Miracle-dz/UniFAR-FTUs huggingface dataset:
79 MECHANISM OF ACTION OF ANTIDEPRESSANTS AND MOOD STABILIZERS

Bipolar disorder (BPD), the province of mood stabilizers, has long been considered a recurrent disorder. For more than 50 years, lithium, the prototypal mood stabilizer, has been known to be effective not only in acute mania but also in the prophylaxis of recurrent episodes of mania and depression. By contrast, the preponderance of past research in depression has focused on the major depressive episode and its acute treatment. It is only relatively recently that investigators have begun to address the recurrent nature of unipolar disorder (UPD) and the prophylactic use of longterm antidepressant treatment. Thus, it is timely that we address in a single chapter the most promising research relevant to the pharmacodynamics of both mood stabilizers and antidepressants. As we have outlined in Fig. 79.1, it is possible to characterize both the course and treatment of bipolar and unipolar disorder in a similar manner. Effective treatments exist for the acute phases of both disorders; maintaining both types of patients on such drugs on a long-term basis decreases the likelihood and intensity of recurrences. Further, because the drugs are given long-term, they produce a cascade of pharmacologic effects over time that are ‘‘triggered’’ by their acute effects. Both classes of psychotropic drugs incur a lag period for therapeutic onset of action, even in the acute phase; therefore, studies during the past two decades have focused on the delayed (subchronic) temporal effects of these drugs over days and weeks. Consequently, it is widely thought that the delayed pharmacologic effects of these drugs are relevant for either the initiation of behavioral improvement or the progression of improvement beyond that initiated by acute pharmacologic actions. The early realization that lithium is effective prophylactically in BPD and
A Three-Dimensional RNA Motif in Potato spindle tuber viroid Mediates Trafficking from Palisade Mesophyll to Spongy Mesophyll in Nicotiana benthamiana[W]

Cell-to-cell trafficking of RNAs plays an important role in coordinating gene expression at the whole-plant level as well as in virus/viroid infection and host defense response. This work identifies a three-dimensional RNA structure motif in a viroid that mediates trafficking between the leaf mesophyll tissues, providing mechanistic insights into trafficking regulation. Cell-to-cell trafficking of RNA is an emerging biological principle that integrates systemic gene regulation, viral infection, antiviral response, and cell-to-cell communication. A key mechanistic question is how an RNA is specifically selected for trafficking from one type of cell into another type. Here, we report the identification of an RNA motif in Potato spindle tuber viroid (PSTVd) required for trafficking from palisade mesophyll to spongy mesophyll in Nicotiana benthamiana leaves. This motif, called loop 6, has the sequence 5′-CGA-3′. 5′-GAC-3′ flanked on both sides by cis Watson-Crick G/C and G/U wobble base pairs. We present a three-dimensional (3D) structural model of loop 6 that specifies all non-Watson-Crick base pair interactions, derived by isostericity-based sequence comparisons with 3D RNA motifs from the RNA x-ray crystal structure database. The model is supported by available chemical modification patterns, natural sequence conservation/variations in PSTVd isolates and related species, and functional characterization of all possible mutants for each of the loop 6 base pairs. Our findings and approaches have broad implications for studying the 3D RNA structural motifs mediating trafficking of diverse RNA species across specific cellular boundaries and for studying the structure-function relationships of RNA motifs in other biological processes.
Integrative Protein-Based Prognostic Model for Early-Stage Endometrioid Endometrial Cancer

Purpose: Endometrioid endometrial carcinoma (EEC) is the major histologic type of endometrial cancer, the most prevalent gynecologic malignancy in the United States. EEC recurrence or metastasis is associated with a poor prognosis. Early-stage EEC is generally curable, but a subset has high risk of recurrence or metastasis. Prognosis estimation for early-stage EEC mainly relies on clinicopathologic characteristics, but is unreliable. We aimed to identify patients with high-risk early-stage EEC who are most likely to benefit from more extensive surgery and adjuvant therapy by building a prognostic model that integrates clinical variables and protein markers. Experimental Design: We used two large, independent early-stage EEC datasets as training (n = 183) and validation cohorts (n = 333), and generated the levels of 186 proteins and phosphoproteins using reverse-phase protein arrays. By applying an initial filtering and the elastic net to the training samples, we developed a prognostic model for overall survival containing two clinical variables and 18 protein markers and optimized the risk group classification. Results: The Kaplan–Meier survival analyses in the validation cohort confirmed an improved discriminating power of our prognostic model for patients with early-stage EEC over key clinical variables (log-rank test, P = 0.565 for disease stage, 0.567 for tumor grade, and 1.3 × 10−4 for the integrative model). Compared with clinical variables (stage, grade, and patient age), only the risk groups defined by the integrative model were consistently significant in both univariate and multivariate analyses across both cohorts. Conclusions: Our prognostic model is potentially of high clinical value for stratifying patients with early-stage EEC and improving their treatment strategies. Clin Cancer Res; 22(2); 513–23. ©2015 AACR.
Do Population Control Policies Induce More Human Capital Investment? Twins, Birthweight, and China's 'One Child' Policy

In this paper we use a new data set describing households with and without twin children in China to quantify the trade-off between the quality and quantity of children using the incidence of twins that for the first time takes into account effects associated with the lower birthweight and closer-spacing of twins compared to singleton births. We show that examining the effects of twinning by birth order, net of the effects stemming from the birthweight deficit of twins, can provide upper and lower bounds on the trade-off between family size and average child quality. Our estimates indicate that, at least in one area of China, an extra child at parity one or at parity two, net of birthweight effects, significantly decreases the schooling progress, the expected college enrollment, grades in school and the assessed health of all children in the family. We also show that estimates of the effects of twinning at higher parities on the outcomes of older children in prior studies do not identify family size effects but are confounded by inter-child allocation effects because of the birthweight deficit of twins. Despite the evident significant trade-off between number of children and child quality in China, however, the findings suggest that the contribution of the one-child policy in China to the development of its human capital was modest.
The evolution of gnathostome development: Insight from chondrichthyan embryology

Chondrichthyans (cartilaginous fishes) represent one of the two lineages of gnathostomes, the other being the osteicthyans (bony fishes). Classical studies on chondrichthyan embryology have strongly impacted our views of vertebrate body plan evolution, while recent studies highlight oviparous chondrichthyans as emerging vertebrate model systems that are amenable to experimental embryological manipulation. Here, we review three particular areas of interest in the field of chondrichthyan developmental biology—gastrulation, neural development, and appendage patterning—and we discuss recentfindings within a broader chondrichthyan‐osteichthyan comparative framework. In some cases, comparative studies of chondrichthyan and osteichthyan development reveal conserved patterns of gene expression in common developmental contexts. Studies of chondrichthyan gastrulation reveal conserved patterns of developmental gene expression, despite highly divergent modes of mesendoderm internalization, while molecular characterization of chondrichthyan neurogenic placodes indicates a conservation of placode transcription factor expression across gnathostome phylogeny. In other cases, comparative studies of chondrichthyan and osteichthyan development yield evidence of shared patterning mechanisms functioning in different developmental contexts. This is exemplified by studies on the development of chondrichthyan appendages—paired fins, median fins, and gill rays. These have demonstrated that a retinoic acid‐responsive Shh‐expressing signaling center functions to pattern the endoskeleton of gnathostome paired fins and chondrichthyan gill rays, while expression patterns of Tbx18 and HoxD family members are shared by gnathostome paired fins and chondrichthyan median fins. These findings fuel novel hypotheses of developmental genetic homology, and demonstrate how comparative studies of gnathostome development can provide insight into the evolutionary processes that underlie morphological diversity. genesis 47:825–841, 2009. © 2009 Wiley‐Liss, Inc.
Effects of intravitreal insulin and insulin signaling cascade inhibitors on emmetropization in the chick

Purpose Intravitreal insulin has been shown to be a powerful stimulator of myopia in chickens, in particular if the retinal image is degraded or defocused. In most tissues, the insulin receptor activates two main signaling pathways: a) the mitogen-activated protein kinase (MAPK) cascade (e.g., mitogen-activated protein kinasem kinase [MEK] and extracellular regulated kinase [ERK]) and b) the phosphatidylinositol 3-kinase (PI3K)/protein kinase B (Akt) pathway. In the current study, insulin was injected, and these pathways were separately inhibited to determine which is activated when the retinal image is defocused by spectacle lenses. Methods Chicks were treated with either +7 D, −7 D, or no lenses. They were intravitreally injected with insulin, the MEK inhibitor U0126, the PI3K inhibitor Ly294002, or a combination of insulin and one of the inhibitors. Refractions and ocular dimension were measured at the beginning and after four days of treatment. The retinal proteins of the chicks were measured with western blots after 2 h and four days of treatment. Incubation occurred with anti-Akt1, anti-Erk1/2, anti-phospho-AktThr308, and anti-phospho-Erk1/2(Thr202/Tyr204) antibodies, and the ratio between the relative intensity of the phospho-form and the total-form was calculated. Results Chicks wearing positive lenses and injected with saline and with PI3K inhibitor compensated for the imposed defocus and became hyperopic. Insulin injections and insulin plus PI3K inhibitor injections prevented lens-induced hyperopia, whereas the MEK inhibitor alone and insulin plus MEK inhibitor had no effect. Obviously, the MEK inhibitor suppressed the effect of insulin on eye growth in the plus lens–treated animals. Chicks treated with negative lenses and injected with insulin, or with insulin plus MEK inhibitor, overcompensated for the imposed defocus. This effect of insulin was not detected in eyes injected with PI3K inhibitor plus insulin, suggesting that the PI3K inhibitor suppressed the effects of insulin in minus lens–treated animals. Insulin increased the ratio of phospho-Akt/total-Akt in animals with normal visual exposure but even more so in chicks wearing plus or minus lenses. The increase was blocked by simultaneous PI3K inhibitor injections in control eyes but not in lens-treated eyes. Insulin also increased the ratio of phospho-ERK/total-ERK in animals with normal visual exposure and in animals wearing positive lenses, compared to U0126- and Ly294002-injected eyes. In contrast, no significant activation of the MEK/ERK pathway was observed in the negative lens–treated animals. Conclusions Intravitreal insulin promoted axial eye growth and stimulated both signaling pathways. The PI3K/Akt pathway was activated in control and plus and minus lens–treated eyes, but the MEK/ERK pathway was activated only with positive lenses or no lenses. With negative lenses, insulin did not stimulate the MEK/ERK signaling cascade. Independent of the pathway stimulated after insulin binding, the effect on insulin was always the same: an increase in eye growth.
Utility of Acute Phase Proteins as Biomarkers of Transport Stress in Ewes and Beef Cattle

The effect of transport on serum amyloid A (SAA), haptoglobin (Hp), Fibrinogen and white blood cells (WBC) was evaluated in 10 ewes and 10 beef cattle. All animals were transported by road for 6 h over a distance of about 490 km with an average speed of 80 km/h. Blood samples, collected via jugular venepuncture, were obtained before and after transport as well as after 12, 24 and 48 h rest time. One-way repeated measures analysis of variance showed a statistically significant effect of sampling time on SAA, Hp, and WBC in ewes and beef cattle. Based on these results, Hp and SAA levels, together with WBC, may be useful indicators of animal health and welfare and in predicting the risk assessment in meat inspection.
Making Roman-Ness and the "Aeneid"

This essay attempts to develop some ideas about national identity as envisioned in the "Aeneid", with two foci: the lack of clarity concerning Aeneas9 own nationality, and the inaccuracies in the descriptions of the foreigners portrayed on Aeneas9 Vulcanian shield. I aim to undermine the notion that Vergil9s own generation and Augustus9 regime should be assumed to be the "climax," "culmination," or "fulfillment" of the historical process as the "Aeneid" imagines it, and to present reasons for thinking that Vergil9s audience was being invited, instead, to imagine a very long-range future-to expand for themselves the scope of the poem and meet its challenge. I discuss the possibility that Vergil himself was not born either Roman or technically Italian and mention also the probable high proportion of his original audience born without the Roman franchise and admitted to it in the 80s or in 49. I argue that the extended historical range-finder through which the poem requires its readers to view themselves and their inheritors is designed to impose upon them the task of seeking a version of mos (civilized traditional customs) that can be made universal, and the task also of regarding present opponents as destined future fellow-Romans.
Evidence for Prion-Like Mechanisms in Several Neurodegenerative Diseases: Potential Implications for Immunotherapy

Transmissible spongiform encephalopathies (TSEs) are fatal, untreatable neurodegenerative diseases. While the impact of TSEs on human health is relatively minor, these diseases are having a major influence on how we view, and potentially treat, other more common neurodegenerative disorders. Until recently, TSEs encapsulated a distinct category of neurodegenerative disorder, exclusive in their defining characteristic of infectivity. It now appears that similar mechanisms of self-propagation may underlie other proteinopathies such as Alzheimer's disease, Parkinson's disease, Amyotrophic lateral sclerosis, and Huntington's disease. This link is of scientific interest and potential therapeutic importance as this route of self-propagation offers conceptual support and guidance for vaccine development efforts. Specifically, the existence of a pathological, self-promoting isoform offers a rational vaccine target. Here, we review the evidence of prion-like mechanisms within a number of common neurodegenerative disorders and speculate on potential implications and opportunities for vaccine development.
Intelligent Tuned PID Controllers for PMSM Drive - A Critical Analysis

This paper presents a critical analysis of intelligent tuned PID controllers for the permanent magnet synchronous motor drive. The PID proportional-integral-derivative (PID) controller is the most popular controller in process industry. The PID algorithm is simple, reliable and robust for the control of first and second order processes and even high order processes with well damped modes. In this paper, PID control strategies, based on fuzzy logic, neural network and genetic algorithms are reviewed and implemented. A mathematical model of the drive is developed to study steady state and transient performance of current regulated voltage source inverter (VSI) fed PMSM in the field oriented mode under different conditions. The drive includes PID controller, vector control structure, the inverter and the machine. Different tuning algorithms and their effect on dynamic performance of PMSM drive in the real time frame are illustrated in terms of starting and speed reversal time, steady state error in speed, overshoot, performance parameters and speed and torque ripple. Good agreements between different methods has been observed and presented.
Improving regular-expression matching on strings using negative factors

The problem of finding matches of a regular expression (RE) on a string exists in many applications such as text editing, biosequence search, and shell commands. Existing techniques first identify candidates using substrings in the RE, then verify each of them using an automaton. These techniques become inefficient when there are many candidate occurrences that need to be verified. In this paper we propose a novel technique that prunes false negatives by utilizing negative factors, which are substrings that cannot appear in an answer. A main advantage of the technique is that it can be integrated with many existing algorithms to improve their efficiency significantly. We give a full specification of this technique. We develop an efficient algorithm that utilizes negative factors to prune candidates, then improve it by using bit operations to process negative factors in parallel. We show that negative factors, when used together with necessary factors (substrings that must appear in each answer), can achieve much better pruning power. We analyze the large number of negative factors, and develop an algorithm for finding a small number of high-quality negative factors. We conducted a thorough experimental study of this technique on real data sets, including DNA sequences, proteins, and text documents, and show the significant performance improvement when applying the technique in existing algorithms. For instance, it improved the search speed of the popular Gnu Grep tool by 11 to 74 times for text documents.
The association between substance use, unplanned sexual intercourse and other sexual behaviours among adolescent students.

AIMS To determine the prevalence of high-risk sexual behaviours and the influence of substance use and unplanned sexual intercourse on multiple sexual partners, inconsistent condom use and reasons for not always using condoms among adolescent students. DESIGN A standardized self-reported anonymous questionnaire administered to a representative sample of students. SETTING The Canadian provinces of Nova Scotia, New Brunswick, Newfoundland and Labrador, and Prince Edward Island in 1998. PARTICIPANTS 9997 students in grades 9, 10 and 12 in the public school system. MEASUREMENTS Items on sexual intercourse, unplanned sexual intercourse, number of sexual partners, condom use, alcohol use, episodes of binge drinking and drunkenness, cigarette smoking and cannabis use. FINDINGS About 37.5% of males and 39.7% of females reported having engaged in sexual intercourse in the 12 months prior to the survey. Of those, 68.0% of males and 61.5% of females reported having engaged in unplanned sexual intercourse, 40.9% of males and 32.1% of females reported having more than one sexual partner, and 49.9% of males and 64.1% of females reported inconsistent condom use. Unplanned sexual intercourse under the influence of alcohol or other drug was found to be an independent risk factor for multiple sexual partners and inconsistent condom use. CONCLUSION The demonstration of an association between substance use, unplanned sexual intercourse and other sexual behaviours lends support to a harm minimization approach, including the provision of non-judgemental information and interventions addressing unplanned sexual intercourse under the influence of a substance.
Enabling the Cloud of Things

This paper intends to contribute to the design of a pervasive infrastructure where new generation services interact with the surrounding environment, collecting data and applying management strategies. According to such perspective computing, storage and sensing become complementary aspects to be coordinated. In this way innovative and value-added services can be implemented by bridging Clouds with the Internet of Things. Heterogeneous resources can be aggregated and abstracted according to tailored thing-like semantics, thus enabling a Things as a Service paradigm, a way to build a "Cloud of Things" (CoT). This paper mainly focuses on the implementation of the underlying infrastructure at the basis of the CoT. An ad-hoc architecture and some preliminary background of this challenging view are provided and discussed, identifying guidelines and future directions.
Real-time combinatorial tracking of a target moving unpredictably among obstacles

Many applications require continuous monitoring of a moving target by a controllable vision system. Although the goal of tracking objects is not new, traditional techniques usually ignore the presence of obstacles and focus on imaging and target recognition issues. For a target moving among obstacles, the goal of tracking involves a complex motion problem: a controllable observer must anticipate that the target may become occluded by an obstacle and move to prevent such an event from occurring. The paper describes a strategy for computing the motions of a mobile robot operating in a 2-D workspace without prior knowledge of the target's intention or the distribution of obstacles in the scene. The proposed algorithm governs the motion of the observer based on current measurements of the target's position and the location of the local obstacles. The approach is combinatorial in the sense that the algorithm explicitly computes a description of the geometric arrangement between the target and the observer's visibility region produced by the local obstacles. The algorithm computes a continuous control law based on this description. The new tracking strategy has been implemented in a real-time robotic system.
Those good Gertrudes: a social history of women teachers in America

people from this conversation, especially when their identities are so often co-opted for the benefit of the ‘LGBT’ movement, it would have been worth considering an extended discourse on trans identities. After reading Sexuality: A Psychosocial Manifesto, I have realised that my own rejection of categorisation and the normative was another way to reproduce the oppression binary of identity and theory. While I am not reconsidering my own queer identity and political frameworks, I am definitely reconsidering my queer praxis in education and research. This text is a notable read. With supplemental reading of black queer feminists and added discourse on trans identities within the LGBT movement, scholars interested in queer theory and subjectivities should incorporate this text into their practice. I applaud Johnson for packing in so much knowledge and critical thought into such a concise and engaging text.