Miracle-dz/UniFAR-FTUs huggingface dataset:
CAMDEX: A Standardised Instrument for the Diagnosis of Mental Disorder in the Elderly with Special Reference to the Early Detection of Dementia

A new interview schedule for the diagnosis and measurement of dementia in the elderly is described. The schedule named the Cambridge Mental Disorders of the Elderly Examination (CAMDEX), consists of three main sections: (1) A structured clinical Interview with the patient to obtain systematic information about the present state, past history and family history; (2) a range of objective cognitive tests which constitute a minineuropsychological battery; (3) a structured Interview with a relative or other Informant to obtain Independent Information about the respondent's present state, past history and family history. The CAMDEX Is acceptable to patients, has a high inter-rater reliability and the cognitive section has been shown to have high sensitivity and specificity.
Self-interference digital holographic camera using geometrical phase lens

A self-interference digital holographic camera with geometrical phase lens used as a passive-type common-path polarization selective wavefront modulator is proposed. A prototype is devised and the demonstration of self-interference is carried out. Since the geometrical phase lens is light weight, thin, transparent, and cost effective, the application toward the consumer level holographic camera capture system is expected.
ANNUAL GRASSES CONTROL WITH TOPRAMEZONE IN MIXTURE WITH ALS-INHIBITING HERBICIDES

Panicoid grasses are major weeds of maize and sugarcane as well as of several other important grains, including sorghum, pearl millet, and foxtail millet. Pot trials were conducted to study the activity and potential interactions of topramezone in mixture with recommended rates of rimsulfuron or nicosulfuron on three annual panicoid grasses (i.e. Echinochloa oryzoides,E.phyllopogon, and Panicum miliaceum). Target weeds were treated at the four- to five-leaf growth stage. On the basis of fresh weight reduction, topramezone alone provided 78% control of E.oryzoides, 68% control of E.phyllopogon, and 99% control of P.miliaceum. Topramezone plus rimsulfuron or nicosulfuron provided decreased control of both Echinochloa spp. compared with topramezone alone. The decreased control of E.oryzoidesand E.phyllopogon was more pronounced with rimsulfuron as a companion herbicide in the mixtures. Slightly decreased control of P.milaceum was observed with topramezone plus rimsulfuron compared with topramezone alone, but this was not the case for topramezone plus nicosulfuron. Increased topramezone rates mixed with rimsulfuron or nicosulfuron did not improve control of E.oryzoides and E.phyllopogon compared with the lowest topramezone rate. Also, increased topramezone rates mixed with rimsulfuron or nicosulfuron showed decreased control of both Echinochloa spp. when compared with either rimsulfuron or nicosulfuron alone, suggesting a two-way interaction between topramezone and the ALS-inhibiting herbicides. The above-mentioned interaction was not observed in P.miliaceum, probably related with species sensitivity to the herbicides tested. Newly introduced or naturalized panicoid grasses in maize fields may complicate selection of companion herbicides and rates for effective weed control.
Understanding User Behavior in Sina Weibo Online Social Network: A Community Approach

Sina Weibo, a Twitter-like microblogging Website in China, has become the main source of different kinds of information, such as breaking news, social events, and products. There is great value to exploiting the actual interests and behaviors of users, which creates opportunity for better understanding of the information dissemination mechanisms on social network sites. In this paper, we focus our attention to characterizing user behaviors in tweeting, retweeting, and commenting on Sina Weibo. In particular, we built a Shenzhen Weibo community graph to analyze user behaviors, clustering the coefficients of the community graph and exploring the impact of user popularity on social network sites. Bipartite graphs and one-mode projections are used to analyze the similarity of retweeting and commenting activities, which reveal the weak correlations between these two behaviors. In addition, to characterize the user retweeting behaviors deeply, we also study the tweeting and retweeting behaviors in terms of the gender of users. We observe that females are more likely to retweet than males. This discovery is useful for improving the efficiency of message transmission. What is more, we introduce an information-theoretical measure based on the concept of entropy to analyze the temporal tweeting behaviors of users. Finally, we apply a clustering algorithm to divide users into different groups based on their tweeting behaviors, which can improve the design of plenty of applications, such as recommendation systems.
Modified mRNA as a therapeutic tool to induce cardiac regeneration in ischemic heart disease

Ischemic heart disease (IHD) is a leading cause of morbidity and mortality in developed countries. Current pharmacological and interventional therapies provide significant improvement in the life quality of patient; however, they are mostly symptom‐oriented and not curative. A high disease and economic burden of IHD requires the search for new therapeutic strategies to significantly improve patients’ prognosis and quality of life. One of the main challenges during IHD is the massive loss of cardiomyocytes that possess minimal regenerative capacity. Recent understanding of the pathophysiological mechanisms underlying IHD, as well as new therapeutic approaches provide new hope for patients suffering from IHD. Synthetic modified mRNA (modRNA) is a new gene delivery vector that is increasingly used in in vivo applications. modRNA is a relatively stable, non‐immunogenic, highly‐expressed molecule that has been shown to mediate high and transient expression of proteins in different type of cells and tissues including cardiomyocytes. modRNA properties, together with its expression kinetics in the heart make it an attractive option for the treatment of IHD, especially after myocardial infarction. In this review we discuss the role of gene therapy in cardiac regeneration as an approach to treat IHD; traditional and innovative gene delivery methods; and focus specifically on modRNA structure, mode of delivery, and its use for the induction of endogenous regenerative capacity, mainly in the context of IHD. WIREs Syst Biol Med 2017, 9:e1367. doi: 10.1002/wsbm.1367
Preclinical Evaluation of 18F-RO6958948, 11C-RO6931643, and 11C-RO6924963 as Novel PET Radiotracers for Imaging Tau Aggregates in Alzheimer Disease

Tau aggregates and amyloid-β (Aβ) plaques are key histopathologic features in Alzheimer disease (AD) and are considered targets for therapeutic intervention as well as biomarkers for diagnostic in vivo imaging agents. This article describes the preclinical in vitro and in vivo characterization of 3 novel compounds—RO6958948, RO6931643, and RO6924963—that bind specifically to tau aggregates and have the potential to become PET tracers for future human use. Methods: RO6958948, RO6931643, and RO6924963 were identified as high-affinity competitors at the 3H-T808 binding site on native tau aggregates in human late-stage AD brain tissue. Binding of tritiated compounds to brain tissue sections of AD patients and healthy controls was analyzed by macro- and microautoradiography and by costaining of tau aggregates and Aβ plaques on the same tissue section using specific antibodies. All 3 tracer candidates were radiolabeled with a PET nuclide and tested in vivo in tau-naïve baboons to assess brain uptake, distribution, clearance, and metabolism. Results: 3H-RO6958948, 3H-RO6931643, and 3H-RO6924963 bound with high affinity and specificity to tau aggregates, clearly lacking affinity for concomitant Aβ plaques in human AD Braak V tissue sections. The specificity of all 3 radioligands for tau aggregates was supported, first, by binding patterns in AD sections comparable to the tau-specific radioligand 3H-T808; second, by very low nonspecific binding in brain tissue devoid of tau pathology, excluding significant radioligand binding to any other central nervous system target; and third, by macroscopic and microscopic colocalization and quantitative correlation of radioligand binding and tau antibody staining on the same tissue section. RO6958948, RO6931643, and RO6924963 were successfully radiolabeled with a PET nuclide at high specific activity, radiochemical purity, and yield. After intravenous administration of 18F-RO6958948, 11C-RO6931643, and 11C-RO6924963 to baboons, PET scans indicated good brain entry, rapid washout, and a favorable metabolism pattern. Conclusion: 18F-RO6958948, 11C-RO6931643, and 11C-RO6924963 are promising PET tracers for visualization of tau aggregates in AD. Head-to-head comparison and validation of these tracer candidates in AD patients and healthy controls will be reported in due course.
Observer-Based Adaptive Fuzzy Decentralized Optimal Control Design for Strict-Feedback Nonlinear Large-Scale Systems

In this paper, the problem of adaptive fuzzy decentralized optimal control is investigated for a class of nonlinear large-scale systems in strict-feedback form. The considered nonlinear large-scale systems contain the unknown nonlinear functions and unmeasured states. By utilizing the fuzzy logic systems to approximate the unknown nonlinear functions and cost functions, a fuzzy state observer is established to estimate the unmeasured states. The control design is divided into two phases. First, by using the state observer and the backstepping design technique, a feedforward decentralized controller with parameters adaptive laws is designed, by which the original controlled strict-feedback nonlinear large-scale system is transformed into an equivalent affine nonlinear large-scale system. Second, by using adaptive dynamic programming theory, a feedback decentralized optimal controller is developed for the equivalent affine nonlinear system. The whole adaptive fuzzy decentralized optimal control scheme consists of a feedforward decentralized controller and a feedback decentralized optimal controller. It is shown that the proposed adaptive fuzzy decentralized optimal control approach can guarantee that all the signals in the closed-loop system are bounded, and the tracking errors converge to a small neighborhood of zero. In addition, the proposed control approach can guarantee that the cost functions are minimized. Simulation results are given to demonstrate the effectiveness of the proposed control approach.
The Structural Interface between HIV-1 Vif and Human APOBEC3H

ABSTRACT Human APOBEC3H (A3H) is a cytidine deaminase that inhibits HIV-1 replication. To evade this restriction, the HIV-1 Vif protein binds A3H and mediates its proteasomal degradation. To date, little information on the Vif-A3H interface has been available. To decipher how both proteins interact, we first mapped the Vif-binding site on A3H by functionally testing a large set of A3H mutants in single-cycle infectivity and replication assays. Our data show that the two A3H α-helixes α3 and α4 represent the Vif-binding site of A3H. We next used viral adaptation and a set of Vif mutants to identify novel, reciprocal Vif variants that rescued viral infectivity in the presence of two Vif-resistant A3H mutants. These A3H-Vif interaction points were used to generate the first A3H-Vif structure model, which revealed that the A3H helixes α3 and α4 interact with the Vif β-sheet (β2-β5). This model is in good agreement with previously reported Vif and A3H amino acids important for interaction. Based on the predicted A3H-Vif interface, we tested additional points of contact, which validated our model. Moreover, these experiments showed that the A3H and A3G binding sites on HIV-1 Vif are largely distinct, with both host proteins interacting with Vif β-strand 2. Taken together, this virus-host interface model explains previously reported data and will help to identify novel drug targets to combat HIV-1 infection. IMPORTANCE HIV-1 needs to overcome several intracellular restriction factors in order to replicate efficiently. The human APOBEC3 locus encodes seven proteins, of which A3D, A3F, A3G, and A3H restrict HIV-1. HIV encodes the Vif protein, which binds to the APOBEC3 proteins and leads to their proteasomal degradation. No HIV-1 Vif-APOBEC3 costructure exists to date despite extensive research. We and others previously generated HIV-1 Vif costructure models with A3G and A3F by mapping specific contact points between both proteins. Here, we applied a similar approach to HIV-1 Vif and A3H and successfully generated a Vif-A3H interaction model. Importantly, we find that the HIV-1 Vif-A3H interface is distinct from the Vif-A3G and Vif-A3F interfaces, with a small Vif region being important for recognition of both A3G and A3H. Our Vif-A3H structure model informs on how both proteins interact and could guide toward approaches to block the Vif-A3H interface to target HIV replication.
Industrial Internet of Things based cycle time control of assembly lines

Dynamic cycle time setting and line balancing are the most significant problems in modular manufacturing. Industry 4.0 and IIoT (Industrial Internet of Things) based production management systems connect decentralized production units and information sources to increase productivity and flexibility. We developed an IIoT based solution to ensure a real-time connection between products and assembly lines. The proposed dynamic cycle time setting algorithm takes into account the varying complexity of the product based on the real-time information provided by smart wireless sensors and an Indoor Positioning System (IPS). In this paper, we overview Industry 4.0 based assembly line management solutions, present the developed IIoT based infrastructure, and demonstrate the applicability of the proposed cycle time setting algorithm in a simulation example motivated by an industrial open station conveyor.
PMP22 antisense oligonucleotides reverse Charcot-Marie-Tooth disease type 1A features in rodent models

Charcot-Marie-Tooth disease type 1A (CMT1A) is caused by duplication of peripheral myelin protein 22 (PMP22) and is the most common hereditary peripheral neuropathy. CMT1A is characterized by demyelination and axonal loss, which underlie slowed motor nerve conduction velocity (MNCV) and reduced compound muscle action potentials (CMAP) in patients. There is currently no known treatment for this disease. Here, we show that antisense oligonucleotides (ASOs) effectively suppress PMP22 mRNA in affected nerves in 2 murine CMT1A models. Notably, initiation of ASO treatment after disease onset restored myelination, MNCV, and CMAP almost to levels seen in WT animals. In addition to disease-associated gene expression networks that were restored with ASO treatment, we also identified potential disease biomarkers through transcriptomic profiling. Furthermore, we demonstrated that reduction of PMP22 mRNA in skin biopsies from ASO-treated rats is a suitable biomarker for evaluating target engagement in response to ASO therapy. These results support the use of ASOs as a potential treatment for CMT1A and elucidate potential disease and target engagement biomarkers for use in future clinical trials.
Proteomics: from single molecules to biological pathways

The conventional reductionist approach to cardiovascular research investigates individual candidate factors or linear signalling pathways but ignores more complex interactions in biological systems. The advent of molecular profiling technologies that focus on a global characterization of whole complements allows an exploration of the interconnectivity of pathways during pathophysiologically relevant processes, but has brought about the issue of statistical analysis and data integration. Proteins identified by differential expression as well as those in protein–protein interaction networks identified through experiments and through computational modelling techniques can be used as an initial starting point for functional analyses. In combination with other ‘-omics’ technologies, such as transcriptomics and metabolomics, proteomics explores different aspects of disease, and the different pillars of observations facilitate the data integration in disease-specific networks. Ultimately, a systems biology approach may advance our understanding of cardiovascular disease processes at a ‘biological pathway’ instead of a ‘single molecule’ level and accelerate progress towards disease-modifying interventions.
Structural Characterization of Human Coronavirus NL63 N Protein

ABSTRACT Coronaviruses are responsible for upper and lower respiratory tract infections in humans. It is estimated that 1 to 10% of the population suffers annually from cold-like symptoms related to infection with human coronavirus NL63 (HCoV-NL63), an alphacoronavirus. The nucleocapsid (N) protein, the major structural component of the capsid, facilitates RNA packing, links the capsid to the envelope, and is also involved in multiple other processes, including viral replication and evasion of the immune system. Although the role of N protein in viral replication is relatively well described, no structural data are currently available regarding the N proteins of alphacoronaviruses. Moreover, our understanding of the mechanisms of RNA binding and nucleocapsid formation remains incomplete. In this study, we solved the crystal structures of the N- and C-terminal domains (NTD, residues 10 to 140, and CTD, residues 221 to 340, respectively) of the N protein of HCoV-NL63, both at a 1.5-Å resolution. Based on our structure of NTD solved here, we proposed and experimentally evaluated a model of RNA binding. The structure of the CTD reveals the mode of N protein dimerization. Overall, this study expands our understanding of the initial steps of N protein-nucleic acid interaction and may facilitate future efforts to control the associated infections. IMPORTANCE Coronaviruses are responsible for the common cold and other respiratory tract infections in humans. According to multiple studies, 1 to 10% of the population is infected each year with HCoV-NL63. Viruses are relatively simple organisms composed of a few proteins and the nucleic acids that carry the information determining their composition. The nucleocapsid (N) protein studied in this work protects the nucleic acid from the environmental factors during virus transmission. This study investigated the structural arrangement of N protein, explaining the first steps of its interaction with nucleic acid at the initial stages of virus structure assembly. The results expand our understanding of coronavirus physiology and may facilitate future efforts to control the associated infections.
Modified toolbox for optogenetics in the nonhuman primate

Abstract. Attracted by the appealing advantages of optogenetics, many nonhuman primate labs are attempting to incorporate this technique in their experiments. Despite some reported successes by a few groups, many still find it difficult to develop a reliable way to transduce cells in the monkey brain and subsequently monitor light-induced neuronal activity. Here, we describe a methodology that we have developed and successfully deployed on a regular basis with multiple monkeys. All devices and accessories are easy to obtain and results using these have been proven to be highly replicable. We developed the “in-chair” viral injection system and used tapered and thinner fibers for optical stimulation, which significantly improved the efficacy and reduced tissue damage. With these methods, we have successfully transduced cells in multiple monkeys in both deep and shallow cortical areas. We could reliably obtain neural modulation for months after injection, and no light-induced artifacts were observed during recordings. Further experiments using these methods have shown that optogenetic stimulation can be used to bias spatial attention in a visual choice discrimination task in a way comparable to electrical microstimulation, which demonstrates the potential use of our methods in both fundamental research and clinical applications.
Activation of AMPK by metformin improves withdrawal signs precipitated by nicotine withdrawal

Significance Cigarette smoking is the leading cause of preventable disease and death in the United States. Severe withdrawal symptoms are the reason most people have a hard time quitting smoking. AMP-activated protein kinase (AMPK) is a master regulator of energy homeostasis and is activated in response to cellular stressors. We discovered that the AMPK pathway is activated following chronic nicotine use but is repressed following nicotine withdrawal. We reasoned that increasing pAMPK levels pharmacologically might reduce symptoms of nicotine withdrawal. After giving mice metformin, an AMPK activator, we were able to reduce nicotine withdrawal, and found that this was dependent on the presence of the AMPK protein in the hippocampus. This study suggests that AMPK activation could be a target for smoking cessation. Cigarette smoking is the leading cause of preventable disease and death in the United States, with more persons dying from nicotine addiction than any other preventable cause of death. Even though smoking cessation incurs multiple health benefits, the abstinence rate remains low with current medications. Here we show that the AMP-activated protein kinase (AMPK) pathway in the hippocampus is activated following chronic nicotine use, an effect that is rapidly reversed by nicotine withdrawal. Increasing pAMPK levels and, consequently, downstream AMPK signaling pharmacologically attenuate anxiety-like behavior following nicotine withdrawal. We show that metformin, a known AMPK activator in the periphery, reduces withdrawal symptoms through a mechanism dependent on the presence of the AMPKα subunits within the hippocampus. This study provides evidence of a direct effect of AMPK modulation on nicotine withdrawal symptoms and suggests central AMPK activation as a therapeutic target for smoking cessation.
Robust Low-Rank Approximation of Images for Background and Foreground Separation

Background and foreground separation is the major task in video surveillance system to detect moving or suspicious objects. Robust Principal Component Analysis, whose formulation relies on low-rank plus sparse matrices decomposition, shows an interestingly suitable framework to separate moving objects from the background. The optimization problem is transformed to a sequence of convex programs that minimize the sum of L1-norm and nuclear norm of the two component matrices, which are efficiently resolved by an Augmented Lagrangian Multiplierss based solver. In this paper, we propose two new robust schemas for low rank approximation of numerical matrices. The proposed algorithms allow batch and incremental robust low-rank approximal of matrices used in static and real-time foreground extraction to detect moving objects. Experiments reveal that the proposed method are both deterministic, converge decently and quickly; besides, they achieve an accurate background and foreground separation outcome.
The impact of learning technologies in classroom instruction

Learning technology is about various related techniques used to communicate or exchange the information either synchronously or asynchronously. There is a necessity to understand the preferences of the learners and the teachers over the various types of learning technologies used when interacting with the pupils, in class room teaching such as document camera, interactive white board, presentations, video conferencing, simulations, information retrieval systems, technical forum's, webinars, vod-casting, pod-casting to acquire or distribute knowledge which help to provide support in effective teaching, monitoring and assessment.