cssi/SciSciGPT-SciSciNet huggingface dataset:
Malleilactone, a Polyketide Synthase-Derived Virulence Factor Encoded by the Cryptic Secondary Metabolome of Burkholderia pseudomallei Group Pathogens

Sequenced bacterial genomes are routinely found to contain gene clusters that are predicted to encode metabolites not seen in fermentation-based studies. Pseudomallei group Burkholderia are emerging pathogens whose genomes are particularly rich in cryptic natural product biosynthetic gene clusters. We systematically probed the influence of the cryptic secondary metabolome on the virulence of these bacteria and found that disruption of the MAL gene cluster, which is natively silent in laboratory fermentation experiments and conserved across this group of pathogens, attenuates virulence in animal models. Using a promoter exchange strategy to activate the MAL cluster, we identified malleilactone, a polyketide synthase-derived cytotoxic siderophore encoded by this gene cluster. Small molecules targeting malleilactone biosynthesis either alone or in conjunction with antibiotics could prove useful as therapeutics to combat melioidosis and glanders.
Synthesis and Reactivity of a Sterically Crowded Tris(pyrazolyl)borate Hafnium Benzyl Complex

The reaction of Hf(CH2Ph)4 and Tl[TpMs*] (TpMs* = HB(3-mesitylpyrazolyl)2(5-mesitylpyrazolyl)−) yields TpMs*Hf(CH2Ph)3 (1), bibenzyl, and Tl0 via ligand exchange followed by thermal decomposition of Tl[CH2Ph]. Compound 1 reacts with [H(OEt2)2][B(C6F5)4] to form TpMs*Hf(CH2Ph)2(OEt2)+ (2, 100%) and with [Ph3C][B(C6F5)4] or B(C6F5)3 to form an unstable species characterized by NMR as TpMs*Hf(CH2Ph)2+. 1/[Ph3C][B(C6F5)4] behaves similarly to TpMs*HfCl3/MAO in olefin polymerization, producing high molecular weight, linear PE, and ethylene/1-hexene copolymer with good hexene incorporation. These results are consistent with the proposal that similar cationic TpMs*Hf(X)R+ species (X = Cl or R) are active species in these catalysts. Ethylene polymerization by 1/[Ph3C][B(C6F5)4] at low temperature proceeds without significant chain transfer, enabling the synthesis of bromo benzyl double-end-capped linear PE (PhCH2(CH2CH2)nBr).
Hydrogel embolic agents. Theory and practice of adding radio-opacity

Rationale and objectives Spheres of hydrogel have been developed as embolic material with the ability to incorporate radio-opaque materials. To optimize particle design for radiographic or fluoroscopic visualization, we have examined the theoretical determinants of particle contrast. In addition, loaded hydrogel particles were tested in a rabbit model. Methods Computer simulations of particle subject contrast were examined regarding particle composition, particle size, patient thickness, and x-ray beam kilovoltage. Embolizations in the rabbit kidney were used to test the practical aspects of the materials. Results Tantalum and tungsten offer some theoretical and practical advantages over other materials. With this particular hydrogel preparation, contrast material loading was limited to 20% of the volume as loaded contrast agent. The soft particles passed through catheters as small as 3 French; they were usually injected as a suspension of saline/contrast material. Tantalum/hydrogel particles as large as 2 mm could be forced through the 140 cm/3-Fr catheter with a guide wire. Conclusions Radio-opacity of embolic material should add an element of control in embolization procedures that is lacking with the current agents. The heavy metals, tungsten and tantalum, are suitable additives for radiopaque material for hydrogel emboli. The input relationship appears predictable with computer monitoring techniques. Initial results in a study of these radiopaque particles are very encouraging. Further studies are underway to evaluate the long-term effects in renal and hepatic circulations.
The chemistry of a mesoscale rainband

A diagnostic modelling study is presented of the chemistry of a cold-frontal rainband observed on the mid-Atlantic coast of the United States. Both the chemical and physical data sets were sufficient to allow realistic evaluation of the 2-D model employed. Utilizing the model, assessment is made of the importance of in-cloud chemical processes to the deposition on the ground of selected trace chemicals; in-cloud sulphate production was found to be of great importance. The effects of the rainband on the vertical transport of trace chemicals, and the effects of precipitation-formation mechanisms on chemical scavenging, are also discussed.
Genetic Models to Study Quiescent Stem Cells and Their Niches

Hematopoietic stem cells (HSC) have been defined by their ability to establish long-term hematopoiesis in myelo-ablated hosts. Prospective isolation using combinations of cell-surface markers and/or dye exclusion can yield highly purified and nearly homogeneous phenotypically defined cells that repopulate irradiated hosts. Although highly informative, these types of analyses may not necessarily reflect ongoing homeostatic hematopoiesis. HSCs are also described as being quiescent. This has been demonstrated by cell cycle analysis of phenotypically defined HSCs. Some studies have challenged the existence of truly quiescent HSCs, suggesting that they continuously cycle, albeit with very slow kinetics. Here we present a pulse-chase system based on the controllable incorporation of H2B-GFP into nucleosomes, which allows the identification, purification, and functional analysis of viable label-retaining cells. Our data complement and extend recent studies using similar strategies. These, together with our present studies, find a rare, quiescent or dormant subset within the population of stringently defined HSC phenotypes. To date, three types of niches, endosteal, vascular, and reticular, have been described; herein we review the cellular and spatial nature of these microenvironments. We propose that HSC label-retention combined with genetically manipulated stem cell niches will allow us to determine their anatomical architecture, to address HSC cell fate proliferation kinetics, and to begin to dissect the molecular cross talk among stem cells and niche cells in vivo during both normal and perturbed homeostasis.
Functional testing of digital microfluidic biochips

Dependability is an important attribute for microfluidic biochips that are used for safety-critical applications such as point-of-care health assessment, air-quality monitoring, and food-safety testing. Therefore, these devices must be adequately tested after manufacture and during bioassay operations. Known techniques for biochip testing are all function-oblivious, i.e., while they can detect and locate defect sites on a microfluidic array, they cannot be used to ensure correct operation of functional units. In this paper, we introduce the concept of functional testing of microfluidic biochips. We address fundamental biochip operations such as droplet dispensing, droplet transportation, mixing, splitting, and capacitive sensing. Long electrode actuation times are avoided to ensure that there is no electrode degradation during testing. We evaluate the proposed test methods using simulations as well as experiments for a fabricated biochip.
Much ado about nothing? World-historical implications of the re-emergence of China and India

China and India's increasing prominence in the world economy has not been accompanied by an equally prominent role for them in world politics. The opening up of the two giant trans-Himalayan neighbors has allowed corporations to fragment production operations into part-processes and distribute them across the planet to benefit from wage and cost differentials. This has significantly impaired the strength of domestic manufacturing lobbies and of industrial labor and led to the hollowing out of manufacturing sectors and the widening of inequalities in income and wealth everywhere. New forms of industrial organizations emerging in China and India – hybrid state–private partnership arrangements and large diversified corporations – have not been conducive to creating well-paying jobs or the self-organization of workers that has thus far been the hallmark of industrial capitalism in leading states. This set the stage for a worldwide depoliticization of politics. In the West, though it was articulated differentl...
Zackfalinus, A New Genus of Xanthopygina (Coleoptera: Staphylinidae: Staphylinini) with Description of 20 New Species

ABSTRACT A new genus of Xanthopygina (Coleoptera: Staphylinidae: Staphylinini) is described here as Zackfalinus, new genus and includes 20 new species: Z. abothros, Z. agrammos, Z. alturas, Z. andersoni, Z. antennatus, Z. bierigi, Z. brzoskai, Z. carinatus, Z. erythrocephalos, Z. hardestae, Z. kitrinos, Z. kokkinos, Z. lamperos, Z. leptophallos, Z. limonus, Z. napus, Z. stenocephalos, Z. surinamus, Z. tricolor, and Z. ziegleri. The antennae in Zackfalinus are sexually dimorphic, with males having an elongate antennomere 11. An identification key, distribution maps, and illustrations of structural features are provided for the identification of species. Parsimony and Bayesian phylogenetic analyses of two outgroup taxa and 19 ingroup taxa were conducted based on 24 morphological characters. The consensus trees were only partly resolved but the results supported the monophyly of Zackfalinus with high bootstrap values and posterior probabilities.
Bounds for parametric sequence comparison

Abstract We consider the problem of computing a global alignment between two or more sequences subject to varying mismatch and indel penalties. We prove a tight 3(n/2π) 2/3 +O(n 1/3 log n) bound on the worst-case number of distinct optimum alignments for two sequences of length n as the parameters are varied. This refines a O(n2/3) upper bound by Gusfield et al., answering a question posed by Pevzner and Waterman. Our lower bound requires an unbounded alphabet. For strings over a binary alphabet, we prove a Ω(n 1/2 ) lower bound. For the parametric global alignment of k⩾2 sequences under sum-of-pairs scoring we prove a 3(( k 2 )n/2π) 2/3 +O(k 2/3 n 1/3 log n) upper bound on the number of distinct optimality regions and a Ω(n 2/3 ) lower bound, partially answering a problem of Pevzner. Based on experimental evidence, we conjecture that for two random sequences, the number of optimality regions is approximately n with high probability.
Formation and sintering characteristics of aluminum borate whiskers

A boric acid-stabilized aluminum acetate powder was decomposed to aluminum borate (Al18B4O33) by calcining at 1000°C. The powder was then ball-milled, compacted, and fired to temperatures of 1500°, 1600°, and 1700°C for a period of 1 h. The resulting aluminum borate ceramic had a whiskerlike grain morphology, with the whisker length approaching 20 μm and a diameter of 2–3 μm. The sintered compact showed no shrinkage upon firing, had a porosity of ∼50%, a narrow pore size distribution, and an average pore size of 1–3 μm.
A New Genus and Species of Tetraphyllidean Cestode from the Spadenose Shark, Scoliodon laticaudus, in Malaysian Borneo

One of 23 specimens of the Spadenose shark, Scoliodon laticaudus (Elasmobranchii: Carcharhiniformes: Carcharhinidae), necropsied for tapeworms in Mukah, Sarawak, in Malaysian Borneo between 2002 and 2003 was found to host a new genus and species of tetraphyllidean tapeworm belonging to the family Phyllobothriidae. Ruhnkecestus latipi n. g., n. sp. is described from 4 specimens, 3 prepared as whole mounts and 1 from which the strobila was prepared as a whole mount, and the scolex prepared for examination with scanning electron microscopy. The genus is unique among phyllobothriids in that each bothridium bears 1 anterior, 3 central, and 2 posterior facial loculi. Its microthrix pattern, proglottid anatomy, and host associations suggest that its affinities are with the Phyllobothriinae. Among the Phyllobothriinae it most closely resembles species of Paraorygmatobothrium in its possession of a scutellate neck and serrated microtriches on its proximal bothridial surfaces, as well as a tetralobed ovary and vitellaria that are interrupted by the ovary. This represents the first report of a tetraphyllidean tapeworm from the monotypic shark genus Scoliodon.
Leptin induces an inflammatory phenotype in lean Wistar rats.

The present study addressed the hypothesis that leptin promotes leukocyte trafficking into adipose tissue. Accordingly, male Wistar rats were treated with saline or recombinant rat leptin (1 mg/kg) via the tail vein. Leukocyte trafficking in mesenteric venules was quantified by intravital microscopy. Treatment with leptin resulted in a 3- and 5-fold increases in rolling and firm adhesion, respectively. Compared to vehicle controls, leptin enhanced mRNA levels of IL-6 (8-fold) and MCP-1 (5-fold) in mesenteric adipose tissue (MAT). Similar increases in these markers were observed in mesenteric venules and in liver. Finally, the direct effect of leptin was assessed in C3A hepatocytes treated with leptin for 24 hours (7.8 ng/mL–125 ng/mL). Consistent with observations in vivo, production of ICAM-1, MCP-1, and IL-6 by hepatocytes was increased significantly. These findings support the hypothesis that leptin directly initiates inflammation in the local environment of mesenteric adipose tissue as well as systemically.
PET, CT, and MR Imaging for Assessment of Thoracic Malignancy : Structure Meets Function

Imaging of patients with thoracic malignancy usually requires a multimodality approach. Each of these modalities has its own strengths and weaknesses. CT remains central to the staging and restaging of thoracic malignancies, but has recently been complemented with [18F]-2-fluoro-2-deoxy-D-glucose(FDG)–positron emission tomography (PET) imaging to maximize its potential. Furthermore, because FDG-PET/CT is useful at all stages of the workup and treatment of these patients, this modality has taken hold in the clinical realm for evaluation of patients with thoracic malignancy and is rapidly replacing PET-only imaging. MR imaging is also occasionally used in some patients with thoracic malignancies to improve disease staging or lesion characterization. PET/MR imaging may come to be used to evaluate patients with thoracic malignancies as well.
Integrating Immigrants: Morality and Loyalty in U.S. Naturalization Practice

The issues of how to integrate immigrants and ensure the integrity of citizenship have become passionate topics of public discourse and policy debate in recent years in a number of immigrant receiving countries. Behind these debates are often unarticulated questions about how to ensure loyalty to the state and to particular conceptions of national identity among prospective citizens. These issues have been explicitly debated in the United States since the enactment of the first naturalization law in 1790, which requires that immigrants who wish to become citizens demonstrate their good moral character and attachment to the country. This article explores the ways that these morality and loyalty requirements have historically been applied and institutionalized in US naturalization practice, particularly through government sponsored immigrant education programs. It does so first through a discussion of the interpretation of these laws, and then through a case study of the original 1914 Bureau of Naturalizati...
Evaluating Complex Development Programs

Evaluators express preferences for certain methods over others. This chapter highlights the debate and assumptions underlying these preferences. There are debates on which methods represent the “gold standard” for evaluation. The key point discussed in this chapter is that the “gold standard” for evaluation methodology is Appropriateness to evaluation questions and the contextual realities of complex programs.
Dosimetry for pulsed laser photodynamic therapy

calculations of the number of photons absorbed per unit volume. These dosimeters have been used to compare the relativepenetration of high intensity pulsed irradiation versus continuous wave for benzoporphyrin derivative monoacid ring 'a'under typical tissue irradiation conditions. Calculations and experiments indicated an increase in relative light penetrationfor high intensity irradiation, due to transient changes in sample absorption. The relative deposited dose of different pulseintensities has been compared with the numerical simulation.1. INTRODUCTIONPhotodynamic Therapy (PDT) is a clinical treatment for cancer of the esophagus and is presently in clinical trialsfor bladder cancer, lung cancer and intrauterine bleeding'. Clinical research in PDT has predominantly used continuouswave (cw) irradiation to selectively excite the photosensitizer in tissue to induce a tumor killing effect in the surface layersof tissue. The average depth of necrosis induced by PDT is limited to approximately 10 mm, and is typically in the rangeof 2 to 5
End-of-Life Care Issues: A Personal, Economic, Public Policy, and Public Health Crisis

Advance directive documents are free, legal, and readily available, yet too few Americans have completed one. Initiating discussions about death is challenging, but progress in medical technology, which leads to increasingly complex medical care choices, makes this imperative. Advance directives help manage decision-making during medical crises and end-of-life care. They allow personalized care according to individual values and a likely reduction in end-of-life health care costs. We argue that advance directives should be part of the public health policy agenda and health reform.
Source configuration and dose rates for the selectron afterloading equipment for gynecologic applicators

This paper describes source train configurations of the Selectron LDR-6 that can be used to duplicate commonly used manually afterloadable source configurations for gynecological intracavitary brachytherapy. We demonstrate that the recommended source configuration using 2.5 mm 137Cs spheres is dosimetrically equivalent to its manually afterloaded counterparts using 3M 137Cs sources (20 mm overall length, 14 mm active length). Isodose distributions are in agreement to within 5% for the Fletcher-Suit-Delclos family of tandems, colpostats, and vaginal cylinders. Our data also demonstrate that the isotropic point source model used by most computerized treatment planning systems is a good approximation to source trains of filtered, spherical sources interspersed with solid steel spacers. We conclude that the use of 2.5 mm 137Cs sources in the Selectron remote afterloading system can accurately reproduce the isodose distribution achieved with linear 137Cs manually afterloaded sources.
Studies on the mechanism of action of calciferol. I. Basic parameters of vitamin D-mediated calcium transport.

Abstract Intestinal calcium transport was studied in vitro in ileal tissue obtained from vitamin D-deficient (-D) chicks which had received a dietary supplementation (+D) of vitamin D3 (cholecalciferol). When the flux measurements were carried out in both the mucosal → serosal and serosal → mucosal directions, under short-circuit conditions in which the transmural potential difference across the cell could be reduced to zero, it was found that calcium transport in the +D system was an active, cation-oriented process operating against an electropotential gradient. Calcium was not actively transported in the vitamin D-deficient chick. The presence or absence of inorganic phosphate had no effect on calcium flux in either the +D or -D system. Both the flux of 3H2O and 14C-thiourea were identical in the +D and -D systems, which is consistent with the concept that the increased calcium flux due to vitamin D3 treatment is not due to a general permeability difference. A carrier was shown to be present at the brush border side of the intestinal mucosal cells of both vitamin D-treated and -deficient chicks. However, kinetic studies and the differential effects of cold, iodoacetamide, and N-ethylmaleimide on calcium flux suggest that the biochemical properties of the calcium carrier in the +D system have been altered in some manner so as to effect a more efficient uptake of calcium into the cell. Also, the increased calcium flux due to vitamin D3 administration was found to require 40 to 50 hours for optimal development and to be blocked by prior actinomycin D treatment. This supports the hypothesis that the vitamin D-mediated enhancement of calcium transport is achieved indirectly through RNA and protein synthesis, rather than through direct participation of the vitamin.
Active truss element and control law for vibration suppression

In order to meet the demands of simplicity and reliability in active control systems for flexible structures, an inexpensive active truss element and control law has been developed in this research. A decentralized switching control law is used along with a compressible fluid in the truss element in order to dissipate energy during the motion of the structure. However, the energy is not absorbed in the same manner as a conventional viscous damper. The truss element retains its maximum stiffness, but has a reset-able nominal unstressed length. Energy is absorbed in the working fluid of the truss element through heat transfer to the environment when the nominal length is reset at the proper switching times. The control law is insensitive to changes in structural parameters such as mass, stiffness, and damping. In this paper, a mathematical model for the system is presented along with a stability analysis and experimental results.© (1995) COPYRIGHT SPIE--The International Society for Optical Engineering. Downloading of the abstract is permitted for personal use only.
Substrate dependent photochemical oxidation of monolayer graphene

In this report we show that the photochemical oxidation of monolayer graphene is strongly dependent on its underlying substrate. It was found that chemical vapor deposition-grown monolayer graphene transferred onto a silicon wafer is more easily oxidized compared to graphene that was left on the copper substrate or transferred onto a H2-annealed copper foil. The differences in the degree of oxidation were tentatively attributed to the varying energies of adhesion between the graphene and the underlying substrate. Our result has significant implications for the outdoor use of graphene as a transparent conducting material.
Radium-223 outcomes after multiple lines of metastatic castration-resistant prostate cancer therapy in clinical practice: implication of pre-treatment spinal epidural disease

Radium-223 outcomes after multiple lines of metastatic castration-resistant prostate cancer therapy in clinical practice: implication of pre-treatment spinal epidural disease
Predict the Severity of Water Lock Using Grey Correlation: A Case History in Gulongnan,Daqing.

Compared with conventional methods of similarity analysis,the grey correlation method has the advantage of being simple and explicit.This method does not need rigorous requirement on the quantity of samples and the typical distribution of the samples analyzed,and the quantitative and qualitative results explain each other.The application of grey correlation in the prediction reservoir damage by water lock in Gulongnan area in Daqing shows that the analysis method is feasible.
Numerical simulation on NO_x emission from a 300 MW unit boiler

Numerical simulation on NOx emission characteristic of a 300 MW subcritical coal fired boiler was performed.The effects of such factors as excess air coefficient,over fire air ratio,coal concentration ratio of coal rich side to the lean side and the primary air speed on the furnace temperature field and NOx emission was investigated.The results showed that,with a drop in excess air coefficient and an increase in over fire air ratio,the NOx emission decreased.The higher the coal concentration ratio of coal rich side to the lean side,the lower the NOx emitted.The increasing primary air speed resulted in high NOx emission.After regulation according to the simulation results,the NOx emission dropped by 52%,namely from 471 mg/m3 to 226.79 mg/m3.
Intelligent Systems: Approximation by Artificial Neural Networks

This brief monograph is the first one to deal exclusively with the quantitative approximation by artificial neural networks to the identity-unit operator. Here we study with rates the approximation properties of the "right" sigmoidal and hyperbolic tangent artificial neural network positive linear operators. In particular we study the degree of approximation of these operators to the unit operator in the univariate and multivariate cases over bounded or unbounded domains. This is given via inequalities and with the use of modulus of continuity of the involved function or its higher order derivative. We examine the real and complex cases.For the convenience of the reader, the chapters of this book are written in a self-contained style.This treatise relies on author's last two years of related research work.Advanced courses and seminars can be taught out of this brief book. All necessary background and motivations are given per chapter. A related list of references is given also per chapter. The exposed results are expected to find applications in many areas of computer science and applied mathematics, such as neural networks, intelligent systems, complexity theory, learning theory, vision and approximation theory, etc. As such this monograph is suitable for researchers, graduate students, and seminars of the above subjects, also for all science libraries.
Coculture of human zygotes on fetal bovine uterine fibroblasts: embryonic morphology and implantation *

Zygotes from in vitro fertilization patients (n = 116) were randomly allocated to culture in either conventional plastic petri dishes or coculture on a monolayer of fetal bovine uterine fibroblasts. Embryos (n = 288) remained 26 to 32 hours in these culture systems. Video tape recording for later morphological analysis (11 parameters) was performed on 117 conventionally cultured and 104 cocultured embryos, shortly before replacement, by an independent observer, unaware of the culture conditions for each embryo. A significantly greater number of cocultured embryos (52%) had "good" morphology (zero or only one abnormal characteristic) as compared with conventionally cultured embryos (30%). The most outstanding morphological characteristic of cocultured embryos was the expanded appearance of their blastomeres. The incidence of implantation per embryo increased from 13% to 19% when the coculture rather than conventional culture system was used, and the incidence of ongoing pregnancy per patient after coculture doubled to 35%.
LINGO-1 Negatively Regulates Oligodendrocyte Differentiation by Blocking the β-integrin Signaling Pathway (I10.002)

Objective: To identify how LINGO-1 (leucine-rich repeat and immunoglobulin domain-containing Nogo receptor-interacting protein-1) and anti-LINGO-1 (BIIB033) affect signaling molecules involved in oligodendrocyte differentiation, myelination and remyelination. Background: LINGO-1 is a negative regulator of oligodendrocyte differentiation, myelination and remyelination, whereas integrin signaling plays an important role in oligodendrocyte survival and differentiation. β1-integrin is known to be required for oligodendrocyte precursor cell (OPC) differentiation. Three separate experiments were performed to determine whether LINGO-1 has a role in downregulating β1-integrin, and if this relationship is affected by anti-LINGO-1. Methods: To assess OPC maturation and myelination, A2B5 + OPCs were cultured in differentiation medium containing neurotrophin-3 and ciliary neurotrophic factor for 3 days. Rat oligodendrocytes and dorsal root ganglion (DRG) neurons were purified and nerve growth factor used in the OPC/DRG co-culture to inhibit basal level myelination. Cells were lysed and Western blotting was performed using antibodies to myelin basic protein (MBP), myelin associated glycoprotein, and actin. In addition, HEK293 cells were transfected with plasmids encoding full length LINGO-1, β1 or α6 integrin. Cells were harvested after 48 hours, lysed, and analyzed by Western blotting using anti-LINGO-1, anti-β1 integrin and anti-α6 integrin antibodies. Finally, RNA was isolated from oligodendrocyte cells and quantitative reverse transcription PCR used to quantify MBP mRNA levels with β-actin used as an internal control. Results: We found that LINGO-1 binds to and down regulates β1-integrin expression. Also, anti-LINGO-1 antibody (BIIB033) enhanced oligodendrocyte differentiation by up-regulating integrin expression. Furthermore, antagonists of the integrin-signaling pathway, including a β1-integrin blocking antibody, are able to block anti-LINGO-1-induced oligodendrocyte differentiation, suggesting that LINGO-1 negatively regulates oligodendrocyte differentiation by down-regulating the β1-integrin signaling pathway. Conclusions: Our data suggest that LINGO-1 and anti-LINGO-1 affect oligodendrocyte differentiation and myelination by regulating the β1-integrin signaling pathway. Study supported by: Biogen. Disclosure: Dr. Mi holds stock and/or stock options in Biogen, which sponsored research in which Dr. Mi was involved as an investigator. Dr. Huang holds stock and/or stock options in Biogen Idec, which sponsored research in which Dr.Huang was involved as an investigator. Dr. Lee holds stock and/or stock options in Biogen, which sponsored research in which Dr. Lee was involved as an investigator. Dr. Shao holds stock and/or stock options in Biogen Idec.
A Comparison of Different Intrusion Detection Approaches in an Advanced Metering Infrastructure Network Using ADVISE

Utilities responsible for Advanced Metering Infrastructure (AMI) networks must be able to defend themselves from a variety of potential attacks so they may achieve the goals of delivering power to consumers and maintaining the integrity of their equipment and data. Intrusion detection systems (IDSes) can play an important part in the defense of such networks. Utilities should carefully consider the strengths and weaknesses of different IDS deployment strategies to choose the most cost-effective solution. Models of adversary behavior in the presence of different IDS deployments can help with making this decision as we demonstrate through a case study that uses a model created in the ADversary VIew Security Evaluation (ADVISE) formalism (which calculates metrics used to compare different IDSes). We show how these metrics give valuable insight into the selection of the appropriate IDS architecture for an AMI network.
Intra-field gate CD variability and its impact on circuit performance

Statistical analysis of an advanced CMOS process reveals a significant systematic within-field variability of gate CD strongly dependent on the local layout patterns. We present a novel modeling methodology for accurate prediction of the effect of such CD variability on circuit performance that enables statistical design for increased performance and yield. We also propose a mask-level gate CD correction algorithm allowing significant reduction of overall variability and provide a model to evaluate the effectiveness of correction.
Predicting Outcomes After Chemo-Embolization in Patients with Advanced-Stage Hepatocellular Carcinoma: An Evaluation of Different Radiologic Response Criteria

The purpse of this study was to evaluate the ability of various radiologic response criteria to predict patient outcomes after trans-arterial chemo-embolization with drug-eluting beads (DEB-TACE) in patients with advanced-stage (BCLC C) hepatocellular carcinoma (HCC). Hospital records from 2005 to 2011 were retrospectively reviewed. Non-infiltrative lesions were measured at baseline and on follow-up scans after DEB-TACE according to various common radiologic response criteria, including guidelines of the World Health Organization (WHO), Response Evaluation Criteria in Solid Tumors (RECIST), the European Association for the Study of the Liver (EASL), and modified RECIST (mRECIST). Statistical analysis was performed to see which, if any, of the response criteria could be used as a predictor of overall survival (OS) or time-to-progression (TTP). 75 patients met inclusion criteria. Median OS and TTP were 22.6 months (95 % CI 11.6–24.8) and 9.8 months (95 % CI 7.1–21.6), respectively. Univariate and multivariate Cox analyses revealed that none of the evaluated criteria had the ability to be used as a predictor for OS or TTP. Analysis of the C index in both univariate and multivariate models showed that the evaluated criteria were not accurate predictors of either OS (C-statistic range: 0.51–0.58 in the univariate model; range: 0.54–0.58 in the multivariate model) or TTP (C-statistic range: 0.55–0.59 in the univariate model; range: 0.57–0.61 in the multivariate model). Current response criteria are not accurate predictors of OS or TTP in patients with advanced-stage HCC after DEB-TACE.
Technology in Mental Health: Creating New Knowledge and Inventing the Future of Services

The mental health services now in place are intrinsically linked with the technology that has been at our disposal for decades of research and practice. Advancements in Web, mobile, sensor, and informatics technology can do more than serve as tools to enhance existing models of care. Novel technologies can help us better understand the very nature of mental illness and revise our fundamental assumptions about the structure, boundaries, and modalities of mental health treatment. Recognizing the unprecedented opportunities new technology offers to improve the outcomes of people with mental illness, Psychiatric Services announces a new column on technology and mental health.
Occult Isolated Articular Branch Cyst of the Lateral Plantar Nerve

We present the first known case of cyst fluid localized to an articular branch without involvement of the larger parent nerve. During a routine tarsal tunnel decompression in a patient with fluctuating plantar foot symptoms and "normal" magnetic resonance imaging findings, we identified cyst fluid within an articular branch of the lateral plantar nerve to the subtalar joint. Our incidental intraoperative discovery was corroborated by retrospective review of the magnetic resonance images. Although we do not know whether this cyst was responsible for the patient's complaints, we believe this finding represents a snapshot into the life cycle of intraneural ganglion cysts: either the "birth" of an ultra-early one or the remnant of a once larger one. Both interpretations are consistent with the unifying articular theory and add further insight into the dynamic phases of the progression of intraneural ganglion cysts.
Three Cultural Revolutions

In the view of the prophets and their allies social injustice was both sinful and avoidable. How simple and obvious was the solution. There need be no national doom, there need be no poverty, if only people behaved correctly: “There shall be no needy among you—since the Lord your God will bless you in the land which the Lord your God is giving you as a hereditary portion—if only you heed the Lord your God and take care to keep all this Instruction that I enjoin upon you this day … You will dominate many nations, but they will not dominate you” (Deut. 15:4–6). But the people were “dull” and “foolish” and, could not seem to grasp “all this Instruction.” Indeed, they were incapable of understanding even the one sentence instruction that covered them all: “Righteousness and only righteousness you shall pursue.”! (Deut. 16:20).
Identifying and Overcoming Crystal Pathologies: Disorder and Twinning

Macromolecular crystals are prone to a number of pathologies that result from aberrant molecular packing. Two common pathologies encountered in macromolecular crystals are rigid-body disorder and twinning. When a crystal displays one of these pathologies, its diffraction pattern is altered in a way that generally complicates structure determination. The severity of the underlying abnormalities varies from case to case, and sometimes the resulting alterations to the diffraction pattern are immediately obvious, while at other times they may go entirely unnoticed. Structure determination from a crystal that suffers from disorder or twinning may or may not be possible, depending on the specific nature of the pathology, and on how the data are handled. This chapter provides an introduction to these pathologies, with an emphasis on providing guidelines for identifying and overcoming them when they pose a threat to successful structure determination.
GLIS1-3: emerging roles in reprogramming, stem and progenitor cell differentiation and maintenance

Recent studies have provided evidence for a regulatory role of GLI-similar (GLIS) transcription factors in reprogramming, maintenance and differentiation of several stem and progenitor cell populations. GLIS1, in conjunction with several other reprogramming factors, was shown to markedly increase the efficiency of generating induced pluripotent stem cells (iPSC) from somatic cells. GLIS2 has been reported to contribute to the maintenance of the pluripotent state in hPSCs. In addition, GLIS2 has a function in regulating self-renewal of hematopoietic progenitors and megakaryocytic differentiation. GLIS3 plays a critical role during the development of several tissues. GLIS3 is able to promote reprogramming of human fibroblasts into retinal pigmented epithelial (RPE) cells. Moreover, GLIS3 is essential for spermatogonial stem cell renewal and spermatogonial progenitor cell differentiation. During pancreas development, GLIS3 protein is first detectable in bipotent pancreatic progenitors and pro-endocrine progenitors and plays a critical role in the generation of pancreatic beta cells. Here, we review the current status of the roles of GLIS proteins in the maintenance and differentiation of these different stem and progenitor cells.
Messenger RNA Processing in Eukaryotes

RNA processing is the term collectively used to describe the sequence of events through which the primary transcript from a gene acquires its mature form. Very soon after synthesis by RNA polymerase II begins, transcripts from nuclear protein-coding genes acquire a 5′ cap structure. The 3′ end of the messenger RNA (mRNA) is modified by the addition of a long string of adenosines in a process tightly linked to transcription termination. Finally, maturation of most eukaryotic mRNA precursors requires a process known as splicing, in which internal noncoding segments known as introns are removed and the coding segments, known as exons, are joined to produce functional mRNAs. In complex eukaryotes, exons are much smaller than introns and provide the functional unit initially recognized by the splicing machinery. Because the splicing signals found at the exon/intron boundaries have low information content, ancillary elements known as splicing enhancers and silencers are required to specify the precise sites of exon joining. Throughout their life cycles, mRNAs are decorated with proteins, some stably bound and others associated only transiently; thus, the functional form recognized by both the RNA-processing machinery and the translating ribosome is a ribonucleoprotein complex (mRNP). An important advance in recent years is the discovery that RNA-processing events are mechanistically coupled to transcription by RNA polymerase II.
Diabetes impairs wound healing by Dnmt1-dependent dysregulation of hematopoietic stem cells differentiation towards macrophages

People with type 2 diabetes mellitus (T2DM) have a 25-fold higher risk of limb loss than non-diabetics due in large part to impaired wound healing. Here, we show that the impaired wound healing phenotype found in T2D mice is recapitulated in lethally irradiated wild type recipients, whose hematopoiesis is reconstituted with hematopoietic stem cells (HSCs) from T2D mice, indicating an HSC-autonomous mechanism. This impaired wound healing phenotype of T2D mice is due to a Nox-2-dependent increase in HSC oxidant stress that decreases microRNA let-7d-3p, which, in turn, directly upregulates Dnmt1, leading to the hypermethylation of Notch1, PU.1, and Klf4. This HSC-autonomous mechanism reduces the number of wound macrophages and skews their polarization towards M1 macrophages. These findings reveal a novel inflammatory mechanism by which a metabolic disorder induces an epigenetic mechanism in HSCs, which predetermines the gene expression of terminally differentiated inflammatory cells that controls their number and function.
The Robust "Maximum Daily Return Effect as Demand for Lottery" and "Idiosyncratic Volatility Puzzle"

Abstract We form indexes of overpriced and underpriced stocks by ranking stocks based on the disposition effect and anchoring bias. We document the negative relation between maximum daily return and future returns (MAX effect) is confined to overpriced stocks which make up about half the entire sample. We find that the average cross-sectional correlation between maximum daily return and idiosyncratic volatility is nearly 90%. Consistent with prior studies the idiosyncratic volatility puzzle disappears after controlling for the MAX effect. However, when using a sample with a $5 price breakpoint and controlling for overpriced stocks the idiosyncratic volatility puzzle and the MAX effect are economically and statistically significant.
Surface enhanced Raman spectroscopy of Chlamydia trachomatis and Neisseria gonorrhoeae for diagnostics, and extra-cellular metabolomics and biochemical monitoring

SERS spectra excited at 785 nm of the bacteria Chlamydia trahomatis (elementary bodies, EB) and Neisseria gonorrheoae, the causative pathogens for the two most common sexually transmitted diseases (STD), chlamydia and gonorrhea, respectively, are reported. Although both are Gram-negative bacteria, the SERS signatures of C. trachomatis and N. gonorrheoae are completely different. N. gonorrheoae SERS spectra are due to the starvation induced nucleotide metabolites adenine and guanine, and the surface associated co-enzyme nicotinamide adenine dinucleotide and are very similar on Au and Ag although the spectrum appears more rapidly on Ag. The C. trachomatis SERS spectrum is dominated by the vibrational features of cell surface proteins. While features attributable to specific residues and the amide backbone characterize the C. trachomatis spectrum on Ag, the corresponding SERS spectrum on Au substrates displays vibrational characteristics of aggregated proteins. The prospects for the development of a SERS based platform for rapid (<one hour), low-cost bacterial STD diagnostics are promising based on these initial studies. Furthermore, this biomedical application demonstrates the potential for SERS to be a sensitive real time probe of the dynamics of biochemical activity in the cell wall and extracellular regions of microorganisms.
Searching for the analyst's reveries.

ABSTRACTOver the last 20 years the post-Bionians have begun nothing less than to spell out the beginning of the metabolizing process (reverie) in the analyst’s mind that takes place with under-repr...
V˙O 2 plateau in treadmill exercise is not dependent on anaerobic capacity

A plateau in oxygen consumption (V˙O2 plateau) remains the definitive criteria for establishing that maximal oxygen consumption (V˙O2max) was achieved during maximal exercise despite its inconsistent presence. Anaerobic capacity may assist in achieving a V˙O2 plateau. To determine if a correlation exists between maximal accumulated oxygen deficit (MAOD) and magnitude of V˙O2 plateau during treadmill exercise. Participants completed submaximal, maximal, and supramaximal exercise treadmill tests on separate occasions. MAOD was determined during the supramaximal test by calculating the difference between oxygen consumption (V˙O2) and predicted V˙O2 based on extrapolation of submaximal data. V˙O2 plateau was determined as a < 50 ml change in V˙O2 over the last 60 s of exercise. Ten of seventeen participants showed a plateau in V˙O2. Oxygen deficit was not different between the plateau and non-plateau groups (44.2 ± 10.8 vs. 44.8 ± 8.5 ml·kg−1, p = 0.906). Oxygen deficit was not correlated with change in V˙O2 (r = − 0.087, p = 0.739). Aerobic training hours·week−1 were higher in the plateau group than non-plateau (4.8 ± 1.5 vs. 1.7 ± 2.1, p = 0.003) and correlated with change in V˙O2 (r = − 0.418, p = 0.048). In treadmill running, there is not a significant correlation between V˙O2 plateau and MAOD as has been seen in cycling.
Parallels and Contrasts Between Deliberate Cloud Seeding and Aerosol Pollution Effects

Deliberate cloud seeding, with the goal of increasing precipitation by the injection of specific types of particles into clouds, has been pursued for over 50 years. Efforts to understand the processes involved have led to a significant body of knowledge about clouds and about the effects of the seeding aerosol. A number of projects focused on the statistical evaluation of whether a seeding effect can be distinguished in the presence of considerable natural variability. Both the knowledge gained from these experiments, and the awareness of the limitations in that understanding, are relevant to the general question of aerosol effects on precipitation. Definite proof from the seeding projects for an induced increase in precipitation as a result of the addition of seeding material to the clouds would represent a powerful demonstration of at least one type of dominant aerosol-precipitation link in the clouds involved.
The multi-faceted roles of the PI3K-AKT pathway in melanoma

Results Proteomic analysis of frozen melanoma clinical specimens and cell lines demonstrated that phosphorylation (activation) of AKT (P-AKT) correlated inversely with PTEN protein expression. Confirmatory analysis of PTEN expression by an immunohistochemical (IHC) assay on archival tumor samples identified a linear correlation between PTEN measurement by IHC and RPPA. Significantly increased expression of P-AKT was observed in melanomas with complete loss of PTEN protein expression compared to tumors with any other pattern of PTEN expression. Integrated analysis of BRAF/NRAS mutation status, PTEN expression, and clinical outcomes was performed using lymphadenectomy specimens from patients who underwent surgery for stage IIIB/C melanoma. Complete loss of PTEN expression correlated with shorter overall survival and time to brain metastasis on univariate and multivariate analyses. Testing of human melanoma cell lines demonstrated that cells with baseline or compensatory activation of the PI3K-AKT pathway were generally resistant to apoptosis induction following BRAF or MEK inhibition. Extended molecular profiling found that a subset of melanoma cell lines with de novo and acquired resistance to MEK inhibitors are characterized by increased expression of PGC1alpha and a metabolic phenotype of high oxidative phosphorylation (OxPhos). The resistant high OxPhos cell lines all demonstrated synergistic growth inhibition and apoptosis induction with combined targeting of MEK and mTORC1/2. mTORC1/2 inhibition decreased PGC1alpha expression in vitro and in vivo, and caused cytosolic localization of MITF. Treatment with a MEK inhibitor and an mTORC1/2 inhibitor demonstrated marked synergy in a BRAF-mutant, MEK inhibitor resistant human melanoma cell line in vivo.
Problematizing information-seeking Wh-questions

Abstract Important conversation analytic work has made evident how responses to questions may be designed to resist the terms, agendas, and constraints of those questions (e.g., Heritage, 1998; Lee, 2013; Stivers & Hayashi, 2010). Based on audio-recordings of 17 publicly-available information webinars delivered by a U. S. philanthropic foundation to prospective applicants, the paper describes three methods leveraged by the institutional representatives that treat wh-questions that seek information during Q&A as somewhat “problematic.” Findings extend the current literature by illuminating how resistance to questions may be implemented in an understudied institutional context and contribute to the knowledge base for identifying “best practices” for webinar facilitation (Zoumenou et al., 2015).
Yuan Shikai and the Significance of his Troop Training at Xiaozhan, Tianjin, 1895–1899

China’s humiliating defeat in the Sino-Japanese War in 1895 shocked a number of high-ranking Qing officials into seeking ways to establish a truly modernized army in the Western fashion. Yuan Shika...