Miracle-dz/UniFAR-FTUs huggingface dataset:
IsK and KvLQT1: mutation in either of the two subunits of the slow component of the delayed rectifier potassium channel can cause Jervell and Lange-Nielsen syndrome.

The Jervell and Lange-Nielsen syndrome (JLNS) comprises profound congenital sensorineural deafness associated with syncopal episodes. These are caused by ventricular arrhythmias secondary to abnormal repolarisation, manifested by a prolonged QT interval on the electrocardiogram. Recently, in families with JLNS, Neyroud et al. reported homozygosity for a single mutation in KVLQT1 , a gene which has previously been shown to be mutated in families with dominantly inherited isolated long QT syndrome [Neyroud et al . (1997) Nature Genet . , 15, 186-189]. We have analysed a group of families with JLNS and shown that the majority are consistent with mutation at this locus: five families of differing ethnic backgrounds were homozygous by descent for markers close to the KVLQT1 gene and a further three families from the same geographical region were shown to be homozygous for a common haplotype and to have the same homozygous mutation of the KVLQT1 gene. However, analysis of a single small consanguineous family excluded linkage to the KVLQT1 gene, establishing genetic heterogeneity in JLNS. The affected children in this family were homozygous by descent for markers on chromosome 21, in a region containing the gene IsK . This codes for a transmembrane protein known to associate with KVLQT1 to form the slow component of the delayed rectifier potassium channel. Sequencing of the affected boys showed a homozygous mutation, demonstrating that mutation in the IsK gene may be a rare cause of JLNS and that an indistinguishable phenotype can arise from mutations in either of the two interacting molecules.
Dynamic Estimation of Rater Reliability in Subjective Tasks Using Multi-armed Bandits

Many application areas that use supervised machine learning make use of multiple raters to collect target ratings for training data. Usage of multiple raters, however, inevitably introduces the risk that a proportion of them will be unreliable. The presence of unreliable raters can prolong the rating process, make it more expensive and lead to inaccurate ratings. The dominant, "static" approach of solving this problem in state-of-the-art research is to estimate the rater reliability and to calculate the target ratings when all ratings have been gathered. However, doing it dynamically while raters rate training data can make the acquisition of ratings faster and cheaper compared to static techniques. We propose to cast the problem of the dynamic estimation of rater reliability as a multi-armed bandit problem. Experiments show that the usage of multi-armed bandits for this problem is worthwhile, providing that each rater can rate any asset when asked. The purpose of this paper is to outline the directions of future research in this area.
A Framework for Designing Embedded Real-Time Controllers

Control systems are typically designed assuming an ideal behavior of the computing infrastructure where controllers execute. In practice, however, in highly loaded computing systems consisting of multiple concurrent controllers, resource constraints may introduce delays and jitter in control loops that may degrade control performance significantly. Hence, taking resource constraints into account since the beginning of the design cycle is crucial for optimizing the performance of a control system. In this paper, we propose a general framework for evaluating the performance of a control system as a function of multiple timing attributes (e.g., sampling frequencies, delays and jitter) and for selecting the proper control task parameters (e.g., periods and deadlines) taking resource constraints into account. The proposed framework is illustrated using a real control plant.
Biomarkers to evaluate the effects of temperature and methanol on recombinant Pichia pastoris

Pichia pastoris is methylotrophic yeast used as an efficient expression system for heterologous protein production. In order to evaluate the effects of temperature (10 and 30 °C) and methanol (1 and 3% (v/v)) on genetically-modified Pichia pastoris, different biomarkers were evaluated: Heat stress (HSF-1 and Hsp70), oxidative stress (OGG1 and TBARS) and antioxidant (GLR). Three yeast cultures were performed: 3X = 3% methanol-10 °C, 4X = 3% methanol-30 °C, and 5X = 1% methanol-10°C. The expression level of HIF-1α, HSF-1, HSP-70 and HSP-90 biomarkers were measured by Western blot and in situ detection was performed by immunocytochemistry. Ours results show that at 3% methanol −30 °C there is an increase of mitochondrial OGG1 (mtOGG1), Glutathione Reductase (GLR) and TBARS. In addition, there was a cytosolic expression of HSF-1 and HSP-70, which indicates a deprotection against nucleolar fragmentation (apoptosis). On the other hand, at 3% methanol −10 °C and 1% and at methanol −10 °C conditions there was nuclear expression of OGG1, lower levels of TBARS and lower expression of GLR, cytosolic expression of HSF-1 and nuclear expression HSP-70. In conclusion, our results suggest that 3% methanol-30 °C is a condition that induces a strong oxidative stress and risk factors of apoptosis in modified-genetically P. pastoris.
Interactions between CdsD, CdsQ, and CdsL, Three Putative Chlamydophila pneumoniae Type III Secretion Proteins

ABSTRACT Chlamydophila pneumoniae is a gram-negative obligate intracellular bacterial pathogen that causes pneumonia and bronchitis and may contribute to atherosclerosis. The developmental cycle of C. pneumoniae includes a morphological transition from an infectious extracellular elementary body (EB) to a noninfectious intracellular reticulate body (RB) that divides by binary fission. The C. pneumoniae genome encodes a type III secretion (T3S) apparatus that may be used to infect eukaryotic cells and to evade the host immune response. In the present study, Cpn0712 (CdsD), Cpn0704 (CdsQ), and Cpn0826 (CdsL), three C. pneumoniae genes encoding yersiniae T3S YscD, YscQ, and YscL homologs, respectively, were cloned and expressed as histidine- and glutathione S-transferase (GST)-tagged proteins in Escherichia coli. Purified recombinant proteins were used to raise hyper-immune polyclonal antiserum and were used in GST pull-down and copurification assays to identify protein-protein interactions. CdsD was detected in both EB and RB lysates by Western blot analyses, and immunofluorescent staining demonstrated the presence of CdsD within inclusions. Triton X-114 solubilization and phase separation of chlamydial EB proteins indicated that CdsD partitions with cytoplasmic proteins, suggesting it is not an integral membrane protein. GST pull-down assays indicated that recombinant CdsD interacts with CdsQ and CdsL, and copurification assays with chlamydial lysates confirmed that native CdsD interacts with CdsQ and CdsL. To the best of our knowledge, this is the first report demonstrating interactions between YscD, YscQ, and YscL homologs of bacterial T3S systems. These novel protein interactions may play important roles in the assembly or function of the chlamydial T3S apparatus.
MAD7: a memory architecture simulator targeted at design space exploration

We introduce MAD7, a tool that rapidly simulates many-core memory architectures at a functional level. MAD7 focuses on tracking access patterns and data spatial localities rather than enforcing any precise on-chip arbitration protocols. Although not cycle accurate by nature, it provides useful insights when comparing different memory architectures under real-world workloads. Potential cache access and on-chip network usage bottlenecks can be easily spotted visually thanks to figures generated by our tool. MAD7 simulations are multi-threaded and are typically up to two orders of magnitude faster than those of a fully cycle accurate simulator.
A Novel Obstacle Detection Method Based on Monocular Camera and Laser Radar

Obstacle detection is an important task in the field of environmental perception for Intelligent Ground Robots. This paper presents a new obstacle detection method which uses visual saliency detection to detect multiple obstacles in the scene. By analyzing the saliency map and the marker-based watershed algorithm, we combine their characteristics creatively to obtain accurate contours of obstacles, and propose a fast method to detect obstacles based on monocular camera and laser radar. The laser radar points representing obstacles are clustered, and projected onto the saliency map as markers of watershed algorithm. The experimental results indicate the effectiveness, robustness and performance of real-time of our method.
Variations of CITED2 Are Associated with Congenital Heart Disease (CHD) in Chinese Population

CITED2 was identified as a cardiac transcription factor which is essential to the heart development. Cited2-deficient mice showed cardiac malformations, adrenal agenesis and neural crest defects. To explore the potential impact of mutations in CITED2 on congenital heart disease (CHD) in humans, we screened the coding region of CITED2 in a total of 700 Chinese people with congenital heart disease and 250 healthy individuals as controls. We found five potential disease-causing mutations, p.P140S, p.S183L, p.S196G, p.Ser161delAGC and p. Ser192_Gly193delAGCGGC. Two mammalian two-hybrid assays showed that the last four mutations significantly affected the interaction between p300CH1 and CITED2 or HIF1A. Further studies showed that four CITED2 mutations recovered the promoter activity of VEGF by decreasing its competitiveness with HIF1A for binding to p300CH1 and three mutations decreased the consociation of TFAP2C and CITED2 in the transactivation of PITX2C. Both VEGF and PITX2C play very important roles in cardiac development. In conclusion, we demonstrated that CITED2 has a potential causative impact on congenital heart disease.
The Fate of Childhood Memories: Children Postdated Their Earliest Memories as They Grew Older

Childhood amnesia has been attributed to the inaccessibility of early memories as children grow older. We propose that systematic biases in the age estimates of memories may play a role. A group of 4- to 9-year-olds children were followed for 8 years, recalling and dating their earliest childhood memories at three time points. Although children retained many of the memories over time, their age estimates of these memories shifted forward in time, to later ages. The magnitude of postdating was especially sizable for earlier memories and younger children such that some memories were dated more than a year later than originally. As a result, the boundary of childhood amnesia increased with age. These findings shed light on childhood amnesia and the fate of early memories. They further suggest that generally accepted estimates for people’s age of earliest memory may be wrong, which has far-reaching implications.
Activation of L-type Calcium Channels Is Required for Gap Junction-mediated Intercellular Calcium Signaling in Osteoblastic Cells*

The propagation of mechanically induced intercellular calcium waves (ICW) among osteoblastic cells occurs both by activation of P2Y (purinergic) receptors by extracellular nucleotides, resulting in “fast” ICW, and by gap junctional communication in cells that express connexin43 (Cx43), resulting in “slow” ICW. Human osteoblastic cells transmit intercellular calcium signals by both of these mechanisms. In the current studies we have examined the mechanism of slow gap junction-dependent ICW in osteoblastic cells. In ROS rat osteoblastic cells, gap junction-dependent ICW were inhibited by removal of extracellular calcium, plasma membrane depolarization by high extracellular potassium, and the L-type voltage-operated calcium channel inhibitor, nifedipine. In contrast, all these treatments enhanced the spread of P2 receptor-mediated ICW in UMR rat osteoblastic cells. Using UMR cells transfected to express Cx43 (UMR/Cx43) we confirmed that nifedipine sensitivity of ICW required Cx43 expression. In human osteoblastic cells, gap junction-dependent ICW also required activation of L-type calcium channels and influx of extracellular calcium.
Does Transcranial Direct Current Stimulation to Prefrontal Cortex Affect Mood and Emotional Memory Retrieval in Healthy Individuals?

Studies using transcranial direct current stimulation (tDCS) of prefrontal cortex to improve symptoms of depression have had mixed results. We examined whether using tDCS to change the balance of activity between left and right dorsolateral prefrontal cortex (DLPFC) can alter mood and memory retrieval of emotional material in healthy volunteers. Participants memorised emotional images, then tDCS was applied bilaterally to DLPFC while they performed a stimulus-response compatibility task. Participants were then presented with a set of images for memory retrieval. Questionnaires to examine mood and motivational state were administered at the beginning and end of each session. Exploratory data analyses showed that the polarity of tDCS to DLPFC influenced performance on a stimulus-response compatibility task and this effect was dependent on participants’ prior motivational state. However, tDCS polarity had no effect on the speed or accuracy of memory retrieval of emotional images and did not influence positive or negative affect. These findings suggest that the balance of activity between left and right DLPFC does not play a critical role in the mood state of healthy individuals. We suggest that the efficacy of prefrontal tDCS depends on the initial activation state of neurons and future work should take this into account.
A Quantitative Analysis of Complexity of Human Pathogen-Specific CD4 T Cell Responses in Healthy M. tuberculosis Infected South Africans

We performed a quantitative analysis of the HLA restriction, antigen and epitope specificity of human pathogen specific responses in healthy individuals infected with M. tuberculosis (Mtb), in a South African cohort as a test case. The results estimate the breadth of T cell responses for the first time in the context of an infection and human population setting. We determined the epitope repertoire of eleven representative Mtb antigens and a large panel of previously defined Mtb epitopes. We estimated that our analytic methods detected 50–75% of the total response in a cohort of 63 individuals. As expected, responses were highly heterogeneous, with responses to a total of 125 epitopes detected. The 66 top epitopes provided 80% coverage of the responses identified in our study. Using a panel of 48 HLA class II-transfected antigen-presenting cells, we determined HLA class II restrictions for 278 epitope/donor recognition events (36% of the total). The majority of epitopes were restricted by multiple HLA alleles, and 380 different epitope/HLA combinations comprised less than 30% of the estimated Mtb-specific response. Our results underline the complexity of human T cell responses at a population level. Efforts to capture and characterize this broad and highly HLA promiscuous Mtb-specific T cell epitope repertoire will require significant peptide multiplexing efforts. We show that a comprehensive “megapool” of Mtb peptides captured a large fraction of the Mtb-specific T cells and can be used to characterize this response.
A Multilevel Traffic Incidents Detection Approach: Identifying Traffic Patterns and Vehicle Behaviours using real-time GPS data

This paper presents a multilevel approach for detecting traffic incidents causing congestion on major roads. It incorporates algorithms to detect unusual traffic patterns and vehicle behaviours on different road segments by utilising the real-time GPS data obtained from vehicles. The incident detection process involves two phases: (1) Identifies of road segments where abnormal traffic pattern is observed and further divides the 'abnormal segments' into smaller segments in order to isolate the potential incident area; (2) Performs a hierarchical analysis of the vehicles' GPS data, using predefined rules to detect any occurrence of abnormal behaviour within the 'abnormal' road section identified in phase 1. The strength of such approach lays in isolating road segments sequentially and then analysing vehicle data specific to the identified road segment. In this way, the processing of vast data is avoided which is an essential requirement for the better performance of such complex systems. The approach is demonstrated using a simulation of motorway segments near Coventry, UK.
Directional predictions for 4-class BCI data

Brain-computer interfaces (BCI) can allow disabled people to drive a wheel chair, just by imagining movement. Therefore, present day BCIs use training data, recorded during four dierent conditions, to calibrate a classier. This, however, causes jerky behavior while abruptly switching between discrete states. We propose a cost-sensitive support vector approach for estimating two-dimensional directions based on four- class BCI data, that is recorded from three subjects. We found that our method reduces the number of severe errors compared to classical support vector machines and results in a smoother trajectory estimate for application in a wheel chair.
Pseudomonas aeruginosa KUCD1, a possible candidate for cadmium bioremediation

A cadmium (8 mM) resistant Pseudomonas aeruginosa strain KUCd1 exhibiting high Cd accumulation under in vitro aerobic condition has been reported. The isolate showed a significant ability to remove more than 75% and 89% of the soluble cadmium during the active growth phase from the growth medium and from Cd-amended industrial wastewater under growth supportive condition. Transmission electron microscopy (TEM) and energy dispersive X-ray spectroscopy (EDXS) suggest the presence of Cd in the cells from mid stationary phase. The cell fractionation study revealed membrane and periplasm to be the major accumulating site in this strain. The chemical nature of the accumulated Cd was studied by X-ray powder diffraction analysis.
Immunological and structural evidence for patterned intussusceptive surface growth in a unicellular organism. A postulated role for submembranous proteins and microtubules

The surface complex of Euglena has been examined intact and after isolation and purification by the use of mild sonication to disrupt cells. In intact cells the surface complex (pellicle complex) is oriented in a series of parallel ridges and grooves, and possesses among other components a characteristic group of four to seven microtubules. Isolated pellicles retain the ridge and groove pattern but no microtubules are present. Isolates yielded at least three major polypeptides on SDS acrylamide gels; one or more of the polypeptides are postulated to be identical with a submembrane layer present in both intact and isolated pellicles; one polypeptide appears to be in or on the surface membrane. Antibodies directed against the isolated pellicles were conjugated directly or indirectly to fluorescein, latex spheres, or ferritin. In appropriate experiments with these antibody conjugates, it has been found that antigenic sites are immobile and that new antigenic sites (daughter strips) are inserted between parental strips in replicating cells. These results together with direct observation of daughter strips by transmission electron microscopy suggest that surface growth in Euglena occurs by intussusception. Microtubules associated with the pellicle complex are postulated to play a role in the development of new daughter strips, and possibly also in cell movements.
Detection of drug-resistant clones in chronic myelogenous leukemia patients during dasatinib and nilotinib treatment.

BACKGROUND Imatinib effectively inhibits the tyrosine kinase activity conferred by the BCR-ABL gene [fusion gene of BCR (breakpoint cluster region) and ABL1 (c-abl oncogene 1, receptor tyrosine kinase)] and thereby appreciably improves outcomes for chronic myelogenous leukemia (CML). A small percentage of patients relapse because of the proliferation of escape clones; such relapses can be treated with second-generation drugs. Early detection and monitoring of resistant clones may provide clinical benefit. We describe the development and testing of a new approach for quantitative monitoring of CML resistance. METHODS We designed mutation-specific assays that use hydrolysis probes and an array of allele-specific primers containing nucleotides mismatched at various positions. All assays were tested with plasmids containing corresponding mutant or wild-type sequences, allowing identification of optimal assays for specific and effective amplification of the target template. Clinical samples were then used to compare the results of selected assays with those of standard genotyping. RESULTS We used a modified amplification refractory mutational system approach and testing with plasmid constructs to design assays that allowed highly selective detection of resistance for all target mutations. By taking advantage of single-step performance and high PCR efficiency, we were able to quantitatively track the absolute amount of resistance conferred by a specific mutation over 4 orders of magnitude. Moreover, we designed an integrated test for dasatinib resistance that uses multiple primers simultaneously. CONCLUSIONS These single-step, closed-tube assays specifically target mutations associated with resistance to dasatinib or nilotinib. Compared with standard genotyping, such biased genotyping improves the detection of resistance or alternative features via quantitative analysis of the absolute amount of resistance.
Motivation and Color-Blind Racial Attitudes Among White Psychology Trainees

This study examined potential antecedents to color-blind racial attitudes in an effort to identify factors that may be necessary for the provision of effective multicultural services and training. Specifically, we examined motivational dynamics related to socially desirable responding (self-deception and impression management) and also to internal and external motivation to respond without prejudice in a sample of 198 psychology trainees. In general, the results indicated that self-deception was related to greater endorsement of color-blind attitudes. At the same time, internal motivation to respond without prejudice was related to greater awareness of the various dimensions of racism. Overall, the results of the present study indicate that helping students and practitioners discover their own internal reasons for developing a nonracist identity may facilitate the formation of a critical consciousness regarding race and racism in society today.
Predictive capacity of a cognitive screen: can the Addenbrooke’s Cognitive Examination - III predict early relapse following inpatient detoxification in severe alcohol dependence?

The remaining 71 articles were reviewed in full, resulting in the exclusion of 53 studies (see Appendix 3 for details and reasons for exclusion). The remaining 18 studies were included in the current review. See Figure 1 for an outline of the search results and selection process. Table 1Inclusion and Exclusion Criteria for studies Inclusion Criteria 1. Primary empirical papers reporting on quantitative data 2. Studies that examined populations of adults aged 18-65yrs 3. Studies that examined participants meeting recognised criteria for alcohol dependence 4. Studies which used the Iowa Gambling Task (IGT) as a measure of emotional decisionmaking ability 5. Studies which measured decision-making in terms of risky performance Exclusion Criteria 1. Studies not published in English 2. Case studies, unpublished dissertations, or review articles 3. Articles which were not peer reviewed 4. Studies which measured performance on the IGT in terms of reaction time or biological/physiological outcomes 5. Studies where participants are known have a significant history of or current dependence to other drugs (i.e. meet diagnostic criteria for two or more substances), or where this has not been explicitly reported