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We have previously demonstrated benefits of kidney preservation utilizing an oxygenated subnormothermic ex vivo perfusion platform. Herein, we aim to compare pulsatile versus centrifugal (steady an...

Introduction The current methods of preserving donor kidneys in nonoxygenated cold conditions minimally protect the kidney against ischemia-reperfusion injury (IRI), a major source of complications in clinical transplantation. However, preserving kidneys with oxygenated perfusion is not currently feasible due to the lack of an ideal perfusion mechanism that facilitates perfusion with blood at warm temperature. Here, we have designed an innovative renal pump circuit system that can perfuse blood or acellular oxygen carrier under flexible temperatures, pressures, and oxygenation. We have tested this apparatus to study optimal conditions of storage of our porcine model of donation after cardiac death (DCD) kidneys. Methods Porcine kidneys were retrieved after 30 minutes of cross-clamping renal pedicles in situ. Cessation of blood mimics postcardiac death in humans and simulates DCD warm ischemic injury. Procured kidneys were flushed and subjected to static cold storage (SCS) for 4 hours. For warm perfusion, kidneys were cannulated for pulsatile oxygenated perfusion with blood:PlasmaLyte for 4 hours at 15 °C, 22 °C, and 37 °C. To mimic posttransplant scenario, all kidneys were reperfused with blood for an additional 4 hours at 37 °C. Results Compared with all other groups, 22 °C perfusion resulted in significant reduction of acute tubular necrosis (ATN), apoptosis, kidney damage markers, Toll-like receptor signaling, and cytokine production. It was associated with maximal renal blood flow and urine output. Kidneys stored at 15 °C thrombosed within 2 hours under this condition. Martius Scarlet Blue staining confirmed that 22 °C was the optimal temperature to minimize hemorrhage and blood clots. Conclusion Our novel study shows that oxygenated perfusion at near-room-temperature provides optimal donor kidney storage conditions., Graphical abstract

Based on the theory of wax deposition dynamics, and the wax deposition rate model of a Tieling–Jinxi insulated crude oil pipeline was established for Daqing–Jilin mixed oil. Based on their physical...

As a hybrid approach to realizing fusion energy, Magnetized Target Fusion (MTF) based on the Field Reversed Configuration (FRC), which has the plasma density and confinement time in the range between magnetic and inertial confinement fusion, has been recently widely pursued around the world. To investigate the formation and confinement of the FRC plasma injector for MTF, the Yingguang-I, which is an FRC test device and contains a multi-bank program-discharged pulsed power sub-system, was constructed at the Institute of Fluid Physics (IFP), China. This paper presents the pulsed power components and their parameters of the device in detail, then gives a brief description of progress in experiments of FRC formation. Experimental results of the pulsed power sub-system show that the peak current/magnetic field of 110 kA/0.3 T, 10 kA/1.2 T and 1.7 MA/3.4 T were achieved in the bias, mirror and θ-pinch circuits with quarter cycle of 80 μs, 700 μs and 3.8 μs respectively. The induced electric field in the neutral gas was greater than 0.25 kV/cm when the ionization bank was charged to 70 kV. With H2 gas of 8 Pa, the plasma target of density 1016 cm−3, separatrix radius 4 cm, half-length 17 cm, equilibrium temperature 200 eV and lifetime 3 μs (approximately the half pulse width of the reversed field) have been obtained through the θ-pinch method when the bias, mirror, ionization and θ-pinch banks were charged to 5 kV, 5 kV, 55 kV and ±45 kV respectively. The images from the high-speed end-on framing camera demonstrate the formation processes of FRC and some features agree well with the results with the two-dimension magneto hydrodynamics code (2D-MHD). Keywords: Magnetized Target Fusion (MTF), Field Reversed Configuration (FRC), Magnetized plasma, Pulsed power, PACS codes: 84.70.+p, 52.55.Lf, 52.25.Xz

Background The optimal method of oxygen delivery to donor kidneys during ex vivo machine perfusion has not been established. We have recently reported the beneficial effects of subnormothermic (22°C) blood perfusion in the preservation of porcine donation after circulatory death kidneys. Since using blood as a clinical perfusate has limitations, including matching availability and potential presence of pathogen, we sought to assess hemoglobin-based oxygen carrier (HBOC-201) in oxygen delivery to the kidney for renal protection. Methods Pig kidneys (n = 5) were procured after 30 minutes of warm in situ ischemia by cross-clamping the renal arteries. Organs were flushed with histidine tryptophan ketoglutarate solution and subjected to static cold storage or pulsatile perfusion with an RM3 pump at 22°C for 4 hours with HBOC-201 and blood. Thereafter, kidneys were reperfused with normothermic (37°C) oxygenated blood for 4 hours. Blood and urine were subjected to biochemical analysis. Total urine output, urinary protein, albumin/creatinine ratio, flow rate, resistance were measured. Acute tubular necrosis, apoptosis, urinary kidney damage markers, neutrophil gelatinase-associated lipocalin 1, and interleukin 6 were also assessed. Results HBOC-201 achieved tissues oxygen saturation equivalent to blood. Furthermore, upon reperfusion, HBOC-201 treated kidneys had similar renal blood flow and function compared with blood-treated kidneys. Histologically, HBOC-201 and blood-perfused kidneys had vastly reduced acute tubular necrosis scores and degrees of terminal deoxynucleotidyl transferase 2'-deoxyuridine, 5'-triphosphate nick end labeling staining versus kidneys treated with cold storage. Urinary damage markers and IL6 levels were similarly reduced by both blood and HBOC-201. Conclusions HBOC-201 is an excellent alternative to blood as an oxygen-carrying molecule in an ex vivo subnormothermic machine perfusion platform in kidneys.

PARP2 belongs to a family of proteins involved in cell differentiation, DNA damage repair, cellular energy expenditure, and chromatin modeling. In addition to these overlapping functions with PARP1, PARP2 participates in spermatogenesis, T-cell maturation, extra-embryonic endoderm formation, adipogenesis, lipid metabolism, and cholesterol homeostasis. Knowledge of the functions of PARP2 is far from complete, and the mechanism(s) by which the gene and protein are regulated are unknown. In this study, we found that two different mechanisms are used in vitro to regulate PARP2 levels. In the presence of serum, PARP2 is degraded through the ubiquitin–proteasome pathway; however, when serum is removed or dialyzed with a 3.5 kDa molecular cut membrane, PARP2 rapidly becomes sodium dodecyl sulphate- and urea-insoluble. Despite the presence of a putative serum response element in the PARP2 gene, transcription is not affected by serum deprivation, and PARP2 levels are restored when serum is replaced. The loss of PARP2 affects cell differentiation and gene expression linked to cholesterol and lipid metabolism. These observations highlight the critical roles that PARP2 plays under different physiological conditions, and reveal that PARP2 is tightly regulated by distinct pathways.

As a typical cylindrical-convergent drive technique, magnetically driven solid liner implosion could compress interior substance with a shock or quasi-isentropic manner, which has been widely used to investigate the hydrodynamic behavior, the dynamic characteristics of material and fusion energy and so on. For aspecific facility, the implosion parameters depend on material, radius and thickness of the liner, and the ablation of liner restrict the optional parameters. The concept of electrical action is introduced via thin shell model, which not only is the representation of states for conductive metal, but also indicates the change of liner velocity under the condition of thin shell hypothesis. The result shows that the outer velocity of liner increases linearly with electrical action and is directly proportional to liner thickness but inversely proportional to liner density. The incompressible zero-dimensional model is used to calculate the dynamic parameters of thin shell liner, including the implosion time, the outer interface velocity, the implosion kinetic energy, and the electrical action under the condition of low linear current density. There exist optimal radius and thickness which can achieve the maximum velocity, momentum, and kinetic energy. The aluminum is suitable for reaching higher velocity and the copper can obtain higher pressure according to a proportionality coefficient Qb/ρ which is an intrinsic quality of metal. A one-dimensional (1D) elastic plastic magnetic hydrodynamic code which is called SOL1D is developed to simulate liner implosion behavior. The modified relationship between resistivity and electrical action is introduced to SOL1D, which can adapt higher hydrodynamic pressure. According to current waves, the 1D code can be used to simulate liner implosion behavior for all kinds of current densities. The 1D simulation liner velocity is in agreement with both the experimental results and the electrical action model for liner implosion experiment on FP-1 facility. The simulation of isentropic compression experiment at ZR facility shows that the magnetic diffusion process is suppressed at extra high current density and hydrodynamic pressure, and the electrical action is larger than the experimental value of wire electrical explosion. The zero-dimensional (0D) and 1D simulation show that estimating the liner velocity and liner phase changing via the electrical action are suitable when thin shell hypothesis and low current density assumption are satisfied.

Background Carbon monoxide (CO) inhalation protects organ by reducing inflammation and cell death during transplantation processes in animal model. However, using CO in clinical transplantation is difficult due to its delivery in a controlled manner. A manganese-containing CO releasing molecules (CORM)-401 has recently been synthesized which can efficiently deliver 3 molar equivalents of CO. We report the ability of this anti-inflammatory CORM-401 to reduce ischemia reperfusion injury associated with prolonged cold storage of renal allografts obtained from donation after circulatory death in a porcine model of transplantation. Methods To stimulate donation after circulatory death condition, kidneys from large male Landrace pig were retrieved after 1 hour warm ischemia in situ by cross-clamping the renal pedicle. Procured kidneys, after a brief flushing with histidine-tryptophan-ketoglutarate solution were subjected to pulsatile perfusion at 4°C with University of Wisconsin solution for 4 hours and both kidneys were treated with either 200 μM CORM-401 or inactive CORM-401, respectively. Kidneys were then reperfused with normothermic isogeneic porcine blood through oxygenated pulsatile perfusion for 10 hours. Urine was collected, vascular flow was assessed during reperfusion and histopathology was assessed after 10 hours of reperfusion. Results We have found that CORM-401 administration reduced urinary protein excretion, attenuated kidney damage markers (kidney damage marker-1 and neutrophil gelatinase-associated lipocalin), and reduced ATN and dUTP nick end labeling staining in histopathologic sections. CORM-401 also prevented intrarenal hemorrhage and vascular clotting during reperfusion. Mechanistically, CORM-401 appeared to exert anti-inflammatory actions by suppressing Toll-like receptors 2, 4, and 6. Conclusions Carbon monoxide releasing molecules-401 provides renal protection after cold storage of kidneys and provides a novel clinically relevant ex vivo organ preservation strategy.

Study on the compression of field-reversed configuration (FRC) by a magnetic-driven solid liner is carried out based on a one-dimensional code. In the investigation, plasma self-heating effect by alpha particles is taken into account. Numerical results show that the self-heating of alpha particles to DT plasma mainly occurs in the vicinity of O-point of the FRC target. The plasma ignition region is divided into two parts: the low-density ignition region near the central axis and the high-density ignition region in the O-point area. Before FRC plasma target expansion, the energy of alpha particles is well confined nearby the O-point by compressed magnetics. The DT plasma volume burning exists in a short time (approximately 0.1 µs) after a maximum convergence ratio of solid liner and the compressed strong magnetic field degrades the propagation of FRC plasma burning.

STUDY DESIGN A biomechanical study of cervical artificial disk replacement (CADR). OBJECTIVE This study aimed to investigate the range of motion (ROM) of the treated segment, the ROM of the adjacent segments, the global ROM in the sagittal plane, and the total neck ROM in the 3 cardinal planes after single-level Discover CADR. SUMMARY OF BACKGROUND DATA CADR could theoretically preserve the motion function of the treated segment without affecting the adjacent segments significantly. Although previous studies have reported excellent clinical outcomes and ROM of the treated segment after CADR, few studies have focused on the ROM of the adjacent segments, the global ROM, and the total neck motion. METHODS C5/6 Discover CADR was performed in 58 patients (37 male and 21 female) between September 2008 and September 2010. Anteroposterior, lateral, and flexion-extension lateral radiographies were performed before operation and at the 1-year follow-up. Clinical parameters, including the Japanese orthopedic association score, the neck disability index, and the visual analogue scale, were evaluated. The ROM of the treated segment (C5/6) and the adjacent segments (C4/5 and C6/7) and the global ROM (C2/7) were measured by radiography. To evaluate the total neck ROM, the cervical ROM device was advocated. Preoperative and postoperative data were compared using the paired t test. RESULTS The Japanese orthopedic association score was 14.3 at the 1-year follow-up as compared with the preoperative score of 8.7. Other scoring systems had improved postoperatively, including the neck disability index from 85.1 to 68.6 and the visual analogue scale from 7.8 to 3.3. Compared with the preoperative ROM, the postoperative ROM increased by 3.0 degrees (27.0%) in C5/6, 1.3 degrees (13.7%) in C4/5, and 1.8 degrees (17.6%) in C6/7. The postoperative global ROM also increased by 6.7 degrees (15.2%) compared with preoperative global data. Compared with the preoperative total neck motion, the postoperative total neck motion increased by 8.3 degrees (9.3%) in the sagittal plane and 6.1 degrees (7.7%) in the coronal plane. There was an insignificant increase of 0.8 degrees (0.6%) in the horizontal plane. CONCLUSIONS This study demonstrated that the single-level Discover CADR increased the ROM of the treated segment and the adjacent segments. There was also an increase in the global ROM and the total neck motion in the sagittal and the coronal planes, although there was no significant difference in the horizontal plane before and after operation.

CASK is a member of the membrane-associated guanylate kinase family. In mammals it is an essential protein, as CASK knockout mice die after birth and its deletion in humans has developmental consequences. CASK plays a role in the transcription of genes required for forebrain development, and in the nervous systems of Drosophila and C. elegans, it participates in receptor localization at the plasma membrane. This role in organizing supramolecular protein complexes to appropriate subcellular regions is shared in mammals and is regulated by phosphorylation. CASK is a kinase and regulator of cell proliferation and adhesion, which adds to an expanding list of roles. In this study we report for the first time that CASK is degraded in a characteristic fashion in mammalian cells. We found that CASK is a long-lived protein despite the fact that it contains three putative PEST sequences. Finally, we provide detailed evidence that CASK degradation is mediated through a ubiquitin-proteasome pathway and this is phosphorylation-dependent. Together, these results provide evidence that post-translational modifications to CASK are major regulatory steps leading to its proteasomal degradation. This regulation not only has important implications on how CASK participates in its many disparate roles, but highlights how altering this regulation may contribute to the pathogenesis of human disease.

Mouse F9 cells differentiate into primitive endoderm when treated with retinoic acid (RA) and into parietal endoderm in response to RA and dibutyryl (db-) cAMP. G protein signaling either blocks or mimics RA-induced differentiation, the latter signaling through the Wnt-beta-catenin pathway. In our study, we found that a constitutively active Galpha13 mutant induces F9 cells to differentiate into parietal endoderm in the absence of exogenous agents. Galpha13 expression and subsequent differentiation are accompanied by beta-catenin translocation to the nucleus. Differentiation and changes in cell morphology are supported by rearrangements to the F-actin cytoskeleton. ERM (ezrin-radixin-moesin) proteins, known to link F-actin to transmembrane receptors, are also redistributed during differentiation. Furthermore, morpholino antisense and shRNA approaches show that moesin expression is essential since its knockdown leads to altered F-actin distribution and subsequent apoptosis. Moesin-depleted cells, however, remain attached to the substrate when Galpha13 is constitutively expressed, but they do not differentiate into extraembryonic endoderm. Our study demonstrates a link between Galpha13 signaling that regulates differentiation of F9 cells through primitive to parietal endoderm and a moesin requirement for cell survival.

Magnetized target fusion is an alternative method to fulfill the goal of controlled fusion, which combines advantages of both magnetic confinement fusion and inertial confinement fusion since its parameter space lies between the two traditional ways. Field reversed configuration (FRC) is a good candidate of magnetized targets due to its translatable, compressible, high β and high energy density properties. Dynamic formation process of high density FRC is observed on the YingGuang 1 device for the first time in China. The evolution of a magnetic field is detected with magnetic probes, and the compression process can be clearly seen from images taken with a high-speed multi-frame CCD camera. The process is also studied with two-dimensional magneto hydrodynamic code MPF-2D theoretically, and the results agree well with the experiment. Combining the experimental data and the theoretical analysis, the length of the formed FRC is about 39 cm, the diameter is about 2–2.7 cm, the average density is 1.3 × 1016 cm−3, and the average temperature is 137 eV.

Platelet-rich plasma (PRP) has a pool of multiple growth factors efficient at inducing the proliferation and osteogenic differentiation of human adipose-derived stem cells (hADSCs). Bone morphogenetic protein (BMP)-2 is a strong stimulator for the osteogenic differentiation of hADSCs. The purpose of this study was to verify the effect of PRP-released growth factors and microsphere-encapsulated BMP-2 on the proliferation and osteoblastic differentiation of hADSCs and to construct a novel tissue-engineered bone. The BMP-2–loaded microspheres and hADSCs were embedded in activated PRP gel. Another 5 composites (hADSCs/platelet-poor plasma [PPP]; hADSCs/PRP; hADSCs/BMP-2/PPP; hADSCs/BMP-2/PRP; and hADSCs/BMP-2+microspheres/PPP) were also constructed. The DNA content, alkaline phosphatase activity, mRNA expression of alkaline phosphatase, osteopontin, osteocalcin, and mineralization of hADSCs in each composite were compared. The DNA content was higher in all PRP-containing composites, meaning that PRP-released growth factors stimulated proliferation of hADSCs. Alkaline phosphatase increased in BMP-2/PRP and BMP-2+microspheres/PRP composites in the first 7 days, meaning that BMP-2 had a synergistic effect with PRP in the early differentiation of hADSCs. Osteopontin, osteocalcin, and mineralization assays were higher in BMP-2+microspheres/PRP composite than in the BMP-2/PRP composite up to 21 days, meaning that a continuous delivery of BMP-2 stimulates osteoblastic differentiation of hADSCs at the early stage and the final maturation stage. These results suggest that sustained delivery of BMP-2 in combination with PRP is better than a single administration of PRP or BMP-2 in the osteogenic differentiation of hADSCs.

Some controversy still exists over the optimal treatment time and the surgical approach for cervical myelopathy due to ossification of the posterior longitudinal ligament (OPLL). The aim of the current study was first to analyze the effect of intramedullary spinal cord changes in signal intensity (hyperintensity on T2-weighted imaging and hypointensity on T1-weighted imaging) on magnetic resonance imaging (MRI) on surgical opportunity and approach for cervical myelopathy due to OPLL. This was a prospective randomized controlled study. Fifty-six patients with cervical myelopathy due to OPLL were enrolled and assigned to either group A (receiving anterior decompression and fusion, n = 27) or group P (receiving posterior laminectomy, n = 29). All the patients were followed up for an average 20.3 months (12–34 months). The clinical outcomes were assessed by the average operative time, blood loss, Japanese Orthopedic Association (JOA) score, improvement rate (IR) and complication. To determine the relevant statistics, we made two factorial designs and regrouped the data of all patients to group H (with hyperintensity on MRI, n = 31), group L (with hypointensity on MRI, n = 19) and group N (no signal on MRI, n = 25), and then to further six subgroups as well: AH (with hyperintensity on MRI from group A, n = 15), PH (with hyperintensity on MRI from group P, n = 16), AL (with hypointensity on MRI from group A, n = 10), PL (with hypointensity on MRI from group P, n = 9), AN (no signal intensity on MRI from group A, n = 12) and PN (no signal intensity on MRI from group P, n = 13). Both hyperintensity on T2-weighted imaging and hypointensity on T1-weighted imaging had a close relationship with the JOA score and IR. The pre- and postoperative JOA score and postoperative IR of either group H or group L was significantly lower than that of group N (P 0.05). In conclusion, regardless of hyperintensity on T2-weighted imaging or hypointensity on T1-weighted imaging in patients with OPLL, severe damage to the spinal cord is indicated. Surgical treatment should be provided before the advent of intramedullary spinal cord changes in signal intensity on MRI. The anterior approach is more effective than posterior approach for treating cervical myelopathy due to OPLL characterized by intramedullary spinal cord changes in signal intensity on MRI.

System isolation, inconsistent information, verifies frequent and so on are the problems facing with of the campus network construction. In order to solve the problems above, we integrated B / S architecture applications with the Single sign-on (SSO) system. A unified personnel database has been established using LDAP server, and creates dynamic groups to manage elements of the database. CAS and Form technology were used to achieve the integration of internal campus network applications and other black-box system with SSO.

The effect of deeply trapped electrons on the collisionless damping of geodesic acoustic modes is studied in the simple toroidal configuration assuming that ?de????be, where ?de and ?be are the geodesic drift frequency and bounce frequency of the trapped electrons. The rate of the damping induced by the trapped electrons is found to be an increasing function of the safety factor q until the edge of the tokamak plasma is reached. In the low q range, the rate of the damping caused by the circulating ions is larger than that of the damping caused by the trapped electrons, but as q increases, the latter becomes comparable with and even exceeds the former at the edge of the tokamak plasma.

A 633 nm laser interferometer has been designed based on a novel concept, which, without the acousto-optic modulator or the demodulator circuit, adopts the fibers to connect all elements except photodetectors and oscilloscope in this system to make it more compact, portable, and efficient. The noteworthy feature is to mathematically compare the two divided interference signals, which have the same phase-shift caused by the electron density but possess the different initial phase and low angular frequencies. It is possible to read the plasma density directly on the oscilloscope by our original mathematic demodulation method without a camera. Based on the Abel inversion algorithm, the radial electron density profiles versus time can be obtained by using the multi-chord system. The designed measurable phase shift ranges from 0 to 2π rad corresponding to the maximum line integral of electron density less than 3.5 × 10(17) cm(-2), and the phase accuracy is about 0.017 rad corresponding to the line integral of electron density accuracy of 1 × 10(15) cm(-2). After the construction of eight-chord interferometer, it will provide the detailed time resolved information of the spatial distribution of the electron density in the field-reversed configuration (FRC) plasma target produced by the "Yingguang-1" programmed-discharge device, which is being constructed in the Key Laboratory of Pulsed Power, China Academy of Engineering Physics.

To produce broadband electromagnetic pulse (EMP) radiation, we design and test a sub-ns pulse system which is utilized to drive an axial mode helix antenna. This sub-ns pulse system consists of a 10-stage Marx generator, an intermediate storage capacitor, an impedance transforming line, and can generate a high voltage of 570 kV with a rise time of 1–1.5 ns on a 300-Ω-resistance load. The diameter, pitch and turns of the helix antenna are 29 cm, 19.5 cm and 5, respectively, with a design frequency of 300 MHz. When the charging voltage of the Marx generator is 30 kV, the electric field of radiated EMP measured 3m from the source is 35 kV/m with a central frequency of 250 MHz. The relatively spectral bandwidth is 25%. The radiated EMP results are reproducible and the system will work in repetition mode if the available dc power is utilized.