Miracle-dz/UniFAR-FTUs huggingface dataset:
Dual factor delivery of CXCL12 and Exendin‐4 for improved survival and function of encapsulated beta cells under hypoxic conditions

A bioartifical pancreas (BAP) remains a promising approach for treating insulin‐dependent diabetes. Several obstacles to the clinical implementation of a BAP remain, including hypoxia following implantation. Within native pancreatic islets, CXCL12 and glucagon‐like peptide‐1 (GLP‐1) act in a paracrine fashion to promote the survival, function, and proliferation of β‐cells. This work sought to investigate if the presentation of CXCL12 and delivery of a GLP‐1 receptor analog, Exendin‐4 (Ex‐4), alone and in combination, conferred pro‐survival and insulinotropic effects on an encapsulated β‐cell line, βTC‐tet, cultured under hypoxic conditions of 7.6 mmHg O2. Our findings indicate that presentation of CXCL12 in the encapsulation matrix completely abrogated apoptosis under hypoxic conditions. Delivery of Ex‐4 increased insulin secretion rate under both normoxic and hypoxic conditions, and additionally reduced apoptosis under hypoxic conditions. Furthermore, presentation of CXCL12 combined with Ex‐4 delivery significantly increased insulin secretion rate under hypoxic conditions compared to delivery of Ex‐4 alone. These findings demonstrate that the presentation of CXCL12 combined with the delivery of Ex‐4 may constitute a promising strategy for supporting β‐cell function and survival following transplantation. Biotechnol. Bioeng. 2013; 110: 2292–2300. © 2013 Wiley Periodicals, Inc.
Toward a More Natural Science: Biology and Human Affairs

Leon Kass, physician-philosopher and student of the classics, has never lost his natural sense of awe and wonder. In discussing our deathdenying technologies he quotes Homer, and in musing on our care of dead bodies, he compares our practices with those of the ancient Persians (who would not permit a male body to be buried until it was torn by either a dog or a bird of prey). An avid bird watcher, he can write eloquently about the intricacy, ornateness, and exuberance of feathers. His quarry in this book is more formidable, and he approaches it with curiosity and respect—closing the gap between nature studied scientifically and life lived naturally. His quest is nothing less ambitious than reconstructing the science side of the split between the sciences and humanities by demonstrating how nature can teach us about ourselves and our place in the universe. Contemporary medical ethics is in danger
Electrostatic properties of confluent Caco‐2 cell layer correlates to their microvilli growth and determines underlying transcellular flow

Recently, Rajapaksa et al. (2010) showed that the rate of uptake of potential vaccine delivery nanoparticles in the mucosal layer is a function of the electrostatic properties of the corresponding solvent. This fundamentally implies that the dominant driving forces that may be capitalized on for mucosal vaccine strategies are electrostatic in nature. We hypothesize that the driving force normal to the cell (in the direction from apical to basolateral across the cell) is of particular importance. In addition, it has been theoretically shown that the electrostatic properties of mucosal cells are directly related to their development of brush border. Here we correlate the development of brush border on a human mucosal epithelial model (Caco‐2) cultured in DMEM on 3.0 µm pore sized polycarbonate membranes to their corresponding electrostatic properties characterized by measuring their normal zeta potential. Properties of normal streaming potential, hydraulic permeability, and brush border development (as determined by size and number) were monitored for 2, 6, and 16 days (after cells were confluent). Human endothelial cells (HECs), which lack brush border, were used as the control. Our results demonstrate that normal zeta potential of Caco‐2 cells significantly changed from −5.7 ± 0.11 mV to −3.4 ± 0.11 mV for a period between 2 and 16 days, respectively. The zeta potential of the control cell line, HECs, stayed constant (statistically not different, P > 0.05) for the duration of the experiments. Our results show that the calculated increase in surface area of the Caco‐2 cells with microvilli from 6 to 16 days was directly proportional to the corresponding measured zeta potential difference. These results imply that microvilli alter the electrostatic local environment around Caco‐2 cells and, hence, enhance the normal electrostatic selective transport of solute across the mucosal barrier. Biotechnol. Bioeng. 2013;110: 2742–2748. © 2013 Wiley Periodicals, Inc.
Dorsal and ventral stimuli in sandwich‐like microenvironments. Effect on cell differentiation

While most of the in vivo extracellular matrices are 3D, most of the in vitro cultures are 2D—where only ventral adhesion is permitted—thus modifying cell behavior as a way to self‐adaptation to this unnatural environment. We hypothesize that the excitation of dorsal receptors in cells already attached on a 2D surface (sandwich culture) could cover the gap between 2D and 3D cell–material interactions and result in a more physiological cell behavior. In this study we investigate the role of dorsal stimulation on myoblast differentiation within different poly(L‐lactic acid) (PLLA) sandwich‐like microenvironments, including plain material and aligned fibers. Enhanced cell differentiation levels were found for cells cultured with dorsal fibronectin‐coated films. Seeking to understand the underlying mechanisms, experiments were carried out with (i) different types of dorsal stimuli (FN, albumin, FN after blocking the RGD integrin‐binding site and activating dorsal cell integrin receptors), (ii) in the presence of an inhibitor of cell contractility, and (iii) increasing the frequency of culture medium changes to assess the effect of paracrine factors. Furthermore, FAK and integrin expressions, determined by Western blotting, revealed differences between cell sandwiches and 2D controls. Results show a stimuli‐dependent response to dorsal excitation, proving that integrin outside‐in signaling is involved in the enhanced cell differentiation. Due to their easiness and versatility, these sandwich‐like systems are excellent candidates to get deeper insights into the study of 3D cell behavior and to direct cell fate within multilayer constructs. Biotechnol. Bioeng. 2013;110: 3048–3058. © 2013 Wiley Periodicals, Inc.
Radiation Therapy for the Treatment of Thymoma in Rabbits (Oryctolagus cuniculus)

The article presents 3 clinical cases of thymoma in rabbits. The diagnosis of thymoma was made in these cases by combining the results of the case history, the physical examination, the blood work, the thoracic and abdominal imaging and the fine needle aspiration of the mass in 2 cases and a biopsy in 1 case. Palliative radiation treatment was elected in all 3 cases. 24 Gy were given in 3 fractions at 8 Gy on day 0, 7 and 21. In all cases the clinical signs and the quality of life significantly improved. Two cases were followed for 6 months post-treatment and no complications or recurrence of the clinical signs were noted, unfortunately the patients were lost for follow up examinations. One case is still in remission at 16 months post-treatment.
Software toolkit for modeling, simulation, and control of soft robots

The technological differences between traditional robotics and soft robotics have an impact on all of the modeling tools generally in use, including direct kinematics and inverse models, Jacobians, and dynamics. Due to the lack of precise modeling and control methods for soft robots, the promising concepts of using such design for complex applications (medicine, assistance, domestic robotics.) cannot be practically implemented. This paper presents a first unified software framework dedicated to modeling, simulation and control of soft robots. The framework relies on continuum mechanics for modeling the robotic parts and boundary conditions like actuators or contacts using a unified representation based on Lagrange multipliers. It enables the digital robot to be simulated in its environment using a direct model. The model can also be inverted online using an optimization-based method which allows to control the physical robots in the task space. To demonstrate the effectiveness of the approach, we present various soft robots scenarios including ones where the robot is interacting with its environment. The software has been built on top of SOFA, an open-source framework for deformable online simulation and is available at https://project.inria. fr/softrobot/
ROLE OF TOLL-LIKE RECEPTOR 4 IN LUNG INFLAMMATION FOLLOWING EXPOSURE TO SWINE BARN AIR

The authors tested a hypothesis that lung inflammation and airway hyperresponsiveness (AHR) induced following barn air exposure are dependent on Toll-like receptor 4 (TLR4) by exposing C3HeB/FeJ (intact TLR4, wild type [WT]) and C3H/HeJ (defective TLR4, mutant) mice either to the barn air (8 hours/day for 1, 5, or 20 days) or ambient air. Both strains of mice, compared to their respective controls, showed increased AHR following 5 exposures but dampened AHR after 20 exposures to show lack of effect of TLR4 on AHR. However, swine barn air induced lung inflammation with recruitment of inflammatory cells and cytokine expression was observed in WT but not in mutant mice. These data show different roles of TLR4 in lung inflammation and AHR in mice exposed to swine barn air.
Mass transfer studies of Geobacter sulfurreducens biofilms on rotating disk electrodes

Electrochemical impedance spectroscopy has received significant attention recently as a method to measure electrochemical parameters of Geobacter sulfurreducens biofilms. Here, we use electrochemical impedance spectroscopy to demonstrate the effect of mass transfer processes on electron transfer by G. sulfurreducens biofilms grown in situ on an electrode that was subsequently rotated. By rotating the biofilms up to 530 rpm, we could control the microscale gradients formed inside G. sulfurreducens biofilms. A 24% increase above a baseline of 82 µA could be achieved with a rotation rate of 530 rpm. By comparison, we observed a 340% increase using a soluble redox mediator (ferrocyanide) limited by mass transfer. Control of mass transfer processes was also used to quantify the change in biofilm impedance during the transition from turnover to non‐turnover. We found that only one element of the biofilm impedance, the interfacial resistance, changed significantly from 900 to 4,200 Ω under turnover and non‐turnover conditions, respectively. We ascribed this change to the electron transfer resistance overcome by the biofilm metabolism and estimate this value as 3,300 Ω. Additionally, under non‐turnover, the biofilm impedance developed pseudocapacitive behavior indicative of bound redox mediators. Pseudocapacitance of the biofilm was estimated at 740 µF and was unresponsive to rotation of the electrode. The increase in electron transfer resistance and pseudocapacitive behavior under non‐turnover could be used as indicators of acetate limitations inside G. sulfurreducens biofilms. Biotechnol. Bioeng. 2014;111: 285–294. © 2013 Wiley Periodicals, Inc.
THE PROTECTIVE EFFECT OF NIGELLA SATIVA ON LUNG INJURY OF SULFUR MUSTARD–EXPOSED GUINEA PIGS

The lung is one of the most exposable organs to chemical warfare agents such as sulfur mustard (SM) gas. Airway hyperresponsiveness and lung inflammation are reported in chemical warfare victims. There is no definite treatment for respiratory disorders induced by SM exposure. However, the protective effect of Nigella sativa on inflammatory process was shown. In the present study, the protective effect of Nigella sativa on tracheal responsiveness and lung inflammation of SM exposed guinea pigs was examined. Guinea pigs were exposed to diluent's solution (ethanol, control group), 100 mg/m3 inhaled sulfur mustard (SME group), and SME treated with Nigella sativa, 0.08 g daily (SME+N), n = 6 for each group. Tracheal responsiveness (TR) to methacholine, total white blood cell (WBC) count of lung lavage, and differential WBC were done 14 days post exposure. The weigh of animal were measured at the beginning, middle (day 7), and the end (day 14) of the study. The TR of SM-exposed guinea pigs was significantly (P <.001) and WBC nonsignificantly higher than those of controls. In SME guinea pigs, there was a weight loss but in the case of SME+N guinea pigs, no obvious weight change thought the study was seen. The eosinophl, monocyte, and lympocytes in SME animals were significantly changed compared to control group (P <.001 for all cases). Monocyte, lymphocyte, and neutrophil number were decreased in SME+N group compared to SME animals, which was significant only for neutrophil (P <.05). These results showed a preventive effect of Nigella sativa on TR of SM-exposed guinea pigs.
Model‐directed engineering of “difficult‐to‐express” monoclonal antibody production by Chinese hamster ovary cells

Despite improvements in volumetric titer for monoclonal antibody (MAb) production processes using Chinese hamster ovary (CHO) cells, some “difficult‐to‐express” (DTE) MAbs inexplicably reach much lower process titers. These DTE MAbs require intensive cell line and process development activity, rendering them more costly or even unsuitable to manufacture. To rapidly and rationally identify an optimal strategy to improve production of DTE MAbs, we have developed an engineering design platform combining high‐yielding transient production, empirical modeling of MAb synthesis incorporating an unfolded protein response (UPR) regulatory loop with directed expression and cell engineering approaches. Utilizing a panel of eight IgG1λ MAbs varying >4‐fold in volumetric titer, we showed that MAb‐specific limitations on folding and assembly rate functioned to induce a proportionate UPR in host CHO cells with a corresponding reduction in cell growth rate. Derived from comparative empirical modeling of cellular constraints on the production of each MAb we employed two strategies to increase production of DTE MAbs designed to avoid UPR induction through an improvement in the rate/cellular capacity for MAb folding and assembly reactions. Firstly, we altered the transfected LC:HC gene ratio and secondly, we co‐expressed a variety of molecular chaperones, foldases or UPR transactivators (BiP, CypB, PDI, and active forms of ATF6 and XBP1) with recombinant MAbs. DTE MAb production was significantly improved by both strategies, although the mode of action was dependent upon the approach employed. Increased LC:HC ratio or CypB co‐expression improved cell growth with no effect on qP. In contrast, BiP, ATF6c and XBP1s co‐expression increased qP and reduced cell growth. This study demonstrates that expression‐engineering strategies to improve production of DTE proteins in mammalian cells should be product specific, and based on rapid predictive tools to assess the relative impact of different engineering interventions. Biotechnol. Bioeng. 2014;111: 372–385. © 2013 Wiley Periodicals, Inc.
Model‐based derivation, analysis and control of unstable microaerobic steady‐states—Considering Rhodospirillum rubrum as an example

Microaerobic (oxygen‐limited) conditions are critical for inducing many important microbial processes in industrial or environmental applications. At very low oxygen concentrations, however, the process performance often suffers from technical limitations. Available dissolved oxygen measurement techniques are not sensitive enough and thus control techniques, that can reliable handle these conditions, are lacking. Recently, we proposed a microaerobic process control strategy, which overcomes these restrictions and allows to assess different degrees of oxygen limitation in bioreactor batch cultivations. Here, we focus on the design of a control strategy for the automation of oxygen‐limited continuous cultures using the microaerobic formation of photosynthetic membranes (PM) in Rhodospirillum rubrum as model phenomenon. We draw upon R. rubrum since the considered phenomenon depends on the optimal availability of mixed‐carbon sources, hence on boundary conditions which make the process performance challenging. Empirically assessing these specific microaerobic conditions is scarcely practicable as such a process reacts highly sensitive to changes in the substrate composition and the oxygen availability in the culture broth. Therefore, we propose a model‐based process control strategy which allows to stabilize steady‐states of cultures grown under these conditions. As designing the appropriate strategy requires a detailed knowledge of the system behavior, we begin by deriving and validating an unstructured process model. This model is used to optimize the experimental conditions, and identify properties of the system which are critical for process performance. The derived model facilitates the good process performance via the proposed optimal control strategy. In summary the presented model‐based control strategy allows to access and maintain microaerobic steady‐states of interest and to precisely and efficiently transfer the culture from one stable microaerobic steady‐state into another. Therefore, the presented approach is a valuable tool to study regulatory mechanisms of microaerobic phenomena in response to oxygen limitation alone. Biotechnol. Bioeng. 2014;111: 734–747. © 2013 Wiley Periodicals, Inc.
Risk Factors for Postoperative Infections After Single-Level Lumbar Fusion Surgery

Study Design. Retrospective multivariate analysis of a prospectively collected, multicenter database. Objective. To identify patient characteristics and perioperative risk factors associated with postoperative infectious complications after single-level lumbar fusion (SLLF) surgery. Summary of Background Data. Postoperative infection is a known complication after lumbar fusion. Risk factors for infectious complications after lumbar fusion have not been investigated using select set of SLLF procedures. Methods. Patients who underwent SLLF between 2006 and 2011 were identified from the American College of Surgeons National Surgical Quality Improvement Program database. Multivariate logistic regression analyses were performed to identify pre- and intraoperative risk factors associated with postoperative infection. Results. A total of 3353 patients were analyzed in this study. Overall, 173 (5.2%) patients experienced a postoperative infection, including 86 (2.6%) surgical site infections (SSIs) and 111 (3.3%) non-SSI infectious complications (pneumonia, urinary tract infection, sepsis/septic shock). Twenty-four (0.7%) patients experienced both SSI and non-SSI infectious complications. Postoperative SSI were associated with obesity (odds ratio [OR], 1.628; 95% confidence interval [CI], 1.042–2.544), American Society of Anesthesiologists class more than 2 (OR, 2.078; 95% CI, 1.309–3.299), and operative time more than 6 hours (OR, 2.573; 95% CI, 1.310–5.056). Risk factors for non-SSI infectious complications included age (60–69 yr; OR, 3.279; 95% CI, 1.541–6.980; and ≥70 yr; OR, 3.348; 95% CI, 1.519–7.378), female sex (OR, 1.791; 95% CI, 1.183–2.711), creatinine more than 1.5 mg/dL (OR, 2.400; 95% CI, 1.138–5.062), American Society of Anesthesiologists class more than 2 (OR, 1.835; 95% CI, 1.177–2.860), and operative time more than 6 hours (OR, 3.563; 95% CI, 2.082–6.097). Conclusion. Across a wide study population, we identified that obesity, advanced American Society of Anesthesiologists classification, and longer operative time were predictive of postoperative SSI. We also demonstrated that increased age, female sex, serum creatinine more than 1.5 mg/dL, and prolonged operative duration are associated with non-SSI infectious complications after SLLF. Continued efforts to elucidate and optimize perioperative risk factors are warranted to improve outcomes in patients requiring spinal fusion. Level of Evidence: 3
Microfluidic perfusion culture of human induced pluripotent stem cells under fully defined culture conditions

Human induced pluripotent stem cells (hiPSCs) are a promising cell source for drug screening. For this application, self‐renewal or differentiation of the cells is required, and undefined factors in the culture conditions are not desirable. Microfluidic perfusion culture allows the production of small volume cultures with precisely controlled microenvironments, and is applicable to high‐throughput cellular environment screening. Here, we developed a microfluidic perfusion culture system for hiPSCs that uses a microchamber array chip under defined extracellular matrix (ECM) and culture medium conditions. By screening various ECMs we determined that fibronectin and laminin are appropriate for microfluidic devices made out of the most popular material, polydimethylsiloxane (PDMS). We found that the growth rate of hiPSCs under pressure‐driven perfusion culture conditions was higher than under static culture conditions in the microchamber array. We applied our new system to self‐renewal and differentiation cultures of hiPSCs, and immunocytochemical analysis showed that the state of the hiPSCs was successfully controlled. The effects of three antitumor drugs on hiPSCs were comparable between microchamber array and 96‐well plates. We believe that our system will be a platform technology for future large‐scale screening of fully defined conditions for differentiation cultures on integrated microfluidic devices. Biotechnol. Biotechnol. Bioeng. 2014;111: 937–947. © 2013 Wiley Periodicals, Inc.
RESVERATROL AMELIORATES LUNG INJURY VIA INHIBITION OF APOPTOSIS IN RATS WITH SEVERE ACUTE PANCREATITIS

The objective of this study was to evaluate the protective effects of resveratrol on lung injury in rats with severe acute pancreatitis. Ninety-six male Sprague-Dawley rats were randomly classified into 4 equal groups (n = 24): control, model, resveratrol-treated, and dexamethasone-treated. The rats were evaluated at 3, 6, and 12 hours after induction of pancreatitis. The following were assessed: PaO2by arterial blood gas analysis; pancreatic and lung injury by histology; and ultrastructure of lung tissue by transmission electron microscopy. The authors investigated mitochondrial cytochrome c release and evaluated the Bax, Bcl-2, and caspase-3 expression levels in lung tissue over the time course of apoptosis. Changes in lung cell mitochondrial membrane potential were evaluated by confocal laser scanning microscopy. In the model group, lung congestion, edema, inflammatory-cell infiltration, mitochondrial swelling, and cell apoptosis were apparent. In the resveratrol and dexamethasone groups, the morphological changes of the lungs were alleviated. The expression level of Bcl-2 was significantly higher and those of Bax, caspase-3, and cytochrome c were significantly lesser in the resveratrol group than in the model group. Apoptosis is involved in lung injury associated with severe acute pancreatitis, and resveratrol can ameliorate this injury, thus protecting lung function in rats with severe acute pancreatitis.