Miracle-dz/UniFAR-FTUs huggingface dataset:
Akt and CHIP coregulate tau degradation through coordinated interactions

A hallmark of the pathology of Alzheimer's disease is the accumulation of the microtubule-associated protein tau into fibrillar aggregates. Recent studies suggest that they accumulate because cytosolic chaperones fail to clear abnormally phosphorylated tau, preserving a pool of toxic tau intermediates within the neuron. We describe a mechanism for tau clearance involving a major cellular kinase, Akt. During stress, Akt is ubiquitinated and degraded by the tau ubiquitin ligase CHIP, and this largely depends on the Hsp90 complex. Akt also prevents CHIP-induced tau ubiquitination and its subsequent degradation, either by regulating the Hsp90/CHIP complex directly or by competing as a client protein with tau for binding. Akt levels tightly regulate the expression of CHIP, such that, as Akt levels are suppressed, CHIP levels also decrease, suggesting a potential stress response feedback mechanism between ligase and kinase activity. We also show that Akt and the microtubule affinity-regulating kinase 2 (PAR1/MARK2), a known tau kinase, interact directly. Akt enhances the activity of PAR1 to promote tau hyperphosphorylation at S262/S356, a tau species that is not recognized by the CHIP/Hsp90 complex. Moreover, Akt1 knockout mice have reduced levels of tau phosphorylated at PAR1/MARK2 consensus sites. Hence, Akt serves as a major regulator of tau biology by manipulating both tau kinases and protein quality control, providing a link to several common pathways that have demonstrated dysfunction in Alzheimer's disease.
Use of the AAEM Guidelines in Electrodiagnosis of Ulnar Neuropathy at the Elbow

Thibault MW, Robinson LR, Franklin G, Fulton-Kehoe D: Use of the AAEM guidelines in electrodiagnosis of ulnar neuropathy at the elbow. Am J Phys Med Rehabil 2005;84:267–273. Objective:The goal of this study was to determine if practice patterns in Washington State were altered by the development and publication of the American Association of Electrodiagnostic Medicine practice parameter for electrodiagnosis of ulnar neuropathy at the elbow. Design:Medical records from 350 workers’ compensation patients who underwent surgery for ulnar neuropathy at the elbow in Washington State were reviewed for the consistency of the electrodiagnosticians’ report and the practice parameter. Statistical analysis (&khgr;2 or Fischer’s exact test) compared prepublication and postpublication patterns of test use. Results:Thirty-one percent of the 153 studies (n = 47) were not consistent with American Association of Electrodiagnostic Medicine guidelines before its publication vs. 34% of the 138 studies (n = 47) after publication. This was not a statistically significant change (P = 0.63). Conclusion:Evaluation of the usefulness and dissemination of the guidelines is warranted. The practice parameter may need to be simplified and educational efforts extended to improve provider use of new guidelines.
Characterization of a Shaw‐related potassium channel family in rat brain.

Previously, we characterized a Shaker‐related family of voltage‐gated potassium channels (RCK) in rat brain. Now, we describe a second family of voltage‐gated potassium channels in the rat nervous system. This family is related to the Drosophila Shaw gene and has been dubbed Raw. In contrast to the RCK potassium channel family the Raw family utilizes extensive alternative splicing for expressing potassium channel subunits with variant C‐termini. These alternative C‐termini do not appear to influence the electrophysiological and pharmacological properties as studied in the Xenopus oocyte expression system. In situ hybridizations to sections of rat brain indicate that members of the Raw family are expressed in distinct areas of the central nervous system. Probably, Raw channels are expressed predominantly as homomultimers. Immunocytochemical experiments with antibodies against Raw3 and RCK4 proteins which form two distinct A‐type potassium channels indicate that in hippocampus the two channels are expressed both in different neurons and in the same ones. In general, properties of Raw potassium channels appeared to be similar to RCK channels. However, Raw outward currents, in contrast to RCK currents, exhibit an intense rectification at test potentials higher than +20 to +40 mV. RCK and Raw channel subunits did not measurably coassemble into RCK/Raw heteromultimers after coinjecting RCK and Raw cRNA into Xenopus oocytes. These results suggest that members of the RCK and the Raw potassium channel families express potassium channels which form independent outward current systems. Combining the results of in situ hybridizations, immunocytochemical staining and expression of the cloned potassium channels in Xenopus oocytes demonstrates that unrestrained mixing of potassium channel subunits to form hybrid channels does not occur in the rat central nervous system. A single neuron is able to express multiple, independently assembled potassium channels.
Public‐Private Partnerships (PPPs) in Development Policy: Exploring the Concept and Practice

Public-private partnerships (PPPs) have proliferated in development studies over the past decades. However, oftentimes the partnership notion remains loosely defined, thus making it difficult to grasp the concept and evaluate practice. This article aims to contribute to conceptual and empirical exploration of the PPP concept. Based on a comprehensive review of the literature, we frame eight characteristics of PPPs in development policy. Turning then to exploration of empirical practice, we present a longitudinal analysis of PPPs in Danish development policy over a twenty-year period. The conceptual and empirical insights target PPP development researchers and practitioners alike. This article is protected by copyright. All rights reserved.
Dynamic Slot-Length Control for Reducing Neighbor Discovery Latency in Wireless Sensor Networks

The state of art protocols in neighbor discovery in wireless sensor networks can be divided into two categories: the quorum based, and the co-primality based protocols, which are confirmed by simulations to have a small "theoretical" latency according to their wake-up schedule designs. However, these works fail to consider the collision of neighbor discovery beacons, when multiple pairs of nodes search for discovery simultaneously, which could lead to a greater "practical" latency. In this paper, we seek to reduce such practical latency in neighbor discovery protocols caused by the collision of neighbor discovery beacons by a dynamic slot-length control mechanism that allows each node to autonomously vary its slot length based on the detection of beacon collisions. We develop a real-world testbed of neighbor discovery on Android smartphones by implementing a few classic neighbor discovery protocols in literature, and evaluate their performance with and without the proposed slot-length control. Experimental results show that the slot-length control can help reduce the practical latency of neighbor discovery by more than 15% under both types of neighbor discovery protocols.
Validation of a QSAR model for acute toxicity

In the present study, a quantitative structure – activity relationship (QSAR) model has been developed for predicting acute toxicity to the fathead minnow (Pimephales promelas), the aim being to demonstrate how statistical validation and domain definition are both required to establish model validity and to provide reliable predictions. A dataset of 408 heterogeneous chemicals was modelled by a diverse set of theoretical molecular descriptors by using multivariate linear regression (MLR) and Genetic Algorithm – Variable Subset Selection (GA-VSS). This QSAR model was developed to generate reliable predictions of toxicity for organic chemicals not yet tested, so particular emphasis was given to statistical validity and applicability domain. External validation was performed by using OECD Screening Information Data Set (SIDS) data for 177 High Production Volume (HPV) chemicals, and a good predictivity was obtained ( = 72.1). The model was evaluated according to the OECD principles for QSAR validation, and compliance with all five principles was established. The model could therefore be useful for the regulatory assessment of chemicals. For example, it could be used to fill data gaps within its chemical domain and contribute to the prioritization of chemicals for aquatic toxicity testing. †Presented at CMTPI 2005: Computational Methods in Toxicology and Pharmacology Integrating Internet resources (Shanghai, China, October 29–November 1 2005).
Thoracic stop-flow perfusion for refractory lymphoma: a phase I-II evaluation trial.

BACKGROUND Management of patients with heavily pretreated malignant lymphoma failing front-line treatment and salvage high-dose chemotherapy and autologous peripheral stem cell rescue is problematic. A phase I-II evaluation trial was conducted to evaluate thoracic stop-flow perfusion. PATIENTS AND METHODS nine refractory patients were enrolled in the study. The schedule of thoracic stop-flow perfusion was based on cisplatin (100 mg/m(2)) and melphalan (25 mg/m(2)). Melphalan pharmacokinetic analyses were performed. All patients received hemofiltration during each procedure. RESULTS Overall 18 cycles of perfusional chemotherapy were administered. During the procedures there were no technical, hemodynamic, or vascular complications, and no deaths occurred during surgery. Hematological and non-hematological toxicity was mild in relation to the use of hemofiltration during the procedures. All 9 patients responded favourably to stop-flow therapy. We observed 5 CR and 4 PR. Four out of five patients in CR relapsed. Three out of these four died of progressive disease after a response duration of 9, 7 and 7 months, respectively. One patient had a duration of CR of 10 months before relapse. He attained a new PR (+ 3 months). The remaining complete responder is still in remission after 37+ months. The 4 patients in PR progressed and died after a response duration of 4, 6, 2 and 1 month, respectively. To date, 8 out of 9 patients have died and one is still alive. CONCLUSION Thoracic stop-flow perfusion seems very active in this kind of patient.
Perinatal exposure to delta 9-tetrahydrocannabinol (delta 9-THC) leads to changes in opioid-related behavioral patterns in rats.

Perinatal exposure to cannabinoids has been shown to elicit central nervous system impairment in rodents. This includes changes in monoaminergic and neuropeptidergic activities. We have examined the effect of perinatal exposure to delta 9-tetrahydrocannabinol (delta 9-THC) on sensitivity to radiant heat in both male and female rats on days 24, 50 and 70 after birth. Animals used in this experiment were born of mothers that received delta 9-THC (5 mg/kg; p.o.) daily from day 5 of pregnancy until day 24 after offspring birth. delta 9-THC perinatally treated males, but not females, showed higher baseline tail-flick values than controls on days 24 and 50 (Day 24, controls: 3.88 +/- 0.18 s; delta 9-THC group: 4.51 +/- 0.18 s; Day 50, controls: 3.16 +/- 0.17 s; delta 9-THC group: 4.38 +/- 0.38 s). In addition, adult males were found to be tolerant to the analgesic effect of morphine (5 mg/kg; i.p.; % analgesia: controls 71.75 +/- 10.20; delta 9-THC 35.5 +/- 10.59). Moreover, recently weaned pups that received 5 mg/kg of naloxone (i.p.) developed an opioid-like withdrawal syndrome. Taken together all these results suggest that perinatal treatment with delta 9-THC may alter the functionality of the endogenous opioid system, including changes in pain sensitivity.
Appropriating Technology-rich Learning Spaces

A number of novel technology-rich learning spaces have been developed over the last few years in UK. Many claims have been made in terms of how they can support and enhance learning, collaboration, community participation, and creativity. This line of research is investigating whether such learning spaces are living up to such claims. The approach is ethnographic, a number of field studies have been conducted examining how people use the spaces in practice. Findings so far have shown that that the spaces are not used in the way anticipated and that flexibility, a sense of ownership and control are key issues.
Expression of Neurogenin 1 in Mouse Embryonic Stem Cells Directs the Differentiation of Neuronal Precursors and Identifies Unique Patterns of Down‐stream Gene Expression

Background: Delineating the cascades of growth and transcription factor expression that shape the developing nervous system will improve our understanding of its molecular histogenesis and suggest strategies for cell replacement therapies. In the current investigation, we examined the ability of the proneural gene, Neurogenin1 (Neurog1; also Ngn1, Neurod3), to drive differentiation of pluripotent embryonic stem cells (ESC). Results: Transient expression of Neurog1 in ESC was sufficient to initiate neuronal differentiation, and produced neuronal subtypes reflecting its expression pattern in vivo. To begin to address the molecular mechanisms involved, we used microarray analysis to identify potential down‐stream targets of Neurog1 expressed at sequential stages of neuronal differentiation. Conclusions: ESC expressing Neurogenin1 begin to withdraw from cycle and form precursors that differentiate exclusively into neurons. This work identifies unique patterns of gene expression following expression of Neurog1, including genes and signaling pathways involved in process outgrowth and cell migration, regional differentiation of the nervous system, and cell cycle. Developmental Dynamics 242:230–253, 2013. © 2013 Wiley Periodicals, Inc.
Correlation between benign prostatic hyperplasia and inflammation

Purpose of reviewThis review aims to evaluate the available evidence on the role of prostatic inflammation in the pathogenesis and progression of benign prostatic hyperplasia (BPH). Recent findingsAlthough there is still no evidence of a causal relation, accumulating evidence suggests that inflammation may contribute to the development of BPH and lower urinary tract symptoms (LUTS). Inflammatory infiltrates are frequently observed in prostate tissue specimens from men with BPH and the presence or degree of inflammation has been found to be correlated with prostate volume and weight. The inflammatory injury may contribute to cytokine production by inflammatory cells driving local growth factor production and angiogenesis in the prostatic tissue. This proinflammatory microenvironment is closely related to BPH stromal hyperproliferation and tissue remodeling with a local hypoxia induced by increased oxygen demands by proliferating cells which supports chronic inflammation as a source of oxidative stress leading to tissue injury in infiltrating area. SummaryAlthough the pathogenesis of BPH is not yet fully understood and several mechanisms seem to be involved in the development and progression, recent studies strongly suggest that BPH is an immune inflammatory disease. The T-cell activity and associated autoimmune reaction seem to induce epithelial and stromal cell proliferation. Further understanding of the role of inflammation in BPH and clinical detection of this inflammation will expand the understanding of BPH pathogenesis and its histologic and clinical progression, allow risk stratification for patients presenting with BPH-related LUTS, and suggest novel treatment strategies.
Autonomy, Incentives, and School Performance: Evidence from the 2009 Autonomous Private High School Policy in Korea

Improving the quality of school education is one of the key policy concerns in Korea. This paper examines whether providing schools with adequate autonomy and incentives can meet the policy goals by looking at a recent policy reform in Korea. In 2009, the Korean government granted autonomy to certain private high schools on the condition that no financial subsidies would be provided to the schools. Because the autonomous private high schools cannot receive a subsidy, they have a strong incentive to meet parental demands because schools failing to meet these demands will lose students and will have to close. Applying the value-added model to longitudinal data at the student level, I find that students entering these autonomous schools show faster growth in their academic achievement than their peers in traditional non-autonomous schools. These results suggest that providing schools with autonomy and incentives can be a useful policy tool for improving school education.
[Working effectively towards rehabilitation goals: long-term outcome of a randomised controlled trial of the Boston psychiatric rehabilitation approach].

BACKGROUND In the Netherlands the Boston psychiatric rehabilitation approach (bpr) is one of the most widely implemented rehabilitation methods. So far, little research has been done on the efficacy of this approach. AIM To investigate the effect of bpr on the attainment of personal rehabilitation goals, social functioning and empowerment and on care requirements and quality of life in persons with severe mental illness (smi) in the Netherlands. METHOD In a multicentre randomised controlled trial (rct: CLINICAL TRIAL REGISTRATION NUMBER isrctn73683215) patients with smi were randomly assigned to bpr (n = 80) or 'care as usual' (cau; n = 76). The primary outcome was the attainment of the rehabilitation goal as formulated by the patient. The secondary outcomes were a change in the work situation and in the degree of independent living, in care requirements (Camberwell Assessment of Needs), in empowerment (Personal Empowerment Scale) and in the quality of life (who-qol). The effects were tested at 12 and 24 months. RESULTS The degree of goal attainment was substantially higher in bpr at both 12 months (adjusted risk difference: 16%; 95%ci, 2 to 31; nnt = 7) and 24 months (adjusted risk difference: 21%, 95%ci, 4% to 38%; nnt = 5). The approach was also more effective in the area of societal participation (bpr: 21% adjusted increase, cau: 0% adjusted increase; nnt = 5), but not in the other secondary outcome measures. CONCLUSION The results suggest that bpr is effective in supporting patients with smi to reach self-formulated rehabilitation goals and in enhancing their societal participation.
Saliva, Diagnostics, and Dentistry

Saliva, a scientific and clinical entity familiar to every oral health researcher and dental practitioner, has emerged as a translational and clinical commodity that has reached national visibility at the National Institutes of Health and the President’s Office of Science and Technology. “Detecting dozens of diseases in a sample of saliva” was issued by President Obama as one of the 14 Grand Challenges for biomedical research in the 21st Century (National Economic Council, 2010). In addition, NIH’s 2011 Government Performance Report Act (GPRA) listed 10 initiatives in the high-risk long-term category (Collins, 2011). The mandate is to determine the efficacy of using salivary diagnostics to monitor health and diagnose at least one systemic disease by 2013. The stage is set for the scientific community to capture these national and global opportunities to advance and substantiate the scientific foundation of salivary diagnostics to meet these goals. A specific calling is to the oral, dental, and craniofacial health community. Three areas will be highlighted in this paper: the concept of high-impact diagnostics, the role of dentists in diagnostics, and, finally, an infrastructure currently being developed in the United Kingdom—The UK Biobank—which will have an impact on the translational and clinical utilizations of saliva.
Customer-Led Online Open Innovation of Consumer Goods: A Multiple-Case Study

Traditionally, studies of open innovation (OI) focused on high-tech industry. Though consumer goods industry is increasingly adopting online open innovation (OOI), managers are unclear about the trends of OOI. This study proposes a new classification of OOI in consumer goods industry: firm-led OOI and customer-led OOI, and identify the evolution trends of customer-led OOI. The finding is based on a longitudinal study of 138 cases. The results highlight the important areas that managers should pay particular attention to.
Legal practice on time: The ethical risk and inefficiency of the six-minute unit

Many law firms use time billing for client work with the ‘six-minute unit’ as the standard measure combined with billing ‘targets’ for employed lawyers, sometimes set at more than three times their salary. Time billing is designed to maximize the productivity of lawyers and provide a quantifiable rationale for billing clients, but is often used to control staff and identify ‘non-performers’. This paper critiques time billing and draws on its history and recent research to argue the practice not only motivates inefficiency, it increases the risk of ethical breaches, enables bullying by supervisors, may cause anxiety and mental health issues among employed lawyers, and contributes to the loss of good lawyers especially of women from the profession. The paper presents alternatives to time billing and suggests leading firms will recognise the advantages of adopting them ahead of professional regulators mandating change.
Familiarity leads to female mate preference for novel males in the guppy, Poecilia reticulata


Guppies are a model vertebrate for studies of sexual selection and life history evolution. None the less, there have been few investigations of the factors responsible for maintaining extreme within-population genetic variation in male coloration. In a laboratory study, we tested the hypothesis that frequency-dependent mate choice contributes to the maintenance of this variation. We attempted to avoid biases inherent in earlier studies of the 'rare male effect' by familiarizing females to males bearing a particular colour pattern and later presenting them with alternate male types, in equal numbers. Females were significantly more likely to mate with males having novel colour patterns than with males having a colour pattern with which they were familiar. This result is consistent with the hypothesis that mate choice is frequency dependent. Other factors such as male and female size were unrelated to mate preference. Implications of the results for theories of sexual selection and the maintenance of variation are discussed. Copyright 1999 The Association for the Study of Animal Behaviour.
Interactions between breast, bone, and brain regulate mineral and skeletal metabolism during lactation

Mammalian reproduction requires that nursing mothers transfer large amounts of calcium to their offspring through milk. As a result, lactation is associated with dramatic alterations in bone and mineral metabolism, including reversible bone loss. One theme that has emerged from recent studies examining these adaptations is that the lactating breast actively participates in regulating bone and mineral metabolism. This review will detail our current knowledge of interactions between the breast, skeleton, and hypothalamus during lactation and will consider implications that this reproductive physiology has for the pathophysiology of osteoporosis and breast cancer.
A socio-historical overview of codeswitching studies in the African languages

South African studies in codeswitching (CS) have tended to follow the history of African linguistics. They also run parallel with studies on CS in the rest of Africa. A socio- historical critique of language contact phenomena reveals perspectives that have evolved hand in hand with the social history, not only of South Africa but also of colonial and postcolonial Africa. This would explain for example the emphasis on the interaction between the colonial languages and the indigenous languages in CS patterns which is a typical feature of CS studies in Africa and other post-colonial societies. The more recent trend to focus on CS between the African languages themselves should further be regarded as a function of socio-historical development. Extensive CS on its part raises theoretical questions about language change, language shift, convergence, the pragmatic issues that are associated with each of them and their effects on the social fibre of Southern Africa.