Miracle-dz/UniFAR-FTUs huggingface dataset:
Dopamine, Salience, and Response Set Shifting in Prefrontal Cortex

Dopamine is implicated in multiple functions, including motor execution, action learning for hedonically salient outcomes, maintenance, and switching of behavioral response set. Here, we used a novel within-subject psychopharmacological and combined functional neuroimaging paradigm, investigating the interaction between hedonic salience, dopamine, and response set shifting, distinct from effects on action learning or motor execution. We asked whether behavioral performance in response set shifting depends on the hedonic salience of reversal cues, by presenting these as null (neutral) or salient (monetary loss) outcomes. We observed marked effects of reversal cue salience on set-switching, with more efficient reversals following salient loss outcomes. l-Dopa degraded this discrimination, leading to inappropriate perseveration. Generic activation in thalamus, insula, and striatum preceded response set switches, with an opposite pattern in ventromedial prefrontal cortex (vmPFC). However, the behavioral effect of hedonic salience was reflected in differential vmPFC deactivation following salient relative to null reversal cues. l-Dopa reversed this pattern in vmPFC, suggesting that its behavioral effects are due to disruption of the stability and switching of firing patterns in prefrontal cortex. Our findings provide a potential neurobiological explanation for paradoxical phenomena, including maintenance of behavioral set despite negative outcomes, seen in impulse control disorders in Parkinson's disease.
A low noise accelerometer with digital PID&#8211;type controller and multibit force feedback

A hybrid acceleration sensing system is presented consisting of a micromachined acceleration sensor and a CMOS-IC. Due to closed loop operation, linearity, measurement range and bandwidth of the sensor device are extended by more than an order of magnitude. The system forms an electromechanical ΔΣ-converter featuring an autozero OP minimizing low frequency noise, a multibit D/A-converter reducing quantization noise and a digital PID-type controller shaping quantization noise and providing high bandwidth. Experimental results show a resolution of 15,5 bit and a linear operation range of ±52g.
Homeodomain-Interacting Protein Kinase-2: A Critical Regulator of the DNA Damage Response and the Epigenome

Homeodomain-interacting protein kinase 2 (HIPK2) is a serine/threonine kinase that phosphorylates and activates the apoptotic program through interaction with diverse downstream targets including tumor suppressor p53. HIPK2 is activated by genotoxic stimuli and modulates cell fate following DNA damage. The DNA damage response (DDR) is triggered by DNA lesions or chromatin alterations. The DDR regulates DNA repair, cell cycle checkpoint activation, and apoptosis to restore genome integrity and cellular homeostasis. Maintenance of the DDR is essential to prevent development of diseases caused by genomic instability, including cancer, defects of development, and neurodegenerative disorders. Recent studies reveal a novel HIPK2-mediated pathway for DDR through interaction with chromatin remodeling factor homeodomain protein 1γ. In this review, we will highlight the molecular mechanisms of HIPK2 and show its functions as a crucial DDR regulator.
The Decision Making Individual Differences Inventory and guidelines for the study of individual differences in judgment and decision-making research

Individual differences in decision making are a topic of longstanding interest, but often yield inconsistent and contradictory results. After providing an overview of individual difference measures that have commonly been used in judgment and decision-making (JDM) research, we suggest that our understanding of individual difference effects in JDM may be improved by amending our approach to studying them. We propose four recommendations for improving the pursuit of individual differences in JDM research: a more systematic approach; more theory-driven selection of measures; a reduced emphasis on main effects in favor of interactions between individual differences and decision features, situational factors, and other individual differences; and more extensive communication of results (whether significant or null, published or unpublished). As a first step, we offer our database—the Decision Making Individual Differences Inventory (DMIDI; http://html://www.sjdm.org/dmidi), a free, public resource that categorizes and describes the most common individual difference measures used in JDM research.
The Circadian Protein Period 1 Contributes to Blood Pressure Control and Coordinately Regulates Renal Sodium Transport Genes

The circadian clock protein period 1 (Per1) contributes to the regulation of expression of the &agr; subunit of the renal epithelial sodium channel at the basal level and in response to the mineralocorticoid hormone aldosterone. The goals of the present study were to define the role of Per1 in the regulation of additional renal sodium handling genes in cortical collecting duct cells and to evaluate blood pressure (BP) in mice lacking functional Per1. To determine whether Per1 regulates additional genes important in renal sodium handling, a candidate gene approach was used. Immortalized collecting duct cells were transfected with a nontarget small interfering RNA or a Per1-specific small interfering RNA. Expression of the genes for &agr;-epithelial sodium channel and Fxyd5, a positive regulator of Na, K-ATPase activity, decreased in response to Per1 knockdown. Conversely, mRNA expression of caveolin 1, Ube2e3, and ET-1, all negative effectors of epithelial sodium channel, was induced after Per1 knockdown. These results led us to evaluate BP in Per1 KO mice. Mice lacking Per1 exhibit significantly reduced BP and elevated renal ET-1 levels compared with wild-type animals. Given the established role of renal ET-1 in epithelial sodium channel inhibition and BP control, elevated renal ET-1 is one possible explanation for the lower BP observed in Per1 KO mice. These data support a role for the circadian clock protein Per1 in the coordinate regulation of genes involved in renal sodium reabsorption. Importantly, the lower BP observed in Per1 KO mice compared with wild-type mice suggests a role for Per1 in BP control as well.
Effects of combined sonodynamic and photodynamic therapies with photolon on a glioma C6 tumor model.

UNLABELLED The aim of this study was to investigate the low-power density sonication, sonodynamic therapy (SDT) with Photolon and combination of SDT and photodynamic therapy (PDT) with Photolon for the ablation of glioma C6 tumor model in rats. METHODS The study was performed on 50 rats bearing glioma C6. The tumors were sonicated with/without prior intravenous injection of photosensitizer (PS) Photolon (2.5 mg/kg b.w). Sonication was performed with 0.4; 0.7 and 1.0 W/cm² power density at 1 MHz frequency for 10 min, 2.0 h after Photolon administration using BTL-5710 Sono (BTL Industries Limited, Great Britain). PDT was carried out 2.5 h after Photolon administration using diode laser with 661 nm wavelength (IMAF-AXICON, Minsk, Republic of Belarus) at doses of 50 and 100 J/cm² with 0,17 W/cm² fluence rate. Assessment of tumor response was performed by vital staining with Evans blue and pathologic examination. RESULTS The maximal tumor necrosis area that underwent sonication (1 MHz; 0.7 W/cm²; 10 min.) followed by PDT at a dose of 100 J/cm² was 100%. CONCLUSION This is the first report to demonstrate the benefits of sono-photodynamic therapy (SPDT) consisting of low-power density ultrasound and PDT for the treatment of malignant glioma models.
Uracil-DNA Glycosylase Is Involved in DNA Demethylation and Required for Embryonic Development in the Zebrafish Embryo

Background: Ung implication in DNA demethylation and embryonic development is poorly understood. Results: unga knockdown in the zebrafish embryo increases global DNA methylation level, inhibits transcription, and causes embryonic lethality whereas its overexpression produces opposite effects on DNA methylation and transcription. Conclusion: Unga is involved in postfertilization DNA demethylation and transcription. Significance: The findings shed new light on Ung function in DNA demethylation and embryonic development. Uracil-DNA glycosylase (Ung) is a component of the base excision repair process and has the ability to remove uracil from U:G mispairs in DNA. However, its implications in development of vertebrate embryos are poorly understood. In this study, we found that zebrafish uracil-DNA glycosylase a (Unga) is maternally expressed at high levels and accumulated in nuclei during cleavage and blastulation periods. Knockdown of unga in zebrafish embryos causes an increase of the global DNA methylation level concomitantly with a reduction of overall transcriptional activity in the nucleus, ultimately resulting in embryonic lethality during segmentation period. Conversely, unga overexpression is sufficient to reduce the global DNA methylation level, to increase H3K4me3 and H3K27me3 marks, and to activate genome transcription. Furthermore, overexpression of unga(D132A) mRNA, encoding a mutant Unga without DNA glycosylase activity, does not affect global DNA methylation level, indicating that its involvement in DNA demethylation is dependent on its glycosylase activity. These results together suggest that Unga is implicated in postfertilization genomic DNA demethylation, zygotic gene transcription, and normal embryonic development in zebrafish.
Sequencing Operator Counts

Operator-counting is a recently developed framework for analysing and integrating many state-of-the-art heuristics for planning using Linear Programming. In cost-optimal planning only the objective value of these heuristics is traditionally used to guide the search. However the primal solution, i.e. the operator counts, contains useful information. We exploit this information using a SAT-based approach which given an operator-count, either finds a valid plan; or generates a generalized landmark constraint violated by that count. We show that these generalized landmarks can be used to encode the perfect heuristic, h*, as a Mixed Integer Program. Our most interesting experimental result is that finding or refuting a sequence for an operator-count is most often empirically efficient, enabling a novel and promising approach to planning based on Logic-Based Benders Decomposition (LBBD).
Elucidating Novel Hepatitis C Virus–Host Interactions Using Combined Mass Spectrometry and Functional Genomics Approaches*

More than 170 million people worldwide are infected with the hepatitis C virus (HCV), for which future therapies are expected to rely upon a combination of oral antivirals. For a rapidly evolving virus like HCV, host-targeting antivirals are an attractive option. To decipher the role of novel HCV–host interactions, we used a proteomics approach combining immunoprecipitation of viral–host protein complexes coupled to mass spectrometry identification and functional genomics RNA interference screening of HCV partners. Here, we report the proteomics analyses of protein complexes associated with Core, NS2, NS3/4A, NS4B, NS5A, and NS5B proteins. We identified a stringent set of 98 human proteins interacting specifically with one of the viral proteins. The overlap with previous virus–host interaction studies demonstrates 24.5% shared HCV interactors overall (24/98), illustrating the reliability of the approach. The identified human proteins show enriched Gene Ontology terms associated with the endoplasmic reticulum, transport proteins with a major contribution of NS3/4A interactors, and transmembrane proteins for Core interactors. The interaction network emphasizes a high degree distribution, a high betweenness distribution, and high interconnectivity of targeted human proteins, in agreement with previous virus–host interactome studies. The set of HCV interactors also shows extensive enrichment for known targets of other viruses. The combined proteomic and gene silencing study revealed strong enrichment in modulators of HCV RNA replication, with the identification of 11 novel cofactors among our set of specific HCV partners. Finally, we report a novel immune evasion mechanism of NS3/4A protein based on its ability to affect nucleocytoplasmic transport of type I interferon-mediated signal transducer and activator of transcription 1 nuclear translocation. The study revealed highly stringent association between HCV interactors and their functional contribution to the viral replication cycle and pathogenesis.
A tissue-engineered subcutaneous pancreatic cancer model for antitumor drug evaluation

The traditional xenograft subcutaneous pancreatic cancer model is notorious for its low incidence of tumor formation, inconsistent results for the chemotherapeutic effects of drug molecules of interest, and a poor predictive capability for the clinical efficacy of novel drugs. These drawbacks are attributed to a variety of factors, including inoculation of heterogeneous tumor cells from patients with different pathological histories, and use of poorly defined Matrigel®. In this study, we aimed to tissue-engineer a pancreatic cancer model that could readily cultivate a pancreatic tumor derived from highly homogenous CD24+CD44+ pancreatic cancer stem cells delivered by a well defined electrospun scaffold of poly(glycolide-co-trimethylene carbonate) and gelatin. The scaffold supported in vitro tumorigenesis from CD24+CD44+ cancer stem cells for up to 7 days without inducing apoptosis. Moreover, CD24+CD44+ cancer stem cells delivered by the scaffold grew into a native-like mature pancreatic tumor within 8 weeks in vivo and exhibited accelerated tumorigenesis as well as a higher incidence of tumor formation than the traditional model. In the scaffold model, we discovered that oxaliplatin-gemcitabine (OXA-GEM), a chemotherapeutic regimen, induced tumor regression whereas gemcitabine alone only capped tumor growth. The mechanistic study attributed the superior antitumorigenic performance of OXA-GEM to its ability to induce apoptosis of CD24+CD44+ cancer stem cells. Compared with the traditional model, the scaffold model demonstrated a higher incidence of tumor formation and accelerated tumor growth. Use of a tiny population of highly homogenous CD24+CD44+ cancer stem cells delivered by a well defined scaffold greatly reduces the variability associated with the traditional model, which uses a heterogeneous tumor cell population and poorly defined Matrigel. The scaffold model is a robust platform for investigating the antitumorigenesis mechanism of novel chemotherapeutic drugs with a special focus on cancer stem cells.
Training data selection for acoustic modeling via submodular optimization of joint kullback-leibler divergence

This paper provides a novel training data selection method to construct acoustic models for automatic speech recognition (ASR). Various training data sets have been developed for acoustic modeling. Each training set was created for a spe-ciﬁc ASR application such that acoustic characteristics in the set, e.g. speakers, noise and recording devices, match those in the application. A mixture of such already-created training sets (an out-of-domain set) becomes a large utterance set containing various acoustic characteristics. The proposed method selects the most appropriate subset of the out-of-domain set and uses it for supervised training of an acoustic model for a new ASR application. The subset that has the most similar acoustic characteristics to the target-domain set (i.e. untranscribed utterances recorded by the target application) is selected based on the proposed joint Kullback-Leibler (KL) divergence of speech and non-speech characteristics. Furthermore, in order to select one of the many subsets in practical computation time, we also propose a selection algorithm based on submodular optimization that minimizes the joint KL divergence by greedy selection with guaranteed optimality. Experiments on real meeting utterances that use deep neural network acoustic models show that the proposed method yields better acoustic models than random or likelihood-based selection.
Novel Primer-Probe Sets for Detection and Identification of Mycobacteria by PCR-Microarray Assay

ABSTRACT A PCR-microarray assay was developed in which PCR primers and hybridization probes were designed for the 16S rRNA genes of 16 clinically relevant mycobacteria and for IS6110 of Mycobacterium tuberculosis. The assay, based on a multiplex PCR followed by hybridization with oligonucleotide probes, was tested against 16 Mycobacterium species and 70 clinical samples.
Biologics: Targets and Therapy

Correspondence: Paul V Licciardi Allergy and Immune Disorders Group, Murdoch Childrens Research Institute, Melbourne, VIC 3052, Australia Email paul.licciardi@mcri.edu. au Abstract: Histone deacetylase (HDAC) inhibitors are an emerging class of therapeutics with potential as anticancer drugs. The rationale for developing HDAC inhibitors (and other chromatin-modifying agents) as anticancer therapies arose from the understanding that in addition to genetic mutations, epigenetic changes such as dysregulation of HDAC enzymes can alter phenotype and gene expression, disturb homeostasis, and contribute to neoplastic growth. The family of HDAC inhibitors is large and diverse. It includes a range of naturally occurring and synthetic compounds that differ in terms of structure, function, and specificity. HDAC inhibitors have multiple cell type-specific effects in vitro and in vivo, such as growth arrest, cell differentiation, and apoptosis in malignant cells. HDAC inhibitors have the potential to be used as monotherapies or in combination with other anticancer therapies. Currently, there are two HDAC inhibitors that have received approval from the US FDA for the treatment of cutaneous T-cell lymphoma: vorinostat (suberoylanilide hydroxamic acid, Zolinza) and depsipeptide (romidepsin, Istodax). More recently, depsipeptide has also gained FDA approval for the treatment of peripheral T-cell lymphoma. Many more clinical trials assessing the effects of various HDAC inhibitors on hematological and solid malignancies are currently being conducted. Despite the proven anticancer effects of particular HDAC inhibitors against certain cancers, many aspects of HDAC enzymes and HDAC inhibitors are still not fully understood. Increasing our understanding of the effects of HDAC inhibitors, their targets and mechanisms of action will be critical for the advancement of these drugs, especially to facilitate the rational design of HDAC inhibitors that are effective as antineoplastic agents. This review will discuss the use of HDAC inhibitors as multitargeted therapies for malignancy. Further, we outline the pharmacology and mechanisms of action of HDAC inhibitors while discussing the safety and efficacy of these compounds in clinical studies to date.
Speech playback geometry for smart homes

Smart homes are environments that intelligently communicate with users, primarily through speech, to control various devices and activities relating to daily living. Both automatic speech recognition and text-to-speech are enabling technologies, however the basic home environment is often acoustically noisy and unconstrained in usage, leading to significant practical difficulties with both key technologies. In addition to interfering noise problems, a home occupant may not always be located physically close to either a microphone or loudspeaker. Speech intelligibility in a smart home depends on many factors including background noise, speech power and content. It is also affected by the orientation of the listeners' ears with respect to the speech source. This paper describes a simple technique to adjust perceived phase angle, and reports results from experiments to assess how the intelligibility of speech heard in such an environment will vary with respect to head position.
Clarifications on Continuous Renal Replacement Therapy and Hemodynamics

Objective: Continuous renal replacement therapy (CRRT) is a continuous process of bedside blood purification which is widely used in the treatment of acute kidney injury (AKI) and for fluid management. However, since AKI and fluid overload are often found to be associated with hemodynamic abnormalities, determining the relationship between CRRT and hemodynamics remains a challenge in the treatment of critically ill patients. The aim of this review was to summarize key points in the relationship between CRRT and hemodynamics and to understand and monitor renal hemodynamics in critically ill patients, especially those with AKI. Data Sources: This review was based on data in articles published in the PubMed databases up to January 30, 2017, with the following keywords: “continuous renal replacement therapy,” “Hemodynamics,” and “Acute kidney injury. ” Study Selection: Original articles and critical reviews on CRRT were selected for this review. Results: CRRT might treat AKI by hemodynamic therapy, and it was an important form of hemodynamic therapy. The targets of hemodynamic therapy should be established when using CRRT. Therefore, hemodynamic management and stability were very important during CRRT. Most studies suggested that renal hemodynamics should be clearly identified. Conclusions: CRRT is not only a replacement for organ function, but an important form of hemodynamic therapy. Improved hemodynamic management of critically ill patients can be achieved by establishing specific therapeutic hemodynamic targets and maintaining circulatory stability during CRRT. Over the long term, observation of renal hemodynamics will provide greater opportunities for the progression of CRRT hemodynamic therapy.
Expression and Stability of Arabidopsis CDC6 Are Associated with Endoreplication Article, publication date, and citation information can be found at www.plantcell.org/cgi/doi/10.1105/tpc.010329.

Studies on the CDC6 protein, which is crucial to the control of DNA replication in yeast and animal cells, are lacking in plants. We have isolated an Arabidopsis cDNA encoding the AtCDC6 protein and studied its possible connection to the occurrence of developmentally regulated endoreplication cycles. The AtCDC6 gene is expressed maximally in early S-phase, and its promoter contains an E2F consensus site that mediates the binding of a plant E2F/DP complex. Transgenic plants carrying an AtCDC6 promoter–β-glucuronidase fusion revealed that it is active in proliferating cells and, interestingly, in endoreplicating cells. In particular, the extra endoreplication cycle that occurs in dark-grown hypocotyl cells is associated with upregulation of the AtCDC6 gene. This was corroborated using ctr1 Arabidopsis mutants altered in their endoreplication pattern. The ectopic expression of AtCDC6 in transgenic plants induced endoreplication and produced a change in the somatic ploidy level. AtCDC6 was degraded in a ubiquitin- and proteosome-dependent manner by extracts from proliferating cells, but it was degraded poorly by extracts from dark-grown hypocotyl endoreplicating cells. Our results indicate that endoreplication is associated with expression of the AtCDC6 gene and, most likely, the stability of its product; it also apparently requires activation of the retinoblastoma/E2F/DP pathway. These conclusions may apply to endoreplicating cells in other tissues of the plant and to endoreplicating cells in other eukaryotes.