gebhart/patrepeval huggingface dataset:
Antitumor activity of MEK and PI3K inhibitors against malignant pleural mesothelioma cells in vitro and in vivo (2012)

Malignant pleural mesothelioma (MPM) is an aggressive malignancy for which there is no approved targeted therapy. We examined the therapeutic efficacy of the mitogen-activated protein kinase kinase (MEK) and phosphatidylinositol 3-kinase (PI3K) inhibitors against human MPM cell lines both in vitro and orthotopically inoculated into severe combined immunodeficient (SCID) mice. In addition, the molecular mechanisms of these agents were confirmed in vitro and in vivo. The MEK or the PI3K inhibitor suppressed MPM cell growth in vitro in a dose-dependent manner via induction of G1 cell cycle arrest and apoptosis. In addition, combined use of the MEK and PI3K inhibitors showed an additive or synergistic inhibitory effect on MPM cell growth compared to treatment with either individual drug. Treatment with MEK or PI3K inhibitor suppressed the production of thoracic tumors and pleural effusion and prolonged the survival time of EHMES-10 cell-bearing SCID mice. The combination therapy more effectively prolonged the survival time compared to treatment with either individual drug. Immunohistochemical and western blot analysis of thoracic tumors suggested that these agents induced cell cycle arrest, apoptosis and inhibition of tumor angiogenesis. Our results suggest that a combination of MEK and PI3K inhibitors is a promising therapeutic strategy for MPM.
Antigenic determinants in proteins coincide with surface regions accessible to large probes (antibody domains). (1986)

We evaluated surface areas on proteins that would be accessible to contacts with large (1-nm radius) spherical probes. Such spheres are comparable in size to antibody domains that contain antigen-combining sites. We found that all the reported antigenic sites correspond to segments particularly accessible to a large sphere. The antigenic sites were also evident as the most prominently exposed regions (hills and ridges) in contour maps of the solvent-accessible (small-probe) surface. In myoglobin and cytochrome c, virtually all of the van der Waals surface is accessible to the large probe and therefore potentially antigenic; in myohemerythrin, distinct large-probe-inaccessible, and nonantigenic, surface regions are apparent. The correlation between large-sphere-accessibility and antigenicity in myoglobin, lysozyme, and cytochrome c appears to be better than that reported to exist between antigenicity and segmental flexibility; that is, surface regions that are rigid often constitute antigenic epitopes, whereas some of the flexible parts of the molecules do not appear antigenic. We propose that the primary reason why certain polypeptide-chain segments are antigenic is their exceptional surface exposure, making them readily available for contacts with antigen-combining sites. Exposure of these segments frequently results in high mobility and, in consequence, to the reported correlation between antigenicity and segmental flexibility.
Human Immunodeficiency Virus Type 1 Expressing the Lamivudine‐Associated M184V Mutation in Reverse Transcriptase Shows Increased Susceptibility to Adefovir and Decreased Replication Capability In Vitro (1999)

In a phase II study of 6-12 months of adefovir dipivoxil treatment in human immunodeficiency virus (HIV)-infected patients, HIV from 8 of 29 patients developed mutations in reverse transcriptase (RT) potentially attributable to adefovir dipivoxil therapy. Recombinant HIV from pre- and posttreatment plasma samples from these 8 patients showed no change or minor decreases in adefovir susceptibility, consistent with the durable antiviral effect observed. Additionally, HIV from 8 patients developed the M184V RT mutation because of concomitant lamivudine use. Recombinant HIV pairs from all 4 patients with zidovudine-resistant HIV showed statistically significant increases in adefovir susceptibility of 3- to 4-fold (to near wild type IC50), and HIV pairs from 2 of 4 patients with zidovudine-sensitive HIV showed a 2- to 3-fold increase in susceptibility. In growth kinetics studies, expression of the M184V RT mutation resulted in attenuated viral growth in peripheral blood mononuclear cell cultures. These studies suggest that patients possessing HIV with zidovudine and lamivudine resistance mutations may benefit from adefovir dipivoxil therapy.
Pleiotrophin and midkine in normal development and tumor biology. (1995)

Pleiotrophin (PTN) and midkine (MK) are members of a family of developmentally regulated, secreted heparin-binding proteins. The proteins are structural homologs, and are highly conserved among species. Although no homology has been detected with other heparin-binding growth factors, their functional similarity to members of the fibroblast growth factor (FGF) family is remarkable. PTN and MK are expressed during embryogenesis, showing an expression pattern that suggests functions in neurogenesis, cell migration, secondary organogenetic induction, and mesoderm-epithelial interaction. The widespread downregulation of PTN and MK in the adult human is reverted in a number of cancers, in which polypeptides are able to act as both transforming growth factors and promoters of angiogenesis. Elucidating the molecular mechanisms of PTN and MK action could lead not only to a deeper understanding of developmental processes, but also to the ultimate identification of targets for tumor therapy.
Optical Network Synthesis Using Birefringent Crystals* I Synthesis of Lossless Networks of Equal-Length Crystals (1964)

A procedure for the synthesis of birefringent networks having arbitrarily prescribed transfer functions is presented. The basic network configuration consists of n identical cascaded birefringent crystals between an input and an output polarizer. The crystals are cut with their optic axes perpendicular to their length. The variables determined by the synthesis procedure are the angles of the optic axes of the crystals and the angle of the output polarizer. Any transfer function which is periodic with frequency and whose corresponding impulse response is real and causal can, in theory, be realized. A network of n crystals allows the approximation of a desired function by (n+1) terms of a Fourier exponential series. Bandwidths of less than 1 Å appear possible.
Mono- and bi-allelic expression of insulin-like growth factor II gene in human muscle tumors (1994)

Insulin-like growth factor II (IGF-II) is a mitogen for many cell types and an important modulator of muscle growth and differentiation. IGF-II gene is prevalently expressed during prenatal development and its gene activity is regulated by genomic imprinting, in that the allele inherited from the father is active and the allele inherited from the mother is inactive in most normal tissues. IGF-II expression is activated in several types of human neoplasms and an alteration of IGF-II imprinting has been described in Beckwith-Wiedemann syndrome and Wilms' tumor. Here we show that monoallelic expression of IGF-II gene is conserved in normal adult muscle tissue whereas two or more copies of active IGF-II alleles, arising by either relaxation of imprinting or duplication of the active allele, are found in 9 out of 11 (82%) rhabdomyosarcomas retaining heterozygosity at 11p15, regardless of the histological subtype. Since IGF-II has been indicated as an autocrine growth factor for rhabdomyosarcoma cells, these findings strongly suggest that acquisition of a double dosage of active IGF-II gene is an important step for the initiation or progression of rhabdomyosarcoma tumorigenesis. Among different types of muscle tumors, relaxation of imprinting seems to arise prevalently in rhabdomyosarcomas, since we have detected only one case of partial reactivation of the maternal IGF-II allele out of 7 leiomyosarcomas tested.
Improving the performance of the SP-3000 PET detector modules (1992)

A major concern in the use of BaF/sub 2/ detectors in a positron emission tomograph is the collection of the UV light from the fast decay component of the scintillator. A series of experiments with the standard SP-3000 commercial detector module confirmed that the coupling compound formulation was reasonable, but that the reflector material used to wrap the crystals was not optimal. Rebuilding the detector modules with PTFE Teflon increased the light output from the detector modules by factors of three. Initial tests with phantoms using two rings of rebuilt detectors in the University of Washington BaF/sub 2/ positron emission tomography system confirmed improvements in resolution and contrast in comparison to the original SP-3000 modules.< <ETX xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">&gt;</ETX>
Analysis of the adaptive rate control for ABR service in ATM networks (2002)

High speed networks based on the asynchronous transfer mode (ATM) will use the available bit rate (ABR) service to support best effort type service. The ABR service will use an end-to-end adaptive feedback based rate control, where the sources adapt their rates (at the cell level) based on the state of the network. The performance of this control mechanism depends on a number of control parameters, as well as the delay of the feedback loop. We analyze the feedback based rate control mechanism (as defined by the ATM Forum) and obtain closed-form (approximate) solutions. These design equations will aid in determining appropriate values for the various control parameters.
Protection of Rhesus Monkeys against Dengue Virus Challenge after Tetravalent Live Attenuated Dengue Virus Vaccination (2006)

Rhesus monkeys develop viremia after dengue virus (DENV) inoculation and have been used as an animal model to study DENV infection and DENV vaccine candidates. We evaluated, in this model, the protective efficacy of a live attenuated tetravalent DENV vaccine (TDV) candidate against parenteral challenge with parental near-wild-type DENV strains. Twenty monkeys were vaccinated with TDV at 0 and 1 month, and 20 unvaccinated monkeys served as controls. Vaccinated animals and their controls were inoculated with 10(3)-10(4) pfu of challenge virus 4.5 months after the second vaccination. Primary vaccination resulted in 95%, 100%, 70%, and 15% seroconversion to DENV serotypes 1, 2, 3, and 4 (DENV-1, -2, -3, and -4), respectively. After the second vaccination, the seropositivity rates were 100%, 100%, 90%, and 70%, respectively. Vaccination with TDV resulted in complete protection against viremia from DENV-2 challenge and in 80%, 80%, and 50% protection against challenge with DENV-1, -3, and -4, respectively. Our results suggest that the TDV can elicit protective immunity against all 4 DENV serotypes. Interference among the 4 vaccine viruses may have resulted in decreased antibody responses to DENV-3 and -4, which would require reformulation or dose optimization to minimize this interference during testing of the vaccine in humans.
Modulation of lymphokine‐activated killer cell‐mediated cytotoxicity by estradiol and tamoxifen (1996)

The effect of tamoxifen (TX) and estradiol (E2) on interleukin-2 (IL-2)-activated killer (LAK) cell-mediated cytotoxicity was examined using spleen cells of Fisher 344 rats as the source of effectors and P815 murine mastocytoma cells as targets. Treatment of target cells with either TX or E2 for 4 or 18 hr rendered them highly sensitive to LAK cell-mediated lysis. When TX and E2 were applied jointly, cytotoxicity remained at the level of TX treatment alone. The cytotoxic potential of IL-2-primed LAK cells was not modified consistently by TX and E2. When TX-treated target and effector cells were combined, high cytotoxicity characteristic of sensitized target cells was observed. In similar experiments with E2-treated cells, both enhancement and inhibition of cytotoxicity by treated effector cells was seen in some designs. Target cells could be sensitized for LAK cell-mediated destruction by physiological concentrations (I nM) of E2 and equimolar concentrations of TX. Sensitization led to the accelerated release of the nuclear label 3H-thymidine from target cells after the cytotoxic insult and could be prevented by treatment with the metabolic inhibitors cycloheximide and actinomycin D. Enhanced 3H-thymidine release from TX-treated targets was also demonstrated after induction of Ca2+ influx by exposure to the ionophore A23187. Neither E2 nor TX exerted a direct cytotoxic effect on P815 cells. P815 cells had no classical receptors for E2 or progesterone. © 1996 Wiley-Liss, Inc.
The immunoglobulin heavy chain switch: structural features of gamma 1 recombinant switch regions. (1987)

The immunoglobulin heavy chain isotype switch is mediated by a DNA rearrangement involving specific genomic segments referred to as switch regions. Switch regions are composed of tandemly repeated simple sequences. The role of the tandemly repeated structure of switch regions in the switch recombination process is not understood. We mapped eight recombination sites--six in the gamma 1 and two in the gamma 3 tandem arrays. In addition, we obtained molecular clones representing three of the six gamma 1 rearrangements, and determined the nucleotide sequences of the recombination sites in each. In general, the rearrangements are confined to the tandem repeat units, and are not clustered in a particular portion of either the gamma 3 or gamma 1 switch region. Nucleotide sequence analysis of one of the recombinant clones, gamma M35, reveals evidence for a successive switch event wherein a recombination between S mu and S gamma 3 was followed by recombination 57 bp downstream with S gamma 1. gamma 1 sequence data from the molecular clones we obtained, together with similar data from other investigators regarding the gamma 1, gamma 2b, and gamma 2a switch regions, reveals that recombinations tend to occur at homologous positions of the respective gamma-unit repeats, adjacent to the elements AGCT and GGGG found in each. This finding suggests that the cutting and religation step of the recombination process is mediated by a recombinase common to the four gamma-isotypes.
The effects of substrate temperature on the donor ionization energy and on the material properties of selectively doped short-period GaAs:Si/AlAs superlattices (1987)

The effects of substrate temperature on the donor ionization energy and on the electrical and photoluminescent properties of selectively doped short-period GaAs:Si/AlAs superlattices are studied. The superlattice structure is characterized by means of double-crystal x-ray diffraction. It is found that the interface between the GaAs and AlAs layers slightly degrades even at a low substrate temperature of 550 °C, and that the degradation is enhanced with an increase in the substrate temperature. The Si donor level is still shallow for substrate temperatures lower than 600 °C, since only a slight degradation occurs in this temperature range. However, the Si donor forms an excess deep DX center near the interface region for higher substrate temperatures. Accordingly, the donor binding energy increases with increasing substrate temperature, since the contribution from the mixed interface region becomes larger. With an increase in the substrate temperature, the photoluminescence peak intensity increases, although the electron concentration at room temperature decreases. This phenomenon is discussed in relation to the formation of donorlike deep levels in AlAs/GaAs short-period superlattices.
Quick tuning of a reference locomotion gait [computer animation] (2002)

This paper presents a comprehensive system for adaptive replay of a computer animation sequence featuring the locomotion of a synthetic animal. The kinematic locomotion gait, which is supposed to be mostly stationary, is tuned before being injected on the dynamic model of the animated animal. The animator can take benefit from this new flexibility in order to fulfil some goals, like steering the animal towards a target. The reference gait kinematic trajectories are expanded on a wavelet redundant bases, and tuned through varying the wavelet parameters. Because the optimization process is time-consuming, we propose to carry-out all optimizations beforehand and send the outcomes in a training set for a neural network, whose role is to compress data and to interpolate in between the training samples. At runtime, the network emulates the behaviour of the optimization process and automatically tailors the gait parameters. This approach paves the way towards the definition of a ready-to-use model for animated gaits.< <ETX xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">&gt;</ETX>
Injury Prevention: Drowning (1989)

<i>Sir</i>.—At the end of her editorial in the June 1988 issue of<i>AJDC</i>, Dr Noyes<sup>1</sup>recommends the formation of several national coalitions to attack the most commonly encountered injuries to children. One of her suggestions is to form a Child Pool Safety Group composed of "health care workers along with swimming pool manufacturers, YMCAs, YWCAs, and others." Such a group is already in existence. Encumbered with an awkward title, the National Swimming Pool Safety Committee has been in existence since 1985. It was organized by the Consumer Product Safety Commission (CPSC) and the National Spa and Pool Institute, the swimming pool industry's trade organization. Specific injuries targeted were childhood drownings and diving accidents. Membership on the various working committees has included representatives of the YMCA, the American Red Cross, and the National Safety Council, as well as attorneys, consumer advocates, educators, and physicians. As part of their work,
Differential type I interferon activation and susceptibility of dendritic cell populations to porcine arterivirus (2006)

Dendritic cells (DCs) play a role in anti-viral immunity by providing early innate protection against viral replication and by presenting antigen to T cells for initiation of the adaptive immune response. Studies show the adaptive response to porcine reproductive and respiratory syndrome virus (PRRSV) is ineffective for complete viral elimination. Other studies describe the kinetics of the adaptive response to PRRSV, but have not investigated the early response by DCs. We hypothesize that there is an aberrant activation of DCs early in PRRSV infection; consequently, the adaptive response is triggered inadequately. The current study characterized a subtype of porcine lung DCs (L-DCs) and investigated the ability of PRRSV to infect and replicate in L-DCs and monocyte-derived DCs (MDDCs). Furthermore, the type I interferon anti-viral response to PRRSV with and without the addition of recombinant porcine IFN-alpha (rpIFN-alpha), an important cytokine that signals for anti-viral mediator activation, was analysed. Results show that PRRSV replicated in MDDCs but not L-DCs, providing evidence that these cells have followed distinct differentiation pathways. Although both cell types responded to PRRSV with an induction of IFN-beta mRNA, the magnitude and duration of the response differed between cell types. The addition of rpIFN-alpha was protective in MDDCs, and mRNA synthesis of Mx (myxovirus resistant) and PKR (double-stranded RNA dependent protein kinase) was observed in both cell types after rpIFN-alpha addition. Overall, PRRSV replicated in MDDCs but not L-DCs, and rpIFN-alpha was required for the transcription of protective anti-viral mediators. DC response to PRRSV was limited to IFN-beta transcription, which may be inadequate in triggering the adaptive immune response.
Antioxidant activity of soya hypocotyl tea in humans (2000)

Antioxidative activity of isoflavones has not been shown in humans. Newly-developed isoflavone-rich soya hypocotyl tea contains about 12 mg isoflavones per liter. 15 tea drinkers and 23 control young female students were randomly selected from volunteers, and underwent physical examination, blood chemistry and urinary analysis before and after one month of tea drinking. A three-day dietary record was taken before each physical examination. The tea drinkers showed a lower level of phosphatidylcholine hydroperoxide (PCOOH) and phosphatidyl-ethanolamine hydroperoxide (PEOOH) in the red blood cells and a significant reduction of 8-hydroxydeoxyguanine (8ohdG) in the urine compared to the controls.
Identification and transfer of spatial transcriptomics signatures for cancer diagnosis (2020)

This concept study suggest that the ST signatures learned from expert selected breast cancer tissue sections can be used to identify breast cancer regions in whole tissue sections including regions not trained on. Furthermore, the identified expression signatures can classify cancer regions in tissue sections not used for training with high accuracy. Expert-generated but even automatically generated cancer signatures from ST data might be able to classify breast cancer regions and provide clinical decision support for pathologists in the future.
Role of Sensory Stimulation in Amelioration of Obstructive Sleep Apnea (2011)

Obstructive sleep apnea (OSA), characterized by recurrent upper airway (UA) collapse during sleep, is associated with significant morbidity and disorders. Polysomnogram is employed in the evaluation of OSA and apnea-hypopnea number per hour reflects severity. For normal breathing, it is essential that the collapsible UA is patent. However, obstruction of the UA is quite common in adults and infants. Normally, important reflex mechanisms defend against the UA collapse. The muscle activity of UA dilators, including the genioglossus, tensor palatini (TP), and pharyngeal constrictors, is due to the integrated mechanism of afferent sensory input → to motor function. Snoring is harsh breathing to prevent UA obstruction. Unfortunately, snoring vibrations, pharyngeal suction collapse, negative pressure, and hypoxia cause pathological perturbations including dysfunctional UA afferent sensory activity. The current paper posits that peripheral sensory stimulation paradigm, which has been shown to be efficacious in improving several neurological conditions, could be an important therapeutic strategy in OSA also.
Cheyne-Stokes Respiration Presenting as Sleep Apnea Syndrome: Clinical and Polysomnographic Features (1990)

This study reports polysomnographic features of five patients with Cheyne-Stokes respiration (CSR). They were referred for evaluation of presumptive sleep apnea syndrome on the basis of history and physical examination, but were found to have predominantly CSR on all-night sleep study. On the initial polysomnographic study, CSR comprised 47 to 86% of all disordered-breathing events. Cheyne-Stokes respiration resulted in considerable oxyhemoglobin desaturation (mean baseline saturation was 95 +/- 4 +/- SD, and lowest saturation was 76 +/- 8). More than one-half of all CSR events resulted in awakenings or arousals. Evidence of upper airway obstruction was noted in the majority of CSR events in three of five patients. Four patients were treated with theophylline; one who refused drug therapy was treated with nasal continuous positive airway pressure (CPAP). Comparison of sleep studies before and after therapy showed a significant decrease in the CSR index (29 +/- 11 versus 2 +/- 2) and in the maximal oxyhemoglobin desaturation associated with CSR (13 +/- 5 versus 3 +/- 2), and an improvement in lowest O2 saturation associated with CSR (76 +/- 8 versus 91 +/- 4). Total disruptions in sleep architecture per hour of sleep improved significantly with therapy (46 +/- 21 versus 20 +/- 8). We conclude that the clinical presentation of CSR can be indistinguishable from that of the "traditional" sleep apnea hypopnea syndrome and can result in major oxyhemoglobin desaturation and sleep fragmentation. Theophylline results in considerable improvement in the disordered breathing of CSR during sleep.