Miracle-dz/UniFAR-FTUs huggingface dataset:
Chloroplast group III twintron excision utilizing multiple 5′‐ and 3′‐splice sites.

The chloroplast genes of Euglena gracilis contain more than 60 group II and 47 group III introns. Some Euglena chloroplast genes also contain twintrons, introns‐within‐introns. Two types of twintrons have previously been described, a group II twintron and a mixed group II/group III twintron. We report that four introns, three within the RNA polymerase subunit gene rpoC1 and one within ribosomal protein gene rpl16, with mean lengths twice typical group III introns, are a new type of twintron. The group III twintrons are composed of group III introns within other group III introns. The splicing of the twintrons was analyzed by PCR amplification, cloning and sequencing of cDNAs, and Northern hybridization. Excision of each group III twintron occurs by a two‐step, sequential splicing pathway. Removal of the internal introns precedes excision of the external introns. Splicing of internal introns in three of the four group III twintrons involves multiple 5′‐ and/or 3′‐splice sites. With two of the twintrons the proximal 5′‐splice site can be spliced to an internal 3′‐splice site, yielding alternative ‘pseudo’ fully spliced mRNAs. Excised group III introns of the rpl16 twintron are not linear RNA molecules but either lariat or circular RNAs, probably a lariat. The origins of alternative splicing and a possible evolutionary relationship between group II, group III and nuclear pre‐mRNA introns are discussed.
A 65-nm CMOS Fully Integrated Transceiver Module for 60-GHz Wireless HD Applications

A fully integrated WirelessHD compatible 60-GHz transceiver module in 65-nm CMOS process is presented, covering the four standard channels. The silicon die is flip-chipped on top of a low-cost HTCC module which also includes an external 65-nm CMOS PA and large beamwidth antennas targeting industrial manufacturability. The module achieves a 16QAM OFDM modulation wireless link with 3.8 Gbps over 1 m. The transceiver consumption is 454 mW in RX mode (including PLL) and 1090 mW in TX mode (including PLL and external PA).
Down‐Regulation of Neuronal Nitric Oxide Synthase by Nitric Oxide After Oxygen‐Glucose Deprivation in Rat Forebrain Slices

Abstract : The precise role that nitric oxide (NO) plays in the mechanisms of ischemic brain damage remains to be established. The expression of the inducible isoform (iNOS) of NO synthase (NOS) has been demonstrated not only in blood and glial cells using in vivo models of brain ischemia‐reperfusion but also in neurons in rat forebrain slices exposed to oxygen‐glucose deprivation (OGD). We have used this experimental model to study the effect of OGD on the neuronal isoform of NOS (nNOS) and iNOS. In OGD‐exposed rat forebrain slices, a decrease in the calcium‐dependent NOS activity was found 180 min after the OGD period, which was parallel to the increase during this period in calcium‐independent NOS activity. Both dexamethasone and cycloheximide, which completely inhibited the induction of the calcium‐independent NOS activity, caused a 40‐70% recovery in calcium‐dependent NOS activity when compared with slices collected immediately after OGD. The NO scavenger oxyhemoglobin produced complete recovery of calcium‐dependent NOS activity, suggesting that NO formed after OGD is responsible for this down‐regulation. Consistently, exposure to the NO donor (Z)‐1‐[(2‐aminoethyl)‐N‐(2‐ammonioethyl)amino]diazen‐1‐ium‐1,2‐diolate (DETA‐NONOate) for 180 min caused a decrease in the calcium‐dependent NOS activity present in control rat forebrain slices. Furthermore, OGD and DETA‐NONOate caused a decrease in level of both nNOS mRNA and protein. In summary, our results indicate that iNOS expression down‐regulates nNOS activity in rat brain slices exposed to OGD. These studies suggest important and complex interactions between NOS isoforms, the elucidation of which may provide further insights into the physiological and pathophysiological events that occur during and after cerebral ischemia.
A novel architecture for a massively parallel low level vision processing engine on chip

Specific architectures for different low level vision modalities have been developed and described using reconfigurable hardware. Each of them tries to solve a single low level vision problem: optical flow, disparity, segmentation, tracking, etc. We introduce a novel architecture that includes multiple processing engines in a massively parallel low level vision processing engine of very high complexity and performance. Our design is able to process input images and extract at the same time different visual features such as multi-scale stereo, optical flow and local contrast descriptors such as local orientation, energy or phase. The latest hardware design techniques have been employed in order to achieve the presented system with more than 2000 basic processing elements running in parallel. We have based our system in a Harmonic filter image decomposition model based on Gabor-like filters. It has been validated in multiple scenarios in previous works and it allows sharing hardware resources among different vision modalities on the same chip. In this paper we present an FPGA based implementation of this intensive processing engine as well as the designing techniques employed. The circuit processes input frames of 512×512 pixels at 28 frames per second.
Clinical Pharmacokinetics of Oral Controlled-Release 5-Fluorocytosine

ABSTRACT 5-Fluorocytosine (5FC) is an oral antifungal that is currently used in combination with amphotericin B to treat Cryptococcus neoformans meningoencephalitis. The oral dosing of 5FC could be optimized by the use of a controlled-release (CR) formulation. The objective of the current study was to develop two prototype 5FC-CR formulations and evaluate the single-dose (1,500-mg) serum pharmacokinetic profiles of those formulations relative to the profile of the commercially available, immediate-release 5FC product (Ancobon) by the use of a phase 1, open-label, randomized, three-phase, crossover pharmacokinetic study design. Hydroxypropyl methylcellulose was utilized as the rate-controlling matrix to compound the 5FC-CR tablets. The two prototype 5FC-CR formulations demonstrated 80% release at 13.0 and 18.4 h, respectively, whereas the immediate-release product demonstrated 80% release at 0.28 h, as determined in vitro by the United States Pharmacopeia apparatus 2 dissolution method. Five subjects completed all three phases of the study without any adverse events. The mean maximum concentration, the area under the curve from time zero to 24 h, and the area under the curve from time zero to infinity were approximately 50% lower (P < 0.01) with the 5FC-CR formulations than with the immediate-release 5FC product. However, no statistically significant differences in the minimum concentrations at 24 h were noted between the formulations. The gastric absorption profile of 5FC-CR was well predicted by in vitro dissolution. Future exploration of a gastroretentive 5FC-CR formulation could overcome the marked lack of bioequivalence observed in the present study.
Stroke caregivers' strain: prevalence and determinants in the first six months after stroke

Purpose. Many disabled stroke survivors live at home supported by informal caregivers. Research has revealed that these caregivers are experiencing strain. This study aims to examine the prevalence and differences over time of caregivers' strain in the first 6 months post-stroke and to predict caregiver strain based on patients' and caregivers' characteristics and service input. Method. Ninety consecutive patients and their caregivers were assessed at 2, 4 and 6 months post-stroke. The Caregiver Strain Index was used to evaluate strain. Patients' motor function, functional ability, health status, emotion and participation and caregivers' gender and relation to the patient and service input after discharge were measured to determine the predictive factors. Results. Nearly one out of three caregivers experienced strain. No differences were seen between 2, 4 and 6 months post-stroke. Correlation and multiple regression analyses revealed that in predicting strain, the patients' functional and activity level plays an important role in the sub-acute phase while the participation level gets more important over time. Conclusions. These findings emphasize the importance of maximal physical recovery and optimal reintegration in the community. This is not only essential for the patients themselves but also a pre-requisite to reduce the strain of their caregivers.
Evaluation of the pharmacokinetics and clinical utility of isavuconazole for treatment of invasive fungal infections

Introduction: Invasive fungal infections remain a leading cause of infectious morbidity and mortality in immunocompromised patients. There are relatively few effective antifungal agents, and currently available agents all have significant limitations. Isavuconazole is a novel second-generation triazole with broad-spectrum antifungal activity, and a favorable pharmacokinetic–pharmacodynamic profile. Isavuconazole is available as an oral and intravenous formulation. Phase III studies that are examining the efficacy of isavuconazole for invasive candidiasis and invasive aspergillosis are currently in progress. Areas covered: This review provides a summary of the pharmacological characteristics of isavuconazole and the potential future use of this agent. The preclinical and clinical pharmacokinetics and pharmacodynamics are discussed. This review was constructed by searching isavuconazole, triazole, pharmacokinetics and pharmacodynamics in PubMed. References and abstracts that were not identified by this method were retrieved from the respective publications. Expert opinion: Isavuconazole has the potential to become an important agent for the treatment of invasive fungal infections, principally because of its relatively broad and potent in vitro antifungal activity, and its favorable pharmacokinetic profile. Further preclinical and clinical studies are required to define the clinical utility of this agent, especially for invasive candidiasis and invasive aspergillosis. Further information is required on the likely drug interactions, and in vitro susceptibility breakpoints for medically important invasive fungal pathogens. Further pharmacokinetic studies are also required in a range of patient populations to quantify the extent and sources of pharmacokinetic variability.
Wnt/frizzled family members mediate olfactory sensory neuron axon extension

A comprehensive model has yet to emerge, but it seems likely that numerous mechanisms contribute to the specificity of olfactory sensory neuron (OSN) axon innervation of the olfactory bulb. Elsewhere in the nervous system the Wnt/Fz family has been implicated in patterning of anterior‐posterior axes, cell type specification, cell proliferation, and axon guidance. Because of our work describing cadherin‐catenin family member expression in the primary olfactory pathway, and because mechanisms of Wnt‐Fz interactions can depend in part on catenins, we were encouraged to explore Wnt‐Fz expression and function in OSN axon extension. Here, we show that OSNs express Fz‐1, Fz‐3, and Wnt‐5a, whereas olfactory ensheathing cells (OECs) express Wnt‐4. Fz‐7 is also expressed in the olfactory nerve by cells that delineate large axon fascicles, but are negative for OEC markers. Fz‐1 showed a developmental downregulation. However, in adults it is expressed at different levels across the olfactory epithelium and in restricted glomeruli across the olfactory bulb, suggesting an important role in the formation and maintenance of OSN connections to the olfactory bulb. Reporter TOPGAL mice demonstrated that some OECs located in the inner olfactory nerve layer can respond to Wnt ligands. Of further interest, we show here with in vitro assays that Wnt‐5a increases OSN axon outgrowth and alters growth cone morphology. Our data point to a key role for Wnt/Fz molecules in the development of the mouse olfactory system, providing complementary mechanisms required for OSN axon extension and coalescence. J. Comp. Neurol. 511:301–317, 2008. © 2008 Wiley‐Liss, Inc.
The Adjustment Disorder–New Module 20 as a Screening Instrument: Cluster Analysis and Cut-off Values

Background: Adjustment disorder (AjD) is a transient mental health condition emerging after stressful life events. Its diagnostic criteria have recently been under revision which led to the development of the Adjustment Disorder–New Module 20 (ADNM-20) as a self-report assessment. Objective: To identify a threshold value for people at high risk for AjD. Methods: As part of a randomized controlled trial evaluating a self-help manual for burglary victims, the baseline data of all participants (n=80) were analyzed. Besides the ADNM-20, participants answered self-report questionnaires regarding the external variables post-traumatic stress disorder symptomatology, depression, anxiety, and stress levels. We used cluster analysis and ROC analysis to identify the most appropriate cut-off value. Results: The cluster analysis identified three different subgroups. They differed in their level of AjD symptomatology from low to high symptom severity. The same pattern of impairment was found for the external variables. The ROC analysis testing the ADNM-20 sum score against the theory-based diagnostic algorithm, revealed an optimal cut-off score at 47.5 to distinguish between people at high risk for AjD and people at low risk. Conclusion: The ADNM-20 distinguishes between people with low, moderate, and high symptomatology. The recommendation for a cut-off score at 47.5 facilitates the use of the ADNM-20 in research and practice.
Treatment effects of olanzapine on homotopic connectivity in drug-free schizophrenia at rest

Abstract Objectives: Deficits in homotopic connectivity have been implicated in schizophrenia. However, alterations in homotopic connectivity associated with antipsychotic treatments in schizophrenia remain unclear due to lack of longitudinal studies. Methods: Seventeen drug-free patients with recurrent schizophrenia and 24 healthy controls underwent resting-state functional magnetic resonance imaging scans. The patients were scanned at three time points (baseline, at 6 weeks of treatment, and at 6 months of treatment). Voxel-mirrored homotopic connectivity (VMHC) was applied to analyse the imaging data to examine alterations in VMHC associated with antipsychotic treatment. Results: The results showed that patients with schizophrenia exhibited decreased VMHC in the default-mode network (such as the precuneus and inferior parietal lobule) and the motor and sensory processing regions (such as the lingual gyrus, fusiform gyrus and cerebellum lobule VI), which could be normalised or denormalised by olanzapine treatment. In addition, negative correlations were found between decreased VMHC and symptom severity in the patients at baseline. Conclusions: The present study shows that olanzapine treatment can normalise or denormalise decreased homotopic connectivity in schizophrenia. The findings also provide a new perspective to understand treatment effects of antipsychotic drugs on homotopic connectivity in schizophrenia that contribute to the disconnection hypothesis of this disease.
Identification and characterization of human PRICKLE1 and PRICKLE2 genes as well as mouse Prickle1 and Prickle2 genes homologous to Drosophila tissue polarity gene prickle.

Drosophila prickle is implicated in tissue polarity or planar polarity. Here, human PRICKLE1 gene corresponding to FLJ31937 cDNA and human PRICKLE2 gene corresponding to DKFZp686D143 cDNA were identified to be homologous to Drosophila prickle gene by using bioinformatics. PRICKLE1 gene was mapped to human chromosome 12p11-q12, and PRICKLE2 gene was mapped to human chromosome 3p14. Mouse Prickle1 and Prickle2 genes were next identified in mouse genome draft sequences NW_000106. 1 and NW_000262. 1, respectively. Human PRICKLE1, PRICKLE2, Xenopus Prickle, and Drosophila prickle were homologous in the PET domain, three LIM domains, and the C-terminal Prickle homologous (PKH) domain. LMO6 and TESTIN, containing the PET domain and three LIM domains, were found to lack the PKH domain. Therefore, PRICKLE1 and PRICKLE2 rather than LMO6 and TESTIN were found to be human homologs of Drosophila prickle. PRICKLE1 and PRICKLE2 mRNAs were expressed together in brain, eye and testis. PRICKLE1 mRNA was expressed in fetal heart and hematological malignancies, while PRICKLE2 mRNA in fetal brain, adult cartilage, pancreatic islet, gastric cancer with signet-ring cell features, and uterus tumors. Because tissue polarity genes frizzled, dishevelled, flamingo, and Vang are evolutionary and functionary conserved from Drosophila to human, PRICKLE1 and PRICKLE2 might be implicated in the localization of Frizzled and Dishevelled proteins, just like Drosophila prickle. This is the first report on identification and characterization of human PRICKLE1, PRICKLE2, mouse Prickle1, and Prickle2 genes.
Updating user profile using ontology-based semantic similarity

The endless amount of information on the web, known as “lost-in-hyper-space syndrome”, easily overwhelms users. User profiles are used as a means to support extracting relevant information by indicating user interests. In this paper, we propose a new method to develop and maintain a user profile by analyzing user's web access behavior. We propose an ontology-based semantic similarity measure and combine it with an importance measure to identify items that are of highest relevance to user interests. The proposed approach is used in a system for updating a user profile in music domain.
A New Transducer for Respiratory Monitoring: A Description of a Hot‐wire Anemometer and a Test Procedure for General Use

A respiratory transducer based on the constant temperature anemometry principle has been developed for respiratory monitoring, and as a tool for bedside evaluation of pulmonary function. The transducer is characterized by a dynamic range from 0–2.5 l/s and an upper limiting frequency of 50 Hz. It is designed with a view to a low pressure drop of 2.5 mbar/l/s and a minimum dead space of 5 ml. The transducer has been tested using a generally applicable procedure which includes both static and dynamic test set‐ups. The influence of variations in gas composition, temperature and pressure, together with variations in tidal volume and respiration rate, have been investigated. The results show that the transducer registers the immediate value of gas flow‐rate with a mean error less than 5–10% in all situations which are predictable in clinical use. The mean error can be reduced to less than 5% when systematic errors are eliminated.
Seeking the Patent Truth: Patents Can Provide Justice and Funding for Inventors

Theoretical arguments, and recent evidence, have led many to conclude that patents should be abolished. But patents have provided just rewards, the democratization of opportunity, incentives, and enabling resources for key inventions in the last 300 years, including machines and engines in the original industrial revolution in Britain, more broadly in the United States in the 1800s, and even today in industries such as pharmaceuticals. The current patent system can be improved through better funding of the patent office, and revised rules, which will result in fewer low quality patents that violate the criteria of being new, useful and non-obvious. Beyond such government policy reforms, entrepreneurial institutional innovations can transform an area of intellectual property from the dysfunctional to the vibrant, as illustrated by Steve Jobs’s creation of iTunes. With the right government policy reforms and entrepreneurial institutional innovations, patents can likewise be transformed to provide inventors justice and the funding to enable them to continue to invent new goods for consumers.
N‐terminal cleavage of Bax by calpain generates a potent proapoptotic 18‐kDa fragment that promotes Bcl‐2‐independent cytochrome C release and apoptotic cell death

Upon apoptosis induction, the proapoptotic protein Bax is translocated from the cytosol to mitochondria, where it promotes release of cytochrome c, a caspase‐activating protein. However, the molecular mechanisms by which Bax triggers cytochrome c release are unknown. Here we report that before the initiation of apoptotic execution by etoposide or staurosporin, an active calpain activity cleaves Bax at its N‐terminus, generating a potent proapoptotic 18‐kDa fragment (Bax/p18). Both the calpain‐mediated Bax cleavage activity and the Bax/p18 fragment were found in the mitochondrial membrane‐enriched fraction. Cleavage of Bax was followed by release of mitochondrial cytochrome c, activation of caspase‐3, cleavage of poly(ADP‐ribose) polymerase, and fragmentation of DNA. Unlike the full‐length Bax, Bax/p18 did not interact with the antiapoptotic Bcl‐2 protein in the mitochondrial fraction of drug‐treated cells. Pretreatment with a specific calpain inhibitor calpeptin inhibited etoposide‐induced calpain activation, Bax cleavage, cytochrome c release, and caspase‐3 activation. In contrast, transfection of a cloned Bax/p18 cDNA into multiple human cancer cell lines targeted Bax/p18 to mitochondria, which was accompanied by release of cytochrome c and induction of caspase‐3‐mediated apoptosis that was not blocked by overexpression of Bcl‐2 protein. Therefore, Bax/p18 has a cytochrome c–releasing activity that promotes cell death independent of Bcl‐2. Finally, Bcl‐2 overexpression inhibited etoposide‐induced calpain activation, Bax cleavage, cytochrome c release, and apoptosis. Our results suggest that the mitochondrial calpain plays an essential role in apoptotic commitment by cleaving Bax and generating the Bax/p18 fragment, which in turn mediates cytochrome c release and initiates the apoptotic execution. J. Cell. Biochem. 80:53–72, 2000. © 2000 Wiley‐Liss, Inc.
Reduced introgression of the Y chromosome between subspecies of the European rabbit (Oryctolagus cuniculus) in the Iberian Peninsula

The role of the Y chromosome in speciation is unclear. Hybrid zones provide natural arenas for studying speciation, as differential introgression of markers may reveal selection acting against incompatibilities. Two subspecies of the European rabbit (Oryctolagus cuniculus) form a hybrid zone in the Iberian Peninsula. Previous work on mitochondrial DNA (mtDNA), Y‐ and X‐linked loci revealed the existence of two divergent lineages in the rabbit genome and that these lineages are largely subspecies‐specific for mtDNA and two X‐linked loci. Here we investigated the geographic distribution of the two Y chromosome lineages by genotyping two diagnostic single nucleotide polymorphisms in a sample of 353 male rabbits representing both subspecies, and found that Y chromosome lineages are also largely subspecies‐specific. We then sequenced three autosomal loci and discovered considerable variation in levels of differentiation at these loci. Finally, we compared estimates of population differentiation between rabbit subspecies at 26 markers and found a surprising bimodal distribution of FST values. The vast majority of loci showed little or no differentiation between rabbit subspecies while a few loci, including the SRY gene, showed little or no introgression across the hybrid zone. Estimates of population differentiation for the Y chromosome were surprisingly high given that there is male‐biased dispersal in rabbits. Taken together, these data indicate that there is a clear dichotomy in the rabbit genome and that some loci remain highly differentiated despite extensive gene flow following secondary contact.