gebhart/patrepeval huggingface dataset:
Multifunctional nanoparticles for multimodal imaging and theragnosis (2011)

Nanomedicine is the biomedical application of nanoscale materials for diagnosis and therapy of disease. Recent advances in nanotechnology and biotechnology have contributed to the development of multifunctional nanoparticles as representative nanomedicine. They were initially developed to enable the target-specific delivery of imaging or therapeutic agents for biomedical applications. Due to their unique features including multifunctionality, large surface area, structural diversity, and long circulation time in blood compared to small molecules, nanoparticles have emerged as attractive preferences for optimized therapy through personalized medicine. Multimodal imaging and theragnosis are the cutting-edge technologies where the advantages of nanoparticles are maximized. Because each imaging modality has its pros and cons, the integration of several imaging agents with different properties into multifunctional nanoparticles allows precise and fast diagnosis of disease through synergetic multimodal imaging. Moreover, nanoparticles are not only used for molecular imaging but also applied to deliver therapeutic agents to the disease site in order to accomplish the simultaneous imaging and therapy called theragnosis. This tutorial review will highlight the recent advances in the development of multifunctional nanoparticles and their biomedical applications to multimodal imaging and theragnosis as nanomedicine.
l-Arginine attenuates trauma-hemorrhage-induced liver injury (2000)

Because citrulline is a by-product of nitric oxide generation by nitric oxide synthase from L-arginine, this amino acid may be a useful adjunct for preventing hepatic injury after trauma-hemorrhage via endothelial derived nitric oxide production.
Resistance to therapy in estrogen receptor positive and human epidermal growth factor 2 positive breast cancers: progress with latest therapeutic strategies (2016)

In this article, we focus on the subtype of estrogen receptor (ER)-positive, human epidermal growth factor 2 (HER2)-positive breast cancer (BC). Preclinical and clinical data indicate a complex molecular bidirectional crosstalk between the ER and HER2 pathways. This crosstalk probably constitutes one of the key mechanisms of drug resistance in this subclass of BC. Delaying or even reversing drug resistance seems possible by targeting pathways implicated in this crosstalk. High-risk patients currently receive anti-HER2 therapy, chemotherapy and endocrine therapy in the adjuvant setting. In metastatic cases, most patients receive a combination of anti-HER2 therapy and chemotherapy. Only selected patients presenting more indolent disease are candidates for combinations of anti-HER2 therapy and endocrine therapy. However, relative improvements in progression-free survival by chemotherapy-based regimens are usually lower in ER-positive patients than the ER-negative and HER2-positive subgroup. Consequently, new approaches aiming to overcome endocrine therapy resistance by adding targeted therapies to endocrine therapy based regimens are currently explored. In addition, dual blockade of HER2 or the combination of trastuzumab and phosphoinositide 3-kinase (PI3K)/protein kinase B (AKT)/mammalian target of rapamycin (mTOP) inhibitors targeting the downstream pathway are strategies to overcome resistance to trastuzumab. This may lead in the near future to the less frequent use of chemotherapy-based treatment options in ER-positive, HER2-positive BC.
Integrating Internet telephony services (2002)

Cost savings and the ease of developing and adding new services have motivated great interest in Internet telephony, which integrates services provided by the Internet with the public switched telephone network (PSTN). Internet telephony relies on several protocols, including the real-time transport protocol (RTP) for multimedia data transport and the session initiation protocol (SIP) or H.323 for establishing and controlling sessions. SIP can integrate with other Internet services, such as email, the Web, voice mail, instant messaging, conference calling, and multimedia collaboration. We have implemented a SIP-based software suite called the Columbia Internet extensible multimedia architecture (Cinema), which we installed and integrated with the existing private branch exchange (PBX) infrastructure in the computer science department at Columbia University. The Cinema environment provides interoperability with the PSTN, programmable Internet telephony services, and IP-based voice mail. It also integrates Web access and e-mail for unified messaging and supports multiparty multimedia conferencing. The setup lets us extend our PBX capacity and will eventually let us replace it while keeping our existing phone numbers. It also provides an environment in which we can easily add new services and features, including interoperation with existing multimedia tools, e-mail access from standard. telephones, network appliance control, and instant messaging support.
Preparation of 4-[Bis(tert-butoxy)phosphorylmethyl]-N-(fluoren-9-ylmethoxycarbonyl)-DL-phenylalanine. A Hydrolytically Stable Analogue ofO-Phosphotyrosine Potentially Suitable for Peptide Synthesis (1991)

Sodium methoxide catalyzed aldol condensation of ethyl α-azidoacetate with 4-[bis-(tert-butoxy)phosphorylmethyl]benzaldehyde (4) provides methyl α-azido-4-[bis(tert-butoxy)phosphorymethyl]cinnamate (5), which undergoes facile hydrogenation in the presence of 10% palladium on carbon to yield methyl 4-[bis(tert-butoxy)phosphorylmethyl]-DL-phenylalaninate (6). Hydrolysis of the methyl ester by brief treatment 1N sodium hydroxide in dioxane, followed by reaction with 1-benzotriazolyl 9-fluorenylmethyl carbonate (Fmoc-OBT) at pH 8 cleanly provides 4-[bis(tert-butoxy) phosphorylmethyl]-N-Fmoc-DL-phenylalanine (3), an orthogonally protected derivative potentially suitable for utilization in the synthesis of peptides containing a hydrolytically stable mimetic of O-phosphotyrosine.
The fission yeast STS5+ gene is required for maintenance of growth polarity and functionally interacts with protein kinase C and an osmosensing MAP-kinase pathway (1996)

Cell morphogenesis is a fundamental phenomenon that involves understanding a number of biological processes including the developmental program, polarity and cell division. Fission yeast sts5 mutant cells are round rather than cylindrical with cortical actin randomly dispersed. Genetic analyses demonstrate that the sts5+ gene is required for maintenance of cell shape during interphase when the cell normally exhibits polarised growth. The sts5 mutant is not defective in cell wall integrity. Deletion of ppe1+, which encodes a type 2A-like protein phosphatase, shows similar phenotypes to the sts5 mutant and these two mutations are synthetically lethal. Multicopy plasmids containing either the protein kinase C-like gene pck1+ or the protein tyrosine phosphatase pyp1+, an inhibitor of an osmosensing Sty1/Spc1 MAP-kinase, are capable of suppressing the sts5 mutation. Consistent with this, we have found that the wis1 mutation, which is defective in a MAP-kinase kinase of the pathway, suppresses the sts5 mutation. The predicted sts5+ gene product exhibits sequence similarity to two yeast proteins, Dis3 and Ssd1 and a nematode protein, F46E8.6, where the former two yeast proteins have been shown to be involved in cell cycle control and cell morphogenesis. The sts5+ gene is not essential for cell viability, but is absolutely required for polarised growth as the gene disruption showed the same phenotypes as those of the original mutants. Overexpression of the sts5+ gene resulted in altered cell morphology and, cortical actin in these overproducing cells was also abnormal, fainter and often dispersed. Anti-Sts5 antibody specifically detected a 130 kDa protein by western blotting. A green fluorescent protein-Sts5 fusion protein localised in the cytoplasm with a discrete punctate pattern, suggesting that the Sts5 protein is a component of a novel structure. These results have indicated that the Sts5 protein is a crucial determinant of polarised growth and that it functionally interacts with the serine/threonine phosphatase, protein kinase C, and an osmosensing MAP-kinase to maintain cell morphology.
Bacterial Toxins: Friends or Foes? (1999)

Many emerging and reemerging bacterial pathogens synthesize toxins that serve as primary virulence factors. We highlight seven bacterial toxins produced by well-established or newly emergent pathogenic microbes. These toxins, which affect eukaryotic cells by a variety of means, include Staphylococcus aureus alpha-toxin, Shiga toxin, cytotoxic necrotizing factor type 1, Escherichia coli heat-stable toxin, botulinum and tetanus neurotoxins, and S. aureus toxic-shock syndrome toxin. For each, we discuss the information available on its synthesis and structure, mode of action, and contribution to virulence. We also review the role certain toxins have played in unraveling signal pathways in eukaryotic cells and summarize the beneficial uses of toxins and toxoids. Our intent is to illustrate the importance of the analysis of bacterial toxins to both basic and applied sciences.
Engineered anti-CD38 monoclonal antibodies for immunotherapy of multiple myeloma (1995)

Multiple myeloma is a malignancy of plasma cells for which there is no effective treatment. To develop an immunotherapeutic agent, we have raised a high affinity mAb (AT13/5) against CD38, one of the few well-characterized surface Ags present on myeloma cells. Since murine monoclonals have many disadvantages as human therapeutics, we prepared two engineered forms of the Ab: a CDR-grafted humanized IgG1 and a chimeric FabFc2 (mouse Fab cross-linked to two human gamma 1 Fc). To retain affinity in the humanized Ab, a number of changes were required to the human framework regions of the heavy chain. In particular, through systematic mutagenesis and computer modeling, we identified a critical interaction between the side chains of residues 29 and 78, which may be important for the humanization of other Abs. The properties of the humanized IgG1 and FabFc2 constructs were compared in a series of in vitro tests. Both constructs efficiently directed Ab-dependent cellular cytotoxicity against CD38-positive cell lines, but C was activated only poorly. Neither construct caused down-modulation of CD38, nor did they affect the NADase activity of CD38. Despite their differing structures, both Abs showed similar activity in most assays, although the humanized IgG1 was more potent at inducing monocyte cytotoxicity. These data represent the first direct comparison of CDR-grafted and chimeric FabFc2 forms of the same Ab, and offer no support for the perceived advantages of the FabFc2. These Abs show promise for therapy of multiple myeloma and other diseases involving CD38-positive cells.
Inhibitory effect and its kinetic analysis of tyrphostin AG1478 on recombinant human protein kinase CK2 holoenzyme. (2002)

The present study indicates that AG1478 is not only an effective inhibitor of protein tyrosine kinases of epidermal growth factor receptor (EGFR), but also a novel potent inhibitor of protein kinase CK2. The recombinant human protein kinase CK2 might be used as a molecular target for simpler screening and development of more effective inhibitors of CK2.
Recent developments in the understanding and management of paroxysmal nocturnal haemoglobinuria (2007)

Paroxysmal nocturnal haemoglobinuria (PNH) has been recognised as a discrete disease entity since 1882. Approximately a half of patients will eventually die as a result of having PNH. Many of the symptoms of PNH, including recurrent abdominal pain, dysphagia, severe lethargy and erectile dysfunction, result from intravascular haemolysis with absorption of nitric oxide by free haemoglobin from the plasma. These symptoms, as well as the occurrence of thrombosis and aplasia, significantly affect patients' quality of life; thrombosis is the leading cause of premature mortality. The syndrome of haemolytic-anaemia-associated pulmonary hypertension has been further identified in PNH patients. There is currently an air of excitement surrounding therapies for PNH as recent therapeutic developments, particularly the use of the complement inhibitor eculizumab, promise to radically alter the symptomatology and natural history of haemolytic PNH.
Video servers take root (1995)

Video servers are a key component of interactive networks. They have been made possible by the development of processors and standards for video compression. The author discusses their role in interactive television systems and considers video server architectures.< <ETX xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">&gt;</ETX>
Attention for Fine-Grained Categorization (2014)

This paper presents experiments extending the work of Ba et al. (2014) on recurrent neural models for attention into less constrained visual environments, specifically fine-grained categorization on the Stanford Dogs data set. In this work we use an RNN of the same structure but substitute a more powerful visual network and perform large-scale pre-training of the visual network outside of the attention RNN. Most work in attention models to date focuses on tasks with toy or more constrained visual environments, whereas we present results for fine-grained categorization better than the state-of-the-art GoogLeNet classification model. We show that our model learns to direct high resolution attention to the most discriminative regions without any spatial supervision such as bounding boxes, and it is able to discriminate fine-grained dog breeds moderately well even when given only an initial low-resolution context image and narrow, inexpensive glimpses at faces and fur patterns. This and similar attention models have the major advantage of being trained end-to-end, as opposed to other current detection and recognition pipelines with hand-engineered components where information is lost. While our model is state-of-the-art, further work is needed to fully leverage the sequential input.
The high‐affinity binding of Clostridium botulinum type B neurotoxin to synaptotagmin II associated with gangliosides GT1b/GD1a (1996)

125I-labeled botulinum type B neurotoxin was shown to bind specifically to recombinant rat synaptotagmins I and II. Binding required reconstitution of the recombinant proteins with gangliosides GT1b/GD1a. Scatchard plot analyses revealed a single class of binding site with dissociation constants of 0.23 and 2.3 nM for synaptotagmin II and synaptotagmin I, respectively, values very similar to those of the high- (0.4 nM) and low-affinity (4.1 nM) binding sites in synaptosomes. The high-affinity binding of neurotoxin to synaptosomes was specifically inhibited by a monoclonal antibody recognizing with the amino-terminal region of synaptotagmin II. These results suggest that this region of synaptotagmin II participates in the formation of the high-affinity toxin binding site by associating with specific gangliosides.
Detection of antigens in urine of mice and humans infected with Borrelia burgdorferi, etiologic agent of Lyme disease (1989)

Lyme disease is a seasonal tick-borne malady which has worldwide distribution. Early and accurate diagnosis of Lyme disease is essential for successful antibiotic therapy. Symptoms are too vague to make an early diagnosis based on conventional criteria. We report the detection of antigens of Borrelia burgdorferi, causative agent of Lyme disease, in the urine of infected mice and humans. This technique may eventually provide a rapid diagnostic test for the early and accurate detection of this illness.
Pre-conceptual Design of a Rapid Cycling Medical Synchrotron (1999)

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Cross-Packaging of a Single Adeno-Associated Virus (AAV) Type 2 Vector Genome into Multiple AAV Serotypes Enables Transduction with Broad Specificity (2002)

The serotypes of adeno-associated virus (AAV) have the potential to become important resources for clinical gene therapy. In an effort to compare the role of serotype-specific virion shells on vector transduction, we cloned each of the serotype capsid coding domains into a common vector backbone containing AAV type 2 replication genes. This strategy allowed the packaging of AAV2 inverted terminal repeat vectors into each serotype-specific virions. Each of these helper plasmids (pXR1 through pXR5) efficiently replicated the transgene DNA and expressed helper proteins at nearly equivalent levels. In this study, we observed a correlation between the amount of transgene replication and packaging efficiency. The physical titer of these hybrid vectors ranged between 1.3 x 10(11) and 9.8 x 10(12)/ml (types 1 and 2, respectively). Of the five serotype vectors, only types 2 and 3 were efficiently purified by heparin-Sepharose column chromatography, illustrating the high degree of similarity between these virions. We analyzed vector transduction in reference and mutant Chinese hamster ovary cells deficient in heparan sulfate proteoglycan and saw a correlation between transduction and heparan sulfate binding data. In this analysis, types 1 and 5 were most consistent in transduction efficiency across all cell lines tested. In vivo each serotype was ranked after comparison of transgene levels by using different routes of injection and strains of rodents. Overall, in this analysis, type 1 was superior for efficient transduction of liver and muscle, followed in order by types 5, 3, 2, and 4. Surprisingly, this order changed when vector was introduced into rat retina. Types 5 and 4 were most efficient, followed by type 1. These data established a hierarchy for efficient serotype-specific vector transduction depending on the target tissue. These data also strongly support the need for extending these analyses to additional animal models and human tissue. The development of these helper plasmids should facilitate direct comparisons of serotypes, as well as begin the standardization of production for further clinical development.
A Multicenter Randomized Trial of Breast Intensity-Modulated Radiation Therapy to Reduce Acute Radiation Dermatitis (2008)

Breast IMRT significantly reduced the occurrence of moist desquamation compared with a standard wedged technique. Moist desquamation was correlated with increased pain and reduction in the quality of life.
Jak3, severe combined immunodeficiency, and a new class of immunosuppressive drugs (2005)

The recent elucidation of the multiple molecular mechanisms underlying severe combined immunodeficiency (SCID) is an impressive example of the power of molecular medicine. Analysis of patients and the concomitant generation of animal models mimicking these disorders have quickly provided great insights into the pathophysiology of these potentially devastating illnesses. In this review, we summarize the discoveries that led to the understanding of the role of cytokine receptors and a specific tyrosine kinase, Janus kinase 3 (Jak3), in the pathogenesis of SCID. We discuss how the identification of mutations of Jak3 in autosomal recessive SCID has facilitated the diagnosis of these disorders, offered new insights into the biology of this kinase, permitted new avenues for therapy, and provided the rationale for a generation of a new class of immunosuppressants.
Isolation and characterization of a new fucoganglioside accumulated in precancerous rat liver and in rat hepatoma induced by N-2-acetylaminofluorene. (1982)

A novel fucoganglioside has been found to be accumulated in the liver of rats fed N-2-acetylaminofluorene before development of hepatoma. This new fucoganglioside persisted in hepatoma in vivo but was completely absent in normal rat liver as well as in livers of rats fed the nonhepatic carcinogen, acetylaminophenanthrene, and a tumor promoter, trichloro-2,2-bis-(chlorophenyl)ethane. The ganglioside was isolated by high performance liquid chromatography and the structure was determined by methylation analysis, sequential degradation by various exoglycosidases, and by direct probe mass spectrometry of the permethylated derivative. This ganglioside, present in precancerous liver and in hepatoma in vivo, was identified as having a new structure with a substitution identical with blood group B determinant as shown below: (formula, see text) A second fucoganglioside was detected in lower quantity in precancerous liver and in hepatoma in vivo but not in control tissue. This ganglioside co-migrated with the fucoganglioside isolated from H-35 hepatoma cells in vitro whose structure was identified (Baumann, H., Nudelman, E., Watanabe, K., and Hakomori, S. (1979) Cancer Res. 39, 2637-2643) as fucosylated GM1 ganglioside (Fuc alpha 1 leads to 2Gal beta 1 leads to 4GalNAc beta 1 leads to 4 [NeuAc alpha 2 leads to 3]Gal beta 1 leads to 4Glc beta 1 leads to 1Cer). The results indicate that synthesis of new fucolipids is already induced at an early stage during the process of chemical carcinogenesis in rat liver which could be a unique membrane marker for diagnosis and therapy of a hepatoma and its premalignancy.
Human dentin phosphophoryn nucleotide and amino acid sequence (1998)

Dentin sialoprotein (DSP) and phosphophoryns (DPP) are major dentin-specific non-collagenous proteins and are synthesized by odontoblasts. DPP are extremely acidic, rich in aspartic acid and serine, possess a high affinity for calcium and collagen, and are believed to function in dentin mineralization. Whereas DSP and DPP are the products of a single gene in mouse and rat, an analogous human gene has not been described. Using RT-PCR based cloning strategies, we have cloned human DPP cDNA from immature molar root total RNA. The open reading frame of this human DPP cDNA comprises 2364 bp encoding 788 amino acids rich in serine (58%), aspartic acid (26%) and asparagine (9%). These are mostly arranged as (DSS)n (n = 1-16), DS and NSS motifs. The N-terminal sequence (DDP) matches that obtained from human DPP extracted from the roots of immature teeth. The core protein of this human DPP was calculated to have a molecular weight of 76,906 Da and a net charge of -206 with an isoelectric point of 2.65. Of the serine residues, 53% can potentially be phosphorylated by casein kinases I and II. Thus, this newly cloned human cDNA, which encodes a protein with characteristics similar to rat and mouse DPP, is identified as a human DPP.
Cells adapted to high NaCl have many DNA breaks and impaired DNA repair both in cell culture and in vivo (2004)

Acute exposure of cells in culture to high NaCl damages DNA and impairs its repair. However, after several hours of cell cycle arrest, cells multiply in the hypertonic medium. Here, we show that, although adapted cells proliferate rapidly and do not become apoptotic, they nevertheless contain numerous DNA breaks, which do not elicit a DNA damage response. Thus, in adapted cells, Mre11 exonuclease is mainly present in the cytoplasm, rather than nucleus, and histone H2AX and chk1 are not phosphorylated, as they normally would be in response to DNA damage. Also, the adapted cells are deficient in repair of luciferase reporter plasmids damaged by UV irradiation. On the other hand, the DNA damage response activates rapidly when the level of NaCl is reduced. Then, Mre11 moves into the nucleus, and H2AX and chk1 become phosphorylated. Renal inner medullary cells in vivo are normally exposed to a variable, but always high, level of NaCl. As with adapted cells in culture, inner medullary cells in normal mice exhibit numerous DNA breaks. These DNA breaks are rapidly repaired when the NaCl level is decreased by injection of the diuretic furosemide. Moreover, repair of DNA breaks induced by ionizing radiation is inhibited in the inner medulla. Histone H2AX does not become phosphorylated, and repair synthesis is not detectable in response to total body irradiation unless NaCl is lowered by furosemide. Thus, both in cell culture and in vivo, although cells adapt to high NaCl, their DNA is damaged and its repair is inhibited.