not disrupt the generalisation of first-learned evaluations or the context-specificity of second-learned evaluations (Experiments 2-4), but the counter-attitudinal retrieval cue did influence evaluations in the absence of context cues (Experiment 1). The current work provides initial evidence that additional counter-attitudinal retrieval cues fail to disrupt the renewal and generalizability of first-learned evaluations

Validation of a two-parameter quantitative structure–activity relationship as a legitimate tool for rational re-design of horseradish peroxidase

Previously reported rates of reaction between six mutant strains of the enzyme horseradish peroxidase (HRP) and a test substrate, 2-methoyxpyhenol, were found to correlate with characteristic binding distances computed using molecular simulation. The correlation ( R 2  = 0.86) bears out a working hypothesis that, based on a quantitative structure–activity relationship (QSAR) we had previously developed for HRP, reductions in binding distances between the HRP enzyme and any selected substrate mediate increased enzyme reactivity towards that substrate. The results validate the use of QSAR as a quantitative means for formulating enzyme mutations designed to achieve enhanced HRP reactivity towards compounds of specific interest. Biotechnol. Bioeng. 2007; 98: 295–299. © 2007 Wiley Periodicals, Inc.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/56109/1/21419_ftp.pd

Advance Equitable Livelihoods : A paper on Action Track 4

Food systems transformation provides the opportunity to shift current trends in all forms of malnutrition, prioritizing nutritious food availability and affordability for all – from shifting priorities in agricultural production, to improved food systems that favour nutrition and sustainability. The task of Action Track 4 is to explore approaches to doing so that will ensure equitable livelihoods for producers, businesses, workers across the food system and consumers, with particular emphasis on addressing inequalities and power imbalances. As the Science Group for AT 4, we explore the nature of these issues, using the drivers of food systems as articulated by the High Level Panel of Experts of the UN Committee on World Food Security1 as framing. Small and medium sized producers and people living on the food system in rural and urban areas are disproportionately affected by all biophysical and environmental drivers including soil and water resources, and climate change. Unequal opportunity in access to all types of resources reduces overall production, resilience, rural transformation. Advances in innovation, technology and infrastructure have had important impacts on food production and sustainability, transportation and processing along food value chains, marketing, and ultimately diets, including consumption of both nutritious and unhealthy foods. But achievement of equitable livelihoods in food systems will require that issues of access to contextually suitable innovation and technology be substantially enhanced, and that such advances better build on and learn from indigenous knowledge. Many economic and political factors are essential causes of inequality and power imbalances at house- hold, community, national and global levels, which constrain the ability of food systems transformation to deliver poverty reduction and sustainable, equitable livelihoods. Finally, vast evidence illustrates that several socio-cultural and demographic drivers underpin inequalities among and within societies and constrain the potential for some to benefit from actions to improve livelihoods, particularly women, youth, disabled, elderly, and indigenous peoples. These issues are exacerbated by the COVID-19 pandemic. The pandemic is having a significant impact on the global commodity markets and trading systems, economic growth, incomes, and poverty levels, with likely disproportionate burden on the vulnerable communities in both urban and rural areas. This is likely to worsen inequalities and under- nutrition including child wasting. To address these issues, we must transform not only food systems, but the structures and systems that continue to enable and exacerbate inequities. Drivers of food systems inequities are highly interconnected and progress to address one will likely require change across several. For example, globalization and trade interact with other powerful drivers, especially technology resource mobilization, and demographic trends, which shape food production, distribution, and consumption. Drawing of this evidence review, in the final section we reflect on several factors that should be part of effective solutions, including grounding in rights-based approaches. We then share a series of recommendations aimed to enhance inclusive decision making, protect the livelihoods of those living in situations of vulnerability while creating opportunities, adapting institutions and policies to favour equitable food systems livelihoods, and increasing investment to realize the potential of improved institutional and policy actions. We invite governments, businesses, and organizations to hold themselves and others to account for ensuring equitable livelihoods, and open avenues to realize the potential of science, innovation, technology, and evidence to favour equitable livelihoods

Extension and approximation of mm-subharmonic functions

Let $\Omega\subset \mathbb C^n$ be a bounded domain, and let $f$ be a real-valued function defined on the whole topological boundary $\partial \Omega$. The aim of this paper is to find a characterization of the functions $f$ which can be extended to the inside to a $m$-subharmonic function under suitable assumptions on $\Omega$. We shall do so by using a function algebraic approach with focus on $m$-subharmonic functions defined on compact sets. We end this note with some remarks on approximation of $m$-subharmonic functions

The Spectrum of Yang Mills on a Sphere

In this note, we determine the representation content of the free, large N, SU(N) Yang Mills theory on a sphere by decomposing its thermal partition function into characters of the irreducible representations of the conformal group SO(4,2). We also discuss the generalization of this procedure to finding the representation content of N=4 Super Yang Mills.Comment: 18 pages v2. references added. typos fixe

Conditional Guide RNAs: Programmable Conditional Regulation of CRISPR/Cas Function in Bacterial and Mammalian Cells via Dynamic RNA Nanotechnology

A guide RNA (gRNA) directs the function of a CRISPR protein effector to a target gene of choice, providing a versatile programmable platform for engineering diverse modes of synthetic regulation (edit, silence, induce, bind). However, the fact that gRNAs are constitutively active places limitations on the ability to confine gRNA activity to a desired location and time. To achieve programmable control over the scope of gRNA activity, here we apply principles from dynamic RNA nanotechnology to engineer conditional guide RNAs (cgRNAs) whose activity is dependent on the presence or absence of an RNA trigger. These cgRNAs are programmable at two levels, with the trigger-binding sequence controlling the scope of the effector activity and the target-binding sequence determining the subject of the effector activity. We demonstrate molecular mechanisms for both constitutively active cgRNAs that are conditionally inactivated by an RNA trigger (ON → OFF logic) and constitutively inactive cgRNAs that are conditionally activated by an RNA trigger (OFF → ON logic). For each mechanism, automated sequence design is performed using the reaction pathway designer within NUPACK to design an orthogonal library of three cgRNAs that respond to different RNA triggers. In E. coli expressing cgRNAs, triggers, and silencing dCas9 as the protein effector, we observe a median conditional response of ≈4-fold for an ON → OFF “terminator switch” mechanism, ≈15-fold for an ON → OFF “splinted switch” mechanism, and ≈3-fold for an OFF → ON “toehold switch” mechanism; the median crosstalk within each cgRNA/trigger library is <2%, ≈2%, and ≈20% for the three mechanisms. To test the portability of cgRNA mechanisms prototyped in bacteria to mammalian cells, as well as to test generalizability to different effector functions, we implemented the terminator switch in HEK 293T cells expressing inducing dCas9 as the protein effector, observing a median ON → OFF conditional response of ≈4-fold with median crosstalk of ≈30% for three orthogonal cgRNA/trigger pairs. By providing programmable control over both the scope and target of protein effector function, cgRNA regulators offer a promising platform for synthetic biology

Impact of patient characteristics on the risk of influenza/ILI-related complications

BACKGROUND: We sought to quantify the impact of patient characteristics on complications and health care costs associated with influenza and influenza-like illness (ILI) in a nonelderly population. METHODS: Patients with medical reimbursement claims for influenza in the 1996–1997 season were identified from the automated database of a large private New England Insurer (NEI). Influenza care during the 21- day follow-up period was characterized according to age, gender, vaccine status, co-morbidities, prior influenza/ILI episodes, treatments, and recent health care costs and related diagnoses. RESULTS: There were 6,241 patients. Approximately 20% had preexisting chronic lung disease. Overall, 23% had health care services for possible complications, among which respiratory diagnoses were the most common (13%). Two percent of the influenza/ILI episodes involved hospitalization, with a median stay of five days. Factors most strongly predictive of hospitalizations and complications were preexisting malignancy (hospitalizations OR = 3.7 and complications OR = 2.4), chronic heart disease (OR = 3.2 and OR = 1.8), diabetes (OR = 2.2 and OR = 1.7) and recent illnesses that would have counted as complications had they occurred during an influenza/ILI episode (hospitalizations OR = 3.2 and complications OR = 1.5). The same factors affected influenza-related costs and total costs of care as dramatically as they affected complication rates. CONCLUSIONS: Influenza/ILI-related costs are driven by the characteristics that predict complications of influenza. Patients with chronic illness and those with recent acute respiratory events are the most likely to experience complications and hospitalizations

C/EBPβ-1 promotes transformation and chemoresistance in Ewing sarcoma cells.

CEBPB copy number gain in Ewing sarcoma was previously shown to be associated with worse clinical outcome compared to tumors with normal CEBPB copy number, although the mechanism was not characterized. We employed gene knockdown and rescue assays to explore the consequences of altered CEBPB gene expression in Ewing sarcoma cell lines. Knockdown of EWS-FLI1 expression led to a decrease in expression of all three C/EBPβ isoforms while re-expression of EWS-FLI1 rescued C/EBPβ expression. Overexpression of C/EBPβ-1, the largest of the three C/EBPβ isoforms, led to a significant increase in colony formation when cells were grown in soft agar compared to empty vector transduced cells. In addition, depletion of C/EBPβ decreased colony formation, and re-expression of either C/EBPβ-1 or C/EBPβ-2 rescued the phenotype. We identified the cancer stem cell marker ALDH1A1 as a target of C/EBPβ in Ewing sarcoma. Furthermore, increased expression of C/EBPβ led to resistance to chemotherapeutic agents. In summary, we have identified CEBPB as an oncogene in Ewing sarcoma. Overexpression of C/EBPβ-1 increases transformation, upregulates expression of the cancer stem cell marker ALDH1A1, and leads to chemoresistance

Cytolethal Distending Toxin-Induced Release of Interleukin-1β by Human Macrophages is Dependent Upon Activation of Glycogen Synthase Kinase 3β, Spleen Tyrosine Kinase (Syk) and the Noncanonical Inflammasome

Cytolethal distending toxins (Cdt) are a family of toxins produced by several human pathogens which infect mucocutaneous tissue and induce inflammatory disease. We have previously demonstrated that the Aggregatibacter actinomycetemcomitans Cdt induces a pro-inflammatory response from human macrophages which involves activation of the NLRP3 inflammasome. We now demonstrate that in addition to activating caspase-1 (canonical inflammasome), Cdt treatment leads to caspase-4 activation and involvement of the noncanonical inflammasome. Cdt-treated cells exhibit pyroptosis characterised by cleavage of gasdermin-D (GSDMD), release of HMGB1 at 24 hr and LDH at 48 hr. Inhibition of either the canonical (caspase-1) or noncanonical (caspase-4) inflammasome blocks both Cdt-induced release of IL-1β and induction of pyroptosis. Analysis of upstream events indicates that Cdt induces Syk phosphorylation (activation); furthermore, blockade of Syk expression and inhibition of pSyk activity inhibit both Cdt-induced cytokine release and pyroptosis. Finally, we demonstrate that increases in pSyk are dependent upon Cdt-induced activation of GSK3β. These studies advance our understanding of Cdt function and provide new insight into the virulence potential of Cdt in mediating the pathogenesis of disease caused by Cdt-producing organisms such as A. actinomycetemcomitans. © 2020 John Wiley & Sons Lt

Palliative Laparoscopic End Colostomy in a Nonagenarian

Patients with advanced gynecologic malignancy often require fecal diversion as a sole procedure in cases of obstruction or fistula formation. This unique patient population has a frequent history of advanced age, prior abdominal surgery, pelvic radiation, poor nutritional status and medical comorbidities. The use of laparoscopic colostomy for palliative fecal diversion in this context has not been well described in the gynecologic oncology literature. We present the first case of palliative laparoscopic end-colostomy in a nonagenarian as a sole procedure for fecal diversion in advanced gynecologic malignancy. Palliative laparoscopic end-colostomy is a safe, feasible, and effective method to optimize quality of life in select elderly women with advanced gynecologic malignancy