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A preterm female infant with a birthweight 1770 g was born via spontaneous vaginal delivery at 34 weeks’ gestation to a 21-yearold mother who received an adequate prenatal care. Routine prenatal ultrasound at 30 weeks revealed a proximal dilatation of the gut and polyhydramnios. At delivery, initial physical exam revealed a soft ‘scaphoid’ abdomen. Apgar score was 7 and 8 at 1st and 5th minute, respectively. A nasogastric tube (NGT) was placed for gastric decompression and bilious drain was observed. Post-natal erect X-ray of the abdomen showed dilated loops in the upper abdomen with the paucity of gas in the pelvis and confirmed proximal bowel obstruction (Fig. 1). After 24 h of stabilisation and care in the neonatal intensive care unit, the patient was taken to the operating room for surgical repair of her presumed jejunal atresia. Surgical exploration revealed a markedly distended atretic jejunum with a ‘type 3B’ intestinal atresia (apple-peel jejunal atresia) and a significant loss of intestinal length. The proximal end of the jejunal atresia was located 15 cm below the ligament of Treitz. On the distal end of ileal atresia, there were two multiple ileal atresias, each 7 cm of length. Approximately, 55 cm of the small bowel distal from the ileal atresias was found to be patent (Fig. 2a). In our case, the total length of small intestine was 70 cm (15 cm distal to the ligament of Treitz and 55 cm proximal to the ileocecal valve). All atretic segments were resected. The remaining segments were preserved (without tapering proximal jejunoplasty) and connected with the end-to-end jejunoileal anastomosis using 5/0 polyglactin sutures in the single extramucosal layer employing the Cheatle technique for size mismatch (Fig. 2b). Appendectomy was also performed. Post-operatively, the patient was placed on mechanical ventilation and extubated on the 6th post-operative day (POD). Total parenteral nutrition (TPN) via a central line along with enteral nutrition via NGT were administered and lasted until the 39th POD. After 2 weeks, enteral feeding gradually improved, so the baby started receiving peroral nutrition via bottle. The patient achieved her full enteral intake on POD 38. The baby was discharged from the hospital on POD 46 with highly improved body weight – 2485 g. At the follow-up of 9 months (Fig. 3), the baby was doing well with a body weight of 7500 g.

E. Omerdic, Petar Trslic, Admir Kaknjo, Anthony Weir, M. Rao, G. Dooly, D. Toal

The overall control system for an open-frame Remotely Operated Vehicle (ROV) is typically built from three subsystems: guidance, navigation and control (GNC). The control allocation plays a vital role in the control subsystem. Typically, open-frame underwater vehicles have p actuators (thrusters) for the motion in the horizontal plane, and the control allocation problem, in this case, is very complex and hard to visualise, because the normalised constrained control subset is a p-dimensional unit cube. The aim of this paper is to give a clear picture and a geometric interpretation of the problem and to introduce a hybrid method, based on the integration of a weighted pseudoinverse and the fixed-point method. The main idea of the hybrid method is visualised, and the deep geometric insight is provided using a “virtual” ROV in low-dimensional control spaces, including visualisation of the attainable command set, solution lines, control energy spheres and the role of pseudoinverse and fixed-point iterations. The same concepts are then extended to higher-dimensional cases, for open-frame ROV with four X-shaped (vectored) horizontal thrusters, which is one of the most common thruster configurations for commercial ROVs. The proposed hybrid method has been developed, integrated into a generic fault-tolerant ROV control system and evaluated in virtual and real-world environments off the west coast of Ireland using observation-class ROV Latis and work-class ROV Étaín.

Abstract:Charitable endowments known as vakıf bolstered the urbanization, Islamization, and Ottomanization of the western Balkans. Some of the wealthiest and the most famous of these endowments were established by Ottoman state officials native to the region. This article focuses on two such officials, Hüseyin Pasha Boljanić (d. 1595) and Kara Sinan Bey Boljanić (d. 1582). These two brothers entered into Ottoman service through the devşirme, a levy of young men from rural and mostly Christian subjects living in parts of Anatolia and the Balkans. Hüseyin Pasha and Kara Sinan Bey are somewhat exceptional because they were Poturnak oğlanları, Muslim recruits for the devşirme. This article examines the motives behind their endowments. It places these motives in the larger context of the brothers’ shared identity as Poturnak oğlanları, their commercial and military interests, their relationship with the republic of Ragusa (Dubrovnik), and their family’s connection to the famed Sokollus. In doing so, this article elucidates how endowments in the western Balkans reflected the backgrounds, regional identities, and personal interests of their benefactors, as well as how they were shaped by their benefactors’ intisap (political clientage) and kinship ties.

M. Grunt, A. Failla, Ines Stevic, T. Hillebrand, H. Schwarzenbach

ABSTRACT The use of disease-specific signatures of microRNAs (miRNAs) in exosomes has become promising for clinical applications, either as biomarkers or direct therapeutic targets. However, a new approach for exosome enrichment and quantification of miRNAs is urgently needed for its clinical application, since the commercial techniques have shortcomings in quantity and quality. To overcome these deficiencies, we developed a new method for purification of exosomes with subsequent miRNA extraction, followed by quantitative reverse transcription polymerase chain reaction (RT-qPCR), and compared our assays with commercial techniques. For the establishment of these methods, numerous reagents, parameters, and combinations thereof were examined. Our new technique for exosome extraction is based on a mannuronate-guluronate polymer (MGP) which avoids co-precipitating plasma proteins. Quality, concentration and biological activity of the isolated exosomes were examined by Western blot, Nanoparticle Tracking Analysis (NTA), and confocal microscopy. A combination of chaotropic and non-chaotropic salts was used to extract miRNAs from plasma, serum, and exosomes, allowing the exclusion of hazardous components, such as phenol/chloroform. The performance of the miRNAs extraction was verified by RT-qPCR. The chemistry and TaqMan probe were also optimized for RT-qPCR. Sensitivity, efficiency, and linearity of RT-qPCR were tested on serial dilutions of synthetic miR-16 and miR-142. Our established procedure covers all steps of miRNA analyses, and measures the levels of either cell-free and exosomal miRNAs in plasma, serum and other body fluids with high performance.

Burak Oztoprak, Eray A. Baran, A. Sabanoviç

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.

Keiko Takahashi, R. Kim, L. Pasic, Lilly He, S. Nagasaka, D. Katagiri, Tracy May, A. Shimizu et al.

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.

Following publication of the original article [1], the authors opted to correct the name of co-author Amra Zalihić from Zahilić to Zalihić. The original article has been corrected.

C. Brennan, S. Cobbe, K. Cremin, Ariana Garotte, E. Grigorenko, Sandra Grüter, S. Mehta, Haris Memisevic et al.

A. Lalève, C. Panozzo, Inge Kühl, A. Bourand-Plantefol, J. Ostojić, A. Sissoko, D. Tribouillard-Tanvier, David Cornu et al.

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 $\hat{Q}_{2}$.

E. Buchberger, Anıl Bilen, Sanem Ayaz, D. Salamanca, Cristina Matas de las Heras, Armin Niksic, I. Almudi, Montserrat Torres-Oliva et al.

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.

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