gebhart/patrepeval huggingface dataset:
BIOCHEMICAL STUDY ON GANGLIOSIDES IN NEURO‐FIBROMAS AND NEUROFIBROSARCOMAS OF RECKLINGHAUSEN'S DISEASE (1984)

ABSTRACT Gangliosides in neurofibromas and neurofibrosarcomas of Recklinghausen's disease and those of neurilemmomas of non Recklinghausen's disease were investigated. Two types of neurofibromas, cutaneous neurofibromas and plexiform neurofibromas, which are considered to originate from Schwann cells and endoneural fibroblasts, showed almost similar ganglioside compositions; both types contained GM3, GD3, GD1a, GD1b and GT1b as the major gangliosides. These ganglioside compositions resembled those of normal whole sciatic nerve, but not those of the myelin of a normal sciatic nerve hitherto reported. The ganglioside compositions of neurilemmomas, which are also considered to be derived from Schwann cells, resembled those of sciatic nerve myelin. In neurofibrosarcomas, the content of gangliosides with longer carbohydrate chains was remarkably decreased, but not in neurofibromas. This finding indicated that the biochemical analysis of ganglioside compositions of such tumors may be a useful tool for the diagnosis of the malignancy of diseases. Major gangliosides extracted from a big plexiform neurofibroma were identified by TLC, GLC and neuraminidase treatment.
Conformational mimicry of a chlamydial neutralization epitope on filamentous phage. (1994)

Conformational constraints were imposed on a peptide epitope from Chlamydia trachomatis to improve its ability to elicit antibodies that cross-react with native antigen. Appropriate constraints were discovered by a strategy that required no prior knowledge of the epitope's native conformation. First, we constructed a library of 3.2 x 10(5) peptides in which the epitope's contact residues were subject to random conformational constraints, each constrained peptide being fused genetically to the surface of a filamentous phage vector. Next, we selected phage displaying the most native-like peptides in the library by affinity purification with antibodies that bind the epitope only in its native conformation. Finally, we immunized mice with the selected phage and titered the resulting antisera against both whole cells and unconstrained peptide. The ratio of anti-cell titer to anti-peptide titer, which reflects the channeling of the antibody response to the native epitope, was up to five times higher for affinity-selected phage than for unselected peptide phage. In this case, therefore, "antigenic fitness," the ability of a peptide to bind antibodies specific for native epitope, correlated with "immunogenic fitness," its ability to elicit antibodies that are effective against the native antigen on an invading pathogen. If the correlation is general, surveying thousands or millions of peptides for antigenic fitness with phage display technology may be a simple but effective pre-screen for immunogenic fitness, which is costly to assess directly.
The Implication of Brown Adipose Tissue for Humans (2011)

We here discuss the role of brown adipose tissue on energy homeostasis and assess its potential as a target for body weight management. Because of their high number of mitochondria and the presence of uncoupling protein 1, brown fat adipocytes can be termed as energy inefficient for adenosine-5'-triphosphate (ATP) production but energy efficient for heat production. Thus, the energy inefficiency of ATP production, despite high energy substrate oxidation, allows brown adipose tissue to generate heat for body temperature regulation. Whether such thermogenic property also plays a role in body weight regulation is still debated. The recent (re)discovery of brown adipose tissue in human adults and a better understanding of brown adipose tissue development have encouraged the quest for new alternatives to treat obesity since obese individuals seem to have less brown adipose tissue mass/activity than do their lean counterparts. In this review, we discuss the physiological relevance of brown adipose tissue on thermogenesis and its potential usefulness on body weight control in humans.
The role of type IX collagen in osteoarthritis and rheumatoid arthritis. (1993)

Articular cartilage consists of a cellular and an extracellular compartment. The extracellular compartment is composed of collagen, proteoglycans, and noncollagenous matrix proteins. Collagen resists tensile forces and serves as an organizing skeleton that helps maintain the structural integrity of cartilage. Fourteen types of collagen have been identified. The cartilage-specific collagens are type II (the principal component), type IX, type X, and type XI. Type IX collagen is hypothesized to be the "glue" that holds together the type II collagen latticework of articular cartilage. Degradation of type IX collagen by proteolytic enzymes has been observed in the primary stages of osteoarthritis and rheumatoid arthritis. This degradation is thought to represent an "ungluing" of the collagen scaffold and has been proposed as the mechanism for the degenerative changes seen in osteoarthritic and rheumatoid cartilage.
The Import Motor of the Yeast Mitochondrial TIM23 Preprotein Translocase Contains Two Different J Proteins, Tim14 and Mdj2 (2005)

The import motor of the mitochondrial (mt)TIM23 complex drives translocation of presequence-containing preproteins across the mitochondrial inner membrane in an ATP-dependent manner. Tim44 is the central component of the motor. It recruits mtHsp70, which binds the incoming preproteins. The J protein Tim14 stimulates the ATPase activity of mtHsp70 and thereby enables efficient binding of mtHsp70 to preproteins. Tim16 is a J-like protein that forms a stable subcomplex with Tim14 and recruits it to the translocase. All subunits of the TIM23 translocase but one are essential for yeast cell viability. Yeast cells contain a close homologue of Tim14, Mdj2. In contrast to Tim14, its deletion leads to no obvious growth defect. In the present study we analyzed Mdj2 and compared it with Tim14. Mdj2 forms a complex with Tim16 and is recruited to the TIM23 translocase. It stimulates the ATPase activity of mtHsp70 to the same extent that Tim14 does. Mdj2 is expressed at a lower level compared with Tim14, and its complex with Tim16 is less stable. However, overexpressed Mdj2 fully restores the growth of cells lacking Tim14. We conclude that Mdj2 is a functional J protein and a component of the mitochondrial import motor.
Culture of human endometrial cells: A new simple technique to completely separate epithelial glands (1993)

In vitro studies on dispersed human endometrial cells are still difficult to perform as the techniques employed do not allow an optimal separation of the cells. In particular, epithelial glands tend to maintain their tubular structure even after enzymatic dispersion. This could be a disadvantage when monolayers of single well dispersed cells are needed. In this paper we describe a new technique to establish monolayer cultures of isolated endometrial stromal and epithelial cell populations. After a first collagenase digestion, stromal and epithelial cells were separated by differential sedimentation at unity gravity. The epithelial glands obtained were further dispersed in single cells using a short incubation with low amount of trypsin. Morphologic characterization was performed using immunohistochemistry for vimentin and cytokeratins. Compared to previous described methods, this procedure is shorter and could better preserve cell surface structures. Thus, it could be successfully employed for in vitro studies of human endometrial pathophysiology.
Current challenges in interventional mitral valve treatment. (2015)

Transcatheter mitral valve therapies have emerged as an alternative option in high surgical risk or inoperable patients with severe and symptomatic mitral regurgitation (MR). As multiple technologies and different approaches will become available in the field of mitral valve interventions, different challenges are emerging, both patient- (clinical challenges) and procedure-related (technical challenges). This review will briefly explore the current open challenges in the evolving fields of interventional mitral valve treatment.
Development of Novel Tetravalent Anti-CD20 Antibodies with Potent Antitumor Activity (2008)

Despite the effectiveness of the anti-CD20 monoclonal antibody (mAb) Rituximab (C2B8) in the treatment of B-cell lymphoma, its efficacy remains variable and often modest. It seems likely that a combination of multiple mechanisms, such as complement-dependent cytotoxicity (CDC) and apoptotic signaling, underlies the therapeutic success of anti-CD20 mAbs. Unfortunately, all the current anti-CD20 mAbs effective in CDC are relatively inactive in signaling cell death and vice versa. In this study, we developed two genetically engineered tetravalent antibodies (TetraMcAb) respectively derived from the anti-CD20 mAbs C2B8 and 2F2. TetraMcAbs, with a molecular mass only 25 kDa higher than native divalent antibodies (DiMcAb), were shown not only to be as effective in mediating CDC and antibody-dependent cellular cytotoxicity against B-lymphoma cells as DiMcAbs but also to have antiproliferative and apoptosis-inducing activity markedly superior to that of DiMcAbs. Interestingly, whereas 2F2 and C2B8 were equally effective in inducing cell growth arrest and apoptosis, the functions of their tetravalent versions, 2F2(ScFvHL)(4)-Fc and C2B8(ScFvHL)(4)-Fc, were significantly different. 2F2(ScFvHL)(4)-Fc exhibited exceptionally more potent antiproliferative and apoptosis-inducing activity than that of C2B8(ScFvHL)(4)-Fc. Immunotherapeutic studies further showed that 2F2(ScFvHL)(4)-Fc was far more effective in prolonging the survival of severe combined immunodeficient mice bearing systemic Daudi or Raji tumors than C2B8, 2F2, and C2B8(ScFvHL)(4)-Fc, suggesting that it might be a promising therapeutic agent for B-cell lymphoma.
Highly Chemoselective and Enantioselective Catalytic Oxidation of Heteroaromatic Sulfides via High-Valent Manganese(IV)–Oxo Cation Radical Oxidizing Intermediates (2017)

A manganese complex with a porphyrin-like ligand that catalyzes the highly chemoselective and enantioselective oxidation of heteroaromatic sulfides, including imidazole, benzimidazole, indole, pyridine, pyrimidine, pyrazine, sym-triazine, thiophene, thiazole, benzothiazole, and benzoxazole, with hydrogen peroxide is described, furnishing the corresponding sulfoxides in good to excellent yields and enantioselectivities (up to 90% yield and up to &gt;99% ee) within a short reaction time (0.5 h). The practical utility of the method has been demonstrated in the gram-scale synthesis of chiral sulfoxide. Mechanistic studies, performed with O-18-labeled water ((H2O)-O-18), hydrogen peroxide ((H2O2)-O-18), and cumyl hydroperoxide, reveal that a high-valent manganese-oxo species is generated as the oxygen atom delivering agent via carboxylic acid assisted heterolysis of O-O bonds. Density functional theory (DFT) calculations were also carried out to give further insight into the mechanism of manganese-catalyzed sulfoxidation. On the basis of the theoretical study, the coupled high-valent manganese(IV)-oxo cation radical species, which bears obvious similarities with that of reactive intermediates in the catalytic oxygenation reactions based on the cytochrome P450 and metalloporphyrin models, has been proposed as the reactive oxidant in the non-heme manganese catalyst system.
High Accuracy Mutation Detection in Leukemia on a Selected Panel of Cancer Genes (2012)

With the advent of whole-genome and whole-exome sequencing, high-quality catalogs of recurrently mutated cancer genes are becoming available for many cancer types. Increasing access to sequencing technology, including bench-top sequencers, provide the opportunity to re-sequence a limited set of cancer genes across a patient cohort with limited processing time. Here, we re-sequenced a set of cancer genes in T-cell acute lymphoblastic leukemia (T-ALL) using Nimblegen sequence capture coupled with Roche/454 technology. First, we investigated how a maximal sensitivity and specificity of mutation detection can be achieved through a benchmark study. We tested nine combinations of different mapping and variant-calling methods, varied the variant calling parameters, and compared the predicted mutations with a large independent validation set obtained by capillary re-sequencing. We found that the combination of two mapping algorithms, namely BWA-SW and SSAHA2, coupled with the variant calling algorithm Atlas-SNP2 yields the highest sensitivity (95%) and the highest specificity (93%). Next, we applied this analysis pipeline to identify mutations in a set of 58 cancer genes, in a panel of 18 T-ALL cell lines and 15 T-ALL patient samples. We confirmed mutations in known T-ALL drivers, including PHF6, NF1, FBXW7, NOTCH1, KRAS, NRAS, PIK3CA, and PTEN. Interestingly, we also found mutations in several cancer genes that had not been linked to T-ALL before, including JAK3. Finally, we re-sequenced a small set of 39 candidate genes and identified recurrent mutations in TET1, SPRY3 and SPRY4. In conclusion, we established an optimized analysis pipeline for Roche/454 data that can be applied to accurately detect gene mutations in cancer, which led to the identification of several new candidate T-ALL driver mutations.
Temporal Processing Deficits of Language-Learning Impaired Children Ameliorated by Training (1996)

Children with language-based learning impairments (LLIs) have major deficits in their recognition of some rapidly successive phonetic elements and nonspeech sound stimuli. In the current study, LLI children were engaged in adaptive training exercises mounted as computer "games" designed to drive improvements in their "temporal processing" skills. With 8 to 16 hours of training during a 20-day period, LLI children improved markedly in their abilities to recognize brief and fast sequences of nonspeech and speech stimuli.
Record Linkage Techniques - 1985: Proceedings of the Workshop on Exact Matching Methodologies (1985)

The Workshop on Exact Matching Methodologies was held on May 9-10, 1985, at the Rosslyn Westpark Hotel in Arlington, Virginia. The conference grew out of the efforts of the Matching Group, Administrative Records Subcommittee, of the Federal Committee on Statistical Methodology. It was co-sponsored with the Washington Statistical Society. This volume is more than just the proceedings of the conference. It is intended to serve as a handbook on modern matching theory, as well as to report on the current state of the art. For this reason, not only were the papers from the Workshop included here, but extensive background material and bibliographic citations have also been added. 8433k, 368p.
The orally‐active and selective c‐Fms tyrosine kinase inhibitor Ki20227 inhibits disease progression in a collagen‐induced arthritis mouse model (2007)

Macrophage colony-stimulating factor (M-CSF) is important in the development of macrophages and osteoclasts. Previous studies have also shown that CD11b(+) myeloblasts and osteoclasts play key roles during inflammation and bone destruction in arthritic lesions. In this study, we investigated whether N-{4-[(6,7-dimethoxy-4-quinolyl)oxy]-2-methoxyphenyl}-N'-[1-(1,3-thiazole-2-yl)ethyl] urea (Ki20227), an inhibitor of the M-CSF receptor (c-Fms), suppressed disease progression in a type II collagen (CII)-induced arthritis (CIA) mouse model. We found that Ki20227 inhibited M-CSF-dependent reactions, such as lipopolysaccharide-induced tumor necrosis factor-alpha production, which were enhanced by M-CSF in vitro. Oral administration of Ki20227 in vivo prevented inflammatory cell infiltration and bone destruction, and consequently suppressed disease progression. In addition, the number of CD11b(+), Gr-1(+), and Ly-6G(+) cells in the spleen decreased in the Ki20227-treated mice, and the CII-induced cytokine production in splenocytes isolated from the Ki20227-treated arthritic mice was also reduced. These observations indicate that Ki20227 might exert its therapeutic effects in the CIA mouse model by suppressing the M-CSF-dependent accumulation of both inflammatory and osteoclast cells, as well as by inhibiting inflammatory cytokine production. Hence, inhibitors of the c-Fms tyrosine kinase might act as anti-inflammatory or anti-osteolytic agents against arthritis.
The emergence of trophoblast cell-surface antigen 2 (TROP-2) as a novel cancer target (2018)

TROP-2 is a glycoprotein first described as a surface marker of trophoblast cells, but subsequently shown to be increased in many solid cancers, with lower expression in certain normal tissues. It regulates cancer growth, invasion and spread by several signaling pathways, and has a role in stem cell biology and other diseases. This review summarizes TROP-2's properties, especially in cancer, and particularly its role as a target for antibody-drug conjugates (ADC) or immunotherapy. When the irinotecan metabolite, SN-38, is conjugated to a humanized anti-TROP-2 antibody (sacituzumab govitecan), it shows potent broad anticancer activity in human cancer xenografts and in patients with advanced triple-negative breast, non-small cell and small-cell lung, as well as urothelial cancers.
Antibody catalysis approaching the activity of enzymes (1988)

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTAntibody catalysis approaching the activity of enzymesAlfonso. Tramontano, Adrian A. Ammann, and Richard A. LernerCite this: J. Am. Chem. Soc. 1988, 110, 7, 2282–2286Publication Date (Print):March 1, 1988Publication History Published online1 May 2002Published inissue 1 March 1988https://pubs.acs.org/doi/10.1021/ja00215a045https://doi.org/10.1021/ja00215a045research-articleACS PublicationsRequest reuse permissionsArticle Views289Altmetric-Citations97LEARN ABOUT THESE METRICSArticle Views are the COUNTER-compliant sum of full text article downloads since November 2008 (both PDF and HTML) across all institutions and individuals. These metrics are regularly updated to reflect usage leading up to the last few days.Citations are the number of other articles citing this article, calculated by Crossref and updated daily. Find more information about Crossref citation counts.The Altmetric Attention Score is a quantitative measure of the attention that a research article has received online. Clicking on the donut icon will load a page at altmetric.com with additional details about the score and the social media presence for the given article. Find more information on the Altmetric Attention Score and how the score is calculated. Share Add toView InAdd Full Text with ReferenceAdd Description ExportRISCitationCitation and abstractCitation and referencesMore Options Share onFacebookTwitterWechatLinked InRedditEmail Other access optionsGet e-Alertsclose Get e-Alerts
Intranasal delivery: An approach to bypass the blood brain barrier (2004)

The blood brain barrier (BBB) represents one of the strictest barriers of in vivo therapeutic drug delivery. The barrier is defined by restricted exchange of hydrophilic compounds, small proteins and charged molecules between the plasma and central nervous system (CNS). For decades, the BBB has prevented the use of many therapeutic agents for treating Alzheimer's disease, stroke, brain tumor, head injury, spinal cord injury, depression, anxiety and other CNS disorders. Different attempts were made to deliver the drug across the BBB such as modification of therapeutic agents, altering the barrier integrity, carrier-mediated transport, invasive techniques, etc. However, opening the barrier by such means allows entry of toxins and undesirable molecules to the CNS, resulting in potentially significant damage. An attempt to overcome the barrier in vivo has focused on bypassing the BBB by using a novel, practical, simple and non-invasive approach i.e. intranasal delivery. This method works because of the unique connection which the olfactory and trigeminal nerves (involved in sensing odors and chemicals) provide between the brain and external environments. The olfactory epithelium acting as a gateway for substances entering the CNS and peripheral circulation is well known. Also, it is common knowledge that viral infections such as common cold, smallpox, measles, and chicken pox take place through the nasopharynx. The neural connections between the nasal mucosa and the brain provide a unique pathway for the non-invasive delivery of therapeutic agents to the CNS. This pathway also allows drugs which do not cross the BBB to enter the CNS and it eliminates the need for systemic delivery and thereby reducing unwanted systemic side effects. Intranasal delivery does not require any modification of therapeutic agents and does not require that drugs be coupled with any carrier. A wide variety of therapeutic agents, including both small molecules and macromolecules can be rapidly delivered to the CNS using this method. The present review discusses the various applications, advantages and limitations of this novel approach.
Temperature Variation and Heat Transfer in Triangular Grooves with an Evaporating Film (1997)

A mathematical model for the evaporating heat transfer coefe cient and temperature variation along the axial direction of a grooved plate has been developed. The model includes the effects of the capillaryinduced e ow in the grooves caused by the surface tension, the two-dimensional heat conduction occurring in the wall and liquid e lm, and the e ow and evaporation of the thin e lm caused by the disjoining pressure and surface tension in the thin e lm region. The results obtained from this model indicate that if a constant heat e ux boundary condition is applied, the heat transfer coefe cient will decrease and the wall temperature will increase along the axial direction. In addition, the apparent contact angle increases with increasing superheat, and hence, the heat transfer rate through the micro region also increases along the axial direction. Finally, it has been demonstrated that the contribution of the surface tension variation caused by temperature increases in the micro region can be neglected. This work will lead to a better understanding of the axial heat transfer coefe cient and temperature distribution on grooved surfaces, and how these parameters affect the e lm thickness.
Aromatic substituent constants for structure-activity correlations (1973)

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTAromatic substituent constants for structure-activity correlationsCorwin Hansch, Albert Leo, Stefan H. Unger, Ki Hwai Kim, Donald Nikaitani, and Eric J. LienCite this: J. Med. Chem. 1973, 16, 11, 1207–1216Publication Date (Print):November 1, 1973Publication History Published online1 May 2002Published inissue 1 November 1973https://pubs.acs.org/doi/10.1021/jm00269a003https://doi.org/10.1021/jm00269a003research-articleACS PublicationsRequest reuse permissionsArticle Views3006Altmetric-Citations1085LEARN ABOUT THESE METRICSArticle Views are the COUNTER-compliant sum of full text article downloads since November 2008 (both PDF and HTML) across all institutions and individuals. These metrics are regularly updated to reflect usage leading up to the last few days.Citations are the number of other articles citing this article, calculated by Crossref and updated daily. Find more information about Crossref citation counts.The Altmetric Attention Score is a quantitative measure of the attention that a research article has received online. Clicking on the donut icon will load a page at altmetric.com with additional details about the score and the social media presence for the given article. Find more information on the Altmetric Attention Score and how the score is calculated. Share Add toView InAdd Full Text with ReferenceAdd Description ExportRISCitationCitation and abstractCitation and referencesMore Options Share onFacebookTwitterWechatLinked InRedditEmail Other access optionsGet e-Alertsclose Get e-Alerts