gebhart/patrepeval huggingface dataset:
Immunotherapy of Non-Hodgkin's Lymphomas (2001)

Recent years have witnessed the development of a variety of promising immunotherapies for treating patients with non-Hodgkin's lymphomas. Foremost among these advances is the exciting success of monoclonal antibodies directed against lymphocyte surface antigens. Rituximab is a chimeric (human-mouse) anti-CD20 antibody that induces responses in approximately half of the patients with relapsed indolent lymphomas and a third of patients with relapsed aggressive lymphomas when used as a single agent. Response rates appear even higher (up to 70%) for newly diagnosed patients treated with Rituximab monotherapy. Other promising antibodies for treatment of B cell malignancies include epratuzumab (anti-CD22), CAMPATH-1H (anti-CD52w), and Hu1D10 (anti-class II HLA). Even more exciting than antibody monotherapy is the prospect of combination antibody therapy (e.g. rituximab + epratuzumab) or combination chemotherapy and antibody therapy. In this regard, a recent phase III randomized trial from the GELA group in France demonstrated statistically significantly superior complete and overall response rates and superior event-free and overall survivals for elderly patients with newly diagnosed diffuse aggressive B cell lymphomas treated with CHOP + rituximab compared with CHOP alone. Confirmatory cooperative group trials combining chemotherapy with antibody therapies are currently underway. Another approach to augment the efficacy of antibodies is to deploy them in radiolabeled form. Iodine-131, Yttrium-90, and Copper-67 labeled monoclonal antibodies targeting CD-20, CD-22, HLA class II, and other cell surface antigens have been tested and demonstrate higher overall response rates (50-80%) and complete response rates (20-40%) than unlabeled antibodies. Pilot studies combining radiolabeled antibodies with either standard dose chemotherapy or myeloablative chemoradiotherapy with stem cell transplantation also appear very promising. Lymphoma vaccines have also produced very encouraging results in single institution studies at Stanford and the National Cancer Institute, with responding patients demonstrating superior event-free and overall survival than historical controls. Phase III randomized trials of idiotype vaccines are currently underway and novel new vaccine approaches are also being tested.
Genome-wide prediction of stop codon readthrough during translation in the yeast Saccharomyces cerevisiae (2004)

In-frame stop codons normally signal termination during mRNA translation, but they can be read as 'sense' (readthrough) depending on their context, comprising the 6 nt preceding and following the stop codon. To identify novel contexts directing readthrough, under-represented 5' and 3' stop codon contexts from Saccharomyces cerevisiae were identified by genome-wide survey in silico. In contrast with the nucleotide bias 3' of the stop codon, codon bias in the two codon positions 5' of the termination codon showed no correlation with known effects on stop codon readthrough. However, individually, poor 5' and 3' context elements were equally as effective in promoting stop codon readthrough in vivo, readthrough which in both cases responded identically to changes in release factor concentration. A novel method analysing specific nucleotide combinations in the 3' context region revealed positions +1,2,3,5 and +1,2,3,6 after the stop codon were most predictive of termination efficiency. Downstream of yeast open reading frames (ORFs), further in-frame stop codons were significantly over-represented at the +1, +2 and +3 codon positions after the ORF, acting to limit readthrough. Thus selection against stop codon readthrough is a dominant force acting on 3', but not on 5', nucleotides, with detectable selection on nucleotides as far downstream as +6 nucleotides. The approaches described can be employed to define potential readthrough contexts for any genome.
Clinical trial of a 7-peptide cocktail vaccine with oral chemotherapy for patients with metastatic colorectal cancer. (2014)

The combination of a peptide vaccine and tegafur-uracil plus leucovorin (UFT/LV) were evaluated in patients with metastatic colorectal cancer refractory to standard chemotherapy.Thirty human leukocyte antigen (HLA)-A2402-positive patients were enrolled in the study. In a cycle of treatment, a vaccine comprising of seven synthetic peptides (five tumor antigen-derived and two vascular endothelial growth factor receptor-derived) was injected weekly, and oral chemotherapy, UFT/LV was given daily for four weeks followed by one week of rest. The immunological and clinical responses were evaluated at the end of every five weeks.Notable adverse events included grade 1 injection site redness/induration in 25 patients. Tumor imaging showed partial response in three patients, stable disease in 15, and progressive disease in 12. Survival analysis indicated that patients who exhibited positive cytotoxic T lymphocyte responses to all seven peptides had longer overall survival compared to other patients.A 7-peptide vaccine used with UFT/LV is safe and is recommended for further trials in patients with metastatic colorectal cancer.
Development of a Peptide–Drug Conjugate for Prostate Cancer Therapy (2011)

TGX-221 is a highly potent phosphoinositide 3-kinase β (PI3Kβ) inhibitor that holds great promise as a novel chemotherapeutic agent to treat prostate cancer. However, poor solubility and lack of targetability limit its therapeutic applications. The objective of this present study is to develop a peptide-drug conjugate to specifically deliver TGX-221 to HER2 overexpressing prostate cancer cells. Four TGX-221 derivatives with added hydroxyl groups were synthesized for peptide conjugation. Among them, TGX-D1 exhibited a similar bioactivity to TGX-221, and it was selected for conjugation with a peptide promoiety containing a HER2-targeting ligand and a prostate specific antigen (PSA) substrate linkage. From this selection, the peptide-drug conjugate was proven to be gradually cleaved by PSA to release TGX-D1. Cellular uptake of the peptide-drug conjugate was significantly higher in prostate cancer cells compared to the parent drug. Moreover, both the peptide-drug conjugate and its cleaved products demonstrated comparable activities as the parent drug TGX-D1. Our results suggest that this peptide-drug conjugate may provide a promising chemotherapy for prostate cancer patients.
Randomized Trial of High-Dose Chemotherapy and Blood Cell Autografts for High-Risk Primary Breast Carcinoma (2000)

No relapse-free or overall survival advantage was associated with the use of high-dose chemotherapy, and morbidity was increased with its use. Thus, high-dose chemotherapy is not indicated outside a clinical trial.
Two-photon excited molecular fluorescence in optically dense media (1977)

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTTwo-photon excited molecular fluorescence in optically dense mediaM. J. Wirth and F. E. LytleCite this: Anal. Chem. 1977, 49, 13, 2054–2057Publication Date (Print):November 1, 1977Publication History Published online1 May 2002Published inissue 1 November 1977https://pubs.acs.org/doi/10.1021/ac50021a041https://doi.org/10.1021/ac50021a041research-articleACS PublicationsRequest reuse permissionsArticle Views126Altmetric-Citations28LEARN 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
Analysis of the Published Calorimetric Evidence for Electrochemical Fusion of Deuterium in Palladium (1989)

Estimates are given of the raw data that are the basis for the claims of excess power production by the electrochemical charging of palladium in deuterium oxide (D(2)O). Calorimetric results are also presented that show no anomalous power production in either 0.1M LiOD/D(2)O or 0.1M LiOH/H(2)O (LiOH is lithium hydroxide). Several possible sources of error in open-system calorimetry are discussed that can confound interpretation of temperature changes in terms of anomalous power production.
The recombinant 120-kilodalton protein of Ehrlichia chaffeensis, a potential diagnostic tool (1996)

DNA encoding two repeat units of 120-kDa protein of Ehrlichia chaffeensis was cloned into the expression vector pGEX and expressed in Escherichia coli. The sensitivity and specificity of a dot blot assay for detection of human antibodies with the recombinant protein were 86 and 100%, respectively, compared with an indirect immunofluorescence assay.
Androgen Deficiency in Women1 (2001)

Physiological and pathological processes as well as iatrogenic interventions may result in androgen deficiency compared with levels in young healthy women. Whether relative androgen deficiency results in a clinical syndrome similar to that reported in men, including osteopenia, increased fat mass, decreased libido, and diminished quality of life, has not been definitively established. However, preliminary data in postmenopausal women suggest that physiological androgen replacement therapy, which involves substantially lower doses than those used in men, may result in increased bone mineral density, increased libido, and improved quality of life. The safety of androgen preparations that result in supraphysiological levels has not been established in women and would be expected to result in hirsutism, acne, and virilization with chronic use. Androgen preparations that avoid liver metabolism and result in physiological serum androgen levels in women with androgen deficiency are not currently available, but are in development. Therefore, although widespread screening and hormone replacement for androgen deficiency cannot be recommended yet, increasing interest in this topic makes consideration of the available data important.
Editorial (1999)

An editor is faced with many decisions.In this issue, for example, where to place the extended book review?Here we have a themed feature on a subject neglected in our literature, the exploration of matters of sexual identity.The papers in this feature will be placed first in the table of contents but to give a unity to this feature and a predominance that it deserves, do I put the review of a book on therapy with lesbians and gays in couples and families with the papers or do I maintain the traditions of journal presentation and place the review at the end?What prejudices do I reveal in my choice?I sought the opinion of others, took advice and decided that only I could decide.My decision is neither right nor wrong but it is an act made with awareness.In many ways this is the theme of this feature for therapists: acting with awareness.I am pleased that we are able to publish the papers on this feature, especially given the clear way in which the authors present their material.I am also pleased that this feature creates two minor innovations for the journal.First, there is the linking of two or three papers as a titled theme.This allows us to put together pieces submitted in the usual way that represent some ongoing interest and concern for the field and also to commission linked papers that will hopefully offer readers a rounded presentation.The second innovation is the introduction of 'Therapist reflections' on particular papers.The journal has a tradition of encouraging debate on a variety of themes, particularly by way of invited comment.'Therapist reflections' provides the opportunity to consider and present ideas from a variety of perspectives and at a variety of levels rather than just a theoretical argument.Again it is hoped that this way of doing things will encourage thinking, discussion and hopefully increase our awareness.It is at this point that we can announce another development that is forthcoming for the journal.With the advance of the information age and the internet, journals are seeking new ways to offer their products to their readership and new ways for there to be interactive dialogue between readers on ideas presented in the journals.There are even thoughts that journals will cease to be composed of pieces of paper that are delivered to your door by a
Finite element model based robust controllers for the MIT Middeck Active Control Experiment (MACE) (2005)

The Middeck Active Control Experiment (MACE) is a space shuttle flight experiment intended to demonstrate high authority active structural control in zero gravity (0-g) conditions based on analysis and ground testing. Finite element structural models are very important for the MACE program because they can be used to predict the on-orbit dynamics of the test article. However, finite element models tend to be inaccurate, requiring the use of parameter robust control techniques to achieve good performance. Several such control techniques and an overall design methodology are discussed in this paper. Experimental results from several tests are used to illustrate the feasibility of achieving good /spl Hscr//sub 2/ performance on the test article with robust controllers based on the finite element model. This demonstration improves confidence in the eventual on-orbit performance of this experiment and other future spacecraft.
Direct Selection of IS 903 Transposon Insertions by Use of a Broad-Host-Range Vector: Isolation of Catalase-Deficient Mutants of Actinobacillus actinomycetemcomitans (1999)

Transposon mutagenesis in bacteria generally requires efficient delivery of a transposon suicide vector to allow the selection of relatively infrequent transposition events. We have developed an IS903-based transposon mutagenesis system for diverse gram-negative bacteria that is not limited by transfer efficiency. The transposon, IS903phikan, carries a cryptic kan gene, which can be expressed only after successful transposition. This allows the stable introduction of the transposon delivery vector into the host. Generation of insertion mutants is then limited only by the frequency of transposition. IS903phikan was placed on an IncQ plasmid vector with the transposase gene located outside the transposon and expressed from isopropyl-beta-D-thiogalactopyranoside (IPTG)-inducible promoters. After transposase induction, IS903phikan insertion mutants were readily selected in Escherichia coli by their resistance to kanamycin. We used IS903phikan to isolate three catalase-deficient mutants of the periodontal pathogen Actinobacillus actinomycetemcomitans from a library of random insertions. The mutants display increased sensitivity to hydrogen peroxide, and all have IS903phikan insertions within an open reading frame whose predicted product is closely related to other bacterial catalases. Nucleotide sequence analysis of the catalase gene (designated katA) and flanking intergenic regions also revealed several occurrences of an 11-bp sequence that is closely related to the core DNA uptake signal sequence for natural transformation of Haemophilus influenzae. Our results demonstrate the utility of the IS903phikan mutagenesis system for the study of A. actinomycetemcomitans. Because IS903phikan is carried on a mobilizable, broad-host-range IncQ plasmid, this system is potentially useful in a variety of bacterial species.
[Changes in protein metabolism in cachexia and catabolism]. (1985)

Cachexia as a consequence of a catabolic state (stress metabolism) and cachexia as a consequence of too small food intake (inanition metabolism) have to be distinguished from each other fundamentally. A typical amino acid distribution in plasma, muscle, and liver can be observed in the protein catabolic patient. The glutamine metabolism seemed to be of special interest in the severe catabolic patient (e. g. sepsis). Glutamine is the amino acid with the biggest part of the free amino acid pool. This glutamine pool is reduced in the protein catabolic patient. A connexion seems to exist between the lower muscle glutamine concentration and the prognosis of the patient. The parenteral nutrition can stimulate the protein synthesis, but not suppress the protein hydrolysis. Perhaps catabolic factors as, for instance, interleucine I take part in that. These stimulate the protein hydrolysis over the prostaglandin metabolism.
p38 Mitogen-activated Protein Kinase Pathway Promotes Skeletal Muscle Differentiation (1999)

Differentiation of muscle cells is regulated by extracellular growth factors that transmit largely unknown signals into the cells. Some of these growth factors induce mitogen-activated protein kinase (MAPK) cascades within muscle cells. In this work we show that the kinase activity of p38 MAPK is induced early during terminal differentiation of L8 cells. Addition of a specific p38 inhibitor SB 203580 to myoblasts blocked their fusion to multinucleated myotubes and prevented the expression of MyoD and MEF2 family members and myosin light chain 2. The expression of MKK6, a direct activator of p38, or of p38 itself enhanced the activity of MyoD in converting 10T1/2 fibroblasts to muscle, whereas treatment with SB 203580 inhibited MyoD. Several lines of evidence suggesting that the involvement of p38 in MyoD activity is mediated via its co-activator MEF2C, a known substrate of p38, are presented. In these experiments we show that MEF2C protein and MEF2-binding sites are necessary for the p38 MAPK pathway to regulate the transcription of muscle creatine kinase reporter gene. Our results indicate that the p38 MAPK pathway promotes skeletal muscle differentiation at least in part via activation of MEF2C.
Simulation levels of detail for real-time animation (1997)

When sufficient computing power is available, dynamic simulation can be used as a source of motion for real-time, interactive virtual environments. In this paper, we explore techniques for reducing the computational cost of simulating groups of creatures by using less accurate simulations for individuals when they are less important to the viewer or to the action in the virtual world. The less accurate, or lower level of detail, simulations can be dynamic with fewer degrees of freedom, hybrid kinematic/dynamic, or purely kinematic. As a test of the effectiveness of this approach, we implemented an environment with dynamically simulated legged creatures. Because the creatures switch smoothly among different levels of detail for the underlying simulation, we can achieve real-time performance for a larger group of creatures than would be possible if each creature were dynamically simulated. To be useful in this test case, the method must meet two criteria: the outcome of the game must be essentially unchanged and the viewer's perception of the motion must be the same. While it is not possible to make definitive measurements of these criteria, we assess the performance gain from using different levels of detail and make a preliminary assessment of the effect that the decreased accuracy has on the outcome of the sample game.
Nucleoside Polyphosphates. X.1 The Synthesis and Some Reactions of Nucleoside-5' Phosphoromorpholidates and Related Compounds. Improved Methods for the Preparation of Nucleoside-5' Polyphosphates1 (1961)

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTNucleoside Polyphosphates. X.1 The Synthesis and Some Reactions of Nucleoside-5' Phosphoromorpholidates and Related Compounds. Improved Methods for the Preparation of Nucleoside-5' Polyphosphates1J. G. Moffatt and H. G. KhoranaCite this: J. Am. Chem. Soc. 1961, 83, 3, 649–658Publication Date (Print):February 1, 1961Publication History Published online1 May 2002Published inissue 1 February 1961https://pubs.acs.org/doi/10.1021/ja01464a034https://doi.org/10.1021/ja01464a034research-articleACS PublicationsRequest reuse permissionsArticle Views1878Altmetric-Citations389LEARN 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
Isolation of the Outer Sheath of Leptospira and Its Immunogenic Properties in Hamsters (1972)

Spherical forms of Leptospira interrogans serotype canicola Hond Utrecht IV were induced with 1 m NaCl. Electron micrographs of these salt-altered cells (SAC) revealed that the outer envelope or sheath had pulled away from the protoplasmic cylinder. Treatment of SAC with 0.02% sodium lauryl sulfate solubilized the sheath and released the protoplasmic cylinder. Further processing of the solubilized sheath yielded a pellet which displayed a membrane structure in electron micrographs. The released protoplasmic cylinder showed loss of intracellular organization and the outer envelope present in normal cells. Immunization of hamsters with whole formalized cells, SAC, or sheath in doses as low as 10 mug/animal protected them from death upon challenge with virulent canicola 27.
LOX-Mediated Collagen Crosslinking Is Responsible for Fibrosis-Enhanced Metastasis (2013)

Tumor metastasis is a highly complex, dynamic, and inefficient process involving multiple steps, yet it accounts for more than 90% of cancer-related deaths. Although it has long been known that fibrotic signals enhance tumor progression and metastasis, the underlying molecular mechanisms are still unclear. Identifying events involved in creating environments that promote metastatic colonization and growth are critical for the development of effective cancer therapies. Here, we show a critical role for lysyl oxidase (LOX) in establishing a milieu within fibrosing tissues that is favorable to growth of metastastic tumor cells. We show that LOX-dependent collagen crosslinking is involved in creating a growth-permissive fibrotic microenvironment capable of supporting metastatic growth by enhancing tumor cell persistence and survival. We show that therapeutic targeting of LOX abrogates not only the extent to which fibrosis manifests, but also prevents fibrosis-enhanced metastatic colonization. Finally, we show that the LOX-mediated collagen crosslinking directly increases tumor cell proliferation, enhancing metastatic colonization and growth manifesting in vivo as increased metastasis. This is the first time that crosslinking of collagen I has been shown to enhance metastatic growth. These findings provide an important link between ECM homeostasis, fibrosis, and cancer with important clinical implications for both the treatment of fibrotic disease and cancer.