This paper investigates the bilateral teleoperation with the possibility of continuously variable scaling during real-time operation. The algorithm proposed for this purpose provides the operator with the ability to change the scaling gains of force and velocity loops during operation. The controllers are derived to enforce exponentially decaying error dynamics on systems which have inner loop disturbance compensation. The proposed architecture assumes the scale factors as continuous functions of time which have continuous derivatives that are also included in the mathematical derivation. Unlike the existing studies, the presented framework allows real-time adaptation of scaling gains, which provides the user with the ability to conduct coarse and fine motion in the same operation. The Lyapunov stability proof of the proposed method is made and the margins of the controller gains are identified for practical operation. Furthermore, the operational accuracy is enhanced by the application of a PD force control loop which is also new for scaled bilateral teleoperation. The realization of PD loop is made using an α - β - γ filter to differentiate the force signal. The algorithm is validated on a setup consisted of two single DOF motion control systems. In order to provide a complete analysis, a wide range of experiments are made, velocity and force scales having sinusoidal patterns with different amplitudes and frequencies. Moreover, comparison with a classical bilateral control architecture is made to highlight the flexibility of the proposed control method. The efficacy of the proposed approach is solidified by the successful tracking responses obtained from these experiments.

CD148 is a transmembrane protein tyrosine phosphatase (PTP) that is expressed in renal vasculature including the glomerulus. Previous studies have shown that CD148 plays a role in negative regulation of growth factor signals (including EGF and VEGF), suppressing cell proliferation and transformation. However, the role of CD148 in kidney disease remains unknown. Here, we have generated an agonistic anti-CD148 antibody and evaluated its effects in murine diabetic nephropathy (DN). Monoclonal antibodies (mAbs) against the mouse CD148 ectodomain sequence were generated by immunizing CD148 knockout (KO) mice. The mAbs that increase CD148 activity were selected by biological (proliferation) and biochemical (PTP activity) assays. The mAb (18E1) that showed strong agonistic activity was injected (10 mg/kg, i.p.) into streptozotocin-induced wild-type (WT) and CD148KO diabetic mice for 6 weeks, then renal phenotype was assessed. The effects of 18E1 mAb in podocyte growth factor signals were also assessed in culture. Compared to control IgG, 18E1 mAb significantly decreased albuminuria and mesangial expansion without altering hyperglycemia and blood pressure in WT diabetic mice. Immunohistochemical evaluation showed that 18E1 mAb significantly prevents the reduction of podocyte number and nephrin expression and decreases glomerular fibronectin expression and renal macrophage infiltration. The 18E1 mAb showed no effects in CD148KO diabetic mice. Furthermore, we demonstrate that 18E1 mAb reduces podocyte EGFR signals in culture and in diabetic mice. These findings suggest that agonistic anti-CD148 mAb attenuates DN in mice, in part by reducing EGFR signals in podocytes. This antibody may be used for the treatment of early DN.

Revealing the mechanisms underlying the breath-taking morphological diversity observed in nature is a major challenge in Biology. It has been established that recurrent mutations in hotspot genes cause the repeated evolution of rather simple morphological traits, such as body pigmentation or the gain and loss of structures. To date, however, it remains elusive whether hotspot genes contribute to natural variation in complex morphological traits, such as the size and shape of organs. Since natural variation in head morphology is pervasive in Drosophila, we studied the molecular and developmental basis of differences in compound eye size and head shape in two closely related Drosophila species. We show that differences in both traits are established late during head development and we applied comparative transcriptomics and chromatin accessibility data to identify the GATA transcription factor Pannier (Pnr) as central factor regulating these differences. Although the genetic manipulation of Pnr affected multiple aspects of dorsal head development, the effect of natural variation is restricted to a subset of the phenotypic space. We present data suggesting that this developmental constraint is caused by the co-evolution of expression of pnr and its co-factor u-shaped (ush). We propose that natural variation in highly connected developmental regulators with pleiotropic functions is a major driver for morphological evolution and we discuss implications on gene regulatory network evolution. In comparison to previous findings, our data strongly suggests that evolutionary hotspots do not contribute to the repeated evolution of eye size and head shape in Drosophila.

The size and shape of an organism is tightly controlled during embryonic and postembryonic development to ensure proper functionality. However, in the light of the breath-taking diversity of body forms observed in nature, developmental processes must have evolved to allow evolutionary changes in adult morphology. Therefore, gene regulatory networks (GRNs) that orchestrate organ development are mostly constrained, but nodes and edges within such networks must change to give rise to morphological divergence. Identifying such tuning nodes remains a major challenge in evolutionary developmental biology. Here, we combined comparative transcriptomics and chromatin accessibility data to study developmental differences leading to natural variation in compound eye size and head shape in the two closely related Drosophila species D. melanogaster and D. mauritiana. We show that variation in expression of the GATA transcription factor Pannier (Pnr) is associated with extensive remodeling of the transcriptomic landscape during head development. Since U-shaped (Ush), a co-factor of Pnr, is involved in the same regulatory context, we argue that variation in expression of both factors may be a driver of divergence in head morphology. Applying functional genetics and geometric morphometrics we confirmed that manipulation of pnr expression in D. melanogaster largely phenocopies D. mauritiana dorsal head shape and ommatidia number. Therefore, we propose that the regulatory module composed of Pnr and Ush represents a tuning node within the otherwise highly conserved GRN underlying head development in Drosophila.

Artemisinin and its derivatives kill malaria parasites and inhibit the proliferation of cancer cells. In both processes, heme was shown to play a key role in artemisinin bioactivation. We found that artemisinin and clinical artemisinin derivatives are able to compensate for a mutation in the yeast Bcs1 protein, a key chaperon involved in biogenesis of the mitochondrial respiratory complex III. The equivalent Bcs1 variant causes an encephalopathy in human by affecting complex III assembly. We show that artemisinin derivatives decrease the content of mitochondrial cytochromes and disturb the maturation of the complex III cytochrome c1. This last effect is likely responsible for the compensation by decreasing the detrimental over-accumulation of the inactive pre-complex III observed in the bcs1 mutant. We further show that a fluorescent dihydroartemisinin probe rapidly accumulates in the mitochondrial network and targets cytochromes c and c1 in yeast, human cells and isolated mitochondria. In vitro this probe interacts with purified cytochrome c only under reducing conditions and we detected cytochrome c-dihydroartemisinin covalent adducts by mass spectrometry analyses. We propose that reduced mitochondrial c-type cytochromes act as both targets and mediators of artemisinin bioactivation in yeast and human cells.

Let $\left(\mathcal{H},\left(.,.\right)\right)$ be a Hilbert space and let $\mathcal{L}\left(\mathcal{H}\right)$ be the linear space of bounded operators in $\mathcal{H}$. In this paper, we deal with $\mathcal{L}(\mathcal{H})$-valued function $Q$ that belongs to the generalized Nevanlinna class $\mathcal{N}_{\kappa} (\mathcal{H})$, where $\kappa$ is a non-negative integer. It is the class of functions meromorphic on $C \backslash R$, such that $Q(z)^{*}=Q(\bar{z})$ and the kernel $\mathcal{N}_{Q}\left( z,w \right):=\frac{Q\left( z \right)-{Q\left( w \right)}^{\ast }}{z-\bar{w}}$ has $\kappa$ negative squares. A focus is on the functions $Q \in \mathcal{N}_{\kappa} (\mathcal{H})$ which are holomorphic at $ \infty$. A new operator representation of the inverse function $\hat{Q}\left( z \right):=-{Q\left( z \right)}^{-1}$ is obtained under the condition that the derivative at infinity $Q^{'}\left( \infty\right):=\lim\limits_{z\to \infty}{zQ(z)}$ is boundedly invertible operator. It turns out that $\hat{Q}$ is the sum $\hat{Q}=\hat{Q}_{1}+\hat{Q}_{2},\, \, \hat{Q}_{i}\in \mathcal{N}_{\kappa_{i}}\left( \mathcal{H} \right)$ that satisfies $\kappa_{1}+\kappa_{2}=\kappa $. That decomposition enables us to study properties of both functions, $Q$ and $\hat{Q}$, by studying the simple components $\hat{Q}_{1}$ and $\hat{Q}_{2}$.

This paper integrates a different perspective into the diaspora literature, by placing it within the frame of digital diasporas and war time engagement in actions and initiatives traditionally considered as diplomatic. We reconstruct how digital diaspora diplomacy developed during a time when the Internet was relatively new and diplomatic tools were limited due to an ongoing conflict in Bosnia and Herzegovina. We examine BOSNET, an online epistemic community of Bosnian diaspora IT pioneers, with a shared set of normative and principled set of beliefs about the independence of their homeland, and collected, shared and spread information about what was going on in their country. We label their work as ‘policy innovation’ engagement and performativity as 'informal' behaviour, as it was unscripted, uncoded and unregulated by any written conventions or state strategies.

The paper proposes a problem-solving approach in the area of underground mining, related to the evaluation and selection of the optimal mining method, employing fuzzy multiple-criteria optimization. The application of fuzzy logic to decision-making in multiple-criteria optimization is particularly useful in cases where not enough information is available about a given system, and where expert knowledge and experience are an important aspect. With a straightforward objective, multiple-criteria decision-making is used to rank various mining methods relative to a set of criteria and to select the optimal solution. The considered mining methods represent possible alternatives. In addition, various criteria and subcriteria that influence the selection of the best available solution are defined and analyzed. The final decision concerning the selection of the optimal mining method is made based on mathematical optimization calculations. The paper demonstrates the proposed approach as applied in a case study.

Background: Necrotizing enterocolitis (NEC) is the most common life-threatening gastrointestinal emergency associated with prematurity. Timely diagnosis and adequate treatment are crucial to reduce the morbidity and mortality of the affected infants. The aim of this study was to evaluate the diagnostic yield of bowel dilatation on plane abdominal radiography (AR) in the early diagnosis and NEC severity in preterm infants. Methods: We retrospectively reviewed initial ARs of 50 preterm infants with NEC ≥ stage II admitted to the neonatal intensive care unit (NICU) in a tertiary-care hospital. The largest bowel loops diameters (AD), the latero-lateral diameters of the peduncle of the first lumbar vertebra (L1), and the distance of the upper edge of the first lumbar vertebra and the lower edge of the second one, including the disc space (L1–L2), were measured. All anteroposterior ARs were done in a supine projection on the day of onset of the initial symptoms of NEC. Results: Preterm infants with surgical NEC showed a statistically significant increase in the AD/L1 ratio (p < 0.001) and AD/L1-L2 ratio (p < 0.001) compared with preterm infants with medical NEC. We found no significant association between the site of the most distended bowel loop and the severity of NEC (p > 0.05). Conclusion: Bowel loop distension on initial AR may serve as an additional diagnostic tool in the early diagnosis and severity of stages II/III NEC. Further prospective clinical studies should validate the results from this study.