gebhart/patrepeval huggingface dataset:
Altropane, a SPECT or PET imaging probe for dopamine neurons: I. dopamine transporter binding in primate brain (1998)

Increasing evidence suggests that the dopamine transporter is an important marker for physiological and pathological changes in dopamine neurons. Potent dopamine transport inhibitors of the phenyltropane series (e.g., WIN 35,428 or CFT) are particularly suitable for PET (positron emission tomography) or SPECT (single photon emission computed tomography) imaging of the dopamine transporter in living brain. We investigated whether altropane, an N-iodoallyl analog of WIN 35,428 (IACFT:E-N-iodoallyl-2β-carbomethoxy-3β-(4-fluorophenyl)tropane), displayed in vitro properties suitable for evaluation as a SPECT imaging agent. In brain striatum of cynomolgus monkey (Macaca fascicularis), the unlabeled E-isomer (IC50: 6.62 ± 0.78 nM) was more potent than the Z-isomer (IC50: 52.6 ± 0.3 nM) and displayed a relatively high dopamine:serotonin transporter selectivity (28-fold). In radiolabeled form, [125I]altropane bound to sites in the striatum with a single high affinity (KD: 5.33 ± 0.55 nM) and with a site density (BMAX: 301 pmol/g original wet tissue weight) that was within the density range reported previously for the dopamine transporter in striatum. Drugs inhibited [125I]altropane binding with a rank order of potency that corresponded closely to their potencies for inhibiting [3H]WIN 35,428 binding (r2: 0.99; P < 0.0001) to the blocking dopamine transport. The favorable binding properties of altropane, together with its rapid entry into primate brain and highly localized distribution in dopamine-rich brain regions, suggest it is a suitable iodinated probe for monitoring the dopamine transporter in vitro and in vivo by SPECT or PET imaging. Synapse 29:93–104, 1998. © 1998 Wiley-Liss, Inc.
Sources of distortion in functional MRI data (1999)

Functional magnetic resonance image (fMRI) experiments rely on the ability to detect subtle signal changes in magnetic resonance image time series. Any areas of signal change that correlate with the neurological stimulus can then be identified and compared with a corresponding high-resolution anatomical scan. This report reviews some of the several artefacts that are frequently present in fMRI data, degrading their quality and hence their interpretation. In particular, the effects of magnetic field inhomogeneities are described, both on echo planar imaging (EPI) data and on spiral imaging data. The modulation of these distortions as the subject moves in the magnet is described. The effects of gradient coil nonlinearities and EPI ghost correction schemes are also discussed.
Surface Studies of the Corrosion of Stainless Steel by Lead Bismuth Eutectic: Surface Preparation Effects on 316 Stainless Steels (2003)

Abstract- The corrosion of stainless steel by Lead Bismuth Eutectic (LBE) is of interest due to the utility of LBE as a coolant and as a target for high-energy spectrum neutron facilities. In previous work, He and Li found that one of the 316 class stainless steels (nuclear rated, cold rolled rod) had an order of magnitude lower corrosion and oxidation than the other steels. The present study examines samples of 316 steel with the same composition but different surface preparation (cold rolled or annealed). Changes in composition and morphology of the surface layers of the 316 class steels are reported. We focus on unexposed samples and samples that were exposed to oxygen-controlled LBE at 823K for 3000 hrs at IPPE in Russia. I.
Pharmacokinetics and Pharmacodynamics of Prasugrel, a Thienopyridine P2Y12 Inhibitor (2009)

Abstract The platelet P2Y(12) receptor has proved an effective target for therapeutic inhibition of arterial thrombosis, as demonstrated by the significant reductions in cardiovascular events in patients receiving the thienopyridine agents ticlopidine and clopidogrel. However, limitations of these drugs have led to the development of alternative antiplatelet agents including prasugrel (CS-747), an oral thienopyridine with a rapid onset of action, consistent antiplatelet activity, and prolonged duration of effect. Prasugrel is a prodrug that is metabolized to one active metabolite (R-138727) and numerous inactive metabolites. Absorption is complete and rapid, with mean time to peak plasma concentration of approximately 30 minutes for R-138727. The pharmacokinetics of prasugrel metabolites were linear and dose proportional in healthy volunteers. Median plasma half-life of the active metabolite is approximately 4 hours, and excretion is mainly urinary. Plasma clearance data suggest that prasugrel metabolism does not vary significantly among individuals. Pharmacodynamic studies have shown potent and selective P2Y(12) blockade and dose-dependent inhibition of platelet aggregation with prasugrel (or R-138727). Onset of antiplatelet action is within 30 minutes, and steady state is reached in 3 days. Inhibition of platelet aggregation by prasugrel has been shown to be more rapid, more potent (on a mg/body-weight basis), and more consistent than that with clopidogrel. Prasugrel does not appear to interact to any clinically relevant extent with other drugs, including those also metabolized by the hepatic cytochrome P450 isoenzymes CYP3A4, CYP2C9, CYP2C19, and CYP2B6, which are responsible for prasugrel metabolism. Thus, prasugrel has a pharmacokinetic and pharmacodynamic profile that compares favorably with those of existing antiplatelet agents.
Carbocyclic Dinucleoside Polyphosphonates:  Interaction with HIV Reverse Transcriptase and Antiviral Activity (2002)

Carbocyclic alpha, gamma-bis(nucleoside)-5,5'-triphosphonates and alpha, delta-bis(nucleoside)-5,5'-tetraphosphonates (Ap4A and Gp4G) analogues were shown to be a new type of terminating substrate of HIV reverse transcriptase. They effectively inhibited the DNA synthesis catalyzed by this enzyme in model cell-free systems, but their antiviral activity both in Rat1 fibroblast cell culture bearing MLV reverse transcriptase and in HIV-infected MT-4 cells was low. When a liposome delivery system was used, the antiviral efficacy of the compounds under study was increased.
Immunodominant CD4 + responses identified in a patient vaccinated with full-length NY-ESO-1 formulated with ISCOMATRIX adjuvant (2004)

There is increasing evidence showing the involvement of CD4(+) T cells in initiating and maintaining antitumor immune responses. NY-ESO-1 is expressed by various tumors but not normal tissues except testis. We conducted a cancer clinical trial by using full-length NY-ESO-1 protein formulated with ISCOMATRIX adjuvant and injected into patients intramuscularly. Autologous dendritic cells pulsed with NY-ESO-1 ISCOMATRIX in combination with overlapping synthetic peptides were used to identify immunodominant T cells from a vaccinated patient. We show here the identification and characterization of two novel CD4(+) T cell epitopes. T cells specific to these epitopes not only recognized autologous dendritic cells loaded with NY-ESO-1 but also NY-ESO-1-expressing tumor cell lines treated with IFN-gamma. One of the two responses identified was greater than the previously identified immunodominant HLA-DP4-restricted response and correlated with NY-ESO-1-specific CD8(+) T cell induction after vaccination. This T cell response was vaccinated in most patients who expressed HLA-DR2. This study has systematically surveyed patients vaccinated with full-length tumor antigen for a vaccinated CD4 helper T cell response.
Motor signs predict poor outcomes in Alzheimer disease (2005)

Motor signs predict cognitive and functional decline, institutionalization, and mortality in Alzheimer disease. Different motor sign domains predict different outcomes.
SEGMENTING TIME SERIES: A SURVEY AND NOVEL APPROACH (2004)

In recent years, there has been an explosion of interest in mining time series databases. As with most computer science problems, representation of the data is the key to efficient and effective solutions. One of the most commonly used representations is piecewise linear approximation. This representation has been used by various researchers to support clustering, classification, indexing and association rule mining of time series data. A variety of algorithms have been proposed to obtain this representation, with several algorithms having been independently rediscovered several times. In this paper, we undertake the first extensive review and empirical comparison of all proposed techniques. We show that all these algorithms have fatal flaws from a data mining perspective. We introduce a novel algorithm that we empirically show to be superior to all others in the literature.
Towards clinical TCR gene therapy: tumor models and receptors (2012)

textabstractDuring the past few decades great progress has been made in the field of cancer immune
therapy. There has been increased understanding on strategies tumors use to induce immune
tolerance and evade immune responses, which enabled the design of clinical immune
therapy trials. Two recent approaches that either oppose or circumvent immune tolerance
towards tumors have successfully been tested in phase I clinical trials.
First, immune tolerance can be opposed by monoclonal antibodies that block T cell inhibitory
molecules. For example, Ipilimumab and MDX-1106 block Cytotoxic T-Lymphocyte Antigen-
4 (CTLA-4) and Programmed Death-1 (PD-1) receptor, respectively, and administration
of these antibodies resulted in anti-tumor activities in patients with metastatic melanoma
and renal cell carcinoma. In fact, the combination of Ipilimumab and Dacarbazine (DTIC,
currently the standard first-line treatment for melanoma) increased the response rates by
three-fold. These results have encouraged further testing of dosing and combinations of
these immune modulating reagents.
Second, immune tolerance can be circumvented by adoptive transfer of autologous and
ex-vivo expanded tumor infiltrating lymphocytes (TILs). TIL therapy preceded by non-myeloablative
lymphodepletion resulted in objective response rates in about 50% of advanced
metastatic melanoma patients in two different medical centers, suggesting, but not yet
proving anti-melanoma activity. Equally interesting were the complete responses observed
in TIL therapy that ranged between 10 and 22% and seem higher than those observed for
other treatments of melanoma (see Table 1). Recently, a simpler and faster method was
developed to generate ‘young’ TILs that harbor characteristics associated with improved T
cell persistence and in vivo survival. This young TIL culture protocol yields bulk T cells, omits
the extensive in vitro testing of tumor reactivity, enriches for CD8+ T cells and depletes suppressive
T cells (Treg cells). Next to TILs, adoptive transfer of tumor specific T cell clones
generated from autologous peripheral T cells resulted in objective responses in 8 out of 10
metastatic melanoma patients. Notably, Butler and colleagues ‘educated’ peripheral T
cells using artificial antigen-presenting cells loaded with HLA-A2-restricted tumor antigens. This protocol yielded tumor-specific T cells that are clinically long-lived and effective in
melanoma patients. Collectively, the above-mentioned studies show the potential of immune
therapy and especially the successes of adoptive therapy with tumor-specific T cells.
Evaluation of Human Papillomavirus Testing in Primary Screening for Cervical Abnormalities (2002)

Testing for HPV has higher sensitivity but lower specificity than thin-layer Pap screening. In some settings, particularly where screening intervals are long or haphazard, screening for HPV DNA may be a reasonable alternative to cytology-based screening of reproductive-age women.
Clinical characteristics and treatment outcome of childhood acute lymphoblastic leukemia with the t(4;11)(q21;q23): a collaborative study of 40 cases [see comments] (1991)

The t(4;11)(q21;q23) chromosomal abnormality was identified in 40 (2%) of 1,986 children with newly diagnosed acute lymphoblastic leukemia (ALL). This translocation was associated with female sex (63%), age less than 1 year (60%), hyperleukocytosis (median leukocyte count, 156.5 x 10(9)/L), CD10-/CD19+ B-precursor cell immunophenotype, and myeloid-associated antigen (CD15) expression (63%). Nearly all cases had at least some CD24- blast cells. The CD10-/CD15%/CD19+/CD24/+ phenotype was found in 20 of the 32 t(4;11) cases tested. None of the 40 cases had the cytogenetic finding of hyperdiploidy greater than 50, which is a favorable prognostic feature. For clinical comparison, the t(4;11) cases were divided into three groups according to age at diagnosis: less than 1 year (n = 24), 1 to 9 years (n = 8), and greater than or equal to 10 years (n = 8). Compared with older patients, infants were more likely to have initial central nervous system leukemia (P = .05) and less likely to have pre-B-cell ALL (P = .05). Complete continuous remission has been maintained in only 7 of 24 infants and 2 of 8 patients aged greater than or equal to 10 years, in contrast to 7 of 8 children in the intermediate age group (P = .048). These findings suggest that the t(4;11) is an adverse prognostic feature in these two age groups.
Safety of UVA-Riboflavin Cross-Linking of the Cornea (2007)

After corneal X-linking, the stroma is depopulated of keratocytes approximately 300 microm deep. Repopulation of this area takes up to 6 months. As long as the cornea treated has a minimum thickness of 400 microm (as recommended), the corneal endothelium will not experience damage, nor will deeper structures such as lens and retina. The light source should provide a homogenous irradiance, avoiding hot spots.
Strategies for the Development of More Effective Adjuvant Therapy of Melanoma: Current and Future Explorations of Antibodies, Cytokines, Vaccines, and Combinations (2006)

Adjuvant trials have evaluated the influence of multiple agents on relapse and mortality for patients with intermediate-risk (stage IIA, American Joint Committee on Cancer staging manual, 6th ed.), high-risk (stage IIB-III), or very high-risk (stage IIIB-IV) operable melanoma. A 25% to 33% reduction of relative relapse risk with high-dose IFN-alpha2b therapy has been documented in stage groups overall, with survival prolongation in two of these trials. In contrast, no large cooperative group trial has ever shown a significant prolongation of survival for inoperable advanced stage IV melanoma. The basis for the failure of therapies in advanced disease may lie in differences in the immune function of patients with active metastatic stage IV disease. These observations argue for the exploration of promising new therapies in adjuvant settings. Past adjuvant studies have targeted stage IIB-III patients, focusing less on the more advanced but resectable stage IIIB and IV (M(1a-b)) disease groups. Current chemobiotherapy (S0008) and granulocyte-macrophage colony-stimulating factor plus peptide vaccination (E4697) trials have now evaluated the higher-risk disease groups where trials may soon be expected to yield results. Predictive markers that would allow us to focus treatment on those patients who are most likely to respond would accelerate our development of adjuvant therapy for melanoma. We have recently developed a neoadjuvant approach to high-dose IFN in which the molecular and immunologic effects of IFN have been correlated with clinical antitumor effects of this therapy. In addition, the Hellenic Oncology group has shown that the benefit of high-dose IFN is closely correlated with serologic and clinical manifestations of autoimmunity. These new insights will allow us to develop more efficient approaches to adjuvant therapy of melanoma, focusing on autoimmunity and antitumor immunity with new immunomodulators, such as anti-CTLA4 antibodies and vaccination.
Biomarker characterization using mass cytometry in a phase 1 trial of urelumab (BMS-663513) in subjects with advanced solid tumors and relapsed/refractory B-cell non-Hodgkin lymphoma. (2014)

3017 Background: Anti-CD137 antibody was shown in both murine cancer models and in a first-in-human, phase I trial (Sznol et al., 2008) to increase peripheral activated CD8 T cells and IFN-inducible genes, thereby facilitating a cytolytic, antitumor, Th1 response. A multiparametric immune pharmacodynamic assessment of the effects of anti-CD137 therapy has not been previously performed. Methods: We employed the novel technology of mass cytometry time of flight (CyTOF) to investigate the patient’s global immune status prior to and during a phase 1 study (NCT01471210) of Urelumab, a fully human anti-CD137 antibody, administered once per 3-week cycle in patients with solid tumors and B-cell non-Hodgkin’s lymphoma. Peripheral blood was obtained at 4 time points throughout treatment (baseline, 24-hrs after 1st dose of cycle 1, immediately before cycle 2, and post cycle 3 at response evaluation, C3R). PBMCs were isolated and stimulated for 4 hours with PMA/ionomycin. Immune cell characterization and function were analyzed in FlowJo and SPADE from mass cytometry results. Results: Preliminary findings from 4 patients show an increase in CD8 T cells up to 40.6% (SEM+/-13%) and NK cells up to 61.7% (SEM+/-20%) with a decrease in CD4 T cells up to 23.2% (SEM+/-6.5%) and regulatory CD4 T cells up to 17.8% (SEM+/-15%) comparing C3R to baseline. CyTOF cytokine analysis, revealed increases in GMCSF and IFN-gamma by C3R. CyTOF cytokine analysis, revealed increases in GMCSF and IFN-gamma by C3R. Conclusions: These preliminary data are consistent with anti-CD137 agonism and generate hypotheses of putative biomarkers of clinical activity now being investigated and to be reported from the ongoing clinical trial. Clinical trial information: NCT01471210.
Expression of four alternative dystrophin transcripts in brain regions regulated by different promoters (1992)

Cognitive impairment occurs in one-third of patients with Duchenne muscular dystrophy, a lethal X-linked, recessive disease caused by mutations in the dystrophin gene which is expressed in both brain and muscle, the two transcripts having alternative first exons. Previous reports have indicated that the 'brain-type' dystrophin transcript predominates in brain. Using in situ hybridisation with antisense oligonucleotides, expression of four distinct mRNAs in specific brain areas is demonstrated here; the 14 kb muscle-type and brain-type transcripts were found to coexist in cortical and hippocampal neurons and two new transcripts have been identified in dentate gyrus and cerebellar Purkinje neurons, respectively. The latter has a novel first exon which was isolated and sequenced from mouse and human, and which would encode a protein with a different amino-terminus from the known muscle- and brain-type isoforms. Mapping in human located this exon in a large intron between the muscle-type promoter and second exon of the dystrophin gene. This finding of four alternative transcripts regulated by different promoters in brain reveals a new complexity to dystrophin expression that may have important insights for mental retardation mechanisms.
Spider Silk Fibers Spun from Soluble Recombinant Silk Produced in Mammalian Cells (2002)

Spider silks are protein-based "biopolymer" filaments or threads secreted by specialized epithelial cells as concentrated soluble precursors of highly repetitive primary sequences. Spider dragline silk is a flexible, lightweight fiber of extraordinary strength and toughness comparable to that of synthetic high-performance fibers. We sought to "biomimic" the process of spider silk production by expressing in mammalian cells the dragline silk genes (ADF-3/MaSpII and MaSpI) of two spider species. We produced soluble recombinant (rc)-dragline silk proteins with molecular masses of 60 to 140 kilodaltons. We demonstrated the wet spinning of silk monofilaments spun from a concentrated aqueous solution of soluble rc-spider silk protein (ADF-3; 60 kilodaltons) under modest shear and coagulation conditions. The spun fibers were water insoluble with a fine diameter (10 to 40 micrometers) and exhibited toughness and modulus values comparable to those of native dragline silks but with lower tenacity. Dope solutions with rc-silk protein concentrations >20% and postspinning draw were necessary to achieve improved mechanical properties of the spun fibers. Fiber properties correlated with finer fiber diameter and increased birefringence.
Estrogen receptor alpha , not beta , is a critical link in estradiol-mediated protection against brain injury (2001)

Estradiol protects against brain injury, neurodegeneration, and cognitive decline. Our previous work demonstrates that physiological levels of estradiol protect against stroke injury and that this protection may be mediated through receptor-dependent alterations of gene expression. In this report, we tested the hypothesis that estrogen receptors play a pivotal role in mediating neuroprotective actions of estradiol and dissected the potential biological roles of each estrogen receptor (ER) subtype, ER alpha and ER beta, in the injured brain. To investigate and delineate these mechanisms, we used ER alpha-knockout (ER alpha KO) and ER beta-knockout (ER beta KO) mice in an animal model of stroke. We performed our studies by using a controlled endocrine paradigm, because endogenous levels of estradiol differ dramatically among ER alpha KO, ER beta KO, and wild-type mice. We ovariectomized ER alpha KO, ER beta KO, and the respective wild-type mice and implanted them with capsules filled with oil (vehicle) or a dose of 17 beta-estradiol that produces physiological hormone levels in serum. One week later, mice underwent ischemia. Our results demonstrate that deletion of ER alpha completely abolishes the protective actions of estradiol in all regions of the brain; whereas the ability of estradiol to protect against brain injury is totally preserved in the absence of ER beta. Thus, our results clearly establish that the ER alpha subtype is a critical mechanistic link in mediating the protective effects of physiological levels of estradiol in brain injury. Our discovery that ER alpha mediates protection of the brain carries far-reaching implications for the selective targeting of ERs in the treatment and prevention of neural dysfunction associated with normal aging or brain injury.
MMSE Equalization of Interference on Fading Diversity Channels (1984)

Adaptive equalization is used in digital transmission systems with parallel fading channels. The equalization combines the diversity channels and reduces intersymbol interference due to multipath returns. When interference is present and correlated from channel to channel, the equalizer can also reduce its effect on the quality of information transfer, important applications for interference cancellation occur in diversity troposcatter systems in the presence of jamming, diversity high frequency (HF) systems which must cope with interfering skywaves, and space diversity line-of-sight (LOS) radio systems where adjacent channel interference is a problem. In this paper we develop the general formulation for minimum mean square error (MMSE) equalization of interference in digital transmission diversity systems. The problem formulation includes the use of available receiver decisions to assist in MMSE processing. The effects of intersymhol interference are included in the analysis through a critical approximation which assumes sufficient processor capability to reduce ISI effects to levels small enough for satisfactory communication. The analysis also develops he concept of additional implicit or intrinsic diversity which results from channel multipath dispersion. It shows how the MMSE processor sacrifices diversity to suppress interference even when the interference arrives in the main beams of the receiver antenna patterns. The condition of near synchronous same-path interference is also addressed. Because the spatial angle of arrival of the interference may result in delay differences between interference signals in different antenna channels, interference delay compensation may be required. We show that this effect is compensated for with a small number of appropriately spaced equalizer taps.