Miracle-dz/UniFAR-FTUs huggingface dataset:
Advances in functional assays for high-throughput screening of ion channels targets

Importance of the field: Ion channels are important targets for many disease areas but are challenging to screen due to lack of technologies enabling robust high-throughput assays, particularly for state-dependent interactions. Areas covered in this review: Current assay technologies used to measure ion channel function are reviewed and assessed for use in high-throughput screening (HTS). An iterative approach to screening is evaluated as an alternative to full collection screening in order to take advantage of low-throughput, high cost assays that yield high quality data. What the reader will gain: The reader will gain an understanding of the advantages and disadvantages of various assay techniques used to screen ion channels and their suitability for use in HTS. Take home message: Assays that directly measure ion channel function are prone to less artifact and higher hit confirmation in screening than those using an indirect measure but they are usually lower throughput. However, an iterative approach to screening can make the relatively lower throughput techniques amenable for use in interrogating large collections of compounds.
Effect of the Children’s Health Activity Motor Program on Motor Skills and Self-Regulation in Head Start Preschoolers: An Efficacy Trial

Self-regulatory skills are broadly defined as the ability to manage emotions, focus attention, and inhibit some behaviors while activating others in accordance with social expectations and are an established indicator of academic success. Growing evidence links motor skills and physical activity to self-regulation. This study examined the efficacy of a motor skills intervention (i.e., the Children’s Health Activity Motor Program, CHAMP) that is theoretically grounded in Achievement Goal Theory on motor skill performance and self-regulation in Head Start preschoolers. A sample of 113 Head Start preschoolers (Mage = 51.91 ± 6.5 months; 49.5% males) were randomly assigned to a treatment (n = 68) or control (n = 45) program. CHAMP participants engaged in 15, 40-min sessions of a mastery climate intervention that focused on the development of motor skills over 5 weeks while control participants engaged in their normal outdoor recess period. The Delay of Gratification Snack Task was used to measure self-regulation and the Test of Gross Motor Development-2nd Edition was used to assess motor skills. All measures were assessed prior to and following the intervention. Linear mixed models were fit for both self-regulation and motor skills. Results revealed a significant time × treatment interaction (p < 0.001). In regard to motor skills, post hoc comparisons found that all children improved their motor skills (p < 0.05), but the CHAMP group improved significantly more than the control group (p < 0.001). Children in CHAMP maintained their self-regulation scores across time, while children in the control group scored significantly lower than the CHAMP group at the posttest (p < 0.05). CHAMP is a mastery climate movement program that enhance skills associated with healthy development in children (i.e., motor skills and self-regulation). This efficacy trial provided evidence that CHAMP helped maintain delay of gratification in preschool age children and significantly improved motor skills while participating in outdoor recess was not effective. CHAMP could help contribute to children’s learning-related skills and physical development and subsequently to their academic success.
The contribution of intrinsically disordered regions to protein function, cellular complexity, and human disease

In the 1960s, Christian Anfinsen postulated that the unique three-dimensional structure of a protein is determined by its amino acid sequence. This work laid the foundation for the sequence–structure–function paradigm, which states that the sequence of a protein determines its structure, and structure determines function. However, a class of polypeptide segments called intrinsically disordered regions does not conform to this postulate. In this review, I will first describe established and emerging ideas about how disordered regions contribute to protein function. I will then discuss molecular principles by which regulatory mechanisms, such as alternative splicing and asymmetric localization of transcripts that encode disordered regions, can increase the functional versatility of proteins. Finally, I will discuss how disordered regions contribute to human disease and the emergence of cellular complexity during organismal evolution.
Multiresolution Based Pattern Recognition Approach for Condition Monitoring of Switchgear

A new multiresolution based pattern recognition approach is proposed for fault diagnosis of distribution switchgear. The wavelet transform is used to extract the key features from the vibration spectra following circuit breaker operation. These features are then used to plot a 2-D diagram or condition map. This map displays clearly the actual condition of the circuit breaker and it can also be used to compare a faulty circuit breaker with a healthy unit. The new method is more reliable than Fourier based condition map analysis.
Advances in Document Classification by Voting of Competitive Approaches

This paper presents a complex approach for the content-based text categorization of printed German business letters into pre-defined message types such as order, invoice, offer, etc. The categorization results of two competing classifiers are combined by means of a voting component embodying knowledge about the strengths and weaknesses of the classifiers. The individual classifiers differ strongly in their basic assumptions: While the first one considers layout and typographic information with respect to certain keywords the second one is a more conventional text categorization approach which merely incorporates textual features. Since this whole categorization tool is embedded into a document analysis system, a highly precise classification is essential for a subsequent goal-directed extraction of structured information aimed at the integration of the document into the current business workflow of a company.
Checking MTL Properties of Discrete Timed Automata via Bounded Model Checking

We investigate a SAT-based bounded model checking (BMC) method for MTL (metric temporal logic) that is interpreted over linear discrete infinite time models generated by discrete timed automata. In particular, we translate the existential model checking problem for MTL to the existential model checking problem for a variant of linear temporal logic (called HLTL), and we provide a SAT-based BMC technique for HLTL. We show how to implement the BMC technique for HLTL and discrete timed automata, and as a case study we apply the technique in the analysis of GTPP, a Generic Timed Pipeline Paradigm modelled by a network of discrete timed automata.
Objective Distances for Transcriptome Analyses According to the Thermodynamic Model

Data analysis and interpretation require intellectual frameworks, and to share the results in a community, scientific bases are preferred for the framework. A variety of indexes have been used for interpreting distances between transcriptome data, however, such indexes always lack necessity since they have been derived for non-biological purposes and their appropriateness have not been verified for transcriptome analyses. Here introduced are a definition of distance and two indexes that are derived from thermodynamic model of transcriptome formation [3, 4], which describes transcriptome by way of interactions between protein factors and nucleic acids. For example, a human cell may have 1,000 species of protein factors, and its transcriptome can be described by the same numbers of dimensions of Gibbs free energies and Arrhenius activation energies. Consequently, distance between any two expression levels can be found as Euclidean distance calculated with the energies. However, unfortunately, such data treatment is presently impossible, since the constant relationship between a protein factor and a gene is not available yet.
[Addictive internet use as a comorbid disorder among clients of an adolescent psychiatry - prevalence and psychopathological symptoms].

OBJECTIVES Excessive and addictive internet use fulfilling criteria of nonsubstance related addiction disorder is increasingly being discussed by scientists and clinicians alike. Its prevalence of about 3 % among minors points to a relatively frequent phenomenon that can lead to functional impairment and distress. However, there is still no evidence concerning its prevalence among underaged patients in psychiatric treatment. METHODS 81 patients between the age of 8 and 17 years were screened by a standardized instrument for internet addiction (AICA-S) to assess the prevalence of internet addiction among minors being treated in psychiatric inpatient settings. Their clinical symptoms were examined using Youth Self-Report and Child Behavior Checklist. RESULTS 11.3 % of the patients fulfilled the criteria of addictive internet use. These patients were older and more often affected by anxiety and depression than patients without internet addiction. CONCLUSIONS Data suggest that internet addiction is a relevant factor among minors in psychiatric institutions. Those with comorbid internet addiction show distinct patterns of psychopathology and may require disorder-specific treatment.
From Speculation to Security: Practical and Efficient Information Flow Tracking Using Speculative Hardware

Dynamic information flow tracking (also known as taint tracking) is an appealing approach to combat various security attacks. However, the performance of applications can severely degrade without hardware support for tracking taints. This paper observes that information flow tracking can be efficiently emulated using deferred exception tracking in microprocessors supporting speculative execution. Based on this observation, we propose SHIFT, a low-overhead, software-based dynamic information flow tracking system to detect a wide range of attacks. The key idea is to treat tainted state (describing untrusted data) as speculative state (describing deferred exceptions). SHIFT leverages existing architectural support for speculative execution to track tainted state in registers and needs to instrument only load and store instructions to track tainted state in memory using a bitmap, which results in significant performance advantages. Moreover, by decoupling mechanisms for taint tracking from security policies, SHIFT can detect a wide range of exploits, including high-level semantic attacks. We have implemented SHIFT using the Itanium processor, which has support for deferred exceptions, and by modifying GCC to instrument loads and stores. A security assessment shows that SHIFT can detect both low-level memory corruption exploits as well as high-level semantic attacks with no false positives. Performance measurements show that SHIFT incurs about 1% overhead for server applications. The performance slowdown for SPEC-INT2000 is 2.81X and 2.27X for tracking at byte-level and wordlevel respectively. Minor architectural improvements to the Itanium processor (adding three simple instructions) can reduce the performance slowdown down to 2.32X and 1.8X for byte-level and word-level tracking, respectively.
Differential patterns of stromelysin-2 (MMP-10) and MT1-MMP (MMP-14) expression in epithelial skin cancers

Co-expression of several members of the matrix metalloproteinase (MMP) family is characteristic of human malignant tumours. To investigate the role of stromelysin-2 (MMP-10) in growth and invasion of skin tumours, we studied cutaneous carcinomas with high metastatic capacity (squamous cell carcinomas, SCCs), only locally destructive tumours (basal cell carcinomas, BCCs) and pre-malignant lesions (Bowen’s disease and actinic keratosis) using in situ hybridization. Expression of MMP-10 was compared with that of stromelysin-1 (MMP-3) and of MT1-MMP, the expression of which has been shown to correlate with tumour invasiveness. MMP-10 was expressed in 13/21 SSCs and 11/19 BCCs only in epithelial laminin-5 positive cancer cells, while premalignant lesions were entirely negative. MT1-MMP mRNA was detected in 19/21 SCCs both in epithelial cancer cells and stromal fibroblasts and in 14/18 BCCs only in fibroblasts. The level of MMP-10 was upregulated in a cutaneous SCC cell line (UT-SCC-7) by transforming growth factor-α and keratinocyte growth factor, and by interferon-γ in combination with transforming growth factor-β1 and tumour necrosis factor-α both in UT-SCC-7 and HaCaT cells. Our results show that MMP-10 expression does not correlate with the invasive behaviour of tumours as assessed by their histology and MT1-MMP expression, but may be induced by the wound healing and inflammatory matrix remodelling events associated with skin tumours. © 2001 Cancer Research Campaign
RIPPLE Authentication for Network Coding

By allowing routers to randomly mix the information content in packets before forwarding them, network coding can maximize network throughput in a distributed manner with low complexity. However, such mixing also renders the transmission vulnerable to {\em pollution attacks}, where a malicious node injects corrupted packets into the information flow. In a worst case scenario, a single corrupted packet can end up corrupting {\it all} the information reaching a destination. In this paper, we propose RIPPLE, a symmetric key based in-network scheme for network coding authentication. RIPPLE allows a node to efficiently detect corrupted packets and encode only the authenticated ones. Despite using symmetric key based homomorphic Message Authentication Code (MAC) algorithms, RIPPLE achieves asymmetry by delayed disclosure of the MAC keys. Our work is the first symmetric key based solution to allow arbitrary collusion among adversaries. It is also the first to consider {\em tag pollution attacks}, where a single corrupted MAC tag can cause numerous packets to fail authentication farther down the stream, effectively emulating a successful pollution attack.
DOMMINO 2.0: integrating structurally resolved protein-, RNA-, and DNA-mediated macromolecular interactions

Macromolecular interactions are formed between proteins, DNA and RNA molecules. Being a principle building block in macromolecular assemblies and pathways, the interactions underlie most of cellular functions. Malfunctioning of macromolecular interactions is also linked to a number of diseases. Structural knowledge of the macromolecular interaction allows one to understand the interaction’s mechanism, determine its functional implications and characterize the effects of genetic variations, such as single nucleotide polymorphisms, on the interaction. Unfortunately, until now the interactions mediated by different types of macromolecules, e.g. protein–protein interactions or protein–DNA interactions, are collected into individual and unrelated structural databases. This presents a significant obstacle in the analysis of macromolecular interactions. For instance, the homogeneous structural interaction databases prevent scientists from studying structural interactions of different types but occurring in the same macromolecular complex. Here, we introduce DOMMINO 2.0, a structural Database Of Macro-Molecular INteractiOns. Compared to DOMMINO 1.0, a comprehensive database on protein-protein interactions, DOMMINO 2.0 includes the interactions between all three basic types of macromolecules extracted from PDB files. DOMMINO 2.0 is automatically updated on a weekly basis. It currently includes ∼1 040 000 interactions between two polypeptide subunits (e.g. domains, peptides, termini and interdomain linkers), ∼43 000 RNA-mediated interactions, and ∼12 000 DNA-mediated interactions. All protein structures in the database are annotated using SCOP and SUPERFAMILY family annotation. As a result, protein-mediated interactions involving protein domains, interdomain linkers, C- and N- termini, and peptides are identified. Our database provides an intuitive web interface, allowing one to investigate interactions at three different resolution levels: whole subunit network, binary interaction and interaction interface. Database URL: http://dommino.org
Estimation of signal and noise for a whole-body photon counting research CT system

Photon-counting CT (PCCT) may yield potential value for many clinical applications due to its relative immunity to electronic noise, increased geometric efficiency relative to current scintillating detectors, and the ability to resolve energy information about the detected photons. However, there are a large number of parameters that require optimization, particularly the energy thresholds configuration. Fast and accurate estimation of signal and noise in PCCT can benefit the optimization of acquisition parameters for specific diagnostic tasks. Based on the acquisition parameters and detector response of our research PCCT system, we derived mathematical models for both signal and noise. The signal model took the tube spectrum, beam filtration, object attenuation, water beam hardening, and detector response into account. The noise model considered the relationship between noise and radiation dose, as well as the propagation of noise as threshold data are subtracted to yield energy bin data. To determine the absolute noise value, a noise look-up table (LUT) was acquired using a limited number of calibration scans. The noise estimation algorithm then used the noise LUT to estimate noise for scans with a variety of combination of energy thresholds, dose levels, and object attenuation. Validation of the estimation algorithms was performed on our whole-body research PCCT system using semianthropomorphic water phantoms and solutions of calcium and iodine. The algorithms achieved accurate estimation of signal and noise for a variety of scanning parameter combinations. The proposed method can be used to optimize energy thresholds configuration for many clinical applications of PCCT.
Plasma adiponectin and endogenous glucose production in humans.

OBJECTIVE High plasma adiponectin is associated with reduced risk of type 2 diabetes, probably a consequence of its insulin-sensitizing properties. In vivo data in rodents suggest that the insulin-sensitization responsible for improvement of glycemia occurs in muscle and liver. Whereas associations of plasma adiponectin with muscle insulin sensitivity in humans have been examined, this has not been done for the liver. RESEARCH DESIGN AND METHODS We therefore analyzed the relationship between fasting plasma adiponectin and basal endogenous glucose production [EGP]-basal) and insulin-suppressed EGP (EGP-insulin, isotope dilution technique) in 143 Pima Indians (94 with normal glucose tolerance, 36 with impaired glucose tolerance, and 16 with type 2 diabetes). RESULTS Fasting plasma adiponectin concentrations were negatively correlated with EGP-basal and EGP-insulin before (P = 0.006 and P < 0.0001, respectively) as well as after adjustment for age, sex, percent body fat, and insulin-stimulated whole-body glucose uptake (P = 0.007 and P = 0.0005, respectively). CONCLUSIONS These findings are compatible with the hypothesis that adiponectin increases hepatic insulin sensitivity. Consistent with data in animals, adiponectin may have generalized insulin-sensitizing effects in humans.
Bis[(diphenylphosphanylmethyl)diphenylphosphane sulfide-κ2 P,S]copper(I) hexafluoridophosphate

In the title compound, [Cu(C25H22P2S)2]PF6, the CuI atom, lying on a twofold rotation axis, adopts a distorted tetrahedral geometry. The (diphenylphosphanylmethyl)diphenylphosphane sulfide ligand coordinates to the CuI atom through one S and one P atom, forming a stable five-membered chelate ring. The P atom of the PF6 − anion also lies on a twofold rotation axis.
A Framework for Personalized Service Website based on TAM

Web personalization is increasingly becoming important service for Web users. Based on some literature review, we describe a general personalized Web service process, and classify them by the way of initiative side. In those personalization researches, some authors focus on users' interactive profile in terms of client-side, others address server-side process, and still others pay their attentions to users' experience with the Web service or Internet. In this paper, we focus on users' attitude towards using personalized Web service in terms of ease of use and usefulness, which is the essential idea to design personalized Web site. Then the technology acceptance model (TAM) is introduced to design personalized service Web site, and three basic factors are proposed: visual, structure, function. We suggest these three factors are the basic designing elements, and impact on the perceived ease of use and usefulness, then have influence on users' attitude toward using the personalized Web site. This research aims to give a general designing framework for Web developer, designer, producer, in order to build a clean, comfortable personalized Web site, to provide more ease of use, useful service
Flow graph balancing for minimizing the required memory bandwidth

In this paper we present the problem of flow graph balancing for minimizing the required memory bandwidth. Our goal is to minimize the required memory bandwidth within the given cycle budget by adding ordering constraints to the flow graph. This allows the subsequent memory allocation and assignment tasks to come up with a cheaper memory architecture with less memories and memory ports. The effect of flow graph balancing is shown on an example. We show that it is important to take into account which data is being accessed in parallel, instead of only considering the number of simultaneous memory accesses. This leads to the optimization of a conflict graph.
Treatment-resistant major depressive disorder and assisted dying: response to comments

The commentaries responding to our article on treatment-resistant depression and assisted dying focus on the following issues: epistemological questions about death, patient competence, the role of doctors, the moral basis of the right to an assisted death, safety and security of patients, and questions about various cases that occurred in the Netherlands. We will address in our response each of these concerns, beginning with the last issue first. Dr den Hartogh mentions a case in the Netherlands where the Dutch review committee deemed ‘the doctor … not careful’. 1 This case was published after we submitted our paper. The case was judged ‘not careful’ because no psychiatrist had been consulted to consider the competence of the patient, and to review whether the patient's situation was truly of a hopelessness nature. In this case, the doctor who performed the euthanasia and the consultant were general practitioners. This case does not undermine our argument. The review committee did not suggest that the patient was incompetent. In our paper, we are careful to consider only treatment-resistant competent patients. Dr Cowley mentions the so-called Chabot case and the Brongersma case.2 In the Netherlands, the Brongersma case is not discussed under the label ‘depression’, but as a case of a patient who was ‘tired of life’. 3 Eighty-six-year-old former politician Edward Brongersma did not suffer from a mental or other illness. It deserves a separate discussion and is outside the scope of our paper. The Chabot case was extraordinary because the patient had no wish to be cured from her depression because she felt depression to be an appropriate state to be in after the premature deaths of her two sons.4 This case also falls outside the scope of our paper. Drs Broome and de Cates begin their discussion with an epistemological argument …