gebhart/patrepeval huggingface dataset:
Neurotoxicity of local anesthetics: altered perineurial permeability, edema, and nerve fiber injury. (1986)

A quantitative, in situ experimental method was developed employing the rat sciatic nerve to study the neurotoxicity of local anesthetic solutions applied directly to an intact peripheral nerve bundle. One-milliliter volumes of 2-chloroprocaine, 3%; tetracaine, 1%; lidocaine, 2%; bupivacaine, 0.75%; or sodium chloride, 0.2%; were injected with a 30-gauge needle beneath the mesoneurium but exterior to the epineurium. The wound was closed and the animals were normally maintained until the nerves were reexposed for quantitative biophysical and morphologic testing 24 h to 4 weeks later. The results indicate that topically applied 2-chloroprocaine and tetracaine produce significant endoneurial edema 48 h after treatment. Horseradish peroxidase was used to verify increased permeability of the perineurium. Endoneurial fluid pressure was significantly increased in edematous nerves. Electron microscopy revealed abnormal mast cells and proliferation of endoneurial fibroblasts in addition to Schwann cell injury and axonal dystrophy. This study shows that extrafascicular administration of clinically used concentrations of local anesthetic solutions can alter perineurial permeability, producing changes in the endoneurial environment that are associated with neurotoxic injury. Perineurial and endoneurial fibrotic changes may be a late consequence of peripheral nerve injury with anesthetic solutions producing altered perineurial permeability with endoneurial edema.
Systematic sequencing of cDNA clones using the transposon Tn5 (2002)

In parallel with the production of genomic sequence data, attention is being focused on the generation of comprehensive cDNA-sequence resources. Such efforts are increasingly emphasizing the production of high-accuracy sequence corresponding to the entire insert of cDNA clones, especially those presumed to reflect the full-length mRNA. The complete sequencing of cDNA clones on a large scale presents unique challenges because of the generally small, yet heterogeneous, sizes of the cloned inserts. We have developed a strategy for high-throughput sequencing of cDNA clones using the transposon Tn5. This approach has been tailored for implementation within an existing large-scale 'shotgun-style' sequencing program, although it could be readily adapted for use in virtually any sequencing environment. In addition, we have developed a modified version of our strategy that can be applied to cDNA clones with large cloning vectors, thereby overcoming a potential limitation of transposon-based approaches. Here we describe the details of our cDNA-sequencing pipeline, including a summary of the experience in sequencing more than 4200 cDNA clones to produce more than 8 million base pairs of high-accuracy cDNA sequence. These data provide both convincing evidence that the insertion of Tn5 into cDNA clones is sufficiently random for its effective use in large-scale cDNA sequencing as well as interesting insight about the sequence context preferred for insertion by Tn5.
Relationship between DCT-II, DCT-VI, and DST-VII transforms (2013)

Discrete Sine Transforms of type VII (DST-VII) have recently received considerable interest in video coding. In this paper, we show that there exists a direct connection between DST-VII and DCT-II transforms, allowing their joint computation for certain transform sizes. This connection also yields fast algorithms for constructing DCT-VI and DCT-VII.
Molecular Genetics of Alzheimer's Disease and the Amyloid β Peptide Precursor Gene (1989)

Alzheimer's disease is a neurodegenerative disorder characterized by global cognitive decline. An autopsy of the Alzheimer patient's brain reveals two major neuropathological lesions: neurofibrillary tangles, and amyloid deposits in the form of senile plaques and cerebrovascular accumulations. While tangles appear to be a universal hallmark of dying neurons in several neurodegenerative diseases, amyloid plaques occur in only three conditions including Alzheimer's disease, Down syndrome, and to a limited extent, normal aging. The frequency of senile plaques appears to correlate well with the degree of dementia in the Alzheimer's patient. It remains unclear, however, whether amyloid formation represents one of the final stages of a long neuropathological process in the brain, or initially participates in promoting neuronal dysfunction. To address this question, we have isolated the gene encoding the precursor of the principle component of the plaque, the amyloid beta peptide. We have mapped this gene to chromosome 21, the same chromosome in which we have detected linkage between anonymous DNA markers and the familial form of Alzheimer's disease. Employing direct genetic linkage analysis, we have shown that the amyloid gene and the familial Alzheimer's disease gene represent two separate and distinct genetic loci. Here we present further information on the location of the familial Alzheimer's disease gene on chromosome 21. We also discuss the recent discovery of an alternate form of the amyloid beta peptide precursor gene which encodes a serine protease inhibitor in the Kunitz family. The presence of a protease inhibitor domain within the amyloid beta peptide precursor, itself, has profound implications for its possible role in the process of amyloid formation.(ABSTRACT TRUNCATED AT 250 WORDS)
체육수업에서 탐구중심모형의 적용 연구 (1999)

본 연구의 목적은 하나의 대안적인 중학교 체육수업방법으로 `탐구중심 수업모형`을 적용하고 설계하는 데 있다. 이러한 연구목적을 달성하기 위하여 연구자 자신이 1999년 4월 초순부터 6월말까지 중학교 2학년 농구 단원수업을 실행하면서 7개 학급 115명을 대상으로 연구를 수행하였다. 연구목적을 달성하기 위해 연구절차는 현장개선연구방법을 사용하였고, 질적연구 방법으로 자료를 분석하였다. 자료는 학생의 수업소감문, 육성녹음, 비디오촬영, 교사의 수업반성일지, 심층면담의 방법을 이용하여 수집하였고, 수집된 자료는 사례기록과 귀납적 범주분석 방법을 이용하였다. 자료의 진실성을 높이기 위하여 구성원간 검토, 동료간 협의, 다각도 분석법 등을 이용하였다.
체육과 `탐구중심 수업모형`은 도입-전개-정리의 단계로 실시하게 되며, 특히 전개단계에서는 탐구중심으로 이루어진 수업 절차인 `과제제시 및 과제파악-예상하기-운동수행-움직임 이해-적용 및 응용`의 순서로 진행된다. 선정한 과제를 제시하여 학생들과 함께 과 과제가 무엇인지, 왜 필요한 지를 파악하는 단계인 `과제제시 및 과제파악`단계, 그 과제를 해결 또는 이해하거나 체득하기에 가장 좋은 방안을 모색하고 탐색하는 과정으로서의 `예상하기`단계, 그리고 체육수업의 핵심적인 과정으로 학생들이 직접 신체활동에 참여하는 신체 움직임의 `체험` 또는 `체득과정`으로써 `운동수행단계`로 진행된다. 네 번째 단계는 `움직임 이해`단계로서, 학생들이 운동수행과정에서 스스로 깨닫고 체득한 `움직임의 원리를 이해하는 단계`이며, 마지막으로 어떤 운동상황에 놓였을 때 그 상황을 이해하고, 그 상황에 알맞게 자신이나 타인이 만들어내는 움직임 즉, 운동치 의미를 파악하는 일이면서 동시에 이를 능숙하지는 않지만 자신의 몸으로 실천하는 과정으로서의 `적용 및 응용`단계로 이루어진다.
FDA Drug Approval Summary: Alemtuzumab as Single-Agent Treatment for B-Cell Chronic Lymphocytic Leukemia (2008)

On September 19, 2007, the U.S. Food and Drug Administration granted regular approval and expanded labeling for alemtuzumab (Campath); Genzyme Corporation, Cambridge, MA) as single-agent treatment for B-cell chronic lymphocytic leukemia (B-CLL). Alemtuzumab was initially approved in 2001 under accelerated approval regulations. Conversion to regular approval was based on a single study submitted to verify clinical benefit. Efficacy and safety were demonstrated in an open-label, international, multicenter, randomized trial of 297 patients with previously untreated, Rai stage I-IV B-CLL experiencing progression of their disease. Patients were randomized to either alemtuzumab, 30 mg i.v. over 2 hours three times per week on alternate days for a maximum of 12 weeks, or chlorambucil, 40 mg/m(2) orally every 28 days for a maximum of 12 months. The progression-free survival time, the primary study endpoint, was significantly longer in the alemtuzumab arm than in the chlorambucil arm. Both the overall and complete response rates were also significantly higher in the alemtuzumab arm. No differences in survival were observed. There were no new safety signals identified in patients receiving alemtuzumab. The most serious, and sometimes fatal, toxicities of alemtuzumab are cytopenias, infusion reactions, and infections.
Chemoresistance in pancreatic cancer: Emerging concepts (2017)

Pancreatic cancer is one of the most lethal types of cancer in the world. The incidence of pancreatic cancer increases each year with no significant decrease in mortality. Pancreatic cancer is a complex disease, and this complexity is partly attributed to late diagnosis, an aggressive phenotype, environmental factors and lack of effective treatment options. Surgical resection followed by adjuvant chemotherapy is the treatment of choice for early stage cancer, whereas gemcitabine is the standard first line therapy for patients with advanced stage disease. Treatment regimens comprising folinic acid, 5-fluorouracil, irinotecan, oxaliplatin and nab-paclitaxel have demonstrated modest effects in improving median survival rates. A number of other chemotherapeutics are currently undergoing clinical trials as components of combination therapies with gemcitabine. An increasing number of novel molecular targets and cellular pathways are being identified, which highlights the complexity of this disease. The development of chemoresistance to gemcitabine is multifactorial and there exists an interplay between pancreatic cancer cells, the tumor microenvironment and cancer stem cells. These components appear to be governed by a complex network of non-coding RNAs such as micro RNAs and long non-coding RNAs. In the present study, studies describing previous research on the understanding of the factors associated with the development of chemoresistance to gemcitabine in pancreatic cancer are reviewed. A comprehensive understanding of the multiple pathways of chemoresistance is key to develop next generation therapeutics to pancreatic cancer.
High incidence of loss of heterozygosity and abnormal imprinting of H19 and IGF2 genes in invasive cervical carcinomas. Uncoupling of H19 and IGF2 expression and biallelic hypomethylation of H19. (1996)

The few imprinted genes characterized so far include the insulin-like growth factor-2 gene (IGF2) coding for a foetal growth factor and the H19 gene whose normal function is unknown but which is likely to act as an RNA with an antitumour effect. IGF2 is expressed by the paternal allele and H19 by the maternal allele. This reciprocal expression is quite interesting because both H19 and IGF2 genes are located close to each other on chromosome 11p15.5 in a region subject to loss of heterozygosity (LOH). Moreover, loss of imprinting (LOI) or biallelic expression has been proposed as an epigenetic mechanism for tumorigenesis in a variety of human cancers including Wilms' tumour. In this study we report the LOH, LOI and methylation status of H19 and IGF2 genes in 29 invasive cervical carcinomas of different clinical stages. Fourteen (48%) and 13 (45%) tumours were heterozygous for H19 and IGF2 respectively. LOH for H19 and IGF2 genes were found in 2 of 14 (14%) and 3 of 13 (23%) informative tumours, respectively. LOI of H19 and IGF2 was detected in 2 of 12 (17%) and 5 of 10 (50%) tumours with no LOH, respectively. More interestingly, monoallelic expression of the otherwise silent H19 allele (allele switch) was observed in 2 of 12 (17%) tumours and biallelic expression of IGF2 was detected in one specimen of normal cervix adjacent to the tumour. The expressing H19 allele, and to a lower degree also the silent allele, were hypomethylated in tumours suggesting that demethylation of both H19 alleles may be associated with an early step of imprinting alteration. In cervical cancer H19 and IGF2 expressions could be independently regulated. In conclusion, our data suggest that H19 and IGF2 genes, via deletions and/or abnormal imprinting, could play a crucial role in a large proportion (58%) of cervical cancers where they may be associated with disease progression.
A MicroRNA Signature Associated with Prognosis and Progression in Chronic Lymphocytic Leukemia (2005)

A unique microRNA signature is associated with prognostic factors and disease progression in CLL. Mutations in microRNA transcripts are common and may have functional importance.
Role of IKKγ/NEMO in Assembly of the IκB Kinase Complex (2001)

IKKgamma/NEMO is a protein that is critical for the assembly of the high molecular weight IkappaB kinase (IKK) complex. To investigate the role of IKKgamma/NEMO in the assembly of the IKK complex, we conducted a series of experiments in which the chromatographic distribution of extracts prepared from cells transiently expressing epitope-tagged IKKgamma/NEMO and the IKKs were examined. When expressed alone following transfection, IKKalpha and IKKbeta were present in low molecular weight complexes migrating between 200 and 400 kDa. However, when coexpressed with IKKgamma/NEMO, both IKKalpha and IKKbeta migrated at approximately 600 kDa which was similar to the previously described IKK complex that is activated by cytokines such as tumor necrosis factor-alpha. When either IKKalpha or IKKbeta was expressed alone with IKKgamma/NEMO, IKKbeta but not IKKalpha migrated in the higher molecular weight IKK complex. Constitutively active or inactive forms of IKKbeta were both incorporated into the high molecular weight IKK complex in the presence of IKKgamma/NEMO. The amino-terminal region of IKKgamma/NEMO, which interacts directly with IKKbeta, was required for formation of the high molecular weight IKK complex and for stimulation of IKKbeta kinase activity. These results suggest that recruitment of the IKKs into a high molecular complex by IKKgamma/NEMO is a crucial step involved in IKK function.
A Novel Design for a Memristor-Based <sc>or</sc> Gate (2015)

This brief proposes a logic gate that performs a stateful or logic operation on memristor memory. The presented logic structure concurrently executes an or operation in the nanocrossbar architecture in a single step, which enables a fast logic operation and reduces the number of required memristors. The proposed circuit completes the in situ logic operation on the memristor memory, which alleviates the burden of the processor significantly. Through analysis and simulation, the feasibility of the or operation is demonstrated, and the parameter optimization is analyzed.
Characterization of low-temperature processed single-crystalline silicon thin-film transistor on glass (2003)

Single-crystalline silicon thin film on glass (cSOG) has been prepared using an "ion-cutting" based "layer-transfer" technique. Low-temperature processed thin-film transistors, fabricated both on cSOG and metal-induced laterally crystallized polycrystalline silicon, have been characterized and compared. The cSOG-based transistors performed comparatively better, exhibiting a significantly higher electron field-effect mobility (/spl sim/430 cm/sup 2//Vs), a steeper subthreshold slope and a lower leakage current that was also relatively insensitive to gate bias.
Capillary pericytes: Perspectives and future trends (1991)

A complete understanding of the microcirculation requires full knowledge of the structure and function of each of the constituent cells, including pericytes. Vascular endothelium and smooth muscle cells have been investigated intensively during the last two decades, but much less is known about the metabolism and function of capillary pericytes. However, the development of new electron microscopy techniques and the application of new cell culture and molecular biology techniques should allow for the rapid elucidation of the cellular biochemistry and the microvascular function and pathology of this ubiquitous capillary cell.
Arithmetic coding for data compression (1987)

The state of the art in data compression is arithmetic coding, not the better-known Huffman method. Arithmetic coding gives greater compression, is faster for adaptive models, and clearly separates the model from the channel encoding.
Direct Conversion of Mouse Fibroblasts to Hepatocyte–Like Cells Using Forced Expression of Endodermal Transcription Factors (2011)

The generation of functional hepatocytes independent of donor liver organs is of great therapeutic interest with regard to regenerative medicine and possible cures for liver disease. Induced hepatic differentiation has been achieved previously using embryonic stem cells or induced pluripotent stem cells. Particularly, hepatocytes generated from a patient's own induced pluripotent stem cells could theoretically avoid immunological rejection. However, the induction of hepatocytes from induced pluripotent stem cells is a complicated process that would probably be replaced with the arrival of improved technology. Overexpression of lineage-specific transcription factors directly converts terminally differentiated cells into some other lineages, including neurons, cardiomyocytes and blood progenitors; however, it remains unclear whether these lineage-converted cells could repair damaged tissues in vivo. Here we demonstrate the direct induction of functional hepatocyte-like (iHep) cells from mouse tail-tip fibroblasts by transduction of Gata4, Hnf1a and Foxa3, and inactivation of p19Arf. iHep cells show typical epithelial morphology, express hepatic genes and acquire hepatocyte functions. Notably, transplanted iHep cells repopulate the livers of fumarylacetoacetate-hydrolase-deficient (Fah -/-) mice and rescue almost half of recipients from death by restoring liver functions. Our study provides a novel strategy to generate functional hepatocyte-like cells for the purpose of liver engineering and regenerative medicine.
Chemokines in Inflammatory Bowel Disease Mucosa: Expression of RANTES, Macrophage Inflammatory Protein (MIP)-1α, MIP-1β, and γ-Interferon-Inducible Protein-10 by Macrophages, Lymphocytes, Endothelial Cells, and Granulomas (1996)

Peripheral blood monocytes are attracted from the circulation to sites of active inflammatory bowel disease. This study sought to determine the role of monocyte-attracting chemokines in inflammatory bowel disease by examining the contribution of the α chemokine interferon-inducible protein-10, and the β chemokines, macrophage inflammatory proteins-1α and -1β and RANTES (Regulated on Activation, Normal T Expressed and Secreted) by using in situ hybridization and immunohistochemistry. Resected colonic tissue was obtained from five patients with ulcerative colitis, nine patients with Crohn's disease, and six with uninflamed mucosa remote from resected colon cancers. In situ hybridization by using riboprobes demonstrated that all four chemokines were expressed by macrophages, T lymphocytes, and endothelial cells in actively inflamed tissue but rarely expressed in uninflamed sections from inflammatory bowel disease or cancer-bearing colons. The frequency of chemokine-expressing cells was significantly greater in severely inflamed than in moderately or mildly inflamed tissue. RANTES was expressed by T lymphocytes in normal colon lamina propria, although infrequently. Granulomas were present in four Crohn's disease resections, and each of the chemokines was expressed by T cells and macrophages in loosely formed granulomas. Immunohistochemistry for macrophage inflammatory protein-1α confirmed the in situ hybridization findings: protein was associated with macrophages, T lymphocytes, and endothelial cells in actively inflamed colon. This study implicated a range of chemokines known to attract monocytes and subsets of T lymphocytes in the pathogenesis of inflammatory bowel disease and suggested significant redundancy in the generation of chemotactic signals in chronic inflammation.
Genetic content of wild-type human cytomegalovirus (2004)

The genetic content of wild-type human cytomegalovirus was investigated by sequencing the 235 645 bp genome of a low passage strain (Merlin). Substantial regions of the genome (genes RL1-UL11, UL105-UL112 and UL120-UL150) were also sequenced in several other strains, including two that had not been passaged in cell culture. Comparative analyses, which employed the published genome sequence of a high passage strain (AD169), indicated that Merlin accurately reflects the wild-type complement of 165 genes, containing no obvious mutations other than a single nucleotide substitution that truncates gene UL128. A sizeable subset of genes exhibits unusually high variation between strains, and comprises many, but not all, of those that encode proteins known or predicted to be secreted or membrane-associated. In contrast to unpassaged strains, all of the passaged strains analysed have visibly disabling mutations in one or both of two groups of genes that may influence cell tropism. One comprises UL128, UL130 and UL131A, which putatively encode secreted proteins, and the other contains RL5A, RL13 and UL9, which are members of the RL11 glycoprotein gene family. The case in support of a lack of protein-coding potential in the region between UL105 and UL111A was also strengthened.
Tumor necrosis factor alpha (TNF-alpha) gene therapy targeted by ionizing radiation selectively damages tumor vasculature. (1996)

Intratumoral injection of an adenoviral vector containing radiation-inducible DNA sequences of the Egr-1 promoter linked to a cDNA encoding tumor necrosis factor (TNF) alpha (Ad.Egr-TNF) enhances the tumoricidal action of ionizing radiation in a human epidermoid carcinoma xenograft (SQ-20B). The dominant histopathological feature in tumor-bearing animals treated with Ad.Egr-TNF and irradiation is extensive intratumoral vascular thrombosis and tumor necrosis. Thrombosis and necrosis are not observed in animals treated with either the viral construct encoding TNF-alpha or radiation and did not occur in irradiated normal tissues adjacent to tumor in animals injected with Ad.Egr-TNF. To determine if the occlusive effects of Ad.Egr-TNF and X-irradiation were specific for tumor vessels, non-tumor-bearing mice were irradiated after receiving i.m. injection of Ad.Egr-TNF at viral titers 20-100 times greater than titers injected intratumorally. No vascular thrombosis was observed in the treated normal tissues. Combined Ad.Egr-TNF and radiation produced occlusion of tumor microvessels without significant normal tissue damage. Taken together, these data suggest that the interaction between radiation inducible TNF-alpha and X-irradiation occurs selectively within the tumor vessels.
[Stem cell and self-renewal]. (2001)

Stem cells are defined as cells with the ability for self-renewal and differentiation. Hematopoietic stem cells are well known, and their application is useful for the treatment of various kinds of diseases. Recently, neural stem cells have been identified even in the adult brain, which has up to now been considered to be a tissue with no regenerative capacity. In addition, it has emerged that tissue stem cells can differentiate into various kinds of cells beyond their original characteristics. Here, we discuss the self-renewal mechanisms of embryonic stem (ES) cells, hematopoietic stem cells and neural stem cells.
Structure and biological activity of v-raf, a unique oncogene transduced by a retrovirus. (1983)

We have molecularly cloned a unique acutely transforming replication-defective mouse type C virus (3611-MSV) and characterized its acquired oncogene. The viral genome closely resembles Moloney (M) murine leukemia virus (MuLV), except for a substitution in M-MuLV in the middle of p30 and the middle of the polymerase gene (pol). Heteroduplex analysis revealed that 2.4 kilobases of M-MuLV DNA were replaced by 1.2 kilobases of cellular DNA. The junctions between viral and cellular sequences were determined by DNA sequence analysis to be 517 nucleotides into the p30 sequence and 1,920 nucleotides into the polymerase sequence. Comparison of the transforming gene from 3611-MSV, designated v-raf, with previously isolated retrovirus oncogenes either by direct hybridization or by comparison of restriction fragments of their cellular homologs shows it to be unique. Transfection of NIH 3T3 cells with cloned 3611-MSV proviral DNA leads to highly efficient transformation and the recovered virus elicits tumors in mice typical of the 3611-MSV virus. Transfected NIH 3T3 cells express two 3611-MSV-specific polyproteins (P75 and P90), both of which contain NH2-terminal gag gene-encoded components linked to the acquired sequence (v-raf) translational product. The cellular homolog, c-raf, is present in one or two copies per haploid genome in mouse and human DNA.