Miracle-dz/UniFAR-FTUs huggingface dataset:
Targeting glycogen synthase kinase-3 as an approach to develop novel mood-stabilising medications

Historically, success in the pharmacological treatment of bipolar disorder has arisen either from serendipitous findings or from studies with drugs (antipsychotics and anticonvulsants) developed for other indications (schizophrenia and epilepsy, respectively). Lithium has been in widespread clinical use in the treatment of bipolar disorder for > 30 years. Development of lithium-mimetic compounds has the potential to result in a more specific medication, with fewer side effects and a less narrow dose range. However, novel medications based upon a known mechanism of action of this drug are yet to be developed. Increasing evidence suggests that a next-generation lithium compound may derive from knowledge of a direct target of lithium, glycogen synthase kinase-3 (GSK-3). GSK-3 is an intracellular enzyme implicated as a critical component in many neuronal signalling pathways. However, despite the large body of preclinical data discussed in this review, definitive validation of GSK-3 as therapeutically relevant target of lithium will require clinical trials with novel GSK-3 inhibitors. A number of recent reports suggest that it is possible to develop selective, small-molecule GSK-3 inhibitors.
Mechanistic Studies of the Dual Phosphorylation of Mitogen-activated Protein Kinase*

Previous work on the responses of mitogen-activated protein (MAP) kinase cascade components in aXenopus oocyte extract system demonstrated that p42 MAP kinase (MAPK) exhibits a sharp, sigmoidal stimulus/response curve, rather than a more typical hyperbolic curve. One plausible explanation for this behavior requires the assumption that MAP kinase kinase (MAPKK) carries out its dual phosphorylation of p42 MAPK by a distributive mechanism, where MAPKK dissociates from MAPK between the first and second phosphorylations, rather than a processive mechanism, where MAPKK carries out both phosphorylations before dissociating. Here we have investigated the mechanism through which a constitutively active form of human MAPKK-1 (denoted MAPKK-1 R4F or MAPKK-1*) phosphorylates Xenopus p42 MAPK in vitro. We found that the amount of monophosphorylated MAPK formed during the phosphorylation reaction exceeded the amount of MAPKK-1* present, which would not be possible if the phosphorylation occurred exclusively by a processive mechanism. The monophosphorylated MAPK was phosphorylated predominantly on tyrosine, but a small proportion was phosphorylated on threonine, indicating that the first phosphorylation is usually, but not invariably, the tyrosine phosphorylation. We also found that the rate at which pulse-labeled monophosphorylated MAPK became bisphosphorylated depended on the MAPKK-1* concentration, behavior that is predicted by the distributive model but incompatible with the processive model. These findings indicate that MAPKK-1* phosphorylates p42 MAPK by a two-collision, distributive mechanism rather than a single-collision, processive mechanism, and provide a mechanistic basis for understanding how MAP kinase can convert graded inputs into switch-like outputs.
Traffic of L‐selectin‐negative T cells to sites of inflammation

T cells responding to antigen in vivo down‐regulate L‐selectin, the lymph node homing receptor, as they develop into activated effector cells. The concomitant up‐regulation of the proinflammatory adhesion molecules LFA‐1, CD44, and VLA‐4 suggests that, after their release into the circulation, they traffic to sites of antigen deposition and inflammation. Previous evidence, however, has suggested a role for L‐selectin in the recruitment of both neutrophils and lymphocytes into sites of inflammation, which would indicate that these L‐selectin– effector cells could not be the precursors of inflammatory cells. We therefore directly tested whether L‐selectin– T cells activated in vivo are capable of homing to model inflammatory sites. L‐selectin– cells isolated from mice primed with alloantigen or with a contact sensitizer migrated to inflammation markedly better than L‐selectin+ cells from the same animals. Furthermore, the analogous population of CD44hiintegrinhi cells from intravenously primed L‐selectin knockout mice traffic efficiently to inflammatory sites and reject allogeneic skin grafts with normal kinetics. These data demonstrate that the previously described L‐selectin– population of T cells that differentiate into effectors in spleen and lymph nodes subsequently traffic to inflammatory sites, due in part to their increased expression of other proinflammatory adhesion molecules.
House prices, household debt and labour supply in Australia

The objective of the research presented in this report is to identify the nature and magnitude of the relationship between house prices, household debt and the labour market decisions of Australian households. It is well known that there is a positive relationship among house prices, household debt and labour supply. However, empirical estimates of the magnitudes of this relationship in Australia are scarce. Therefore, this project analyses the link between house prices, mortgage debt, and labour supply using rich and contemporary data drawn from the Household, Income and Labour Dynamics in Australia (HILDA) survey for the period of 2001 to 2012 (waves 1–12). The findings presented in this report have important implications for public policy and national wellbeing. Specifically, our findings relate to labour force productivity growth, the performance of the retirement income system and the stability of the macro-economy. Our results also highlight the importance of considering the links between, and the impact of policy on, labour supply, debt, and house prices separately for different demographic groups.
Analytical Modeling of Mode Selection for Moving D2D-Enabled Cellular Networks

Device-to-device (D2D) communications have been proposed as a promising technology to improve network capacity and user experiences. In this letter, we make theoretical analyses on D2D mode selection with user mobility. Using the stochastic geometry, we deduced that the D2D communication range can be well represented by biased circles with varying radius. Besides, a tractable analytical framework considering both absolute movement and relative movement for mode selection in moving D2D scenarios is presented. Under the proposed model, the closed-form expressions of D2D mode transition rate and D2D mode residence time are derived, which are the key parameters for moving D2D mode selection performance.
Staining of Pulmonary Allograft Biopsies : An mmunoperoxidase Study

ackground: The role of antibody-mediated/humoral rejection in lung allografts is not fully elucidated. In other organ systems, deposition of a specific complement product, C4d, is a sensitive and specific marker for humoral rejection. C4d can be evaluated in tissue biopsies by immunofluorescence or light microscopic immunohistochemical staining techniques. Using immunohistochemical staining techniques we sought to determine whether there was any specific staining pattern for C4d in lung allograft biopsies with or without the diagnosis of acute or chronic cellular or humoral rejection. ethods: A total of 68 lung transplant biopsies, performed at UCLA Medical Center from January 2002 to August 2004, were collected and the paraffin blocks were re-cut and stained for C4d by an immunoperoxidase technique. The cases were separated by the presence or absence of features of acute and/or chronic rejection based on the International Society for Heart and Lung Transplantation working formulation for the classification of pulmonary allograft rejection, revised 1995. The pattern of staining for C4d was then systematically examined. esults: Positive staining in a variable, focal non-specific pattern was observed. There was no consistent staining pattern within the different diagnostic groups. onclusions: C4d staining of paraffin-embedded lung allograft biopsies, using currently available techniques, does not identify acute or chronic cellular or humoral rejection in lung allograft tissue. J Heart Lung Transplant 2005;24:1565–70. Copyright © 2005 by the International Society for Heart and Lung Transplantation.
An introduction to hydrogen bond scalar couplings

The hydrogen bond (H-bond) has been recognized in science for more than 80 years as a concept to explain situations where a hydrogen atom is simultaneously binding to two other atoms. Due to the moderate energies necessary for their formation and rupture, hydrogen bonds play a fundamental role in many chemical reactions and most, if not all, interactions involving biological macromolecules. For both proteins and nucleic acids, H-bonds are the essential element in the formation of secondary structures and often they also participate in the stabilization of tertiary structures. Many properties of H-bonds have been studied by a large variety of experimental methods, including NMR spectroscopy. Recently, electron-mediated scalar couplings have been observed which connect magnetic nuclei on both sides of the hydrogen bridge. In contrast to earlier NMR observables, these couplings can be used to "see" all partners of the hydrogen bond, the donor, the proton, and the acceptor in a single COSY experiment. In addition, the size of the coupling constant can be related to hydrogen bond distances and angles. This article should serve as an introduction to these findings and illustrate their use by various examples. (C) 2001 John Wiley & Sons, Inc.
Acoustic evaluation of Isshiki type III thyroplasty for treatment of mutational voice disorders

Abstract The goal of this study was to determine if there are acoustical differences between pre- and post-surgical voices and to evaluate the effectiveness of Isshiki type III thyroplasty in 11 male patients with mutational voice disorders. Acoustic measures were obtained both pre- and post-operatively. A comparison of pre-and post-operative fundamental frequency (Fo), voice frequencies, and vocal intensity obtained from a sustained vowel /i/ during different phonatory tasks was made. The results from the present study demonstrated that after operation the voice frequencies were significantly decreased (p<0.05). The vocal intensity tended to reduce slightly as the voice frequency lowered. However, there were no statistically significant differences in the pre- and post-operative measures of vocal intensity (p>0.5). The preoperative high pitched voices of all the male patients were lowered up to the normal value by the type III thyroplasty.
Normal metabolism but different physical properties of myelin from mice deficient in proteolipid protein

Proteolipid protein (PLP) is the primary protein component of CNS myelin, yet myelin from the PLPnull mouse has only minor ultrastructural abnormalities. Might compensation for a potentially unstable structure involve increased myelin synthesis and turnover? This was not the case; neither accumulation nor in vivo synthesis rates for the myelin‐specific lipid cerebroside was altered in PLPnull mice relative to wild‐type (wt) animals. However, the yield of myelin from PLPnull mice, assayed as levels of cerebroside, was only about 55% of wt control levels. Loss of myelin occurred during initial centrifugation of brain homogenate at 20,000g for 20 min, which is sufficient to sediment almost all myelin from wt mice. Cerebroside‐containing fragments from PLPnull mice remaining in the supernatant could be sedimented by more stringent centrifugation, 100,000g for 60 min. Both the rapidly and the more slowly sedimenting cerebroside‐containing membranes banded at the 0.85/0.32 M sucrose interface of a density gradient, as did myelin from wt mice. These results suggest at least some myelin from PLPnull mice differs from wt myelin with respect to physical stability (fragmented into smaller particles during dispersion) and/or density. Alternatively, slowly sedimenting cerebroside‐containing particles could be myelin precursor membranes that, lacking PLP, were retarded in their processing toward mature myelin and thus differ from mature myelin in physical properties. If this is so, recently synthesized cerebroside should be preferentially found in these “slower‐sedimenting” myelin precursor fragments. Metabolic tracer experiments showed this was not the case. We conclude that PLPnull myelin is physically less stable and/or less dense than wt myelin. © 2003 Wiley‐Liss, Inc.
Time Domain Optical Coherence Tomography Evaluation of the Human Skin

MIRCEA TAMPA1, CLARA MATEI2*, SIMONA-ROXANA GEORGESCU1, TEODOR POTECA2, COSMIN SINESCU3, FLORIN IONEL TOPALA3, MEDA LAVINIA NEGRUTIU3, ADRIAN PODOLEANU4 1Dermatology Department, “Carol Davila” University of Medicine and Pharmacy, Faculty of Dentistry, 5 Calea Plevnei Str. , 050051, Bucharest, Romania 2 "Carol Davila” University of Medicine and Pharmacy, Faculty of General Medicine,37 Dionisie Lupu Str. , 020021, Bucharest, Romania 3University of Medicine and Pharmacy Victor Babes from Timisoara, Faculty of Dentistry, 2 Eftimie Murgu Sq. , 300041, Timisoara, Romania 4University of Kent, Canterbury, UK
Factors supporting change implementation at individual level Readiness to Change in a Project-based Organization Maja

Problem The challenge investigated in this present study is for a project-based organization to create a well-planned implementation by knowing the current state of the organization and its readiness for a change. This while also taking the time for unexpected events and communicating the issue while also taking their organizational structure into consideration. Purpose The purpose of this study is to analyze the readiness to change for the case company with focus on three aspects of readiness: information sharing, common views and implementation approach, while also taking into account the distinct features of a PBO-structured organization. The study aims to identify supporting factors for successfully managing an implementation of a new business system at the individual level. Method This study is a case study based on a single case company: Sweco, which is a Swedish technical consulting firm that is about to change their business system. A literature review was conducted in order to collect previously conducted research within the research area. The primary methods used for data collection in this study have been semi-structured interviews and a questionnaire, the data was mainly analyzed though thematic analysis. Results – The readiness for change for the case company is affected by their organizational structure. The results of the questionnaire show that collaboration within Sweco works relatively well, but there are some aspects that can be improved, such as communication and information sharing. The results of the conducted interviews show that most employees at the case company perceive the change of business system to be good, but they were unsure about why it would be carried through. Guides on how the change would affect the specific individual and knowing where to turn for feedback and information was pointed out as a suggested improvement by the employees. A lot of responsibility of implementing the new system was put on the unit managers. Conclusions The study strengthens the existing theory regarding change readiness and individual supporting factors for successful change implementation. It confirms some of the strengths and drawbacks for organizations working with projects. The study also concludes how the case-company and other companies in a similar situation can utilize some advantages of being familiar with working in projects.
Collaborative manipulation of 3D virtual objects in augmented reality scenarios using mobile devices

Interaction in augmented reality environments may be very complex, depending on the degrees of freedom (DOFs) required for the task. In this work we present a 3D user interface for collaborative manipulation of virtual objects in augmented reality (AR) environments. It maps position - acquired with a camera and fiducial markers - and touchscreen input of a handheld device into gestures to select, move, rotate and scale virtual objects. As these transformations require the control of multiple DOFs, collaboration is proposed as a solution to coordinate the modification of each and all the available DOFs. Users are free to decide their own manipulation roles. All virtual elements are displayed directly on the mobile device as an overlay of the camera capture, providing an individual point of view of the AR environment to each user.
Technology strategy in the solar and wind renewable energy industries

The objective of this study is to investigate the different technology strategies for companies in the solar and wind industries given the dynamics of the renewable energy industry in general. We will investigate how these companies are creating value, capturing value, and delivering value. We looked at the internal and external factors that drove the competitiveness of the solar and wind companies. Literature review was conducted on the technology strategies as well as solar and wind renewable industries around the globe. Five case studies including solar and wind companies from around the world were carried out in order to understand their technologies strategies. Based on this, effective technology strategies to create, capture, and deliver value in the solar and wind renewable industries are identified.
A view of sur/KIR6.X, KATP channels.

ATP-sensitive potassium channels, termed KATP channels, link the electrical activity of cell membranes to cellular metabolism. These channels are heteromultimers of sulfonylurea receptor (SUR) and KIR6.X subunits associated with a 1:1 stoichiometry as a tetramer (SUR/KIR6.X forms the pores, whereas SUR regulates their activity. Changes in [ATP]i and [ADP]i gate the channel. The diversity of KATP channels results from the assembly of SUR and KIR6.X subtypes KIR6.1-based channels differ from KIR6.2 channels mainly by their smaller unitary conductance. SUR1- and SUR2-based channels are distinguished by their differential sensitivity to sulfonylureas, whereas SUR2A-based channels are distinguished from SUR2B channels by their differential sensitivity to diazoxide. Mutations that result in the loss of KATP channels in pancreatic beta-cells have been identified in SUR1 and KIR6.2. These mutations lead to familial hyperinsulinism. Understanding the mutations in SUR and KIR6.X is allowing insight into how these channels respond to nucleotides, sulfonylureas, and potassium channel openers, KCOs.
Classification of bladder cancer by microarray expression profiling: towards a general clinical use of microarrays in cancer diagnostics

At present there are no clinically useful markers available for identifying bladder cancer patients with a high risk of disease recurrence or progression. Thus, identification and tailor-suited treatment, for example radical cystectomy and adjuvant therapy, of patients with a poor prognosis is not possible using current methods. The completion of the Human Genome Project and the simultaneous advances in microarray technology have paved the way for performing systematic, full genome screens for prognostic and diagnostic molecular cancer markers. Furthermore, utilization of microarray technology for identifying clinically relevant subclasses of cancer patients and for discovering new potential drug targets seems promising. This article summarizes some of the clinical aspects of bladder cancer and reviews the potential of using tumor expression profiling for the identification of new molecular cancer markers and drug targets, and for generating disease classifiers and outcome predictors using several key gene markers.
Different Effects of Cabergoline and Bromocriptine on Metabolic and Cardiovascular Risk Factors in Patients with Elevated Prolactin Levels

Hyperprolactinaemia is suggested to be associated with metabolic and hormonal complications. No previous study has compared the effect of different dopamine agonists on plasma lipids, carbohydrate metabolism markers and cardiovascular risk factors in patients with elevated prolactin levels. The study included eight bromocriptine‐resistant women with prolactinoma (group 1) and twelve matched women with hyperprolactinaemia unrelated to prolactinoma (group 2). Group 1 was then treated with cabergoline, while group 2 with bromocriptine. Plasma lipids, glucose homeostasis markers and plasma levels of prolactin, insulin‐like growth factor‐1 (IGF‐1) and cardiovascular risk factors were assessed before and after 6 months of therapy. Both treatments normalized plasma prolactin levels. Cabergoline reduced triglycerides, 2‐hr post‐challenge plasma glucose, the homeostatic model assessment of insulin resistance (HOMA‐IR), and circulating levels of IGF‐1, free fatty acids (FFA), uric acid, high‐sensitivity C‐reactive protein (hsCRP), homocysteine and fibrinogen, as well as increased HDL cholesterol and 25‐hydroxyvitamin D. With the exception of a reduction in HOMA‐IR, bromocriptine treatment produced no significant effect on the investigated biomarkers. Cabergoline was superior to bromocriptine in affecting 2‐hr post‐challenge plasma glucose levels, HOMA‐IR, as well as circulating levels of IGF‐1, FFA, uric acid, hsCRP, homocysteine, fibrinogen and 25‐hydroxyvitamin D. Our results may suggest that cabergoline is superior to bromocriptine when it comes to affecting atherogenic dyslipidaemia, insulin sensitivity and circulating levels of cardiovascular risk factors in hyperprolactinaemic patients. These findings seem to support previous observations that cabergoline may be a better treatment for patients with elevated prolactin levels than bromocriptine.
Lumbar Hernia: An Unusual Presentation of Bear Maul

Introduction: Typical lumbar hernias are very rare surgical conditions. Lumbar hernias can be congenital or acquired. About 25% of all lumbar hernias have a traumatic etiology. Case-Report: We here reported a case of a 55-year-old male who was mauled by a bear. The patient developed an atypical lumbar hernia after 6 months of sustaining craniofacial and abdominal trauma. Open hernioplasty, which was a very challenging job, was done in this patient. Conclusion: Post traumatic lumbar hernias have been reported but till today no case of lumbar hernia following an attack by a bear has been reported in literature. Both acute and long-standing post-traumatic lumbar hernias are rare but challenging conditions. The corrective surgical procedure becomes more complex as hernial defect enlarges. Reconstruction is a challenging aspect of lumbar hernia surgery.
Something Old, Something New, Something Borrowed, Something Blue Part 1: Alan Turing, Hypercomputation, Adam Smith and Next Generation Intelligent Systems

Abstract. In this article intelligent systems are placed in the context of accelerated Turing machines. Although such machines are not currently a reality, the very real gains in computing power made over previous decades require us to continually reevaluate the potential of intelligent systems. The economic theories of Adam Smith provide us with a useful insight into this question.