Concise Review: The Potential Use of Intestinal Stem Cells to Treat Patients With Intestinal Failure.

: Intestinal failure is a rare life-threatening condition that results in the inability to maintain normal growth and hydration status by enteral nutrition alone. Although parenteral nutrition and whole organ allogeneic transplantation have improved the survival of these patients, current therapies are associated with a high risk for morbidity and mortality. Development of methods to propagate adult human intestinal stem cells (ISCs) and pluripotent stem cells raises the possibility of using stem cell-based therapy for patients with monogenic and polygenic forms of intestinal failure. Organoids have demonstrated the capacity to proliferate indefinitely and differentiate into the various cellular lineages of the gut. Genome-editing techniques, including the overexpression of the corrected form of the defective gene, or the use of CRISPR (clustered regularly interspaced short palindromic repeats)/Cas9 to selectively correct the monogenic disease-causing variant within the stem cell, make autologous ISC transplantation a feasible approach. However, numerous techniques still need to be further optimized, including more robust ex vivo ISC expansion, native ISC ablation, and engraftment protocols. Large-animal models can to be used to develop such techniques and protocols and to establish the safety of autologous ISC transplantation because outcomes in such models can be extrapolated more readily to humans.The field of intestinal stem cell biology has exploded over the past 5 years with discoveries related to in vivo and in vitro stem cell identity and function. The goal of this review article is to highlight the potential use of these cells to treat various epithelial disorders of the gut and discuss the various roadblocks that will be encountered in the coming years

Implicit Theories and Their Role in Judgments and Reactions: A Word From Two Perspectives

In this target article, we present evidence for a new model of individual differences in judgments and reactions. The model holds that people's implicit theories about human attributes structure the way they understand and react to human actions and outcomes. We review research showing that when people believe that attributes (such as intelligence or moral character) are fixed, trait-like entities (an entity theory), they tend to understand outcomes and actions in terms of these fixed traits ('I failed the test because I am dumb' or 'He stole the bread because he is dishonest'). In contrast, when people believe that attributes are more dynamic, malleable, and developable (an incremental theory), they tend to focus less on broad traits and, instead, tend to understand outcomes and actions in terms of more specific behavioral or psychological mediators ('I failed the test because of my effort or strategy' or 'He stole the bread because he was desperate'). The two frameworks also appear to foster different reactions: helpless versus mastery-oriented responses to personal setbacks and an emphasis on retribution versus education or rehabilitation for transgressions. These findings are discussed in terms of their implications for personality, motivation, and social perception.published_or_final_versio

Quantum well intermixing for the fabrication of InGaAsN/GaAs lasers with pulsed anodic oxidation

Quantum well (QW) intermixing was carried out by post-growth rapid thermal annealing in InGaAsN/GaAs QW laser structures grown by solid-source molecular-beam epitaxy. The intensity and width of the photoluminescence peak showed a dependence on annealing temperature and time, and the maximum intensity and minimum linewidth were obtained after the wafer was annealed at 670 °C for 60 s. The peak luminescence energy blueshifted with increasing annealing time, although it plateaued at an annealing time that corresponded to that yielding the maximum luminescence intensity. The diffusion coefficient for indium was determined from a comparison between experimental data and modeling, but showed that QW intermixing alone was not sufficient to account for the relatively large blueshift after annealing. Defects related to the incorporation of nitrogen in the QW layer were responsible for the low photoluminescence efficiency in the as-grown samples and were annealed out during rapid thermal annealing. During annealing, nitrogen interstitials moved to vacancy sites within the QW and thus suppressed QW intermixing. After annealing wafers under conditions giving the maximum luminescence intensity, lasers were fabricated with pulsed anodic oxidation. © 2004 American Institute of Physics.published_or_final_versio

Intestinal epithelial replacement by transplantation of cultured murine and human cells into the small intestine.

Adult intestinal epithelial stem cells are a promising resource for treatment of intestinal epithelial disorders that cause intestinal failure and for intestinal tissue engineering. We developed two different animal models to study the implantation of cultured murine and human intestinal epithelial cells in the less differentiated "spheroid" state and the more differentiated "enteroid" state into the denuded small intestine of mice. Engraftment of donor cells could not be achieved while the recipient intestine remained in continuity. However, we were able to demonstrate successful implantation of murine and human epithelial cells when the graft segment was in a bypassed loop of jejunum. Implantation of donor cells occurred in a random fashion in villus and crypt areas. Engraftment was observed in 75% of recipients for murine and 36% of recipients for human cells. Engrafted spheroid cells differentiated into the full complement of intestinal epithelial cells. These findings demonstrate for the first time successful engraftment into the small bowel which is optimized in a bypassed loop surgical model

Effects of an On-Board Safety Device on the Emissions and Fuel Consumption of a Light Duty Vehicle

© 2018 SAE International. All Rights Reserved. Vehicle emissions and fuel consumption are significantly affected by driving behavior. Many studies of eco-driving technology such as eco-driving training, driving simulators and on-board eco-driving devices have reported potential reductions in emissions and fuel consumption. Use of on-board safety devices is mainly for safety, but also affects vehicle emissions and fuel consumption. In this study, an on-board safety device was installed to alert the driver and provide several types of warning to the driver (e.g. headway monitoring warning, lane collision warning, speed limit warning, etc.) to improve driving behavior. A portable emissions measurement system (PEMS) was used to measure vehicle exhaust concentrations, including hydrocarbons (HC), carbon monoxide (CO), carbon dioxide (CO2) and nitrogen oxides (NOx). The driving parameters including vehicle speed, acceleration and position were also recorded. A specific test route was designed for the experiment to investigate both urban and highway conditions. The driving parameters and emissions data were compared before and after the installation of the on-board safety device with the same driver. The Vehicle Specific Power (VSP) methodology was applied to evaluate the effects of the on-board safety device on driving behavior. The results indicated that the device had a positive effect on the driver's driving behavior. The percentage of time spent on excessive speeding and strong acceleration decreased from 22.2% to 14.7%. As a result, an average reduction of 25% in fuel consumption was observed. In addition, HC, CO2 and NOx emissions showed a reduction of 57%, 25% and 9% respectively. However, CO emission was increased and the time spent on idling showed no change with the installation of the device

Effects of tachyplesin on the morphology and ultrastructure of human gastric carcinoma cell line BGC-823

AIM To investigate the morphological and ultrastructural changes in the human gastric carcinoma cell line BGC-S23 after being treated with tachyplesin, METHODS Tachyplesin was isolated from acid extracts of Chinese horseshoe crab (Tachypleus tridentatus) hemocytes, BGC-823 cells and the cells treated with 2.0 mg/L tachyplesin were examined respectively under light microscope, scanning and transmission electron microscope. RESULTS BGC-823 cells had undergone the restorational alteration in morphology and ultrastructure after tachyplesin treatment. The changes were as follows: the shape of cells was unanimous, the volume enlarged and cells turned to be flat and spread, the nucleocytoplasmic ratio lessened and nuclear shape became rather regular, the number of nucleolus reduced and its volume lessened, heterchromatin decreased while euchromatin increased in nucleus. In the cytoplasm, mitochondria grew in number with consistent structure relatively, Golgi complex turned to be typical and well-developed, rough endoplasmic reticulum increased and polyribosome decreased. The microvilli at cellular surface were rare and the filopodia reduced while lamellipodia increased at the cell edge. CONCLUSION Tachyplesin could alter the malignant morphological and ultrastructural characteristics of human gastric carcinoma cells effectively and have a certain inducing differentiation effect on human gastric carcinoma cells

Monitoring and analysis of internal displacements of a slope and relationship with rainfall infiltration

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International Consensus on Differential Diagnosis and Management of Patients With Danon Disease: JACC State-of-the-Art Review

Danon disease is a rare X-linked autophagic vacuolar cardioskeletal myopathy associated with severe heart failure that can be accompanied with extracardiac neurologic, skeletal, and ophthalmologic manifestations. It is caused by loss of function variants in the LAMP2 gene and is among the most severe and penetrant of the genetic cardiomyopathies. Most patients with Danon disease will experience symptomatic heart failure. Male individuals generally present earlier than women and die of either heart failure or arrhythmia or receive a heart transplant by the third decade of life. Herein, the authors review the differential diagnosis of Danon disease, diagnostic criteria, natural history, management recommendations, and recent advances in treatment of this increasingly recognized and extremely morbid cardiomyopathy

Addressing Reported Pro-Apoptotic Functions of NF-κB: Targeted Inhibition of Canonical NF-κB Enhances the Apoptotic Effects of Doxorubicin

The ability of the transcription factor NF-κB to upregulate anti-apoptotic proteins has been linked to the chemoresistance of solid tumors to standard chemotherapy. In contrast, recent studies have proposed that, in response to doxorubicin, NF-κB can be pro-apoptotic through repression of anti-apoptotic target genes. However, there is little evidence analyzing the outcome of NF-κB inhibition on the cytotoxicity of doxorubicin in studies describing pro-apoptotic NF-κB activity. In this study, we further characterize the activation of NF-κB in response to doxorubicin and evaluate its role in chemotherapy-induced cell death in sarcoma cells where NF-κB is reported to be pro-apoptotic. Doxorubicin treatment in U2OS cells induced canonical NF-κB activity as evidenced by increased nuclear accumulation of phosphorylated p65 at serine 536 and increased DNA–binding activity. Co-treatment with a small molecule IKKβ inhibitor, Compound A, abrogated this response. RT–PCR evaluation of anti-apoptotic gene expression revealed that doxorubicin-induced transcription of cIAP2 was inhibited by Compound A, while doxorubicin-induced repression of other anti-apoptotic genes was unaffected by Compound A or siRNA to p65. Furthermore, the combination of doxorubicin and canonical NF-κB inhibition with Compound A or siRNA to p65 resulted in decreased cell viability measured by trypan blue staining and MTS assay and increased apoptosis measured by cleaved poly (ADP-ribose) polymerase and cleaved caspase 3 when compared to doxorubicin alone. Our results demonstrate that doxorubicin-induced canonical NF-κB activity associated with phosphorylated p65 is anti-apoptotic in its function and that doxorubicin-induced repression of anti-apoptotic genes occurs independent of p65. Therefore, combination therapies incorporating NF-κB inhibitors together with standard chemotherapies remains a viable method to improve the clinical outcomes in patients with advanced stage malignancies

A quaternary solid-form of ritonavir: an oxalate salt oxalic acid co-crystal acetone solvate

Ritonavir has been reported in seven crystal forms notably form I, II, IIIb and IV, as well as a hydrate, an L-tyrosine co-crystal and a formamide solvate. A new form is reported here with a novel quaternary structure with ritonavir as an oxalate salt, oxalic acid co-crystal and acetone solvate in a 1 : 1 : 0.5 : 0.5 stoichiometry. The new oxalate salt form (CCDC deposition number 2009282), was co-crystallised with oxalic acid from a supersaturated acetone solution, and exhibits a polar monoclinic crystal structure with a blocky needle-like crystal habit. The molecular conformation of ritonavir for the new form shows significant differences with respect to the well-characterised form I, II and IIIb polymorphs. Its crystallography is characterised by a 2-fold screw axis along the b axis, in a structure that exhibits multiple hydrogen bonds formed between amide–ureido, oxalate–oxalic acid and amide–amide groups in a layered intermolecular packing structure. Intermolecular stacking of the benzene and thiazole rings takes place along the crystallographic a axis with the needle axis growth of the crystals being likely to be governed by these interactions. The oxalate salt form co-crystal is found to have the characteristic conformations of the N-methyl urea and carbamate groups being in a trans and trans conformation respectively, as is the case for the recently discovered form IIIb, but in distinct contrast to cis and trans for form I, and trans and cis for form II. This may suggest that a cis and cis conformation for another new form may be feasible. The recovery of the form IV crystals at the lower concentrations of oxalic acid is perhaps indicative of its close similarity with the new oxalate salt co-crystal solvate form presented here