cssi/SciSciGPT-SciSciNet huggingface dataset:
Phospholipase D enzymes facilitate IL-17- and TNFα-induced expression of proinflammatory genes in rheumatoid arthritis synovial fibroblasts (RASF)

In rheumatoid arthritis, the synovium exhibits fibroblast hyperplasia and dynamic infiltration of activated T cells. Interaction between rheumatoid arthritis synovial fibroblasts (RASF) and T cell subsets such as Th17 cells can stimulate RASF to express IL-6, IL-8, CCL20, and other proinflammatory mediators of joint destruction. PLD enzymes specifically cleave phosphatidyl choline (PC) producing phosphatidic acid (PA) and choline. Agonist-induced PLD activation results in PA synthesis, which is thought to be involved in a variety of rapid cellular responses such as cytokine secretion. Furthermore, the cellular response to TNF-mediated signaling in myeloid cells is in part mediated by PLD1. However, very few studies have examined the role of PLD enzymes in pro-inflammatory responses of RASF to key pathogenic cytokines such as TNF and IL-17. Microarray analysis of RASF showed that phospholipase D1 (PLD1) is among genes significantly induced by IL-17. We therefore hypothesized that PLD1 might have a role in RASF responses to proinflammatory cytokines. We used 1-butanol, PLD1-specific siRNAs, and small molecule inhibitors specific for PLD1 or PLD2, to investigate the possible role of PLD enzymes in basal, IL-17-, and/or TNFα-evoked expression of proinflammatory cytokines and chemokines by RASF. We studied the in vitro responses of RASF to IL-17A and/or TNFα, with particular attention to effects on IL-6, IL-8 and CCL20 mRNA and secretion as determined by RT-QPCR and ELISA, respectively. Transcriptional and prominent post-transcriptional effects were demonstrated, with robust decreases in RASF secretion of IL-6, IL-8, and CCL20 when both PLD isoforms were inhibited together. Moreover, RA synovial biopsy explants cultured in media containing PLD isoform-specific inhibitors showed significantly reduced constitutive secretion of IL-6 and IL-8. PLD enzymes could be promising targets for controlling proinflammatory gene expression in the treatment of RA in view of roles for PLD in cytokine-evoked transcription and secretion/exocytosis.
The All E. coli TX-TL Toolbox 2.0: A Platform for Cell-Free Synthetic Biology.

We report on and provide a detailed characterization of the performance and properties of a recently developed, all Escherichia coli, cell-free transcription and translation system. Gene expression is entirely based on the endogenous translation components and transcription machinery provided by an E. coli cytoplasmic extract, thus expanding the repertoire of regulatory parts to hundreds of elements. We use a powerful metabolism for ATP regeneration to achieve more than 2 mg/mL of protein synthesis in batch mode reactions, and more than 6 mg/mL in semicontinuous mode. While the strength of cell-free expression is increased by a factor of 3 on average, the output signal of simple gene circuits and the synthesis of entire bacteriophages are increased by orders of magnitude compared to previous results. Messenger RNAs and protein degradation, respectively tuned using E. coli MazF interferase and ClpXP AAA+ proteases, are characterized over a much wider range of rates than the first version of the cell-free t...
Continent appendicocolostomy: a variation of the Mitrofanoff principle in pediatric urinary tract reconstruction.

AbstractThere are numerous options for continent urinary reconstruction in children. If the appendix is available and the bladder capacity is satisfactory, a Mitrofanoff procedure may be performed using the appendix as a catheterizable tube implanted into the bladder. However, in many patients the bladder is absent or too small for this type of reconstruction. An alternative technique, termed appendicocolostomy, is to implant the appendix under the tenia of a detubularized patch of cecum or sigmoid colon, which becomes part of a continent neobladder or is attached to the bladder itself. This procedure has been used in 12 children and 1 adult undergoing continent reconstruction. Urological diseases included bladder exstrophy (10 patients) and a neuropathic bladder (3). Two patients underwent undiversion of a sigmoid conduit, while in 7 of the remaining patients the bladder was included in the reservoir. In 1 patient histological examination of the tip of the appendix revealed an incidental invasive carcino...
Juvenile growth reduces the influence of epithelial sodium channels on myogenic tone in skeletal muscle arterioles.

Previous studies have documented that rapid juvenile growth is accompanied by functional changes in the arteriolar endothelium, but much less is known about functional changes in arteriolar smooth muscle over this period. In this study, we investigated the possible contribution of epithelial sodium channels (ENaC) to the myogenic behavior of arterioles at two stages of juvenile growth. The effects of the ENaC inhibitor benzamil on different levels of myogenic tone were studied in isolated gracilis muscle arterioles from rats aged 21-28 days (“weanlings”) and 42-49 days (“juveniles”). ENaC subunit expression in the arteriolar wall was also determined, and the interaction between ENaC and nitric oxide (NO) in regulating vascular tone was explored by combined use of benzamil and NG-monomethyl-L-arginine (L-NMMA). At physiological pressures, both steady-state myogenic tone and the dynamic adjustments in this tone triggered by acute pressure changes were less in juvenile arterioles than in weanling arterioles. α, β and γ ENaC protein was present in arterioles at both ages, but benzamil only had an effect on myogenic tone in weanling arterioles. In these vessels, benzamil increased, rather than decreased, myogenic tone, and this effect was prevented by L-NMMA or endothelial removal. These findings suggest that although ENaC is present in gracilis muscle arterioles of both weanling and juvenile rats, it is not obligatory for the genesis of myogenic activity in these vessels at either age. However, ENaC activity can significantly modulate the level of myogenic tone through stimulation of endothelial NO release at an early stage of growth. This article is protected by copyright. All rights reserved.
Extended spectrum beta lactamase (ESBL) producing bacteria urinary tract infections and complex pediatric urology.

Abstract Aim of the study Extended spectrum beta lactamase (ESBL) producing bacteria are resistant to most beta-lactam antibiotics including third-generation cephalosporins, quinolones and aminoglycosides. This resistance is plasmid-borne and can spread between species. Management of ESBL is challenging in children with recurrent urinary tract infections (UTIs) and complex urological abnormalities. We aim to quantify the risk in children and specifically in urological patients. Methods Retrospective review of a microbiology database (April 2014 to November 2015). This identified urine isolates, pyuria, ESBL growth and patient demographics. Data analysis was by Chi square, Mann–Whitney U-test and ANOVA. A P value of Main results Analysis of 9418 urine samples showed 2619 with pure isolates, of which 1577 had pyuria (>10×10 6 WC/L). 136 urine cultures (n=79 patients) grew purely ESBL. Overall, 5.2% of urine isolates were ESBL and 9.5% isolates with pyuria (>100×10 6 WC/L) had ESBL, whereas only 22/1032 (2.1%) with no pyuria, ( P Urology patients had 86/136 (63%) ESBL positive cultures. These represented 86/315 (27%) of all positive cultures for urology patients vs. 50/2267 (2.2%) for all other specialties ( P Over the study period, there was no significant rise of the monthly incidence between 2014 and 2015 (ANOVA P =0.1). Conclusion This study is the first to document the incidence of ESBL in children (5%), and estimate the frequency of possible plasmid transmission between bacterial species in children. This quantifies the risk of ESBL, especially to urology patients, and mandates better antibiotic stewardship. Level of evidence Level IIc.
Epileptiform abnormalities predict delayed cerebral ischemia in subarachnoid hemorrhage

Abstract Objective To identify whether abnormal neural activity, in the form of epileptiform discharges and rhythmic or periodic activity, which we term here ictal-interictal continuum abnormalities (IICAs), are associated with delayed cerebral ischemia (DCI). Methods Retrospective analysis of continuous electroencephalography (cEEG) reports and medical records from 124 patients with moderate to severe grade subarachnoid hemorrhage (SAH). We identified daily occurrence of seizures and IICAs. Using survival analysis methods, we estimated the cumulative probability of IICA onset time for patients with and without delayed cerebral ischemia (DCI). Results Our data suggest the presence of IICAs indeed increases the risk of developing DCI, especially when they begin several days after the onset of SAH. We found that all IICA types except generalized rhythmic delta activity occur more commonly in patients who develop DCI. In particular, IICAs that begin later in hospitalization correlate with increased risk of DCI. Conclusions IICAs represent a new marker for identifying early patients at increased risk for DCI. Moreover, IICAs might contribute mechanistically to DCI and therefore represent a new potential target for intervention to prevent secondary cerebral injury following SAH. Significance These findings imply that IICAs may be a novel marker for predicting those at higher risk for DCI development.
mTOR activity in AIDS-related diffuse large B-cell lymphoma.

BACKGROUND Patients infected with HIV have a significantly increased risk of developing non-Hodgkin lymphomas despite the widespread use of HAART. To investigate mTOR pathway activity in acquired immunodeficiency syndrome (AIDS) related diffuse large B-cell lymphoma AR-DLBCL, we used immunohistochemistry to examine the presence of the phosphorylated 70 ribosomal S6 protein-kinase (p70S6K), an extensively studied effector of mTOR Complex 1 (mTORC1) and the phosphorylated phosphatase and tensin homolog (pPTEN), a negative regulator of mTORC1 pathway. MATERIALS AND METHODS We evaluated tissue samples from 126 patients with AR-DLBCL. Among them, 98 samples were from tissue microarrays (TMAs) supplied by the Aids and Cancer Specimen Resource (ACSR), the remaining 28 samples were from cases diagnosed and treated at the University of California, San Diego (UCSD). The presence of p70S6K was evaluated with two antibodies directed against the combined epitopes Ser235/236 and Ser240/244, respectively; and additional monoclonal anti-bodies were used to identify pPTEN and phosphorylated proline-rich Akt substrate of 40kDa (pPRAS40). The degree of intensity and percentage of cells positive for p70S6K and pPTEN were assessed in all the samples. In addition, a subgroup of 28 patients from UCSD was studied to assess the presence of pPRAS40, an insulin-regulated activator of the mTORC1. The expression of each of these markers was correlated with clinical and histopathologic features. RESULTS The majority of the patients evaluated were males (88%); only two cases (1.6%) were older than 65 years of age. We found high levels of both p70S6K-paired epitopes studied, 48% positivity against Ser235/236 (44% in ACSR and 64% in UCSD group), and 86% positivity against Ser240/244 (82% in ACSR and 100% in UCSD group). We observed more positive cells and stronger intensity with epitope Ser240/244 in comparison to Ser235/236 (p<0.0001). The degree of intensity and percentage of cells positive for pPTEN was positively correlated with p70S6K levels (p = 0.016 for 235/236 and p = 0.007 for 240/244). High levels of pPRAS40 were observed in the majority of the cases evaluated (64.3%), but no correlation was found with either pPTEN (p = 0.9) or p70S6K (p = 0.9) levels. CONCLUSION AR-DLBCL frequently contain p70S6K, a main downstream effector of the mTOR pathway. The presence of p70S6K is positively correlated with pPTEN, an inactive form of PTEN, which makes mTORC1 activated. The presence of p70S6K was independent of HIV viral load or CD4 (+) counts. These results suggest that the mTOR pathway is active in the majority of AR-DLBCL, and p70S6K, particularly the Ser240/244 epitope immunohistochemistry is an excellent surrogate biomarker, which could be used to identify cases expected to be responsive to mTOR inhibitors.
Effect of instantaneous stirring process on mixing between initially distant scalars in turbulent obstacle wakes

A two-channel planar laser-induced fluorescence technique is used to study mixing and reactions between two initially distant scalars in the turbulent wake of a cylindrical obstacle. The scalars are released continuously and isokinetically upstream of the cylinder, with a lateral separation that initially impedes mixing between them. The effect of the turbulent wake on mixing and reaction enhancement is determined by measuring the segregation parameter for cases with and without the cylinder obstruction. Results indicate that scalar mixing and reaction rates (in the low-Damkohler limit) increase significantly in the presence of the cylinder wake. The study also shows that the dominant contribution of total reaction derives from the scalar covariance associated with instantaneous flow processes, and depends strongly on streamwise location within the wake. The results have broad implications for mixing processes in engineering and ecology.
Considering the Business in Business Ethics: An Exploratory Study of the Influence of Organizational Size and Structure on Individual Ethical Predispositions

This paper explores the relationship between organizational size, structure and the strength of organization members' ethical predispositions. It is hypothesized that individuals in smaller, more flexible, organic organizations will display stronger ethical predispositions. Survey results from 209 individuals across eleven organizations indicate that contrary to expectations, larger, more rigid, mechanistic structures were associated with higher levels of ethical formalism and utilitarianism. Implications of these findings are discussed.
Operating and Geometrical Arrangement Requirements for Fusion Neutronics Testing

Neutronics tests in a fusion engineering test device will be required to verify the neutronics prediction capabilities (calculational methods and data base). This paper presents the requirements related to the neutronics test. These requirements include those associated with the operational environment (e.g., wall load, fluence, plasma burn time, etc.) and the ones related to the test module configuration (geometrical arrangements, minimum size for meaningful test information, boundary conditions, etc.). Both experimental consideration and neutronic analyses were carried out to quantify these conditions.
An Axiomatic Approach to IR--UIUC TREC 2005 Robust Track Experiments.

In this paper, we report our experiments in the TREC 2005 Robust Track. Our focus is to explore the use of a new axiomatic approach to information retrieval. Most existing retrieval models make the assumption that terms are independent of each other. Although such simplifying assumption has facilitated the construction of successful retrieval systems, the assumption is not true; words are related by use, and their similarity of occurrence in documents can reflect underlying semantic relations between terms. Our new method aims at incorporating term dependency relations into the axiomatic retrieval model in a natural way. In this paper, we describe the method and present analysis of our Robust-2005 evaluation results. The results show that the proposed method works equally well as the KL-divergence retrieval model with a mixture model feedback method. The performance can be further improved by using the external resources such as Google.
A marginalized unscented Kalman filter for efficient parameter estimation with applications to finite element models

Abstract This paper focuses on the problem of combined state/parameter estimation in dynamical systems with many degrees of freedom, for instance finite element models, using measured data from the system and nonlinear Bayesian filtering techniques for the estimation. A highly efficient nonlinear Kalman filtering technique is developed, based on a combination of linear or extended Kalman filtering for state estimation and unscented filtering for parameter learning. Such a combination is implemented by applying the principle of marginalization to the unscented transform. This method leads to a very efficient state/parameter filtering algorithm by taking advantage of the fact that Jacobians of the system equations with respect to the dynamic states, required in extended Kalman filtering, can be easily related to outputs of the finite element analysis required for forward propagation. For linear dynamical systems this approach yields an algorithm with identical accuracy as the UKF but reduced computational time, as demonstrated on several medium-size examples. For nonlinear systems, the resulting algorithm is also superior to the UKF in terms of computational time, due to the fact that Jacobians are functions of the tangent stiffness matrix of the system, whose computation is required for propagation in finite element analysis. It is also shown that, even though this algorithm relies on linearization for propagation of moments of the dynamic states, this reduction in accuracy compared to a generic UKF does not affect learning of the parameters for the systems considered herein.
The impact of an evolving profession on the frequency and perceived difficulty of ethical encounters among physical therapists in the clinic.

Background: Ethical decision making is situated within dynamic contexts specific to practice standards and environments, contemporary policy, and responsive educational systems. Reflecting on an ev...
Lawn mowing frequency and its effects on biogenic and anthropogenic carbon dioxide emissions

Abstract Decision makers in urban areas actively pursue strategies to decrease carbon dioxide (CO2) emissions and other greenhouse gases. Lawns dominate urban lands in the U.S. and require intensive management, including frequent mowing, which may influence CO2 emissions from both biogenic and anthropogenic sources. We tested whether different lawn mowing frequencies (every one, two or three weeks) affected soil respiration (i.e., biogenic CO2 emissions), by changing soil moisture and temperature, and the gasoline emissions associated with lawn maintenance via lawn mowing (i.e., anthropogenic CO2 emissions). Sixteen yards in Springfield, Massachusetts USA were assigned a mowing frequency for two seasons (2013–2014). We measured grass height, air and soil temperature, soil moisture, soil CO2 flux, lawn mower emissions, tree canopy coverage and precipitation. We used a mixed effects modeling approach to test how these variables interacted with each other and responded to mowing frequency. Lawn-mowing frequency did not influence soil temperature, moisture, or biogenic soil CO2 fluxes. Soil microclimate and soil respiration varied more with ambient climatic fluctuations and tree canopy cover. By contrast, anthropogenic emissions increased with more frequent mowing due to emissions associated with the mower. When scaled to the entire mowing season, biogenic CO2 fluxes far exceeded the anthropogenic fluxes, thus requiring consideration for accurate accounting of urban greenhouse gas emissions. The interplay between biogenic (e.g., increasing tree canopy in lawn-dominated yards) and anthropogenic (i.e., mowing less frequently) methods of reducing CO2 emissions in cities highlights the need for more rigorous accounting processes for cities to meet climate action goals.
In vitro and ex vivo implantation of cystine crystals and treatment by contact lens

Abstract Cystinosis is a rare genetic disorder order affecting the transport of the amino acid cystine across the lysosomal membrane, leading to crystal formation throughout the body. The formation of these crystals in the cornea leads to photophobia and other ocular complications. The current treatment is to use eye drops of a thiol called cysteamine, delivered at a rate about 8–12 drops per day due to very low bioavailability intrinsic to eye drops. This paper examines an alternative and possibly more effective method of using contact lenses, which are suggested to have a bioavailability of around 50%, to deliver cysteamine to the cornea. This paper focuses on first designing in vitro, ex vivo and in vivo rabbit models of cornea containing cystine crystals and testing for feasibility of crystal dissolution by using contact lenses. In each model, cystine crystals were formed by loading cysteine into the cornea followed by oxidation to form cystine crystals. In some cases, cystine was directly transported into the cornea to form the crystals. The in vitro model—using a cystine-laden hydroxyl ethyl methacrylate hydrogel in the shape of a cornea—demonstrated an effectiveness of roughly 52% of loaded cysteamine reaching the “hydrogel cornea.” The ex vivo model—using rabbit cadaver eyes impregnated with cystine crystals—again showed a near 50% bioavailability—using 27 ± 2 lenses to lead to crystal dissolution when 13 lenses were needed if 100% bioavailability could be reached. The in vivo studies showed that exposing the cornea of a normal animal can lead to crystal formation but the crystals dissolve rapidly likely due to clearance through the aqueous humor. Thus, efficacy of eluting contacts at dissolving crystals could not be tested in vivo. These results suggest that cysteamine loaded contact lens could transport cysteamine into the cornea at higher bioavailability compared to the eye drops and thus be potentially effective at treating cystinosis.
Social Networks and Ethical Choice

Although organizational leaders frequently engage in formal attempts to promote organizational environments supportive of employees’ ethical behaviors, the informal structure of social relations in...
AGA Technical Review on the Management of Mild-to-Moderate Ulcerative Colitis

Most patients with ulcerative colitis (UC) have mild-to-moderate disease activity, with low risk of colectomy, and are managed by primary care physicians or gastroenterologists. Optimal management of these patients decreases the risk of relapse and proximal disease extension, and may prevent disease progression, complications, and need for immunosuppressive therapy. With several medications (eg, sulfasalazine, diazo-bonded 5-aminosalicylates [ASA], mesalamines, and corticosteroids, including budesonide) and complex dosing formulations, regimens, and routes, to treat a disease with variable anatomic extent, there is considerable practice variability in the management of patients with mild–moderate UC. Hence, the American Gastroenterological Association prioritized clinical guidelines on this topic. To inform clinical guidelines, this technical review was developed in accordance with the Grading of Recommendations Assessment, Development and Evaluation framework for interventional studies. Focused questions included the following: (1) comparative effectiveness and tolerability of different oral 5-ASA therapies (sulfalsalazine vs diazo-bonded 5-ASAs vs mesalamine; low- ( 3 g/d) mesalamine); (2) comparison of different dosing regimens (once-daily vs multiple times per day dosing) and routes (oral vs rectal vs both oral and rectal); (3) role of oral budesonide in patients mild–moderate UC; (4) comparative effectiveness and tolerability of rectal 5-ASA and corticosteroid formulations in patients with distal colitis; and (5) role of alternative therapies like probiotics, curcumin, and fecal microbiota transplantation in the management of mild–moderate UC.
Transparency and Algorithmic Governance

Machine-learning algorithms are improving and automating important functions in medicine, transportation, and business. Government officials have also started to take notice of the accuracy and speed that such algorithms provide, increasingly relying on them to aid with consequential public-sector functions, including tax administration, regulatory oversight, and benefits administration. Despite machine-learning algorithms’ superior predictive power over conventional analytic tools, algorithmic forecasts are difficult to understand and explain. Machine learning’s “black-box” nature has thus raised concern: Can algorithmic governance be squared with legal principles of governmental transparency? We analyze this question and conclude that machine-learning algorithms’ relative inscrutability does not pose a legal barrier to their responsible use by governmental authorities. We distinguish between principles of “fishbowl transparency” and “reasoned transparency,” explaining how both are implicated by algorithmic governance but also showing that neither conception compels anything close to total transparency. Although machine learning’s black-box features distinctively implicate notions of reasoned transparency, legal demands for reason-giving can be satisfied by explaining an algorithm’s purpose, design, and basic functioning. Furthermore, new technical advances will only make machine-learning algorithms increasingly more explainable. Algorithmic governance can meet both legal and public demands for transparency while still enhancing accuracy, efficiency, and even potentially legitimacy in government.
Self-Diagnosable and Self-Reconfigurable VLSI Array Structures

The issue of self-testing and self-reconfiguration of two-dimensional VLSI array structures are discussed in this paper. Analysis and synthesis are facilitated by separating redundant circuits into two separate categories. ST-redundancy which represents built-in circuitry used solely for self-diagnosis, and SR-redundancy which represents extra resources used for fault-tolerance. The amount of redundancy can vary, e.g. a BIST method for self-testability employs approximately 10% ST-redundant circuitry while 200% of SR-redundancy plus a voter which is ST-redundant represents a signal-fault tolerant device. The concept is implemented as a double-layered VLSI array architecture. The developed model is very general. Some important arrangements like a centralized host system, a fault-tolerant distributed multiprocessor array developed by Kuhl and Reddy, or Koren’s self-reconfigurable VLSI array are special cases of S(M, N, t o ) systems, as introduced here. In one special case, 100% of ST-redundancy allows the testing to be performed at a polynomial time regardless of the array size.
The Association Between Insurance Status and the Transfer of Children with a Mental Health Diagnosis from Emergency Departments

The Association between Insurance Status and the Transfer of Children with a Mental Health Diagnosis from Emergency Departments Purpose: Previous research suggests differences in the quality of care provided to patients associated with various non-medical factors, including insurance status. This study sought to examine the association between a child’s insurance status and an Emergency Department’s (EDs) decision to admit or transfer to another hospital among pediatric patients with a primary mental health diagnosis. Methods: We used the Healthcare Cost and Utilization Project 2012 Nationwide Emergency …
Stable suppression of membrane type 1 matrix metalloproteinase impairs MMP-2 activation, cell invasion, and tumorigenesis.

2295 Cell invasiveness toward extracellular matrix components plays an essential role in tumor angiogenesis and metastasis. Membrane type 1 matrix metalloproteinase (MT1-MMP) has been proposed to be a key cell surface protease involved in extracellular matrix degradation and the activation of other proteolytic enzymes that are necessary for the cell invasive phenotype. Specifically, MT1-MMP has been shown to degrade such extracellular matrix components as collagen I, II, and III; laminin-1 and -5; fibronectin; vitronectin; fibrin. Likewise, MT1-MMP can activate proteolytic enzymes such as proMMP-2 and proMMP-13. We have used RNA interference to suppress gene expression that enables us to further analyze the function of MT1-MMP. An invasive fibrosarcoma cell line, HT1080, which has a high endogenous level of MT1-MMP and proMMP-2, was used to generate stable cells with suppressed cell surface proteolytic activity by utilizing shRNAs to stably suppress MT1-MMP. Parental cells were transfected with a vector containing a U6 promoter, a short MT1-MMP specific DNA encoding shRNA to target MT1-MMP mRNA, GFP expression cassette, and a G418 selection cassette. Clones were selected based on drug resistance and green color detection. Suppression of MT1-MMP mRNA and protein were confirmed using quantitative Real-Time PCR and Western immunoblotting, respectively. In addition, genomic DNA was isolated from each clone and insertion of the vector into the genomic DNA was confirmed using PCR. When cells were cultured in serum free media containing DQ gelatin, MT1-MMP suppressed cells showed significantly less degradation of the gelatin when compared to parental cells. Gelatin zymography of conditioned media by cells with contrasting levels of MT1-MMP expression showed that MT1-MMP suppression eliminated proMMP-2 activation and did not have any effect on MMP-9 activation. When cells were cultured on fluorescently labeled fibronectin-coated gelatin films, cells with MT1-MMP expression generated black holes in the fibronectin-gelatin film. In contrast, MT1-MMP suppressed cells reduced their abilities to remove the fibronectin-gelatin film. When parental HT1080 cells were injected subcutaneously into female nude mice, tumors grew rapidly within 20 days. However, when MT1-MMP suppressed cells were injected, the tumors that formed were 5-10 fold smaller than tumors formed by parental cells, thus suggesting MT1-MMP plays a role in tumorigenesis. In conclusion, we confirmed that MT1-MMP is responsible for gelatin degradation and proMMP-2 activation. In addition, we found that MT1-MMP is required for the degradation of fibronectin-gelatin films in vitro and the growth of tumors in nude mice, suggesting that MT1-MMP may be required for cellular invasion and tumorigenesis of HT1080 cells.
Exploring the Usage of a Violence Prevention and Response App Among Community College Students

Sexual assault is a significant problem on college campuses. To date, much of the research on prevention and response has been conducted with students enrolled at traditional 4-year institutions. Limited research exists on 2-year institutions (also known as community colleges), which enroll a more diverse population (e.g., economic, gender, racial, and ethnic minorities) who are more vulnerable to victimization. Yet, 2-year institutions have few resources dedicated to the prevention of and response to sexual violence. Advances in technology, including mobile apps, have provided additional avenues to easily disseminate prevention and response information to college students. Mobile apps may be especially beneficial for community colleges given their diverse population and limited resources. Therefore, the present study examined a sample of community college students who reported downloading a violence prevention and response mobile app, uSafeUS, and their reasons for downloading. Participants were recruited from seven community colleges in a northeastern state and completed an online campus climate survey. Results indicate that participants who downloaded uSafeUS were more likely to perceive they were safe from campus sexual violence and receive information regarding campus sexual violence from their college than participants who did not download the app. Participants also reported downloading uSafeUS to keep themselves safe, to help a friend, and because they liked the sexual violence prevention and resource features. Female participants were more likely than male participants to download uSafeUS to keep themselves safe and because they liked the sexual violence resource information. Implications for research and practice are discussed.
Delay in IVF treatment up to 180 days does not affect pregnancy outcomes in women with diminished ovarian reserve.

Study question Will a delay in initiating IVF treatment affect pregnancy outcomes in infertile women with diminished ovarian reserve? Summary answer A delay in IVF treatment up to 180 days does not affect the live birth rate for women with diminished ovarian reserve when compared to women who initiate IVF treatment within 90 days of presentation. What is known already In clinical practice, treatment delays can occur due to medical, logistical or financial reasons. Over a period of years, a gradual decline in ovarian reserve occurs which can result in declining outcomes in response to IVF treatment over time. There is disagreement among reproductive endocrinologists about whether delaying IVF treatment for a few months can negatively affect patient outcomes. Study design, size, duration A retrospective cohort study of infertile patients in an academic hospital setting with diminished ovarian reserve who started an IVF cycle within 180 days of their initial consultation and underwent an oocyte retrieval with planned fresh embryo transfer between 1 January 2012 and 31 December 2018. Participants/materials, setting, methods Diminished ovarian reserve was defined as an anti-Mullerian hormone (AMH) 40 years old with an AMH Main results and the role of chance The mean ± SD number of days from presentation to IVF start was 50.5 ± 21.9 (immediate) and 128.8 ± 25.9 (delayed). After embryo transfer, the live birth rate was similar between groups (immediate: 23.9%; delayed: 25.6%; OR 1.08, 95% CI 0.85-1.38). Additionally, a similar live birth rate was observed in a subgroup analysis of patients with an AMH 40 years old with an AMH Limitations, reasons for caution There is the potential for selection bias with regard to the patients who started their IVF cycle within 90 days compared to 91-180 days after initial consultation. In addition, we did not include patients who were seen for initial evaluation but did not progress to IVF treatment with oocyte retrieval; therefore, our results should only be applied to patients with diminished ovarian reserve who complete an IVF cycle. Finally, since we excluded patients who started their IVF cycle greater than 180 days from their first visit, it is not known how such a delay in treatment affects pregnancy outcomes in IVF cycles. Wider implications of the findings A delay in initiating IVF treatment in patients with diminished ovarian reserve up to 180 days from the initial visit does not affect pregnancy outcomes. This observation remains true for patients who are in the high-risk categories for poor response to ovarian stimulation. Providers and patients should be reassured that when a short-term treatment delay is deemed necessary for medical, logistic or financial reasons, treatment outcomes will not be affected. Study funding/competing interest(s) No financial support, funding or services were obtained for this study. The authors do not report any potential conflicts of interest. Trial registration number Not applicable.
Epidemiology, Prevention, Diagnosis, and Management of Venous Thromboembolism in Gastrointestinal Cancers

Venous thromboembolism (VTE) is a leading cause of cardiovascular death and is associated with significant morbidity. Patients with cancer, and gastrointestinal (GI) malignancies in particular, are at increased risk of VTE, increased risk of bleeding with VTE treatment, and increased risk of recurrent VTE compared with the general population. VTE has been shown to be a leading cause of death among patients with cancer. This review will discuss special considerations in the prevention, diagnosis, and management of VTE in patients with GI malignancies. Given the increased risk of VTE observed in ambulatory patients with GI malignancies, multiple trials have examined and demonstrated the efficacy of prophylactic anticoagulation in high-risk patients with cancer undergoing chemotherapy, particularly in patients with gastric and pancreatic cancers. Patients with GI malignancies have also played a central role in discussions of the risks and benefits of the use of direct oral anticoagulants in patients with cancers, with first-line anticoagulation options expanding to include low-molecular-weight heparin, rivaroxaban, edoxaban, and apixaban. However, there continue to be concerns regarding an increased risk of bleeding with edoxaban and rivaroxaban in patients with GI malignancies. In addition to anticoagulation, individualized risk and benefit analysis should be undertaken for interventions including inferior vena cava (IVC) filter placement and catheter-directed thrombolysis in the setting of increased risk of bleeding and recurrent VTE for patients with GI malignancies. Several unique scenarios that may be seen with GI malignancies, including incidental VTE, splanchnic vein thrombosis, IVC thrombosis, and iliac vein compression, require individualized decision making.
Ecological Networks as a Framework for Understanding and Predicting Contaminant Movement Across the Land-Water Interface

Models of interaction networks among species (i.e., network models) can be used to predict behavior of complex adaptive systems, such as ecosystems at the land-water interface. As theoretical and empirical understanding of ecological networks continues to grow, network models are increasingly used to quantify and predict ecosystem stability, metapopulation dynamics, disease spread, and social behavior. Here, we propose that ecological networks can also be used to synthesize many of the dynamics that regulate the movement of contaminants between aquatic and terrestrial systems. We discuss how network models can predict aquatic-terrestrial contaminant transport via food-web interactions, animal movement, and mutualistic interaction webs. In addition, we discuss how knowledge of social-ecological networks can help address contaminant exposure and risk to humans. To illustrate an application of network models in the field of contaminants and subsidies, we provide an empirical example of the responses of ecological networks to dam removal in a temperate river system. In this example, we observed that shifts in species composition (especially losses of larger-bodied, often predatory, sport fish) and subsequent changes to feeding relationships could reduce biomagnification of contaminants in the food web and thus reduce exposure to humans and other terrestrial consumers in the short term. In summary, we propose that ecological networks will be a valuable framework for understanding and forecasting temporally and spatially dynamic aquatic to terrestrial contaminant transport.
Government Regulation and the Quality of Health Care: Evidence from Minimum Staffing Legislation for Nursing Homes

This paper investigate the causal e ect of a regulation for California nursing homes that required a minimum number of nurse hours per patient day on the quality of health care measured both by patient outcomes and de ciency citations from facility inspections. The research design employed is based on the insight that compliance with the law induces a kinked relationship between average nurse employment increases and initial stang levels in the period following adoption: firms should increase employment of nurses in proportion to the gap between their initial staffing level and the legislated minimum threshold. If higher nurse stang causes better quality, then the changes in quality outcomes should mirror these changes. Despite inducing increases in nurse aide hours worked of up to 30 percent for some firms, and about 10 percent across all firms initially out of compliance, I find no impact of the staffing regulation on patient outcomes or overall facility quality.
Integrated student to school assignment and school bus routing problem for special needs students

Abstract In this paper, we address the combined problem of assigning students to schools and generating school bus routes for special needs students. Special needs students typically require additional accommodations, both in terms of the services available at school and during pick-ups and drop-offs. This introduces additional complexities to the problems of assignment and routing for students. We develop a mathematical model that jointly addresses these problems, and incorporate multi-loads and heterogeneous bus fleet features. The model simultaneously assigns special needs students to schools based on their level of need and the availability of resources, and generates efficient routes to transport them to their designated schools. We propose a two-phase heuristic approach using the capacitated clustering problem, which is capable of generating high-quality solutions. We evaluate our proposed methodology using several randomly generated instances, and a real-world case study in Fort Smith, Arkansas. The results from the case study demonstrate that the proposed methodology can reduce the total miles traveled by buses by over 35% on average, when compared to previously developed heuristics in the literature for the same case study.
Adjusting for selection bias due to missing data in electronic health records-based research.

While electronic health records data provide unique opportunities for research, numerous methodological issues must be considered. Among these, selection bias due to incomplete/missing data has rec...
Long Term Follow Up of the CAR T Recipient

Abstract T-cell therapy has emerged as transformative therapy for blood cancers. Autologous and allogeneic T-cells that have been genetically modified to express a chimeric antigen receptor, or CAR, have been shown to induce long-term remissions in patients with B-cell lymphoma, B-cell leukemia, and multiple myeloma. The delivery of cell-based therapies, whether autologous or allogeneic, is complex and requires collection, processing, and tracking systems that result in significant challenges to patients, their doctors, and the healthcare system. We will discuss the current clinical status of CAR T-cell therapies and important factors for physicians to consider in the long-term follow up of patients who have received any form of CAR T-cell or engineered T-cell therapy.
Influence of small-scale heterogeneity on upward CO2 plume migration in storage aquifers

Abstract Recent advancements in experimental techniques allow sub-core-scale heterogeneities to be quantified in a high resolution. Based on the observations of heterogeneity distributions in natural core samples, we perform simulations to study the influence of small-scale heterogeneities on large-scale CO2 migration during geological storage. We observe that even the heterogeneities at millimeter scale (the scale of a Representative Elementary Volume for sandstones) can affect large-scale buoyancy-driven upward CO2 migration. For the representative examples we study, ignoring small-scale heterogeneities can lead to an overestimation of the migration speed by a factor of two. To analyze the cause of such overestimation, we introduce a dimensionless heterogeneity factor to characterize different levels of heterogeneity. The influence on CO2 migration is quantified with respect to a variety of heterogeneity factors, correlation lengths, and fluid viscosity ratios for isotropic and anisotropic media. Our findings suggest that small-scale heterogeneities should not be ignored in core analysis, even for cores that appear relatively homogeneous and do not have distinguishable heterogeneous patterns. In addition, relative-permeability curves measured from core-flood experiments under high-flow-velocity conditions (a common practice to eliminate capillary end-effects) should not be directly used in modeling low-velocity CO2 migration if small-scale heterogeneities are present.
Generation of Micropatterned Substrates Using Micro Photopatterning

Micro photopatterning (µPP) has been developed to rapidly test and generate different patterns for extracellular matrix adsorption without being hindered with the process of making physical stamps through nanolithography techniques. It uses two-photon excitation guided through a point-scanning confocal microscope to locally photoablate poly(vinyl) alcohol (PVA) thin films in user-defined computer-controlled patterns. PVA thin films are ideal for surface blocking, being hydrophilic substrates that deter protein adsorption and cell attachment. Because gold substrates are not used during µPP, all live-cell fluorescent imaging techniques including total internal reflection fluorescence microscopy of GFP–linked proteins can be performed with minimal loss of fluorescence signal. Furthermore, because µPP does not require physical stamps for pattern generation, multiple ECMs or other proteins can be localized within microns of each other. This unit details the setup of µPP as well as giving troubleshooting techniques.
A simplified message-passing library

A simplified interface to MPI, the standard library for message-passing in distributed computing, is presented. This simplified library is based on a minimalist subset of MPI with the goal of allowing students to program and execute simple message-passing programs on a network of workstations. Standard mode point-to-point and environmental functions are included, as well as a small number of collective communication functions.
Optimal Immigration, Assimilation and Trade

The paper develops a general equilibrium model of migration, assimilation and trade, using a random matching framework of culture and trade. The market equilibrium and the social plannerOs solution are contrasted and policy implications are given. The model predicts that the presence of immigrants who do not assimilate into the mainstream culture is economically inefficient, but whether such migration occurs depends on the underlying parameters. Because of the endogeneity of the migration decision, care must be taken to select the optimal policy instruments. In particular, subsidizing assimilation or auctioning immigration permits do not achieve the first best. Instead, a mix of selective immigration, border control and aid to the source country can be used to promote efficiency.
Abstract 165: cAMP-Phosphodiesterase 1C Regulates Neointimal Hyperplasia by Controlling Platelet-Derived Growth Factor Receptor ß Degradation via the Endosome-Lysosome Pathway

Neointimal hyperplasia is associated with the development of diverse vascular diseases such as atherosclerosis, vein bypass graft disease and restenosis after percutaneous coronary interventions. Vascular injury-mediated neointimal hyperplasia involves the phenotypic modulation, migration and proliferation of vascular smooth muscle cells (VSMCs). Cyclic nucleotide is vital in regulating VSMC migration and proliferation, which are controlled by cyclic nucleotide phosphodiesterase (PDE) isozymes. To identify the regulation and function of PDEs in VSMC pathogenesis of vascular diseases, we performed systematic screening for all 22 known PDE genes in normal contractile VSMCs and proliferating synthetic VSMCs. Interestingly, we observed that expression of PDE1C was very low in normal contractile VSMCs but drastically elevated in synthetic VSMCs in vitro as well as in vivo in various mouse models of vascular injuries, including carotid artery ligation, femoral artery wire injury and vein bypass graft. Consistently, PDE1C is also highly induced in VSMCs in neointimal lesion of human coronary artery. More importantly, injury-induced neointimal formation was significantly attenuated in pde1c-deficient mice or by perivascular administration of PDE1 inhibitor. Furthermore, PDE1 inhibition also reduced the spontaneous vascular remodeling of human saphenous vein explant in an ex vivo culture model. Mechanistic studies revealed that PDE1C plays a critical role in regulating the stability of PDGF receptor beta (PDGFR-β). We found that PDE1C knockdown or inhibition markedly decreased the levels of PDGFR-β protein but not mRNA, which was blocked by endosome and lysosome inhibitors. Furthermore, PDE1C inhibition is capable of promoting PDGFR-β internalization and attenuating PDGFR-β membrane accumulation. Finally, we found that PDE1C co-localized with PDGFR-β on cell membrane, which was able to regulate PDGFR-β protein degradation through modulating a transmembrane adenylyl cyclase-cAMP-PKA signaling. Taken together, our present data demonstrated that PDE1C plays a critical role in regulating VSMC proliferation and neointimal hyperplasia, in part, through promoting endosome/lysosome dependent PDGFR-β protein degradation.