gebhart/patrepeval huggingface dataset:
The Impact of Hand-Held and Hands-Free Cell Phone Use on Driving Performance and Safety-Critical Event Risk (2013)

This study investigated the effects of distraction from the use of three types of cell phones: (1) hand-held (HH), (2) portable handsfree (PHF), and (3) integrated hands-free (IHF). Through a naturalistic driving study (NDS), 204 drivers were continuously recorded for an average of 31 days. Only drivers who reported talking on a cell phone while driving at least once per day were recruited. A key feature was that drivers provided their cell phone records for analysis, making this the first NDS to date to combine call and text records with continuous naturalistic driving data. Results show that drivers talked on a cell phone 10.6 percent of the time the vehicle was in operation (28% of all calls and 10% of all text messages occurred while the vehicle was being operated). Talking on a cell phone, of any type, while driving was not associated with an increased safety-critical event (SCE) risk. SCEs comprised crashes, near-crashes, and crash-relevant conflicts. Visual-manual (VM) subtasks performed on an HH cell phone, however, were associated with an increased SCE risk. HH cell phone use in general was thus found to be associated with an increased SCE risk. In contrast, PHF and IHF cell phone use, absent of any VM HH cell phone subtasks, were not found to be associated with an increased SCE risk. However, VM HH cell phone subtasks were frequently observed during hands-free cell phone use. Driver performance when using a cell phone was also investigated through a within-subject comparison. VM HH cell phone subtasks were found to significantly increase the percentage of time drivers took their eyes off the forward roadway, while talking on an HH cell phone significantly decreased the percentage of time drivers took their eyes off the forward roadway. The effects of cell phone use on vehicle control were less pronounced.
S-100 protein and neuron-specific enolase in CSF after experimental traumatic or focal ischemic brain damage (1989)

Cerebrospinal fluid (CSF) markers of brain damage are potentially capable of providing quantitative information about the extent of certain neurological injury. The presence of such markers in CSF after brain damage is transient and it is essential to understand their kinetics if they are to be used in clinical practice. In the present study, the CSF concentrations of two neurospecific proteins. S-100 protein and neuron-specific enolase (NSE), were determined in rats before and repeatedly after one of two types of experimental brain damage: traumatic cortical injury and focal cerebral ischemia induced by middle cerebral artery (MCA) occlusion. The two types of experimental brain damage resulted in significant differences in the kinetics of S-100 and NSE concentrations in CSF. Cortical contusion was followed by a rapid increase in both S-100 and NSE and a peak occurred in both after about 7 1/2 hours, at which time the values declined toward normal. A second, smaller peak was seen after about 1 1/2 days. The increase and decrease in S-100 and NSE levels in CSF was slower after MCA occlusion; a peak was seen after 2 to 4 days. Furthermore, S-100 was generally higher than NSE after trauma, whereas after MCA occlusion the NSE concentration was slightly higher than the S-100 value. These results support the use of CSF markers for estimation of the extent of brain damage in experimental models and forms a basis for the understanding of their kinetics, which is important for their use in clinical practice.
Abstract 2113: Caveolae-mediated endocytosis as a novel mechanism of resistance to T-DM1 ADC (2016)

Abstract Trastuzumab emtansine (T-DM1) is an antibody-drug conjugate (ADC) comprised of the HER2-targeting antibody trastuzumab and DM1, a microtubule depolymerizing agent covalently attached via a non-cleavable thioether linker. T-DM1 has demonstrated clinical benefit for patients with metastatic breast cancer, however activity may be limited by inherent or acquired resistance during prolonged treatment periods. The molecular mechanisms that drive clinical resistance to T-DM1, especially in HER2 positive tumors, are not well understood. We used the HER2+ cell line N87 to develop a model of T-DM1 resistance utilizing a cyclical dosing schema in which cells received T-DM1 in an “on-off” routine until a T-DM1 resistant population of N87 cells (N87-TM) was generated. N87-TM cells displayed 103-fold resistance toward T-DM1 treatment compared to the parental N87 cells. The N87-TM cells were cross-resistant to a panel of trastuzumab-ADCs (T-ADCs) with non-cleavable-linked auristatins. N87-TM cells do not have a decrease in HER2 protein levels or an increase in drug efflux pump (e.g. MDR1) protein expression compared to parental N87 cells. Comparative proteomic profiling suggested an enrichment in proteins (e.g. caveolin-1, CAV1) that mediate caveolae formation and endocytosis in the N87-TM cells. Indeed, N87-TM cells internalize ADCs into intracellular CAV1+ puncta and alter their trafficking to the lysosome compared to N87 cells. Intriguingly, T-ADCs utilizing auristatin payloads attached via an enzymatically cleavable linker (i.e. ValCit linker) overcome T-DM1 resistance in N87-TM cells. Importantly, N87-TM cells implanted into athymic mice in vivo formed T-DM1 refractory tumors which remain sensitive to T-ADCs with cleavable-linked auristatin payloads. When comparing antigen positive patient-derived xenograft models that were refractory to T-DM1 yet responded to T-ADCs with ValCit linker-payloads, CAV1 was found to be a predictive protein biomarker identifying T-DM1 refractory tumors. These data implicate caveolae-mediated endocytosis in ADC biology and suggest that alterations in this pathway may impact a tumor's response profile to ADCs with non-cleavable linkers. We also propose CAV1 as a novel protein biomarker whose high tumoral expression predicts a refractory response to the T-DM1 ADC. Citation Format: Matthew S. Sung, Xingzhi Tan, Christine Hosselet, Michael Cinque, Erik Upeslacis, Jonathon Golas, Fang Wang, Bingwen Lu, Laurie Tylaska, Lindsay King, Jeremy Myers, Edward Rosfjord, Judy Lucas, Hans-Peter Gerber, Frank Loganzo. Caveolae-mediated endocytosis as a novel mechanism of resistance to T-DM1 ADC. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr 2113.
Analysis of segmentation and tracking algorithms for time lapse microscopic progenitor cell images (2010)

In this paper we analyze the neural progenitor cells in a time-lapse sequence to find position, shape, motility and ancestor of each cell in the frame. Because of the complex nature of cells, the ability to distinguish a cell from the background of an image for automatic quantification remains a challenging task. By using morphological techniques we are able to make a better selection of blob-like objects. The cells are detected using h-maxima transform and the cell contours are selected using watershed algorithm. The cells are tracked in an image sequence using multiple matching object method based on modified Mahalanobis distance algorithm. The proposed method has been successfully applied to a large number of images and showed promising results for tracking cells between consecutive images.
Fast protein fold recognition via sequence to structure alignment and contact capacity potentials. (1996)

We propose new empirical scoring potentials and associated alignment procedures for optimally aligning protein sequences to protein structures. The method has two main applications: first, the recognition of a plausible fold for a protein sequence of unknown structure out of a database of representative protein structures and, second, the improvement of sequence alignments by using structural information in order to find a better starting point for homology based modelling. The empirical scoring function is derived from an analysis of a nonredundant database of known structures by converting relative frequencies into pseudoenergies using a normalization according to the inverse Bolzmann law. These-so called contact capacity-potentials turn out to be discriminative enough to detect structural folds in the absence of significant sequence similarity and at the same time simple enough to allow for a very fast optimization in an alignment procedure.
An embryonic DNA-binding protein specific for a region of the human IFN 1, promoter (1988)

Embryonal carcinoma (EC) cells are unable to make interferon in response to inducing agents. This block disappears after differentiation. We have found that nuclear extracts from undifferentiated P19 EC cells contain a DNA-binding activity which specifically recognizes a region within the human interferon-beta 1 promoter. This activity is absent from differentiated cell types, both of EC and non-EC origin. The binding of the factor in undifferentiated EC cells leads to dramatic changes in the overall protein binding pattern of the interferon promoter as compared with differentiated cells, and may be responsible for repression of the endogenous interferon-beta gene prior to differentiation.
Simultaneous saccharification and fermentation of steam‐pretreated bagasse using Saccharomyces cerevisiae TMB3400 and Pichia stipitis CBS6054 (2007)

Sugarcane bagasse--a residue from sugar and ethanol production from sugar cane--is a potential raw material for lignocellulosic ethanol production. This material is high in xylan content. A prerequisite for bioethanol production from bagasse is therefore that xylose is efficiently fermented to ethanol. In the current study, ethanolic fermentation of steam-pretreated sugarcane bagasse was assessed in a simultaneous saccharification and fermentation (SSF) set-up using either Saccharomyces cerevisiae TMB3400, a recombinant xylose utilizing yeast strain, or Pichia stipitis CBS6054, a naturally xylose utilizing yeast strain. Commercial cellulolytic enzymes were used and the content of water insoluble solids (WIS) was 5% or 7.5%. S. cerevisiae TMB3400 consumed all glucose and large fraction of the xylose in SSF. Almost complete xylose conversion could be achieved at 5% WIS and 32 degrees C. Fermentation did not occur with P. stipitis CBS6054 at pH 5.0. However, at pH 6.0, complete glucose conversion and high xylose conversion (>70%) was obtained. Microaeration was required for P. stipitis CBS6054. This was not necessary for S. cerevisiae TMB3400.
A Robust Monte Carlo Model for the Extraction of Biological Absorption and Scattering In Vivo (2008)

We have a toolbox to quantify tissue optical properties that is composed of specialized fiberoptic probes for UV-visible diffuse reflectance spectroscopy and a fast, scalable inverse Monte Carlo (MC) model. In this paper, we assess the robustness of the toolbox for quantifying physiologically relevant parameters from turbid tissue-like media. In particular, we consider the effects of using different instruments, fiberoptic probes, and instrument-specific settings for a wide range of optical properties. Additionally, we test the quantitative accuracy of the inverse MC model for extracting the biologically relevant parameters of hemoglobin saturation and total hemoglobin concentration. We also test the effect of double-absorber phantoms (hemoglobin and crocin to model the absorption of hemoglobin and beta carotene, respectively, in the breast) for a range of absorption and scattering properties. We include an assessment on which reference phantom serves as the best calibration standard to enable accurate extraction of the absorption and scattering properties of the target sample. We found the best reference-target phantom combinations to be ones with similar scattering levels. The results from these phantom studies provide a set of guidelines for extracting optical parameters from clinical studies.
Histone Deacetylase Is a Direct Target of Valproic Acid, a Potent Anticonvulsant, Mood Stabilizer, and Teratogen (2001)

Valproic acid is widely used to treat epilepsy and bipolar disorder and is also a potent teratogen, but its mechanisms of action in any of these settings are unknown. We report that valproic acid activates Wntdependent gene expression, similar to lithium, the mainstay of therapy for bipolar disorder. Valproic acid, however, acts through a distinct pathway that involves direct inhibition of histone deacetylase (IC(50) for HDAC1 = 0.4 mm). At therapeutic levels, valproic acid mimics the histone deacetylase inhibitor trichostatin A, causing hyperacetylation of histones in cultured cells. Valproic acid, like trichostatin A, also activates transcription from diverse exogenous and endogenous promoters. Furthermore, valproic acid and trichostatin A have remarkably similar teratogenic effects in vertebrate embryos, while non-teratogenic analogues of valproic acid do not inhibit histone deacetylase and do not activate transcription. Based on these observations, we propose that inhibition of histone deacetylase provides a mechanism for valproic acid-induced birth defects and could also explain the efficacy of valproic acid in the treatment of bipolar disorder.
Analysis of array CGH data: from signal ratio to gain and loss of DNA regions (2004)

Abstract Motivation: Genomic DNA regions are frequently lost or gained during tumor progression. Array Comparative Genomic Hybridization (array CGH) technology makes it possible to assess these changes in DNA in cancers, by comparison with a normal reference. The identification of systematically deleted or amplified genomic regions in a set of tumors enables biologists to identify genes involved in cancer progression because tumor suppressor genes are thought to be located in lost genomic regions and oncogenes, in gained regions. Array CGH profiles should also improve the classification of tumors. The achievement of these goals requires a methodology for detecting the breakpoints delimiting altered regions in genomic patterns and assigning a status (normal, gained or lost) to each chromosomal region. Results: We have developed a methodology for the automatic detection of breakpoints from array CGH profile, and the assignment of a status to each chromosomal region. The breakpoint detection step is based on the Adaptive Weights Smoothing (AWS) procedure and provides highly convincing results: our algorithm detects 97, 100 and 94% of breakpoints in simulated data, karyotyping results and manually analyzed profiles, respectively. The percentage of correctly assigned statuses ranges from 98.9 to 99.8% for simulated data and is 100% for karyotyping results. Our algorithm also outperforms other solutions on a public reference dataset. Availability: The R package GLAD (Gain and Loss Analysis of DNA) is available upon request
Targeted gene expression as a means of altering cell fates and generating dominant phenotypes (1993)

We have designed a system for targeted gene expression that allows the selective activation of any cloned gene in a wide variety of tissue- and cell-specific patterns. The gene encoding the yeast transcriptional activator GAL4 is inserted randomly into the Drosophila genome to drive GAL4 expression from one of a diverse array of genomic enhancers. It is then possible to introduce a gene containing GAL4 binding sites within its promoter, to activate it in those cells where GAL4 is expressed, and to observe the effect of this directed misexpression on development. We have used GAL4-directed transcription to expand the domain of embryonic expression of the homeobox protein even-skipped. We show that even-skipped represses wingless and transforms cells that would normally secrete naked cuticle into denticle secreting cells. The GAL4 system can thus be used to study regulatory interactions during embryonic development. In adults, targeted expression can be used to generate dominant phenotypes for use in genetic screens. We have directed expression of an activated form of the Dras2 protein, resulting in dominant eye and wing defects that can be used in screens to identify other members of the Dras2 signal transduction pathway.
Non-steroidal Anti Inflammatory Drugs and Gastrointestinal Toxicity (2010)

Non-steroidal anti inflammatory drugs (NSAIDs) because of their high efficacy as both anti-inflammatory and analgesic agents, are one of the most commonly prescribed drugs world-wide. They are used in treatment of many commonly occurring disorders such as chronic arthropathies, headache and low back pain. Their widespread and uncontrolled use is promoted by their over the counter availability. This acts as a double edge sword. One of the most common adverse effects that add largely to its morbidity and mortality is the gastrointestinal tract damage.
A Neutronic Study of an Accelerator-Based Neutron Irradiation Facility for Boron Neutron Capture Therapy (1989)

A neutronic study of an accelerator-based neutron irradiation facility (ANIF) for boron neutron capture therapy (BNCT) was performed using three-dimensional Monte Carlo transport calculations. The major components of the ANIF are a radio-frequency quad-rupole proton accelerator, a 7Li target, and a moderator assembly. Neutrons are generated by bombarding the 7Li target with 2.5-MeV protons. The neutrons emerging from the 7Li target are too energetic to be used for BNCT and must therefore be moderated.Calculations show that, among all materials for the ANIF, beryllia (BeO) and heavy water (D2O) are the best moderators. Between them, beryllia provides better neutron spectra, but D2O gives higher neutron intensities. Adding alumina (Al2O3) to D2O improves the neutron spectra, but it also increases gamma-ray contamination.The overall performance of an ANIF was evaluated for a moderator assembly composed of a 20.0-cm-high x 12.5-cm-radius beryllia cylinder reflected by 30.0 cm of alumina. Calculations show that the addition of the alumina reflector doubles the epithermal neutron intensity at the irradiation port. A 0.05 g/cm2 thick layer of 6Li was placed between the beryllia moderator and the alumina reflector to reduce the number of thermal neutrons escaping from the beryllia to the alumina, and therefore the capture gamma rays produced by aluminum in the reflector. Also, a 0.025 g/cm2 thick layer of 6Li was placed at the irradiation port of the moderator assembly to remove thermal neutrons from the field. Finally, a neutron shield of 10.0-cm-thick D2O wrapped with 6LiF was placed around the moderator assembly except at the irradiation port.The useful neutron flux (which is the flux of neutrons with energies greater than ∼1 eV) at the irradiation point, which is in front of the moderator assembly, is 4.87 x 108 n/cm2.s for a 10-mA proton beam. The corresponding total absorbed dose rates for neutron and gamma rays are 1.9 and 0.64 cGy/min, respectively. The ratio of the total neutron absorbed dose rate to the useful neutron flux is 6.5 x 10-11 cGy/n·cm-2, which is slightly higher than, but comparable to, the value of this ratio that has been estimated for moderated reactor neutron fields. The maximum usable depth (MUD) in a head phantom is calculated to be ∼7.5 cm assuming that the 10B concentration is 30 µg/g in tumor and 10 µg/g in blood, and the singlesession treatment time is 1.6 h. If the beryllia cylinder in the moderator assembly were replaced by a 15.0-cm-high x 12.5-cm-radius cylinder of heavy water, the treatment time would be reduced to 30 min, at the price of a higher entrance neutron dose to normal tissue and thus lower therapeutic gains and MUD.
Chromosomal Integration Pattern of a Helper-Dependent Minimal Adenovirus Vector with a Selectable Marker Inserted into a 27.4-Kilobase Genomic Stuffer (2001)

Helper-dependent minimal adenovirus vectors are promising tools for gene transfer and therapy because of their high capacity and the absence of immunostimulatory or cytotoxic viral genes. In order to characterize this new vector system with respect to its integrative properties, the integration pattern of a minimal adenovirus vector with a neo(r) gene inserted centrally into a noncoding 27.4-kb genomic stuffer element derived from the human X chromosome after infection of a sex chromosome aneuploid (X0) human glioblastoma cell line was studied. Our results indicate that even extensive homologies and abundant chromosomal repeat elements present in the vector did not lead to integration of the vector via homologous or homology-mediated mechanisms. Instead, integration occurred primarily by insertion of a monomer with no or little loss of sequences at the vector ends, apparently at random sites, which is very similar to E1 deletion adenovirus vectors. It is therefore unlikely that the incorporation of stuffer elements derived from human genomic DNA, which were shown to allow long-term transgene expression in vivo in a number of studies, leads to an enhanced risk of insertional mutagenesis. Furthermore, our findings indicate that the potential of minimal adenovirus vectors as tools for targeted insertion and gene targeting is limited despite the possibility of incorporating long stretches of homologous sequences. However, we found an enhanced efficiency of stable neo(r) transduction of the minimal adenovirus vector compared to an E1 deletion adenovirus vector, possibly caused by the absence of potential growth-inhibitory viral genes. Complete integration of the vector and tolerance of the integrated vector sequences by the cell might indicate a potential use of these vectors as tools for stable transfer of (large) genes.
Pharmacokinetics of recombinant interleukin-2 in children with malignancies: a Pediatric Oncology Group study. (1990)

To develop effective interleukin-2 (IL-2) protocols for pediatric malignancies, it is important to define IL-2 pharmacokinetics in children. In a phase I trial, we studied IL-2 pharmacokinetics in seven children, aged 6-18, five with leukemia, one with neuroblastoma, and one with rhabdomyosarcoma. IL-2 was administered as a 15-min i.v. infusion of either 1 X 10(6) CU/m2/dose or 3 X 10(6) CU/m2/dose (every Monday, Wednesday, and Friday for 3 weeks). IL-2 levels were determined using an IL-2-dependent murine T lymphocyte cell line bioassay. Peak IL-2 levels of 120-426 and 330-740 CU/ml were achieved after the lower and higher doses, respectively. Pediatric IL-2 kinetics resembled data reported for adults, fitting a two-compartment model (least-squares-regression technique), with an alpha half-life of 14.0 +/- 5.6 min (range, 6.3-23.1) and a beta half-life of 51.4 +/- 10.7 min (range, 33.0-66.0). The volume of distribution approximated total extracellular fluid (mean, 0.18 L/kg). Further clinical trials are needed to identify which pediatric malignancies are sensitive to immunotherapy and to establish the optimal treatment regimens.
Neonatal testosterone exposure influences neurochemistry of non-opioid swim stress-induced analgesia in adult mice (1995)

The effects of neonatal hormone manipulations on swim stress-induced analgesia (SSIA) magnitude and neurochemical quality were examined in Swiss-Webster mice of both sexes. Previous research has indicated that non-opioid SSIA mechanisms in adult Swiss-Webster mice are sexually dimorphic. Male mice exhibit non-opioid SSIA following a 3-min swim in cold (15 degrees C) water that is antagonized by the non-competitive NMDA antagonist MK-801 (dizocilpine; 0.075 mg/kg), whereas female mice do not display NMDA-mediated analgesia in the presence of estrogen. Since male and female mice show equipotent magnitudes of SSIA, it was concluded that female mice display a neurochemically distinct, estrogen-dependent SSIA mechanism specific to their gender. In the present study, female mice exposed to testosterone during the neonatal period display NMDA-mediated analgesia even in the presence of estrogen in adulthood. Thus, expression of the female-specific, estrogen-dependent SSIA mechanism previously described may be dependent on the absence of testosterone during early ontogeny.