Miracle-dz/UniFAR-FTUs huggingface dataset:
Brexpiprazole II: Antipsychotic-Like and Procognitive Effects of a Novel Serotonin-Dopamine Activity Modulator

Brexpiprazole (OPC-34712, 7-{4-[4-(1-benzothiophen-4-yl)piperazin-1-yl]butoxy}quinolin-2(1H)-one) is a novel serotonin-dopamine activity modulator with partial agonist activity at serotonin 1A (5-HT1A) and D2/3 receptors, combined with potent antagonist effects on 5-HT2A, α1B-, and α2C-adrenergic receptors. Brexpiprazole inhibited conditioned avoidance response (ED50 = 6.0 mg/kg), apomorphine- or d-amphetamine-induced hyperactivity (ED50 = 2.3 and 0.90, respectively), and apomorphine-induced stereotypy (ED50 = 2.9) in rats at clinically relevant D2 receptor occupancies. Brexpiprazole also potently inhibited apomorphine-induced eye blinking in monkeys. The results suggest that brexpiprazole has antipsychotic potential. Brexpiprazole induced catalepsy (ED50 = 20) well above clinically relevant D2 receptor occupancies, suggesting a low risk for extrapyramidal side effects. Subchronic treatment with phencyclidine (PCP) induced cognitive impairment in both novel object recognition (NOR) and attentional set-shifting (ID-ED) tests in rats. Brexpiprazole reversed the PCP-induced cognitive impairment in the NOR test at 1.0 and 3.0 mg/kg, and in the ID-ED test at 1.0 mg/kg. However, aripiprazole (10 mg/kg) was ineffective in both tests, despite achieving relevant D2 occupancies. In the NOR test, the 5-HT1A agonist buspirone and the 5-HT2A antagonist M100907 [(R)-(2,3-dimethoxyphenyl)[1-(4-fluorophenethyl)piperidin-4-yl]methanol] partially but significantly reversed PCP-induced impairment. Furthermore, the effect of brexpiprazole was reversed by cotreatment with the 5-HT1A antagonist WAY100635 (N-[2-[4-(2-methoxyphenyl)-1-piperazinyl]ethyl]-N-2-pyridinylcyclohexanecarboxamide maleate). The results indicate that brexpiprazole has antipsychotic-like activity and robust efficacy in relevant models of cognitive impairment associated with schizophrenia. The effects of brexpiprazole in the cognitive tests are superior to those of aripiprazole. We propose that the pharmacologic profile of brexpiprazole be based on its balanced effects on 5-HT1A, D2, and 5-HT2A receptors, with possible modulating activity through additional monoamine receptors.
Quantitative structure activity relationship analys is of a series of antibacterial 3-bromo-4-(1-H-3-indolyl)-2, 5-dihydro-1H-2, 5- pyrroledione derivatives

The use of quantitative structure‐activity relation ships, since its advent, has become increasingly helpful in understanding many aspects of biochemical interactions in drug research. This approach was utilized to explain the relationship o f structure with biological activity of antibacterial. For the development of new fungici des against, the quantitative structural‐activity relationship (QSAR) analyses for fungicidal activit ies of Pyrroledione Derivatives were carried out using multiple linear regression (MLR) Quantita tive structure‐activity relationship (QSAR) analysis was performed on a series of 3-Bromo-4-(1- H-3-Indolyl)-2, 5-Dihydro-1H-2, 5Pyrroledione Derivatives.QSAR investigations were based on Hansch's extra thermodynamic multi-parameter approach. QSAR investigations reveal that steric and electrostatic interactions are primarily responsible for enzyme‐ligand interac tion . These studies produced good predictive models and give statistically significant correlati ons of selective COX-2 inhibitory with physical property, connectivity and conformation of molecule . Also when available COX-1 inhibitory data was analyzed with descriptors obtained from ch em. Office 2007, partial charge descriptor, van der Waal’s surface area and solvation energy ga ve statistically significant results . The results obtained by combining these methodologies give insights into the key features for designing more potent analogs antibacterial.
mSin3A Regulates Murine Erythroleukemia Cell Differentiation through Association with the TAL1 (or SCL) Transcription Factor

ABSTRACT Activation of the TAL1 (or SCL) gene is the most frequent gain-of-function mutation in T-cell acute lymphoblastic leukemia (T-ALL). TAL1 belongs to the basic helix-loop-helix (HLH) family of transcription factors that bind as heterodimers with theE2A and HEB/HTF4 gene products to a nucleotide sequence motif termed the E-box. Reported to act both as an activator and as a repressor of transcription, the mechanisms underlying TAL1-regulated gene expression are poorly understood. We report here that the corepressor mSin3A is associated with TAL1 in murine erythroleukemia (MEL) and human T-ALL cells. Interaction mapping showed that the basic-HLH domain of TAL1 was both necessary and sufficient for TAL1-mSin3A interaction. TAL1 was found, in addition, to interact with the histone deacetylase HDAC1 in vitro and in vivo, and a specific histone deacetylase inhibitor, trichostatin A (TSA), relieved TAL1-mediated repression of an E-box-containing promoter and a GAL4 reporter linked to a thymidine kinase minimal promoter. Further, TAL1 association with mSin3A and HDAC1 declined during dimethyl sulfoxide-induced differentiation of MEL cells in parallel with a decrease in mSin3A abundance. Finally, TSA had a synergistic effect with enforced TAL1 expression in stimulating MEL cells to differentiate, while constitutive expression of mSin3A inhibited MEL cell differentiation. These results demonstrate that a corepressor complex containing mSin3A and HDAC1 interacts with TAL1 and restricts its function in erythroid differentiation. This also has implications for this transcription factor's actions in leukemogenesis.
Identification of the Preferential Ubiquitination Site and Ubiquitin-dependent Degradation Signal of Rpn4*

Lysine selection is a long-standing problem in protein ubiquitination catalyzed by the RING ubiquitin ligases. It is well known that many substrates carry multiple lysines that can be ubiquitinated. However, it has seldom been addressed whether one lysine is preferred for ubiquitin conjugation when all other lysines exist. Here we studied the mechanism underlying ubiquitin-dependent degradation of Rpn4, a transcription activator of the Saccharomyces cerevisiae proteasome genes. We found that the ubiquitin-dependent degradation of Rpn4 can be mediated by six different lysines. Interestingly, we showed through in vivo and in vitro assays that lysine 187 is selected for ubiquitination when all other lysines are available. To the best of our knowledge, this is the first demonstration of a preferential ubiquitination site chosen from a group of lysines susceptible for ubiquitination. We further demonstrated that lysine 187 and a proximal acidic domain constitute a portable degradation signal. The implications of our data are discussed.
A Low-Loss Planar Ka-Band Antenna Subarray for Space Applications

This paper presents the design, optimization, and experimental characterization of a planar antenna subarray for space applications. The proposed component is intended to be used as a building block for a large Ka-band antenna systems. It is a one-dimensional linear array fed using a standard rectangular waveguide. It includes a transition between the waveguide and the beam forming network (BFN), the BFN itself and six radiators. A planar BFN and planar radiating aperture-fed double stacked circular patches are used to guarantee the low-profile of the proposed element. To ensure low losses and to reduce the mutual coupling inside the BFN, the suspended stripline (SSL) is selected as the transmission line. Due to the tight requirements on RF performance and the limited space available, novel components, such as waveguide to SSL transition and SSL power dividers, are proposed. The design is optimized using a step-by-step procedure. A complete subarray prototype has been fabricated requiring no-less than six different manufacturing technologies. The experimental results have validated the numerical simulations and show a good overall performance and low losses with efficiency above 70% in the frequency band 25.5-27 GHz (5.7%).
Binding dynamics of single-stranded DNA binding proteins to fluctuating bubbles in breathing DNA

We investigate the dynamics of a single local denaturation zone in a DNA molecule, a so-called DNA bubble, in the presence of single-stranded DNA binding proteins (SSBs). In particular, we develop a dynamical description of the process in terms of a two-dimensional master equation for the time evolution of the probability distribution of having a bubble of size m with n bound SSBs, for the case when m and n are the slowest variables in the system. We derive explicit expressions for the equilibrium statistical weights for a given m and n, which depend on the statistical weight u associated with breaking a base-pair interaction, the loop closure exponent c, the cooperativity parameter σ0, the SSB size λ, and binding strength κ. These statistical weights determine, through the detailed balance condition, the transfer coefficient in the master equation. For the case of slow and fast binding dynamics the problem can be reduced to one-dimensional master equations. In the latter case, we perform explicitly the adiabatic elimination of the fast variable n. Furthermore, we find that for the case that the loop closure is neglected and the binding dynamics is vanishing (but with arbitrary σ0) the eigenvalues and the eigenvectors of the master equation can be obtained analytically, using an orthogonal polynomial approach. We solve the general case numerically (i.e., including SSB binding and the loop closure) as a function of statistical weight u, binding protein size λ, and binding strength κ, and compare to the fast and slow binding limits. In particular, we find that the presence of SSBs in general increases the relaxation time, compared to the case when no binding proteins are present. By tuning the parameters, we can drive the system from regular bubble fluctuation in the absence of SSBs to full denaturation, reflecting experimental and in vivo situations.
A systematic review of ketamine as an analgesic agent in adult burn injuries.

OBJECTIVE To assess the current literature regarding the effectiveness and side-effect profile of intravenous ketamine as a means of pain relief when compared with placebo or as an adjunct to opioid analgesia in patients exposed to burn injury. DESIGN Electronic searches of MEDLINE, CINAHL, Embase, and The Cochrane Library databases from 1966 onward were used to identify clinical trials comparing ketamine with placebo in the adult burn population. OUTCOMES MEASURED Effectiveness and side-effect profile of ketamine as an analgesic agent in burn injuries. RESULTS Four experimental trials involving 67 patients were identified. Due to heterogeneity of studies, pooling of the results and meta-analysis were not possible. Intravenous ketamine showed some efficacy as an analgesic for burn injuries, with a reduction in secondary hyperalgesia when compared with opioid analgesia alone. Combination therapy of ketamine and morphine resulted in the abolishment of windup pain phenomena. The side-effect profile did not result in the withdrawal of any participants included in the studies' results. CONCLUSIONS Further well-designed randomized controlled trials conducted in burn-specific populations are warranted, thus enabling the development of a relevant evidence base to support its clinical use.
Paracetamol – accumulating reports of an association with allergy and asthma

In the last 10 years, several different studies have reported an association between paracetamol (acetaminophen) and asthma or allergy (1–6). Two years ago, an article from the well-known International Study of Asthma and Allergies in Childhood (ISAAC) received large interest in international media, as well as within the medical profession (7). In the ISAAC analysis, it was found that the use of paracetamol in the first year of life was associated with an increased risk of asthma symptoms at the age of 6–7 years (7). Paracetamol use in infancy was also associated with an increased risk of symptoms of rhinoconjunctivitis and eczema (7). A recent systematic review that included 19 different studies confirmed an increased risk of asthma and wheezing in both children and adults exposed to paracetamol (8). It has also been noted that the increased use of paracetamol during the last five decades has coincided with the increased prevalence of allergy and asthma (9). For children, aspirin has been avoided since the beginning of the 1980s because of its link to Reye’s syndrome and replaced by paracetamol (10). In this issue of Acta Paediatrica, Bakkeheim et al. present results from the prospective birth cohort Environment and Childhood Asthma study in Oslo (11). The authors investigated whether paracetamol exposure in pregnancy and until 6 months of age was associated with allergic disease at school age. Maternal paracetamol use in the first trimester increased the risk of allergic rhinitis at 10 years. In girls, paracetamol use before 6 months increased the risk of allergic sensitization and a history of asthma. The effect remained also when adjusting for upper and lower airway infections during the first 6 months of life. The authors, however, conclude that causality could not be determined in the study. An important strength of the Bakkeheim study is that the recordings of maternal and infant use of paracetamol were made at the maternity ward and at age 6 months, respectively. This reduces the risk of recall bias. In the ISAAC study, the information on paracetamol use in infancy was obtained at the age of 6–7 years (7).
Drugs in the peri-operative period: 4 - Cardiovascular drugs

Many patients undergoing elective surgery will be taking medicines for cardiovascular disorders. Here, in the fourth and final article in our series on drug therapy in the peri-operative period, we review the management of patients taking certain antithrombotic, antihypertensive, anti-anginal or anti-arrhythmic drugs.
Achieving throughput and functionality in a common architecture: the Datacycle experiment

Summary form only given. The Datacycle database architecture is based on repetitive broadcast of database contents over high bandwidth channels and on-the-fly filtering of database contents to extract records of interest. These two mechanisms-high speed broadcast and on-the-fly filtering-result in a system that achieves the goals of high performance transaction processing, a powerful and flexible query capability, and high levels of concurrent access to a single database by multiple applications. The prototype system comprises multiple pump boards, each of which stores up to 128 Mbytes of database contents, and multiple access manager boards, each of which contains three on-board VLSI data filter chips. Each VLSI filter executes queries against the contents of a 53 Mbyte/second broadcast channel; selected records and/or computed aggregate values are returned to the host application. <<ETX>>
Mean platelet volume in myocardial infarction.

SIR,-Dr J van der Lelie and Dr J A C Brakenhoffconclude their letter (12 November, p 1471): "measurement of the mean platelet volume in the coronary care unit has no clinical relevance. " This negative assertion must be in serious doubt as it is based on a study of 12 patients with myocardial infarction, whereas the study by Dr H A Cameron and others (13 August, p 449) came to the opposite conclusion after studying mean platelet volume in 100 men with myocardial infarction using the same methodology (Coulter counter S plus). We should like to make some observations about methodology, theory, and interpretation.
A Robust Online Signature Based Cryptosystem

Cryptography is the backbone for the security systems. The main challenge in use of the Cryptosystems is maintaining the confidentiality of the cryptographic key. A Cryptosystem which encrypts the data using biometric features improves the security of the data and overcomes the problems of key management and key confidentiality. Fuzzy Vault Scheme proposed by Juels and Sudan [1] binds the secret key and the biometric template, so that extraction of the secret without the biometric data is infeasible. Physical signature is a biometric that is widely accepted and is used for proving the authenticity of a person in legal documents, bank transactions etc. Electronic devices such as digital tablets capture azimuth, altitude and pressure along with x any y coordinates at fixed time interval. This paper describes a robust online signature based cryptosystem to hide the secret by binding it with invariant online signature templates. The invariant templates of the signature are derived from artificial neural network based classifier. The entire signature is divided into fixed number of time slices. Important features are extracted based on the consistency of the feature in the slices of the genuine signature. Binary back propagation based neural network for each feature, each subset of slices for a user is trained by a weighted back propagation algorithm. The decisions of these networks are combined using AdaBoost algorithm. The proposed scheme is highly robust as it works well for all kinds of signatures and is independent of the number of zero crossing and high curvature points in the signature trajectory.
The Use of Seat Belt by Motor Vehicle Occupants in South Africa

Objective. The purpose of this article was to examine the use of seat belt by motor vehicle users in the various provinces in South Africa. Methods. Data were abstracted from published reports of the national Department of Transport. Percentage distribution and correlation of road safety variables and seat belt wearing rates for motor vehicle users were calculated for the different provinces. Results. High seat belt wearing rates by the drivers (between 75.1% and 88.1%, national rate was 81%). The seat belt wearing rates for the front and back seat passengers were much lower than for the drivers. The seat belt wearing rates for front seat passengers (44.5% to 60.5%, national − 50.1%) and back seat passengers (1% to 16%, national − 7.6%) were much lower than for the drivers. The national seat belt wearing rate for all vehicles between 1982 and 1995 was between 46.9% and 69.2%, but this has generally declined. Conclusion. There is a need for the implementation of strategies to increase the use of seat belts to reduce injuries and fatalities.
Design of business intelligence applications using big data technology

The present article concerns about the knowledge of a new technology called Big Data to manage information, replacing traditional systems for data management. An analysis of its components and new software to use is done. Specifically, the way to perform the design of business intelligence applications is proposed, and all this for the decision making at management level making use of Big Data tools.
Impact of crystallographic orientation and impurity scattering in Graphene-Base Heterojunction Transistors for Terahertz Operation

The influence of the crystal orientation on the performance of silicon-based Graphene-Base Heterojunction Transistors (GBHTs) for terahertz operation is investigated by means of an in-house developed simulator based on quantum transport coupled with Poisson equation. The effect of impurity scattering is included, finding that terahertz operation is possible even considering the reduction of the mobility due to dopants.
Human U19 intron-encoded snoRNA is processed from a long primary transcript that possesses little potential for protein coding.

While exons were originally defined as coding regions of split eukaryotic genes, introns have long been considered as mainly noncoding "genetic junk. " However, recognition that a large number of small nucleolar RNAs (snoRNAs) are processed from introns of pre-mRNAs demonstrated that introns may also code for functional RNAs. Moreover, recent characterization of the mammalian UHG gene that encodes eight box C/D intronic snoRNAs suggested that some genes generate functional RNA products exclusively from their intron regions. In this study, we show that the human U19 box H/ACA snoRNA, which is encoded within the second intron of the U19H gene, represents the only functional RNA product generated from the long U19H primary transcript. Splicing of the U19H transcript, instead of giving rise to a defined RNA, produces a population of diverse U19H RNA molecules. Although the first three exons of the U19H gene are preserved in each processed U19H RNA, the 3' half of the RNA is generated by a series of apparently random splicing events. Because the U19H RNA possesses limited potential for protein coding and shows a predominant nucleoplasmic localization, we suggest that the sole function of the U19H gene is to express the U19 intronic snoRNA. This suggests that, in marked contrast to our previous dogmatic view, genes generating functionally important RNAs exclusively from their intron regions are probably more frequent than has been anticipated.
An Energy Aware Genetic Algorithm Based Scheduling Model For Cloud Computing

Cloud computing has emerged as a revolutionary technology in the recent past. It has gained huge popularity among organizations due to its business oriented nature. Being a business model, the service provider and the customer both are concerned about economies of the services. Scheduling is responsible for utilization of resources to a large extent. Good scheduling policies result in optimal usage of the resources. Energy is a significant resource in the field of computing which should be emphasized to be utilized optimally with the help of a good scheduling policy. Moreover energy conservation can a play major role in system reliability and environmental protection. Scheduling in cloud has been proven to be an NP hard problem due to the heterogeneity of the participating resources and huge search space. GA has gained popularity among the evolutionary techniques to deal with NP hard problems like scheduling. The proposed work presents a model with scheduling strategy to minimize the energy consumption of a job submitted to the cloud. It is done ensuring resource assignment according to the precedence and communication cost constraints. The work includes the analysis of the experimental results under various conditions. Keywords– cloud computing, Genetic Algorithm (GA), Scheduling, Directed Acyclic Graph (DAG), EnergyEfficient.
Secondary cell-mediated cytotoxic response to syngeneic mouse tumor challenge.

When C57BL/6 mice previously immunized with murine sarcoma virus (MSV) were challenged with a Rauscher virus-induced lymphoma, RBL-5, a secondary cell-mediated cytotoxic response could be detected by the Cr release cytotoxicity assay. The level and distribution of the secondary cytotoxic response was affected by the route of challenge. Animals injected i.p. demonstrated a high level of cytotoxicity in the peritoneal exudate cells 3 days after challenge and subsequently cytotoxicity was detected in most lymphoid organs, although at lower levels. However, when the animals were challenged intramuscularly in the leg, the response was not detected as rapidly and furthermore cytotoxic lymphocytes were found only in the draining lymph node and not in other lymphoid organs. Treatment of the effector cells with anti-theta and complement showed the secondary response to be predominately dependent on T cells. In addition, the cytotoxicity was specific in that cells lacking cross-reacting antigens were not killed by these attacker cells from mice undergoing a secondary response.
Some More Noiseless Coding Theorem on Generalized R-Norm Entropy

A parametric mean length is defined as the quantity$L_{R}^{\beta}=\frac{R}{R-1}\left[1-\frac{\sum_{i=1}^{N}p_{i}^{\beta}D^{-n_{i}\left(\frac{R-1}{R}\right)}}{\sum_{j=1}^{N}p_{j}^{\beta}}\right]$\noindent where $R>0\left(\ne 1\right),\beta >0,\, p_{i} >0,\, \sum p_{i} =1,\, \, i=1,2,\dots,N. $ This beingthe mean length of code words. Lower and upper bounds for $L_{R}^{\beta}$ are derived in terms of R-norminformation measure for the incomplete power distribution.