Additional Key Elements Research Articles

Microenvironment Matters: Unique Conditions Within Gut-Draining Lymph Nodes Favor Efficient De Novo Induction of Regulatory T Cells.

The gastrointestinal tract constitutes the largest surface of the body and thus has developed multitude mechanisms to either prevent pathogen entry or to efficiently eliminate invading pathogens. At the same time, the gastrointestinal system has to avoid unwanted immune responses against self and harmless nonself antigens, such as nutrients and commensal microbiota. Therefore, it is somewhat not unexpected that the gastrointestinal mucosa serves as the largest repository of immune cells throughout the body, harboring both potent pro- as well as anti-inflammatory properties. One additional key element of this regulatory machinery is created by trillions of symbiotic commensal bacteria in the gut. The microbiota not only simply contribute to the breakdown of nutrients, but are essential in limiting the expansion of pathogens, directing the development of the intestinal immune system, and establishing mucosal tolerance by fostering the induction of regulatory T cells (Tregs). In this review, we will discuss our current understanding about the microenvironmental factors fostering the de novo generation of Tregs within the gastrointestinal immune system, focusing on unique properties of antigen-presenting cells, tolerogenic cytokines, commensal-derived metabolites and the contribution of lymph node stromal cells.

A critical revisit of the key parameters used to describe microbial electrochemical systems

Many microorganisms have the innate capability to discharge and/or receive electrons to and from solid state materials such as electrodes. This ability is now used towards innovative processes in wastewater treatment, power generation, production of fuels and biochemicals, bioremediation, desalination and resource recovery, among others. Despite being a dynamic field in science and technology, significant challenges remain towards industrial implementation which include representation of judicious performance indicators. This critical review outlines the progress in current density evaluated per projected surface area of electrodes, the most wide-spread performance indicator. It also proposes guidelines to correct current and exchange current per porous surface area, biofilm covered area, electrochemically- or bioelectrochemically- active surface area, of the electrodes. Recommendations for indicators to describe the environmental and electrochemical robustness of electrochemically-active biofilms are portrayed, including preservation of the predominant functionality as well as electrochemical mechanistic and phenomenological features. A few additional key elements for industrial processing are depicted. Whereas Microbial Fuel Cells (MFCs) are the main focus, some important parameters for reporting on cathodic bioproduction performance are also discussed. This critical revision aims to provide key parameters to compare the whole spectrum of microbial electrochemical systems in a consistent way.

Fundamental Rights and the European Union: How Does and How Should the EU Agency for Fundamental Rights Relate to the EU Charter of Fundamental Rights?

This paper looks at the mandate of the European Union Agency for Fundamental Rights (FRA), established in 2007, from the perspective of the Charter of Fundamental Rights of the European Union, which entered into force in 2009. It explores the relationship between FRA and the Charter by looking at the agency’s institutional practice, its founding regulation and its Multiannual Framework, on which the Council of the European Union agrees every five years. The Florence-based European University Institute (EUI) proposed some 15 years ago an European Union (EU) human rights agenda for the new millennium. Many of the agenda’s policy proposals have materialised ever since, including the establishment of a ‘European Human Rights Monitoring Agency’. The Charter was not part of this set of proposals. However, this prominent bill of rights and the new Agency in Vienna are obviously closely related to each other. The author concludes that the agency, despite certain limitations in its mandate, is a ‘full-Charter-body’ which could unfold its potential better following a revision of its founding regulation. Such a revision should reflect that the EU Charter for Fundamental Rights has entered into force in the meantime. The author identifies two additional key elements for the need of revision: FRA’s mandate should include the possibility for the agency to deliver opinions on proposed EU legislation on its own motion, and the agency should autonomously adopt its multiannual priorities.

Developing a New Model for Conversion Rate Optimization: A Case Study

This paper will discuss conversion rate optimization in online retail environments. The paper reviews previousliterature on the topic and then examines how one company has created its own model and used the model tosuccessfully to enhance Internet businesses’ conversion rate optimization. The paper will then synthesize all ofthe factors seen in the literature and the case study model into a new model.A variety of academic papers on the factors affecting the decision-making process of online customers from2004 through 2012 were examined and an in-depth face-to-face interview was conducted with the founder ofClixo at a 2012 United States “online marketing” forum, with a follow-up interviews conducted via email. Thepaper discusses the effectiveness of the new model.This paper identifies the variables that influence online customer behavior and discusses the importance each ofthe seven elements; catalyst, persuasion, usability, interactivity, trust, aesthetics, and marketing mix. Theinterrelationship of the elements at each stage of the customer decision-making process is reviewed.The paper illustrates how e-Retailers can apply the elements of the framework in delivering a website experiencelikely to maximize the number of purchases from online visitors, and to reinforce post-purchase confidence.The paper identifies two additional key elements in conversion rate optimization and develops a new model thatincorporates the two new elements. This new hierarchical model presents the elements stage-by-stage to helponline retailers to convert visitors into customers.

Gene—Environment Interaction in Panic Disorder and Posttraumatic Stress Disorder

Gene-environment interaction is a form of causal interplay, whereby genetic effects on phenotypic variation change as a function of environmental exposure. While conceptually appealing, there is still much debate on the veracity and the relevance of this form of etiological interdependence for psychiatric disorders. By focusing on panic disorder (PD) and posttraumatic stress disorder (PTSD), this article outlines why gene-environment interaction is controversial, why it can be important for both researchers and clinicians, and how it is investigated by quantitative genetic, molecular genetic, and genomic strategies. It is suggested that gene-environment interaction effects are more reliable and meaningful when they can be harnessed to pinpoint specific biological pathways and mechanisms. In psychiatry, this can be guided by phenotypic dissection and realized by adopting intermediate phenotypes of a physiological nature, such as carbon dioxide sensitivity for PD, or gene expression profiling after stress for PTSD. A developmental framework of reference and the possibility of transferring the investigation to animal models are additional key elements in this debate.

A 5-MHz 11-Bit Self-Oscillating $\Sigma\Delta$ Modulator With a Delay-Based Phase Shifter in 0.025 mm$^2$

Self-oscillating ΣΔ modulators are a class of ΣΔ modulators that combines noise shaping with pulsewidth modulation (PWM). Moreover, in such a modulator, the PWM carrier is generated by a self-oscillation mode that is deliberately introduced. In our approach, this self-oscillation is accurately controlled by a digital delay in the feedback loop. The concept is elaborated for a second-order self-oscillating ΣΔ modulator with 5-MHz bandwidth. Here, the clock frequency equals 850 MHz, but the loop only has to process signals that are maximally at the self-oscillation frequency (at 106.25 MHz). An additional key element in this design is the use of a feedback FIRDAC which reduces the jitter sensitivity and further relaxes the slewing requirements of the first opamp in the loop. The prototype modulator is fabricated in a 0.18-μm CMOS process and achieves a dynamic range of 66 dB. Due to the simplicity of the circuit, the modulator core area is only 0.025 mm <sup xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">2</sup> . The power consumption of the modulator is 6 mW.

Revised STRICTA as an Extension of the CONSORT Statement: More Items Should Be Involved in the Checklist

Dear Editor: The revised standards for reporting interventions in clinical trials of acupuncture (STRICTA) as a formal extension to Consolidated Standards of Reporting Trials (CONSORT) has been published in PLoS Medicine recently. It includes 6 items and 17 subitems, which set the reporting guidelines for the acupuncture rationale, the details of needling, the treatment regimen, other components of treatment, the practitioner background, and the control or comparator intervention. Also, the examples for the explanation of each item have been provided. The aim of this revision is first, to extend the STRICTA under the CONSORT roof, and second, to help authors of acupuncture trials provide readers with a clear, accurate, and transparent account of their acupuncture protocols as well as their control and/or comparator procedures. To some extent, we believe that it will provide help in improving the quality of reporting. Based on the nature of acupuncture and the necessity of reporting, however, some additional key elements should be involved in the reporting about acupuncture trials. These additional key elements are as follows.

Self-Consistent Algorithm for Calibrating Spectrometers to Picometer Accuracy over the Entire Wavelength Range

Spectrometer calibration accuracies are of high importance for a wide range of applications. Typically, one calibrates the spectrometer with a calibration lamp, providing distinct and well-defined calibration lines. However, for small spectral ranges, where only two calibration lines are present, the calibration becomes inaccurate. We present a high-precision nonlinear wavelength calibration method, which is based on two or more reference lines from a calibration lamp. The additional key element introduced is a Fabry-Perot multilayer structure that yields multiple sharp transmission maxima of similar intensity over the full spectrometer range under broad-band illumination (e.g., white-light source). An iterative algorithm is put forward to obtain a self-consistent calibration of picometer precision over the full spectrometer range. In regions distant from calibration lines the accuracy is enhanced by at least a factor of two compared to conventional methods.

The Day Care Ritual Abuse Moral Panic: A Sociological Analysis

AbstractA new type of sex crime was discovered in the United States in the 1980s – the sexual abuse of young children in ghastly rituals performed by devil worshippers who happened to be their day care providers. ‘Ritual abuse’, as this new sex crime came to be termed, appeared to be epidemic during that decade; hundreds of day care centers were investigated and scores of providers were arrested and prosecuted. This article asserts that the day care ritual abuse scare was a moral panic, in fact, the ‘purest example’ of a moral panic in that the putative threat to children had to be wholly constructed. Using the key sociological elements set out by Cohen (1972/2002), this article analyzes the day care ritual abuse moral panic and concludes by discussing additional key elements that will facilitate future sociological analyses of moral panics.

Diversity-Oriented Synthesis of a Drug-Like System Displaying the Distinctive N→C═O Interaction

This study describes the syntheses and characterization of two hydrazino ureas. These fold into a six-membered ring by virtue of the infrequently observed (delta+)N-->C=O (delta-) interaction when solvated by polar protic media. The highly polar functional group resulting from this interaction is hypothesized to especially reproduce electronic but also steric features of the transition states of peptide hydrolysis. The urea moiety constitutes an additional key element of modern HIV-1 protease (HIV PR) inhibitors and is meant to interact with the enzyme flaps. We have developed an efficient, convergent synthetic route to enantiopure compounds that uses CDI to couple two independent building blocks, one derived from amino acids and the other one from easily accessible hydrazines. It is thus amenable to rapid generation of diversity in order to screen for novel HIV PR inhibitors. A complete study using one- and two-dimensional NMR as well as UV spectroscopy confirmed the sole existence of the cyclic constitution of target compounds 7 and 8 in methanol. Total reversal to the linear aldehydic form is observed upon passage to apolar media.

Management of soft-tissue trauma to the face

The management of acute soft-tissue trauma can be very challenging for the facial plastic surgeon. The goals of management of facial trauma are the preservation of form and function. These goals are particularly important in facial soft-tissue trauma, where injuries can cause not only esthetic deformities but also can affect neural function, normal mastication, visual fields, and salivary outflow. This article outlines the evaluation and treatment of acute soft-tissue facial trauma. The key components include allowing for the stabilization of the patient, complete examination of the injury and face, thorough wound irrigation and debridement of necrotic tissue, preservation of all viable tissue, tension-free closure, and realignment of important facial esthetic structures. Special consideration must be given to injuries of functional structures such as the facial nerve, ductal systems or organs, and ensuring appropriated management of these structures.

Total Synthesis of Piericidin A1 and B1

The first total syntheses of piericidin A1 and B1 are disclosed and unambiguously establish the relative and absolute stereochemistry of the natural products by an approach that will facilitate the synthesis of a series of analogues. Central to the approach is an inverse electron demand Diels-Alder reaction of a N-sulfonyl-1-aza-1,3-butadiene with tetramethoxyethene followed by Lewis acid-promoted aromatization used to assemble the functionalized pyridine core. Additional key elements in the convergent approach include the use of an anti-aldol reaction to install the C9 and C10 relative and absolute stereochemistry, a modified Julia olefination for formation of the C5-C6 trans double bond with convergent assemblage of the side chain, and a penultimate heterobenzylic Stille cross-coupling reaction of the pyridyl core with the fully elaborated side chain.

Prefrontal cortex and dynamic categorization tasks: representational organization and neuromodulatory control.

We present a computational model of the intradimensional/ extradimensional (ID/ED) task (a variant of the Wisconsin card sorting task) that simulates the performance of intact and frontally lesioned monkeys on three different kinds of rule changes (Dias et al., 1997, J Neurosci 17:9285-9297). Although Dias et al. interpret the lesion data as supporting a model in which prefrontal cortex is organized into different processing functions, our model suggests an alternative account based on representational content. A key aspect of the model is that prefrontal cortex representations are organized according to different levels of abstraction, with orbital areas encoding more specific featural information and dorsolateral areas encoding more abstract dimensional information. This representational scheme of the model is integrated with two additional key elements: (i) activation-based working memory representations controlled by a dynamic gating mechanism that simulates the hypothesized phasic actions of dopaminergic neuromodulation in prefrontal cortex, which acts to stabilize or destabilize frontal representations based on success in the task; and (ii) a weight-based associative learning system simulating posterior cortex and other subcortical areas, where the stimulus-response mappings are encoded. Frontal cortex contributes to the task via top-down activation-based biasing of task-appropriate features and dimensions in this posterior cortex system - this top-down biasing is specifically important for overcoming prepotent associations after a sorting rule reverses. The ability of the model to capture the double-dissociation observed by Dias et al. with orbital versus dorsolateral lesions supports the validity of these principles, many of which have also been useful in accounting for other frontal phenomena.

The PDX-1 activation domain provides specific functions necessary for transcriptional stimulation in pancreatic beta-cells.

PDX-1 is a homeodomain transcription factor whose targeted disruption results in a failure of the pancreas to develop. Mutations in the human pdx-1 gene are linked to an early onset form of non-insulin-dependent diabetes mellitus. PDX-1 binds to and transactivates the promoters of several physiologically relevant genes within the beta-cell, including insulin, glucose transporter 2, glucokinase, and islet amyloid polypeptide. This study focuses on the mechanisms by which PDX-1 activates insulin gene transcription. To evaluate the role of PDX-1 in transcription of the insulin gene, a chloramphenicol acetyltransferase reporter construct was designed with a single yeast GAL4-DNA binding site in place of the A3/PDX-1 binding element in the rat insulin II enhancer. In the presence of GAL4:PDX chimeras containing N-terminal transactivation domain sequences, this GAL4-substituted insulin construct was active in PDX-1-expressing beta-cells and not non-beta-cells. PDX-1 activation was mediated through three highly conserved segments of the transactivation domain. In addition, when cotransfected together with the GAL4-substituted insulin enhancer reporter gene in glucose-responsive MIN-6 beta-cells, glucose-induced activation is observed with GAL4:PDX-1 but not with fusions of the heterologous activation domains from herpes virus VP16 or adenovirus-5 E1A proteins. Using A3 element-substituted GAL4 insulin enhancer reporter constructs containing mutations in two additional key control elements, E1 and C1, we also show that full activation requires cooperative interactions between other enhancer-bound factors, particularly the E1 element activators. In contrast, the activity of the VP16 activation factor was not dependent on the activators of either the E1 or C1 sites. These results suggest that the PDX-1 transactivation domain is specifically required for appropriate regulation of insulin enhancer function in beta-cells.