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Summary Therapeutic monoclonal antibodies (mAb) are usually of the IgG1, IgG2, and IgG4 classes, and their heavy chains may be modified by amino acid (aa) changes involved in antibody‐dependent cellular cytotoxicity (ADCC), antibody‐dependent cellular phagocytosis (ADCP), complement‐dependent cytotoxicity (CDC), and/or half‐life. Allotypes and Fc‐engineered variants are classified using IMGT/HGNC gene nomenclature (e.g., Homo sapiens IGHG1). Allotype names follow the WHO/IMGT nomenclature. IMGT‐engineered variant names use the IMGT nomenclature (e.g., Homsap G1v1), which comprises species and gene name (both abbreviated) followed by the letter v (for variant) and a number. Both allotypes and engineered variants are defined by their aa changes and positions, based on the IMGT unique numbering for C domain, identified in sequence motifs, referred to as IMGT topological motifs, as their limits and length are standardized and correspond to a structural feature (e.g., strand or loop). One hundred twenty‐six variants are displayed with their type, IMGT numbering, Eu‐IMGT positions, motifs before and after changes, and their property and function (effector and half‐life). Three motifs characterize effector variants, CH2 1.6–3, 23‐BC‐41, and the FG loop, whereas three different motifs characterize half‐life variants, two on CH2 13‐AB‐18 and 89–96 with H93, and one on CH3 the FG loop with H115. [ABSTRACT FROM AUTHOR]

Laser interstitial thermal therapy (LITT) is a minimally invasive surgical treatment for drug-resistant, focal epilepsies. With MRI guidance, LITT can also be used to treat hypothalamic hamartoma. Here, we report on the first European case of LITT for hypothalamic hamartoma. No complication occurred except a transitory peripheral facial paralysis. The short- and long term outcomes (for both epilepsy and cognitive development) were excellent. [ABSTRACT FROM AUTHOR]

Background: Nitric oxide (NO) is a strong vasodilator, selectively directed on pulmonary circulation through inhaled administration. In adult intensive care units (ICU), it is mainly used for refractory hypoxemia in mechanically ventilated patients. Several medical delivery devices have been developed to deliver inhaled nitric oxide (iNO). The main purpose of those devices is to guarantee an accurate inspiratory NO concentration, whatever the ventilator used, with NO2 concentrations lower than 0.3 ppm. We hypothesized that the performances of the different available iNO delivery systems could depend on their working principle and could be influenced by the ventilator settings. The objective of this study was to assess the accuracy of seven different iNO-devices combined with different ICU ventilators' flow-by to reach inspiratory NO concentration targets and to evaluate their potential risk of toxicity. Methods: We tested seven iNO-devices on a test-lung connected to distinct ICU ventilators offering four different levels of flow-by. We measured the flow in the inspiratory limb of the patient circuit and the airway pressure. The nitric oxide/nitrogen (NO/N2) flow was measured on the administration line of the iNO-devices. NO and NO2 concentrations were measured in the test-lung using an electrochemical analyzer. Results: We identified three iNO-device generations based on the way they deliver NO flow: "Continuous", "Sequential to inspiratory phase" (I-Sequential) and "Proportional to inspiratory and expiratory ventilator flow" (Proportional). Median accuracy of iNO concentration measured in the test lung was 2% (interquartile range, IQR -19; 36), -23% (IQR -29; -17) and 0% (IQR -2; 0) with Continuous, I-Sequential and Proportional devices, respectively. Increased ventilator flow-by resulted in decreased iNO concentration in the test-lung with Continuous and I-Sequential devices, but not with Proportional ones. NO2 formation measured to assess potential risks of toxicity never exceeded the predefined safety target of 0.5 ppm. However, NO2 concentrations higher than or equal to 0.3 ppm, a concentration that can cause bronchoconstriction, were observed in 19% of the different configurations. Conclusion: We identified three different generations of iNO-devices, based on their gas administration modalities, that were associated with highly variable iNO concentrations' accuracy. Ventilator's flow by significantly impacted iNO concentration. Only the Proportional devices permitted to accurately deliver iNO whatever the conditions and the ventilators tested. [ABSTRACT FROM AUTHOR]

Objectives Caspofungin is an echinocandin antifungal agent that inhibits synthesis of glucan required for the fungal cell wall. Resistance is mediated by mutation of Fks1 glucan synthase, among which S645P is the most common resistance-associated polymorphism. Rapamycin is a macrolide that inhibits the mechanistic target of rapamycin (mTOR) protein kinase activity. This study investigated the interaction between rapamycin and caspofungin in inhibiting the growth of WT Candida albicans and Fks1 S645P mutant clinical isolate, and WT Candida lusitaniae and genetically engineered isogenic strain with Fks1 S645P mutation at equivalent position. Methods Interactions between caspofungin and rapamycin were evaluated using the microdilution chequerboard method in liquid medium. The results were analysed using the Loewe additivity model (FIC index, FICI) and the Bliss independence model (response surface, RS, analysis). Results Synergy between rapamycin and caspofungin was shown for C. albicans and C. lusitaniae strains by RS analysis of the chequerboard tests. Synergy was observed in strains susceptible and resistant to caspofungin. Weak subinhibitory concentrations of rapamycin were sufficient to restore caspofungin susceptibility. Conclusions We report here, for the first time, synergy between caspofungin and rapamycin in Candida species. Synergy was shown for strains susceptible and resistant to caspofungin. This study highlights the possible implication of the TOR pathway in sensing antifungal-mediated cell wall stress and in modulating the cellular response to echinocandins in Candida yeasts. [ABSTRACT FROM AUTHOR]

Power Electronics (PE) is pivotal in fostering renewable energy. However, focusing on usage efficiency shifts environmental impacts across its life cycle, leading to excessive resource extraction and waste accumulation. Integrating environmental impact indicators in PE development is crucial for informed design decisions. Nevertheless, the current literature lacks the provision of adequate understanding of the PE product development process for successful ecodesign in PE industry. To effectively tackle the industrial integration aspect of ecodesign that enable functional and system innovation, this study employs empirical research, combining literature analysis with in-depth interviews with PE designers. Requirements for an ecodesign support to integrate ecodesign practices into the Product Development Process (PDP) of PCB-based Power Electronic Components (PECs) is proposed in this paper based on the interview results. These specifications are delineating the necessary working and decision- making steps. Subsequently, a parameterized Functional Block-based Life Cycle Analysis (FB-LCA) model is proposed under the requirement. A five-step methodology is proposed to operationalise the implementation of the FB-LCA model, aiming to supporting the definition of functional structure, configuration of technical solutions and choice of hardware components by considering environmental impacts generated all along life cycle, from manufacturing, transport, use, circularity scenario, end-of-life .The case study of a PCB-based boost converter design is conducted in collaboration with a PE engineer to test the practical implementation of FB-LCA model. [ABSTRACT FROM AUTHOR]

Human immunoglobulin allotypes are allelic antigenic determinants (or "markers") determined serologically, classically by hemagglutination inhibition, on the human immunoglobulin (IG) or antibody heavy and light chains. The allotypes have been identified on the gamma1, gamma2, gamma3, and alpha2 heavy chains (designated as G1m, G2m, G3m, and A2m allotypes, respectively) and on the kappa light chain (Km allotypes). Gm and Am allotypes have been one of the most powerful tools in population genetics, as they are inherited in fixed combinations, or Gm–Am haplotypes, owing to the linkage of the human IGHC genes in the IGH locus on chromosome 14. They have been very instrumental in molecular characterization of the human IGHC genes (gene polymorphisms or alleles, and IG heavy-chain structure in domains) and of the IGH locus (IGHC gene order, gene conversion, and copy number variation (CNV)). They represent a major system for understanding immunogenicity of the polymorphic IG chains in relation to amino acid and conformational changes. The WHO/IMGT allotype nomenclature and the IMGT unique numbering for constant (C) domain bridge Gm–Am and Km alleles to IGHC and IGKC gene alleles and structures and, by definition, to IG chain immunogenicity, opening the way for immunoinformatics of personalized therapeutic antibodies and engineered variants. [ABSTRACT FROM AUTHOR]

The constant region of the immunoglobulin (IG) or antibody heavy gamma chain is frequently engineered to modify the effector properties of the therapeutic monoclonal antibodies. These variants are classified in regards to their effects on effector functions, antibody-dependent cytotoxicity (ADCC), antibody-dependent phagocytosis (ADCP), complement-dependent cytotoxicity (CDC) enhancement or reduction, B cell inhibition by the coengagement of antigen and FcγR on the same cell, on half-life increase, and/or on structure such as prevention of IgG4 half-IG exchange, hexamerisation, knobs-into-holes and the heteropairing H-H of bispecific antibodies, absence of disulfide bridge inter H-L, absence of glycosylation site, and site-specific drug attachment engineered cysteine. The IMGT engineered variant identifier is comprised of the species and gene name (and eventually allele), the letter 'v' followed by a number (assigned chronologically), and for each concerned domain (e.g, CH1, h, CH2 and CH3), the novel AA (single letter abbreviation) and IMGT position according to the IMGT unique numbering for the C-domain and between parentheses, the Eu numbering. IMGT engineered variants are described with detailed amino acid changes, visualized in motifs based on the IMGT numbering bridging genes, sequences, and structures for higher order description. [ABSTRACT FROM AUTHOR]

The flux of CO2 diffusing inside a new type of bioreactors has been measured experimentally. This geoinspired bioreactor consists of a partially filled cylinder rotating around its axis tilted vertically, thus mimicking the precession motion of the Earth. The height of fluid is chosen equal to two radii in order for the first Kelvin mode to be resonant. The CO2 diffuses through a membrane located at the bottom of the liquid. The partial pressure of CO2 above the free surface is measured as a function of time. This temporal evolution is modeled by the presence of diffusive layers with no advection at the top and the bottom of the liquid. This basic model leads to an experimental value for the flux of CO2 at the membrane, which is found to be proportional to the inverse square root of the Ekman number. This is in agreement with the presence of Ekman layers of thickness proportional to the square root of the Ekman number. At a given Ekman number, the flux weakly depends on the tilt angle α with a scaling as α 1 / 4 . [ABSTRACT FROM AUTHOR]

IMGT®, the international ImMunoGeneTics information system®, created in 1989, by Marie-Paule Lefranc (Université de Montpellier and CNRS), marked the advent of immunoinformatics, a new science which emerged at the interface between immunogenetics and bioinformatics for the study of the adaptive immune responses. IMGT® is based on a standardized nomenclature of the immunoglobulin (IG) and T cell receptor (TR) genes and alleles from fish to humans and on the IMGT unique numbering for the variable (V) and constant (C) domains of the immunoglobulin superfamily (IgSF) of vertebrates and invertebrates, and for the groove (G) domain of the major histocompatibility (MH) and MH superfamily (MhSF) proteins. IMGT® comprises 7 databases, 17 tools and more than 25,000 pages of web resources for sequences, genes and structures, based on the IMGT Scientific chart rules generated from the IMGT-ONTOLOGY axioms and concepts. IMGT® reference directories are used for the analysis of the NGS high-throughput expressed IG and TR repertoires (natural, synthetic and/or bioengineered) and for bridging sequences, two-dimensional (2D) and three-dimensional (3D) structures. This manuscript focuses on the IMGT®Homo sapiens IG and TR loci, gene order, copy number variation (CNV) and haplotypes new concepts, as a paradigm for jawed vertebrates genome assemblies. [ABSTRACT FROM AUTHOR]

Individuals with transtibial amputation (TTA) experience altered gait mechanics, which are primarily attributed to the functional loss of the ankle plantarflexors. The plantarflexors contribute to body support and propulsion and play an important role in adapting to different load carriage conditions. However, how muscle function is altered across different prosthetic foot types and load carriage scenarios for individuals with TTA remains unclear. This study used musculoskeletal modeling and simulation of human movement in OpenSim to investigate the effects of a range of prosthetic feet and load conditions on individual muscle and prosthetic foot contributions to body support and propulsion. Twenty walking trials were collected from five individuals with TTA, consisting of five loading conditions (no-load; 30 lbs (13.6 kg) carried as a front-load, back-load, intact-side-load and residual-side-load) while wearing four prosthetic feet (their passive standard of care (SOC) foot, their SOC foot one category stiffer, their SOC foot with a heel stiffening wedge, and a dual-keel foot). Two participants also wore a powered ankle–foot prosthesis, thus completing an additional five trials each. The results indicated that the front-load condition may be more challenging because it required overall increased muscle contributions to body support and propulsion. However, the front- and residual-side-loads required reduced intact-side plantarflexor contributions to support and propulsion, and thus may be advantageous for individuals with plantarflexor weakness. Further, the large variability across contributions suggests that individuals with TTA may rely on a variety of compensatory mechanisms depending on the load condition and prosthetic foot used. [ABSTRACT FROM AUTHOR]

This study assesses the production potential, environmental impact, and economic viability of generating biohydrogen from biomethane obtained from the organic fraction of municipal solid waste (MSW) using steam methane reforming with carbon capture and storage (CCS). As the emissions are biogenic, CCS results in negative emissions. The methodology is based on a previously developed model, including techno-economic analysis based on the levelised cost of hydrogen (LCOH) and mobility (LCOM), and environmental assessment, focusing on production potential, cost estimates, and emissions impact. A case study is conducted to assess the feasibility of using this biohydrogen with negative emissions to decarbonize Madrid's public bus fleet. The findings reveal that Madrid's MSW could meet the entire hydrogen fuel demand if the fleet consisted of fuel-cell buses. However, given the high costs of replacing the entire fleet, a net-zero solution is proposed, combining 60% fuel-cell buses with existing natural gas-powered buses. In this configuration, the negative emissions from biohydrogen offset the fossil emissions from natural gas and 40% of biomethane is saved. The cost of the net-zero fleet ranges between 192.55 and 209.37 €/100 km, comparable with 100% natural gas fleet, which ranges between 176.19 and 217.69 €/100 km. [Display omitted] • Biohydrogen from SMR of biomethane with CCS using MSW as feedstock is proposed. • Potential and costs in Madrid are assessed for a net-zero emissions bus fleet. • Biohydrogen's negative emissions offset CO 2 emissions from natural gas engines. • Hybrid fleet (60% FCEV and 40% ICE with natural gas) achieves net-zero emissions. • Hybrid fleet costs (192.55–209.37 €/100 km) similar to pure natural gas fleet. [ABSTRACT FROM AUTHOR]

Endocrine disruptors and their effects on the reproductive axis are being mentioned more and more as one of the possible explanations for the increasing number of infertile couples. In women, they are incriminated both in pubertal advances and in cases of premature ovarian failure. They are also involved in the physiopathogenesis of endometriosis and polycystic ovary syndrome. In men, they are incriminated in various malformations of the genital tract. Their effects on the structure of the testicle have also been described as responsible for sperm abnormalities. Recent studies in Assisted Reproductive Technologies have shown their implication in the number and quality of oocytes during in vitro fertilization attempts, but also in implantation rates and miscarriage risks. Endocrine disruptors are omnipresent in everyday life, and it is difficult to clearly establish a harmful level of exposure. The lack of data on their long-term effects and the lack of awareness of their existence in the reproductive age population gives healthcare professionals a major role in primary prevention. [ABSTRACT FROM AUTHOR]

Simple Summary: Pathologies of the bladder are called cystitis. They cause discomfort for the patient. Due to persistent pain, bleeding, urinary incontinence, and uncontrolled urination, the chronic forms cause considerable degradation to patient quality of life. Currently, there is no curative treatment for the most severe forms. This is both an economic and a societal problem. Although the different forms of cystitis have different causes, they share common mechanisms. We propose to describe in detail the key processes and the associated mechanisms involved in abacterial cystitis. Cystitis is a bladder disease with a high rate of prevalence in the world population. This report focuses on Interstitial Cystitis (IC), Hemorrhagic Cystitis (HC) and Chronic Radiation Cystitis. These pathologies have different etiologies, but they share common symptoms, for instance, pain, bleeding, and a contracted bladder. Overall, treatments are quite similar for abacterial cystitis, and include bladder epithelium protective or anti-inflammatory agents, alleviating pain and reducing bleeding. This review summarizes the mechanisms that the pathologies have in common, for instance, bladder dysfunction and inflammation. Conversely, some mechanisms have been described as present in only one pathology, such as neural regulation. Based on these specificities, we propose identifying a mechanism that could be common to all the above-mentioned pathologies. [ABSTRACT FROM AUTHOR]

Most living organisms in both the plant and animal kingdoms have evolved processes to stay in tune with the alternation of day and night, and to optimize their physiology as a function of light supply. In mammals, a circadian clock relying on feedback loops between key transcription factors will thus control the temporally regulated pattern of expression of most genes. Modern ways of life have highly altered the synchronization of human activities with their circadian clocks. This review discusses the links between an altered circadian clock and the rise of pathologies. We then sum up the proofs of concept advocating for the integration of circadian clock considerations in chronotherapy for health care, medicine, and pharmacotherapy. Finally, we discuss the current challenges that circadian biology must face and the tools to address them. [ABSTRACT FROM AUTHOR]

Keywords: cochlear implantation; minimal invasive surgery; robot; robot-assisted surgery EN cochlear implantation minimal invasive surgery robot robot-assisted surgery 1326 1330 5 10/14/21 20211101 NES 211101 Key Points Cochlear implants are medical devices indispensable for the treatment of severe-to-profound bilateral sensorineural hearing loss. Improvements in robot-assisted surgery since 2010 have raised questions about the possibility of "simplifying" cochlear implant surgery. Cochlear implantation, minimal invasive surgery, robot, robot-assisted surgery The most commonly used surgical procedure for cochlear implantation involves temporal bone drilling associating mastoidectomy with a facial recess approach. [Extracted from the article]

This article presents a cascaded gate drive power supply configuration to reduce the common mode (CM) current in phase-shifted full-bridge (PSFB) converters. In such converters, there are at least two $dV/dt$ sources generated at different floating points associated to the parasitic capacitances of the isolated barriers of the gate drivers (power supplies, and control signal isolation units), which can increase the conducted electromagnetic interference perturbations. This article is focused on the analysis of a new gate drive power supply configuration, which reduces the CM currents that circulate in the control part of the switching cells. This improvement is achieved by modifying the impedance network of CM current pathways. Experimental results are provided to prove the effectiveness of the new gate drive power supply configuration on a PSFB converter based on SiC-MOSFET devices. [ABSTRACT FROM AUTHOR]

This article presents the design and optimization of a suitable topology for an isolated dc–dc auxiliary power supply with high isolation voltage and low coupling capacitance. The converter consists of a GaN HEMT inverter operating at 6.78 MHz, an LCC resonance tank, and a class-E low dv/dt rectifier. Furthermore, the galvanic isolation is implemented using a coreless planar transformer that enables higher insulation voltage with similar or better converter efficiency compared to designs using a magnetic material. An analytical design methodology is developed, however, SPICE investigations show that optimal designs might lie outside the validity of the design equations. Consequently, a virtual prototyping tool is developed based on a genetic algorithm with numerical simulations, and in turn, is used to optimize the converter. The optimization algorithm maximizes the converter efficiency while minimizing the transformer size. Prototypes are constructed based on the resulting Pareto front. Experimental results show the validity of the simulated results. Prototypes transferring power up to 15 W with a peak efficiency of 81% are shown. The selected topology enables insulating voltages exceeding 40 kV and coupling capacitances below 10 pF. [ABSTRACT FROM AUTHOR]

The existence of the cult to Luis Banchero Rossi --Peruvian businessman of the fish industry, who was murdered in 1972--, in the Angel cemetery, it demands the interest for its genesis, being that it is a religious cult to a secular character. The present text find that this is possible for two reasons: the violent death produce holiness; and the sacralization is not restricted to the limits of the institutionalized religion. Moreover, it proposes that, in the efficient, a factor that explains the cult is the book El caso Banchero (1973), of the journalist and writer Guillermo Thorndike. Furthermore, it practices an anthropological exegesis of it; and it evidences in this, mystified and messianic traits of the character, his life and his death; and they are understood like antecedents of the cult. Popular cults are disseminated fundamentally through of the orality, not by the written word; nevertheless, in this case the limits between the popular culture and the written text become blurred, which intermediary is the press. [ABSTRACT FROM AUTHOR]

Dear Editor, We were most interested to read Zhang et al.'s report on robot-assisted anterior cruciate ligament (ACL) reconstruction in skeletally immature patients [[1]]. With regard to accuracy, we imaged and registered the femur and tibia with distal tracers; we considered that each bone should be imaged separately because the joint can move when the tibia is being drilled. [Extracted from the article]

Background: Oropharyngeal squamous carcinoma (OPSC) continues to increase in incidence secondary to human papillomavirus (HPV) infection. Despite the good overall prognosis for these patients, treatment with chemoradiation is associated with morbidity and treatment failure. Better predictors for disease outcome are needed to guide de-intensification regimens. We hypothesized that estrogen receptor α (ERα), a prognostic biomarker in oncology with therapeutic implications, might have similar utility in OPSC.Methods: To investigate associations among ERα and demographics, HPV status, and survival, we analyzed ERα mRNA expression of head and neck squamous carcinomas (HNSC) from The Cancer Genome Atlas (TCGA) and immunohistochemistry (IHC) of pretreatment biopsy specimens from an independent group of 215 OPSC patients subsequently treated with primary chemoradiation (OPSC-CR). Associations among variables were evaluated with Fisher exact tests and logistic regression; associations with survival were evaluated with log-rank tests and Cox proportional hazards regression.Results: Among 515 patients in TCGA, ERα mRNA expression was highest in HPV-positive OPSC. High ERα mRNA expression was associated with improved survival among those receiving chemoradiation (hazard ratio adjusted for HPV status = 0.44, 95% confidence interval = 0.21 to 0.92). In OPSC-CR, ERα was positive by IHC in 51.6% of tumors and was associated with improved overall, disease-specific, progression-free, and relapse-free survival (log-rank tests: P < .001, P < .001, P = .002, P = .003, respectively); statistically significant associations of ERα positivity with improved survival were maintained after adjusting for clinical risk factors including HPV status.Conclusion: In two independent cohorts, ERα is a potential biomarker for improved survival that also may represent a therapeutic target in OPSC. [ABSTRACT FROM AUTHOR]

Covering: 1957 to 2017 Algae constitute a heterogeneous group of eukaryotic photosynthetic organisms, mainly found in the marine environment. Algae produce numerous metabolites that help them cope with the harsh conditions of the marine environment. Because of their structural diversity and uniqueness, these molecules have recently gained a lot of interest for the identification of medicinally useful agents, including those with potential anticancer activities. In the current review, which is not a catalogue-based one, we first highlight the major biological events that lead to various types of cancer, including metastatic ones, to chemoresistance, thus to any types of current anticancer treatment relating to the use of chemotherapeutics. We then review algal metabolites for which scientific literature reports anticancer activity. Lastly, we focus on algal metabolites with promising anticancer activity based on their ability to target biological characteristics of cancer cells responsible for poor treatment outcomes. Thus, we highlight compounds that have, among others, one or more of the following characteristics: selectivity in reducing the proliferation of cancer cells over normal ones, potential for killing cancer cells through non-apoptotic signaling pathways, ability to circumvent MDR-related efflux pumps, and activity in vivo in relevant pre-clinical models. [ABSTRACT FROM AUTHOR]

This paper presents a study on the gate driver circuitries that need to be implemented to drive several power devices when associated in series connection. More specifically, the propagation paths of parasitic currents through the gate driver circuitries, exited under high switching speeds, are studied in different configurations trying to minimize common mode currents generated. In a gate driver circuitry for a regular low side–high side switching cell configuration with one upper switch and one lower switch, the voltage transient dv/dt at the middle point applied across the primary-secondary parasitic capacitance of gate driver supplies, and control signal isolation units are the reasons for the generation of conducted electromagnetic interference (EMI) perturbations. In complex power converters, multicell, multilevel, or even series connection of power devices, many driver circuits are required and implemented. Similarly, in such converters, there are several dv/dt sources generated at different floating points producing conducted EMI perturbations from the power part to the control part through many gate driver circuitries. Based on previous works, this paper analyzes the best configuration to minimize parasitic currents, especially reducing the conducted common mode currents in series connected transistors topologies. Simulations and practical results validate the analysis for two power devices in series connection, and then the extrapolations for more power devices in series connection, up to six are discussed and analyzed with the help of simulations results. [ABSTRACT FROM AUTHOR]

Obesity is a multifaceted, chronic, low-grade inflammation disease characterized by excess accumulation of dysfunctional adipose tissue. It is often associated with the development of cardiovascular (CV) disorders, insulin resistance and diabetes. Under pathological conditions like in obesity, adipose tissue secretes bioactive molecules called 'adipokines', including cytokines, hormones and reactive oxygen species (ROS). There is evidence suggesting that oxidative stress, in particular, the ROS imbalance in adipose tissue, may be the mechanistic link between obesity and its associated CV and metabolic complications. Mitochondria in adipose tissue are an important source of ROS and their dysfunction contributes to the pathogenesis of obesity-related type 2 diabetes. Mitochondrial function is regulated by several factors in order to preserve mitochondria integrity and dynamics. Moreover, the renin-angiotensin-aldosterone system is over-activated in obesity. In this review, we focus on the pathophysiological role of the mineralocorticoid receptor in the adipose tissue and its contribution to obesity-associated metabolic and CV complications. More specifically, we discuss whether dysregulation of the mineralocorticoid system within the adipose tissue may be the upstream mechanism and one of the early events in the development of obesity, via induction of oxidative stress and mitochondrial dysfunction, thus impacting on systemic metabolism and the CV system. [ABSTRACT FROM AUTHOR]

In this anatomy report, we describe the first case of abducens nerve duplication limited to the sphenopetroclival venous gulf and the cavernous sinus. The objective point of division of the two duplicated roots was localized at the gulfar face of the dural porus, just distal to the unique cisternal trunk of the abducens nerve, as it pierced the petroclival dural mater. In the gulfar segment, both roots traveled through a variant of Dorello’s canal called the “petrosphenoidal canal” and remained separated through the posterior half of the cavernous sinus. Both roots finally fused in the anterior half of the cavernous sinus to innervate the lateral rectus muscle as a single trunk. Although many variants of the abducens nerve have been reported over the recent decades, this anatomic variation has never been previously described and enriches the continuum of abducens nerve variations reported in the literature data. Awareness of this variation is crucial for neurosurgeons, especially during clival or petrosal surgical approaches used for resection of skull base chordomas. [ABSTRACT FROM AUTHOR]

In this article, I sketch out something of a manifesto for the writing of queer theology. Beginning with a glimpse of the ways that anxieties about non-normative bodies and sexualities implicate all queer identity and practice (including so-called 'straight' sex which is considered transgressive for some other reason), I then suggest ways that an awareness of the values and practices of the bondage, discipline, dominance and submission, sadomasochism (BDSM) community can illuminate the indecency of theological reflection. I believe that kink represents a valuable approach to meaning-making which holds great possibilities for the theological discipline, particularly its unique relationship to social and interpersonal power dynamics, as well as its willingness to 'dig around in the dirt' of those things which are scary or taboo and find satisfying, sexy ways of relating to that fear. Above all, I hope to provoke new ways of thinking that challenge our easy answers about what progressive or liberative theology might look like, with deliberate attention to what is indecent in our frameworks. [ABSTRACT FROM AUTHOR]

Cytochrome c , an iron containing metalloprotein in the mitochondria of the cells with an oxide/redox property, plays key role in the cell apoptotic pathway. In this study, the interaction of silver nanoparticles (AgNPs) with cytochrome c (Cyt c) was investigated by using a combination of spectroscopic, imaging and thermodynamic techniques, including dynamic light scattering (DLS), ultraviolet–visible (UV–vis) spectroscopy, transmission electron microscopy (TEM), fluorescence spectroscopy, near and far circular dichroism (CD) spectroscopy, and isothermal titration calorimetry (ITC). DLS and UV–vis analysis evidenced the formation of surface complexes of Cyt c on AgNPs. The saturation of surface coverage of AgNPs was observed at 4.36 Cyt c molecules per nm2 of AgNPs. The surface complexation resulted in a promotion of the Ag dissolution overtime. The negative sign of enthalpic (ΔH) contribution suggested that electrostatic forces are indicative forces in the interaction between protein and AgNPs. Moreover, the fluorescence spectra revealed that the conformation of protein was altered around tryptophan (Trp) and tyrosine (Tyr) residues indicating the alteration of the tertiary structure of Cyt c. CD analysis evidenced that the secondary structure of Cyt c was modified under AgNPs-Cyt c interactions and the binding of Cyt c onto AgNPs resulted in remarkable structural perturbation around the active site heme, which in turn alter the protein enzymatic activity. The results of the present study contributed to a deeper insight on the mechanisms of interaction between NPs and biomacromolecules and could help establish the in vivo fate of AgNPs on cellular redox homeostasis. [Display omitted] • Cyt c - AgNPs interaction induced the formation of Cyt c /AgNP surface complexes. • Electrostatic forces are predominant forces in the Cyt c - AgNPs interaction. • Binding of Cyt c to AgNPs promoted AgNPs dissolution over time. • Binding of Cyt c to AgNPs altered the secondary and tertiary structure of Cyt c. • AgNPs changed the heme environment of Cyt c and activated the peroxidase-like activity. [ABSTRACT FROM AUTHOR]

Cells fine-tune microtubule assembly in both space and time to give rise to distinct edifices with specific cellular functions. In proliferating cells, microtubules are highly dynamics, and proliferation cessation often leads to their stabilization. One of the most stable microtubule structures identified to date is the nuclear bundle assembled in quiescent yeast. In this article, we characterize the original multistep process driving the assembly of this structure. This Aurora B-dependent mechanism follows a precise temporality that relies on the sequential actions of kinesin-14, kinesin-5, and involves both microtubule-kinetochore and kinetochore-kinetochore interactions. Upon quiescence exit, the microtubule bundle is disassembled via a cooperative process involving kinesin-8 and its full disassembly is required prior to cells re-entry into proliferation. Overall, our study provides the first description, at the molecular scale, of the entire life cycle of a stable microtubule structure in vivo and sheds light on its physiological function. [ABSTRACT FROM AUTHOR]

Equality of opportunity is usually defined as a situation where the effect of circumstances on outcome is nullified (compensation principle) and effort is rewarded (reward principle). We propose a new version of the reward principle based on the idea that effort deserves reward for it is costly. We show that luck can be introduced in two ways in the definition of these principles, depending on whether the correlation between luck and circumstances should be nullified and whether the correlation between luck and effort should be rewarded. In this regard, the timing of luck with respect to effort decisions is crucial, as is exemplified by moral hazard where effort choice influences the lottery of future uncertain events. [ABSTRACT FROM AUTHOR]

Starting from questions about the nature of cultural diversity, this paper examines the pace and tempo of change and the relative importance of continuity and discontinuity. To unravel the cultural project of the past, we apply chronological modelling of radiocarbon dates within a Bayesian statistical framework, to interrogate the Neolithic cultural sequence in Lower Alsace, in the upper Rhine valley, in broad terms from the later sixth to the end of the fifth millennium cal BC. Detailed formal estimates are provided for the long succession of cultural groups, from the early Neolithic Linear Pottery culture (LBK) to the Bischheim Occidental du Rhin Supérieur (BORS) groups at the end of the Middle Neolithic, using seriation and typology of pottery as the starting point in modelling. The rate of ceramic change, as well as frequent shifts in the nature, location and density of settlements, are documented in detail, down to lifetime and generational timescales. This reveals a Neolithic world in Lower Alsace busy with comings and goings, tinkerings and adjustments, and relocations and realignments. A significant hiatus is identified between the end of the LBK and the start of the Hinkelstein group, in the early part of the fifth millennium cal BC. On the basis of modelling of existing dates for other parts of the Rhineland, this appears to be a wider phenomenon, and possible explanations are discussed; full reoccupation of the landscape is only seen in the Grossgartach phase. Radical shifts are also proposed at the end of the Middle Neolithic. [ABSTRACT FROM AUTHOR]

The course of alcohol withdrawal is fairly well known in its first week, but medium-or long-term changes after cessation of alcohol consumption need special attention, in order to be supported in the best ways by the various caregivers. This text reviews the various somatic or psychic signs, appearing or changing during the weeks and the months after alcoholic withdrawal. This knowledge can help to optimize the methods of accompanying the patient after alcoholic withdrawal and supports the place of the general physician who works between specialized structures in charge of addiction therapy andmutual help groups. [ABSTRACT FROM AUTHOR]

This review is part of a special issue entitled “ Role of dietary pattern, foods, nutrients and nutraceuticals in supporting cancer prevention and treatment ” and describes a pharmacological strategy to determine the potential contribution of food-related components as anticancer agents against established cancer. Therefore, this review does not relate to chemoprevention, which is analysed in several other reviews in the current special issue, but rather focuses on the following: i) the biological events that currently represent barriers against the treatment of certain types of cancers, primarily metastatic cancers; ii) the in vitro and in vivo pharmacological pre-clinical tests that can be used to analyse the potential anticancer effects of food-related components; and iii) several examples of food-related components with anticancer effects. This review does not represent a catalogue-based listing of food-related components with more or less anticancer activity. By contrast, this review proposes an original pharmacological strategy that researchers can use to analyse the potential anticancer activity of any food-related component—e.g., by considering the crucial characteristics of cancer biological aggressiveness. This review also highlights that cancer patients undergoing chemotherapy should restrict the use of “food complements” without supervision by a medical nutritionist. By contrast, an equilibrated diet that includes the food-related components listed herein would be beneficial for cancer patients who are not undergoing chemotherapy. [ABSTRACT FROM AUTHOR]

Background: Clinicians, researchers and politicians are seeking to better assess caregiver's needs. Challenges exist in broadly implementing this so as to provide appropriate support. The aim of this review was to compile self-administered instruments for assessment of caregiver's needs that are deemed to be scientifically robust. Methods: The Medline database was searched for publications reporting self-administered instruments assessing caregiver's needs with acceptable psychometric properties. These instruments were analyzed in terms of the development context, target population, concept, purpose, structure, content and psychometric properties. The dimensions of the needs were listed and categorized. Results: A total of nine self-administered instruments were analyzed. They averaged 32 items, they were specifically developed for a targeted subpopulation of caregivers and dedicated to epidemiological research. Response devices were based on Likert scales. The main dimensions of the needs identified were 'Health and Care', 'Psychological - Emotional Support', 'Information--Knowledge', 'Social Life--Work--Finance'. None was specifically geared toward caregivers for the elderly, children or teenagers. In the absence of transcultural validation, no instrument was directly usable in Europe. Conclusions: Assessing caregivers' needs is a key part in providing caregivers with appropriate support. The development of self-administered instruments constitutes a complex field that is still underexplored at the international level; strict specifications with psychometric validation are essential. To be efficient, the instrument should be integrated in a larger process including: upstream, recognition, identification and assessment of the overall situation of the caregiver; and downstream, guidance, establishment and follow-up of a suitable action plan. [ABSTRACT FROM AUTHOR]

This article discusses the feelings of vengeance experienced by victims of crime and violence. The author comments on the military dictatorships of Latin America during the 1970s and 1980s and describes the clashes between the governments and political dissenters. An examination of the violations of human rights at the time is also provided.

Fretting wear is a surface degradation process caused by oscillatory motion and contact slipping. During gross slip, high local stresses and plastic deformation in the surface and subsurface can lead to the creation of a nanosized grained structure called Tribologically Transformed Structure (TTS). The current paper studies the formation of TTS in an alpha-beta Ti–6Al–4V alloy under fretting loading while changing the contact pressure and the number of fretting cycles. Cross-sections of wear scars are observed after polishing and chemical etching. Above a threshold pressure of 300 MPa, TTS appears early in the contact (before 1000 cycles) along with two other structures: a Third Body Layer (TBL) made of compacted debris and a General Deformed Layer (GDL) which is the plastic zone under the TTS. TTS first appears as islands and merges in the middle of the contact after enough cycles. Below 200 MPa, only TBL and GDL are formed. At 200 MPa, only small, localized TTS is found. All structures have the same chemical compositions as the initial bulk material except for the nitrided TBL. TTS has a very high hardness compared to the bulk. TTS was carefully extracted using a Focused Ion Beam (FIB) and its microstructure was observed with a Transmission Electron Microscope (TEM). It shows extreme grain refinement and is composed of two alternated zones. The first zone I is composed of α grains with a size of 20–50 nm with crystallographic texture. Zone II comprises nanosized equiaxed grains whose sizes range from 5 to 20 nm without texture. The results made it possible to establish a scenario of the appearance of the TTS according to the conditions of contact pressure and number of fretting cycles. • The fretting behaviour of Ti–6Al–4V is examined under different pressures and number of cycles. • Different stages of the subsurface microstructure transformation are observed. • The TTS is formed above a threshold contact pressure. • The TTS takes the form of a sandwich-like heterogeneous nanostructure at high pressures. [ABSTRACT FROM AUTHOR]

Abstract: Diffuse reflectance UV (DR-UV) spectroscopy was used for the first time to quantity the amount of creatinine adsorbed onto mordenite type zeolite from two different media: Phosphate Buffered Saline solution (D-PBS) and D-PBS solution containing albumin at a concentration corresponding to human serum conditions (50g/L). The UV spectra of creatinine adsorbed onto mordenite zeolites was quantitatively treated using the Kubelka–Munk formalism. Quantification by diffuse reflectance UV spectroscopy after microporous solids extraction was linearly correlated with creatinine concentration whatever the medium. This study evidences that DR-UV spectroscopy may be an efficient method to directly quantify the amount of chosen molecules present in a liquid medium by pre-concentrating them on a specific solid adsorbent like in the solid phase extraction (SPE) procedure. The results on hand also prove that this is even possible in rather complex conditions. The method is simple, fast, and with a low detection threshold. [Copyright &y& Elsevier]

Abstract: Mordenite framework type zeolites with different Si/Al ratios and H+ as charge compensating cation were found to be specific adsorbents for creatinine. Adsorption isotherms were determined varying the composition of the solvent systematically from pure water to physiological buffered saline solutions containing albumin. The adsorption mechanism is studied using different experiments: by following pH, ionic exchange and adsorption enthalpies during the adsorption process and by analyzing ex situ the chemical form of the adsorbate by 13C MAS-NMR. It is shown that creatinine adsorption, which is the highest when adsorbed from pure water, is reduced when adsorbed from sodium chloride solution or from physiological buffered saline solutions. Once adsorbed, creatinine is present in protonated form within the zeolite, in equilibrium with other cations of the medium. The level of this chemisorption is higher than the one determined in case of carbon type samples. When albumin is added to the physiological buffered saline solutions, adsorption level is only slightly modified, indicating that the weak albumin adsorption observed on the external surface of zeolite particles does not prevent creatinine access to the micropores. Adsorption by zeolites could, thus, be a complementary method for uremic toxins elimination during haemodialysis. [Copyright &y& Elsevier]

Abstract: IMGT, the international ImMunoGeneTics information system® (http://imgt.cines.fr) provides a common access to expertly annotated data on the genome, proteome, genetics and structure of immunoglobulins (IG), T cell receptors (TR), major histocompatibility complex (MHC), and related proteins of the immune system (RPI) of human and other vertebrates. The NUMEROTATION concept of IMGT-ONTOLOGY has allowed to define a unique numbering for the variable domains (V-DOMAINs) and constant domains (C-DOMAINs) of the IG and TR, which has been extended to the V-LIKE-DOMAINs and C-LIKE-DOMAINs of the immunoglobulin superfamily (IgSF) proteins other than the IG and TR (Dev Comp Immunol 27:55–77, 2003; 29:185–203, 2005). In this paper, we describe the IMGT unique numbering for the groove domains (G-DOMAINs) of the MHC and for the G-LIKE-DOMAINs of the MHC superfamily (MhcSF) proteins other than MHC. This IMGT unique numbering leads, for the first time, to the standardized description of the mutations, allelic polymorphisms, two-dimensional (2D) representations and three-dimensional (3D) structures of the G-DOMAINs and G-LIKE-DOMAINs in any species, and therefore, is highly valuable for their comparative, structural, functional and evolutionary studies. [Copyright &y& Elsevier]

Abstract: IMGT, the international ImMunoGeneTics information system® (http://imgt.cines.fr) provides a common access to expertly annotated data on the genome, proteome, genetics and structure of immunoglobulins (IG), T cell receptors (TR), major histocompatibility complex (MHC), and related proteins of the immune system (RPI) of human and other vertebrates. The NUMEROTATION concept of IMGT-ONTOLOGY has allowed to define a unique numbering for the variable domains (V-DOMAINs) and for the V-LIKE-DOMAINs. In this paper, this standardized characterization is extended to the constant domains (C-DOMAINs), and to the C-LIKE-DOMAINs, leading, for the first time, to their standardized description of mutations, allelic polymorphisms, two-dimensional (2D) representations and tridimensional (3D) structures. The IMGT unique numbering is, therefore, highly valuable for the comparative, structural or evolutionary studies of the immunoglobulin superfamily (IgSF) domains, V-DOMAINs and C-DOMAINs of IG and TR in vertebrates, and V-LIKE-DOMAINs and C-LIKE-DOMAINs of proteins other than IG and TR, in any species. [Copyright &y& Elsevier]

IMGT, the international ImMunoGeneTics information system© (http://imgt.cines.fr), is a high quality integrated knowledge resource specialized in immunoglobulins (IG), T cell receptors (TR), major histocompatibility complex (MHC) and related proteins of the immune system (RPI) of human and other vertebrates, created in 1989, by the Laboratoire d'ImmunoGénétique Moléculaire LIGM. IMGT provides a common access to standardized data which include nucleotide and protein sequences, oligonucleotide primers, gene maps, genetic polymorphisms, specificities, 2D and 3D structures. IMGT consists of several sequence databases (IMGT/LIGM-DB, IMGT/MHC-DB, IMGT/PRIMER-DB), one genome database (IMGT/GENE-DB) and one three-dimensional structure database (IMGT/3Dstructure-DB), interactive tools for sequence analysis (IMGT/V-QUEST, IMGT/JunctionAnalysis, IMGT/PhyloGene, IMGT/Allele-Align), for genome analysis (IMGT/GeneSearch, IMGT/GeneView, IMGT/LocusView) and for 3D structure analysis (IMGT/StructuralQuery), and Web resources ("IMGT Marie-Paule page") comprising 8000 HTML pages. IMGT other accesses include SRS, FTP, search by BLAST, etc. By its high quality and its easy data distribution, IMGT has important implications in medical research (repertoire in autoimmune diseases, AIDS, leukemias, lymphomas, myelomas), veterinary research, genome diversity and genome evolution studies of the adaptive immune responses, biotechnology related to antibody engineering (scFv, phage displays, combinatorial libraries) and therapeutical approaches (grafts, immunotherapy). IMGT is freely available at http://imgt.cines.fr. [ABSTRACT FROM AUTHOR]

Hydrogenation and transfer hydrogenation of imines with cyclohexa-1,4-dienes, as well as with a representative Hantzsch ester dihydrogen surrogate, are reported. Both processes are catalyzed by tethered Ru-S complexes but differ in the activation mode of the dihydrogen source: cooperative activation of the H-H bond at the Ru-S bond leads to the corresponding Ru-H complex and protonation of the sulfur atom, whereas the same cationic Ru-S catalyst abstracts a hydride from a donor-substituted cyclohexa-1,4-diene to form the neutral Ru-H complex and a low-energy Wheland intermediate. A sequence of proton and hydride transfers on the imine substrate then yields an amine. The reaction pathways are analyzed computationally, and the established mechanistic pictures are in agreement with the experimental observations. [ABSTRACT FROM AUTHOR]

Hydrogenation and transfer hydrogenation of imines with cyclohexa-1,4-dienes, as well as with a representative Hantzsch ester dihydrogen surrogate, are reported. Both processes are catalyzed by tethered Ru-S complexes but differ in the activation mode of the dihydrogen source: cooperative activation of the H-H bond at the Ru-S bond leads to the corresponding Ru-H complex and protonation of the sulfur atom, whereas the same cationic Ru-S catalyst abstracts a hydride from a donor-substituted cyclohexa-1,4-diene to form the neutral Ru-H complex and a low-energy Wheland intermediate. A sequence of proton and hydride transfers on the imine substrate then yields an amine. The reaction pathways are analyzed computationally, and the established mechanistic pictures are in agreement with the experimental observations. [ABSTRACT FROM AUTHOR]

Segregating the human cortex into distinct areas based on structural connectivity criteria is of widespread interest in neuroscience. This paper presents a groupwise connectivity-based parcellation framework for the whole cortical surface using a new high quality diffusion dataset of 79 healthy subjects. Our approach performs gyrus by gyrus to parcellate the whole human cortex. The main originality of the method is to compress for each gyrus the connectivity profiles used for the clustering without any anatomical prior information. This step takes into account the interindividual cortical and connectivity variability. To this end, we consider intersubject high density connectivity areas extracted using a surface-based watershed algorithm. A wide validation study has led to a fully automatic pipeline which is robust to variations in data preprocessing (tracking type, cortical mesh characteristics and boundaries of initial gyri), data characteristics (including number of subjects), and the main algorithmic parameters. A remarkable reproducibility is achieved in parcellation results for the whole cortex, leading to clear and stable cortical patterns. This reproducibility has been tested across non-overlapping subgroups and the validation is presented mainly on the pre- and postcentral gyri. [ABSTRACT FROM AUTHOR]

IMGT, the international ImMunoGeneTics database (http://imgt.cines.fr) is a high quality integrated information system specializing in immunoglobulins (IG), T cell receptors (TR) and major histocompatibility complex (MHC) of human and other vertebrates. IMGT provides a common access to expertly annotated data on the genome, proteome, genetics and structure of the IG and TR, based on the IMGT Scientific chart and IMGT-ONTOLOGY. The IMGT unique numbering defined for the IG and TR variable regions and domains of all jawed vertebrates has allowed a redefinition of the limits of the framework (FR-IMGT) and complementarity determining regions (CDR-IMGT), leading, for the first time, to a standardized description of mutations, allelic polymorphisms, 2D representations (Colliers de Perles) and 3D structures, whatever the antigen receptor, the chain type, or the species. The IMGT numbering has been extended to the V-like domain and is, therefore, highly valuable for comparative analysis and evolution studies of proteins belonging to the IG superfamily. [Copyright &y& Elsevier]

La cystite radique chronique est une pathologie consécutive d'une irradiation pelvienne caractérisée, par une inflammation chronique évoluant parfois vers une fibrose, avec des symptômes tels que des douleurs et des saignements. Des études précédentes sur la rectite radique ont montré que les cellules souches mésenchymateuses peuvent moduler l'inflammation chronique et la fibrose après l'irradiation. Notre étude était divisée en deux parties, la modélisation de la cystite radique chronique chez le rat puis l'effet du traitement par les cellules souches mésenchymateuses. La cystite radique chronique a été induit par une irradiation localisée de l'intégralité de la vessie à l'aide du Small Animal Radiation Research Platform (SARRP). Une gamme de doses de 20 à 80 Gy a été délivrée et un suivi de 3 à 12 mois après l'irradiation a été réalisé. Pour le traitement nous avons retenu la dose de 40 Gy, suivie 4 mois après l'irradiation d'une injection intraveineuse de 5 millions de cellules souches mésenchymateuses, administrée toutes les deux semaines (trois injections en tout). Un suivi physiologique, histologique et moléculaire a été réalisé pendant 12 mois après l'irradiation. Les résultats ont montré l'apparition de la cystite radique chronique dès 6 mois après l'irradiation, avec une inflammation chronique, une hématurie, une désorganisation de l'urothélium et une fibrose, augmentant avec le temps. L'analyse transcriptomique a indiqué un profil en faveur d'une inflammation chronique par rapport au témoin non irradié, avec la surexpression des gènes CCL5 (5 fois ; valeur p < 0,05), IL1β (7 fois ; p < 0,001) et IL6 (7,5 fois ; p < 0,01), dès 6 mois après l'irradiation. La fibrose était observable à partir de 6 mois après l'irradiation et augmentait proportionnellement au temps et à la dose d'irradiation. Des lésions de l'urothélium (basées sur les zones sans urothélium avec une diminution de l'uroplakine III) apparaissent à 6 mois après l'irradiation. À dix mois, une régénération de l'urothélium semblait mise en évidence par la surexpression de la cytokératine 5 (marqueur des cellules souches basales). Cependant, cette régénération paraissait défectueuse, puisque à 12 mois, une hyperplasie a été confirmée chez les rats irradiés (p < 0,01). Nous avons observé que l'intensité et la fréquence de l'hématurie étaient proportionnelles à la dose d'irradiation avec un seuil à 40 Gy et l'apparition de saignements à partir de 60 jours après l'irradiation. Le traitement par les cellules souches mésenchymateuses retarde l'apparition des saignements jusqu'à 300 jours après l'irradiation. Ces résultats sont en corrélation avec la réduction des lésions vasculaires observables jusqu'à 12 mois après l'irradiation. Le traitement par les cellules souches mésenchymateuses semble diminuer l'hyperplasie par rapport au témoin irradié. Il permet également de retarder l'hématurie, de diminuer les lésions vasculaires et l'hyperplasie. L'analyse de l'effet des cellules souches mésenchymateuses sur l'inflammation et la régénération de l'urothélium est en cours. [ABSTRACT FROM AUTHOR]

The Hill function is commonly used as a building block to model different dynamic patterns found in the response of genetic regulatory circuits within microorganisms and cells. These circuits are characterized by fast response and robustness against unmeasured disturbances. Therefore, microorganisms and cells can survive even if they are subjected to strong changes in their environment. However, as far as we know, the Hill function has not been used before to design process control systems. In this work, the repressor Hill function is applied to control the level of a conic tank. To eliminate the offset, we added integrative action. A local analysis was applied to define stability limits for the control parameters. A cost function that includes the error and the control effort was used to compare the performance of the Hill control against a standard PI and a PID-Dahlin controller. [ABSTRACT FROM AUTHOR]

A direct construction of bicyclo[3.2.1]octanes by an organocatalytic domino Michael/Aldol reaction of cyclic 1,3-keto esters with β,γ-unsaturated 1,2-keto amides is reported. Formation of a precipitate corresponding to the racemic co-crystals of the bicyclic compound was observed in toluene, whereas a homogeneous solution was obtained in dichloromethane. Preliminary mechanistic investigations on the reversibility of the system allowed enhancing the selectivity (>20:1 dr, 73% ee). Relative configuration of the bicyclic compound was determined by X-ray crystal structure analyses. [ABSTRACT FROM AUTHOR]

A direct construction of bicyclo[3.2.1]octanes by an organocatalytic domino Michael/Aldol reaction of cyclic 1,3-keto esters with β,γ-unsaturated 1,2-keto amides is reported. Formation of a precipitate corresponding to the racemic co-crystals of the bicyclic compound was observed in toluene, whereas a homogeneous solution was obtained in dichloromethane. Preliminary mechanistic investigations on the reversibility of the system allowed enhancing the selectivity (>20:1 dr, 73% ee). Relative configuration of the bicyclic compound was determined by X-ray crystal structure analyses. [ABSTRACT FROM AUTHOR]