cssi/SciSciGPT-SciSciNet huggingface dataset:
Associations and Heritability of Auditory Encoding, Gray Matter, and Attention in Schizophrenia.

Background Auditory encoding abnormalities, gray-matter loss, and cognitive deficits are all candidate schizophrenia (SZ) endophenotypes. This study evaluated associations between and heritability of auditory network attributes (function and structure) and attention in healthy controls (HC), SZ patients, and unaffected relatives (UR). Methods Whole-brain maps of M100 auditory activity from magnetoencephalography recordings, cortical thickness (CT), and a measure of attention were obtained from 70 HC, 69 SZ patients, and 35 UR. Heritability estimates (h2r) were obtained for M100, CT at each group-difference region, and the attention measure. Results SZ patients had weaker bilateral superior temporal gyrus (STG) M100 responses than HC and a weaker right frontal M100 response than UR. Abnormally large M100 responses in left superior frontal gyrus were observed in UR and SZ patients. SZ patients showed smaller CT in bilateral STG and right frontal regions. Interrelatedness between 3 putative SZ endophenotypes was demonstrated, although in the left STG the M100 and CT function-structure associations observed in HC and UR were absent in SZ patients. Heritability analyses also showed that right frontal M100 and bilateral STG CT measures are significantly heritable. Conclusions Present findings indicated that the 3 SZ endophenotypes examined are not isolated markers of pathology but instead are connected. The pattern of auditory encoding group differences and the pattern of brain function-structure associations differ as a function of brain region, indicating the need for regional specificity when studying these endophenotypes, and with the presence of left STG function-structure associations in HC and UR but not in SZ perhaps reflecting disease-associated damage to gray matter that disrupts function-structure relationships in SZ.
Cognitive development in digital contexts

Researchers are only beginning to explore the impact of growing up with sustained exposure to digital content, as the access children have to technology today is unprecedented (Rideout, 2016, 2017)...
Modulation of Opioid Transport at the Blood-Brain Barrier by Altered ATP-Binding Cassette (ABC) Transporter Expression and Activity

Opioids are highly effective analgesics that have a serious potential for adverse drug reactions and for development of addiction and tolerance. Since the use of opioids has escalated in recent years, it is increasingly important to understand biological mechanisms that can increase the probability of opioid-associated adverse events occurring in patient populations. This is emphasized by the current opioid epidemic in the United States where opioid analgesics are frequently abused and misused. It has been established that the effectiveness of opioids is maximized when these drugs readily access opioid receptors in the central nervous system (CNS). Indeed, opioid delivery to the brain is significantly influenced by the blood-brain barrier (BBB). In particular, ATP-binding cassette (ABC) transporters that are endogenously expressed at the BBB are critical determinants of CNS opioid penetration. In this review, we will discuss current knowledge on the transport of opioid analgesic drugs by ABC transporters at the BBB. We will also examine how expression and trafficking of ABC transporters can be modified by pain and/or opioid pharmacotherapy, a novel mechanism that can promote opioid-associated adverse drug events and development of addiction and tolerance.
Chronic stress induces cell type-selective transcriptomic and electrophysiological changes in the bed nucleus of the stria terminalis

Distinct regions and cell types in the anterolateral group of the bed nucleus of the stria terminalis (BNSTALG) act to modulate anxiety in opposing ways. A history of chronic stress increases anxiety-like behavior with lasting electrophysiological effects on the BNSTALG. However, the opposing circuits within the BNSTALG suggest that stress may have differential effects on the individual cell types that comprise these circuits to shift the balance to favor anxiogenesis. Yet, the effects of stress are generally examined by treating all neurons within a particular region of the BNST as a homogenoeus population. We used patch-clamp electrophysiology and single-cell quantitative reverse transcriptase PCR (scRT-PCR) to determine how chronic shock stress (CSS) affects electrophysiological and neurochemical properties of Type I, Type II, and Type III neurons in the BNSTALG. We report that CSS resulted in changes in the input resistance, time constant, action potential waveform, and firing rate of Type III but not Type I or II neurons. Additionally, only the Type III neurons exhibited an increase in Crf mRNA and a decrease in striatal-enriched protein tyrosine phosphatase (Ptpn5) mRNA after CSS. In contrast, only non-Type III cells showed a reduction in calcium-permeable AMPA receptor (CP-AMPAR) current and changes in mRNA expression of genes encoding AMPA receptor subunits after CSS. Importantly, none of the effects of CSS observed were seen in all cell types. Our results suggest that Type III neurons play a unique role in the BNSTALG circuit and represent a population of CRF neurons particularly sensitive to chronic stress.
Pre-operative factors that predict trifecta and pentafecta in robotic assisted partial nephrectomy

To prospectively evaluate factors that predict achievement of trifecta and pentafecta following robotic-assisted partial nephrectomy (RAPN). Clinical variables of 330 RAPNs performed for a single renal tumor were analyzed for association with post-operative trifecta and pentafecta achievement. Trifecta was defined as warm ischemia time (WIT) ≤ 25 min, negative surgical margins, and no post-operative complications ≥ Clavien grade 3. Pentafecta was defined as trifecta criteria plus > 90% preservation of estimated glomerular filtration rate (eGFR) and no stage upgrade of chronic kidney disease from pre-operative up to 12 months post-RAPN. After adjustment for multiple testing, p < 0.007 was considered statistically significant. Among 330 patients, trifecta was achieved in 280 patients (84.8%). Among the 152 patients with eGFR available at 12 months following RAPN, pentafecta was achieved in 39 (25.8%). A lower R.E.N.A.L. score was associated with increased odds of achieving trifecta (OR 3.38, p < 0.001) and pentafecta (OR 2.83 p < 0.001). No other pre-operative characteristics were associated with trifecta or pentafecta. Patients who achieved trifecta had a lower median estimated blood loss (EBL) (300 vs 400, p = 0.029) and shorter operative time (223 vs 234 min, p = 0.004) compared to patients without trifecta. There were no significant differences in EBL or operative time in patients who achieved or failed to achieve pentafecta. R.E.N.A.L score is the only pre-operative variable associated with achieving trifecta and pentafecta following RAPN. Lower EBL and operative time are associated with trifecta but not pentafecta outcomes.
Genes associated with bowel metastases in ovarian cancer

Abstract Objective This study is designed to identify genes and pathways that could promote metastasis to the bowel in high-grade serous ovarian cancer (OC) and evaluate their associations with clinical outcomes. Methods We performed RNA sequencing of OC primary tumors (PTs) and their corresponding bowel metastases (n = 21 discovery set; n = 18 replication set). Differentially expressed genes (DEGs) were those expressed at least 2-fold higher in bowel metastases (BMets) than PTs in at least 30% of patients (P Results Among 27 DEGs in the discovery set, 21 were confirmed in the replication set: SFRP2, Col11A1, LRRC15, ADAM12, ADAMTS12, MFAP5, LUM, PLPP4, FAP, POSTN, GRP, MMP11, MMP13, C1QTNF3, EPYC, DIO2, KCNA1, NETO1, NTM, MYH13, and PVALB. Higher expression of more than half of the genes in the PT was associated with an increased requirement for bowel resection at primary surgery and an inability to achieve complete cytoreduction. Increased expression of LRRC15 in BMets was confirmed by immunohistochemistry and knockdown of LRRC15 significantly inhibited tumor progression in mice. Conclusions We identified 21 genes that are overexpressed in bowel metastases among patients with OC. Our findings will help select potential molecular targets for the prevention and treatment of malignant bowel obstruction in OC.
Development of a dual fluorescence system for simultaneous detection of two cell populations in a 3D coculture

Abstract A dual fluorescence system consisting of enhanced green fluorescent protein (EGFP) and red fluorescent protein (Ds-red) signals was developed for monitoring cellular activities. For system validation, MCF-7 breast cancer cells were engineered to express EGFP and Ds-red, respectively. Cells were cultured in three-dimensional (3D) polymer-based scaffolds on a 40-microbioreactor platform (40-MBR) with real-time monitoring of fluorescence signals without significant background fluorescence noises from culture medium and 3D scaffold. The fluorescence kinetics study showed that both EGFP and Ds-red signals in the 3D coculture could be simultaneously detected without interference with each other. The cytotoxicity study of tamoxifen and the survivin promoter test of doxorubicin demonstrated that both EGFP and Ds-red signals provided high sensitivity to evaluate drug effectiveness. These studies suggested that the novel dual fluorescence system could provide a simple, real-time, and rapid cell detection in 3D coculture assay, which could be used for in vitro high throughput drug screening.
GaN High-Power Lasers for solid-state lighting

We discuss the use of GaN high-power laser diode in general lighting applications. After reviewing the laser diode achievements; the phosphors materials, the optical design and the possible performances of these devices are discussed.
The Introduction of ICTs in Chilean Schools – An Analysis of the Various Initiatives Since Enlaces and the Issues Faced by the Mapuche

The Introduction of ICTs in Chilean Schools - The Various Initiatives since Enlaces and the Issues Faced by Mapuche Students.
Predictors of Taking Elective Music Courses in Middle School Among Low-SES, Ethnically Diverse Students in Miami:

Researchers attempting to show that music has positive effects on children need to understand and control for preexisting differences between those who do and do not select into musical participati...
Um caso de rinorreia doce

Introducao: A fistula espontânea de liquido cefalorraquidiano e uma doenca rara e de etiologia pouco esclarecida, havendo alguma associacao com hipertensao intracraniana benigna. O diagnostico nem sempre e imediato, podendo constituir um desafio, por poder ser uma doenca facilmente confundida com causas mais comuns de rinorreia. A sua detecao atempada pelo medico de familia e essencial para prevenir complicacoes potencialmente graves, como as infecoes do sistema nervoso central. Descricao do caso: Mulher de 64 anos, apresenta-se com rinorreia aquosa e tosse, com meses de evolucao. Foram pedidos exames auxiliares de diagnostico para despiste de patologia neoplasica, infeciosa e alergica, cujo resultado foi negativo. A tosse desapareceu com a cessacao do inibidor da enzima conversora da angiotensina, com o qual a doente estava medicada. A rinorreia aquosa permaneceu e meses mais tarde veio a assumir caracteristicas que fizeram suspeitar de fistula espontânea de liquido cefalorraquidiano. A tomografia computorizada nao revelou a fistula, mas a pesquisa de glicose no liquido nasal foi compativel com esse diagnostico. Enquanto aguardava por consulta urgente de neurocirurgia, a doente desenvolveu meningite complicada com abcesso cerebral. A presenca de solucao de continuidade foi confirmada em ressonância magnetica cerebral, associada a sinais de hipertensao intracraniana benigna. A doente recuperou sem sequelas e a fistula encerrou espontaneamente. Apresenta-se assintomatica ate a data, sem rinorreia ou recorrencia de infecoes do sistema nervoso central. Comentario: A suspeita de fistula espontânea de liquido cefalorraquidiano foi levantada com base na clinica apresentada pela doente, ainda antes de esta desenvolver complicacoes. Os exames de diagnostico mais fidedignos para a confirmacao desta entidade nao estao facilmente acessiveis nos cuidados de saude primarios. No entanto, e apesar da medicao da glicose no liquido nasal nao ser o metodo mais recomendado atualmente, neste caso cumpriam-se os criterios para a sua fiabilidade, tendo sido um elemento fundamental para a orientacao do caso. Perante uma entidade clinica rara, mas potencialmente grave, o conhecimento da semiologia e a correta utilizacao de recursos simples podem ser suficientes para a confirmacao diagnostica.
Nanosensors for checking noise of physical agents

Abstract To monitor noise and human noise behavior in a city, a review of nanosensors for sensing noise of physical agents is performed. For example, monitoring an improved transportation system would not only result in energy conservation and economical affordability but also result in generating less noise⁎. As is the case of increased energy consumption, increased quantities of goods and services result in generation of more noise behavior⁎⁎ in a city. Nanosensors for sensing noise of physical agents (light, sound, heat, fluid, electricity, fire, and the sun) are discussed. With integrated environmental control, these environmental parameters are to be characterized and checked for comfort and wellness, and controlled through various environmental monitoring sensors. The effect of these human behavioral parameters is characterized and measured on a logarithmic noise scale. Sensing and monitoring of human noise behavior from human systems in a city requires real-time informatics capabilities. Sensing capabilities as well as measurement systems for noise can be “in vivo” and “in vitro.” The signals can be classified as bioelectric, biosound sample, biomechanical, bi-chemical, biomagnetic, bio-optic, and bioimpedance depending upon the origin of “stresses and oscillations” in a noise system. A theory on noise-measurement equations due to noise of physical agents is devised. A slide rule for noise measurement is also presented. Noise calculations charts are presented for calculating noises of oncisol, oncisip, and oncibel based on pressure and intensity ratios. Noise-measurement sensing system along with its brief description is also elaborated. ⁎Noise is defined as a sensation of unwanted intensity of a wave. It is perception of a pollutant and a type of environmental stressor. An environmental stressor such as noise may have detrimental effects on various aspects of health. The unwanted intensity of a wave is a propagation of noise due to transmission of waves (viz., physical agents) such as sun, light, sound, heat, electricity, fluid, and fire. ⁎⁎Noise behavior is checked by identifying a source and a sink of noise, i.e., a person making noise in the environment and a person affected by such noise in the environment.
Stimulation of immunity-linked genes by membrane disruption is linked to Golgi function and the ARF-1 GTPase

Immune-linked genes (ILGs) are activated in response to pathogens but can also be activated by lipid imbalance. Why pathogen attack and metabolic changes both impact ILG activation is unclear. Organelles in the secretory pathway have distinct protein and lipid components and genetically separable stress programs. These stress pathways activate restorative transcriptional programs when lipid ratios become unbalanced or during dysregulated protein folding and trafficking. We find that ILGs are specifically activated when membrane phosphatidylcholine ratios change in the secretory pathway. Consistent with this result, disruption of Golgi function in mutations targeting the ADP-ribosylation factor ARF-1 also activates ILG expression. Since increased protein secretion is altered by metabolic changes and pathogen responses, our data argue that ILG upregulation is a conserved, coordinated response to changes in trafficking resulting from intrinsic cues (lipid changes) or extrinsic stimulation (during the immune response). These findings uncover important and previously unexplored links between metabolism and the stress response.
Neoadjuvant therapy for esophageal cancer

Esophageal cancer is increasing in incidence more than any other visceral malignancy in North America. Adenocarcinoma has become the most common cell type. Surgery remains the primary treatment modality for locoregional disease. Overall survival with surgery alone has been dismal, with metastatic disease the primary mode of treatment failure after an R0 surgical resection. Cure rates with chemotherapy or radiation therapy alone have been disappointing as well. For these reasons, over the last decade multi-modality treatment has gained increasing acceptance as the standard of care. This review examines the present data and role of neoadjuvant treatment using chemotherapy and radiation therapy followed by surgery for the treatment of esophageal cancer.
Sozialisierung und Planung

Seit dem Auftreten des modernen Konstitutionalismus im 17. und 18. Jahrhundert haben sich innerhalb der gesamten abendlandischen Gesellschaft unvorhergesehene Spannungen entwickelt. Einige dieser Spannungen sind geistiger und sittlicher Natur und stehen in Zusammenhang mit dem Niedergang des Christentums als einer lebendigen und das ganze Leben bestimmenden Kraft. Unter diesem Gesichtspunkt betrachtet, fallen sie auserhalb des Rahmens der vorliegenden Arbeit1. Andere dieser Spannungen sind mehr diesseitiger und pragmatischer Natur und sind selbst wenigstens bis zu einem gewissen Grad durch Konstitutionalismus und Demokratie verstarkt worden. In diesem Zusammenhang sind von besonderer Wichtigkeit Wirtschaftskrisen, Massenpropaganda und das plebiszitare Handeln der Masse. Sie haben ihrerseits den Anstos dazu gegeben, das immer haufiger von Notrechten Gebrauch gemacht wurde. Die sich daraus ergebende „konstitutionelle Diktatur“ wurde in einer Reihe von Landern durch die totalitare Diktatur sowohl der Rechten als auch der Linken abgelost. Die aggressiven Neigungen dieser Diktatur, ob nun im Zeichen der Weltrevolution oder unter dem Banner der Welteroberung, haben die Volker in „heise und kalte“ Kriege gesturzt, die die Anwendung der Notvollmachten noch weiter ausdehnten und Planung, Propaganda und plebiszitares Handeln der Masse in einem unerhorten Umfang notwendig machten.
Tornado Technology and Professional Practice

Advancements in tornado technology make it possible to plan and design for the tornado. Tornado proof designs are being employed in the nuclear industry and in the design of shelters. Understandings of the tornado and design experiences can be utilized to plan facilities and to design conventional buildings to resist the tornado. Literature which represents modern tornado technology is summarized, examples of designs for tornadoes are presented, and potential uses for tornado technology in engineering practice are outlined. Barriers to the effective use of tornado technology are discussed.
Development of solid-liquid separation technologies in bioprocessing

An innovative bioprocess utilizing thin stillage from dry-­‐grind corn ethanol plants was used to produce a valuable filamentous fungus (R. microsporus var. oligosporus). A 1,500-­‐L bioreactor was built to optimize operating parameters, produce fungal biomass for animal feed trials and develop equipment and processes for industrialization. Dewatering equipment was tested to determine proper solid-­‐liquid separation equipment for the industrial process. Studies indicate that a two-­‐step dewatering process is most effective utilizing a gravity fed, concave screen followed by a centrifuging filter. Solids content greater than 30 percent is not possible, as this value approaches theoretical limits due to intracellular water. This new fungal co-­‐product has some superior feed properties in comparison to distillers grains. Selection of proper processing equipment minimizes capital and operating costs, making this process economically feasible for ethanol producers or other investors. Methods to concentrate and remove phosphorus from a waste bioprocessing stream utilized as a fertilizer was investigated to produce two more desirable products, liquid fertilizer with a larger nitrogen to phosphorus (N:P) ratio and a “solid” phase with a lower N:P. A large percentage of phosphorus in this liquid slurry, left over from an industrial fermentation process, is tied up in the suspended solids. The study focuses on the use of coagulants and polymers to aid separation of suspended solids from the bulk liquid, ultimately producing a liquid fertilizer with a higher nitrogen to phosphorus ratio over the initial liquid slurry.
Sparse and cross-term free time-frequency distribution based on Hermite functions

Hermite functions are an effective tool for improving the resolution of the single-window spectrogram. In this paper, we analyze the Hermite functions in the ambiguity domain and show that the higher order terms can introduce undesirable cross-terms in the multiwindow spectrogram. The optimal number of Hermite functions depends on the location and spread of signal auto-terms in the ambiguity domain. We apply and compare several sparsity measures, namely l 1 norm, the Gini index and the time-frequency concentration measure, for determining the optimal number of Hermite functions, leading to the most desirable time-frequency representation. Among the employed measures, the Gini index provides the sparsest solution. This solution corresponds to a well-concentrated and cross-term reduced time-frequency signature.
Heating rates and surface dimming due to black carbon aerosol absorption associated with a major U.S. city

[1] In situ airborne measurements of actinic flux and the mass and mixing state of individual refractory black carbon (BC) particles were made in the lower troposphere around a major U.S. metropolitan area. These data were used to estimate atmospheric heating rates and surface dimming due to absorption of solar radiation by refractory BC. Direct absorption by ozone is also calculated and averages 10% of that of BC below 4 km but becomes dominant above this altitude. Variability in BC absorption is large due to source variability and clouds. Average BC heating rates are much smaller than those associated with BC and other absorbing aerosol components in global hotspot regions. These results, which are specific to refractory BC absorption, will help determine the value of short-term climate-change mitigation strategies involving BC emission reductions. They may also be used to estimate refractory BC contributions to total aerosol absorption.
Potential energy landscape of the (H2O)6- cluster

Abstract Local minima and first-order saddle points on the potential energy surface of the ( H 2 O ) 6 - cluster as described by a recently introduced one-electron model Hamiltonian are located using a combination of the basin-hopping Monte Carlo, doubly-nudged elastic band, and eigenvector-following methods. The minimum energy pathways connecting the transition states and minima are identified and used to construct disconnectivity diagrams. The implications of the calculated rearrangement pathways for experimental studies of ( H 2 O ) 6 - are discussed.
Further Studies on the Mechanism of Action of the Anti-Estrogen (U11555A) in the Inhibition of Pregnancy in the Rat

Previously it was shown that diphenylenedene (U11555A) an effective antiestrogen given at levels of 5 and 10 mg/kg of Day 1 (the day of finding sperm) caused an increased rate of passage of blastocysts out of the tube into the uterus in the rat. Only a small proportion of these eggs were recoverable from the uterine cavity on Day 4 of gestation at the lower dose and none at the 10 mg/kg level. 2 experiments are reported which were conducted in order to answer questions which arose from the initial experiment. The first group of experiments was concerned with the ability of compound U11555A to suppress deciduomas in rats. The second was undertaken to determine whether the apparent loss of blastocysts from the uterus is due to increased rate of transport through the uterus or whether the blastocysts degenerate in the uterus owing to too early arrival or to a direct effect of the compound. In the first experiment there were 17 controls and 15 in the experimental group. No suppression of the deciduomas induced by placement of threads or scratching the endometrial was evident in 3 animals given 2.5 mg of U11555A per kilogram on Day 1 or in 12 animals who were treated similarly except that the compound was given not on the day of finding sperm but on the day of induction of the deciduomata the fourth day of pseudopregancy. In the second experiment when U11555A was given at levels of 2.5 and 10 mg/kg on either the third or fourth day of pregnancy implantation of blastocysts was prevented. When the blastocysts were recovered from the uterine horns and vagina and histologic sections were prepared it was determined that though some loss of the blastocysts occurred in the vagina the majority of the blastocysts remained in the uterine cavity but without implantation. Even in the blastocysts recovered from the vagina mitosis was still demonstrable. The antiestrogen appears to focus on the implanting blastocysts rather than affect the endometrium and its response.
Evaluation of an Automatic Calcium Titrator

An automatic calcium titrator for determining total serum calcium concentration has been evaluated. The instrument incorporates a motorized buret, a fluorometer, and a digital readout that is responsive to the quenching of the fluorescent calcium—calcein complex by the chelating agent, ethyleneglycol-bis(2-aminoethyl ether)-N,N,N',N'-tetraacetic acid. Analyses made with the calcium titrator were compared with those made with the SMA 12/60 and atomic absorption spectrophotometry. Good correlation was obtained in each instance. Slight hemolysis and bilirubin concentrations near normal did not affect the results; however, increased concentrations of these substances resulted in decreased values. The precision of analysis depends on the technique used in pipetting the sample. A single analysis of 0.1 ml of serum can be completed in 1 to 2 min. With careful analytical technique, precision is good (CV, 0.72%).
A Microdischarge-Based Monolithic Pressure Sensor

This paper describes the investigation of a microdischarge-based approach for sensing the diaphragm deflec- tion in a monolithically fabricated pressure sensor. This transduc- tion approach is appealing from the viewpoint of miniaturization. The device consists of a deflecting Si diaphragm with a sensing cathode, and a glass substrate with an anode and a reference cath- ode. The total exterior volume of the device is 0.05 mm 3 ; typical electrode size and separations are 35 and 10 µm. Pulsed microdis- charges are initiated in a sealed chamber formed between Si and glass chips, and are filled with Ar gas. External pressure deflects the Si diaphragm and changes the interelectrode spacing, thereby redistributing the current between the anode and two competing cathodes. The differential current is indicative of the diaphragm deflection which is determined by the external pressure. A 6-mask microfabrication process is investigated for device fabrication. Electrode connections to the interior of the chamber are provided by laser drilling and copper electroplating through high aspect ratio glass vias. The Si and glass substrates are bonded by Au-In eutectic. The redistribution of plasma current between competing cathodes, as a consequence of diaphragm deflection over a range of pressure, was experimentally demonstrated. First principles modeling of transient microdischarges have provided insights to the fundamental processes responsible for the differential current and guidance for scaling the device to smaller dimension. (2013-0200)
Investigation of MALDI-TOF and FT-MS Techniques for Analysis of Escherichia coli Whole Cells

Recently, it has been demonstrated that bacteria can be characterized using whole cells and matrix-assisted laser desorption/ionization mass spectrometry (MALDI-MS). However, identification of specific bacterial proteins usually requires analysis of cellular fractions or purified extracts. Here, the first application of Fourier transform mass spectrometry (FTMS) to analysis of bacterial proteins directly from whole cells is reported. It is shown that accurate mass MALDI-FTMS can be used to characterize specific ribosomal proteins directly from Escherichia coli cells. High-accuracy mass measurements and high-resolution isotope profile data confirm posttranslational modifications proposed previously on the basis of low-resolution mass measurements. Seven ribosomal proteins from E. coli whole cells were observed with errors of less than 27 ppm. This was accomplished directly from whole cells without fractionation, concentration, or overt overexpression of characteristic cellular proteins. MALDI-FTMS also pro...
Can drug users be effective change agents? Yes, but much still needs to change.

The answer to the question of whether drug users can be effective change agents is yes, although the extent to which they are successful as change agents depends on whether they are acting to change their individual behaviors, the behavior of other drug users, or the laws and policies that negatively impact their health. Drug users have been successful in reducing their individual risk behaviors, and controlling and managing their drug use while still actively using drugs. They have also been successful in advocating risk reduction among their drug using peers. The success of drug users in changing policies that increase their risk for contracting HIV and other diseases, and improving their lives has been more mixed. In spite of these successes, drug use continues to be criminalized and viewed as a moral failure rather than an illness in the belief that drug users are incapable of change. This essay addresses the major myths still common to misunderstanding drug users and behavior change. These attitudes, in turn, limit drug users’ ability to effectively act to improve their lives.
Reducing clock jitter by using Muller-C elements

A simple method for reducing the cycle-to-cycle jitter of clock signals is described. The method uses Muller-C elements to merge redundant clock signals. If the two clock signals have nearly the same average phase and independently-distributed phase noise, then the jitter at the Muller-C element's output is less than that of the input signals. This method can be used to reduce jitter in sampling clocks for analogue-to-digital conversion, and in clock distribution networks for VLSI systems.
A Sleeping Beauty screen reveals NF-kB activation in CLL mouse model

TCL1 oncogene is overexpressed in aggressive form of human chronic lymphocytic leukemia (CLL) and its dysregulation in mouse B cells causes a CD5-positive leukemia similar to the aggressive form of human CLLs. To identify oncogenes that cooperate with Tcl1, we performed genetic screen in Eμ−TCL1 mice using Sleeping Beauty transposon-mediated mutagenesis. Analysis of transposon common insertion sites identified 7 genes activated by transposon insertions. Overexpression of these genes in mouse CLL was confirmed by real time reverse transcription-polymerase chain reaction. Interestingly, the main known function of 4 of 7 genes (Nfkb1, Tab2, Map3K14, and Nfkbid) is participation in or activation of the nuclear factor-kB (NF-kB) pathway. In addition, activation of the NF-kB is 1 of main functions of Akt2, also identified in the screen. These findings demonstrate cooperation of Tcl1 and the NF-kB pathway in the pathogenesis of aggressive CLL. Identification cooperating cancer genes will result in the development of combinatorial therapies to treat CLL.
Endogenous Inhibition of the Trigeminally Evoked Neurotransmission to Cardiac Vagal Neurons by Muscarinic Acetylcholine Receptors

Stimulation of the nasal mucosa by airborne irritants or water evokes a pronounced bradycardia accompanied by peripheral vasoconstriction and apnea. The dive response, which includes the trigeminocardiac reflex, is among the most powerful autonomic responses. These responses slow the heart rate and reduce myocardial oxygen consumption. Although normally cardioprotective, exaggeration of this reflex can be detrimental and has been implicated in cardiorespiratory diseases, including sudden infant death syndrome (SIDS). An essential component of the diving response and trigeminocardiac reflex is activation of the parasympathetic cardiac vagal neurons (CVNs) in the nucleus ambiguus that control heart rate. This study examined the involvement of cholinergic receptors in trigeminally evoked excitatory postsynaptic currents in CVNs in an in vitro preparation from rats. CVNs were identified using a retrograde tracer injected into the fat pads at the base of the heart. Application of the acetylcholinesterase inhibitor neostigmine significantly decreased the amplitude of glutamatergic neurotransmission to CVNs on stimulation of trigeminal fibers. Whereas nicotine did not have any effect on the glutamatergic responses, the muscarinic acetylcholine receptor (mAChR) agonist bethanechol significantly decreased the excitatory neurotransmission. Atropine, an mAChR antagonist, facilitated these responses indicating this trigeminally evoked brain stem pathway in vitro is endogenously inhibited by mAChRs. Tropicamide, an m4 mAChR antagonist, prevented the inhibitory action of the muscarinic agonist bethanechol. These results indicate that the glutamatergic synaptic neurotransmission in the trigeminally evoked pathway to CVNs is endogenously inhibited in vitro by m4 mAChRs.
Antibacterial effect of zinc oxide nanoparticles combined with ultrasound.

Using Staphylococcus aureus (S. aureus), the present study investigated the antibacterial effect of ZnO nanoparticles both in the absence and presence of ultrasound stimulation. While the antibacterial effect of control nanoparticle chemistries (Al2O3) alone was either weak or unobservable under the conditions tested, the antibacterial effect of ZnO alone was significant, providing over a four log reduction (equivalent to antibiotics) compared to no treatment after just 8 h. The antibacterial effect was enhanced as ZnO particle diameter decreased. Specifically, when testing the antibacterial effect against bacteria populations relevant to infection, a 500 μg ml−1 dose of zinc oxide nanoparticles with a diameter of 20 nm reduced S. aureus populations by four orders of magnitude after 8 and 24 h, compared to control groups with no nanoparticles. This was accomplished without the use of antibiotics, to which bacteria are developing a resistance anyway. The addition of ultrasound stimulation further reduced the number of viable colony-forming units present in a planktonic cell suspension by 76% compared to nanoparticles alone. Lastly, this study provided a mechanism for how ZnO nanoparticles in the presence of ultrasound decrease bacteria functions by demonstrating greater hydrogen peroxide generation by S. aureus compared to controls. These results indicated that small-diameter ZnO nanoparticles exhibited strong antibacterial properties that can be additionally enhanced in the presence of ultrasound and, thus, should be further studied for a wide range of medical device anti-infection applications.
IMAGING RNA IN LIVING CELLS WITH MOLECULAR BEACONS: CURRENT PERSPECTIVES AND CHALLENGES

There is a growing realization that cell-to-cell variations in gene expression have important biological consequences underlying phenotype diversity and cell fate. Although analytical tools for measuring gene expression, such as DNA microarrays, reverse-transcriptase PCR and in situ hybridization have been widely utilized to discover the role of genetic variations in governing cellular behavior, these methods are performed in cell lysates and/or on fixed cells, and therefore lack the ability to provide comprehensive spatial-dynamic information on gene expression. This has invoked the recent development of molecular imaging strategies capable of illuminating the distribution and dynamics of RNA molecules in living cells. In this review, we describe a class of molecular imaging probes known as molecular beacons (MBs), which have increasingly become the probe of choice for imaging RNA in living cells. In addition, we present the major challenges that can limit the ability of MBs to provide accurate measurements of RNA, and discuss efforts that have been made to overcome these challenges. It is envisioned that with continued refinement of the MB design, MBs will eventually become an indispensable tool for analyzing gene expression in biology and medicine.
On recursive estimation for hidden Markov models

Abstract Hidden Markov models (HMMs) have during the last decade become a widespread tool for modelling sequences of dependent random variables. In this paper we consider a recursive estimator for HMMs based on the m -dimensional distribution of the process and show that this estimator converges to the set of stationary points of the corresponding Kullback-Leibler information. We also investigate averaging in this recursive scheme and show that conditional on convergence to the true parameter, and provided m is chosen large enough, the averaged estimator is close to optimal.
Impact of Indian Mustard (Brassica juncea) and Flax (Linum usitatissimum) Seed Meal Applications on Soil Carbon, Nitrogen, and Microbial Dynamics

There is a critical need to investigate how land application of dedicated biofuel oilseed meals affects soil ecosystems. In this study, mustard (Brassica juncea) and flax (Linum usitatissimum) seed meals and sorghum-sudangrass (Sorghum bicolor) were added to soil at levels of 0, 1, 2.5, and 5% (w/w). Both the type of amendment and application rate affected soil organic C, total C & N, and C & N mineralization. Mustard meal amendment initially inhibited C mineralization as compared to flax, but >50% of mustard and flax organic C was mineralized within 51 d. Nitrogen mineralization was similar for flax and mustard, except for the 2.5% rate for which a lower proportion of mustard N was converted to nitrate. The mustard meal greatly impacted microbial community composition, appearing to select for specific fungal populations. The potential varying impacts of different oilseed meals on soil ecosystems should be considered when developing recommendations for land application.
TH-C-T-617-05: Monte Carlo Simulations of a Nozzle for the Treatment of Ocular Tumors with High-Energy Proton Beams

Purpose: To develop a Monte Carlo simulation model for ocular proton beam therapy, validate its predictions with measurements, and commission an ocular treatment planning system using simulated proton beam data. Method and Materials: We commissioned the EYEPLAN ocular treatment planning system for protonradiotherapy using only dosimetric data from Monte Carlo simulations. The commissioning comprised two main tasks: generating nozzle‐specific parameters and dose profiles and entering them into the treatment planning system, and testing the accuracy of the planning system's dose predictions under various beam conditions that are representative of ocular melanoma treatments. The MCNPXMonte Carlo simulation code was used with a detailed, 3‐dimensional model of an ocular beamline. Simulations were carried out to generate both input dose distributions for the treatment planning system as well as validation data to test the accuracy of the TPS predictions. The simulation model was benchmarked against measured dose distribution from Harvard Cyclotron Laboratory (Cambridge) and the Northeast Proton Therapy Center (Boston). Measurements were made with ionization chambers, diodes, and radiographic film. Results: Benchmark comparisons revealed maximum differences between absorbed dose profiles from simulations and measurements of 6% and 0.6 mm, while typical differences were less than 2% and 0.2 mm. The computation time for the entire virtual commissioning process is less than one day. Conclusion: The study revealed that, after a significant development effort, a Monte Carlo model of a proton therapy apparatus is sufficiently accurate and fast for commissioning a treatment planning system. With relatively little additional effort, additional capability can be added to the model, such as the prediction of output factors.
The Evolution of Happiness

The authors reveal a dramatic but previously unsuspected pattern in archaeological illustration: the presence of smiling faces composed of artifacts arranged in plates of archaeological illustrations and photographs. In this paper, we explore the possible meanings that lurk behind and emerge from these mysterious portraits, questioning whether they are byproducts of human agency or whether, instead, they represent new examples of how material objects act back on (or “interfere with”) human agency.
Erosion of cohesive sediments as a rate process

Abstract The problems associated with the erosion of cohesive sediment in the marine environment are well recognized. However, the mechanisms of controlling erosion are not well understood. The research to be presented was directed at characterizing the erosion resistance of cohesive sediment through the application of rate process and double layer theories. Additionally, relationships between erodability and temperature, salinity, pore water content and erosional shear stress were studied. A total of 50 tests were conducted in a refrigerated water tunnel. These included tests in which temperature was incremented at constant erosional shear stress and tests within which the erosional stress was varied at constant temperature. The material tested was a remoulded illitic-silt (Grundite). Tests were performed at constant pH and at five different water contents ranging from 40 to 80%. For each water content, samples were tested at five different salinities varying from 0 to 10% NaCl. Results are as follows: (1) the erosional response of cohesive sediments can be described with rate process and double layer throries, (2) the magnitude of experimental activation energies suggest solid-to-solid bonding and are essentially independent of salinity and water content, (3) experimental flow volumes were essentially invariant with water content, but decreased with salinity in accordance with the double layer theory, which suggest that the dominant interparticle forces in surface cohesive erosion are physico-chemical rather than mechanical.
Twenty-five years of pioneering accomplishments by CINDAS—A retrospective review

A brief presentation is given on the establishment and history of the Center for Information and Numerical Data Analysis and Synthesis (CINDAS), along with the scope of its activities and accomplishments. In line with the Center's prime involvement, special emphasis is given to the existence of discord in numerical data in the literature, and the role of critical data analysis and synthesis is provided through illustrations. Statistical data are presented showing the growth of the literature on thermophysical properties between 1780 and 1980.
Aptamer sandwich assays: label-free and fluorescence investigations of heterogeneous binding events

We studied aptamer binding events in a heterogeneous format using label-free and fluorescence measurements for the purpose of developing an aptamer-based sandwich assay on a standard microtiter plate platform. The approach allowed visualization of the underlying aptamer immobilization and target binding events rather than relying on only an endpoint determination for method optimization. This allowed for a better understanding of these multi-step assays and optimal conditions specific to aptamers. α-thrombin was chosen as a prototypical analyte as two well-studied aptamers (15 and 29-mer) binding distinct epitopes are available. The Corning Epic® system, which utilizes a resonance waveguide diffraction grating in a 384-well microtiter plate format, was employed to measure relative immobilization and binding levels for various modified aptamers. Parameters investigated included the effects of aptamer orientation, label orientation, spacer length, spacer type, immobilization concentration, and binding buffer. Most notably, the 15-mer aptamer was preferable for capture over the 29-mer aptamer and aptamers with increasing poly(dT) spacer length between the biotin modification and the aptamer yielded decreased immobilization levels. This decreased immobilization resulted in increased α-thrombin binding ability for 15-mer aptamers with the poly(dT) spacer. Fluorescence measurements of fluorescein-labeled 29-mer aptamers with varying spacers were used to visualize sandwich complex formation. Using both label-free and traditional fluorescence measurements, an in-depth understanding of the overall assay was obtained, thus the inclusion of label-free measurements is recommended for future method development.
On the optimality of the (S — 1,S) policy

The one-for-one (S - 1,S) inventory policy, which calls for a replenishment order after each demand equal in magnitude to the size of the demand, is often advocated for controlling the stock levels of expensive, slow-moving items. In particular, this policy has frequently been promoted for use in recoverable-item inventory systems. An important managerial question is: When is the (S - 1,S) policy optimal? Results in this article provide guidance for the selection of this policy. Conditions under which it is not economical to batch demands are developed, provided the renewal function of the renewal process of demand sizes is concave. This includes the important case of unit-sized demands. The inventory system considered is one with continuous review, constant lead times, general interarrival and discrete demand distributions, complete backlogging, and linear holding and penalty costs per unit per unit time. Examples are given for the special case when the demand process is Poisson and when the demand process is a particular compound Poisson distribution known as the stuttering Poisson distribution.
Strategic Differences in Mental Rotation Tasks Based on Gaze Durations

The objective of this study is to investigate whether strategy differences in mental rotation performance can be explained using gaze durations collected from an eye tracker. To investigate this, 36 participants were administered an electronic version of the Purdue Spatial Visual Test: Rotation. Three questions (out of 30) were selected based on the overall response accuracy to represent an easy, moderately difficult, and difficult question. Participants were then segmented into two groups (high accuracy and low accuracy) based on test scores. Significant interaction effects between the groups and the five possible choices were observed for the gaze durations of each question (easy: F(4,170) = 9.05, p < 0.0001; moderately difficult: F(4,170) = 41.12, p < 0.0001; difficult: F(4,170) = 2.89, p< 0.05). The gaze durations of the high accuracy group were primarily skewed towards one of the five potential response choices suggesting a holistic approach. For the low accuracy group, an analytic approach appears l...
The aromatic binding site for tetraethylammonium ion on potassium channels

K+ channels are quite variable in their sensitivity to the pore-blocking agent tetraethylammonium ion (TEA) when it is applied to the extracellular side of the membrane. A Shaker K+ channel can be made highly sensitive by introducing a tyrosine (or phenylalanine) at residue 449 in each of the four subunits. A shift in the voltage dependence of blockade indicates that TEA senses a smaller fraction of the transmembrane electric field in the highly sensitive channels. There is a linear relationship between the free energy for TEA blockade and the number of subunits (zero, two, or four) containing tyrosine at 449, as if these four residues interact simultaneously with a TEA molecule to produce a high affinity binding site. The temperature dependence of blockade suggests that the interaction is not purely hydrophobic. These findings are consistent with a TEA-binding site formed by a bracelet of pore-lining aromatic residues. The center of the bracelet could bind a TEA molecule through a cation-pi orbital interaction.