Managing Apparent Loss and Real Loss from the Nexus Perspective Using System Dynamics

When water utilities establish water loss control programs, they traditionally focus on apparent loss rather than real loss when considering economic feasibility in the water sector. There is an urgent need for new management approaches that can address complex relationships and ensure the sustainability of natural resources among different sectors. This study suggests a novel approach for water utilities to manage water losses from the water-energy (WE) Nexus perspective. The Nexus model uses system dynamics to simulate twelve scenarios with the differing status of water loss and energy intensities. This analysis identifies real loss as one of the main causes of resource waste and an essential factor from the Nexus perspective. It also demonstrates that the energy intensity of each process in the urban water system has a significant impact on resource use and transfer. The consumption and movement of resources can be quantified in each process involved in the urban water system to distinguish central and vulnerable processes. This study suggests that the Nexus approach can strongly contribute to quantifying the use and movement of resources between water and energy sectors and the strategic formulation of sustainable and systematic water loss management strategies from the Nexus perspective.

Modeling of Cross Work Hardening and Apparent Normality Loss after Biaxial–Shear Loading Path Change

The specific loading-path change during sheet metal forming may lead to some abnormal deformation phenomena. Two-stage orthogonal loading paths without elastic unloading have revealed a phenomenon of apparent loss of normality, further modeled in the literature by non-normality theories. In this paper, a particular orthogonal strain-path change is investigated using the Teodosiu–Hu hardening rule within an associated plasticity framework. The results indicate that cross work-hardening has a significant contribution to the apparent loss of normality and subsequent asymmetric yield surface evolution. Detailed contributions of the model’s ingredients and features are clarified. The developed material model is intended for sheet metal forming simulation applications.

FID-calibrated simultaneous multi-slice fast spin echo with long trains of hard pulses

Objective: To develop a novel, free-induction-decay (FID)-calibrated single-shot simultaneous multi-slice fast spin echo (SMS-FSE) with very long hard pulse trains for high encoding efficiency and low energy deposition. Approach: The proposed single-shot SMS-FSE employs a mixed pulse configuration in which a long excitation pulse that is spatially multi-band (MB) selective is used in conjunction with short spatially nonselective refocusing pulses. To alleviate energy deposition to tissues while reducing signal modulation along the echo train, variable low flip angles with signal prescription are utilized in the refocusing pulse train. A time-efficient FID-calibration and correction method is introduced before aliased voxels in the slice direction are resolved. Simulations and experiments are performed to demonstrate the feasibility of the proposed method as an alternative to conventional HASTE for generating T2-weighted images. Main results: Compared with conventional HASTE, the proposed method enhances imaging speed effectively by an MB factor up to 5 without apparent loss of image contrast while successfully eliminating FID artifacts. Significance: We successfully demonstrated the feasibility of the proposed method as an encoding- and energy-efficient alternative to conventional HASTE for generation of T2-weighted contrast.

Medievalism Disoriented

This chapter examines the valency of the Middle Ages in the recent French political imaginary, tracing how the nationalist medievalisms of recent decades can be read as a response to the perceived threats and uncertainties of globalization. The chapter explores the heated debates sparked by neoreactionary commentator Éric Zemmour’s use of the Middle Ages to account for France’s apparent loss of identity in the era of multiculturalism and the globalized economy. It also analyses how these debates play out in three recent novels that offer medievalist explorations of contemporary French identity: Jérôme Ferrari’s Sermon on the Fall of Rome (2012), Michel Houellebecq’s notorious 2015 novel Submission, and Mathias Enard’s 2015 novel Compass. By examining these texts together, the chapter offers an account of how France in the age of globalization has used the Middle Ages to understand its own long, contradictory love affair with ideas of nation, empire, and world.

The Free-of-Charge Phenomena in the Network Economy—A Multi-Party Value Exchange Model

The long-standing economic model is one where customers receive and pay for goods and services. However, in today’s modern network economy, why are vendors willing to provide free services and goods to free-riders at an apparent loss? The objective of this study is to provide a theoretical framework explaining why free network services emerge and how they work. This study adopted the multi-case study method, summarized 28 types of revenue model patterns from 51 indicative free network services, and inferred the causes for the antecedent conditions of each revenue model with Qualitative Comparative Analysis (QCA), in order to confirm the causal relationship between the various antecedent conditions, configurations, and revenue models as conclusive evidence. In addition, this study established seven conditional propositions via their links with related theories, which were taken as the basis for providing in-depth explanations of the revenue model of the free network service, and expanded the demonstration of the original network economy.

Sudden perceived absence of foetal movement – a unique presentation of a vertebral haemangioma in pregnancy

Objective: Symptomatic vertebral haemangiomas that present during pregnancy are extremely uncommon with few cases reported in literature. Epidural haemangiomas are rarer still with few documented. Methods: In this report, we describe the case of a 22-year-old pregnant patient who presented with apparent loss of foetal movement at 38 weeks’ gestation. Clinical review demonstrated the foetus was well but neurological examination revealed lower limb paresthesia, paresis, and evident uterine hypoesthesia. An MRI scan illustrated a haemangioma in the T1 vertebral body with an epidural component causing cord compression. Results: The management of spinal haemangiomas that present during pregnancy is a complex clinical scenario which requires careful multidisciplinary consideration to determine if surgical intervention is appropriate. In this case, the patient had an emergency caesarean section followed by posterior decompression and laminectomy of the T1 vertebra with excellent post-operative recovery. Conclusion: Gestational increase in the size of vertebral haemangiomas is well documented. We discuss a rare case in which a young pregnant patient presents with an atypical symptom of a vertebral haemangioma (uterine hypoesthesia). This case highlights the importance of prompt imaging in these scenarios and a cohesive multidisciplinary approach in order to provide optimal treatment for the patient.

Methodological Considerations in the Assessment of Effectiveness of Homeopathic Care: A Critical Review of the EPI3 Study

Background EPI3 is an observational study of a representative sample of general practitioners (GPs) and patients in France, demonstrating that patient characteristics differ according to the prescribing preferences of their GPs for homeopathy. For selected conditions (musculoskeletal disorders, sleep disorders, anxiety/depression, upper respiratory tract infections), progression of symptoms and adverse events over follow-up in the homeopathy preference group did not significantly differ from other practice preferences, but there was a two-fold to four-fold lower usage of conventional medicines. The EPI3 study's validity was challenged due to absence of head-to-head comparison of medicines to conclude on a causal association between homeopathy and outcomes. Methods A critical review of the nine EPI3 publications was conducted, focusing on generalizability, selection bias, outcome measurements and confounding. Results The conceptual framework of EPI3 rests on a systemic construct, i.e., the homeopathic treatment concept assessed using the type of GP prescribing preference, taking into account the clinical, human and social aspects. The enrollment process enhanced the generalizability of findings. Validated instruments for outcome measurements were used for three conditions, and control of confounding was rigorous. Conclusion EPI3 was conducted according to best practices. Homeopathy prescribing preference met specific patient needs with less use of conventional medicines and without an apparent loss in therapeutic opportunity.

Abstract P-9: Excess of Nhp6 over Spt16/Pob3 is Necessary for Efficient Nucleosome Unfolding by yFACT

Background: DNA accessibility in chromatin is important for proper gene expression and is regulated by multiple factors. One of them is histone chaperone FACT, which conducts large-scale ATP-independent nucleosome unfolding that increases the accessibility of nucleosomal DNA. FACT binding results in dramatic DNA uncoiling from nucleosome, occurs without apparent loss of histones, and proceeds via an ‘all-or-none’ mechanism, but the detailed mechanism of this process is still unknown. FACT-dependent nucleosome unfolding modulates the accessibility of nucleosomal DNA, and it is an important function of FACT in the processes of transcription, DNA replication, and repair in vivo. Methods: Nucleosome-positioning DNA sequences containing fluorescent labels (Cy3 and Cy5) at positions 13/91 or 35/112 from the nucleosome boundary were used. Nucleosomes were assembled by transfer of histone octamers from chicken chromatin to nucleosomal DNA during dialysis from 2M NaCl. After dialysis nucleosomes were gel purified and used at a final concentration of 0.5nM for spFRET measurements or at 10nM for EMSA analysis. For complex formation nucleosomes were incubated in the presence of Spt16/Pob3(0.13μM) and Nhp6(1.3μM) for 10 min at 30°C in buffer containing 17mM HEPES, 2mM Tris-HCl, 0.8mM Na3EDTA, 0.11mM 2-merсaptoethanol, 150mM KCl, 11mM NaCl, 1.1%glycerin, 12% sucrose. In spFRET microscopy analysis, the proximity ratio EPR from each nucleosome was calculated based on the intensity of the signals, corrected to the background and plotted as relative frequency distribution. Each plot was fitted as a sum of two Gaussians to describe two conformational states of nucleosomes. The fractions of nucleosomes in different states were estimated by calculating the surface of areas under the corresponding Gaussian peaks as a fraction of the total area of the plot. Results: Here we report the results of our analysis of nucleosome unfolding by yeast FACT (yFACT) at different ratios of Spt16/Pob3 and Nhp6 using single-particle Förster resonance energy transfer (spFRET) microscopy. Our analysis suggests that the optimal ratio of Spt16/Pob3 to Nhp6 for the most efficient FACT-dependent nucleosome unfolding is 1:10. Importantly, a mere increase in the concentration of FACT results in a decrease of the functional activity, suggesting that the formation of a functional complex having a certain stoichiometry of Spt16/Pob3 to Nhp6 is essential for efficient FACT-dependent nucleosome unfolding. Conclusion: We determined that a certain ratio of Spt16/Pob3 to Nhp6 is essential for efficient FACT-dependent nucleosome unfolding, suggesting the formation of a functional FACT: Nhp6 complex.

CRISPR-Cas9 Editing of Human Histone Deubiquitinase Gene USP16 in Human Monocytic Leukemia Cell Line THP-1

USP16 is a histone deubiquitinase which facilitates G2/M transition during the cell cycle, regulates DNA damage repair and contributes to inducible gene expression. We mutated the USP16 gene in a high differentiation clone of the acute monocytic leukemia cell line THP-1 using the CRISPR-Cas9 system and generated four homozygous knockout clones. All were able to proliferate and to differentiate in response to phorbol ester (PMA) treatment. One line was highly proliferative prior to PMA treatment and shut down proliferation upon differentiation, like wild type. Three clones showed sustained expression of the progenitor cell marker MYB, indicating that differentiation had not completely blocked proliferation in these clones. Network analysis of transcriptomic differences among wild type, heterozygotes and homozygotes showed clusters of genes that were up- or down-regulated after differentiation in all cell lines. Prior to PMA treatment, the homozygous clones had lower levels than wild type of genes relating to metabolism and mitochondria, including SRPRB, encoding an interaction partner of USP16. There was also apparent loss of interferon signaling. In contrast, a number of genes were up-regulated in the homozygous cells compared to wild type at baseline, including other deubiquitinases (USP12, BAP1, and MYSM1). However, three homozygotes failed to fully induce USP3 during differentiation. Other network clusters showed effects prior to or after differentiation in the homozygous clones. Thus the removal of USP16 affected the transcriptome of the cells, although all these lines were able to survive, which suggests that the functions attributed to USP16 may be redundant. Our analysis indicates that the leukemic line can adapt to the extreme selection pressure applied by the loss of USP16, and the harsh conditions of the gene editing and selection protocol, through different compensatory pathways. Similar selection pressures occur during the evolution of a cancer in vivo, and our results can be seen as a case study in leukemic cell adaptation. USP16 has been considered a target for cancer chemotherapy, but our results suggest that treatment would select for escape mutants that are resistant to USP16 inhibitors.