gebhart/patrepeval huggingface dataset:
FOLFIRINOX in Locally Advanced and Metastatic Pancreatic Cancer: A Single Centre Cohort Study (2016)

<b>Introduction:</b> FOLFIRINOX is emerging as new standard of care for fit patients with locally advanced pancreatic cancer (LAPC) and metastatic pancreatic cancer (MPC). However, some of the physicians are reluctant to use FOLFIRINOX due to high toxicity rates reported in earlier studies. We reviewed our experience with FOLFIRINOX in LAPC and MPC, focussing on dose adjustments, toxicity and efficacy. <b>Methods:</b> We reviewed all patients with LAPC or MPC treated with FOLFIRINOX in our institution between April 2011 and December 2015. Unresectability (stage III and IV) was determined by the institution's multidisciplinary team for pancreatic cancer. <b>Results:</b> Fifty patients (18 LAPC and 32 MPC) were enrolled, with a median age of 55 years (IQR 49-66) and WHO performance status of 0/1. FOLFIRINOX was given as first-line treatment in 82% of patients. Dose modifications were applied in 90% of patients. The median number of completed cycles was 8 (IQR 5-9). Grade 3-4 toxicity occurred in 52% and grade 5 toxicity in 2%. The response rate was 25% (12% in LAPC, 32% in MPC). Median overall survival and progression-free survival were 14.8 and 10.3 months in LAPC, and 9.0 and 5.9 months in MPC, respectively. Overall 1- and 2-year survival was 65% and 10% in LAPC and 40% and 5% in MPC. Within the LAPC group, 6 patients (33%) underwent local ablative therapy and 1 patient (6%) a resection, leading to a median survival of 21.8 months. <b>Conclusion:</b> FOLFIRINOX treatment with nearly routine dose modification was associated with acceptable toxicity rates, relatively high response rates and an encouraging overall survival.
Glycoconjugate vaccines (2012)

Continued surveillance is necessary to recognise any epidemiological changes influenced by the impact of glycoconjugate vaccines and is crucial in guiding future vaccination strategies. Although, in general, the immunogenicity of glycoconjugate vaccines results in robust immune responses in all ages, subsequent booster doses may be necessary to sustain protection. Challenges in addressing inequities in vaccine availability between industrialised and developing countries are still there. The limitations of plain polysaccharide vaccines make immunisation with glycoconjugates a more sustainable long term option.
The T lymphocyte response to cytochrome c. IV. Distinguishable sites on a peptide antigen which affect antigenic strength and memory. (1983)

The murine T cell proliferative response to the carboxyl terminal cyanogen bromide cleavage fragment 81-104 of pigeon cytochrome c (cyt) has been studied. Two interesting properties of this response have been previously described. First, T cells from B10.A mice primed with pigeon cyt 81-104 show more vigorous proliferation when restimulated with moth cyt 81-103 than when stimulated with pigeon cyt 81-104; that is, the B10.A T cell response to pigeon shows heteroclitic restimulation by moth. Second, T cells primed with the acetimidyl derivative (Am) of pigeon cyt 81-104 did not cross-react with the unmodified cyt fragments, but Am-moth cyt 81-103 still stimulated Am-pigeon cyt 81-104 primed T cells better than the Am-pigeon cyt 81-104 fragment. These results raised the issue of whether the antigenic sites on the fragments responsible for the specificity of T cell priming in vivo differed from the residues that contributed to the heteroclitic response of pigeon (or Am pigeon)-primed T cells to moth cyt c fragments. In this paper, synthetic peptide antigens were tested in order to identify which residues caused the heterocliticity of the moth fragment and which residues were involved in the antigenic differentiation of native and derivatized fragments. The heterocliticity of the T cell response to moth fragment 81-103 was found to be due to the deletion of the penultimate residue (Ala103) from the pigeon fragment. However, the ability to cause heterocliticity was not uniquely a property of this deletion. T cells from animals primed with peptides containing substitutions at positions 100 or 102 were also heteroclitically stimulated by the moth-like antigen. The observation that T cells could not be primed for recognition of the changes in peptide sequence that caused heteroclitic stimulation suggests that T cells do not directly recognize determinants in this region. The antigenically significant site of derivatization for T cell priming was found to be Lys99. Furthermore, substitution of a Gln at position 99 also resulted in elicitation of yet a third set of T cell clones specific for the presence of that residue. That is, the specificity of the primed T cell population was found to be altered by changes at residue-99, but no such alterations in specificity were demonstrable when T cells primed with peptides altered at residue-103, residue-102, or residue-100 were compared. Overall, the results demonstrate that the antigen can be divided into two functionally distinct sites that are in close physical proximity.
MEK1 Inhibition and Arsenic Trioxide Synergize To Induce Apoptosis of Acute Myeloid Leukemia Blasts. (2004)

Abstract We recently demonstrated that the combined treatment with PD184352, a highly selective inhibitor of MEK1 phosphorylation and activation (kindly provided to us by Dr J. S. Sebolt-Leopold, Cancer Molecular Sciences, Pfizer Global Research &amp; Development, Ann Arbor, MI) and arsenic trioxide (ATO) strikingly potentiates apoptotic cell death induced by ATO in K562 and NB4 leukemic cells through the up-regulation of the proapoptotic p53AIP1 protein (p53-regulated Apoptosis-Inducing Protein 1), via p73 activation (Blood104: 519–525, 2004). Moreover, we showed that MEK1 inhibition sensitizes both parental and arsenic resistant NB4 cell lines to ATO-induced apoptosis through the MEK1 inhibition-mediated dephosphorylation of Bad, increasing its capacity to heterodimerize with Bcl-xL and Bcl-2 thereby blocking theirs antiapoptotic functions (ASH 2003, Abstract 61). p53AIP1 interacts with Bcl-2, affecting p53AIP1-mediated apoptosis through regulation of the mitochondrial transmembrane potential, thus supporting a model in which both pathways (p73-p53AIP1 and Bad phosphorylation) contribute to ATO induced apoptosis and its enhancement by MEK1 inhibitor co-treatment. Collectively, our results prompted us to investigate whether the combination of PD184352 and ATO was effective in inducing apoptosis of primary acute myeloid leukemia (AML) blasts. Twenty primary AML samples with different FAB classification were analyzed at diagnosis. Immunological and genetic characteristics were defined. Primary AML samples were cultured in presence of escalating doses of PD184352 (0.1–20 μM), ATO (0.125–10 μM) or combinations of the 2 agents at a 1:1 ratio (0.25/0.25, 0.5/0.5, 1/1, 1.5/1.5, 2/2). After 48 h of treatment the cells were harvested for mitochondrial transmembrane potential, annexin V and sub-G1 DNA content detection. Combination Index (CI) plots were then generated using the Chou-Talalay method and Calcusyn software (Biosoft, Ferguson, MO). CI less than 1.0 indicates synergism; CI = 1.0 indicates additive effect; CI more than 1.0 indicates antagonistic effect. Interestingly, MEK1 inhibition strikingly increased the apoptosis induced by ATO in sixteen of twenty primary AML samples analyzed. Isobologram analysis confirmed the additive or synergistic nature of this interaction. Five responder patients showed additive effect (one M0, two M2, two M4), eleven synergism (one M1, three M2, three M3, two M4, two M5). In the responsive AML samples the combined treatment with PD184352 and ATO strikingly potentiated loss of mitochondrial transmembrane potential induced by ATO. Treatment with MEK1 inhibitor down-modulated the steady level of ERK and Bad phosphorylation and prevented theirs phosphorylation in rensponse to ATO treatment. Moreover, p53AIP1 expression was enhanced after PD184352 plus ATO treatment compared to ATO alone. In conclusion these results demonstrated a cooperation between these two agents in this setting, and could provide an experimental basis for combined or sequential MEK1 inhibition plus ATO therapy in AML.
A Mechanism for Prompt Notification of Zone Changes (DNS NOTIFY) (1996)

This memo describes the NOTIFY opcode for DNS, by which a master server advises a set of slave servers that the master's data has been changed and that a query should be initiated to discover the new data.
MicroRNAs in Skin and Wound Healing (2012)

MicroRNAs (miRNAs) are small noncoding RNA molecules ∼22 nucleotides in length that can post-transcriptionally repress gene expression. MiRNAs bind to their target messenger RNAs (mRNAs), leading to mRNA degradation or suppression of translation. miRNAs have recently been shown to play pivotal roles in skin development and are linked to various skin pathologies, cancer, and wound healing. Chronic wounds represent a major health burden and drain on resources and developing more effective treatments is therefore a necessity. Increase in the understanding of the regulation of chronic wound biology is therefore required to develop newer therapies. This review focuses on the role of miRNAs in cutaneous biology, the various methods of miRNA modulation, and the therapeutic opportunities in treatment of skin diseases and wound healing.
In vivo assessment of bifurcation optimal viewing angles and bifurcation angles by three-dimensional (3D) quantitative coronary angiography (2011)

Evaluation and stenting of coronary bifurcation lesions may benefit from optimal angiographic views. The anatomy-defined bifurcation optimal viewing angle (ABOVA) is characterized by having an orthogonal view of the bifurcation, such that overlap and foreshortening at the ostium are minimized. However, due to the mechanical constraints of the X-ray systems, certain deep angles cannot be reached by the C-arm. Therefore, second best or, so-called obtainable bifurcation optimal viewing angle (OBOVA) has to be used as an alternative. This study assessed the distributions of ABOVA and OBOVA using 3D quantitative coronary angiography in a typical patient population. In addition, the bifurcation angles in four main coronary bifurcations were assessed and compared. Patients with obstructive coronary bifurcation disease were included in this multicenter registry. A novel and validated 3D QCA software package was applied to reconstruct the bifurcations and to calculate the bifurcation angles in 3D. A list of optimal viewing angle candidates including ABOVA was also automatically proposed by the software. In a next step, the operator selected the best viewing angle as OBOVA, while applying a novel overlap prediction approach to assure no overlap between the target bifurcation and other major coronary arteries. A total of 194 bifurcations from 181 patients were assessed. The ABOVA could not be reached in 56.7% of the cases; being 40 (81.6%), 40 (78.4%), 9 (17.6%), and 21 (48.8%) cases for LM/LAD/LCx, LAD/Diagonal, LCx/OM, and PDA/PLA, respectively. Both ABOVA and OBOVA distributed sparsely with large ranges of variance: LM/LAD/LCx, 5 ± 33 RAO, 47 ± 35 Caudal versus 4 ± 39 LAO, 35 ± 16 Caudal; LAD/Diagonal, 4 ± 38 RAO, 50 ± 14 Cranial versus 14 ± 28 LAO, 33 ± 5 Cranial; LCx/OM, 21 ± 32 LAO, 27 ± 17 Caudal versus 18 ± 31 LAO, 25 ± 13 Caudal; PDA/PLA, 34 ± 21 LAO, 36 ± 21 Cranial versus 28 ± 25 LAO, 29 ± 15 Cranial. LM/LAD/LCx had the smallest proximal bifurcation angle (128° ± 24°) and the largest distal bifurcation angle (80° ± 21°), as compared with LAD/Diagonal (151° ± 13º and 48° ± 16º), LCx/OM (146° ± 18º and 57° ± 16°), and PDA/PLA (145° ± 19° and 59° ± 17°). In conclusion, large variabilities in optimal viewing angles existed for all main coronary bifurcations. The anatomy-defined bifurcation optimal viewing angle could not be reached in vivo in roughly half of the cases due to the mechanical constraints of the current X-ray systems. Obtainable bifurcation optimal viewing angle should be provided as an alternative or second best. The bifurcation angles in the left main bifurcation demonstrated the largest variabilities.
Amyloid fibril formation requires a chemically discriminating nucleation event: studies of an amyloidogenic sequence from the bacterial protein OsmB (1992)

The sequence of the Escherichia coli OsmB protein was found to resemble that of the C-terminal region of the beta amyloid protein of Alzheimer's disease, which seems to be the major determinant of its unusual structural and solubility properties. A peptide corresponding to residues 28-44 of the OsmB protein was synthesized, and its conformational properties and aggregation behavior were analyzed. The peptide OsmB(28-44) was shown to form amyloid fibrils, as did two sequence analogs designed to test the sequence specificity of fibril formation. These fibrils bound Congo red, and two of the peptides showed birefringence. The peptide fibrils were analyzed by electron microscopy and Fourier transform infrared spectroscopy. Subtle differences were observed which were not interpretable at the molecular level. The rate of fibril formation by each peptide was followed by monitoring the turbidity of supersaturated aqueous solutions. The kinetics of aggregation were characterized by a delay period during which the solution remained clear, followed by a nucleation event which led to a growth phase, during which the solution became viscous and turbid due to the presence of insoluble fibrils. The observation of a kinetic barrier to aggregation is typical of a crystallization event. The delay period could be eliminated by seeding the supersaturated solution with previously formed fibrils. Each peptide could be nucleated by fibrils formed from that same peptide, but not by fibrils from closely related sequences, suggesting that fibril growth requires specific hydrophobic interactions. It appears likely that this repeated sequence motif, which comprises most of the OsmB protein sequence, dictates the structure and possibly the function of that protein.(ABSTRACT TRUNCATED AT 250 WORDS)
Synaptic vesicle recycling studied in transgenic mice expressing synaptopHluorin (2005)

Synaptic vesicles are recycled locally within presynaptic specializations. We examined how vesicles are reused after endocytosis, using transgenic mice expressing the genetically encoded fluorescent indicator synaptopHluorin in subsets of neurons. At both excitatory and inhibitory synapses in cultured hippocampal neurons, newly endocytosed vesicles did not preferentially enter the releasable pool of vesicles. Rather, they entered the reserve pool first and subsequently the readily releasable pool over a period of several minutes. All vesicles in the recycling pool could be accessed by spaced stimuli, arguing against preferential local reuse of the readily releasable vesicles. Interestingly, nearly half the vesicles at excitatory synapses, and a third at inhibitory synapses, could not be recruited for release even by sustained stimuli. We conclude that, at presynaptic terminals in the hippocampus, most vesicles vacate release sites after exocytosis and are replaced by existing vesicles from the reserve pool, placing constraints on kiss-and-run recycling.
Dinitrogen Complexes of Sulfur-Ligated Iron (2011)

We report a unique class of dinitrogen complexes of iron featuring sulfur donors in the ancillary ligand. The ligands utilized are related to the recently studied tris(phosphino)silyl ligands (2-R(2)PC(6)H(4))(3)Si (R = Ph, iPr) but have one or two phosphine arms replaced with thioether donors. Depending on the number of phosphine arms replaced, both mononuclear and dinuclear iron complexes with dinitrogen are accessible. These complexes contribute to a desirable class of model complexes that possess both dinitrogen and sulfur ligands in the immediate iron coordination sphere.
Variant Ciz1 is a circulating biomarker for early-stage lung cancer (2012)

There is an unmet need for circulating biomarkers that can detect early-stage lung cancer. Here we show that a variant form of the nuclear matrix-associated DNA replication factor Ciz1 is present in 34/35 lung tumors but not in adjacent tissue, giving rise to stable protein quantifiable by Western blot in less than a microliter of plasma from lung cancer patients. In two independent sets, with 170 and 160 samples, respectively, variant Ciz1 correctly identified patients who had stage 1 lung cancer with clinically useful accuracy. For set 1, mean variant Ciz1 level in individuals without diagnosed tumors established a threshold that correctly classified 98% of small cell lung cancers (SCLC) and non-SCLC patients [receiver operator characteristic area under the curve (AUC) 0.958]. Within set 2, comparison of patients with stage 1 non-SCLC with asymptomatic age-matched smokers or individuals with benign lung nodules correctly classified 95% of patients (AUCs 0.913 and 0.905), with overall specificity of 76% and 71%, respectively. Moreover, using the mean of controls in set 1, we achieved 95% sensitivity among patients with stage 1 non-SCLC patients in set 2 with 74% specificity, demonstrating the robustness of the classification. RNAi-mediated selective depletion of variant Ciz1 is sufficient to restrain the growth of tumor cells that express it, identifying variant Ciz1 as a functionally relevant driver of cell proliferation in vitro and in vivo. The data show that variant Ciz1 is a strong candidate for a cancer-specific single marker capable of identifying early-stage lung cancer within at-risk groups without resort to invasive procedures.
Biologically Inspired Artificial Compound Eyes (2006)

This work presents the fabrication of biologically inspired artificial compound eyes. The artificial ommatidium, like that of an insect's compound eyes, consists of a refractive polymer microlens, a light-guiding polymer cone, and a self-aligned waveguide to collect light with a small angular acceptance. The ommatidia are omnidirectionally arranged along a hemispherical polymer dome such that they provide a wide field of view similar to that of a natural compound eye. The spherical configuration of the microlenses is accomplished by reconfigurable microtemplating, that is, polymer replication using the deformed elastomer membrane with microlens patterns. The formation of polymer waveguides self-aligned with microlenses is also realized by a self-writing process in a photosensitive polymer resin. The angular acceptance is directly measured by three-dimensional optical sectioning with a confocal microscope, and the detailed optical characteristics are studied in comparison with a natural compound eye.
Mechanism for the increase in solubility of deoxyhemoglobin S due to crosslinking the .beta. chains between Lys-82.beta.1 and Lys-82.beta.2 (1982)

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTMechanism for the increase in solubility of deoxyhemoglobin S due to crosslinking the .beta. chains between Lys-82.beta.1 and Lys-82.beta.2Ranjit Chatterjee, Roxanne Y. Walder, Arthur Arnone, and Joseph A. WalderCite this: Biochemistry 1982, 21, 23, 5901–5909Publication Date (Print):November 9, 1982Publication History Published online1 May 2002Published inissue 9 November 1982https://pubs.acs.org/doi/10.1021/bi00266a027https://doi.org/10.1021/bi00266a027research-articleACS PublicationsRequest reuse permissionsArticle Views70Altmetric-Citations26LEARN 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
Transforming growth factor-beta1 is a mediator of androgen-regulated growth arrest in an androgen-responsive prostatic cancer cell line, LNCaP. (1996)

LNCaP is an androgen-responsive prostatic cancer cell line that exhibits a bell-shaped growth response to increasing doses of dihydrotestosterone (DHT) in culture. Although the precise mechanism responsible for this growth response to androgen stimulation remains unclear, many studies have suggested that androgen modulates the level of various growth factors. In the present study, the role of transforming growth factor-beta (TGF-beta) in mediating the androgen-regulated growth arrest of LNCaP cells was investigated. The following concentrations of DHT were used: 0, 10(-12), 10(-10), and 10 (-7) M. These concentrations were selected because they represent the zero DHT control, the low-proliferative dose, the high-proliferative dose, and the growth arrest dose, respectively. Results of RT-PCR showed that LNCaP cells express TGF-beta1 but not -beta2 and -beta3 messenger RNA. Competitive quantitative RT-PCR demonstrated that the level of TGF-beta1 messenger RNA increased approximately 7-fold when cells were treated with 10(-7) M DHT. Results of Western blot analysis showed a dramatic increase in the level of latent TGF-beta1 protein in cell lysates with increasing concentrations of DHT. In addition, results of enzyme-linked immunoadsorbent assay for TGF-beta1 indicated that treatment of LNCaP cells with DHT led to a dose-dependent increase in both total and biologically active TGF-beta1 in the conditioned media. To determine the role of TGF-beta1 in regulating LNCaP proliferation, the action of TGF-beta1 was blocked by two different but complementary approaches. First, TGF-beta1 neutralizing antibody was added to the culture medium with varying concentrations of DHT. Second, mannose-6-phosphate, which has been demonstrated to inhibit the activation of latent TGF-beta1, was added in a similar manner to the culture. Results demonstrated that the characteristic bell- shaped growth response following treatment with increasing doses of DHT was converted to a linear dose-response curve as the growth of inhibition seen at the high dose by DHT was abolished. These observations, taken together, indicate that TGF-beta1 mediates at least in part the growth arrest observed at the high concentration of DHT in LNCaP cells.
Decoding Randomly Ordered DNA Arrays (2004)

We have developed a simple and efficient algorithm to identify each member of a large collection of DNA-linked objects through the use of hybridization, and have applied it to the manufacture of randomly assembled arrays of beads in wells. Once the algorithm has been used to determine the identity of each bead, the microarray can be used in a wide variety of applications, including single nucleotide polymorphism genotyping and gene expression profiling. The algorithm requires only a few labels and several sequential hybridizations to identify thousands of different DNA sequences with great accuracy. We have decoded tens of thousands of arrays, each with 1520 sequences represented at approximately 30-fold redundancy by up to approximately 50,000 beads, with a median error rate of <1 x 10(-4) per bead. The approach makes use of error checking codes and provides, for the first time, a direct functional quality control of every element of each array that is manufactured. The algorithm can be applied to any spatially fixed collection of objects or molecules that are associated with specific DNA sequences.