cssi/SciSciGPT-SciSciNet huggingface dataset:
Mechanisms and consequences of hepatic regulation of mTORC1 by metformin

Background In mammals, the ability to sense and respond to both intracellular and extracellular nutrient levels requires the integration and cooperation of multiple complex metabolic regulatory networks. Key among these are the mTOR and AMPK signaling pathways, which are activated in response to increased or decreased cellular energy levels, respectively. These pathways control cell growth, proliferation, metabolism and autophagy, and their dysregulation has been associated with both cancer and metabolic disease. The anti-diabetes drug metformin has been shown to function, at least in part, through activation of AMPK, however it also inhibits mTORC1 signaling, suggesting a potential role for mTORC1 inhibition in the beneficial effects of metformin. AMPK can suppress mTORC1 through activation of the TSC complex, an inhibitor of mTORC1, or inhibition of Raptor, an essential component of mTORC1. The liver plays a critical role in the maintenance of systemic metabolic homeostasis, and is thought to be the major target organ for the physiological effects of metformin, thus we are investigating the hepatic regulation of mTORC1 by metformin. Materials and methods The effects of metformin on mTORC1 were assessed in livers and primary hepatocytes from LTSC1KO mice that have conditional loss of TSC1 in the liver. mTORC1 activity was determined by analysis of the phosphorylation state of its targets, and the rate of protein synthesis using 35S-methionine incorporation. Physiological effects of metformin were determined using glucose and metformin tolerance tests. Results
Increased Incidence of Neoplasia in Association with Chronic Lymphocytic Leukaemia

Etiologic factors were evaluated in an attempt to answer the question: ‘Does chronic lymphocytic leukaemia predispose to other neoplasms?’ The occurrence of the CLL prior to or simultaneous with the second neoplasm in 70% of instances, the known loss of immunologic function, both in the circulating immunoglobulins and in the fixed tissue response in the patient with CLL, and in some instances the use of immunosuppressive drugs and/or radiotherapy as well as prolongation of life, may be the important factors in the increased incidence of second neoplasms demonstrated in patients with chronic lymphocytic leukaemia. A further evaluation of this possible reduced immunity to neoplasms in the patient with CLL is certainly justified.
Mental illness made public: ending the stigma?

1that she complains about her illness having been trivialised because depression is so common. Such a complaint would have been unthinkable a generation ago, and it may still be unthinkable to many who suffer from mental illness today. Wurtzel claims, however, that her experience is typical of members of her generation, 1 Generation X (the post-babyboom generation), 2 now in their twenties, who suffer depression at a rate three times higher than that of people born before 1955. 3 Whether the incidence of depression or merely the incidence of reporting has risen, new drugs such as fluoxetine (Prozac) offer treatments that are far less stigmatising than those that were available to previous generations of patients. Wurtzel’s experience may not be unique, but it was certainly different from that of William Styron, who was already a Pulitzer prize-winning novelist when he experienced an episode of depression in 1985 at the age of 60. Although Styron’s depression did not yield to psychotherapy or drugs, his psychiatrist advised him “to avoid the hospital at all costs, owing to the stigma [he] might suffer”.
Polymers with a graphitic‐type structure. II

Further work has been done on the synthesis of a polymer from 1,4,5,8-tetraaminoanthraquinone on 1,3,6,8-tetraketo-1,2,3,6,7,8-hexahydropyrene which has a graphitic-type structure. Improved purity of the starting materials, particularly of the tetraketone, has given a final product of better quality. The reaction conditions have been improved by lowering the temperature and increasing the time of the reaction.
Part I: characterization of the extracellular proteome of the extreme thermophile Caldicellulosiruptor saccharolyticus by GeLC-MS2.

The proteome of extremely thermophilic microorganisms affords a glimpse into the dynamics of microbial ecology of high temperature environments. The secretome, or extracellular proteome of these microorganisms, no doubt harbors technologically important enzymes and other thermostable biomolecules that, to date, have been characterized only to a limited extent. In the first of a two-part study on selected thermophiles, defining the secretome requires a sample preparation method that has no negative impact on all downstream experiments. Following efficient secretome purification, GeLC-MS2 analysis and prediction servers suggested probable protein secretion to complement experimental data. In an effort to define the extracellular proteome of the extreme thermophilic bacterium Caldicellulosiruptor saccharolyticus, several techniques were considered regarding sample processing to achieve the most in-depth analysis of secreted proteins. Order of operation experiments, all including the C18 bead technique, demonstrated that two levels of sample purification were necessary to effectively desalt the sample and provide sufficient protein identifications. Five sample preparation combinations yielded 71 proteins and the majority described, as enzymatic and putative uncharacterized proteins, anticipate consolidated bioprocessing applications. Nineteen proteins were predicted by Phobius, SignalP, SecretomeP, or TatP for extracellular secretion, and 11 contained transmembrane domain stretches suggested by Phobius and transmembrane hidden Markov model. The sample preparation technique demonstrating the most effective outcome for C. saccharolyticus secreted proteins in this study, involved acetone precipitation followed by the C18 bead method in which 2.4% (63 proteins) of the predicted proteome was identified, including proteins suggested to have secretion and transmembrane moieties.
Neoadjuvant Concurrent Paclitaxel and Radiation in Stage II/III Breast Cancer

Purpose: The aim of this study was to determine the safety and pathologic response rates following neoadjuvant paclitaxel and radiation in patients with stage II/III breast cancer and to evaluate the use of sequential biopsies to allow an in vivo assessment of biological markers as potential predictive markers of response to this regimen. Patients and Methods: Patients with high-risk, operable breast cancer were treated with three cycles of paclitaxel 175 mg/m 2 every 3 weeks, followed by twice-weekly paclitaxel 30 mg/m 2 and concurrent radiation. Core biopsies were obtained at baseline and 24 to 72 hours after the first cycle of paclitaxel. After completing neoadjuvant treatment, patients underwent definitive surgery. The primary end point was pathologic complete response, which is defined as the absence of any invasive cancer at surgery. Potential markers of therapeutic response were evaluated including markers of proliferation, apoptosis, p21, HER2, estrogen receptor, and progesterone receptor status. Results: Of the 38 patients enrolled, 13 (34%) had a pathologic complete response. There was no significant difference in baseline Ki-67 between responders (35%) and nonresponders (28%; P = 0.45). There was also no significant change in Ki-67 following paclitaxel administration. Despite this lack of immunohistologic change in proliferative activity, baseline mitotic index was higher for patients with pathologic complete response over nonresponders (27 versus 10, P = 0.003). Moreover, the increase in mitotic index following paclitaxel administration was associated with pathologic complete response. Conclusions: Neoadjuvant paclitaxel/radiation is effective and well tolerated. Tumor proliferation at baseline and response to chemotherapy as measured by mitotic activity may serve as an important indicator of pathologic response to neoadjuvant paclitaxel/radiation.
Legislative Advocacy Under Competitive Authoritarian Regimes: The Case of Civil Society in Jordan

This article expands the limited literature on civil society legislative advocacy in the Arab world by examining the frequency of Civil Society Institutions’ (CSIs) legislative advocacy in Jordan, an Arab competitive authoritarian monarchy. The article explores the impact of authoritarian control and organizational factors on CSIs’ legislative advocacy. Based on 82 semi-structured interviews, this qualitative study finds that there is a low frequency of legislative advocacy among Jordanian CSIs. Financial resources, access to legislators, and perceptions of legislators’ interest in advocacy affect CSI legislative advocacy. In contrast, public funding and the law governing CSIs do not affect CSI legislative advocacy. The findings add to both the literature on advocacy in general and on legislative advocacy in particular, and open up new areas for research.
Human Immunodeficiency Virus Type 1 Nef Associates with Lipid Rafts To Downmodulate Cell Surface CD4 and Class I Major Histocompatibility Complex Expression and To Increase Viral Infectivity

Lipid rafts are membrane microdomains that are functionally distinct from other membrane regions. We have shown that 10% of human immunodeficiency virus type 1 (HIV-1) Nef expressed in SupT1 cells is present in lipid rafts and that this represents virtually all of the membrane-associated Nef. To determine whether raft targeting, rather than simply membrane localization, has functional significance, we created a Nef fusion protein (LAT-Nef) containing the N-terminal 35 amino acids from LAT, a protein that is exclusively localized to rafts. Greater than 90% of the LAT-Nef protein was found in the raft fraction. In contrast, a mutated form, lacking two cysteine palmitoylation sites, showed less than 5% raft localization. Both proteins were equally expressed and targeted nearly exclusively to membranes. The LAT-Nef protein was more efficient than its nonraft mutant counterpart at downmodulating both cell surface CD4 and class I major histocompatibility complex (MHC) expression, as well as in enhancing first-round infectivity and being incorporated into virus particles. This demonstrates that targeting of Nef to lipid rafts is mechanistically important for all of these functions. Compared to wild-type Nef, LAT-Nef downmodulated class I MHC nearly as effectively as the wild-type Nef protein, but was only about 60% as effective for CD4 downmodulation and 30% as effective for infectivity enhancement. Since the LAT-Nef protein was found entirely in rafts while the wild-type Nef protein was distributed 10% in rafts and 90% in the soluble fraction, our results suggest that class I MHC downmodulation by Nef may be performed exclusively by raft-bound Nef. In contrast, CD4 downmodulation and infectivity enhancement may require a non-membrane-bound Nef component as well as the membrane-bound form.
Impact of Joint Position and Joint Morphology on Assessment of Thumb Metacarpophalangeal Joint Radial Collateral Ligament Integrity

Purpose A 2-part biomechanical study was constructed to test the hypothesis that coronal morphology of the thumb metacarpophalangeal joint impacts the assessment of instability in the context of radial collateral ligament (RCL) injury. Methods Fourteen cadaveric thumbs were disarticulated at the carpometacarpal joint. Four observers measured the radius of curvature of the metacarpal (MC) heads. In a custom jig, a micrometer was used to measure the RCL length as each thumb was put through a flexion and/or extension arc under a 200 g ulnar deviation load. Strain was calculated at maximal hyperextension, 0°, 15°, 30°, 45°, and maximal flexion. Radial instability was measured with a goniometer under 45 N stress. The RCL was then divided and measurements were repeated. Analysis of variance and Pearson correlation metrics were used. Results The RCL strain notably increased from 0° to 30° and 45° of flexion. With an intact RCL, the radial deviation was 15° at 0° of flexion, 18° at 15°, 17° at 30°, 16° at 45°, and 14° at maximal flexion. With a divided RCL, instability was greatest at 30° of flexion with 31° of deviation. The mean radius of curvature of the MC head was 19 ± 4 mm. Radial instability was inversely correlated with the radius of curvature to a considerable degree only in divided RCL specimens, and only at 0° and 15° of flexion. Conclusions The RCL contributes most to the radial stability of the joint at flexion positions greater than 30°. The results suggest that flatter MC heads contribute to stability when the RCL is ruptured and the joint is tested at 0° to 15° of metacarpophalangeal flexion. Clinical relevance The thumb MC joint should be examined for RCL instability in at least 30° of flexion.
Newborn Presentation of Connective Tissue Disorders

Connective tissue disorders are a relatively common group of disorders that should be considered in any baby who has hypermobility or related multisystem involvement. Early diagnosis can decrease morbidity and improve many features of connective tissue disorders, including gross motor development, ambulation, and vision and hearing outcomes. Early echocardiography can identify congenital defects that need to be addressed surgically, treated prophylactically, or followed over time. Timely orthopedic management can address serious issues such as scoliosis, hip dysplasia, or fractures that must be treated to assure the best outcome possible. A genetic specialist often can aid in the initial recognition of signs and symptoms, guide molecular or protein analysis, explain information regarding recurrence risk and prognosis, and provide coordination of care throughout life.
RANKING HABITAT FOR MARBLED MURRELETS: NEW CONSERVATION APPROACH FOR SPECIES WITH UNCERTAIN DETECTION

An essential element in the conservation of rare species is the ranking of some aspects of habitat quality. We developed a method to rank the importance of individual habitat patches to Marbled Murrelets (Brachyramphus marmoratus) in 26 old-growth forest stands in northern California, using estimates of stand occupancy as an index of nesting activity. We used survey data collected in the stands from 1992 to 1997. The analysis was based on an adjustment that incorporates uncertainty of detection into a binomial model. Maximum likelihood estimators were used for the proportion P of the stands occupied by murrelets and the conditional probability p of detection with each visit to an occupied survey station, and bootstrapping methods were used for error estimates. We were able to rank a single stand most important, three other stands second in importance, and eight additional stands third in importance to murrelet nesting activity. For the murrelets in our study area, these results provided information useful in negotiations between government agencies and a private company in efforts to preserve some of the stands. Our methodology also has potential application for other flora and fauna of management concern, when sampling for presence or absence with uncertain detection. This technique can be applied at a variety of scales depending upon the species and habitat. Although conservation issues require consideration of many factors, including political, social, economic, and biological, our methods are helpful in providing science-based information from sample data to assist in the decision-making process.
Identification and cloning potentially protective antigens of Coxiella burnetii using sera from mice experimentally infected with Nine Mile phase I.

: Coxiella burnetii is an obligate intracellular bacterium that causes acute Q fever and occasional chronic infections in humans. To determine the immunodominant antigens during infection with C. burnetii, sera from mice experimentally infected with Nine Mile phase I were tested by immunoblotting. The mouse sera recognized antigens with a variety of molecular weights, including proteins of 14, 22, 28, 34, and 60 kDa as immunodominant antigens. In order to clone potential protective antigens, a genomic DNA library of Nine Mile phase I was constructed in the expression vector Lambda ZAP Express and screened with sera from mice that recovered from C. burnetii infection. A total of 102 immunoreactive clones with various signal intensities were identified from about 8,000 plaques. These clones were purified and expressed in the excised plasmid pBK-CMV. The proteins expressed by these recombinant plasmids were analyzed by SDS-PAGE and immunoblotting. Fifty-four clones expressed immunoreactive proteins of molecular masses ranging from approximately 14 to 60 kDa. Sequence analysis and BLAST search of the recently completed genome sequence identified a variety of novel immunoreactive proteins. These proteins are logical vaccine candidates for testing protective activity against C. burnetii challenge. We established a sublethal challenge model in BALB/c mice with protection from the development of severe splenomegaly as an indicator of vaccinogenic activity. Further characterization of these proteins will provide essential information for developing novel, specific diagnostic reagents and potential subunit vaccine candidates against C. burnetii infection.
Genipin‐induced changes in collagen gels: Correlation of mechanical properties to fluorescence

Controlled crosslinking of collagen gels has important applications in cell and tissue mechanics as well as tissue engineering. Genipin is a natural plant extract that has been shown to crosslink biological tissues and to produce color and fluorescence changes upon crosslinking. We have characterized the effects of genipin concentration and incubation duration on the mechanical and fluorigenic properties of type I collagen gels. Gels were exposed to genipin (0, 1, 5, or 10 mM) for a defined duration (2, 4, 6, or 12 h). Mechanical properties were characterized using parallel plate rheometry, while fluorigenic properties were examined with a spectrofluorimetric plate reader and with a standard, inverted epifluorescent microscope. Additionally, Fourier transform infrared spectroscopy was used to characterize and track the crosslinking reaction in real-time. Genipin produced significant concentration- and incubation-dependent increases in the storage modulus, loss modulus, and fluorescence intensity. Storage modulus was strongly correlated to fluorescence exponentially. Minimal cytotoxicity was observed for exposure of L929 fibroblasts cultured within collagen gels to 1 mM genipin for 24 h, but significant cell death occurred for 5 and 10 mM genipin. We conclude that genipin can be used to stiffen collagen gels in a relatively short time frame, that low concentrations of genipin can be used to crosslink cell-populated collagen gels to affect cell behavior that is influenced by the mechanical properties of the tissue scaffold, and that the degree of crosslinking can be reliably assayed optically via simple fluorescence measurements.
On adaptive vision feedback control of robotic manipulators

An adaptive vision feedback control system for a manipulator for grasping a moving object is described. The pose (position and orientation) of the object is determined from camera images and its time history is described by an AR (autoregressive) model. Because of the inherent delay caused by the image processing unit, the object pose is predicted for the controller using the AR model. An adaptive controller is designed using the discrete-time Lyapunov theory. The error which is defined in the joint space as the difference between the pose of the end-effector of the manipulator and the predicted pose of the object is shown to approach zero asymptotically by the second method of Lyapunov. The construction of the controller also gives an updating scheme for estimating unknown constant parameters of the manipulator model. >
Acute and chronic toxicity of technical‐grade pesticides to glochidia and juveniles of freshwater mussels (unionidae)

Chemical contaminants are among many potential factors involved in the decline of freshwater mussel populations in North America, and the effects of pesticides on early life stages of unionid mussels are largely unknown. The objective of this study was to determine the toxicity of technical-grade current-use pesticides to glochidia and juvenile life stages of freshwater mussels. We performed acute toxicity tests with glochidia (five species) and juveniles (two species) exposed to a suite of current-use pesticides including herbicides (atrazine and pendimethalin), insecticides (fipronil and permethrin), and a reference toxicant (NaCl). Because of limited availability of test organisms, not all species were tested with all pesticides. Toxicity tests with fungicides (chlorothalonil, propiconazole, and pyraclostrobin) were performed with one species (Lampsilis siliquoidea). Lampsilis siliquoidea glochidia and juveniles were highly sensitive to the fungicides tested but the technical-grade herbicides and insecticides, at concentrations approaching water solubility, were not acutely toxic to this or the other unionid species. In a 21-d chronic test with four-month-old juvenile L. siliquoidea, the 21-d median effective concentration (EC50) with atrazine was 4.3 mg/L and in atrazine treatments ≥3.8 mg/L mussel growth was significantly less than controls. The relatively high sensitivity of L. siliquoidea to chlorothalonil, propiconazole, and pyraclostrobin is similar to that reported for other aquatic organisms commonly used for toxicity testing. The relative risk associated with acute exposure of early life stages of mussels to technical-grade atrazine, pendimethalin, fipronil, and permethrin is likely low; however, survival and growth results with juvenile L. siliquoidea indicate that chronic exposure to high concentrations (≥3.8 mg/L) of atrazine may have the potential to impact mussel populations and warrants further investigation.
FRUITS AND VEGETABLES | Advances in Processing Technologies to Preserve and Enhance the Safety of Fresh and Fresh-Cut Fruits and Vegetables

The challenge of providing fruits and vegetables free from contamination with human pathogens has led to the development and optimization of a variety of postharvest-processing technologies. This chapter summarizes recent research related to chemical and physical treatments for fresh and fresh-cut produce. The technologies discussed range from optimizations and advances in conventional treatments, such as antimicrobial sanitizers and modified atmosphere packaging, to applications of established nonthermal processes, such as irradiation and ultraviolet light treatment. Novel tools such as cold plasma also are reviewed. Finally, the criteria for successful commercial adoption of new fresh produce processing tools are summarized.
Strange Fruit: What Happened to the United States Doctrine of Precedent?

This Article generates a critical history of the binary United States doctrine of precedent as it has developed since the mid-twentieth century, which history supplements a body of scholarly work that largely (i) fails to account for the doctrine of precedent we actually have and instead (ii) theorizes a practice that has long since ceased to exist herein the United States, and indeed probably never existed at all.
Hepatitis C Virus Testing and Treatment Among Persons Receiving Buprenorphine in an Office-Based Program for Opioid Use Disorders.

Aims In the United States, hepatitis C virus (HCV) infection is primarily spread through injection drug use. There is an urgent need to improve access to care for HCV among persons with opioid use disorders who inject drugs. The purpose of our study was to determine the prevalence of HCV, patient characteristics, and receipt of appropriate care in a sample of patients treated with buprenorphine for their opioid use disorders in a primary care setting.
Consumption and the extended family

This study examines whether resources of the extended family influence consumption. Extending prior tests on just food consumption to total consumption, little to no evidence is found in support of the strict definition of altruism among related households. However, resources of the extended family / dynasty do affect one’s own consumption.
Soups 2005

The first Symposium on Usable Privacy and Security (SOUPS 2005) brought together a variety of academic and industry researchers from the emerging field of human-computer interaction and security (HCISEC). The symposium helped to define the challenges that HCISEC researchers face, and provide an overview of many of today's most important usable security-and-privacy problems.
[Ir(N^N^N)(C^N)L]+: a new family of luminophores combining tunability and enhanced photostability.

The relatively unexplored luminophore architecture [Ir(N^N^N)(C^N)L]+ (N^N^N = tridentate polypyridyl ligand, C^N = 2-phenylpyridine derivative, and L = monodentate anionic ligand) offers the stability of tridentate polypyridyl coordination along with the tunability of three independently variable ligands. Here, a new family of these luminophores has been prepared based on the previously reported compound [Ir(tpy)(ppy)Cl]+ (tpy = 2,2′:6′,2″-terpyridine and ppy = 2-phenylpyridine). Complexes are obtained as single stereoisomers, and ligand geometry is unambiguously assigned via X-ray crystallography. Electrochemical analysis of the materials reveals facile HOMO modulation through ppy functionalization and alteration of the monodentate ligand’s field strength. Emission reflects similar modulation shifting from orange to greenish-blue upon replacement of chloride with cyanide. Many of the new compounds exhibit impressive room temperature phosphorescence with lifetimes near 3 μs and quantum yields reaching 28...
Performance Evaluation of a DENSO developed Micro-Laser Ignition System on a Natural Gas Research Engine

The performance of a prototype micro-laser ignition system developed by DENSO was evaluated on a single cylinder natural gas research engine. Several geometric combinations of pre-chamber spacing and hole sizes were tested at two engine load conditions. Significant improvements in brake thermal efficiency (BTE) were realized due to the extension of the lean ignition limit with a slight penalty in NOx.
Defining Reactivity Differences in Sterically Crowded (η5-C5Me5)3M Complexes Based on Metal Size and Lanthanide vs Actinide Effects

Reactions between (η5-C5Me5)3M and (η5-C5Me5)2M′(μ-Ph)2BPh2 (M, M′ = La, Ce, Pr, Nd, Sm, and U; M radius < M′ radius) were examined to evaluate the relative steric crowding in the (C5Me5)3M series ...
Adhesive-Bonded Shape Memory Alloy Strip Joint for Composite Fan Blade Shape Changing Concept

Adaptive polymer matrix composites (PMCs) fan blade concept is being explored by incorporating shape memory alloys (SMAs) either inside the composite or as a surface layer. The performance of the SMA-PMC fan blade system would be strongly dependent on the interfacial adhesion between the constituents. Characterizing interface strength-resistance and effective load transfer between PMC and SMA under engine service loads is an essential step to evaluate the feasibility of SMA strip (ribbon) as a potential actuator for the PMC fan airfoil shape change concept. Different finite element modeling techniques along with performing experimental coupon testing were examined with adhesive-bonded shape memory alloy strip joint configuration to validate whether this concept would be feasible for needs and aid in providing a fast and consistent modeling method to accurately characterize the stress distributions and potential bond failure locations along the bond line paths between SMA and PMC layers.
The On-line Detector of Temperature for the Contact Inside the H.V. Switchgear

The on-line detector of temperature for switchgear has functions of optoelectric data transmission, data processing and network configuration. It has also good electro-magnetic compatibility and good thermal stability. The application in electric power distribution system can improve the operation reliability and safety of power system.
A latent profile analysis of drinking patterns among nonstudent emerging adults.

Research indicates that nonstudent emerging adults, as compared to their college-attending peers, are at higher risk for experiencing alcohol-related problems, including alcohol use disorders. The present study sought to extend the limited research on nonstudent drinking by (1) identifying sub-groups of nonstudent drinkers based on their drinking patterns and (2) determining the extent to which social-cognitive between-person factors related to drinking (i.e., social expectancies, perceived drinking norms, social drinking motivations) distinguish these sub-groups. Participants were 195 (65.1% men) nonstudent emerging adult heavy episodic drinkers recruited from the community. Mean age was 21.88 (SD=2.08) years and 45.4% were unemployed. Latent profile analysis identified two classes based on drinking across 30days. The "moderate drinkers" group (n=143; 73.3%) reported consuming 10-11 drinks weekly and drinking two to three times per week, on average. The "heavy drinkers" class (n=52; 26.7%) reported consuming 42-43 drinks weekly and drinking six to seven days per week. Both groups exhibited a cyclic pattern of drinking whereby weekday drinking was lower, with increases on the weekend; the heavy drinkers class had stronger weekend increases starting earlier. Heavy drinkers reported greater volume, frequency, and problematic drinking behaviors, as compared to the moderate drinkers. The heavy drinkers class also endorsed stronger social motives and perceived their peers to drink more. The present study offered unique insights into nonstudent emerging adult drinking patterns by identifying sub-populations of drinkers based on their past 30-day use. Knowledge gained from this study could aide in tailoring existing alcohol interventions to nonstudents to reduce alcohol-related harms.Copyright © 2016 Elsevier Ltd. All rights reserved. Language: en
Color Perception in Sociology: Materiality and Authenticity at the Gods in Color Show

Color is a central feature of social life, yet its value in sociological theory is ambiguous. This paper establishes an approach to a social theory of color by focusing on color perception. Using t...
152. Retinal Tropism of Exosome-Associated AAV Vector Via Intravitreal Delivery

Recent clinical studies have validated the use of adeno-associated viral vectors (AAV) as a safe and efficient gene delivery vehicle for the treatment of retinal disorders. Different studies targeting the retina using AAV vectors have been achieved transduction of retinal cells via one of two delivery routes: subretinal or intravitreal injections, with subretinal delivery by far the most efficient method. Current treatments for age-related macular degeneration (AMD) heavily rely on protein drug delivery via regular and repeated intravitreal injections making the current standard of care clearly not optimal. One alternative for AMD treatment would be to use an AAV-based gene delivery and indeed preclinical studies in both mouse and non-human primates have shown that intravitreal delivery of AAV2 can mediate sustained expression of transgenes in the vitreous cavity following a single injection. Since the DNA is encapsulated in the AAV capsid, it is the capsid that determines the majority of the pharmacological interactions with the host, including cellular specificity, binding and uptake, immune activation and stability. However intravitreal injections using AAV vectors are inefficient regarding expression levels and poses higher inflammatory risk to vector or transgene antigens.In the current study we evaluated the retinal tropism of exosome-associated AAV9 vector (vexosomes). Exosomes are naturally secreted membrane nanovesicles involved in intercellular communication. We have previously shown that vexosomes highly outperforms regular AAV in efficacy in vitro and in vivo, and are resistant to neutralizing antibodies due to shielding of the AAV by the exosomal membrane.AAV9-vexosomes were isolated from AAV-producer cell (293T) media by ultracentrifugation. AAV vexosomes were injected into C57bl/6 wild type mice and transgene expression was evaluated at 2 and 4 weeks post injections via in vivo fundus imaging. Eyes were collected at 4 weeks post injections and retinal cell tropism was analyzed. Comparison of transgene expression levels between the different vexosomes and traditionally formulated AAV vectors was done using real time PCR.Intravitreal delivery of AAV9-vexosomes showed increased level of retinal cells transduction compared to regular AAV9 vectors which show very poor transduction. Apparently, vexosomes were able to penetrate through the ILM and transduce the retina in patches, as assessed by fundus imaging. Due to the immune issues surrounding gene delivery in the eye via an intravitreal route, the results presented here indicate a promising alternative gene delivery platform using vexosomes that could circumvent the inflammatory risks expected by intravitreal injection. Further studies in assessing the extent vexosomes evade neutralization in the vitreous will be extremely important to complement the results presented here.
The Theory of an International Committee Requiring a Unanimous Decision

Clubs or governmental assemblies sometimes require a special majority of say, two-thirds or perhaps three-quarters, of the members voting, in order to make any change in their constitution and sometimes company law requires a special majority of the shareholders, for example, to make an alteration in the rights attaching to the company’s shares. The underlying idea is that a change of a fundamental rights should be made only with widespread agreement among the members about its desirability. The larger the size of the majority required, the greater is the width of agreement ensured.
On the Shape of the Eshelby Inclusions

It is shown, based on properties of analytic functions, that for inclusions of constant eigenstrain and eigenstress that the shape of the inclusion is restricted and any part of a plane (i.e. polyhedral inclusion) is prohibited.
Utilizing Selenocysteine for Expressed Protein Ligation and Bioconjugations.

Employing selenocysteine-containing protein fragments to form the amide bond between respective protein fragments significantly extends the current capabilities of the widely used protein engineering method, expressed protein ligation. Selenocysteine-mediated ligation is noteworthy for its high yield and efficiency. However, it has so far been restricted to solid-phase synthesized seleno-peptides and thus constrained by where the selenocysteine can be positioned. Here we employ heterologously expressed seleno-fragments to overcome the placement and size restrictions in selenocysteine-mediated chemical ligation. Following ligation, the selenocysteine can be deselenized into an alanine or serine, resulting in nonselenoproteins. This greatly extends the flexibility in selecting the conjugation site in expressed protein ligations with no influence on native cysteines. Furthermore, the selenocysteine can be used to selectively introduce site-specific protein modifications. Therefore, selenocysteine-mediated ex...
Predictive Value of Dobutamine Stress Perfusion Echocardiography in Contemporary End-Stage Liver Disease.

BackgroundThe assessment of cardiac risk in contemporary liver transplantation (LT) has required more sensitive testing for the detection of occult coronary artery disease as well as microvascular ...
THREE TYPES OF PRODUCER'S AND CONSUMER'S RISKS IN THE SINGLE SAMPLING PLAN

The classical producer's risk and the classical consumer's risk are defined in acceptance sampling based on the assumption that the proportion defective of incoming lots is a constant. This assumption has been a focus of much of the criticism of accepta..
Simultaneous Streptococcus pneumoniae empyema in fraternal twins

Streptococcus pneumoniae is the most common bacterial cause of community acquired pneumonia. The current trend in Streptococcus pneumoniae infections has been the rise of multi-drug resistance in the last two decades. We present the case of a pair of 16-month old African-American fraternal twins who presented to the emergency room on the same day for symptoms consistent with pneumonia. Upon further examination, the twins showed remarkably similar symptoms, and cultures revealed penicillin-resistant Streptococcus pneumoniae in both twins. The pneumonia affected both twins in the same way, but a tomography scan did not reveal any shared anatomical abnormalities to account for this near-identical progression. In a review of literature and case reports, there are no reported cases of fraternal twins with simultaneous or non-simultaneous pneumococcal pneumonia or effusions. This case suggests that there may be possible anatomical abnormalities in the fraternal twins which were not evident in routine testing that may have led to near-identical illnesses. The pathophysiology of the simultaneous and near identical infections is not clear but may reflect subtle genetic factors in the siblings.
The Leasing Decisions of Startup Firms

Small business owners use a variety of bootstrap financing methods to acquire the needed resources necessary to survive and eventually grow their businesses. One such method is to lease equipment and/or machinery. Leasing is a viable alternative to bank financing and for small businesses, leasing is a flexible strategy to preserve cash. In this study, we analyze the impact of asset specificity and growth opportunities on leasing decisions of a large cohort of startup businesses. To test our hypotheses, we use a unique dataset provided by the Kauffman Foundation1. Our longitudinal analyses show that startups with unique/specific assets have a lower propensity to lease whereas startups with high growth opportunities are more likely to lease their assets. We also argue that the owners’ demographic and socioeconomic characteristics are likely to impact their individual risk-taking behavior. Thus, factors such as owners’ experience, education, age, gender, and race are likely to impact the decision to lease assets. Our results show that owners’ characteristics do have a significant impact on these decisions. The findings reveal that female and older entrepreneurs as well as highly educated owners are less likely to lease. Our work advances prior research on the determinants of leasing in large, publicly traded firms and provides additional insights on entrepreneurial bootstrapping.
Novel Options Generation

Option generation, and especially the generation of novel options, is a critical capability that is needed during upfront engineering and especially during system architecting. Systems architecting is an integrative, decision-rich activity that requires the generation and evaluation of novel options (i.e., alternatives) to exploit technological advances and assure compliance with changes in programmatic and institutional constraints. From a decision making perspective, option generation circumscribes the set of potential decisions/actions available to the decision maker. It makes the decision maker (e.g., system architect or designer) define the decision parameters of the problem in precise terms. It sets upper and lower bounds on the quality of the decision maker’s choices. Surprisingly, option generation is not given the attention it deserves, because many decision-theoretic models assume that the decision maker already has a predefined set of options. With this mindset, the problem becomes one of representing available options in a formal decision support framework [2, 3]. Even when the assumption of having a predefined set of options at the start was removed in subsequent methods [4], option generation remains a difficult task because it requires substantial knowledge of the problem domain (e.g., air traffic control, healthcare) and understanding of the decision context. Reducing the effort required to extract, process, and represent knowledge in usable form is a key challenge in option generation today. This chapter presents a framework for enhancing novel generation, along with principles for stimulating novel option generation. It describes the architecture and capabilities of an option generation aid along with metrics to evaluate the quality of options that are generated. It concludes by stressing the importance of novel option generation in the interconnected, hyper-competitive world of today.
Neuroemergencies in Critical Care Patients

Abstract Neurological disorders are common among critically ill patients. Abnormal physical exam findings may signal a neurological emergency or a complication of critical illness itself. Timely diagnosis of bacterial meningitis, spinal cord compression, stroke, and status epilepticus is essential as early therapy improves outcomes for patients with these conditions. More commonly however, alterations in mental status and muscle strength in critically ill patients are due to the effects of systemic organ failure and ICU medications. While there are no pharmacologic treatments for delirium and ICU-acquired weakness, their presence has both short- and long-term prognostic implications.
Dataset on a 173 region awake resting state quantitative cerebral blood volume rat brain atlas and regional changes to cerebral blood volume under isoflurane anesthetization and CO2 challenge.

Abstract The data in this article provide detail regarding the rat brain atlas measurements discussed in our research article, “Quantitative vascular neuroimaging of the rat brain using superparamagnetic nanoparticles: New insights on vascular organization and brain function” (Gharagouzloo et al., 2017) [1] . This article provides datasets of quantitative cerebral blood volume (qCBV) measurements across 173 regions of the rat brain in 11 healthy rats. State-changes from this baseline during isoflurane and CO2 administration are provided for all regions and all animals.
Cannabinoids and immunity to viruses.

The ability of marijuana to alter the course of viral infections was initially reported by Juel-Jensen in 1972.1. In this report, the author associated marijuana smoking with more frequent recurrences of herpes simplex virus (HSV) infections. This anecdotal report was made concerning only a few patients but was the impetus for examining the relationships among cannabinoids, immunity and progression of viral infections. The ability of cannabinoids, especially delta-9-tetrahydrocannabinol (THC), to alter immune functions is well described and has been reviewed.2 A summary of these findings is listed in Table 1.
Challenges and experiences in building an efficient apache beam runner for IBM streams

This paper describes the challenges and experiences in the development of IBM Streams runner for Apache Beam. Apache Beam is emerging as a common stream programming interface for multiple computing engines. Each participating engine implements a runner to translate Beam applications into engine-specific programs. Hence, applications written with the Beam SDK can be executed on different underlying stream computing engines, with negligible migration penalty. IBM Streams is a widely-used enterprise streaming platform. It has a rich set of connectors and toolkits for easy integration of streaming applications with other enterprise applications. It also supports a broad range of programming language interfaces, including Java, C++, Python, Stream Processing Language (SPL) and Apache Beam. This paper focuses on our solutions to efficiently support the Beam programming abstractions in IBM Streams runner. Beam organizes data into discrete event time windows. This design, on the one hand, supports out-of-order data arrivals, but on the other hand, forces runners to maintain more states, which leads to higher space and computation overhead. IBM Streams runner mitigates this problem by efficiently indexing inter-dependent states, garbage-collecting stale keys, and enforcing bundle sizes. We also share performance concerns in Beam that could potentially impact applications. Evaluations show that IBM Streams runner outperforms Flink runner and Spark runner in most scenarios when running the Beam NEXMark benchmarks. IBM Streams runner is available for download from IBM Cloud Streaming Analytics service console.
Neutrality and epistasis in program space

Neutral networks in biology often contain diverse solutions with equal fitness, which can be useful when environments (requirements) change over time. In this paper, we present a method for studying neutral networks in software. In these networks, we find multiple solutions to held-out test cases (latent bugs), suggesting that neutral software networks also exhibit relevant diversity. We also observe instances of positive epistasis between random mutations, i.e. interactions that collectively increase fitness. Positive epistasis is rare as a fraction of the total search space but significant as a fraction of the objective space: 9% of the repairs we found to look (and 4.63% across all programs analyzed) were produced by positive interactions between mutations. Further, the majority (62.50%) of unique repairs are instances of positive epistasis.
Global Longitudinal Strain by Echocardiography Predicts Long-Term Risk of Cardiovascular Morbidity and Mortality in a Low-Risk General Population: The Copenhagen City Heart Study.

Background—Global longitudinal strain (GLS) is prognostic of adverse cardiovascular outcomes in various patient populations, but the prognostic utility of GLS for long-term cardiovascular morbidity...
1571. Cost-Effectiveness Analysis of Duration of Valganciclovir Prophylaxis Among CMV Serology Mismatched (Donor+/Recipient−) Lung Transplant Recipients

Background Cytomegalovirus (CMV) is the most common cause of opportunistic infection (OI) following lung transplant (LTx), with incidence of 30–90%. CMV is associated with direct morbidity and indirect effects (e.g., graft failure, development of OIs and graft rejection (ACR), etc.), all of which lead to poor outcomes. Donor CMV positive, recipient negative (D+/R−) patients have the highest risk of CMV infections, for which they typically receive prolonged durations (≥1 year) of valganciclovir prophylaxis (Px). Px is limited by toxicity and ganciclovir-resistance. We performed a cost effectiveness analysis of differing lengths of Px in CMV D+/R− LTx patients.
Pathological Remodeling of Mitral Valve Leaflets from Unphysiologic Leaflet Mechanics after Undersized Mitral Annuloplasty to Repair Ischemic Mitral Regurgitation.

Background Undersized ring annuloplasty is a commonly used surgical repair for ischemic mitral regurgitation, in which annular downsizing corrects regurgitation, but alters valve geometry and eleva...
An In-Vitro Flow Study Using an Artificial Circle of Willis Model for Validation of an Existing One-Dimensional Numerical Model

A one-dimensional (1D) numerical model has been previously developed to investigate the hemodynamics of blood flow in the entire human vascular network. In the current work, an experimental study of water–glycerin mixture flow in a 3D-printed silicone model of an anatomically accurate, complete circle of Willis (CoW) was conducted to investigate the flow characteristics in comparison with the simulated results by the 1D numerical model. In the experiment, the transient flow and pressure waveforms were measured at 13 selected segments within the flow network for comparisons. In the 1D simulation, the initial parameters of the vessel network were obtained by a direct measurement of the tubes in the experimental setup. The results verified that the 1D numerical model is able to capture the main features of the experimental pressure and flow waveforms with good reliability. The mean flow rates measurement results agree with the predictions of the 1D model with an overall difference of less than 1%. Further experiment might be needed to validate the 1D model in capturing pressure waveforms.
British Surrenders and the South African War, 1899–1902

Based on primary research, this article examines more than 1000 cases of surrender in the British Army during the South African War, 1899–1902. It concludes that the majority of surrenders were cau...