Miracle-dz/UniFAR-FTUs huggingface dataset:
Modulation of EGF receptor-mediated vulva development by the heterotrimeric G-protein Gαq and excitable cells in C. elegans

The extent to which excitable cells and behavior modulate animal development has not been examined in detail. Here, we demonstrate the existence of a novel pathway for promoting vulval fates in C. elegans that involves activation of the heterotrimeric Gαq protein, EGL-30. EGL-30 acts with muscle-expressed EGL-19 L-type voltage-gated calcium channels to promote vulva development, and acts downstream or parallel to LET-60 (RAS). This pathway is not essential for vulval induction on standard Petri plates, but can be stimulated by expression of activated EGL-30 in neurons, or by an EGL-30-dependent change in behavior that occurs in a liquid environment. Our results indicate that excitable cells and animal behavior can provide modulatory inputs into the effects of growth factor signaling on cell fates, and suggest that communication between these cell populations is important for normal development to occur under certain environmental conditions.
Bupropion in Parkinson's disease

Bupropion is an antidepressant, thought to be an indirect dopaminergic agonist. No significant sympathomimetic, anticholinergic, or MA0 inhibitor effects have been reported. We evaluated this drug in 20 patients with idiopathic Parkinson's disease. Parkinsonism lessened by at least 30% (Northwestern University Disability Scale or Modified New York University Parkinson's Disease Scale) in half the patients. Depression, present in 12 of 20, was alleviated in only 5. Bupropion is mildly efficacious in Parkinson's disease, although side effects were frequent and were dose-limiting in five patients.
Human Immunodeficiency Virus Type 1 Recombinant Reverse Transcriptase Enzymes Containing the G190A and Y181C Resistance Mutations Remain Sensitive to Etravirine

ABSTRACT Etravirine (ETR) is a second-generation nonnucleoside reverse transcriptase (RT) inhibitor (NNRTI) active against common human immunodeficiency virus type 1 (HIV-1) drug-resistant strains. This study was designed to determine the extent to which each of the Y181C or G190A mutations in RT might confer resistance to ETR and other members of the NNRTI family of drugs. Recombinant HIV-1 RT enzymes containing either the Y181C or the G190A mutation, or both mutations in tandem, were purified. Both RNA- and DNA-dependent DNA polymerase assays were performed in order to determine the extent to which each of these mutations might confer resistance in cell-free biochemical assays against each of ETR, efavirenz, and nevirapine. Both the biochemical and the cell-based phenotypic assays confirmed the susceptibility of G190A-containing enzymes and viruses to ETR. The results of this study indicate that the G190A mutation is not associated with resistance to ETR.
Class-D Audio Amplifiers with Negative Feedback

There are many different designs for audio amplifiers. Class-D, or switching, amplifiers generate their output signal in the form of a high-frequency square wave of variable duty cycle (ratio of on time to off time). The square-wave nature of the output allows a particularly efficient output stage, with minimal losses. The output is ultimately filtered to remove components of the spectrum above the audio range. Mathematical models are derived here for a variety of related class-D amplifier designs that use negative feedback. These models use an asymptotic expansion in powers of a small parameter related to the ratio of typical audio frequencies to the switching frequency to develop a power series for the output component in the audio spectrum. These models confirm that there is a form of distortion intrinsic to such amplifier designs. The models also explain why two approaches used commercially succeed in largely eliminating this distortion; a new means of overcoming the intrinsic distortion is revealed by the analysis. Copyright (2006) Society for Industrial and Applied Mathematics
Early Life Public Health Intervention and Adolescent Cognition : Evidence from the Safe Motherhood Program in Indonesia

Between 1990 and 1996, over 54,000 midwives were introduced in most of Indonesia’s nonmetropolitan villages as part of its safe motherhood strategy. I combine the variation in the availability and timing of the program arrival with the biology of cognition and the panel dimension of Indonesia Family Life Survey to carefully examine the long run impact of the program on cognition. In addition, I also examine program impacts on measures of schooling. The paper empirically tests and corroborates the findings in the biological literature that the fetal period and the first two years of life are critical periods in brain development during which environmental influences could have persistent effects on cognitive development. In addition, the results also support recent biological findings that show the importance of maternal health and nutritional status prior to conception for child’s long term development. ∗I am grateful to Elizabeth Frankenberg, Amar Hamoudi, John Strauss, Alessandro Tarozzi, Duncan Thomas, and Jacob Vigdor as well as to the participants of 2011 NEUDC and Duke Economics Development Lunch seminar, particularly Ryan Brown and Dan LaFave for helpful comments and suggestions. This work is supported by International Institute for Education/Hewlett Foundation Dissertation Fellowship Program, the Population Reference Bureau Fellows Program and partly by World Bank (Indonesia). All opinions and errors are mine. Please direct correspondence to: ava.cas@duke.edu.
Period Doubling Route to Chaos in a RLD Circuit

Using a function generator to drive a circuit consisting of a resistor, inductor, and diode, the period doubling route to chaos was observed. Through varying the frequency of the function generator at a constant voltage, both chaotic and periodic regimes were found. By determining the frequencies at which period bifurcations occurred and averaging the results of several trials, the Feigenbaum constant δ was determined to be 4.6± 0.3, which is within 1.5% of the known value.
Maturational differences between vascular and bladder smooth muscle during ovine development.

Maturation rates of vascular and visceral smooth muscle (SM) during ovine development were compared by quantifying contractile protein, myosin heavy chain (MHC) isoform contents, and contractile properties of aortas and bladders from female fetal (n = 19) and postnatal (n = 21) sheep. Actin, myosin, and protein contents rose progressively throughout development in both tissues (P </= 0.003); however, expression patterns differed. During the last trimester, i. e. , 101-130 days (term approximately 145 days), bladder actin and MHC contents were approximately twofold greater (P < 0.04) than those in the aorta. Although the fractional content of 204-kDa SM1 MHC in the bladder decreased from 74 +/- 3% at midgestation to 48 +/- 2% 3 mo postnatal, the aorta exhibited an increase from 30 +/- 2% to 65 +/- 2%. Bladder MHC (MHC-B) migrating at 200 kDa contained only SM2 throughout development. In contrast, 200-kDa MHC in the aorta was predominantly nonmuscle MHC-B at midgestation, which was gradually replaced by SM2 as development progressed. Along with its early expression of SM2, bladder muscle obtained maximal stress generating capacity (1.7 x 10(5) N/m(2)) by term gestation, whereas the aorta exhibited no contractions until after birth. We conclude that whereas aortic SM maturation is delayed until after birth, bladder SM matures biochemically and functionally during prenatal development, thus supporting early requirements for micturition.
Effects of cigarette smoke exposure and its cessation on body weight, food intake and circulating leptin, and ghrelin levels in the rat.

INTRODUCTION Smoking is associated with loss of body weight (BW) and reduced appetite, while smoking abstinence with the opposite effect. The role of peripheral signaling by appetite-controlling hormones leptin and ghrelin is not clear. In the present study, the relationship of circulating leptin and ghrelin with BW and food intake rate (FIR) changes was studied during cigarette smoke exposure (CSE) and after its cessation in the rat. METHODS Male Wistar rats were subjected to CSE for 8 weeks by confinement to plexiglass chambers (Group S). Control animals were confined to identical chambers without smoke (Group C). During CSE and an equivalent follow-up period, BW and FIR was recorded and serum leptin and ghrelin levels were measured. RESULTS A sharp decrease in BW was noted during the first 4 weeks of CSE, while FIR, after a substantial decrease noted at Week 1, returned to control levels. Thereafter, rats started to regain their BW until they reached control levels by the 1st week postCSE. BW regain was accompanied by a rebound increase of FIR, which plateaued during the first 4 weeks postCSE and then normalized. Serum leptin was decreased in Group S during both periods, normalizing at the 7th week postCSE. Ghrelin levels did not differ between groups. CONCLUSIONS Circulating leptin could not explain by its own BW and FIR changes during the first few week of CSE in rats, in contrast to the rest of the CSE period as well as after its cessation. Serum ghrelin levels did not justify BW and FIR changes.
Influences of soil acidity on Streptomyces populations inhabiting forest soils

The Streptomyces populations inhabiting five acidic forest soils were examined. It was found that lowering the pH of a medium selective for streptomycetes (starch-casein agar) to the pH of the particular soil horizon being plated influenced both the total numbers and types of streptomycetes that were isolated from the soils examined in this study. On the acidified medium both the numbers of streptomycetes and the percentage of total bacteria on the plates represented by streptomycetes increased (as compared with the same medium with a pH of 7.2). These differences were greatest on the isolations from the most acid soils. The largest concentrations of streptomycetes were found in the surface horizon (0 to 15 cm) and the litter layer immediately over the surface mineral horizon. Acidity tolerance tests demonstrated that random samplings of isolates contained acidophilic, neutrophilic, and acidoduric strains, with the largest numbers of acidophiles being found on the acidified media from the most acid soils. There were no differences between overall utilization of selected carbohydrates among the isolates taken from either the neutral or acidic media, although a larger proportion of the acid media isolates produced acid from the carbohydrates. Evidence is presented which indicates that different types of streptomycetes were isolated on the acid media, and possible reasons for the presence of these acid-tolerant populations are discussed.
Supracondylar fractures of the humerus in children. Technique and results of crossed percutaneous K-wire fixation.

Displaced extension type supracondylar fractures of the humerus are associated with neurovascular injuries and malunion (cubitus varus). Reduction is not usually difficult during the first few hours, but it is a problem to maintain. After reduction, the shoulder is placed in abduction external-rotation with the elbow flexed under the C-arm. This position locks the proximal segment of the fracture, and the posteromedially rotated distal segment can then be brought back into an anatomic position under the "medial pillar. " In this position, an excellent lateral view is obtained and the "fish tail" deformation can be corrected. Crossed percutaneous K-wires are introduced to maintain reduction. An anteroposterior radiograph can then be freely obtained, and there is no need for hyperflexion at the elbow. Twenty-six children were treated between 1987 and 1992. Excellent results were obtained.
Bicuculline Infusions Advance the Timing of Luteinizing Hormone Surge in Proestrous Rats: Comparisons with Naloxone Effects

The role of GABA neurons in the control of the surge of LH secretion was investigated by examining whether GABAA receptor antagonist bicuculline (BIC) infusion prior to the LH surge could advance the timing of the proestrous surge in the rat. The effect of the opioid receptor antagonist naloxone (NAL) was also examined for comparison. Female rats in proestrus were iv infused with NAL (2 or 5 mg/hr) or BIC (50 mg/kg/hr) for a 3-hr (1000-1300 hr) period during which blood samples were collected at 6-min intervals through an intraatrial cannula in freely moving rats. The animals that received infusion were bled again over a 7-hr period (1400-2000 hr) at 1-hr intervals. NAL infusions at 2 mg/hr induced an increase in pulsatile LH secretion, but did not affect the timing, magnitude, and duration of the LH surge. NAL infusions at 5 mg/hr not only induced a greater increase in pulsatile LH secretion but also resulted in a pronounced LH surge prematurely. In contrast, during BIC infusion, no significant changes in LH secretion were seen until 1200 hr, but afterward a rapid and sharp rise in LH secretion occurred, suggesting the premature LH surge. These results are consistent with the hypothesis that the tonic LH secretion is sensitive to NAL, but not to BIC, whereas the surge of LH secretion is sensitive to barbiturates that have been known as the activator of GABAA receptor complex. Therefore, we suggest that there is a LHRH surge generator, distinct from the pulse generator, in the brain, and it has GABA neurons in its circuitry.
Coping with Crises: The Management of Disasters, Riots and Terrorism

The editors of Coping with Crises look for similarities among such diverse events as natural disasters, industrial accidents, acute social conflicts, riots, and terrorist hostage takings. They argue that all of these seemingly different events are crises because each of them confronts organizational decision makers with a threatening situation that demands urgent decisions under conditions of uncertainty. Rosenthal, Charles, and 't Hart contend that decision makers respond to these different crises in remarkably similar ways. By comparing across this collection of case studies, the editors also attempt to identify patterns in decision making that precipitate crisis development. The strength of this book is in its individual case studies; they provide a concise and interdisciplinary introduction to crisis research. However, the editors set themselves a difficult task in searching for the regularities that order such a diverse array of crises. Their search for the common characteristics of crisis decision making is hampered both by their choice of an overly diverse collection of crisis studies and by the lack of a consistent, comprehensive analytic framework.
Prevalence and molecular characterisation of the sessile serrated adenoma in a subset of the Chinese population

Aims The incidence and mortality rates from right-sided colorectal cancers (CRCs) have not decreased in recent years. It is very likely that a significant proportion of these cancers evolve from undetected sessile serrated adenomas (SSAs). The prevalence and molecular features of the SSAs in the Chinese population have seldom been investigated. Methods We retrospectively reviewed the colonoscopy database and pathology archives in our medical centre. Adenomatous polyposis coli (APC) and β-catenin expressions were examined in 28 right hyperplastic polyps (RHPs) and 21 SSAs by immunohistochemical staining. The mutations of BRAF, KRAS, APC and β-CATENIN were analysed by direct sequencing. The methylation status of APC promoter in these polyps was analysed by methylation-specific PCR and bisulfite sequencing. Samples of left hyperplastic polyps, traditional adenomas and CRC were used as controls. Results SSAs accounted for 4.9% of serrated polyps and 1.0% of all colorectal polyps. BRAF(V600E) mutations were found in 14.3% of SSAs and 7.1% of RHPs. Nuclear accumulation of β-catenin was seen in 28.6% of SSAs and 17.9% of RHPs. APC mutations were detected in 57.1% of SSAs and 67.9% of RHPs. APC methylation was detected in 14.3% of RHPs and 23.8% of SSAs. Conclusions The prevalence of SSAs in a subset of the Chinese population is much lower than that in the Western population. BRAF(V600E) mutation is not a frequent event in right colon serrated polyps in a subset of the Chinese population. APC mutation is possibly the main cause for the Wnt signalling activation in right colon serrated polyps.
Probabilistic Paths and Centrality in Time

Traditionally, graph centrality measures such as betweenness centrality are applied to discrete, static graphs, where binary edges represent the ‘presence’ or ‘absence’ of a relationship. However, when considering the evolution of networks over time, it is more natural to consider interactions at particular timesteps as observational evidence of the latent (i.e., hidden) relationships among entities. In this formulation, there is inherent uncertainty about the strength of the underlying relationships and/or whether they are still active at a particular point in time. For example, if we observe an email communication between two people at time t, that indicates they have an active relationship at t, but at time t + k we are less certain the relationship still holds. In this work, we develop a framework to capture this uncertainty, centered around the notion of probabilistic paths. In order to model the effect of relationship uncertainty on network connectivity and its change over time, we formulate a measure of centrality based on most probable paths of communication, rather than shortest paths. In addition to the notion of the relationship strength, we also incorporate uncertainty with regard to the transmission of information using a binomial prior. We show that shortest paths in a unweighted, discrete graph can be formulated using probabilistic paths with a prior and we develop an algorithm to compute the most likely paths in O ` |V ||E| + |V | 2 log |V | ´ . We demonstrate the effectiveness of our approach by computing probabilistic betweenness centrality over time in the the Enron email dataset.
Neuronal cotransport of glycine receptor and the scaffold protein gephyrin

The dynamics of postsynaptic receptor scaffold formation and remodeling at inhibitory synapses remain largely unknown. Gephyrin, which is a multimeric scaffold protein, interacts with cytoskeletal elements and stabilizes glycine receptors (GlyRs) and individual subtypes of γ-aminobutyric acid A receptors at inhibitory postsynaptic sites. We report intracellular mobility of gephyrin transports packets over time. Gephyrin units enter and exit active synapses within several minutes. In addition to previous reports of GlyR–gephyrin interactions at plasma membranes, we show cosedimentation and coimmunoprecipitation of both proteins from vesicular fractions. Moreover, GlyR and gephyrin are cotransported within neuronal dendrites and further coimmunoprecipitate and colocalize with the dynein motor complex. As a result, the blockade of dynein function or dynein–gephyrin interaction, as well as the depolymerization of microtubules, interferes with retrograde gephyrin recruitment. Our data suggest a GlyR–gephyrin–dynein transport complex and support the concept that gephyrin–motor interactions contribute to the dynamic and activity-dependent rearrangement of postsynaptic GlyRs, a process thought to underlie the regulation of synaptic strength.
Abnormal Pitch Perception Produced by Cochlear Implant Stimulation

Contemporary cochlear implants with multiple electrode stimulation can produce good speech perception but poor music perception. Hindered by the lack of a gold standard to quantify electric pitch, relatively little is known about the nature and extent of the electric pitch abnormalities and their impact on cochlear implant performance. Here we overcame this obstacle by comparing acoustic and electric pitch perception in 3 unilateral cochlear-implant subjects who had functionally usable acoustic hearing throughout the audiometric frequency range in the non-implant ear. First, to establish a baseline, we measured and found slightly impaired pure tone frequency discrimination and nearly perfect melody recognition in all 3 subjects’ acoustic ear. Second, using pure tones in the acoustic ear to match electric pitch induced by an intra-cochlear electrode, we found that the frequency-electrode function was not only 1–2 octaves lower, but also 2 times more compressed in frequency range than the normal cochlear frequency-place function. Third, we derived frequency difference limens in electric pitch and found that the equivalent electric frequency discrimination was 24 times worse than normal-hearing controls. These 3 abnormalities are likely a result of a combination of broad electric field, distant intra-cochlear electrode placement, and non-uniform spiral ganglion cell distribution and survival, all of which are inherent to the electrode-nerve interface in contemporary cochlear implants. Previous studies emphasized on the “mean” shape of the frequency-electrode function, but the present study indicates that the large “variance” of this function, reflecting poor electric pitch discriminability, is the main factor limiting contemporary cochlear implant performance.
Legionella contamination of dental-unit waters

Water samples collected from 28 dental facilities in six U.S. states were examined for the presence of Legionella pneumophila and other Legionella spp. by the PCR-gene probe, fluorescent-antibody microscopic, and viable-plate-count detection methods. The PCR and fluorescent-antibody detection methods, which detect both viable and viable nonculturable Legionella spp. , gave higher counts and rates of detection than the plate count method. By the PCR-gene probe detection method, Legionella spp. were detected in 68% of the dental-unit water samples and L. pneumophila was detected in 8%. Concentrations of Legionella spp. in dental-unit water reached 1,000 organisms per ml or more in 36% of the samples, and 19% of the samples were in the category of 10,000/ml or above. L. pneumophila, when present in dental-unit water, never reached concentrations of 1,000/ml or more. Microscopic examination with fluorescent-antibody staining indicated that the contamination was in the dental-unit water lines rather than in the handpieces. Legionella spp. were present in 61% of potable water samples collected for comparative analysis from domestic and institutional faucets and drinking fountains; this percentage was not significantly different from the rate of detection of Legionella spp. in dental-unit water. However, in only 4% of the potable water samples did Legionella spp. reach concentrations of 1,000 organisms per ml, and none was in the 10,000 organisms-per-ml category, and so health-threatening levels of Legionella spp. in potable water were significantly lower than in dental-unit water. L. pneumophila was found in 2% of the potable water samples, but only at the lowest detectable level. (ABSTRACT TRUNCATED AT 250 WORDS)