cssi/SciSciGPT-SciSciNet huggingface dataset:
Effects of natural images on the detectability of simple and compound wavelet subband quantization distortions

Quantization of the coefficients within a discrete wavelet transform subband gives rise to distortions in the reconstructed image that are localized in spatial frequency and orientation and are spatially correlated with the image. We investigated the detectability of these distortions: Contrast thresholds were measured for both simple and compound distortions presented in the unmasked paradigm and against two natural-image maskers. Simple and compound distortions were generated through uniform scalar quantization of one or two subbands. Unmasked detection thresholds for simple distortions yielded contrast sensitivity functions similar to those reported for 1-octave Gabor patches. Detection thresholds for simple distortions presented against two natural-image backgrounds revealed that thresholds were elevated across the frequency range of 1.15–18.4 cycles per degree with the greatest elevation for low-frequency distortions. Unmasked thresholds for compound distortions revealed relative sensitivities of 1.1–1.2, suggesting that summation of responses to wavelet distortions is similar to summation of responses to gratings. Masked thresholds for compound distortions revealed relative sensitivities of 1.5–1.7, suggesting greater summation when distortions are masked by natural images.
Adenosine receptor antagonism in refractory asystolic cardiac arrest: results of a human pilot study.

Primary objective: To determine if adenosine receptor antagonism has any beneficial impact on victims of asystolic cardiac arrest and whether or not it warrants further clinical study as a treatment for cardiac asystole. Materials and methods: A 6-month prospective, randomized, double-blinded, placebo-controlled trial, set in an urban emergency medical services system, in adults with nontraumatic asystolic out-of-hospital cardiac arrest. Patients in whom standard advanced cardiac life support pharmacotherapy failed were randomized to receive placebo or aminophylline, a nonspecific competitive adenosine receptor antagonist. Rhythms were recorded before and after intervention. Results: Twenty-two patients were appropriately entered into the trial. Eight patients served as controls and 14 patients received aminophylline. The groups were similar in all measured parameters except for initial rhythm. None of the patients in the placebo group responded to the intervention. Half of the patients in the treatment group had return of organized cardiac electrical activity. Conclusion: Our results suggest that adenosine receptor antagonism may have a role in the treatment of cardiac asystole. Further clinical studies to validate these findings and clarify the appropriate use of adenosine receptor antagonists in cardiac asystole may be justified.
A CMOS IC nonlinear resistor for Chua's circuit

The first monolithic realization of the nonlinear element in Chua's circuit, now generally called Chua's diode, is reported. The element has been fabricated using a CMOS integrated circuit technology. It can be used as the basic nonlinear component for the experimental synthesis of a broad class of circuits, including cellular neural networks, which exhibits an extremely rich variety of bifurcation, chaotic, and nonlinear wave phenomena. >
Genetic analysis of the dumpy complex locus in Drosophila melanogaster: complementation, fine structure and function.

An extensive genetic analysis of the dumpy locus is presented. This study includes complementation, fine structure mapping and allelic interaction. A number of complementing recessive lethals of the dp complex have been genetically mapped. Two alleles of the ol(v) type that complement l alleles map to the left portion of the locus. A number of olv alleles that complement both l and lv lethals map within the right portion of the locus.——Fine-structure analysis demonstrated that both olv and o alleles are distributed among various subloci. Evidence for spacer regions between subloci is presented.——An extensive discussion of the data considers whether the locus is unicistronic or multicistronic. The conclusion reached is that the locus is not a single functional cistron. The possibility of a single cistron encoding a multifunctional polypeptide is discussed.——The hypothesis is proposed that the left portion of the map and the l mutations function as regulatory sequences and that the right portion of the map encodes structural sequences.
Nuclear Lamins a and B1: Different Pathways of Assembly during Nuclear Envelope Formation in Living Cells

At the end of mitosis, the nuclear lamins assemble to form the nuclear lamina during nuclear envelope formation in daughter cells. We have fused A- and B-type nuclear lamins to the green fluorescent protein to study this process in living cells. The results reveal that the A- and B-type lamins exhibit different pathways of assembly. In the early stages of mitosis, both lamins are distributed throughout the cytoplasm in a diffusible (nonpolymerized) state, as demonstrated by fluorescence recovery after photobleaching (FRAP). During the anaphase-telophase transition, lamin B1 begins to become concentrated at the surface of the chromosomes. As the chromosomes reach the spindle poles, virtually all of the detectable lamin B1 has accumulated at their surfaces. Subsequently, this lamin rapidly encloses the entire perimeter of the region containing decondensing chromosomes in each daughter cell. By this time, lamin B1 has assembled into a relatively stable polymer, as indicated by FRAP analyses and insolubility in detergent/high ionic strength solutions. In contrast, the association of lamin A with the nucleus begins only after the major components of the nuclear envelope including pore complexes are assembled in daughter cells. Initially, lamin A is found in an unpolymerized state throughout the nucleoplasm of daughter cell nuclei in early G1 and only gradually becomes incorporated into the peripheral lamina during the first few hours of this stage of the cell cycle. In later stages of G1, FRAP analyses suggest that both green fluorescent protein lamins A and B1 form higher order polymers throughout interphase nuclei.
Developmental effects of selective breeding for an infantile trait: the rat pup ultrasonic isolation call.

This article describes how continued selection for divergent levels of the 10-day-old infant rat's ultrasonic vocal (USV) response to isolation affects the time course of development of that and other possible co-selected traits from 3 to 21 days postnatally. Since selective breeding for an infantile trait has not been reported before, we collected from colleagues a number of predicted outcomes that reflect the wide range of current opinion on the relationship between microevolutionary and developmental processes. After 15 generations of selective breeding, we found widely divergent USV responses between 10-day-old High USV line (300 USV/2 min) and low USV line (15 USV/2 min) pups. The developmental trajectory of USV responses at 3 and 7 days of age also was markedly altered in both these lines in comparison to the randomly bred controls, but was much less affected in 14-, 18-, or 21-day-old pups, contrary to all predictions. The development of other behavioral responses to isolation generally remained unaffected by the continued selection as did physical traits, measures of temperature regulation and classic developmental milestones. Only two traits showed evidence of co-selection: High line pups showed more urination/defecation in response to isolation from 10 days on, and more rapid ear canal opening at 10 days. These and other findings are presented and discussed in relation to the developmental and evolutionary concepts on which the different predictions were based.
The Politics of Causes: Mass Shootings and the Cases of the Virginia Tech and Tucson Tragedies†

Objective We employ theories of causal reasoning to understand attributions about the 2007 Virginia Tech and 2011 Tucson shootings. We argue that attributions stem from two motives: (1) a partisan motivation to perceive events consistent with party attachments, and (2) a drive to minimize the cognitive burdens associated with extensive reasoning processes. The latter motive is expected to produce a fundamental attribution bias: the least educated respondents attribute blame for the shootings to the individual assailant while the most educated attribute blame to environmental conditions. Methods We test hypotheses using 2007 and 2011 national surveys reported just after the shootings. Results Our findings suggest a major partisan divide on the causes of tragedy; Democrats believed social and political forces were responsible whereas Republicans blamed individual gunmen. Considerable differences between the least and most educated respondents were also discovered. Greater educational attainment was associated with environmental attributions. Finally, the analyses revealed that education had virtually no influence on Republican attributions, but enhanced Democrats’ penchant to blame the tragedy on environmental factors. Conclusion Our study highlights the utility of using motivational theories of causal attributions to understanding and modeling the cognitive processes involved in perceived causes about gun-related tragedies.
Route optimization among a group of multihomed stub networks

Multihoming is used by stub networks to improve the reliability of their Internet connectivity. In recent years, commercial "intelligent route control" devices are used by multihomed stub networks to optimize the routing of their Internet traffic. In this work, we first conduct measurement of qualities of alternate paths through multihoming. In the remaining part, we study the route control of traffic among a group of multihomed stub networks which may belong to an organization and exchange data regularly. This type of route control is special because the access links of such networks may not be over-provisioned and are shared by traffic controlled by multiple route control devices. Such shared bottlenecks may affect the effectiveness of uncoordinated "intelligent route control". We propose a global optimization based approach to coordinate the route control among such a group of networks. Our approach can avoid oscillations which may be caused by uncoordinated route control. Simulation results show that our approach has advantages over equal-splitting based static load-balancing.
Profiling Systems Using the Defining Characteristics of Systems of Systems (SoS)

Abstract : The concept of a system of systems (SoS) has become very popular over the last decade, resulting in books, conferences, technical papers, and reports. However, there is no consensus as to exactly what the term means, and it has been given many different, though re-lated, definitions. This technical note identifies and describes the characteristics that have been used in various definitions of the term system of systems. These SoS characteristics vary along corresponding scales and can form the basis of corresponding ?meters? that serve as indicators of where a system lies along the associated scale. This technical note also discusses two other classes of system characteristics: quality characteristics and programmatic characteristics and how similar meters can be used to describe where systems lie along the scales associated with these two additional sets of system characteristics. Finally, this technical note discusses the various benefits of using these system of systems characteristics to profile systems.
“Trapped rainbow” storage of light from THz to telecom domain

We show a metallic graded grating structure is able to achieve the function of ldquotrapped rainbowrdquo storage of light at both THz and telecom frequencies for potential nanophotonic applications including optical communications.
Second-level interconnects reliability for large-die flip chip lead-free BGA package in power cycling and thermal cycling tests

In this paper, an advanced 40nm, Cu/low-K 22×18mm2 Si chip with 42.5×42.5mm2 flip chip BGA-1681L package was used with substrate core material split on CTE ∼12ppm vs. 17ppm, and underfill material split on high Tg vs. low Tg. The packages were mounted on PWB (printed wiring board) for second-level interconnect SAC405 BGA reliability characterization. Thermal heaters and sensors were built-in the chip with first-level and second-level interconnect daisy chain designs to enable power cycling and thermal cycling reliability characterization. Experiments with variety of temperature range were conducted to compare second-level interconnects reliability under power cycling and thermal cycling tests. The results showed that thermal cycling with 25∼125°C profile could accelerate the test compared with 0∼100°C and reflected the similar failure ball location in the die-shadow edge as that from power cycling test. However, the typical thermal cycling ranging between 0°C and 100°C showed different worst cracked balls location around the package edge. An acceleration stress methodology for second-level interconnects reliability had been established on power cycling by increasing temperature ramp rate and raising peak temperature, while still keeping the same failure phenomenon. Underfill Tg effect was observed on solder fatigue performance that high Tg underfill resulted in shorter fatigue cycle. Failure analysis was performed to understand the failure mode and failure location differences. A non-linear 3D board-level finite-element analysis (FEA) was carried out to characterize the second-level interconnect BGA strain distribution difference under power cycling and thermal cycling tests with underfill and substrate core material splits.
JAK inhibition for the treatment of rheumatoid arthritis: a new era in oral DMARD therapy

Introduction: In rheumatoid arthritis (RA) there is a significant medical need for safe and effective oral disease-modifying anti-rheumatic drugs (DMARDs) for patients who respond inadequately to methotrexate, the first-line therapy in RA. Oral agents targeting Janus-associated kinases (JAKs) are the most promising new agents in clinical development. This review describes the preclinical and clinical activities of the most advanced JAK inhibitors with different JAK selectivity profiles. Areas covered: This review first describes the current treatment landscape and the pathophysiology of RA. Role for cytokines in the disease pathogenesis followed by significance of JAK/STAT pathway in cytokine signaling are discussed. Available chemical description and enzymatic data on the most advanced JAK inhibitors in clinical development are provided. Preclinical and clinical results that are publicly available are summarized. Review of literature was conducted using National Library of Medicine (NLM) database, ‘PubMe...
Dissipative differential inclusions, set-valued energy storage and supply rate maps, and discontinuous dynamical systems

In this paper, we develop dissipativity notions for dynamical systems with discontinuous vector fields. Specifically, we consider dynamical systems with Lebesgue measurable and locally essentially bounded vector fields characterized by differential inclusions involving Filippov set-valued maps specifying a set of directions for the system velocity and admitting Filippov solutions with absolutely continuous curves. In particular, we introduce a generalized definition of dissipativity for discontinuous dynamical systems in terms of set-valued supply rate maps and set-valued storage maps consisting of locally Lebesgue integrable supply rates and Lipschitz continuous storage functions, respectively. In addition, we introduce the notion of a set-valued available storage map and a set-valued required supply map, and show that if these maps have closed convex images they specialize to single-valued maps corresponding to the smallest available storage and the largest required supply of the differential inclusion, respectively. Furthermore, we show that all system storage functions are bounded from above by the largest required supply and bounded from below by the smallest available storage, and hence, a dissipative differential inclusion can deliver to its surroundings only a fraction of its generalized stored energy and can store only a fraction of the generalized work done to it.
Temporary Transumbilical Stenting of the Ductus Venosus in Neonates with Obstructed Infradiaphragmatic Total Anomalous Pulmonary Venous Return

Newborns with obstructed infradiaphragmatic total anomalous pulmonary venous return (TAPVR) are often clinically unstable. Temporary relief of the pulmonary venous obstruction may improve their clinical status before surgical repair. Three neonates (two premature and one full-term) with obstructed infradiaphragmatic TAPVR at the ductus venosus (DV) underwent stenting of the DV by way of an umbilical venous approach. Their clinical condition stabilized, thus allowing subsequent elective surgical repair.
Simulation of Doubly-Selective Compound K Fading Channels for Mobile-to-Mobile Communications

A computer simulation model is proposed for discrete-time doubly-selective compound-K fading channel. It first generates multiple independent mobile-to-mobile Rayleigh fading Channel Impulse Response (CIR) using the non-isotropic scattering model, then generates the cross- and auto-correlated gamma shadowing matrix using the combination of the memoryless nonlinear transformation (MNLT) method and the decomposition methods. It then combines the complex Rayleigh CIR with the gamma shadowing matrix to yield the doubly-selective fading channel CIR whose envelop follows the compound K distribution. Simulation examples demonstrate that the proposed method can effectively produce compound K fading channel responses with satisfactory statistical properties.
Disposition and metabolism of topically administered α‐tocopherol acetate: A common ingredient of commercially available sunscreens and cosmetics

Skin cancers are a serious health problem in the United States. One common method of skin cancer primary prevention is use of sunscreens. Research has been conducted to ascertain the role of active ingredients of sunscreen products in photoprotection and possible carcinogenesis. In contrast, little is known about the "other ingredients", listed or unlisted, on sunscreen product labels. One such ingredient is vitamin E. usually in the form of alpha-tocopherol acetate. Results of recent studies of skin carcinogenesis in an ultraviolet (UV) B mouse carcinogenesis model suggest that topically applied alpha-tocopherol acetate does not prevent and, under some conditions, enhances skin cancer development and growth, whereas the free unesterified from of alpha-tocopherol significantly reduces experimental UVB carcinogenesis. We have performed a Phase II cancer prevention study to evaluate whether topically applied alpha-tocopherol acetate is absorbed in human skin and metabolizes to the free or other forms. In this double-blind study, 19 men and women > 30 years of age who had at least three actinic keratoses on their forearms were randomly assigned to apply alpha-tocopherol acetate (125 mg/g) or difluoromethylornithine cream to their arms twice daily for three months. Blood samples and photographs and punch biopsies of actinic keratoses were obtained before and at the end of the study (Month 4). Plasma and skin concentrations of free alpha-tocopherol, alpha-tocopherol acetate, and gamma-tocopherol were analyzed by high-performance liquid chromatography at Month 4. The results of this report focus only on data obtained from the 11 participants randomized to the alpha-tocopherol acetate arm of the study. Topically applied alpha-tocopherol acetate was substantially absorbed in skin, with no evidence of conversion within skin to its unesterified form (i.e., free alpha-tocopherol). There was no evidence of systemic availability or biotransformation of topically applied alpha-tocopherol acetate. In summary, we have determined that alpha-tocopherol acetate is not metabolized to the free form of alpha-tocopherol in plasma or skin.
Membranes, ions, and impulses: Dedication to Kacy Cole

The title of the Colloquium on Membranes, Ions, and Impulses was chosen from Cole’s book, and it is a pleasure to dedicate this collection of papers given at the Colloquium to Kacy. It is a privilege to be in the unique position of having been associated with both Kacy Cole and Dan Tosteson, our American Physiological Society President for 1974.
Non-academic Self-Concept Among Urban Youth: Associations with Academic Success

An extensive literature demonstrates the relationship between academic self-concept and academic achievement, but the relationship between non-academic subdomains of the self and academic success in children and adolescents remains less clear. The current study examined longitudinal associations between social and behavioral self-concept, mental health symptoms, and indicators of academic achievement. Children (n = 364) from 36 classrooms across five elementary schools participated in the study. Children reported attitudes about the self, and teachers assessed children’s mental health symptoms and academic functioning at two time points. Structural equation models indicated that behavioral self-concept predicts subsequent academic engagement and study skills in low-income urban youth through improvement in academic self-concept and reduction in mental health symptoms. Findings point toward the potential promise of non-academic self-concept as a target for intervention to improve youth academic outcomes.
e e COLLISIONS AT CESR

The experimental results from CESR — the Cornell Electron Storage Ring — concern the physics of the b-quark. The spectroscopy of the bound states of the bb system — the T(1S), T(2S), and T(3S) enables us to test QCD, while the decays of the b-flavored mesons produced at the T(4S) provide tests of the standard six-quark model of weak interactions.
A Lawyer Looks at U.S. Antiquities Laws

The legal issues involved in trading antiquities across international borders are very complex; cases hinge on points that, to archaeologists, often seem to have little relevance to archaeological issues, or even to our sense of what the law "ought to be". A New York City art dealer was caught red-handed bringing into the U.S. Peruvian antiquities worth, reputedly, about a million dollars (see below). He had no export permit from Peru. Peru's antiquities laws require a permit for the export of all antiquities. It would seem very clear, then, that this dealer was engaged in an illegal activity. Unfortunately, perhaps, it is not that simple.
Effects of Training on Decision-Making

The experiment was designed to test whether training on one simulated problem would upgrade decisions on an entirely different one. The training problem required groups to contribute three solution...
Dietary gamma-linolenic acid supports arachidonic acid accretion and associated Δ-5 desaturase activity in feline uterine but not ovarian tissues.

Arachidonic acid (ARA) is essential in felines because conversion of dietary linoleic acid (LA) to ARA is rate-limited by low Δ6-desaturase. Dietary γ-linolenic acid (GLA) may serve as an ARA precursor by-passing this initial rate-limiting step. This possibility was investigated using twenty-six adult female domestic shorthair cats divided into three groups and fed on complete and balanced diets containing high GLA (GL), high LA (HL) or low LA (LL, control) diets, for 300 d prior to ovariohysterectomy. Plasma was obtained 1–2 d before surgery and uterine, ovarian and associated adipose tissues were reserved for lipid analysis. Fatty acid profiles of the plasma phospholipid (PL) fractions and adipose lipids were performed. In the GL group, plasma and uterine tissue PL were significantly enriched in GLA, di-homo GLA (DGLA) and ARA compared with control. However, ovarian and adipose tissue PL were only enriched in DGLA. Enrichment of uterine tissues with DGLA and ARA probably supplies the essential eicosanoid precursors for reproduction when GLA is fed consistently with an active Δ5-desaturase in uterus. By contrast, this enzyme appears less active in ovary because ARA was not higher compared with control. Earlier reports concluded that ARA was not necessary for fertilisation (an ovarian function), but required for successful pregnancy and reproduction (a uterine function). Adipose tissue DGLA may be a reservoir for ARA synthesis by other tissues upon mobilisation. Dietary GLA may meet feline ARA requirements in the absence of an animal-based preformed source of ARA.
Operating IGBTs above rated junction temperature limits: Impacts to reliability and electrical performance

A fixture was designed and built to test power cycling reliability at maximum junction temperatures of 150°C and 175°C. A 1200V, 150A IGBT six pack module was mounted on a single cold plate and three sets of cold plates were connected to DC power supplies controlled by LabView. The IGBTs on each cold plate were cycled to give a junction-to-case temperature rise of 100°C with a maximum junction temperature of 150°C. Every 2000 elapsed power cycles, the cold plates were removed from the test setup and the junction-to-case thermal resistance and collector-emitter saturation voltage was measured. Power cycle tests were run until all IGBT modules exceed the failure criteria (5% change in collector-emitter saturation voltage or 20% change in junction-case thermal resistance). The power cycle test was repeated on a new set of IGBTs with the same temperature rise of 100°C, but at 175°C maximum. Weibull analyses of the power cycle test data resulted in shape parameters of 8.6 and 8.8 for the 150°C and 175°C maximum junction temperature data, respectively, that is indicative of rapid wear out. Inspections of the failed modules indicated wire lift-off. The B5 life at 175°C was found to be 36% lower than the B5 life at 150°C. The power cycling test result at 150°C; however, was over two times higher than the life specified by the manufacturer. High temperature reverse bias testing at 175°C was also performed to stress silicon die and packaging materials under a DC bias in order to accelerate migration of ionic contaminants and silicon die impurities. Die temperatures of 175°C caused no degradation of the key electrical static parameter in 1400 hours, which exceeded industry standard test of 1000 hours.
Detection and Quantification of CWD Prions in Fixed Paraffin Embedded Tissues by Real-Time Quaking-Induced Conversion.

Traditional diagnostic detection of chronic wasting disease (CWD) relies on immunodetection of misfolded CWD prion protein (PrPCWD) by western blotting, ELISA, or immunohistochemistry (IHC). These techniques require separate sample collections (frozen and fixed) which may result in discrepancies due to variation in prion tissue distribution and assay sensitivities that limit detection especially in early and subclinical infections. Here, we harness the power of real-time quaking induced conversion (RT-QuIC) to amplify, detect, and quantify prion amyloid seeding activity in fixed paraffin-embedded (FPE) tissue sections. We show that FPE RT-QuIC has greater detection sensitivity than IHC in tissues with low PrPCWD burdens, including those that are IHC-negative. We also employ amyloid formation kinetics to yield a semi-quantitative estimate of prion concentration in a given FPE tissue. We report that FPE RT-QuIC has the ability to enhance diagnostic and investigative detection of disease-associated PrPRES in prion, and potentially other, protein misfolding disease states.
Analyzing results of IgM antibody in suspected measles and rebulla cases in Puning during 2005-2009

Objective:Testing IgM antibody of measles in Puning during 2005-2009 to analyze the epidemic features and provide strategies for its prevention and control.Methods:IgM antibody was measured by IgM-capture ELISA in all suspected measles cases between 2005-2009.Results:The overall positive rate of IgM in measles is 86.42%.Patients were between 0～10 years old.86.98% of Patients with measles came from Puning.Conclusion:The control of measles is very impactful,due to the incidence of measles in 2009 is much lower than that between 2006-2008.We will elimcnate measle in 2012.
Pure Consumption Cases under the Federal "Crackhouse" Statute

The federal “crackhouse” statute, 21 USC § 856, makes it a felony to “knowingly open, lease, rent, use, or maintain any place . . . for the purpose of manufacturing, distributing, or using any controlled substance.” 1 This Comment focuses on what it means for a defendant to open or maintain a place “for the purpose of . . . using” a controlled substance 2 under § 856(a)(1). In cases involving the manufacture or distribution of drugs (or both), circuit courts have struggled to determine exactly what kind of “purpose” is sufficient for criminal liability under the statute. These circuit courts agree that the statute covers more than just those who open or maintain facilities solely for the purpose of drug activities 3 (as is often the case with a traditional “crackhouse”). They have also assumed, in dicta, that the statute does not apply to drug activities that are merely an “incidental” purpose of the place 4 (such as a high school student smoking the occasional gram of marijuana in his parents’ house). However, between these two poles, circuit courts are split over the proper test for determining whether a defendant’s purpose for opening or maintaining a place is sufficiently related to his particular use, manufacture, or distribution of drugs to qualify him for criminal liability. The Tenth and Fifth Circuits have approached the issue by broadly defining “purpose” in terms of the importance of the drug activities to the defendant but have disagreed on whether the manufacture, distribution, or use must be either: (1) at least one of the “primary purpos-
Privacy and the Internet

Abstract This chapter summarizes the fundamental questions underlying the economics of privacy. It highlights the tension between the multifaceted concept of privacy as commonly used in policy debates and its conceptualization as part of a utility function. The chapter then sets out new challenges for the economics of privacy in a variety of online settings with particular reference to the media industry. These settings include advertising, social networks, data security, and government surveillance.
Effect of order on MCM implementations of FIR filters

Field Programmable Gate Arrays (FPGAs) are becoming a popular choice for digital filter implementation over DSP processors for reasons of higher sampling rates and more flexibility in design. Designing an efficient digital filter can be achieved using Multiple Constant Multiplication (MCM). MCM implements multiplication by constants through the use of shifts and adds/subtracts. Using MCM to design a filter circuit and selecting FPGAs for its implementation results in area savings and higher speed. This paper demonstrates how area is impacted through the use of MCM for FPGA implementation.
IFITM3 (CD225) Links the B Cell Antigen CD19 to PI3K-AKT Signaling in Human ALL Cells

Background & Hypothesis: IFITM3 (Interferon-induced transmembrane protein 3) also known as CD225/Leu-13 was identified as interferon-inducible molecule in the context of viral infection. IFITM3 encodes a surface receptor, basally expressed on the plasma membrane, that is associated with known B cell co-receptors including CD19, CD81 and CD21. Recent immunotherapy approaches based on CD19-specific engineered chimeric antigen receptors (CART19) have achieved spectacular successes in eliminating pre-B ALL cells based on surface expression of CD19 (Grupp et al., 2013). However, in some cases, CART19 treatment was followed by ALL relapse developing from clones that lacked CD19 surface expression. Therefore, we studied factors that regulate CD19 surface expression on human pre-B ALL cells. Results: Studying IFITM3 mRNA levels in ALL cells at the time of diagnosis in clinical trials for childhood (COG P9906) and adult ALL (ECOG E2993), we found that higher than median expression levels of IFITM3 predicted shorter overall and relapse-free survival (P=0.014). In addition, patients with higher than median IFITM3 mRNA levels at the time of diagnosis were significantly more likely to experience ALL relapse and had a higher risk of a positive MRD status at the end of induction chemotherapy. To study the function of Ifitm3 in a model for human pre-B ALL, pre-B cells from Ifitm3 -/- mice were transformed with BCR-ABL1. Strikingly, deletion of IFITM3 resulted in loss of CD19 expression on the surface of normal and leukemic pre-B cells. Besides loss of surface expression, loss of Ifitm3 also caused impaired phosphorylation of CD19-Y513, which mediates downstream activation of PI3K-AKT signaling in both B cell progenitors and pre-B ALL cells. These changes were paralleled by G0/1 cell cycle arrest (P Conversely, forced expression of IFITM3 in patient-derived pre-B ALL cells increased phosphorylation of CD19-Y513 together with downstream SRC, SYK, PI3K signaling. Although human IFITM1 has known as a component of B cell receptor complex, co-immunoprecipitation experiments revealed that the cytoplasmic tail of IFITM3 interacts with CD19, LYN, SYK, PI3K p110δ and AKT. In addition, agonistic antibodies against IFITM3/CD225 trigger CD19/PI3K-AKT signaling, which caused massively increased proliferation of pre-B ALL cells. Interestingly, agonistic antibodies against CD19 had no effect on the proliferation of pre-B ALL cells despite their ability to activate CD19/PI3K-AKT signaling. These findings indicate a specific role of IFITM3 in regulating CD19/PI3K-AKT signaling in malignant pre-B ALL cells compared to their normal pre-B cell counterparts. Conclusion: These findings identify novel role of the IFITM3 (CD255) surface receptor in regulating CD19 phosphorylation and CD19-Y513 mediated PI3K-AKT signaling in pre-B ALL cells. IFITM3 is a central mediator of CD19 surface trafficking and mediates the proliferation and survival signaling via PI3K-AKT in normal pre-B cells and various subtypes of human pre-B ALL. Disclosures No relevant conflicts of interest to declare.
The Economic Impact of Moore's Law: Evidence from When it Faltered

“Computing performance doubles every couple of years” is the popular re-phrasing of Moore’s Law, which describes the 500,000-fold increase in the number of transistors on modern computer chips. But what impact has this 50-year expansion of the technological frontier of computing had on the productivity of firms?This paper focuses on the surprise change in chip design in the mid-2000s, when Moore’s Law faltered. No longer could it provide ever-faster processors, but instead it provided multicore ones with stagnant speeds. Using the asymmetric impacts from the changeover to multicore, this paper shows that firms that were ill-suited to this change because of their software usage were much less advantaged by later improvements from Moore’s Law. Each standard deviation in this mismatch between firm software and multicore chips cost them 0.5-0.7pp in yearly total factor productivity growth. These losses are permanent, and without adaptation would reflect a lower long-term growth rate for these firms. These findings may help explain larger observed declines in the productivity growth of users of information technology.
Treatment of Urticaria

Urticaria represents a wide variety of conditions characterized by urticarial papules, wheals, and angioedema. The number of potential causes of urticaria is legion, but a diligent search by careful history and examination is indicated. Laboratory testing depends upon the specific situation, but routine screening examinations are not cost effective. Histamine from mast cells plays an important role in urticaria. Multiple factors, such as aspirin and other nonsteroidal anti-inflammatory agents, direct histamine-releasing agents (including benzoates), tartrazine and other azo dyes, and perhaps blockers of beta 2-adrenergic activity and H2 receptors, adversely influence histamine release either directly or indirectly. Vasodilation is also detrimental. Treatment of both acute and chronic urticaria necessitates removal of the patient from aggravating factors as well as the cause of the outbreak (if one can be found), along with effective antihistaminic agents and perhaps beta 2-adrenergic agonists. Treatment of specific entities within the urticarial group is briefly outlined in this article.
Acidocalcisome-Mitochondrion Membrane Contact Sites in Trypanosoma brucei.

Membrane contact sites are regions of close apposition between two organelles, typically less than 30 nanometers apart, that facilitate transfer of biomolecules. The presence of contact sites has been demonstrated in yeast, plants, and mammalian cells. Here, we investigated the presence of such contact sites in Trypanosoma brucei. In mammalian cells, endoplasmic reticulum-mitochondria contact sites facilitate mitochondrial uptake of Ca2+ released by the ER-located inositol 1,4,5-trisphosphate receptor (InsP3R). However, the InsP3R in trypanosomes localizes to acidocalcisomes, which serve as major Ca2+ stores in these parasites. In this work, we have used super-resolution structured illumination microscopy and electron microscopy to identify membrane contact sites that exist between acidocalcisomes and mitochondria. Furthermore, we have confirmed the close association of these organelles using proximity ligation assays. Characterization of these contact sites may be a necessary starting point towards unraveling the role of Ca2+ in regulating trypanosome bioenergetics.
PBTI in InGaAs MOS capacitors with Al 2 O 3 /HfO 2 /TiN gate stacks: Interface-state generation

Using devices with well passivated interfaces and reduced electron trapping, it is demonstrated that significant interface-state generation occurs during PBTI stress in InGaAs MOS capacitors with Al 2 O 3 /HfO 2 /TiN gate stacks. These observations on capacitors imply that the impact of interface-state generation on mobility and subthreshold-degradation need to be monitored in III-V nFET in addition to electron trapping in the gate stack.
Development of novel Cu-Cr-Nb-Zr alloys with the aid of computational thermodynamics

Abstract Multi-modal precipitate distribution in the microstructure, with coarse precipitates pinning the grain boundaries and finer precipitates strengthening the matrix, is beneficial to suppress grain boundary sliding and dislocation creep, respectively, of structural materials. However, achievement of a multi-modal precipitate distribution remains a challenge in developing creep-resistant advanced Cu alloys while retaining high strength and high conductivity at elevated temperature. This work overcame this challenge with the aid of computational thermodynamics. Thermodynamic models for Gibbs energy functions of phases in the Cu-Cr-Nb-Zr system have been developed in this study. These models were then used to calculate solidification paths and phase equilibria at different temperatures, guiding the design of chemical composition and heat treatment parameters of novel copper alloys with a target multi-modal distribution of precipitates. The new alloy, fabricated through traditional ingot metallurgy method, has achieved the desired microstructure as validated by optical and transmission electron microscopy. Electrical conductivity and mechanical properties were screened and compared with the existing commercial Cu alloys.
Acquired cellular responsiveness in cattle cleared of Anaplasma marginale 28 months earlier.

Abstract The leukocyte migration inhibition test (LMIT) was used to assess cell-mediated immune responses of cattle against Anaplasma marginale . Leukocytes from 7 of 11 cows that had been cleared of the carrier state by antibiotic therapy 28 months earlier were inhibited from their normal migration by A. marginale antigens ( P ). After reexposure to virulent organisms, all animals were positive to the LMIT. There was not a significant relationship (r=0.49) between LMIT values before and after reexposure. Results suggest that animals free of anaplasmosis for more than 2 years are capable of cell-mediated immune responses, despite decreased in vitro responsiveness at the time of reexposure. Acquired cellular responses did not prevent reinfection as all animals became A. marginale carriers.
Lipid Gene Trasfer, a Story of Simplicity and Complexity

It is 10 years since the first description of the use of a positively charged lipid to deliver nucleic acids to mammalian cells (Feigner et al., 1987). In essence the methodology of liposome-mediated transfer of nucleic acids is very simple. Cells are exposed to a complex of nucleic acid and lipid formed by simply mixing the two components together. The lipid in some way facilities both uptake of the nucleic acid by, and transport within a cell, usually enhancing transfer many fold over that seen if nucleic acid alone is used. However, this description is proving to be something of an over simplification of what is probably a much more complex process. This review will discuss the basic chemistry of the most widely used cationic liposomes, current models for DNA-liposome complexes, the chemical and biological factors that effect the efficiency of DNA transfer, and the proposed trafficking mechanisms that facilitate DNA transfer to the nucleus.
Acoustic receptivity and evolution of two-dimensional and oblique disturbances in a Blasius boundary layer

An experimental investigation was conducted to examine acoustic receptivity and subsequent boundary-layer instability evolution for a Blasius boundary layer formed on a flat plate in the presence of two-dimensional and oblique (three-dimensional) surface waviness. The effect of the non-localized surface roughness geometry and acoustic wave amplitude on the receptivity process was explored. The surface roughness had a well-defined wavenumber spectrum with fundamental wavenumber k w . A planar downstream-travelling acoustic wave was created to temporally excite the flow near the resonance frequency of an unstable eigenmode corresponding to k ts = k w . The range of acoustic forcing levels, e, and roughness heights, Δh, examined resulted in a linear dependence of receptivity coefficients; however, the larger values of the forcing combination eΔh resulted in subsequent nonlinear development of the Tollmien-Schlichting (T-S) wave
Treating Sleep-Related Breathing Disorders

The mainstay treatment for sleep-disordered breathing is positive airway pressure therapy. There is robust evidence to suggest PAP therapy improves cardiovascular, metabolic, psychiatric, and mental health outcomes. In addition, patients enjoy significant symptomatic benefit as well as improvement in neuropsychomotor function. Unfortunately, many patients also experience side effects, and as a result PAP tolerability and adherence are low. As a result, research is ongoing to determine means of improving PAP adherence, as well as to develop effective alternatives.
Suppression of Wnt/β-catenin signaling by EGF receptor is required for hair follicle development

Mice that lack the epidermal growth factor receptor (EGFR) fail to develop a hair coat, but the mechanism responsible for this deficit is not completely understood. Here, we show that EGFR plays a critical role to attenuate wingless-type MMTV integration site family member (Wnt)/β-catenin signaling during postnatal hair follicle development. Genetic ablation of EGFR in mice resulted in increased mitotic activity in matrix cells, apoptosis in hair follicles, and impaired differentiation of epithelial lineages that form hair. EGFR is activated in wild-type hair follicle stem cells marked with SOX9 or NFATc1 and is essential to restrain proliferation and support stem cell numbers and their quiescence. We observed elevated levels of Wnt4, 6, 7b, 10a, 10b, and 16 transcripts and hyperactivation of the β-catenin pathway in EGFR knockout follicles. Using primary keratinocytes, we linked ligand-induced EGFR activation to suppression of nascent mRNA synthesis of Wnt genes. Overexpression of the Wnt antagonist sFRP1 in mice lacking EGFR demonstrated that elevated Wnts are a major cause for the hair follicle defects. Colocalization of transforming growth factor α and Wnts regulated by EGFR in stem cells and progeny indicates that EGFR autocrine loops control Wnts. Our findings define a novel mechanism that integrates EGFR and Wnt/β-catenin pathways to coordinate the delicate balance between proliferation and differentiation during development.
The structural and functional domains of plant thylakoid membranes

In plants, the stacking of part of the photosynthetic thylakoid membrane generates two main subcompartments: the stacked grana core and unstacked stroma lamellae. However, a third distinct domain, the grana margin, has been postulated but its structural and functional identity remains elusive. Here, an optimized thylakoid fragmentation procedure combined with detailed ultrastructural, biochemical, and functional analyses reveals the distinct composition of grana margins. It is enriched with lipids, cytochrome b6 f complex, and ATPase while depleted in photosystems and light-harvesting complexes. A quantitative method is introduced that is based on Blue Native Polyacrylamide Gel Electrophoresis (BN-PAGE) and dot immunoblotting for quantifying various photosystem II (PSII) assembly forms in different thylakoid subcompartments. The results indicate that the grana margin functions as a degradation and disassembly zone for photodamaged PSII. In contrast, the stacked grana core region contains fully assembled and functional PSII holocomplexes. The stroma lamellae, finally, contain monomeric PSII as well as a significant fraction of dimeric holocomplexes that identify this membrane area as the PSII repair zone. This structural organization and the heterogeneous PSII distribution support the idea that the stacking of thylakoid membranes leads to a division of labor that establishes distinct membrane areas with specific functions.
Image Disguising for Privacy-preserving Deep Learning

Due to the high training costs of deep learning, model developers often rent cloud GPU servers to achieve better efficiency. However, this practice raises privacy concerns. An adversarial party may be interested in 1) personal identifiable information encoded in the training data and the learned models, 2) misusing the sensitive models for its own benefits, or 3) launching model inversion (MIA) and generative adversarial network (GAN) attacks to reconstruct replicas of training data (e.g., sensitive images). Learning from encrypted data seems impractical due to the large training data and expensive learning algorithms, while differential-privacy based approaches have to make significant trade-offs between privacy and model quality. We investigate the use of image disguising techniques to protect both data and model privacy. Our preliminary results show that with block-wise permutation and transformations, surprisingly, disguised images still give reasonably well performing deep neural networks (DNN). The disguised images are also resilient to the deep-learning enhanced visual discrimination attack and provide an extra layer of protection from MIA and GAN attacks.
Necrotizing enterocolitis leads to disruption of tight junctions and increase in gut permeability in a mouse model.

Necrotizing enterocolitis (NEC) is a leading cause of death in preterm infants. Neonates weighing 50% of experimental pups, pups lost nearly 40% of weight and their intestines showed gross changes and microscopic changes associated with NEC. There were inflammatory changes with loss of tight junction barrier function and disruption of tight junction claudin proteins in the intestines of NEC mouse model. We have demonstrated for the first time that NEC intestines develop increased leakiness as visualized by biotin tracer leakage. NEC leads to breakdown of epithelial barrier due to changes in tight junction proteins with increased leakiness which may explain the transmigration of microbes and microbial products from the gut lumen into the blood stream leading to sepsis like signs clinically witnessed.