Counter-intuitive moral judgement following traumatic brain injury

Several neurological patient populations, including Traumatic Brain Injury (TBI), appear to produce an abnormally ‘utilitarian’ pattern of judgements to moral dilemmas; they tend to make judgements that maximise the welfare of the majority, rather than deontological judgements based on the following of moral rules (e.g., do not harm others). However, this patient research has always used extreme dilemmas with highly valued moral rules (e.g., do not kill). Data from healthy participants, however, suggests that when a wider range of dilemmas are employed, involving less valued moral rules (e.g., do not lie), moral judgements demonstrate sensitivity to the psychological intuitiveness of the judgements, rather than their deontological or utilitarian content (Kahane et al., 2011). We sought the moral judgements of 30 TBI participants and 30 controls on moral dilemmas where content (utilitarian/deontological) and intuition (intuitive/counterintuitive) were measured concurrently. Overall TBI participants made utilitarian judgements in equal proportions to controls; disproportionately favouring utilitarian judgements only when they were counterintuitive, and deontological judgements only when they were counterintuitive. These results speak against the view that TBI causes a specific utilitarian bias, suggesting instead that moral intuition is broadly disrupted following TBI

Fibre Channel Switch Modeling at Fibre Channel-2 Level for Large Fabric Storage Area Network Simulations using OMNeT++

Abstract—Typically, in the current enterprise data centers dedicated fabrics or networks are implemented to meet their LAN, Inter-Processor communication and storage traffic requirements. The storage traffic requirements of a group of servers are met through multiple storage area networks based on fibre channel, which has become the standard connection type. Typically, this fibre channel storage area networks are small (maximum of 32 switches/directors in a single fabric) and do not experience any scaling, stability and other performance issues.The advent of I/O consolidation in enterprise data centers for multiple traffic types to converge on to a single fabric or network (typically Ethernet platform) to reduce hardware, energy and management costs has also the potential to allow implementation of large storage area networks based on the fibre channel standards. Large storage area networks are being planned with more than two hundred switches/directors in a single fabric or network in addition to servers and storages connected to the fabric on Ethernet platforms. Even though these large storage area networks are envisioned to operate on Ethernet platform, they still have to satisfy the stringent operating and performance requirement set forth by the fibre channel standards. The two important issues of concern with large storage area networks are scaling and stability. The scaling and stability issues are dependent on the interactions and performance capabilities of various fabric servers located on each switch/director in the fabric in order to provide fabric services. In order to determine the extent of scaling and stability issues of a large fabric first the detailed models of the switch/director addressing the operations of the individual fabric servers are required. Next, the interactions of the switches/directors using the detailed models are to be simulated to study the scaling and stability issues.In this paper, the detailed modeling of the fibre channel switch and the fabric servers using the OMNeT++ discrete event simulator is presented first. Detailed models are developed addressing the behavior of the switch at the level-2 of the fibre channel protocol since this layer addresses the requirements and operations of various mandatory fabric services like fabric build, directory, login, nameserver, management, etc. Next, using the OMNET++ discrete event simulator large fabrics are simulated. The results from the simulation are compared against the test bed traffic and the accuracy is demonstrated. Also, results and analysis of multiple simulations with increasing fabric size are presented

Cognitive correlates of pragmatic language comprehension in adult traumatic brain injury: A systematic review and meta-analyses

Effective pragmatic comprehension of language is critical for successful communication and interaction, but this ability is routinely impaired following Traumatic Brain Injury (TBI) [1,2]. Individual studies have investigated the cognitive domains associated with impaired pragmatic comprehension, but there remains little understanding of the relative importance of these domains in contributing to pragmatic comprehension impairment following TBI. This paper presents a systematic meta-analytic review of the observed correlations between pragmatic comprehension and cognitive processes following TBI. Five meta-analyses were computed, which quantified the relationship between pragmatic comprehension and five key cognitive constructs (declarative memory; working memory; attention; executive functions; social cognition). Significant moderate-to-strong correlations were found between all cognitive measures and pragmatic comprehension, where declarative memory was the strongest correlate. Thus, our findings indicate that pragmatic comprehension in TBI is associated with an array of domain general cognitive processes, and as such deficits in these cognitive domains may underlie pragmatic comprehension difficulties following TBI. The clinical implications of these findings are discussed

Mouse frontal cortex mediates additive multisensory decisions

The brain can combine auditory and visual information to localize objects. However, the cortical substrates underlying audiovisual integration remain uncertain. Here, we show that mouse frontal cortex combines auditory and visual evidence; that this combination is additive, mirroring behavior; and that it evolves with learning. We trained mice in an audiovisual localization task. Inactivating frontal cortex impaired responses to either sensory modality, while inactivating visual or parietal cortex affected only visual stimuli. Recordings from >14,000 neurons indicated that after task learning, activity in the anterior part of frontal area MOs (secondary motor cortex) additively encodes visual and auditory signals, consistent with the mice's behavioral strategy. An accumulator model applied to these sensory representations reproduced the observed choices and reaction times. These results suggest that frontal cortex adapts through learning to combine evidence across sensory cortices, providing a signal that is transformed into a binary decision by a downstream accumulator

Micro-volume couette flow sample orientation for absorbance and fluorescence linear dichroism

Linear dichroism (LD) can be used to study the alignment of absorbing chromophores within long molecules. In particular, Couette flow LD has been used to good effect in probing ligand binding to DNA and to fibrous proteins. This technique has been previously limited by large sample requirements. Here we report the design and application of a new micro-volume Couette flow cell that significantly enhances the potential applications of flow LD spectroscopy by reducing the sample requirements for flow linear dichroism to 25 μL (with concentrations such that the absorbance maximum of the sample in a 1-cm pathlength cuvette is not, vert, similar1). The micro-volume Couette cell has also enabled the measurement of fluorescence-detected Couette flow linear dichroism. This new technique enables the orientation of fluorescent ligands to be probed even when their electronic transitions overlap with those of the macromolecule and conversely. The potential of flow-oriented fluorescence dichroism and application of the micro-volume Couette LD cell are illustrated by the collection of data for DNA with minor groove and intercalating ligands: DAPI, Hoechst, and ethidium bromide. As with conventional fluorescence, improved sensitivity compared with absorbance LD is to be expected after instrumentation optimization

Cell origin-dependent cooperativity of mutant Dnmt3a and Npm1 in clonal hematopoiesis and myeloid malignancy.

In adult acute myeloid leukemia (AML), the acquisition of driver somatic mutations may be preceded by a benign state termed clonal hematopoiesis (CH). To develop therapeutic strategies to prevent leukemia development from CH, it is important to understand the mechanisms by which CH-driving and AML-driving mutations cooperate. Here, we use mice with inducible mutant alleles common in human CH (DNMT3AR882; mouse Dnmt3aR878H) and AML (NPM1c; mouse Npm1cA). We find that Dnmt3aR878H/+ hematopoietic stem cells (HSCs), but not multipotent progenitor cell (MPP) subsets, have reduced cytokine expression and proinflammatory transcriptional signatures and a functional competitive advantage over their wild-type counterparts. Dnmt3aR878H/+ HSCs are the most potent cell type transformed by Npm1cA, generating myeloid malignancies in which few additional cooperating somatic mutation events were detected. At a molecular level, Npm1cA, in cooperation with Dnmt3aR878H, acutely increased the accessibility of a distinct set of promoters in HSCs compared with MPP cells. These promoters were enriched for cell cycling, PI3K/AKT/mTOR signaling, stem cell signatures, and targets of transcription factors, including NFAT and the chromatin binding factor HMGB1, which have been implicated in human AML. These results demonstrate cooperativity between preexisting Dnmt3aR878H and Npm1cA at the chromatin level, where specific loci altered in accessibility by Npm1cA are dependent on cell context as well as Dnmt3a mutation status. These findings have implications for biological understanding and therapeutic intervention in the transformation from CH to AML

Anti-trypanosomal 8-hydroxyl naphthyridines are chelators of divalent transition metals

The lack of information regarding the mechanisms of action (MoA) or specific molecular targets of phenotypically active compounds can prove a barrier to their development as chemotherapeutic agents. Here, we report the results of our orthogonal genetic, molecular, and biochemical studies to determine the MoA of a novel 7-substituted 8-hydroxy-1,6-naphthyridine (8-HNT) series that displays promising activity against Trypanosoma brucei and Leishmania donovani . </jats:p

Introducing discrete frequency infrared technology for high-throughput biofluid screening

Accurate early diagnosis is critical to patient survival, management and quality of life. Biofluids are key to early diagnosis due to their ease of collection and intimate involvement in human function. Large-scale mid-IR imaging of dried fluid deposits offers a high-throughput molecular analysis paradigm for the biomedical laboratory. The exciting advent of tuneable quantum cascade lasers allows for the collection of discrete frequency infrared data enabling clinically relevant timescales. By scanning targeted frequencies spectral quality, reproducibility and diagnostic potential can be maintained while significantly reducing acquisition time and processing requirements, sampling 16 serum spots with 0.6, 5.1 and 15% relative standard deviation (RSD) for 199, 14 and 9 discrete frequencies respectively. We use this reproducible methodology to show proof of concept rapid diagnostics; 40 unique dried liquid biopsies from brain, breast, lung and skin cancer patients were classified in 2.4 cumulative seconds against 10 non-cancer controls with accuracies of up to 90%

MicroRNA transcriptome profiles during swine skeletal muscle development

<p>Abstract</p> <p>Background</p> <p>MicroRNA (miR) are a class of small RNAs that regulate gene expression by inhibiting translation of protein encoding transcripts. To evaluate the role of miR in skeletal muscle of swine, global microRNA abundance was measured at specific developmental stages including proliferating satellite cells, three stages of fetal growth, day-old neonate, and the adult.</p> <p>Results</p> <p>Twelve potential novel miR were detected that did not match previously reported sequences. In addition, a number of miR previously reported to be expressed in mammalian muscle were detected, having a variety of abundance patterns through muscle development. Muscle-specific miR-206 was nearly absent in proliferating satellite cells in culture, but was the highest abundant miR at other time points evaluated. In addition, miR-1 was moderately abundant throughout developmental stages with highest abundance in the adult. In contrast, miR-133 was moderately abundant in adult muscle and either not detectable or lowly abundant throughout fetal and neonate development. Changes in abundance of ubiquitously expressed miR were also observed. MiR-432 abundance was highest at the earliest stage of fetal development tested (60 day-old fetus) and decreased throughout development to the adult. Conversely, miR-24 and miR-27 exhibited greatest abundance in proliferating satellite cells and the adult, while abundance of miR-368, miR-376, and miR-423-5p was greatest in the neonate.</p> <p>Conclusion</p> <p>These data present a complete set of transcriptome profiles to evaluate miR abundance at specific stages of skeletal muscle growth in swine. Identification of these miR provides an initial group of miR that may play a vital role in muscle development and growth.</p