Miracle-dz/UniFAR-FTUs huggingface dataset:
Repair of craniotomy defects using bone marrow stromal cells.

BACKGROUND Techniques used to repair craniofacial skeletal defects parallel the accepted surgical therapies for bone loss elsewhere in the skeleton and include the use of autogenous bone and alloplastic materials. Transplantation of a bone marrow stromal cell population that contains osteogenic progenitor cells may be an additional modality for the generation of new bone. METHODS Full thickness osseous defects (5 mm) were prepared in the cranium of immunocompromised mice and were treated with gelatin sponges containing murine alloplastic bone marrow stromal cells derived from transgenic mice carrying a type I collagen-chloramphenicol acetyltransferase reporter gene to follow the fate of the transplanted cells. Control surgical sites were treated with spleen stromal cells or gelatin sponges alone, or were left untreated. The surgical defects were analyzed histologically for percent closure of the defect at 2, 3, 4, 6, and 12 weeks. RESULTS Cultured bone marrow stromal cells transplanted within gelatin sponges resulted in osteogenesis that repaired greater than 99.0+/-2.20% of the original surgical defect within 2 weeks. In contrast, cranial defects treated with splenic fibroblasts, vehicle alone, or sham-operated controls resulted in minimal repair that was limited to the surgical margins. Bone marrow stromal cells carrying the collagen transgene were immunodetected only in the newly formed bone and thus confirmed the donor origin of the transplanted cells. CONCLUSIONS These studies demonstrate that mitotically expanded bone marrow cells can serve as an abundant source of osteoprogenitor cells that are capable of repairing craniofacial skeletal defects in mice without the addition of growth or morphogenetic factors.
The normal surface of corneal epithelium: a scanning electron microscopic study.

The corneal epithelial surfaces of the rabbit, rat, cat, dog, and monkey are covered by myriads of fine microvilli. This study is in agreement with transmission electron reports showing only microvilli and no microplicae of surface corneal epithelium. Surface corneal epithelial cells have been characterized by scanning electron microscopy (SEM) as light, medium, and dark, depending on the density of secondary electrons. This SEM study shows that the dark-cell surface has twice as many microvilli per square micron than the light cell (dark cells 26 microvilli per square micron, light cells 13 microvilli per square micron) but the microvilli of the dark cell are less than one-half the length of light-cell microvilli (dark cell, 0.25 /xm; light cell, 0.6 fim). Random groups of dark cells were found to contain depressions and full-thickness holes varying from 1 to 10 n in diameter. The microvilli of the second-layer cell seen at the base of the hole had the appearance, length, and density consistent with a light cell. The findings are interpreted as the sequential development of a hole in an aging, dark-surface cell which expands in a controlled manner to expose its succeeding second-layer cell. This unique process of surface cellular destruction could impart considerable stability to the normal tear film.
Using Time Decompositions to Analyze PubMed Abstracts

Constructing time decompositions of time stamped documents is an important step for uncovering temporal relationships and trends of keywords and topics contained in the document set. This paper describes the use of time decompositions to extract temporal information from a small set of PubMed abstracts related to the Wnt signaling pathway. A time decomposition of the document set is constructed to identify temporal information such as keywords/topics significant in some time interval and to also identify temporal progression of the significant keywords. Keywords were assigned temporal significance values using two different measure functions based on notions of entropy and ratio. It is shown how optimal lossy decompositions of the document set are effective in reducing noise both in terms of the number of keywords as well as in terms of smoothing out the temporal progressions of keywords. Several optimal lossy decompositions for the document set are constructed and it is shown that the temporal information captured by an optimal lossy decomposition increases as its size (number of intervals) increases
AI TURNS FIFTY: REVISITING ITS ORIGINS

The expression “artificial intelligence” (AI) was introduced by John McCarthy, and the official birth of AI is unanimously considered to be the 1956 Dartmouth Conference. Thus, AI turned fifty in 2006. How did AI begin? Several differently motivated analyses have been proposed as to its origins. In this paper a brief look at those that might be considered steps towards Dartmouth is attempted, with the aim of showing how a number of research topics and controversies that marked the short history of AI were touched on, or fairly well stated, during the year immediately preceding Dartmouth. The framework within which those steps were taken was the development of digital computers. Earlier computer applications in areas such as complex decision making and management, at that time dealt with by operations research techniques, were important in this story. The time was ripe for AI's intriguingly tumultuous development, marked as it has been by hopes and defeats, successes and difficulties.
Integral variable structure current control of DFIG-based wind turbines near cut-in speed

Based on the grid voltage orientated vector control technique, a novel integral variable structure controller for current control of variable speed doubly fed induction generator (DFIG) wind turbines near cut-in wind speed is proposed. The proposed current controller can not only ensure generators' safe cut-in switches to the grid, but also maximum energy capture after switch motion without any regulations. By these, simulations of a 1.5 MW DFIG-based wind turbine near cut-in wind speed are separately conducted under integral variable structure control (IVSC) and PI control. The results show that IVSC strategy, which gives better dynamic response, less static error, smaller controller output dithering, stronger global robustness against generator parameters uncertainty and the grid voltage fluctuation, as well as needless controller regulation after cutting-in the grid, obviously preponderates over traditional PI control for DFIG-based wind turbines near cut-in speed.
Phase III study comparing methotrexate and tacrolimus (prograf, FK506) with methotrexate and cyclosporine for graft-versus-host disease prophylaxis after HLA-identical sibling bone marrow transplantation.

We report the results of a phase III open-label, randomized, multicenter trial comparing tacrolimus/methotrexate to cyclosporine/methotrexate for graft-versus-host disease (GVHD) prophylaxis after HLA-identical sibling marrow transplantation in patients with hematologic malignancy. The primary objective of this study was to compare the incidence of moderate to severe (grade II-IV) acute GVHD. Secondary objectives were to compare the relapse rate, disease-free survival, overall survival, and the incidence of chronic GVHD. Patients were stratified according to age (<40 v >/=40) and for male recipients of a marrow graft from an alloimmunized female. There was a significantly greater proportion of patients with advanced disease randomized to tacrolimus arm (P = . 02). The incidence of grade II-IV acute GVHD was significantly lower in patients who received tacrolimus than patients in the cyclosporine group (31.9% and 44.4%, respectively; P = .01). The incidence of grade III-IV acute GVHD was similar, 17.1% in cyclosporine group and 13.3% in the tacrolimus group. There was no difference in the incidence of chronic GVHD between the tacrolimus and the cyclosporine group (55.9% and 49.4%, respectively; P = .8). However, there was a significantly higher proportion of patients in the cyclosporine group who had clinical extensive chronic GVHD (P = . 03). The relapse rates of the two groups were similar. The patients in the cyclosporine arm had a significantly better 2-year disease-free survival and overall survival than patients in the tacrolimus arm, 50.4% versus 40.5% (P = .01) and 57.2% versus 46.9% (P = .02), respectively. The significant difference in the overall and disease-free survival was largely the result of the patients with advanced disease, 24.8% with tacrolimus versus 41.7% with cyclosporine (P = .006) and 20.4% with tacrolimus versus 28% with cyclosporine (P = .007), respectively. There was a higher frequency of deaths from regimen-related toxicity in patients with advanced disease who received tacrolimus. There was no difference in the disease-free and overall survival in patients with nonadvanced disease. These results show the superiority of tacrolimus/methotrexate over cyclosporine/methotrexate in the prevention of grade II-IV acute GVHD with no difference in disease-free or overall survival in patients with nonadvanced disease. The survival disadvantage in advanced disease patients receiving tacrolimus warrants further investigation.
Sacsinopathies: Sacsin-related ataxia

Autosomal recessive spastic ataxia of Charlevoix-Saguenay (ARSACS) was originally found among inhabitants of the Charlevoix-Saguenay region of northeastern Quebec in Canada. This disease is a neurodegenerative disorder characterized by early-onset spastic ataxia, dysarthria, nystagmus, distal muscle wasting, finger and foot deformities, and retinal hypermyelination. The principal neuropathology comprises atrophy of the upper vermis and the loss of Purkinje cells in the cerebellum. The SACS gene was originally reported to consist of a single gigantic exon spanning 12.8 kb with an 11.5-kb open reading frame (ORF), and to encode the protein sacsin. Recently, eight exons upstream from the original gigantic one, however, have been found, and the new ORF has elongated to 13.7 kb. To date, at least 28 mutations have been found in Quebec and non-Quebec patients including ones in Italy, Japan, Spain, Tunisia, and Turkey, and ARSACS thus shows a worldwide occurrence. Although most of the mutations reported have been in the gigantic exon, the genotype is now expanding upstream from this gigantic exon. Therefore, the new exons upstream of the gigantic one should be analyzed when a case is clinically compatible with ARSACS, even without any mutation in the gigantic exon. Although Quebec patients show a homogeneous phenotype, non-Quebec patients exhibit some atypical clinical features, as follows: slightly later onset than that in Quebec patients, absence of retinal hypermyelination, intellectual impairment, and lack of spasticity. Thus, since ARSACS shows the clinical diversity, the SACS gene should be analyzed not only in typical cases as Quebec patients but also in atypical cases as non-Quebec patients. As more SACS mutations are identified worldwide, the clinical spectrum of ‘sacsinopathies’ will expand, and a finer genotype-phenotype correlation study will become possible and shed light on the molecular mechanism underlying ARSACS.
Inhibition of Adenosine Kinase Attenuates Acute Lung Injury*

Objectives:Extracellular adenosine has tissue-protective potential in several conditions. Adenosine levels are regulated by a close interplay between nucleoside transporters and adenosine kinase. On the basis of the evidence of the role of adenosine kinase in regulating adenosine levels during hypoxia, we evaluated the effect of adenosine kinase on lung injury. Furthermore, we tested the influence of a pharmacologic approach to blocking adenosine kinase on the extent of lung injury. Design:Prospective experimental animal study. Setting:University-based research laboratory. Subjects:In vitro cell lines, wild-type and adenosine kinase+/– mice. Interventions:We tested the expression of adenosine kinase during inflammatory stimulation in vitro and in a model of lipopolysaccharide inhalation in vivo. Studies using the adenosine kinase promoter were performed in vitro. Wild-type and adenosine kinase+/– mice were subjected to lipopolysaccharide inhalation. Pharmacologic inhibition of adenosine kinase was performed in vitro, and its effect on adenosine uptake was evaluated. The pharmacologic inhibition was also performed in vivo, and the effect on lung injury was assessed. Measurements and Main Results:We observed the repression of adenosine kinase by proinflammatory cytokines and found a significant influence of nuclear factor kappa-light-chain-enhancer of activated B-cells on regulation of the adenosine kinase promoter. Mice with endogenous adenosine kinase repression (adenosine kinase+/–) showed reduced infiltration of leukocytes into the alveolar space, decreased total protein and myeloperoxidase levels, and lower cytokine levels in the alveolar lavage fluid. The inhibition of adenosine kinase by 5-iodotubercidin increased the extracellular adenosine levels in vitro, diminished the transmigration of neutrophils, and improved the epithelial barrier function. The inhibition of adenosine kinase in vivo showed protective properties, reducing the extent of pulmonary inflammation during lung injury. Conclusions:Taken together, these data show that adenosine kinase is a valuable target for reducing the inflammatory changes associated with lung injury and should be pursued as a therapeutic option.
A recurrent large Alu‐mediated deletion in the hypoxanthine phosphoribosyltransferase (HPRT1) gene associated with Lesch‐Nyhan syndrome

We identified the identical large genomic deletion in the hypoxanthine phosphoribosyltransferase (HPRT1) gene in two Japanese patients with Lesch‐Nyhan (LN) syndrome. This deletion spanned from an Alu sequence in the promoter region to another Alu‐sequence in intron 1, a length of 2,969 base pairs including exon 1. In order to ask whether this deletion was a recurrent mutation, we developed a simple alternative method to determine the separate origin of the HPRT1 mutation of the patients as assessed with an apparent mtDNA polymorphism. Considering that an LN syndrome‐causing mutation is not transmitted from patient to offspring as LN syndrome is a fatal disease in childhood and that mtDNA is maternally inherited, HPRT1 mutations and mtDNA would be co‐transmitted from carrier mother to offspring since both appeared in females. Two bases were different in the hypervariable region I of the mtDNA between the two patients, indicating the separate origin of their mtDNA over at least several thousand years as calculated based on the molecular evolution rate in this region. We thus conclude that the identical deletion found in HPRT1 of the two patients was derived from recurrent events of genomic recombination. Given that the same Alu‐mediated deletion of HPRT1 has not been reported among somatic mutations at the same locus, this region of the HPRT1 gene flanked by Alu‐sequences is likely a mutational hot spot in the germline but not in somatic cells. In addition, we also report novel LN‐syndrome‐conferring mutations in intron 6 (IVS6+1G → C) and intron 8 (IVS7‐9T → G) that resulted in exclusions of exon 6 and exon 8, respectively. Hum Mutat 18:435–443, 2001. © 2001 Wiley‐Liss, Inc.
Where, when, and in what form does sporadic Alzheimer's disease begin?

PURPOSE OF REVIEW Intraneuronal lesions consisting of abnormal tau protein are seen to develop from the beginning until the end-phase of the pathological process underlying Alzheimer's disease. This review highlights the earliest phase of this process. RECENT FINDINGS Development of abnormal tau frequently begins during childhood or puberty in nuclei of the lower brainstem sending diffuse projections to the cerebral cortex. Nonfibrillar abnormal tau material first occurs in the proximal axon of projection neurons in the locus coeruleus. Subsequently, a similar material (pretangle material) fills the somatodendritic compartment. In contrast with the pretangle material in cell bodies and dendrites, the nonfibrillar material in the axon normally does not convert into stable fibrillary inclusions. SUMMARY Projection neurons (not only those of the locus coeruleus) are sturdy and can survive for a lifetime despite the existence of Alzheimer-related abnormal tau. Currently, little understood mechanisms most probably exist that enable neurons to fulfill their general functions even when severe tau pathology is present. The proclivity of predisposed neuronal types to develop abnormal tau may be intrinsic to the human brain. However, the tempo of disease progression reveals considerable individual differences, thereby offering opportunities to study conditions that may modify disease progression.
Deep Learning Architectures for Novel Problems

With convolutional neural networks revolutionizing the computer vision field it is important to extend the capabilities of neural-based systems to dynamic and unrestricted data like graphs. Doing so not only expands the applications of such systems, but also provide more insight into improvements to neural-based systems. Currently most implementations of graph neural networks are based on vertex filtering on fixed adjacency matrices. Although important for a lot of applications, vertex filtering restricts the applications to vertex focused graphs and cannot be efficiently extended to edge focused graphs like social networks. Applications of current systems are mostly limited to images and document references. Beyond the graph applications, this work also explored the usage of convolutional neural networks for intelligent character recognition in a novel way. Most systems define Intelligent Character Recognition as either a recurrent classification problem or image classification. This achieves great performance in a limited environment but does not generalize well on real world applications. This work defines Intelligent Character Recognition as a segmentation problem which we show to provide many benefits. The goal of this work was to explore alternatives to current graph neural networks implementations as well as exploring new applications of such system. This work also focused on improving Intelligent Character Recognition techniques on isolated words using deep learning techniques. Due to the contrast between these to contributions this documents was divided into Part I focusing on the graph work, and Part II focusing on the intelligent character recognition work.
Acrosin activity in human spermatozoa in relation to semen quality and in-vitro fertilization.

Acrosin, a sperm proteinase released during acrosomal exocytosis, facilitates penetration through the oocyte vestments. The purpose of this investigation was to determine if a correlation exists between the acrosin activity of ejaculated human spermatozoa, before motility enrichment techniques, and in-vitro fertilization (IVF) success using selected (glass wool or swim-up) spermatozoa. Since all the oocytes were retrieved from women receiving exogenous hormonal stimulation and a mixed population of mature and immature oocytes were encountered, only cases with > or = 50% mature oocytes were analysed. Under these conditions, the acrosin activity was significantly greater (P < 0.01) in the ejaculates in which spermatozoa ultimately fertilized > or = 70% of the mature oocytes, than in the ejaculates in which spermatozoa ultimately fertilized < 70% of the mature oocytes. Furthermore, a strong correlation (r = 0.962, P = 0.0001) was detected between pre-IVF acrosin activity and subsequent high (> or = 70%) IVF success. Acrosin activity from normozoospermic and oligo-asthenozoospermic men was also compared and was significantly (P < 0.01) higher for the normozoospermic group. These data suggest that measurement of acrosin activity may be a valuable clinical laboratory assay for assessing the sperm fertilizing potential and that low acrosin activity is associated with abnormal semen characteristics.
Mechanisms of Gambogic Acid-Induced Apoptosis in Non-Small Cell Lung Cancer Cells in Relation to Transferrin Receptors

Abstract Gambogic acid (GA) is one of the important active ingredients of gamboge. Our study examined the expression of transferrin receptors (TFR) on the cell surface of human lung SPC-A1 and SK-MES-1 cells and measured their GA-induced apoptosis rate. The results showed that SPC-A1 cells with a higher TFR expression were more sensitive at the same GA concentrations. To examine its distribution in cultured cells and study the mechanisms of apoptosis, we labeled GA with a 125I tracer and examined the expression of apoptosis-related proteins. We found that GA uptake into SPC-A1 cells was higher than into SK-MES-1 cells; apoptosis-related proteins Caspase 2, Caspase 9, Caspase 10, Bax and p53 were involved in GA-induced apoptosis. We conclude that GA has an apoptosis-promoting effect on non small cell lung cancer cells. In clinical practice, the histopathological quantitation of TFR expression levels in tumor tissues may become a predictor of the sensitivity of patients' tumors to GA treatment.
The impact of reserve price on publisher revenue in real-time bidding advertising markets

With the rapid development of big data analytics in online marketing, real-time bidding (RTB) has emerged as a promising business model in recent years, and now becomes one of the major online advertising channels. Based on analysis of Web Cookies, RTB platforms are able to precisely identify the features and preferences of target audiences visiting publishers' websites, and forward the generated ad impressions to competing advertisers who submit bids for their best-matched audience in real-time ad auctions. In RTB markets, reserve price serves as an important tuner to exclude advertisers with low estimated values, and hence can guarantee a desirable result for the publisher from ad impression auctions. In this paper, we strive to study publishers' strategy on the reserve price, and probe the impact of reserve price on their revenues. We first analyze the ad impression auction under a direct auction mechanism. We then introduce the reserve price and study its impact on publishers' revenues under an indirect auction mechanism, and our research findings indicate that a rational positive reserve price will always improve publishers' revenues even if it is not optimal. Also, the optimal reserve price is figured out based on the advertisers' bid distributions for publishers' revenue maximization. Finally, experiments using empirical log data from real-world RTB markets are designed to validate our model and analysis, and the results provide strong support to our theoretical analysis. The experimental results also indicate that although the number of bids does not impose any influence on the optimal reserve price, it has significant impacts on publishers' revenues.