cssi/SciSciGPT-SciSciNet huggingface dataset:
Epibatidine Activates Muscle Acetylcholine Receptors with Unique Site Selectivity

Abstract We recently showed that at desensitized muscle nicotinic receptors, epibatidine selects by 300-fold between the two agonist binding sites. To determine whether receptors in the resting, activatible state show similar site selectivity, we studied epibatidine-induced activation of mouse fetal and adult receptors expressed in 293 HEK cells. Kinetic analysis of single-channel currents reveals that (−)-epibatidine binds with 15-fold selectivity to sites of adult receptors and 75-fold selectivity to sites of fetal receptors. For each receptor subtype, site selectivity arises solely from different rates of epibatidine dissociation from the two sites. To determine the structural basis for epibatidine selectivity, we introduced mutations into either the γ or the δ subunit and measured epibatidine binding and epibatidine-induced single-channel currents. Complexes formed by α and mutant γ (K34S+F172I) subunits bind epibatidine with increased affinity compared to αγ complexes, whereas the kinetics of α 2 βδγ (K34S+F172I) receptors reveal no change in affinity of the low-affinity site, but increased affinity of the high-affinity site. Conversely, complexes formed by α and mutant δ (S36K+I178F) subunits bind epibatidine with decreased affinity compared to αδ complexes, whereas the kinetics of α 2 βγδ (S36K+I178F) and α 2 β ϵ δ (S36K+I178F) receptors show markedly reduced sensitivity to epibatidine. The overall data show that epibatidine activates muscle receptors by binding with high affinity to αγ and α ϵ sites, but with low affinity to the αδ site.
TU-A-WAB-06: Evaluation of Articulated Registration and Application to Metastatic Bone Lesions Identification

Purpose: Accurate skeleton registration is required to identify corresponding metastatic bone lesions over multiple scans to assess therapeutic responses of individual lesions. In articulated registration, whole‐body skeletons are registered by auto‐segmenting individual bones, then rigidly aligning them. We evaluated if articulated registration outperforms other registration algorithms in skeleton registration and lesion identification. Methods: Six prostate cancer patients with 128 total bone lesions were treated with molecular targeted therapy. Serial whole‐body [18F]NaF PET/CT images were acquired throughout treatment. Skeletons were extracted from the CT images by thresholding (HU>150). Serial skeletons were registered using rigid, deformable, and articulated registration algorithms. The registration performance was quantified as the overlapped volume (OV) of the registered skeletons. The corresponding lesions were contoured and identified on serial PET images under the guidance of a nuclear medicine physician. Each algorithm was evaluated for its ability to accurately align corresponding lesions via skeleton registration. A lesion matching score (LMS) was measured for each lesion, which quantified the percent overlap between a lesion's two corresponding contours. Results: Articulated (OV=90+/–1%) and deformable registration algorithms (OV=90+/–1%) outperformed rigid registration algorithm (OV=50+/–7%) in the skeleton registration as the rigid registration algorithm failed to capture the skeleton flexibility in the joints. The performance of articulated registration (LMS=75+/–23%) in lesion identification was also significantly better than rigid (LMS=59+/–32%, p=0.018) and deformable (LMS=46+/–39%, p=0.0003) registration algorithms. Despite superior skeleton registration performance, deformable registration algorithm failed to preserve the local rigidity of bones leading to undesirable lesion deformation and poor performance in lesion identification, leaving articulated registration as the best choice. Conclusion: Articulated registration is superior to rigid and deformable registrations by capturing global flexibility while preserving local rigidity inherent in skeleton registration. Articulated registration facilitates treatment response assessment of individual bone lesions by potentially reducing physician workload and error in lesion identification throughout treatment.
Large-scale computation of pediatric growth percentiles with fuzzy logic justification of parameter selection

The electronic health record is now becoming a hot topic in the medical community largely owing to the rapid advances in both information technology and emerging personalized medicine. In pediatric research and clinical care, an important issue is to find the physical growth percentiles. Prior to the advent of electronic medical records, height and weight were measured and manually plotted on the growth charts for a rough estimate. In research, especially population studies, circumstances often arise that require large-scale clinical computation, which is not yet satisfactorily solved. This paper implements a fast approximate method to enable large-scale percentile computation available online. Additionally, the fuzzy logic approach is presented to justify the parameter selection.
A MicroRNA Gene is Hosted in an Intron of a Schizophrenia-susceptibility Gene

Schizophrenia (SZ) is a neuropsychiatric disorder that affects about 1% of the adult population. Numerous genes have been implicated in SZ susceptibility. MicroRNAs (miRNA) are small RNA molecules that regulate the translation of mRNAs via interactions with their 3' untranslated regions. Identification of known miRNA targets on all human genes indicated that miRNA-346 targets SZ susceptibility genes listed in the SchizophreniaGene database twice as frequently as expected relative to other genes in the genome. The gene encoding this miRNA, miR-346, is located in intron 2 of the glutamate receptor ionotropic delta 1 (GRID1) gene, which has been previously implicated in SZ susceptibility. We used quantitative real-time PCR to determine the expression levels of miR-346 and GRID1 using brain RNA samples from the Stanley Array Collection, Stanley Medical Research Institute. Expression of both miR-346 and GRID1 is lower in SZ patients than that in normal controls (P=0.017 and 0.086, respectively). However, the expression of miR-346 and GRID1 is less correlated in SZ patients than in bipolar patients or in normal controls. This study implicates the importance of a miRNA in SZ.
Effects of hexavalent and trivalent chromium on the reproduction of Neanthes arenaceodentata (polychaeta)

Abstract This study compared the very different responses of the polychaete Neanthes arenaceodentata to chronic exposure of hexavalent (Cr VI) and trivalent (Cr III) chromium. The polychaetes were exposed to sublethal concentrations of Cr VI and Cr III for periods of 440 days (three generations) and 293 days (two generations), respectively. In the Cr VI test, polychaete reproduction ceased at 100 μg litre−1, and the number of young produced was reduced at the 12·5 to 50 μg litre−1 levels and above. However, polychaetes that lived in Cr III during the test showed no adverse effects in 50400 μg litre−1.
Herpes Simplex Virus Hepatitis after Solid Organ Transplantation in Adults

Twelve patients developed herpes simplex (HSV) hepatitis a median of 18 days after solid organ transplantation. This is earlier than cytomegalovirus hepatitis, which usually occurs 30-40 days after transplantation. Eight recipients (67%) died, and in seven, the diagnosis was made at autopsy or less than 48 h before death. Clinical manifestations associated with mortality were hypotension, disseminated intravascular coagulation (DIC), metabolic acidosis, gastrointestinal bleeding, and bacteremia. Laboratory abnormalities at diagnosis associated with mortality were high creatinine, low platelet counts, prolonged partial thromboplastin time, and a high percentage of band forms on the blood smear. Disseminated HSV disease was noted in four of six patients who had an autopsy and included involvement of lungs in three and the gastrointestinal tract in three. Five recipients developed DIC and all died. Pathologically, HSV hepatitis has two forms, focal and diffuse. All three patients with diffuse liver pathology died. However, three of seven with focal liver pathology survived with antiviral therapy, which suggests that early diagnosis and treatment may be lifesaving. None of these patients had received prophylactic acyclovir. It is possible that acyclovir prophylaxis may be able to prevent this disease.
Language fantasy approach: A therapeutic intervention by creating myths with children

The Language Fantasy Approach (LFA), originally developed as an approach for reading instruction, is presented here as an effective therapeutic intervention for children who demonstrate fears and who need to improve social skills. The LFA is demonstrated and explained as a three-stage process that involves children creating a myth in which their story characters meet and overcome challenges. A group of three or four children learn to cooperate and gain courage as their story characters work together to deal with monsters and other villains. Children learn to take appropriate risks and to realize the consequences initially in their stories and then in their own lives.
Anticipation for learning, cognition and education

Predictions, desires, or intentions have recently shown to strongly influence behavior, adaptation, and learning. These anticipations influence behavior mediating decision making and action execution as well as attention. Although it is not the future itself that influences the present but the anticipated future states or future properties, the difference to purely stimulus‐driven behavior and learning is highly significant. Recent analyses investigate under which environmental properties which type of anticipatory mechanism is helpful to improve behavior. Vice versa, since anticipatory mechanisms also bias attention, future sensory processing and thus future learning capabilities are immediately influenced by current anticipations. The impact on the understanding of the world, social systems, human learning and understanding, as well as education principles might be immense. The perspective of expectation and purpose as part of the cause in the general case might have been underestimated and requires further investigations and considerations.
Mammalian chemosensory receptors.

Chemosensory receptors are critical for the survival of many mammalian species, and their genes can comprise up to 1% of mammalian genomes. Odorant, taste, and vomeronasal receptors are being discovered and functionally characterized at a rapid pace which has been further accelerated by the availability of the human genome sequence. Five multigene families, consisting of > 1000 genes in the mouse, have been proposed to encode functional chemoreceptors. Although all of the chemoreceptor gene families encode G-protein coupled receptors, they are largely unrelated and uniquely specialized for the processing of different chemosensory modalities. Using members of the families as molecular probes, great insights are being gained into the different organizational strategies used by these sensory systems to encode information in both the periphery and the brain.
Missionaries, Anthropologists, and Human Rights

Missionaries, Anthropologists, and Human Rights. THOMAS H. HEADLAND and DARRELL L. WHITEMAN. eds. Theme issue, Missiology: An International Review24(2). Scottsdale, PA: American Society of Missiology, 1996.157 pp., notes, references cited, contributors.
Measurement of effective oxygen diffusivity in electrodes for proton exchange membrane fuel cells

Abstract This paper describes a novel method to measure directly effective diffusivity in electrodes as a function of temperature and relative humidity (RH) at conditions that are relevant for proton exchange membrane fuel cells (PEMFCs). The efficacy of this method to measure effective oxygen diffusivity ( D O 2 e f f ) is demonstrated with measurements of a series of electrodes of varying the ionomer-to-carbon weight ratio (I/C ratio). The measured D O 2 e f f decreases sharply with increasing I/C ratio from 0.5 to 1.5 at the same RH, and reduces gradually with increasing RH from 0% to 100% at the same I/C ratio. The measured D O 2 e f f is considerably smaller than the calculated one using the Bruggeman correction, indicating the Bruggeman correction drastically underestimates the tortuosity with increasing I/C ratio in PEMFC electrodes.
Photoreceptors of Nrl −/− Mice Coexpress Functional S- and M-cone Opsins Having Distinct Inactivation Mechanisms

The retinas of mice null for the neural retina leucine zipper transcription factor (Nrl −/−) contain no rods but are populated instead with photoreceptors that on ultrastructural, histochemical, and molecular criteria appear cone like. To characterize these photoreceptors functionally, responses of single photoreceptors of Nrl −/− mice were recorded with suction pipettes at 35–37°C and compared with the responses of rods of WT mice. Recordings were made either in the conventional manner, with the outer segment (OS) drawn into the pipette (“OS in”), or in a novel configuration with a portion of the inner segment drawn in (“OS out”). Nrl −/− photoreceptor responses recorded in the OS-out configuration were much faster than those of WT rods: for dim-flash responses tpeak = 91 ms vs. 215 ms; for saturating flashes, dominant recovery time constants, τD = 110 ms vs. 240 ms, respectively. Nrl −/− photoreceptors in the OS-in configuration had reduced amplification, sensitivity, and slowed recovery kinetics, but the recording configuration had no effect on rod response properties, suggesting Nrl −/− outer segments to be more susceptible to damage. Functional coexpression of two cone pigments in a single mammalian photoreceptor was established for the first time; the responses of every Nrl −/− cell were driven by both the short-wave (S, λmax ≈ 360 nm) and the mid-wave (M, λmax ≈ 510 nm) mouse cone pigment; the apparent ratio of coexpressed M-pigment varied from 1:1 to 1:3,000 in a manner reflecting a dorso-ventral retinal position gradient. The role of the G-protein receptor kinase Grk1 in cone pigment inactivation was investigated in recordings from Nrl −/−/Grk1−/− photoreceptors. Dim-flash responses of cells driven by either the S- or the M-cone pigment were slowed 2.8-fold and 7.5-fold, respectively, in the absence of Grk1; the inactivation of the M-pigment response was much more seriously retarded. Thus, Grk1 is essential to normal inactivation of both S- and M-mouse cone opsins, but S-opsin has access to a relatively effective, Grk1-independent inactivation pathway.
Estimating the temporal interval entropy of neuronal discharge

To better understand the role of timing in the function of the nervous system, we have developed a methodology that allows the entropy of neuronal discharge activity to be estimated from a spike train record when it may be assumed that successive interspike intervals are temporally uncorrelated. The so-called interval entropy obtained by this methodology is based on an implicit enumeration of all possible spike trains that are statistically indistinguishable from a given spike train. The interval entropy is calculated from an analytic distribution whose parameters are obtained by maximum likelihood estimation from the interval probability distribution associated with a given spike train. We show that this approach reveals features of neuronal discharge not seen with two alternative methods of entropy estimation. The methodology allows for validation of the obtained data models by calculation of confidence intervals for the parameters of the analytic distribution and the testing of the significance of the fit between the observed and analytic interval distributions by means of Kolmogorov-Smirnov and Anderson-Darling statistics. The method is demonstrated by analysis of two different data sets: simulated spike trains evoked by either Poissonian or near-synchronous pulsed activation of a model cerebellar Purkinje neuron and spike trains obtained by extracellular recording from spontaneously discharging cultured rat hippocampal neurons.
Degradation Kinetics of Hydrogenated Amorphous Silicon: The Effect of Embedded Microcrystallites

We have studied the degradation kinetics of undoped a-Si:H films which contain a significant fraction of silicon microcrystallites. The degradation rate is found to be exceptionally slow in the first stage of degradation, then the defect density follows the “normal” t1/3rate and finally saturates. We present a model which relates this abnormal kinetics to the microcrystallites which are embedded in the amorphous matrix.
Congestion minimization during placement

Typical placement objectives involve reducing net-cut cost or minimizing wirelength. Congestion minimization is the least understood, however, it models routability most accurately. In this paper, we study the congestion minimization problem during placement. First, we show that a global placement with minimum wirelength has minimum total congestion. We show that minimizing wirelength may (and in general, will) create locally congested regions. We test seven different congestion minimization objectives. We also propose a post processing stage to minimize congestion. Our main contribution and results can be summarized as follows. (1) Among a variety of cost functions and methods for congestion minimization (including several currently used in industry), wirelength alone followed by a post processing congestion minimization works the best and is one of the fastest. (2) Cost functions such as a hybrid length plus congestion (commonly believed to be very effective) do not always work very well. (3) Net-centric post-processing techniques are among the best congestion alleviation approaches. (4) Congestion at the global placement level, correlates well with congestion of detailed placement.
Teaching Rhetoric of Health and Medicine to Undergraduates: Citizens, Interdisciplinarity, and Affect

The challenge of improving the position of rhetorical studies of health and medicine within the more established field of health communication suggests something of the perils and possibilities tha...
Cavity perturbation measurement of dielectric and magnetic properties of ferrite materials in microwave frequency range

In this paper, complex permittivity and permeability of three types of YIG specimen and one nickel ferrite have been measured all in demagnetized state. The YIGs under measurement are 99.9% pure YIG (4piMs=1800plusmn5% Gauss), Aluminum-Substituted YIG (4piMs=1000plusmn5% Gauss) and Gadolinium-Substituted YIG (4piMs = 1200plusmn5% Gauss). Nickel ferrite has the magnetic saturation, 4piMs of 5000plusmn5% Gauss. Though quite a few methods have been developed for material permittivity and permeability measurement, the cavity perturbation technique has been implemented to carry out the measurement tasks here due to both simplicity and accuracy reasons.
Variety-Seeking and Time of Day: Why Leader Brands Hope Young Adults Shop in the Afternoon, but Follower Brands Hope for Morning

The relationship between variety-seeking behaviors and the time of day at which choices are made is investigated. It is proposed that more variety-seeking will typically occur during times of day when people are experiencing arousal lows rather than arousal peaks. Two studies support this view. Moreover, it is also shown that the incidence of choice is greater for follower brands during day periods when variety-seeking is heightened, whereas leader brands fare better in periods when variety-seeking is relatively minimal.
Gender equality and the right to health.

Expanding access to health is fundamental to human security and human rights. People who are poor daily face health-related insecurity from food shortages to limited access to drinkable water physical violence or ignorance about disease prevention. In our globalised world the transnational flows of ideas people and new lifestyles but also diseases have created new challenges for those who are already left behind in the journey of human development. The vast majority of them are women. The world must commit to an international health framework that shapes universal access to health care. This framework should include provisions for health education and knowledge sharing as well as north-south technology transfer and negotiations to waiver drug patents. The framework should also emphasise the importance of sexual and reproductive health as an essential step towards the MDGs. (excerpt)
Has Central Tokyo Experienced Uneven Development? An Examination of Tokyo's 23 Ku Relative to America's Largest Urban Centers

: Does uneven development exist within central Tokyo? This study assesses the degree of place stratification by income, population, and private employment among the 23 Ku of Tokyo over the past 30 years. It then compares these levels among the Ku for the 1990s relative to those for New York's five boroughs and among census-defined places within the central counties of Los Angeles, Chicago, and Detroit. It finds that income, population, and private employment growth were more unevenly distributed among the Ku during the 1990s than they were in 1970s and 1980s; this was especially true for population change and income. Additionally, it finds that although the distributions of income and private employment growth among the Ku were noticeably lower than within America's largest urban core counties, population change actually occurred more unevenly among the Ku than in these areas during the 1990s. Therefore, it concludes that the 23 Ku did experience a notable degree of uneven residential development during the 1990s. The study then argues that the development strategies of the Tokyo Metropolitan Government (TMG), which have become increasingly entrepreneurial since the mid-1980s, were the lead catalysts fostering this situation. Its approach, however, was not an attempt to circumvent the central state. In fact, its activities remain tightly nested within the Japanese Capitalist Developmental State. The TMG's recent policymaking represents a Japanized version or offshoot of Harvey and Jessop's entrepreneurial city, which is sanctioned, guided, encouraged, and sometimes even led by the Japanese Government's desire to improve Tokyo's international competitiveness.
Early home environment and retrospective recall: a test for concordance between siblings with and without psychiatric disorders

Case control studies are a reasonably rapid and inexpensive method of developing causal hypotheses concerning the role of early environment on the development of psychiatric pathology. The current study tested an interview designed to assess early home environment on a group of patients with alcoholism or depression, on a control group free of psychiatric disorder, and on close-in-age siblings in each group. Findings demonstrated substantial agreement, suggesting that interviews requiring recall of childhood environment may be reasonably valid; patient status did not appear to influence agreement or, presumably, validity.
Optimal Methods for Power System Operation and Management

This research is aimed at evaluating new advances in optimization and its applications to power system operation and planning. In this paper we present unique methodologies for solving special class of power system problems that are challenged by classical operational research optimization techniques. These methodologies include network reconfiguration and unit commitment (UC) using adaptive dynamic programming (ADP). The ADP method provides optimal reconfiguration to achieve minimum real power losses in the network. It is also used to solve the UC problem as a two-stage optimization problem whereby one stage searches for the optimal solution and the other stage evaluates the objective function of the UC problem. The performance of the proposed schemes developed to highlight new optimization applications to power system operation and management challenges was tested on small-scale power system networks
Fortune favors the ( ): Effects of disfluency on educational outcomes

Previous research has shown that disfluency – the subjective experience of difficulty associated with cognitive operations – leads to deeper processing. Two studies explore the extent to which this deeper processing engendered by disfluency interventions can lead to improved memory performance. Study 1 found that information in hard-to-read fonts was better remembered than easier to read information in a controlled laboratory setting. Study 2 extended this finding to high school classrooms. The results suggest that superficial changes to learning materials could yield significant improvements in educational outcomes.
η, η' mixing and anomalies

We discuss the effects of q, ~' mixing and of the gluon anomaly in the decays q~3n °, q' o3n °, ~¢~y and ~rl' 7. These effects are particularly important for 11' ~ 3n ° in reducing the total rate by about two orders of magnitude from the naive estimate. The decay rates are calculated for various values of the 1], rl' mixing angle (0) and a reasonable fit with experiment is obtained for -20 °~0~ for the 11, analogously for the q'. The mixing between the rl and 11' is characterized by a mixing angle 0 and an analysis based on the Gell-Mann-Okubo quadratic mass formula for broken SU (3) gave an estimate of 0.~ - 10 °. A more recent analysis [ 1 ] allows a value closer to - 20 °. With a view to further testing the above picture, in this paper we will consider decays involving pseudoscalar mesons that are sensitive to the mixing angle, to the gluon anomaly and to the non-vanishing topological charges ( 01 GGI q >, < 01GGI q' ) of the physical q and q' respectively.
Knowledge Transfer for Feature Generation in Document Classification

One important problem in machine learning is how to extract knowledge from prior experience, then transfer and apply this knowledge in new learning tasks. To address this problem, transfer learning leverages information from (supervised) learning on related tasks to facilitate the current learning task. Self-taught learning uses information extracted from (unsupervised) learning on related data. In this paper, we propose a new method for knowledge extraction, transfer and application in classification. We consider document classification where we mine correlation relationships among the words from a set of documents and compile a collection of correlation relationships as prior knowledge. This knowledge is then applied to generate new features for classifying documents in classes/types different from the ones from which we obtain the correlation relationships. Our experiment results show that the correlation-based knowledge transfer helps to reduce classification errors.
Quantitative genetics and the evolution of ontogeny: I. Ontogenetic changes in quantitative genetic variance components in randombred mice

Determination de l'importance relative des effets maternels et des effets genetiques directs sur le developpement de souris ICR
α-Lytic Protease Precursor: Characterization of a Structured Folding Intermediate†

The bacterial alpha-lytic protease (alphaLP) is synthesized as a precursor containing a large N-terminal pro region (Pro) transiently required for correct folding of the protease [Silen, J. L., and Agard, D. A. (1989) Nature 341, 462-464]. Upon folding, the precursor is autocatalyticly cleaved to yield a tight-binding inhibitory complex of the pro region and the fully folded protease (Pro/alphaLP). An in vitro purification and refolding protocol has been developed for production of the disulfide-bonded precursor. A combination of spectroscopic approaches have been used to compare the structure and stability of the precursor with either the Pro/alphaLP complex or isolated Pro. The precursor and complex have significant similarities in secondary structure but some differences in tertiary structure, as well as a dramatic difference in stability. Correlations with isolated Pro suggest that the pro region part of the precursor is fully folded and acts to stabilize and structure the alphaLP region. Precursor folding is shown to be biphasic with the fast phase matching the rate of pro region folding. Further, the rate-limiting step in oxidative folding is formation of the disulfide bonds and autocatalytic processing occurs rapidly thereafter. These studies suggests a model in which the pro region folds first and catalyzes folding of the protease domain, forming the active site and finally causing autocatalytic cleavage of the bond separating pro region and protease. This last processing step is critical as it allows the protease N-terminus to rearrange, providing the majority of net stabilization of the product Pro/alphaLP complex.
Cardiorespiratory Fitness Is Associated With Cognitive Performance in Older But Not Younger Adults

Objectives. Aging is associated with declines in e function and episodic memory. Cardiorespiratory fitness (CRF) has been associated with enhanced executive function in older adults (OA), but the relationship with episodic memory remains unclear. The purpose of the study was to examine the relationship between CRF and cognition in young and OA and whether CRF mitigates age-related cognitive decline. Methods. P articipants completed exercise testing to evaluate CRF (peak VO 2) and neuropsychological testing to assess cognition. Results. In O A, peak VO2 was positively related to executive function, as well as to accuracy on an experimental face– name memory task and visual episodic memory. In young adults (YA), a relationship between peak VO 2 and cognition was not evident. High-fit OA performed as well as YA on executive function measures. On episodic memory measures, YA performed better than high-fit OA, who in turn performed better than low-fit OA. Conclusions. CRF is positi vely associated with executive function and episodic memory in OA and attenuates agerelated cognitive decline. We provide preliminary support for the age-dependence hypothesis, which posits that cognition and CRF relationships may be most readily observed during lifetime periods of significant neurocognitive development.
Factors Affecting Health-Related Quality of Life in Children Undergoing Curative Treatment for Cancer: A Review of the Literature.

Background: Health-related quality of life (HRQoL) is an important measure to evaluate a child’s reported treatment experience. Although there are numerous studies of HRQoL in children undergoing curative cancer treatment, there is limited literature on factors that influence this. Objective: To review published studies that describe the HRQoL and associated factors in children undergoing curative cancer treatment. Method: Full-text publications in English from January 2005 to March 2013 were searched in PubMed, PsychINFO, and CINAHL for children ≤18 years of age undergoing curative cancer treatment. HRQoL-associated factors were categorized as cancer diagnosis, treatment, child, family, and community. Results: Twenty-six studies met the inclusion criteria. The most frequently used generic and cancer-specific instruments were PedsQL (Pediatric Quality of Life Inventory) Generic and PedsQL Cancer, respectively. Cancer diagnosis and treatment were the most frequently identified variables; fewer studies meas...
Bowditch Lecture. Renal afferent inputs to ascending spinal pathways

Studies of renal afferent fibers and their functions have continued since the work of Pines in 1959 (Fiziol. Zh. SSSR Im. I M Sechenova 45: 1339-1347, 1959). The kidney contains mechanoreceptors and chemoreceptors that appear to have two major functions. First, renal mechano- and chemoreceptors evoke a variety of renorenal reflexes, while more global cardiovascular reflexes are primarily evoked by renal mechanoreceptors. A second function of renal afferent fibers is to cause the pain of renal disease. Recent studies suggest that renal afferent fibers may also regulate secretion of vasopressin from the pituitary gland. Substantial evidence indicates that, although most renal afferent fibers enter the spinal cord, their functions depend to a large extent on supraspinal circuitry. Thus our research has focused on defining characteristics of spinal neurons that relay renal information to the brain. In the cat, neurons in the L2-T11 segments with excitatory responses to renal A delta and C fiber input project to the medial medullary reticular formation and to the caudal and rostral ventrolateral medulla. Renal afferent information reaches these cells by way of the least splanchnic nerve and by way of more than one dorsal root. In the monkey spinothalamic neurons in the L3-T10 segments respond to renal nerve stimulation. Excitatory responses predominate, but inhibitory responses occur in L2 and L3. These cells also respond to renal A delta and C fibers. Stimulation of renal mechanoreceptors by occlusion of the ureteropelvic junction or renal vein excites feline spinoreticular neurons. Graded increases in renal vein pressure produce graded increases in cell responses. Activation of renal chemoreceptors increases activity of spinal interneurons. Within the L2-T11 segments, cells responding to ureteral occlusion are located caudally, cells with responses to renal artery occlusion are located rostrally, and cells responding to renal vein occlusion are located in between. The differential locations of cells with these inputs suggests the existence of a coding mechanism for different renal receptor populations. Distention of the renal pelvis is a potent stimulator of primate spinothalamic neurons. These neurons encode renal pelvic pressures in the noxious range and appear to be important in mechanisms of renal pain.
A Keystroke Biometric System for Long-Text Input

A novel keystroke biometric system for long-text input was developed and evaluated for user identification and authentication applications. The system consists of a Java applet to collect raw keystroke data over the Internet, a feature extractor, and pattern classifiers to make identification or authentication decisions. Experiments on over 100 participants investigated two input modes – copy and free-text input – and two keyboard types – desktop and laptop keyboards. The system can accurately identify or authenticate individuals if the same type of keyboard is used to produce the enrollment and questioned input samples. Longitudinal experiments quantified performance degradation over intervals of several weeks and over an interval of two years. Additional experiments investigated the system’s hierarchical model, parameter settings, assumptions, and sufficiency of enrollment samples and inputtext length. Although evaluated on input texts up to 650 keystrokes, we found that input of 300 keystrokes, roughly four lines of text, is sufficient for the important applications described.
Targeted genome and epigenome editing using engineered TALE and CRISPR/Cas9 technologies

The impact of reverse genetics, synthetic biology, and gene therapy has been restricted by the limitations of conventional genetic engineering technologies. To expand the capacity for genetic modification of mammalian cells, we are engineering artificial DNA-binding proteins, including zinc finger proteins, TAL effectors, and CRISPR/Cas9 to regulate and edit endogenous mammalian genes. For example, we have engineered both protein-based and RNA-guided transcriptional activators and repressors targeted to human genes relevant to medicine, science, and biotechnology. Delivery of combinations of transcription factors led to synergistic effects on gene activation and tunable expression levels. This approach recapitulates the previously intractable complexity of natural regulation of mammalian genes that is the product of cooperative actions of many transcription factors. We have also developed novel methods for controlling the activity of these proteins, such as optogenetic regulation of protein dimerization with blue light. Genome-wide analysis of the DNA-binding, gene regulation, and chromatin remodeling of these targeted epigenome modifiers has demonstrated their exceptional specificity. In other studies we have engineered synthetic nucleases to stimulate gene targeting to genomic safe harbor sites. This approach is particularly useful for generating isogenic cell lines. We showed that this method leads to a decrease in the variability of transgene expression within a clonal cell line and between multiple clones relative to conventional techniques. Finally, we have used similar methods to correct mutations causing genetic disease. We engineered synthetic nucleases targeted to the human dystrophin gene that is mutated in Duchenne muscular dystrophy patients. When we delivered these nucleases to cells from patients with this disease, the correct gene reading frame and expression of the functional dystrophin protein were restored in vitro and following cell transplantation in vivo. We further demonstrated that these nucleases were well-tolerated and did not lead to off-target alterations of the exome in several corrected clonal cell populations. Collectively, these studies demonstrate the potential of engineered DNA-binding proteins to enable new approaches in medicine, science, and technology.
Effects of natriuretic peptides and nitroprusside on venous function in trout

Active venous regulation of cardiovascular function is well known in mammals but has not been demonstrated in fish. In the present studies, the natriuretic peptides (NP) rat atrial natriuretic peptide (ANP) and trout ventricular natriuretic peptide (VNP), clearance receptor inhibitor SC-46542, and sodium nitroprusside (SNP) were infused into unanesthetized trout fitted with pressure cannulas in the ventral aorta, dorsal aorta, and ductus Cuvier, and a ventral aorta (VA) flow probe was used to measure cardiac output (CO). In another group, in vivo vascular (venous) capacitance curves were obtained during ANP or SNP infusion. The in vitro effects of NP on vessels and the heart were also examined. ANP, VNP, and SC-46542 decreased central venous pressure (PVen), CO, stroke volume (SV), and gill resistance (RG), whereas systemic resistance (RS) and heart rate (HR) increased. Dorsal aortic pressure (PDA) transiently increased and then fell even though RS remained elevated. ANP decreased mean circulatory filling pressure (MCFP), increased vascular compliance at all blood volumes, and increased unstressed volume in hypovolemic fish. ANP had no direct effect on the heart. ANP responses in vivo were not altered in trout made hypotensive by prior treatment with the angiotensin-converting enzyme inhibitor lisinopril. SNP reduced ventral aortic pressure (PVA), PDA, and RS, increased CO and HR, but did not affect PVen, SV, or RG. SNP slightly decreased MCFP but did not affect compliance or unstressed volume. In vitro, large systemic arteries were more responsive than veins to NP, whereas SNP relaxed both. These results show that, in vivo, NP decrease venous compliance, thereby decreasing venous return, CO, and arterial pressure. Conversely, SNP hypotension is due to decreased RS. This is the first evidence for active regulation of venous capacitance in fish, which probably occurs in small veins or venules. The presence of venous baroreceptors is also suggested.
Abstract 2896: Nanoparticle co-delivery of RNAi and chemotherapy for the treatment of drug-resistant cancers

The emergence of drug resistance has been a critical barrier for effective cancer chemotherapy. Recently, RNA interference (RNAi) has shown promise in suppressing the over-expression of drug resistance-associated proteins such as P-glycoprotein and Prohibitin1, and in treating multidrug resistant cancers through combination with chemotherapy. Nevertheless, the safe and effective delivery of RNAi therapeutics (e.g., siRNA and miRNA) to target cells remains a major hurdle for their clinical applications, and the co-delivery of RNAi and chemotherapeutic agents in a controlled fashion requires specific delivery vehicles. Herein, we present a novel nanoparticle (NP) platform to tackle the challenges associated with the delivery of siRNA and chemotherapeutic drugs, using biodegradable and biocompatible polymers and lipids. The hybrid lipid-polymer NP has a differentially charged hollow core/shell nanostructure which provides the delivery system with three distinct functional features: (i) a positively charged inner hollow core for dense loading of siRNA; (ii) a middle hydrophobic polymer layer for the encapsulation of anti-cancer drugs (e.g., taxanes) and for the controlled release of both siRNA and drug; and (iii) a relatively neutral lipid-polyethylene glycol (PEG) surface to keep the NP stable and prolong its systematic circulation. Moreover, such hybrid NPs can be formulated in a simple and robust way that could facilitate future scale-up. By screening various factors, such as inner cationic lipids, outer PEG chain length, and formulation parameters, the hybrid lipid-polymer NPs show excellent in vitro knockdown efficacy at low doses of siRNA, with greater than 80% luciferase silencing at an siRNA dose of 0.4 pmol (4.0 nM) and ∼ 95% silencing at a dose of 2.0 pmol (20 nM). These NPs can also efficiently reduce the expression of drug resistance-associated proteins (e.g., MDR1 and Prohibitin1), as evidenced by qPCR. Cellular cytotoxicity experiments further confirm that this NP co-delivery strategy can drastically improve the sensitivity of drug-resistant cells to chemotherapy. In addition, these hybrid NPs demonstrate promising in vivo results for co-delivering siRNA and chemotherapeutic drugs to treat drug-resistant cancers. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 2896. doi:1538-7445.AM2012-2896
Can intuition in surgery by learned

Intuition, even at the end of the 20th century, has decisive significance in the field of medicine. Intuition within the medical field is understood to be a type of thinking based on experience, but without conscious recourse to its situations and thought processes; rather, it represents an act without reflection and one determining our medical actions to some extent. It is a cognitive process, an intuitive gain in recognition on the basis of experiential values called up from memory. Intuition is a combination of knowledge, ability, endurance, intellectual abilities, and discoursive methods of recognition, in short, the abilities of an expert. To become an expert, one must go through the stations of surgical training. In these the knowledge is imparted, which leads via decision-making to diagnosis and therapy. Intuition in the sense of the definition as experiential thinking cannot be learnt, but it can be schooled. The prerequisites for this are analytic thinking, expert knowledge, and metacognitive knowledge.
Piecewise Cox models with right-censored data

ABSTRACTWe study a general class of piecewise Cox models. We discuss the computation of the semi-parametric maximum likelihood estimates (SMLE) of the parameters, with right-censored data, and a simplified algorithm for the maximum partial likelihood estimates (MPLE). Our simulation study suggests that the relative efficiency of the PMLE of the parameter to the SMLE ranges from 96% to 99.9%, but the relative efficiency of the existing estimators of the baseline survival function to the SMLE ranges from 3% to 24%. Thus, the SMLE is much better than the existing estimators.
A Bayesian framework for robust Kalman filtering under uncertain noise statistics

In this paper, we propose a Bayesian framework for robust Kalman filtering when noise statistics are unknown. The proposed intrinsically Bayesian robust Kalman filter is robust in the Bayesian sense meaning that it guarantees the best average performance relative to the prior distribution governing unknown noise parameters. The basics of Kalman filtering such as the projection theorem and the innovation process are revisited and extended to their Bayesian counterparts. These enable us to design the intrinsically Bayesian robust Kalman filter in a similar way that one can find the classical Kalman filter for a known model.
Half Scale, Full Engagement: Uniting Art, History and Technology to Teach Patternmaking

We present a project designed to engage freshman students in a beginning patternmaking class using art deco and pochoir fashion art of the late teens and early 1920s, from Gazette du Bon Ton and Vogue. Students used half scale forms to drape silhouettes depicted in these graphic images. Dress forms were custom-made for the project from a 3D body scan. Students learned about the period and patternmaking techniques by examining garments from the period, looking at patternmaking books and Sears catalogs from the period, and lecture/discussion about world history and fashion history. Students created patterns and display models, pinning to the form. Results were positive, with student improvement in judging proportions, understanding body/garment interactions, and learning alternate patternmaking techniques. Students also gained confidence in patternmaking. Use of the half scale forms was successful overall, though students generally found the increased precision needed when working in half scale more difficult.
Peripheral viral challenge triggers hippocampal production of inflammatory proteins

Peripheral viral infections increase seizure propensity and intensity in susceptible individuals. We have modeled this comorbidity by demonstrating that intraperitoneal (ip) injection of the conventional viral mimetic, polyinosinic-polycytidylic acid (PIC), renders the brain hypersusceptible to seizures induced by kainic acid (KA). At the molecular level, the hippocampus, which is the ictal site of KA-induced seizures, exhibits upregulated expression of messages encoding several inflammatory genes. Here, we profiled temporal expression of these genes at the protein level. Briefly, eight-week old female C57BL/6 mice were ip injected with 12 mg/kg of PIC and inflammatory proteins were quantified in the hippocampus and blood by ELISA. We found a robust but transient increase in blood concentration of IL-6, CXCL10, CCL2, CXCL9, CCL7 and CCL12 six hours after PIC challenge. CXCL1, IL1β, TNFα and CXCL2 featured a moderate increase. However, only four chemokines were increased in the hippocampus. CXCL10 showed the highest increase 6-12 h after PIC challenge, and its level dwindled to the baseline by 48 h. CXCL1, CXCl9 and CXCL2 were also transiently elevated but their maximal values were by an order of magnitude lower than the values for CXCL10. These results indicate that CXCL10 is the primary inflammatory protein generated in the hippocampus in response to PIC challenge, and that this chemokine may drive the development of seizure hypersusceptibility. In addition, the hippocampus featured a protracted increase in the levels of anaphylatoxins C3a and C5a, indicating the activation of the complement cascades.
The Consequences of Emotional Labor: Effects on Work Stress, Job Satisfaction, and Well-Being

Although early research suggested that the performance of emotional labor had deleterious effects on workers, recent empirical investigations have been equivocal. The performance of emotional labor appears to have diverse consequences for workers—both negative and positive. Variation in the consequences of emotional labor may be due to the different forms of emotion management involved. There is also evidence that the effects of emotional labor are specified by other work conditions. The effects of two forms of emotional labor on work stress, job satisfaction, and psychological distress—self-focused and other-focused emotion management—are explored using data from a survey of workers in a large organization. Results indicate that both forms of emotional labor have uniformly negative effects on workers, net of work complexity, control, and demands. Emotional labor increases perceptions of job stress, decreases satisfaction, and increases distress. Self-focused emotion management has the most pervasive and detrimental impacts. There is little evidence of interaction effects of work conditions and emotional labor.