cssi/SciSciGPT-SciSciNet huggingface dataset:
Events Associated with Mouse Skin Tumor Promotion with Respect to Arachidonic Acid Metabolism: A Comparison between SENCAR and NMRI Mice

NMRI and SENCAR, two stocks of mice commonly used in multistage skin carcinogenesis studies, were compared with respect to the effects of inhibitors of arachidonic acid metabolism for the following 12-O-tetra-decanoylphorbol-13-acetate (TPA)-elicited events: tumor promotion, DNA synthesis in vivo and in vitro, ornithine decarboxylase induction, and prostaglandin (PG) E2 synthesis. Previous work had shown that the cyclooxygenase inhibitor indomethacin enhanced TPA promotion in SENCAR mice. We report here that over the same dose range (50 to 200 micrograms) indomethacin caused a dose-dependent inhibition of promotion in NMRI mice. Significant reversal of this inhibition was achieved with concomitant application of 10 micrograms PGF2 alpha but not PGE2. DNA synthesis studies showed that low doses of indomethacin and flurbiprofen increased TPA-stimulated DNA synthesis in primary cultures from SENCAR mice; indomethacin suppressed this response in NMRI cultures. In vivo DNA synthesis studies showed the same pattern: indomethacin enhanced TPA-stimulated DNA synthesis in SENCAR mice but inhibited in NMRI mice. Other classes of inhibitors of arachidonate metabolism (i.e., the cyclooxygenase-lipoxygenase inhibitors 5,8,11,14-eicosatetraynoic acid and phenidone and the phospholipase A2 inhibitor dibromoacetophenone) had inhibitory activity in vitro and in vivo in both stocks of mice. Indomethacin was found to inhibit TPA-induced ornithine decarboxylase activity to the same extent in both mice. Indomethacin was also very effective in inhibiting TPA-induced PGE2 synthesis in both stocks of mice. 5,8,11,14-Eicosatetraynoic acid and phenidone were likewise suppressive in both stocks of mice. It is concluded that the NMRI and SENCAR mice respond similarly to TPA with respect to promotion, DNA synthesis, ornithine decarboxylase induction, and PG synthesis. The difference appears to be in the degree of involvement of the lipoxygenase pathway.
Letter by Doraiswamy Regarding Article, “Intensifying Platelet Inhibition With Tirofiban in Poor Responders to Aspirin, Clopidogrel, or Both Agents Undergoing Elective Coronary Intervention: Results From the Double-Blind, Prospective, Randomized Tailoring Treatment With Tirofiban in Patients Showing Resistance to Aspirin and/or Resistance to Clopidogrel Study”

To the Editor: Valgimigli et al1 conducted an interesting prospective study on the effect of tirofiban in poor responders to aspirin, clopidogrel, or both undergoing elective coronary intervention. Although the reasons for recruiting low-risk patients in the study are explained,2 this study cannot be incorporated into commonly encountered advanced cardiac patients. Certain additional details and controversies need to be addressed. I find that the placebo group …
The costs of financial distress across industries

I estimate the market's opinion of ex-ante costs of financial distress (CFD) from a structurally motivated model of the industry, using a panel dataset of monthly market values of debt and equity for 269 firms in 23 industries between 1994 and 2004. CFD are identified from market values and betas of a company's debt and equity. The market expects costs of financial distress of 5% of firm value for observed leverage ratios. In bankruptcy, distress costs can rise as high as 31%. Across industries, CFD are driven primarily by the potential for debt overhang problems and distressed asset fire-sales. There is considerable empirical support for the hypothesis that firms choose a leverage ratio based on the trade-off between tax benefits and CFD. The results do not confirm the under-leverage puzzle for firms with publicly traded debt.
Towards a 2D tactile vocabulary for navigation of blind and visually impaired

In this paper we present research work towards a 2D tactile vocabulary for training visually impaired for their independent mobility. The vocabulary is associated to a 2D tactile array (vibration array), which is a part of a wearable navigation prototype (Electronic Travel Aid) called Tyflos. The vibration array is currently consisting of 16 vibrating elements arranged in a 4×4 manner. Each motor can be independently driven with square pulses of varying frequencies. The vibration array can represent dynamically the 3D space of the user's field of view: the 2D arrangement represent the x-y coordinates while the frequencies represent the z coordinate (which is the distance of an obstacle from the user). Different navigation and human factor criteria have been used to create the 2D tactile vocabulary. Finally, using the continuous feedback from the users, the goal is to balance between a minimal vocabulary for easy learning and a rich vocabulary that will still be able to represent efficiently the 3D navigation space.
High Resolution Electron Microscopy of Twist Grain Boundaries

Preliminary experimental high resolution micrographs have been obtained for a Au thin film containing a [001], Σ=5 (θ=36.5 °) twist boundary. Other twist boundary cases such as the [001], Σ=13 (θ= 22.6°) and [111] low angle (˜3°) have also been fabricated. In order to assess whether the atomistic boundary structure is being imaged, extensive computer simulations of the Σ=5 bicrystal images have also been undertaken. Structurally, several contributions to the scattering must be considered which include: both upper and lower surface layers, bulk contributions above and below the interface and the relaxed interfacial structure at the composite film midplane. The effect of specimen orientation on image features is also evaluated for dynamical diffraction conditions. Likewise, the types of image features which arise by including bulk lattice reflections or alternately including only the reflections arising from the interface and surfaces will be discussed. Several schemes for analyzing twist boundary structures flat-on or near flat-on will be presented for a wide range of microscope conditions for a 400 kV microscope.
Improving sound spatialization by modifying head-related transfer functions to emulate protruding pinnae

Head-related transfer functions (HRTF) are widely used for the synthesis of binaural sound, which can produce in the listener the illusion of a sound that originates at a virtual location around him/her. The accuracy in the perception of these sounds, however, is compromised by the "cone of confusion" effect. Due to this effect, a source in the back hemisphere is perceived to be in the front hemisphere, and vice versa. This effect is particularly noticeable in the front (azimuth 0/spl deg/) and the back (azimuth 180/spl deg/). Preliminary observations suggested that the HRTF of individuals with particularly protruding ears show more accentuated spectral differences between symmetric locations. These HRTF were helpful in resolving the cone of confusion when used by subjects with average or small pinna protrusions. This paper describes the design of attenuation/amplification spectral profiles based on those seen in HRTF from protruding ears and how they are applied to modify the HRTF of several subjects. Listening tests showed that the HRTF so modified yielded enhanced front-back differentiation, with respect to the original HRTF of the test subjects.
Amino Acid Signaling to mTOR Mediated by Inositol Polyphosphate Multikinase

mTOR complex 1 (mTORC1; mammalian target of rapamycin [mTOR] in complex with raptor) is a key regulator of protein synthesis and cell growth in response to nutrient amino acids. Here we report that inositol polyphosphate multikinase (IPMK), which possesses both inositol phosphate kinase and lipid kinase activities, regulates amino acid signaling to mTORC1. This regulation is independent of IPMK's catalytic function, instead reflecting its binding with mTOR and raptor, which maintains the mTOR-raptor association. Thus, IPMK appears to be a physiologic mTOR cofactor, serving as a determinant of mTORC1 stability and amino acid-induced mTOR signaling. Substances that block IPMK-mTORC1 binding may afford therapeutic benefit in nutrient amino acid-regulated conditions such as obesity and diabetes.
Shape description and grasping for robot hand-eye coordination

The successful execution of grasping by a robot hand requires translation of visual information into control signals to the hand, which produce the desired spatial orientation and preshape for grasping an arbitrary object. An approach to this problem that is based on separation of the task into two modules is presented. A vision module is used to transform an image into a volumetric shape description using generalized cones. The data structure containing this geometric information becomes an input to the grasping module, which obtains a list of feasible grasping modes and a set of control signals for the robot hand. Features of both modules are discussed. >
Area postrema lesion attenuates the long-term hypotensive effects of losartan in salt-replete rats

We reported that the AT1 receptor antagonist losartan decreases arterial pressure in sodium-replete rats and that this response is attenuated in area postrema-lesioned (APx) rats (J. P. Collister, ...
Optimum wireless communication through unknown obscuring environments using the time-reversal principle: theory and experiments

Wireless communication in unknown and cluttered environments is an important problem which has several practical applications such as communication in urban areas and disaster areas. This paper presents a method to optimize communication efficiency in such environments. The method applies to communication between a transmitting array and receiving array where the transmitting array sends out a 'probe' signal and, at the receiving array, the transfer matrix can be constructed. From this measurement, we perform time-reversal and eigen analysis. The highest eigen value is the best possible transmission efficiency and its corresponding eigen vector represents the transmitting excitation at the transmitting elements to achieve maximum efficiency. The nature of this method makes it possible to operate and optimize in unknown, random, and cluttered environments. Here, we present the theory of time-reversal communication, show relevant numerical examples, and illustrate the experimental verification.
Cannabinoid Receptor Type 2 (CB2) Dependent and Independent Effects of WIN55,212-2 on Atherosclerosis in Ldlr-null Mice.

Purpose : WIN55,212-2, a potent synthetic agonist of cannabinoid receptor type 1 (CB1) and cannabinoid receptor type 2 (CB2), reduces atherosclerosis in apolipoprotein E (ApoE) null mice. Although pharmacologic evidence suggests the anti-atherosclerotic effects of WIN55,212-2 are mediated via CB2, this remains to be confirmed by genetic studies. Therefore, in this study, we investigated the effects of WIN55,212-2 on development of atherosclerosis in low-density lipoprotein receptor (Ldlr) null mice with and without homozygous deletion of the CB2 gene. Methods : After 6 weeks on an atherogenic diet, groups of CB2 +/+ and CB2 -/- Ldlr-null mice received a daily intraperitoneal injection of WIN55,212-2 or vehicle. After two weeks, plasma lipid levels and atherosclerosis in the aortic root were quantified. Results : Plasma cholesterol and triglyceride levels did not differ between CB2 +/+ and CB2 -/- mice and WIN55,212-2 had no effect on total cholesterol levels in either genotype. However, triglyceride levels in both CB2 +/+ and CB2 -/- mice were significantly lowered by WIN55,212-2. The size of aortic root lesions did not differ significantly between CB2 +/+ and CB2 -/- mice with or without WIN55,212-2 treatment. However, WIN55,212-2 treatment significantly lowered lesional macrophage accumulation in CB2 +/+ mice, and lesional smooth muscle content in both CB2 +/+ and CB2 -/- mice. Lesional apoptosis was also greater in CB2 +/+ mice compared to CB2 -/- mice, and only reduced by WIN55,212-2 in CB2 +/+ mice. Collagen content and elastin fiber fragmentation were unaffected by genotype or WIN55,212-2. Conclusions : WIN55,212-2 treatment does not alter lesion size in Ldlr null-mice, but does modify lesion cellularity via CB2-dependent and CB2-independent mechanisms
Machinery Diagnostics: Fundamentals and Tribosystem Applications

Machinery Diagnostics deals with the “health” of machines – characterized by “structural integrity” and “functional performance” – and the examination of faults and failures by nondestructive evaluation. The aim of this chapter of the Tribologie-Handbuchis to present the fundamentals of machinery diagnostics and to apply them to tribosystems, which are technical entities containing interacting components in relative motion, subject to friction and wear. The presentation of failure prevention strategies includes root-cause analysis, statistical control, reliability engineering, and asset maintenance. Condition monitoring deals with vibration monitoring, oil monitoring, corrosion monitoring, thermal monitoring, and electrical signature analysis. The application of machinery diagnostics to tribosystems is exemplified with bearings, gears, seals, lubricants and hydraulic systems.
Synthesis and Photocleavage of Quinoline Methyl Ethers: A Mild and Efficient Method for the Selective Protection and Deprotection of the Alcohol Functionality

The synthesis and photocleavage of quinolinyl methyl ether-protected alcohols is reported in this study. A variety of quinoline methyl chlorides were synthesized, and protection of the various alcohols was performed via a substitution reaction in the presence of a strong base. Photocleavage of the quinolinyl methyl ether moiety proceeded under visible light with the formation of the charged quinolinyl radical intermediate through a single-electron transfer in the presence of a photosensitizer dye leading to the deprotected alcohol in excellent yields. The utility of triethylamine as a sacrificial reductant and d-sorbitol as a radical scavenger were also investigated in this study.
Civil Society and Politics: The Locus of Ferguson’s Progress and Decline Discussion

In the lecture notes of Ferguson’s Moral Philosophy class, there is a clear distinction between the expressly under-theorized ‘history of the species’ with which he begins his course, in conjunction with the section on the ‘political science’ with which he ends, on the one hand, and the lectures—amounting to more than half of the total—in which he attempts to work through a systematic relationship between a science of human nature (pneumatics) and moral science. Ferguson expressly treats the introductory section as heuristic propaedeutic to the systematic effort and the conclusion as matter for the ‘professional’ education of ‘the statesman or warrior’. Together, these two constitute the practical interdependence of history and judgment, manifestly reminiscent of the civic humanist method and distinct from his systemically linked pneumatics and moral science. The dualism corresponds precisely to Francis Bacon’s own distinction between studies grounded in civil and natural history;8 and the introductory and concluding segments, taken together, correspond to the contents of An Essay on the History of Civil Society. This is the face of Ferguson to be examined below.
The Development of Social Indicators for Quality of Life Research

Social indicators of spiritual well-being (SWB) are desirable for quality of life studies. They also are needed in the sociology of religion because promotion of spiritual health is a central objective of most religious institutions, because evaluation of the alleged functional and dysfunctional consequences of their endeavors is of increasing social significance, and because the claim that SWB is promoted more effectively by non-religious than by religious agencies should be tested.Several strands of exploratory research which aim at the eventual development of an index of SWB are summarized. For example, questionnaires of 123 respondents indicate that seven-tenths believe it is possible for people to know whether or not they possess SWB. Two-thirds believe they possess it, but most think that only few or half of the population have SWB.The conceptual, theoretical, and empirical problems which spring from diverse definitions and divergent criteria of SWB are typical of most subjects when they are first introduced into the social sciences.
Motivations, barriers and ethical understandings of healthcare student volunteers on a medical service trip: a mixed methods study.

The motivation to volunteer on a medical service trip (MST) may involve more than a simple desire for philanthropy. Some volunteers may be motivated by an intrinsic interest in volunteering in which the context of the volunteer activity is less important. Others may volunteer because the context of their volunteering is more important than their intrinsic interest in volunteering. Furthermore, MSTs may pose a variety of ethical problems that volunteers should consider prior to engaging in a trip. This study evaluated the motivations and barriers for graduate health care students volunteering for an MST to either the Dominican Republic or Mississippi. Volunteers’ understanding of some of the ethical issues associated with MSTs was also assessed. Thirty-five graduate health professions students who volunteered on an MST were asked to complete an online survey. Students’ motivations and barriers for volunteering were assessed using a 5-point Likert scale and Fisher’s exact test. Ethical understanding of issues in volunteering was assessed using thematic analysis. Students’ motivations for volunteering appeared to be related to the medical context of their service more than an inherent desire for volunteer work. Significant differences were seen in motivations and barriers for some student groups, especially those whose volunteer work had less opportunity for clinical service. Thematic analysis revealed two major themes and suggested that students had an empirical understanding that volunteer work could have both positive and negative effects. An understanding of students’ motivations for volunteering on an MST may allow faculty to design trips with activities that effectively address student motivations. Although students had a basic understanding of some of the ethical issues involved, they had not considered the impact of a service group on the in-country partners they work with.
A New Form of Virus Pneumonitis Occurring Epidemically Among Newborn Infants

SummaryA new form of primary, acute pneumonitis of infants is described. The disease is characterized by its predilection for young infants, its epidemic nature or high degree of contagiousness, the constancy of its symptomatology from case to case and its pathology, including the occurrence of typical cytoplasmic inclusion bodies in the epithelial cells of the bronchial tree.
Disordered Media as Efficient Optical Devices

Homogeneous materials are ubiquitous in optical systems. Disordered media are usually considered a nuisance since they cause intricate scattering. However, we show they can act as linear devices and demonstrate their operation as efficient polarimeters.
A High-Performance Solution-Processable Hybrid Thermoelectric Material

Thermoelectrics have the potential to become an alternative power source for distributed electrical generation as they could provide co-generation anywhere thermal gradients exist. More recent material and manufacturing advances have further suggested that thermoelectrics could independently generate primary power [1]. However, due to cost, manufacturability, abundance, and material performance, the full potential of thermoelectrics has yet to be realized. In the last decade, thermoelectric material improvements have largely been realized by diminishing thermal conductivities via nanostructuring without sacrificing performance in electrical transport [2]. An alternative approach is to decouple and optimize the electrical conductivity and thermopower using the unique properties of organic-inorganic interfaces [3]. One method to do this could leverage the electrical properties of a conducting polymer in combination with the thermoelectric proprieties of an inorganic semiconductor in such a way that the interaction between these materials breaks mixture theory. Furthermore, it is expected that the thermal conductivity of this hybrid material would be low due to the inherent vibration mode mismatch between polymers and inorganics. Previously, we have developed a method for producing a solution-processable thermoelectric material suitable for thin film applications using a hybrid polymer-inorganic systems consisting of crystalline tellurium nanowires coated in a thin layer of a conducting polymer (i.e., PEDOT:PSS) [4]. The interfacial properties could be realized in bulk and films demonstrate enhanced transport properties beyond those of either component. More recently, we have been able to significantly improve the thermoelectric properties of these materials by morphological and chemical modifications. Here, we present our methodology and experimental transport properties of this new material where the thermal conductivity, electrical conductivity, and thermopower predictably vary as a function of composition, size, and the structural conformation caused by the solvent. The mechanism for these improvements is currently under investigation, but experimental results suggest that transport is dominated by interfacial phenomena. Furthermore, experiments suggest that both the electrical conductivity and thermopower can be independently increased without appreciably increasing the thermal conductivity. These improvements, in concert with the solution processable nature of this material, make it ideal for new thermoelectric applications.Copyright © 2012 by ASME
Epidote-rich talc-kyanite-phengite eclogites, Sulu terrane, eastern China: P-T-fo2 estimates and the significance of the epidote-talc assemblage in eclogite

Eclogites interlayered with gneiss and minor quartzite in the Qinglongshan near Donghai are characterized by unusually abundant (15–40 vol%) hydrous phases including talc, phengite, and epidote; many also contain kyanite. Garnet hosts both prograde (paragonite, amphibole, epidote) and peak stage (omphacite, epidote, phengite, kyanite) mineral inclusions. Several eclogites contain talc rimmed by barroisite; optically and compositionally similar coarse-grained amphibole in other samples indicates that the reaction Omp + Tlc = Amp has completely consumed talc. Estimated peak conditions of 30–35 kbar, 600–700 °C, are consistent with polycrystalline quartz pseudomorphs after coesite included in garnet, omphacite, epidote, and kyanite, and up to 3.6 Si pfu (11 O atom basis) in phengite. Garnet-epidote oxygen barometry on the peak metamorphic assemblage indicates oxygen fugacities above the Hem-Mag buffer, consistent with the epidote + talc assemblage and 5–20 mol% aegerine component in omphacite. The high oxygen fugacity calculated in this study as well as previously documented negative oxygen isotope values recorded by these rocks may both reflect alteration by oxidizing, meteoric water in a hydrothermal system. Oxidized conditions during peak metamorphism may explain the extreme scarcity of microdiamond in this area. The Ep + Tlc assemblage is stabilized by high oxygen fugacity, and demonstrates that talc-bearing eclogites are not restricted only to unusually Mg-rich bulk compositions.
Penicillin for Streptococcal Pharyngitis: Has Anything Changed?

It used to be simple: A single IM injection or 10 days of oral therapy would cure the sore throat and prevent rheumatic fever. Post-treatment carriage of group A does not seem to be adequate reason to switch strategies today.
Poly-ADP-ribose polymerase inhibition enhances ischemic and diabetic wound healing by promoting angiogenesis

Objective Chronic nonhealing wounds are a major health problem for patients in the United States and worldwide. Diabetes and ischemia are two major risk factors behind impaired healing of chronic lower extremity wounds. Poly-ADP-ribose polymerase (PARP) is found to be overactivated with both ischemic and diabetic conditions. This study seeks a better understanding of the role of PARP in ischemic and diabetic wound healing, with a specific focus on angiogenesis and vasculogenesis. Methods Ischemic and diabetic wounds were created in FVB/NJ mice and an in vitro scratch wound model. PARP inhibitor PJ34 was delivered to the animals at 10 mg/kg/d through implanted osmotic pumps or added to the culture medium, respectively. Animal wound healing was assessed by daily digital photographs. Animal wound tissues, peripheral blood, and bone marrow cells were collected at different time points for further analysis with Western blot and flow cytometry. Scratch wound migration and invasion angiogenesis assays were performed using human umbilical vein endothelial cells (HUVECs). Measurements were reported as mean ± standard deviation. Continuous measurements were compared by t -test. P Results A significant increase in PARP activity was observed under ischemic and diabetic conditions that correlated with delayed wound healing and slower HUVEC migration. The beneficial effect of PARP inhibition with PJ34 on ischemic and diabetic wound healing was observed in both animal and in vitro models. In the animal model, the percentage of wound healing was significantly enhanced from 43% ± 6% to 71% ± 9% ( P + /CD133 + and VEGFR2 + /CD34 + ) into the systemic circulation. Furthermore, under in vitro hyperglycemia and hypoxia conditions, PARP inhibition enhanced HUVEC migration and invasion in Boyden chamber assays by 80% and 180% ( P Conclusions Delayed healing in ischemic and diabetic wounds is caused by PARP hyperactivity, and PARP inhibition significantly enhanced ischemic and diabetic wound healing by promoting angiogenesis.
Closing a loop around a market mechanism using the transactive control and coordination framework

The proposed Transactive Control and Coordination (TC2) Framework has been tested in large-scale demonstration and shown to work as predicted in real life deployment. The demonstrations, however, have also illustrated the need for a better understanding of closed-loop behavior and for systematic approaches for choosing the parameters of the TC2 framework appropriately for a given application. In this lecture, we shall describe the theoretical underpinnings of TC2, give an overview of the implications of closing a loop around a market mechanism with TC2 as a leading example, and describe the closed-loop properties of systems with a large number of aggregated units being controlled in this framework.
Random Variables and Probability Distributions

A random variable is a function with a certain restrictive property. This chapter provides an overview of the random variables and probability distributions. It illustrates algebraic operations on random variables and explains that the new functions formed are also random variables. The chapter describes the simplest kind of random variables, the indicators, with their properties. The simplest type of random variable is that which indicates an event. With every random variable, another function is associated, which is known as its distribution function. Random variables possess individual distribution functions and joint distribution functions. Joint distribution functions have the same properties as the distribution functions of one random variable.
Phosphatase RNA-Interference Lethality Screening with Suberoylanilide Hyrdoxamic Acid In Myeloid Cell Lines

Abstract 1851 Background: In previous work we performed RNAi sensitizer screening of epigenetic modulation with 5-Azacytidine and the human kinome. Few kinase hits were identified. Therefore we asked if phosphatases might be involved in modulating epigenetic therapies. Thus in order to identify potentiators of the histone deacetylase inhibitor suberoylanilide hydroxamic acid (SAHA) we performed high-throughput RNA-interference (RNAi) lethality screening using the myeloid cell lines HEL, THP-1 and TF-1 in combination with SAHA. Methods: A small-interfering RNA (siRNA) library targeting 206 phosphatases with 4 sequences per target gene was used for this study. siRNA were transfected in a single-siRNA-per-well format in 384-well plates using commercial lipid-based transfection reagents. Non-silencing siRNA were included as negative controls to access non-specific siRNA toxicity and universal lethal siRNA were included as positive controls to indirectly assess functional transfection efficiency. After a 96 hour incubation period, cell viability/proliferation was measured with Cell Titer Glo. For analysis of screen data, log2 values of (SAHA + siRNA treatment/siRNA treatment only) were calculated. Potentiation was defined as two standard deviations from the median log2 ratio of all siRNA (excluding positive controls) on a plate-by-plate basis. Hits were defined as ≥ 2/4 siRNA sequences meeting potentiation criteria. Results: Transfection efficiency was 95, 90 and 70% for HEL, THP-1 and TF-1, respectively. All three cell lines were similarly sensitive to SAHA with IC 50 values of 0.3, 0.4 and 0.6 μM for HEL, THP-1 and TF-1, respectively. Resulting SAHA concentrations for screens were between the IC 5 to IC 30 . For THP-1, 5 phosphatases qualified according to the hit selection criteria applied indicating strong potentiation to SAHA. Of these 5 hits, 3 did not exhibit strong reductions in viability with siRNA alone, suggesting a SAHA-dependent relationship. For HEL and TF-1, although no phosphatases met the strict selection cutoff, there were several phosphatases exhibiting potentiation, suggesting biological relevance. The primary screening data and preliminary analysis will be validated with rigorous secondary experimentation and top hits for all cell lines will be investigated and advanced. Conclusions: While there are numerous kinase inhibitors in the clinic and in preclinical development, phosphatases are much less explored as therapeutic targets. Validated potentiating targets from this RNAi screen can facilitate the development of rational SAHA combination therapies. Disclosures: No relevant conflicts of interest to declare.
Hydrogen by photocatalysis with nitrogen codoped titanium dioxide

Abstract Titanium dioxide TiO 2 remains a benchmark photocatalyst with high stability, low toxicity and cost, but it is active only under the UV light. To increase photocatalytic activity, TiO 2 is “doped” with metals and nonmetals; nitrogen doped titania N-TiO 2 has been extensively investigated since the early 2000s. In the recent decade, an increased attention has been paid to additional dopant aka “codopant” added to N-TiO 2 to increase the photocatalytic rate. This focused critical Review covers the research on N-TiO 2 codoped with an additional element for the photocatalytic hydrogen generation, namely: (1) mechanistic studies of charge separation aimed to understand and predict photocatalytic activity; (2) nonmetal codoped N-X-TiO 2 ; (3) base metal codoped N-M-TiO 2 ; (4) noble metal codoped N-M-TiO 2 . Suitability and limitations of experimental methods for characterization of codoped N-TiO 2 are discussed. The following mechanisms of photocatalysis with codoped N-TiO 2 are reviewed: (a) excitation of TiO 2 ; (b) excitation of N dopant induced states; c) an increased electron-hole (e-h) separation; (d) lowering over potential of hydrogen reduction; (e) excitation of the surface plasmon resonance (SPR) in N-TiO 2 codoped with nanoparticles (NPs) of noble metals. Temporal stability of codoped N-TiO 2 in H 2 generation and transformation pathways of sacrificial electron donors are discussed as well.
Neuroelectronic device process development and challenge

We investigated the fabrication of small neuroelectronic device consisting of four shanks with 16 electrodes per shank for simultaneous neurochemical and brain activity monitoring. The 16 electrodes on each shank have a separation distance of 100 microns (μm). Each shank has a width of 40 μm with separation distance of 7750 μm. This design eliminates single-site recording with limited individual conductors and permits rapid characterization of multiple neurons simultaneously at multiple brain depth/sites, consequently providing ground-breaking capabilities for parsing neurochemical release and brain activity. The device is fabricated on (100) silicon substrate and is fully integrated with electrode, interconnect and bond pad fabricated on one chip. Gold rectangular pyramid electrodes are selected as the recording electrodes to enhance the non-invasiveness associated with heating and minimizing surrounding biological tissue damage. The gold electrodes are deposited on the etched silicon substrate with 600 nanometer (nm) low temperature oxide (LTO) sacrificial layer. Each electrode has top area of 6 μm x 60 μm and depth of 750 μm. The interconnects provide electrical connection between electrodes and bond pads and are sandwiched between thin polyimide layers to prevent them from breaking while maintaining the flexibility. Final bond pads and electrodes are all passivated with polyimide to provide mechanical support. Upon device release, the recording electrodes are exposed to directly contact brain structure, and the exposed bond pads are soldered on the circuit board to transport signals to the measurement instrument. The entire process involves five photomasks. Process development and integration challenges will be reviewed and discussed in the paper.
Identifying and Communicating the Importance of the Variable Nature of SyS Data

Objective This roundtable will provide a forum for national, state, and local managers of syndromic surveillance systems to discuss how they identify, monitor, and respond to changes in the nature of their data. Additionally, this session will focus on the strengths and weakness of the syndromic surveillance systems for supporting program evaluation and trend analysis. This session will also provide a forum where subject matter experts can discuss the ways in which this deep understanding of their data can be leveraged to forge and improve partnerships with academic partners. Introduction As syndromic surveillance systems continue to grow, new opportunities have arisen to utilize the data in new or alternative ways for which the system was not initially designed. For example, in many jurisdictions syndromic surveillance has recently become population-based, with 100% coverage of targeted emergency department encounters. This makes the data more valuable for real- time evaluation of public health and prevention programs. There has also been increasing pressure to make more data publicly available – to the media, academic partners, and the general public.
A magnetic resonance compatible E4D ultrasound probe for motion management of radiation therapy

We developed a magnetic resonance compatible real-time, three-dimensional imaging ultrasound probe for motion management of radiation therapy for liver cancer. The probe contains an 18,000-element, 46.8 mm × 21.5 mm matrix array constructed from three tiled transducer modules with integrated beamforming ASICs. The center frequency and −6 dB fractional bandwidth of the probe was 3.6 MHz and 85 percent respectively. Ferromagnetic materials in the acoustic stack, flex interconnect and electronics boards were greatly minimized for magnetic resonance compatibility. The probe and cable were shielded to minimize the impact of radiofrequency noise on both the ultrasound and magnetic resonance images. The probe's low-profile, side-viewing design allows it to be strapped to a patient so that images may be acquired hands-free. We present simultaneously acquired ultrasound and 3 Tesla magnetic resonance images with minimal artifacts in both images.
Field- and Carrier-Induced Nonlinear Metamaterials

We explore active and nonlinear plasmonic metamaterials by leveraging the field-induced disruption of the inversion symmetry for second-order optical processes, and exploiting the hot-carrier-induced perturbation of the dielectric permittivity for ultrafast all-optical modulation.
Mechanism of the Magnesium Ion Activation of the Catalytic Activity of Horse Liver Aldehyde Dehydrogenase

The activity of the pI 5 isozyme of horse liver aldehyde dehydrogenase is markedly enhanced by some divalent metal ions (Ca, Mn, Mg), inhibited by others (Fe, Cu, Cd), totally inhibited by Hg, and not significantly affected by still others (Zn, Ni, Co). Steady-state kinetics show that with 0.5 mM Mg or Mn a 2-fold activation of the velocity measured at pH 7.5 occurs when propionaldehyde is the substrate. In the pre-steady state, the magnitude burst of NADH formulation is increased from 2 moles formed per mole of tetrameric enzyme to 4 moles formed in the presence of Mg. The stoichiometry of coenzyme (NADH, NAD, e-NAD) binding is also increased from essentially 2 moles binding to 4 moles binding per mole enzyme in the presence of Mg. It appears that the enzyme exhibits half of the site reactivity in the absence of metal but has a full complement of catalytic sites in the presence.
Moving the River? China’s South–North Water Transfer Project

The Chinese government has embarked upon an earth engineering project of unprecedented scale to address increasingly worrisome trends in freshwater resources in the northern part of the country. The South-North Water Transfer (nanshui beidiao) project will bring water from the relatively water-rich Yangtze River basin in the south to the relatively water-scarce (and exceedingly over-abstracted) Yellow River basin in the north. The project involves three channels (east, central, and west) of varying length, complexity, ecological and socioeconomic impact, and technical and economic feasibility. In this chapter, I briefly outline the overall situation of China’s freshwater resources and sketch the details of the SNWT project. I then use the newly engineered watersheds as analytical scales for a discussion of potential (and in some cases, extant) socioeconomic, biophysical, and geopolitical impacts from the project.
Optimality: Value Function

Chapter 3 dealt with the abstract property of controllability, the possibility of using inputs in order to force a system to change from one state to another. Often, however, one is interested not merely in effecting such a transition, but in doing so in a “best” possible manner. One example of this was provided in that chapter, when we calculated the control of minimal norm that achieved a given transfer, in a fixed time interval.
Structural complexity of ω-automata

In this paper we relate expressiveness of ω-automata to their complexity. Expressiveness is related to the different subclasses of the ω-regular languages that are accepted by automata that arise by restrictions on the acceptance conditions used. For example, different subclasses of the ω-regular languages arise from identifying the ω-languages with different classes and levels in the Borel hierarchy. Within the class of ω-regular languages, Wagner and Kaminski identified a strict hierarchy of languages induced by restricting the number of pairs allowed in a deterministic Rabin automaton (DRA).
mTORC1/2 and Protein Translation Regulate Levels of CHK1 and the Sensitivity to CHK1 Inhibitors in Ewing Sarcoma Cells

The treatment of Ewing sarcoma has changed very little in the past two decades and novel treatment approaches are needed. We recently identified that Ewing sarcoma cells are uniquely vulnerable to inhibitors of ribonucleotide reductase (RNR), the rate-limiting enzyme in the synthesis of deoxyribonucleotides. We subsequently found that the inhibition of checkpoint kinase 1 (CHK1) increases the sensitivity of Ewing sarcoma cells to inhibitors of RNR, such as gemcitabine. However, Ewing sarcoma cells exhibit high levels of the CHK1 protein, which may represent an adaptive response to elevated levels of endogenous DNA replication stress. Consequently, we began this work with the aim of determining the impact of CHK1 levels on drug sensitivity, as well as identifying the mechanisms and pathways that regulate CHK1 levels in Ewing sarcoma cells. In this report, we show that the high levels of the CHK1 protein in Ewing sarcoma cells limit the efficacy of CHK1 inhibitors. However, inhibition of mTORC1/2 activates the translational repressor 4E-BP1, reduces protein synthesis, and decreases levels of the CHK1 protein in Ewing sarcoma cells. Similarly, we identified that the CHK1 inhibitor prexasertib also activates 4E-BP1, inhibits protein synthesis, and reduces CHK1 protein levels in Ewing sarcoma cells. Moreover, the combination of prexasertib and gemcitabine was synergistic in vitro, caused tumor regression in vivo, and significantly prolonged mouse survival in a Ewing sarcoma xenograft experiment. Overall, our results provide insight into Ewing sarcoma biology and support further investigation of the CHK1 pathway as a therapeutic target in Ewing sarcoma tumors.
Explaining the Impact of Non-state Security, Victimization, and Insecurity on Voting in South Africa

This chapter explores the impact of non-state security, victimization, and insecurity on voting in South Africa. The security variables examined here, to the extent that they have an effect, tend to suppress participation in electoral politics. I suggest that those who rely on non-state providers for security and those who have been victims of violent crime may have lost faith in their ability to affect change through elections in South Africa. The nature of the party system in South Africa may further contribute to this outcome.
ON HANKEL MATRIX APPROXIMATIONS AND STOCHASTIC MODEL REDUCTION

Abstract A procedure for stochastic model reduction is presented by using the Hankel matrix results of Adamjan, Arov and Krein. It is shown that the error of the resulting Mth-order approximation is bounded from above by the M + 1 singular value of the system's Hankel matrix.
SPNS2 enables T cell egress from lymph nodes during an immune response.

Summary T cell expression of sphingosine 1-phosphate (S1P) receptor 1 (S1PR1) enables T cell exit from lymph nodes (LNs) into lymph, while endothelial S1PR1 expression regulates vascular permeability. Drugs targeting S1PR1 treat autoimmune disease by trapping pathogenic T cells within LNs, but they have adverse cardiovascular side effects. In homeostasis, the transporter SPNS2 supplies lymph S1P and enables T cell exit, while the transporter MFSD2B supplies most blood S1P and supports vascular function. It is unknown whether SPNS2 remains necessary to supply lymph S1P during an immune response, or whether in inflammation other compensatory transporters are upregulated. Here, using a model of dermal inflammation, we demonstrate that SPNS2 supplies the S1P that guides T cells out of LNs with an ongoing immune response. Furthermore, deletion of Spns2 is protective in a mouse model of multiple sclerosis. These results support the therapeutic potential of SPNS2 inhibitors to achieve spatially specific modulation of S1P signaling.
Near-ideal behavior of compressed sensing algorithms

Compressed sensing theory addresses the problem of recovering a nearly sparse signal from a noise-corrupted linear measurement of far smaller dimension. In some recent papers, it is shown that the LASSO algorithm exhibits near-ideal behavior, in the following sense: If x is a sparse signal, and if an estimate x-hat of x is found using LASSO, then the Euclidean norm of the residual error is bounded by a universal constant times the error achieved by an “oracle” that knows the support set of x. The LASSO algorithm has been generalized in several directions such as the group LASSO, the sparse group LASSO, either without or with tree-structured overlapping groups, and most recently, the sorted LASSO. This raises the question as to which if any of these algorithms also exhibits near-ideal behavior. In this paper we present a unified theory by showing that any algorithm exhibits near-ideal behavior in the above sense, provided that three conditions are satisfied: (i) the norm used to define the sparsity index is “decomposable,” (ii) the penalty norm that is minimized in an effort to enforce sparsity is gamma-decomposable, and (iii) a “compressibility condition” in terms of a group restricted isometry property is satisfied. Our results imply that the group LASSO, and the sparse group LASSO (with some permissible overlap in the groups), as well as the sorted l 1 -norm minimization all exhibit near-ideal behavior. Explicit bounds on the residual error are derived that contain previously known results as special cases.
Gene Expression in Torn Rotator Cuff Tendons Determined by RNA Sequencing.

Background:Although the cause of rotator cuff tearing is likely multifactorial and a genetic predisposition has been proposed, the biochemical basis remains unknown.Purpose:To determine gene expres...
Active Time-Restricted Feeding Protects the Blood Pressure Circadian Rhythm in Diabetic Mice

The quantity and quality of food intake have been considered crucial for peoples9 wellness. Only recently has it become appreciated that the timing of food intake, independent of total calorie consumption, is also critical. The involvement and contribution of the timing of food intake in nondipping blood pressure (BP), the most common disruption of the BP circadian rhythm in diabetes, however, remains uncertain. Here, we demonstrate that the loss of diurnal rhythm in food intake coincided with nondipping BP in type 2 diabetic db/db mice, and imposing a food intake diurnal rhythm by active time-restricted feeding (ATRF) remarkably prevented db/db mice from the development of nondipping BP. Moreover, ATRF, independent of calorie restriction, also effectively restored the already disrupted BP circadian rhythm in db/db mice. Mechanistically, ATRF reduced the sympathetic vascular tone and BP during the light phase via fasting, thus protecting the BP circadian rhythm in db/db mice. Moreover, we identified BMAL1, an obligatory core clock gene, as a potentially key molecule that links ATRF, sympathetic vascular tone, and BP circadian rhythm. Collectively, these data reveal an important but previously unrecognized role of the timing of food intake in the onset, prevention, and treatment of nondipping BP in diabetes.
Treatments Associated with Mental Health Disorders and Functional Assessment

Functional assessment strategies may be used to augment the treatment of mental health disorders. Several treatments have been developed through the study of behavioral analysis and behavioral theories of mental health disorders (e.g., anxiety disorders, depression). Due to the high prevalence and burden of mental health disorders, providing informed treatment strategies is paramount. An overview of behavioral theories of prominent mental health disorders and behaviorally based treatments is presented. Behavioral functions, functional assessment methods, and the use of functional assessment to inform treatments of anxiety disorders and depression are discussed.