Miracle-dz/UniFAR-FTUs huggingface dataset:
Paired Helical Filaments from Alzheimer Disease Brain Induce Intracellular Accumulation of Tau Protein in Aggresomes*

Background: Misfolded aggregated tau protein released by degenerating neurons could spread toxicity to neighboring cells. Results: We found that cultured cells internalized paired helical filaments and developed intracellular tau aggregates with attributes of aggresomes. Conclusion: Paired helical filaments could mediate spreading of pathological tau aggregation. Significance: Paired helical filament-mediated formation of aggresome-like bodies may be an important step in neurodegeneration. Abnormal folding of tau protein leads to the generation of paired helical filaments (PHFs) and neurofibrillary tangles, a key neuropathological feature in Alzheimer disease and tauopathies. A specific anatomical pattern of pathological changes developing in the brain suggests that once tau pathology is initiated it propagates between neighboring neuronal cells, possibly spreading along the axonal network. We studied whether PHFs released from degenerating neurons could be taken up by surrounding cells and promote spreading of tau pathology. Neuronal and non-neuronal cells overexpressing green fluorescent protein-tagged tau (GFP-Tau) were treated with isolated fractions of human Alzheimer disease-derived PHFs for 24 h. We found that cells internalized PHFs through an endocytic mechanism and developed intracellular GFP-Tau aggregates with attributes of aggresomes. This was particularly evident by the perinuclear localization of aggregates and redistribution of the vimentin intermediate filament network and retrograde motor protein dynein. Furthermore, the content of Sarkosyl-insoluble tau, a measure of abnormal tau aggregation, increased 3-fold in PHF-treated cells. An exosome-related mechanism did not appear to be involved in the release of GFP-Tau from untreated cells. The evidence that cells can internalize PHFs, leading to formation of aggresome-like bodies, opens new therapeutic avenues to prevent propagation and spreading of tau pathology.
Repair Pathways for Processing of 8-Oxoguanine in DNA by Mammalian Cell Extracts*

The repair pathways involved in the removal of 8-oxo-7,8-dihydroguanine (8-oxoguanine) in DNA by mammalian cell extracts have been examined. Closed circular DNA constructs containing a single 8-oxoguanine at a defined site were used as substrates to determine the patch size generated after in vitro repair by mammalian cell extracts. Restriction analysis of the repair incorporation in the vicinity of the lesion indicated that up to 75% of the 8-oxoguanine was repaired via the single nucleotide replacement mechanism in both human and mouse cell extracts. Approximately 25% of the 8-oxoguanine lesions were repaired by the long patch repair pathway. Repair incorporation 5′ to the lesion, characteristic for nucleotide excision repair, was not significant. Elimination of the DNA polymerase β (polβ)-dependent single nucleotide base excision repair pathway in extracts prepared from polβ-deficient mouse cells resulted in extension of the repair gap to 4–5 nucleotides 3′ to the lesion in 50% of the repair events, suggesting the increased involvement of the long patch repair pathway. However, about one-half of the 8-oxoguanine repair was still accomplished through replacement of only one nucleotide in the polβ-deficient cell extracts. These data indicate the existence of an alternative polβ-independent single nucleotide repair patch pathway for processing of 8-oxoguanine in DNA.
The Economic Burden of Schizophrenia in Canada

Objective: To estimate the financial burden of schizophrenia in Canada in 1996. Method: Using a prevalence-based approach, all direct health care costs, administrative costs of income assistance plans, and costs of incarceration attributable to schizophrenia were determined. Also included was the value of lost productivity associated with premature mortality and morbidity. In addition to using published papers and documents, direct contact was made with representatives from various provincial and federal programs for estimates of the direct health care and non-health care costs. Results: The estimated number of persons with schizophrenia in Canada in 1996 was 221 000, with equal distribution between males and females. The direct health care and non-health care cost was estimated to be $1.12 billion in 1996. In addition, another $1.23 billion in lost productivity associated with morbidity and premature mortality was attributable to schizophrenia. Conclusions: The total financial burden of schizophrenia in Canada was estimated to be $2.35 billion in 1996. The largest category of cost was morbidity (52%), followed by acute care and psychiatric hospital admissions (14% and 10% respectively). Given the magnitude of these cost estimates, there are large potential cost savings with more effective management and control of this debilitating disease.
Droperidol Causes a Dose‐dependent Prolongation of the QT Interval

To further investigate possible prolongation of the frequency-corrected QT interval (QTc interval) after administration of droperidol (DRO), we studied 40 surgical patients who were randomly assigned to one of three groups, receiving an intravenous (IV) injection of either 0.1 mg/kg (Group 1, n = 10), 0.175 mg/kg (Group 2, n = 10), or 0.25 mg/kg (Group 3, n = 20) of DRO at induction of anesthesia. The QTc interval, heart rate, and arterial pressure were registered before and 1, 2, 3, 4, 5, 7.5, and 10 min after the respective dose injection. Significant prolongations of the median QTc interval were found in patients from all groups, ranging from 37 ms (8.0%) in Group 1, to 44 ms (10.6%) in Group 2, to 59 ms (14.9%) in Group 3, when compared with control. The heart rate showed a significant increase in all groups. Mean arterial pressure (MAP) was slightly but significantly decreased in Groups 1 and 3. Prolongation of the QTc interval is a predictable and dose-dependent side effect after injection of high-dose DRO.
Epidemiology of genital herpes simplex virus infection.

This paper offers a comprehensive review of the literature on the epidemiology of genital herpes simplex virus infection. Topics covered include its microbiology, immunology, incidence, prevalence, pathogenesis and clinical course, diagnosis, treatment, transmission, prevention, and effect on pregnancy outcome. The prevalence of genital herpes is estimated at 20 million persons in the US, about 25% of whom are symptomatic. Determination of the actual incidence and prevalence of genital herpes requires the availability of methods able to distinguish precisely between type 1 and type 2 antibody. Indirect evidence suggests an increasing incidence of the disease over the past 15 years. Asymptomatic infected persons may shed virus in the absence of lesions and thus transmit genital herpes to their sexual partners. Of particular concern is vertical transmission of virus from the maternal genital tract to newborns. In the majority of documented cases of neonatal herpes, the mothers were asymptomatic at the time of delivery. Because of the severe morbidity and mortality associated with neonatal herpes infection, studies are urgently needed to identify risk factors for vertical transmission and to design and test appropriate preventive intervention strategies. At present, treatment of genital herpes is limited to palliative therapy. No known antiviral agent either prevents or eliminates viral latency, although vaccines are under development for primary prevention. The role of contraceptive practice in the prevention of genital herpes infection is unclear. Although theoretically plausible, the efficacy of barrier methods in decreasing the risk of acquiring or transmitting infection has not yet been demonstrated. Virus may be present in areas not covered by condoms. Use of a spermicidal cream or jelly with a diaphragm may reduce the risk of virus infection and transmissions, but, again, this method cannot protect from virus transmission to or from the external genitalia.
The Correspondence Problem in the Optical Shape and Deformation Measurement Methods

How to correctly locate and uniquely index the same image point during the optical measurements is known as the correspondence problem. It occurs when there is a need for tracking features in all of the recorded images, regardless of the number of used cameras and the number of recorded images. In this paper, we have compared the correspondence problem solutions for the passive and active single, stereo and multi-camera systems, with a special focus to the active multi-camera system, for which we present the absolute method for unique stereo pair indexing. By using a modified projection approach, we have showed that it is possible to eliminate the need for the epipolar principle from the correspondence problem solving. With the new indexing method, each pixel can be used as a separate measuring point since it has been indexed with two independent absolute phases. Searching for stereo pairs has also been reduced from the two-dimensional image domain to a one-dimensional array, where the next stereo pair is most likely the nearest neighbor to the observed one.
Wood energy: the dangers of combustion.

We agree with the recent Policy Forum (“Wood energy in America,” D. deB. Richter Jr. et al. , 13 March, p. [1432][1]) that renewable, clean, and affordable energy sources are desirable; however, there may be detrimental health outcomes associated with widespread adoption of advanced wood
Leveraging on-chip DRAM stacking in an embedded 3D multi-core DSP system

Embedded multi-core systems are gaining popularity for many embedded applications. Compared to the multi-core design for general purpose high performance computing, the memory design for an embedded multi-core processor should be customized and adapt to embedded application's characteristics, because it usually has significant impact on the system performance. In this paper, we study a 3D embedded multi-core DSP processor called 3D-iSPA, which is targeted for multimedia applications with two unique design features and leverages 3D DRAM stacking to improve performance. Many memory controller and wider memory data bus are proposed to make better use of the vertical through-silicon-via (TSV). The experimental results shows that duplicating memory controller can provide 10X speedup. The pure wider memory bus, however, has weak impact on the performance due to the limitation of on-chip interconnect.1
A possible sequence of events for the generalized glacial‐interglacial cycle

There is not yet widespread agreement as to the underlying cause of the 80–100 ppmv roughly 100‐kyr‐duration glacial‐interglacial cycles in atmospheric pCO2. Most of the mechanisms which have been proposed to account for the observed pCO2 variations appear to in some way violate interpretations of paleo proxy data. The inability of a single mechanism to explain the observed cycles in atmospheric CO2 (which show amazing similarity over the past 430,000 years) is perplexing, and leads us to consider whether a combination of mechanisms might be consistent with available evidence. Consistent with previous work, we find that physical changes (ocean circulation, temperature, mixing) can only explain part of the observed atmospheric pCO2 variability; changes in ocean chemistry are invoked to explain the remainder. In order to account for the initial pCO2 drawdown (from “interglacial” to “intermediate” levels), we invoke physical changes in the ocean (mixing, temperature). The transition from intermediate atmospheric pCO2 levels to full glacial conditions involves a small increase in mean ocean nutrient levels and mean ocean alkalinity, accomplished by falling sea level and subsequent erosion of organic‐rich shelf sediments. The first part of the transition out of full glacial conditions is achieved through increased temperature and increased mixing in the Southern Ocean. The final part of the atmospheric pCO2 rise up to full interglacial conditions is accomplished through rising sea level and the subsequent change in mean ocean alkalinity and phosphate, and a rise in the Northern Hemisphere temperature and ocean mixing. The proposed sequence of events is consistent with most existing proxy evidence for paleo‐nutrient levels and changes in export production over the last glacial‐interglacial cycle. Furthermore, it is consistent with evidence for a whole‐ocean shift in δ13C toward significantly more negative values in the late glacial. The proposed scenario is also consistent with ice core‐based timing constraints, as summarized by Broecker and Henderson (1998). We show that we are able to explain the full magnitude of the glacial‐interglacial cycle in atmospheric pCO2 without the need to invoke iron‐fertilization in the Southern Ocean.
A Joint Scheduling and Content Caching Scheme for Energy Harvesting Access Points with Multicast

In this work, we investigate a system where users are served by an access point that is equipped with energy harvesting and caching mechanism. Focusing on the design of an efficient content delivery scheduling, we propose a joint scheduling and caching scheme. The scheduling problem is formulated as a Markov decision process and solved by an on-line learning algorithm. To deal with large state space, we apply the linear approximation method to the state-action value functions, which significantly reduces the memory space for storing the function values. In addition, the preference learning is incorporated to speed up the convergence when dealing with the requests from users that have obvious content preferences. Simulation results confirm that the proposed scheme outperforms the baseline scheme in terms of convergence and system throughput, especially when the personal preference is concentrated to one or two contents.
Catalytic antibodies.

The synthesis of catalysts with tailored specificities and catalytic properties is a challenging problem to chemists and biologists alike. A key element in the design of enzyme-like catalysts is the rational generation of receptors capable of discriminating ligands with high selectivity. Most efforts in this regard have focused on either the synthesis and functionalization of relatively small cavity-containing hosts or on the alteration of the natural specificity of enzymes by chemical modification, oligonucleotide-directed mutagenesis, or genetic selections or screens. Although these approaches hold great promise, only a limited number of successes have been realized to date. Hybridoma technology (1) permits the exploitation of the tremendous diversity 008-1010 different specificities) of the humoral immune system to generate monoclonal antibodies specific for virtually any biopolymer, natural product or synthetic molecule of interest. Consequently, the development of strategies for introducing catalytic activity into antibody combining sites should lead to a new class of enzyme-like catalysts with tailored specificities. Recently, principles of enzymic catalysis have been applied to the generation of antibodies that catalyze a wide variety of chemical reactions including ester and amide bond hydrolysis, concerted Claisen rearrangements, elimination reactions, photochemical thymine dimer cleavage, redox reactions, lactonization reactions, and bimolecular amide bond formation. In every example the high specificity of antigen recognition is reflected in high substrate selectivity. The development of catalytic antibodies of defined specificity promises to be of considerable value to biology, chemistry, and medicine. Catalytic
The Impact of Decision Agency & Granularity on Aptitude Treatment Interaction in Tutoring

In this study, we explored the impact of the decision agency (Student vs. Tutor) and granularity (Problem vs. Step) across students with different levels of incoming competence (High vs. Low). Students were randomly assigned to four conditions and split into High and Low groups based on their pre-test scores. All students used the same Intelligent Tutoring System (ITS) called Pyrenees, followed the same general procedure, studied the same training materials, and worked through the same training problems. The only substantive differences among the four conditions were decision agency and granularity. That is: who decided to present an example or to solve a problem: the student or the ITS tutor; and was the decision made problem-by-problem or step-by-step? Our overall results showed that there were significant different impacts of the decision agency and granularity between High and Low students on learning performance. More specifically, for High students granularity was the more dominant factor in that step level decisions can be more effective than problem level decisions regardless of the decision agency; for Low students there was a significant interaction effect in that: Low students benefit significantly more when they were making problem-level decisions than making step-level decisions, but no significant difference was not found when the decisions were made by the tutor. Much to our surprise, both High and Low groups showed strong decision-making preference for problem solving over worked example at both problem and step levels.
Polarization insensitive waveguide grating routers in InP

We demonstrate a 16-channel waveguide grating router (WGR) in the InP-based material system. The channel spacing of the WGRs is 100 GHz and the maximum interchannel crosstalk is -28 dB. The polarization related (TE-TM modal) wavelength shift is approximately 0.08 nm and the polarization dependent variation in peak signal is less than 0.2 dB. 2.60-/spl mu/m-wide /spl times/1.90-/spl mu/m-thick raised-stripe InGaAsP Quaternary (/spl lambda//sub g/=1.17 /spl mu/m) waveguides on an n-type InP substrate make up the basis paths of the WGR. In this letter, we describe the design, fabrication and the results of measurement of the 16-channel polarization-insensitive WGR.
Testosterone selectively increases serum follicle-stimulating hormonal (FSH) but not luteinizing hormone (LH) in gonadotropin-releasing hormone antagonist-treated male rats: evidence for differential regulation of LH and FSH secretion.

Both testosterone (T) and gonadotropin-releasing hormone (GnRH)-antagonist (GnRH-A) when given alone lower serum luteinizing hormone (LH) and follicle-stimulating hormone (FSH) in intact and castrated rats. However, when graded doses of testosterone enanthate (T.E.) were given to GnRH-A-treated intact male rats, a paradoxical dose-dependent increase in serum FSH occurred; whereas serum LH remained suppressed. This surprising finding led us to ask whether the paradoxical increase in serum FSH in GnRH-A-suppressed animals was a direct stimulatory effect of T on the hypothalamic-pituitary axis or the result of a T effect on a testicular regulator of FSH. To test these hypotheses, we treated adult male castrated rats with GnRH-A and graded doses of T.E. In both intact and castrated rats, serum LH remained undetectable in GnRH-A-treated rats with or without T.E. However, addition of T.E. to GnRH-A led to a dose-dependent increase in serum FSH in castrated animals as well, thus pointing against mediation by a selective testicular regulator of FSH. These data provide evidence that pituitary LH and FSH responses may be differentially regulated under certain conditions. When the action of GnRH is blocked (such as in GnRH-A-treated animals), T directly and selectively increases pituitary FSH secretion.
COMPARISON OF ELECTRON TRANSPORT SYSTEMS IN VEGETATIVE CELLS AND SPORES OF BACILLUS CEREUS

There have been several reports that spores of bacilli differ from their vegetative cells in cytochrome content (Keilin and Hartree, 1949) and cyanide sensitivity (Spencer and Powell, 1952; Nakada et al., 1957; Hachisuka et al., 1956). High levels of diaphorase, DPNH2 cytochrome c reductase, and flavoproteins have been reported in spores (Spencer and Powell, 1952; Halvorson, Doi, and Church, 1958). Since vegetative cells of Bacillus possess a typical cytochrome pattern (Smith, 1954), it was suggested that spores contained an alternate path of electron transport, perhaps through flavoproteins which were replaced by a functional cytochrome system during outgrowth. To compare the respiratory pathways of spores and cells, a direct analysis of the extracts was undertaken. The results demonstrated that although vegetative cell respiration proceeds through a particulate cytochrome system, spore electron transport occurs primarily through a soluble flavoprotein oxidase and secondarily through an atypical particulate enzyme fraction.
Supervised learning-based cell image segmentation for P53 immunohistochemistry

In this paper, we present two new algorithms for cell image segmentation. First, we demonstrate that pixel classification-based color image segmentation in color space is equivalent to performing segmentation on grayscale image through thresholding. Based on this result, we develop a supervised learning-based two-step procedure for color cell image segmentation, where color image is first mapped to grayscale via a transform learned through supervised learning, thresholding is then performed on the grayscale image to segment objects out of background. Experimental results show that the supervised learning-based two-step procedure achieved a boundary disagreement (mean absolute distance) of 0.85 while the disagreement produced by the pixel classification-based color image segmentation method is 3.59. Second, we develop a new marker detection algorithm for watershed-based separation of overlapping or touching cells. The merit of the new algorithm is that it employs both photometric and shape information and combines the two naturally in the framework of pattern classification to provide more reliable markers. Extensive experiments show that the new marker detection algorithm achieved 0.4% and 0.2% over-segmentation and under-segmentation, respectively, while reconstruction-based method produced 4.4% and 1.1% over-segmentation and under-segmentation, respectively.
Multivessel Off‐Pump Coronary Bypass with the Octopus Experience in 226 Patients

Coronary artery bypass graft (CABG) surgery has traditionally required cardiopulmonary bypass (CPB) and global cardioplegic arrest. Surgeons have had still and bloodless fields in which to perform accurate microvascular anastamoses. Morbidity and mortality rates have continuously declined despite worsening patient demographics. Concern for the unwanted sequelae of CPB in this higher-risk patient population has prompted surgeons to re-explore the feasibility of "offpump" CABG (OPCAB). Several groups reported successful series of OPCAB in the 1980s but interest was not ~ idespread. ' -~ In the mid-l990s, single bypass of the left anterior descending artery (LAD) through small anterior thoracotomy incisions began to gain in pop~larity. ~,5 With the advent of mechanical stabilization of target coronary arteries, the reported patency rates for beating heart CABG approached or equaled those obtained with CPB-supported CABG.6 In 1996, Borst et al. reported the development of a novel suction-based stabilizer (Medtronic Octopus) and described its use in 100 patient^. ^-^ Their animal studies explored the hemodynamic consequences of vertical cardiac displacement, which is necessary for posterior and lateral vessel grafting.l0,l Several other surgeons developed techniques to allow complete revascularization of the beating heart with reliably good hemodynam-