Miracle-dz/UniFAR-FTUs huggingface dataset:
Small Molecule Target Identification using Drug Affinity Responsive Target Stability (DARTS)

Small molecule target identification is a monumental task. Knowledge of the binding interactions between small molecule compounds and cellular macromolecules such as proteins is crucial for understanding their biological properties and mechanisms of action, yet discovering these interactions remains a considerable challenge. To overcome the limitations of current target ID methods, we developed a novel technique that can identify direct binding interactions using the native, unmodified compounds. This method, called drug affinity responsive target stability (DARTS), takes advantage of the stabilization of protein structure upon drug binding that provides the target protein with resistance to protease degradation. When a small molecule is incubated with protein lysates, it binds and protects target proteins from proteolysis while degradation of non-target proteins is unaffected. Using proteomics, target proteins are then identified based on their enrichment in the compound-treated sample versus a control sample post-proteolysis. After demonstration of DARTS using a variety of known drug-protein pairs, DARTS was used to discover that the protein translation initiation machinery is a novel target of resveratrol. Then, to improve the sensitivity of DARTS, it was combined with a powerful gel-free fractionation technique and mass spectrometry analysis, which allowed for the identification of several potential new targets for the anti-cancer marine natural product didemnin B (DB). The TCP1 chaperonin complex (TRiC) was validated to be a target of DB using both biochemical and cell-based assays. Importantly, this is the first non ATP-mimetic compound reported to bind and inhibit TRiC, and could help design more specific and potent inhibitors of this complex. Finally, we demonstrated that DARTS can also be used for mapping the binding domains of small molecules within their target proteins. DARTS provided the first experimental evidence that DB binds both domains 1 and 2 of the eukaryotic elongation factor-1 alpha and verified the binding of pateamine A and hippuristanol to the N-terminal and C-terminal domains of the eukaryotic translation initiation factor 4a, respectively. Collectively, the results presented in this dissertation establish DARTS as a powerful technique for identifying and studying protein-small molecule interactions that will have a profound impact on the chemical biology field.
Identification for nonlinear singularly perturbed system using recurrent high-order multi-time scales neural network

A new identification algorithm for nonlinear singularly perturbed system using multi-time scales recurrent high-order neural networks is proposed in this paper. The high-order neural networks have simple structure and strong nonlinear approximation capability, which enables it to model the nonlinear singularly perturbed systems more accurately with less computation complexity, compared to multilayer neural networks. The optimal bounded ellipsoid algorithm, which is originally designed for discrete time systems, is introduced to update the weights of continuous multi-time scales neural networks. Compared to other widely used gradient-like updating methods, the on-line identification algorithm proposed in this paper can realize faster convergence, due to the adaptive “learning rate” of the weights updating laws. The effectiveness of the proposed scheme is demonstrated by simulation results.
Pancreatobiliary and peripancreatobiliary tuberculosis: a rare cause of obstructive jaundice

Tuberculosis (TB) is one of the most common and well-described infectious diseases, with a worldwide distribution and a vast spectrum of clinical manifestations. Tuberculosis involvement of the bile duct, pancreatic, periportal and/or peripancreatic lymph nodes is, however, surprising rare [1]. Patients with TB of the bile duct, pancreatic, periportal and/or peripancreatic lymph nodes usually present with protracted illness and obstructive jaundice, which may be confused with cholangiocarcinoma or pancreatic malignancies. During a 13-year period we encountered 6 patients with TB of the bile duct, pancreatic, periportal and/or peripancreatic lymph nodes. We describe our experience with the management of this condition and emphasize the importance of a tissue diagnosis in all patients with obstructive jaundice to avoid missing this rare but curable disease, which can elude diagnosis and might prove to be potentially fatal if left untreated. Records of all patients with obstructive jaundice treated in the Department of General Surgery, Zhongshan Hospital, Medical School of Fudan University between January 1995 and January 2008 were retrieved and reviewed retrospectively, to find patients with a histologically proven diagnosis of TB of the bile duct, pancreatic, periportal and/or peripancreatic lymph nodes. Demographic details, presentation, clinic and radiologic findings, endoscopic and surgical treatment, complications, and follow-up were recorded. Written informed consent was obtained from all patients or patients’ relatives, and this study was approved by the local ethical committees. During the above-mentioned period, of a total of 1400 patients treated for various types of obstructive jaundice in our department, there were 6 (0.43%) patients with TB of the bile duct, pancreatic, periportal and/or peripancreatic lymph nodes. There were 4 males and 2 females with a mean age of 41.3 (range: 24– 54 years). These patients were symptomatic for a mean duration of 2 weeks (range 1 week to 4 weeks). The main presenting symptoms were: jaundice (n = 6); epigastric (upper abdominal) pain (n = 4); anorexia and weight loss (n = 3); fever (n = 4) (Table I). All patients were previously healthy and none gave a history of any recent or past contact with tuberculosis. Two patients had a history of alcohol abuse while one was a known diabetic. Chest radiographs were normal in 5 patients and one patient with pulmonary TB. Human immunodeficiency virus status was negative in all patients. The mean total serum bilirubin level was raised at 192 μmol/l (range: 89–253 μmol/l; normal: 2–24 μmol/l). The mean serum alkaline phosphatase, γ-glutamyl transpeptidase, and alanine transaminase levels Corresponding author: Dr Houbao Liu Zhongshan Hospital of Fudan University No. 180, Fenglinqiao Rd 200032 Shanghai, China Phone: +86-21-64041990 E-mail: drhoubao.liu@gmail.com Letter to the Editor
Excited-State Proton Transfer and Phototautomerism in Nucleobase and Nucleoside Analogs: A Mini-Review

Intermolecular excited-state proton transfer (ESPT) has been observed in several fluorescent nucleobase and/or nucleoside analogs. In the present work, some new examples of ESPT in this class of compounds are presented together with a brief recapitulation of the previously published data. The nucleobases, nucleosides, and their analogs contain many basic and acidic centers and therefore their ESPT behavior may be complex. To interpret the complex data, it is usually necessary to determine the microscopic pK* values for each (or most) of the possible ESPT centers. Typical approach to solve this problem is by analysis of the alkyl derivatives, in which the possibility of the ESPT is reduced. Of particular interest are examples of “phototautomerization via the cation,” observed in several systems, which in the neutral media do not undergo ESPT. Protonation of the molecule in the ground state facilitates the two-step phototautomerism in several systems, including formycin A and 2-amino-8-azadenine. Fluorescence of the nucleobase and nucleoside analogs undergoing ESPT is usually solvent-, isotope-, and buffer-ion sensitive, and in some systems the ESPT can be promoted by environmental factors, e.g., the presence of buffer ions. This sensitivity to the microenvironment parameters makes the ESPT systems potentially useful for biological applications.
Fuzzy-rough set based attribute reduction with a simple fuzzification method

The fuzzy-rough set based attribute reduction, which can get better reducts than the crisp rough set approach, has been paid more attention recently. Fuzzification is a step of data preprocess which was studied less in the application of fuzzy-rough set. In this paper, a simple fuzzification method deriving fuzzy discretization from K most important cuts in the application of feature selection is proposed. A comparative experiment between the proposed fuzzification method and a general fuzzy c-means based method is constructed on the UCI machine learning data repository. The experimental results show the obtained reducts using the proposed method can get higher classification accuracies and less number of selected attributes.
Levels of expression of hRPB 11 , a core subassembly subunit of human RNA polymerase II , a ¡ ect doxorubicin sensitivity and cellular di ¡ erentiation

We have previously shown that the human RNA polymerase II subunit 11 (hRPB11) is among the proteins specifically downregulated upon Doxorubicin (Dox) treatment of human cancer cell lines, and that Dox resistant clones derived upon drug selection express about 20% of the protein present in the original parental cell line. Given the prominent role that this subunit appears to have in eukaryotic cells, and the fact that its deletion causes lethality in yeast, we wanted to test the effect of the reintroduction of parental cell line levels of this subunit in Dox resistant colon cancer cells (LoVoDX). Stable transfectants of LoVoDX expressing parental (LoVoH) levels of hRPB11 showed a reduced sensitivity to the drug without changing the response of these cells to other chemotherapeutic agents, confirming a specific inverse correlation between cellular Dox sensitivity anti-hRPB11 levels of expression. In addition we show here that the levels of expression of this same RNA polymerase II subunit directly affect cellular differentiation, reducing the rate of cell proliferation, clonogenicity and increasing the expression of E-cadherin, a marker of epithelial cell differentiation. As expected from cells with these characteristics, upon in vivo administration of these clones in nude mice, we detected a significant reduction in the size and time of appearance of the primary tumors and overall metastatic capability. Finally, the role played by hRPB11 in regulating the transcription of specific genes is underlined by transient transfection experiments that show transactivation of the E-cadherin promoter by this protein. z 1998 Federation of European Biochemical Societies.
Point Estimation Using A Recursive Neural Network

3D reconstruction and pose estimation have been huge areas of research in recent years. Success in these two areas have allowed enormous strides in augmented reality, 3D scanning, and interactive gaming. However, utilizing machine learning in this realm has been a difficulty since creating relevant datasets is extremely time consuming. Additionally, 3D annotated video datasets do not exist yet. By rendering 3D objects, we create a dataset of image sequences to emulate video frame data. Using a VGG net [Simonyan and Zisserman 2014] and a RNN, we introduce a model that can predict a object’s 3D bounding box based on synthetic video-like image sequences. Our model can be extended to predict 3D feature points to create point cloud data for 3D reconstruction.
Development of cholinergic amacrine cells is visual activity‐dependent in the postnatal mouse retina

In the present study, we used immunocytochemistry to study the temporal and spatial arrangement of mouse cholinergic amacrine cells during postnatal retinal development under normal light/dark cycles and during visual deprivation. Choline acetyltransferase (ChAT)‐immunolabeled cells were detected in the neuroblastic layer (NBL) and in the ganglion cell layer (GCL) at postnatal day 0 (P0). Between P3–5, two characteristic cholinergic bands were clearly identified in the inner plexiform layer (IPL). The signal intensity of somas and processes progressively increased over the first 2 postnatal weeks. Around eye opening at P12, cholinergic neurons were mature‐like. This early developmental process was not altered by visual deprivation. After eye opening, the space between the two cholinergic bands increased continuously and the spatial regularity index changed constantly, indicating that the cholinergic neurons possibly underwent refinement during later postnatal development. The changes occurring following eye opening were retarded by visual deprivation. The morphologies of photoreceptors, horizontal cells, recoverin‐positive OFF‐cone bipolar cells, rod bipolar cells, dopaminergic amacrine cells, and Müller cells appeared normal. Their stratification in the outer plexiform layer (OPL) and the IPL was not affected by visual deprivation. However, glial cells grew vertically across the entire thickness of dark‐reared retinas. Our results suggest that the development of cholinergic neurons before eye opening is independent of the lighting conditions. Their development after eye opening is greatly impeded by visual deprivation. This visual activity‐dependent phase of development may be a critical period for the maturation and synaptic wiring of cholinergic amacrine cells in the mammalian retina. J. Comp. Neurol. 484:331–343, 2005. © 2005 Wiley‐Liss, Inc.
Factor-dependent archaeal transcription termination

Significance Proper transcription regulation is necessary for timely and accurate gene expression underlying growth and development. Transcription is regulated at each stage of the transcription cycle—initiation, elongation, and termination—and it is critical to define the factors and sequences regulating RNA polymerase activity. Many studies have investigated the mechanisms used by transcription factors involved in regulation of transcription initiation and elongation, but a mechanistic understanding of transcription termination has been slower to emerge. Here we characterize the first archaeal transcription termination factor, termed euryarchaeal termination activity (Eta). The mechanisms of Eta-mediated termination provide the first understanding of archaeal factor-dependent termination and provide insight into and contrast with the mechanisms used for factor-dependent termination in extant life. RNA polymerase activity is regulated by nascent RNA sequences, DNA template sequences, and conserved transcription factors. Transcription factors promoting initiation and elongation have been characterized in each domain, but transcription termination factors have been identified only in bacteria and eukarya. Here we describe euryarchaeal termination activity (Eta), the first archaeal termination factor capable of disrupting the transcription elongation complex (TEC), detail the rate of and requirements for Eta-mediated transcription termination, and describe a role for Eta in transcription termination in vivo. Eta-mediated transcription termination is energy-dependent, requires upstream DNA sequences, and disrupts TECs to release the nascent RNA to solution. Deletion of TK0566 (encoding Eta) is possible, but results in slow growth and renders cells sensitive to DNA damaging agents. Our results suggest that the mechanisms used by termination factors in archaea, eukarya, and bacteria to disrupt the TEC may be conserved, and that Eta stimulates release of stalled or arrested TECs.
Reductive evolution of proteomes and protein structures

The lengths of orthologous protein families in Eukarya are almost double the lengths found in Bacteria and Archaea. Here we examine protein structures in 745 genomes and show that protein length differences between superkingdoms arise as much shorter prokaryotic nondomain linker sequences. Eukaryotic, bacterial, and archaeal linkers are 250, 86, and 73 aa residues in length, respectively, whereas folded domain sequences are 281, 280, and 256 residues, respectively. Cryptic domains match linkers (P < 0.0001) with probabilities ranging between 0.022 and 0.042; accordingly, they do not affect length estimates significantly. Linker sequences support intermolecular binding within proteomes and they are probably enriched in intrinsically disordered regions as well. Reductively evolved linker sequence lengths in growth rate maximized cells should be proportional to proteome diversity. By using total in-frame coding capacity of a genome [i.e., coding sequence (CDS)] as a reliable measure of proteome diversity, we find linker lengths of prokaryotes clearly evolve in proportion to CDS values, whereas those of eukaryotes are more randomly larger than expected. Domain lengths scarcely change over the entire range of CDS values. Thus, the protein linkers of prokaryotes evolve reductively whereas those of eukaryotes do not.
ANALYSIS OF INDUSTRY PERCEPTIONS AND EXPECTATIONS OF TOURISM STUDENTS: A CASE STUDY IN TURKEY

Tourism and Hospitality Management Schools’ students must complete their internship before graduation in four or five stars hotels or travel agencies in Turkey. Some students may have negative perceptions of tourism education and working conditions in the industry, after they have worked as trainees in the industry. The aim of the study is to compare the perceptions and expectations of students in relation to tourism industry who have done their internship with those who have not and is to explore the differences in their future expectations and any changes in their career plans. For the purpose of the study a questionnaire was prepared, based on relevant literature, and the survey was conducted in the School of Tourism and Hotel Management at Anadolu University in Turkey. 204 students were selected by the use of stratified sampling as the study sample from the first, second, third and the fourth year. Half of the questionnaires were distributed to students who had done their internship and the rest to the students who had not undertaken internship yet. Results indicate that the respondents’ perceptions and expectations of the industry were not significant according to their experience. Finally, the differences between respondents are summarized and implications are drawn for the educational institutions and further studies.
Adding Knowledge Extracted by Association Rules into Similarity Queries

In this paper, we propose new techniques to improve the quality of similarity queries over image databases performing association rule mining over textual descriptions and automatically extracted features of the image content. Based on the knowledge mined, each query posed is rewritten in order to better meet the user expectations. We propose an extension of SQL aimed at exploring mining processes over complex data, generating association rules that extract semantic information from the textual description superimposed to the extracted features, thereafter using them to rewrite the queries. As a result, the system obtains results closer to the user expectation than it could using only the traditional, plain similarity query execution.
High-performance jumping movements by pendulum-type jumping machines

On vertical jumping movements of humans, swings of arms and counter movements of legs are essential. In this paper, the swings of arms are focused, and two pendulum-type jumping machines are presented. The aim of our research is to show that the presented mechanism, to which the swings of arms am applied, is effective to perform jumping movements. These pendulum-type jumping machines demonstrate abilities of jumping up, soft landing, and going up and down stairs. Consequently, it is concluded that the swings of arms will contribute toward high-performance jumping movements.
The Clk2 and Clk3 dual-specificity protein kinases regulate the intranuclear distribution of SR proteins and influence pre-mRNA splicing.

The three members of the Clk family of kinases (Clk1, 2, and 3) have been shown to undergo conserved alternative splicing to generate catalytically active (Clk) and inactive (ClkT) isoforms. The prototype, murine Clk1 (mClk1), is a nuclear dual-specificity kinase that can interact with, and cause the nuclear redistribution of, SR proteins. In this study, we demonstrate that the human Clk2 and Clk3 (hClk2 and 3) are also found within the nucleus and display dual-specificity kinase activity. The truncated isoforms, hClk2(T) and hClk3(T), colocalize with SR proteins in nuclear speckles. We also show catalytically active hClk2 and hClk3 cause the redistribution of SR proteins and can regulate the alternative splicing of a model precursor mRNA substrate in vivo.
Data-Driven Neuro-Optimal Temperature Control of Water–Gas Shift Reaction Using Stable Iterative Adaptive Dynamic Programming

In this paper, a novel data-driven stable iterative adaptive dynamic programming (ADP) algorithm is developed to solve optimal temperature control problems for water-gas shift (WGS) reaction systems. According to the system data, neural networks (NNs) are used to construct the dynamics of the WGS system and solve the reference control, respectively, where the mathematical model of the WGS system is unnecessary. Considering the reconstruction errors of NNs and the disturbances of the system and control input, a new stable iterative ADP algorithm is developed to obtain the optimal control law. The convergence property is developed to guarantee that the iterative performance index function converges to a finite neighborhood of the optimal performance index function. The stability property is developed to guarantee that each of the iterative control laws can make the tracking error uniformly ultimately bounded (UUB). NNs are developed to implement the stable iterative ADP algorithm. Finally, numerical results are given to illustrate the effectiveness of the developed method.
EMPLOYEE MOTIVATION AND ORGANIZATIONAL OUTPUT: RELATIONAL MAPPING IN SELECTED SMES

Amidst a challenging and competitive environment, Small and medium enterprises (SMEs) have stood out as the major support to the developing nations in enhancing their economic as well as social conditions. These labor dependent industries focusses mainly to retain their employees by the means of motivation. Employees’ motivation levels are considered to have a direct impact on their productivity (Veliu, Manxhari, & Ujkani, 2015). In recent years Pakistan has experienced several highs and lows with respect to its SMEs (Dar, Ahmed, & Raziq, 2017). Therefore the present study seeks to identify the relation between employee’s motivation and their overall work performance in selected SMEs of Karachi. Using regression analysis, the present study encountered that there exists a relation between employees’ motivation and the overall work performance at their organization but fails to establish the positive relation between them. Lastly the study presents few implications and limitations of this research.
Plasmacytoid Dendritic Cells in Lymph Nodes of Patients With Human Immunodeficiency Virus

Circulating plasmacytoid dendritic cells (PDC) decrease in human immunodeficiency virus (HIV) infection, either from loss or redistribution to lymph nodes (LN). Limited animal and human studies variably showed increased or decreased nodal PDC. CD123 immunostaining was performed on 28 archived LN biopsies (20 reactive) from 25 HIV patients. PDC clustering was graded (1: none; 2: rare small; 3: medium-sized, loose; and 4: large tight clusters) and correlated with HIV-lymphadenitis stage, blood CD4 counts, time since HIV diagnosis, and treatment duration. Increased PDC clustering was seen with decreasing CD4 counts (P=0.001), shorter treatment duration (P=0.0268), and advancing HIV-lymphadenitis stage (P=0.06). No correlation with time since HIV diagnosis was noted. To our knowledge, this is the first human study assessing relationship of nodal PDC in HIV to CD4 counts, treatment duration, and lymphadenitis pattern. Our findings suggest that PDC redistribute to LN with advancing immunodeficiency and stage of HIV infection.