Miracle-dz/UniFAR-FTUs huggingface dataset:
Frenquel, a Blocking Agent Against Experimental LSD‐25 and Mescaline Psychosis

THE PRESENT STUDY of the effects of Frenquel in patients and in normal subjects stems from earlier observations on Meratran. Brown and Werner1 found that Meratran, a-( 2-piperidyl) benzhydrol hydrochloride, differed significantly from other central nervous system stimulants such as the amphetamines. No cardiovascular pressor reactions, no appetite loss, and little disturbance in nocturnal sleep have been observed with this compound, which may be used therapeutically in mild depressive states2 as well as in narcolepsy and certain selected motor tic syndromes.3 Himwich and his associates4 state that Meratran is not a sympathomimetic drug. They have demonstrated that the central reticular substance of the rabbit brain is stimulated by the compound, followed by cortical stimulation, and Heath5 found that Meratran has an unique ability to cause rapid high voltage activity in the septa1 area of the monkey electrographically. Because Meratran appeared to be a truly central-acting compound without observable concomitant effects on the autonomic nervous system, and because its site of action appeared to be, at least in part, in the upper brainstem tegmentum, it was felt that other compounds of similar chemical configuration might also be of value as therapeutic agents in disorders of the central nervous system. A study of a group of isomers and congeners of Meratran is now in progress, and Frenquel is the first of these upon which clinical experience has been reported.6 Frenquel is the gamma-isomer of Meratran. It will be noted in the structural formulas that the NH radical is moved from the 2-position to the 4-position in the piperidyl ring in the synthesis of this benzhydrol compound. Brown' has found that this Meratran isomer of close structural similarity, a white crystalline substance, bitter in taste, and soluble 1 part in 50 of water, is far different from the parent compound neuropharmacologically. It is not a central excitant, but rather is an antagonist of central stimulation produced by other agents in the mouse, including amphetamine, morphine, cocaine, and Meratran. In a dose of 20 mg. /kg. it almost doubles the sleeping time produced in mice by the intraperitoneal injection of 100 mg. /kg. of hexobarbital. It is of
Regulation of muscle acetylcholine receptor turnover by β subunit tyrosine phosphorylation

At the neuromuscular junction (NMJ), the postsynaptic localization of muscle acetylcholine receptor (AChR) is regulated by neural signals and occurs via several processes including metabolic stabilization of the receptor. However, the molecular mechanisms that influence receptor stability remain poorly defined. Here, we show that neural agrin and the tyrosine phosphatase inhibitor, pervanadate slow the degradation of surface receptor in cultured muscle cells. Their action is mediated by tyrosine phosphorylation of the AChR β subunit, as agrin and pervandate had no effect on receptor half‐life in AChR‐β3F/3F muscle cells, which have targeted mutations of the β subunit cytoplasmic tyrosines. Moreover, in wild type AChR‐β3Y muscle cells, we found a linear relationship between average receptor half‐life and the percentage of AChR with phosphorylated β subunit, with half‐lives of 12.7 and 23 h for nonphosphorylated and phosphorylated receptor, respectively. Surprisingly, pervanadate increased receptor half‐life in AChR‐β3Y myotubes in the absence of clustering, and agrin failed to increase receptor half‐life in AChR‐β3F/3F myotubes even in the presence of clustering. The metabolic stabilization of the AChR was mediated specifically by phosphorylation of βY390 as mutation of this residue abolished β subunit phosphorylation but did not affect δ subunit phosphorylation. Receptor stabilization also led to higher receptor levels, as agrin increased surface AChR by 30% in AChR‐β3Y but not AChR‐β3F/3F myotubes. Together, these findings identify an unexpected role for agrin‐induced phosphorylation of βY390 in downregulating AChR turnover. This likely stabilizes AChR at developing synapses, and contributes to the extended half‐life of AChR at adult NMJs. © 2013 Wiley Periodicals, Inc. Develop Neurobiol 73: 399–410, 2013
Introduction: autism--the challenges ahead.

There have been many important advances in research into the nature of autism and, as a result, our concepts of autism have undergone a radical change (Rutter 1999). At one time, the prevailing view was that autism was an unusually early variety of schizophrenia that had been caused, in large part, by so-called refrigerator parenting. It became clear that that was a wholly mistaken concept and that, instead, autism constitutes a neurodevelopmental disorder with a rather distinctive pattern of cognitive de¢cits, and that it is strongly genetically in£uenced. Nevertheless, we are a longway fromunderstanding the basic pathophysiology, and numerous puzzles and paradoxes remain. The aim of this symposium is to grapple with these issues, tackling the challenges from a range of di¡erent perspectives in the hope that a coming together of minds, and of di¡erent research strategies, may point the way ahead. My task is to set the scene by outlining some of these challenges in order to provoke us all to abandon the safety of our own research territory, and of the ¢ndings that are well established, in order to focus on the di⁄culties that are inherent in our favoured theories. We need to begin with implications of the huge rise in diagnosed autism (Baird et al 2000, Chakrabarti & Fombonne 2001, Fombonne 1999). To a substantial extent, this rise is a consequence of a major broadening of the concept of autism together with better ascertainment. However, is that all? When like is compared with like, has there been a real rise in the rate of autism? If that should prove to be the case, what is the environmental factor that has brought this about (the rise is unlikely to have been genetically determined)? There have been claims that the rise is due to the use of the combined measles/mumps/rubella (MMR) vaccine but that does not seem very likely. The rise began before the introduction of MMR and it continued to rise, without any plateauing, after MMR was used with the vast majority of the population (Dales et al 2001, Farrington et al 2001, Taylor et al 1999). But, if that is not the cause, what is?
Differential Na+–K+‐ATPase activity in rat lemniscal and non ‐ lemniscal auditory Thalami

1 Using whole‐cell recording and confocal immunofluorescent microscopy, we have investigated the differential electrogenic activity, subunit expression and subcellular distribution of the Na+–K+‐ATPase in the lemniscal (ventral) and non‐lemniscal (dorsal) pathways of the rat medial geniculate body (MGB) in vitro. 2 Bath application of Na+–K+‐ATPase inhibitors strophanthidin or dihydroouabain produced a transient, dose‐dependent inward current or membrane depolarization which were significantly larger in dorsal MGB neurones than in ventral cells (45.9 ± 6.45 vs. 24.3 ± 4.l pA; P < 0.05). Electrophysiological and morphometric measurements showed that the dorsal MGB neurones had a significantly lower input conductance and a smaller somata than their ventral counterparts. The level of the resting membrane potential also differed by about 6 mV between the two cell populations, with the dorsal cells being more hyperpolarized (−74.2 ± 0.6 vs. −67.7 ± 1.3 mV; P < 0.001). 3 Incubation of enzymatically dissociated MGB neurones with fluorescent monoclonal antibodies against α1‐α3 isoforms of Na+–K+‐ATPase showed that both dorsal and ventral cells expressed primarily α3 subunits. Confocal laser scanning revealed, however, that the mean pixel density of α3 fluorescent antibodies in the plasma membrane domain, but not in the cytoplasmic compartment, was about 40 % higher in dorsal neurones than in the ventral cells (29.7 ± 4.7 vs. 16.9 ± 2.3 grey shadow per pixel; P < 0.05). 4 The above results suggest that the electrogenic activity of the Na+–K+‐ATPase is differentially regulated between lemniscal and non‐lemniscal auditory thalami through a mechanism that probably involves differential pump densities in the cell membrane.
Agents of Media Innovations: Actors, Actants, and Audiences

In the contemporary media environment, media managers have been forced to reassess everything from editorial workflows to business models to technological platforms. Amid such challenges, legacy news media organizations are encouraged to innovate. Contemporary scholarly literature on media innovation typically adopts a relatively narrow approach when defining and studying the agents involved in shaping media innovations. Ultimately, many studies focus on individual parts of the organization rather than the complete system. There is thus a need to theorize and conceptualize the agents of media innovations in order to understand and improve activities of media innovations. This article presents the AMI approach (Agents of Media Innovations) as a holistic theoretical construct for understanding the agents of media innovation activities. We conceptualize this approach through a systematic discussion of four interlinked factors: actors, actants, audiences, and activities. These are used to compose and outline what we call the 4A Matrix, encompassing seven distinct and typological ways in which actors, actants, and audiences might intersect in the activities of media innovation. In mapping this interplay, the 4A Matrix serves as a heuristic for the scholarly study of media innovations, as well as a conceptual tool for envisioning, at a practical level, how media managers might act strategically.
The Reformation in Print: German Pamphlets and Propaganda

Scholars toward the end of the fifteenth century enjoyed a perfected printing technology and its products, beautiful folio Bibles, dictionaries, classical and medieval works, and a variety of secular publications. The sixteenth-century pamphlet represents a marked shift in the use of the printing press, a shift most noticeable in German areas and one coinciding with Reformation. The brief, blunt, and vulgar reformation tract intended for a wide and unlearned if not confused audience became a major tool of those who sought diange in the religious loyalities of large numbers of people. There is some evidence to illustrate the contention that those holding firmly to Catholicism ignored the propagandistic potential of the printing press. It is possible that Catholic theologians and statesmen who were long accustomed to power and authority felt little need to experiment with radically new methods of mass communication. Catholic reluctance was reinforced by tactile medieval habits of oral, visual, and ceremonial methods of communication. As late as 1590, for example, hand written liturgical books were still in demand for use in Catholic diurches and there were a number of ecclesiastics who would not pray from a printed book. For Protestants the power of the spoken word in and out of the pulpit or in disputation was important; yet, the print dimension appears to be a primary if not generic aspect of the Reformation process. The influence of Reformation events on communication forms has not received adequate attention. Fortunately for students of sixteenth-century pamphlet literature, a large and representative sample collected by the nineteenth century man of letters, Gustav Freytag, is extant and has been superbly catalogued by Paul Hohenemser for the City and University Library in Frankfurt am Main. Hohenemser was familiar with the collecting methods of Gustav Freytag and realized that Freytag's collection is a reasonable sample of small book and pamphlet production. When viewed against what is commonly known about
Prevalence of psychiatric disorders among incarcerated women. II. Convicted felons entering prison.

BACKGROUND No unbiased estimates of the rates of psychiatric disorder among women prison inmates are available. Nonetheless, available data suggest that some psychiatric disorders are prevalent in this population. The objective of the study was to determine the rates, risk factors, and outcomes of specific psychiatric disorders among women prison inmates. METHODS A virtual census of women felons (N = 805) entering prison in North Carolina was assessed using in-person interviews. Assessments were conducted for 8 disorders, using the Composite International Diagnostic Interview as the primary assessment measure. For validation purposes, one quarter of the inmates were reassessed for 2 of these disorders, using structured clinical interviews. RESULTS Inmates were found to have high rates of substance abuse and dependence and antisocial and border-line personality disorders compared with women in community epidemiologic studies. Rates among inmates were also somewhat elevated for mood disorders but not for anxiety disorders. The rate of reports of lifetime exposure to traumatic events was also high. Rates of disorder tended to be higher among white than among African American women. CONCLUSION High rates of substance abuse, psychiatric disorder, and psychological distress associated with exposure to traumatic events suggest that women in prison have a need for treatment for substance abuse and other mental health problems.
Achieving IT Acceptance – An Outcome Control Perspective

This paper provides a framework that describes the role organisational control can play in user acceptance of an information technology (IT). Using the case study approach, we adopted the "soft positivism" research philosophy, to investigate the development and acceptance of an IT from the outcome control perspective. Our framework highlights how outcome control mechanisms exercised during the development and acceptance/usage stages of an IT respectively. The framework also helps indicate that outcome control, which is conceptualised in the literature as deliberate and forceful in nature, could also, unlike behaviour control, be exercised in measures that do not need to coerce or be forceful. By adopting a control perspective on IT development and acceptance/usage, the framework can inform how senior management can influence the achievement of user acceptance of an IT after members' resistance had occurred.
A structural and functional analysis of walking in the turtle, Chrysemys picta marginata

Walking of Chrysemys has been studied by cinephotography and x‐rays. The lateral sequence, diagonal couplet gait, limb support sequence, and wide track provide great stability, yet a slight pitch and roll cause some plastral drag. Velocity ranges from 28 mm to 51 mm/second, and fluctuates within a stride. Limb movements and structure resemble those of other ectotherms, but incorporate modifications reflecting the animal's short, broad trunk encased in a shell and carried close to the ground. The triradiate pectoral girdle so articulates with the shell as to act as a truss for weight transfer to the ground. Girdle rotation increases the efficiency of the girdle as a truss, and contributes to locomotor efficiency. The glenoid cavities are more than twice as far apart as the acetabula, so a thrust from the pectoral girdle has less propulsive efficiency on the center of gravity than one from the acetabulum. The humerus and femur are protracted to a greater extent than in other ectotherms and their horizontal arcs of retraction are less. Rotation of these elements about their longitudinal axes contributes to the length of a stride and to foot placement and withdrawal. Differences in the movements of comparable segments of front and hind limbs correlate with differences in the width of the girdles, a crus longer than the antebrachium, and different capacities for joint rotation.
Histology and affinity of the earliest armoured vertebrate

Arandaspids are the earliest skeletonizing vertebrates known from articulated remains. Despite a wealth of data, their affinity remains questionable because they exhibit a random mixture of primitive and derived characteristics. We constrain the affinity of arandaspids by providing the first detailed characterization of their dermoskeleton which is revealed to be three-layered, composed of a basal laminated, cancellous middle and tubercular superficial layers. All three layers are composed of acellular bone but the superficial layer also includes dentine and enameloid, comprising the tubercles. As such, the composition of the arandaspid dermoskeleton is common to heterostracans and astraspids, supporting existing hypotheses of early vertebrate phylogeny. This emphasizes the peculiarity of existing interpretations of aranadaspid anatomy and there is need for a complete reappraisal of the existing anatomical data.
Plasma Cholecystokinin, Plasma Peptide YY and Gallbladder Motility in Patients with Slow Transit Constipation: Effect of Intestinal Stimulation

Background/Aim: Because cholecystokinin and peptide YY are gut hormones with potent effects on gastrointestinal motility, we determined whether abnormalities of cholecystokinin and peptide YY exist in slow transit constipation. Methods: Plasma concentrations of these hormones before, during and after intraduodenal infusion of a liquid meal in 21 patients with slow transit constipation were compared with the results in 8 healthy controls. Results: Fasting levels of plasma cholecystokinin (3.1 ± 0.2 vs. 2.4 ± 0.2 pM; p = 0.02) were higher in patients. Basal plasma peptide YY (11.4 ± 1.4 vs. 8.9 ± 0.7 pM; p = 0.1) tended to be higher in patients. After the meal (60–90 min), incremental cholecystokinin (p < 0.05), but not peptide YY, was significantly higher in patients. During intraduodenal infusion of the meal (0–60 min), incremental plasma cholecystokinin (251 ± 20 pM·min) and peptide YY (1,146 ± 186 pM·min) in patients were almost similar to control values (262 ± 22 and 901 ± 166 pM·min). Gallbladder volumes before, during and after the meal were not different between the 2 groups. Gastric emptying of a solid meal was delayed in the majority of patients (12 of 18). Abnormalities of plasma cholecystokinin were observed only in patients with delayed gastric emptying. Conclusion: Plasma levels of cholecystokinin are elevated in the fasting state and decrease more slowly after stimulation, but maximum release in response to intestinal nutrients is not altered in patients with slow transit constipation. The abnormality seems to be confined to a subgroup of patients with delayed gastric emptying.
The case for vaccine development in the strategy to eradicate river blindness (onchocerciasis) from Africa

Onchocerciasis or river blindness is a neglected parasitic disease causing severe dermatitis and visual impairment, predominantly in Africa. Historically, onchocerciasis control targeted vector breeding sites, but the current strategy relies on mass administration of a single drug, ivermectin. As programmatic goals shift from reducing public health impact to active elimination, sole reliance on ivermectin is threatened by contraindications in areas coendemic for loiasis, an inability to break transmission in some foci, and the emergence of drug resistance. Here, we argue that prophylactic and therapeutic vaccines would accelerate elimination efforts and safeguard the enormous strides made in onchocerciasis control. These vaccines could be based on one or more of three lead candidates identified by a newly formed transatlantic partnership, The Onchocerciasis Vaccine for Africa Initiative.
HIV prevention with young men who have sex with men: What young men themselves say is needed

Young men who have sex with men (YMSM), and particularly ethnic minority YMSM, experience high incidence HIV infection due to continued patterns of high-risk sexual behaviour. The intent of this research was to systematically solicit input and recommendations from YMSM themselves concerning the kinds of HIV prevention programmes that would best meet their needs and would address risk issues they believed are critical. In-depth qualitative interviews were conducted with a sample of 72 purposively selected YMSM to identify necessary components of HIV prevention targeting YMSM. Respondents noted a need for comprehensive HIV prevention programmes that addressed issues related to dating and intimacy, sexuality and arousal, drugs and alcohol, self-esteem and self-worth, abuse and coercion, and sexual identity. Respondents emphasized the importance of keeping programmes confidential, fun, comfortable, accepting and open to all YMSM regardless of sexual identity. Identified community resource needs included safe havens for youth, more peer educators and older MSM mentors, increased school-based sexuality education, and greater support from the society at large as well as from churches, the gay community and communities of Color. Implications of these findings for HIV prevention are discussed.
Analyse de réseaux sur les personnages des Confessions de Jean-Jacques Rousseau

Yannick RochatFrederic KaplanDanscetarticle,nouspresentonslesmethodesdel’analysedereseauxlit-teraires. Cette discipline se situe a la croisee de la narratologie, du « distantreading»etdel’analysedesreseauxsociaux.Nousl’illustronsparuneanalysesurLesConfessionsdeJean-JacquesRousseauutilisantleconceptdecentralite,et permettant ainsi de caracteriser certains aspects des roles des personnagesdurecitsurlabasedeleursco-occurrencesdansletexte.
Growth and Transcription Factors in Tooth Development

Introduction The embryonic process of odontogenesis is originated by two main embryonic tissues which are ectoderm and the underlying ectomesenchyme. The interaction between both two components leads tooth development throughout different phases known as initial stage, bud stage, cap stage, bell stage, appositional stage and root development [1].
Lithium inhibits caspase 3 activation and dephosphorylation of PKB and GSK3 induced by K+ deprivation in cerebellar granule cells

Lithium protects cerebellar granule cells from apoptosis induced by low potassium, and also from other apoptotic stimuli. However, the precise mechanism by which this occurs is not understood. When cerebellar granule cells were switched to low potassium medium, the activation of caspase 3 was detected within 6 h, suggesting a role of caspase 3 in mediating apoptosis under conditions of low potassium. In the same conditions, lithium (5 mm) inhibited the activation of caspase 3 induced by low potassium. As lithium did not inhibit caspase 3 activity in vitro, these results suggest that this ion inhibits an upstream component that is required for caspase 3 activation. Lithium is known to inhibit a kinase termed glycogen sythase kinase 3 (GSK3), which is implicated in the survival pathway of phosphatidylinositol 3‐kinase/protein kinase B (PI3K/PKB). Here we demonstrate that low potassium in the absence of lithium induces the dephosphorylation, and therefore the activation, of GSK3. However, when lithium was present, GSK3 remained phosphorylated at the same level as observed under conditions of high potassium. Low potassium induced the dephosphorylation and inactivation of PKB, whereas when lithium was present PKB was not dephosphorylated. Our results allow us to propose a new hypothesis about the action mechanism of lithium, this ion could inhibit a serine‐threonine phosphatase induced by potassium deprivation.