gebhart/patrepeval huggingface dataset:
CTLA-4 and PD-1/PD-L1 Blockade: New Immunotherapeutic Modalities with Durable Clinical Benefit in Melanoma Patients (2013)

Immune checkpoint blockade with monoclonal antibodies directed at the inhibitory immune receptors CTLA-4, PD-1, and PD-L1 has emerged as a successful treatment approach for patients with advanced melanoma. Ipilimumab is the first agent associated with a documented improved overall survival benefit in this patient population. A striking attribute of CTLA-4 blockade is the durability of objective responses, leading to speculation of a possible cure for some patients. Many tumor responses achieved with PD-1 and PD-L1 inhibition were durable in the phase I trials and were seen in a higher proportion of patients with melanoma than typically observed with ipilimumab. Biomarker development to identify the subset of patients with melanoma who will achieve durable clinical benefit with checkpoint blockade is critical; tumor PD-L1 expression has been promising in early studies. The contrast between unprecedented response rates but limited durability of responses achieved with BRAF and MEK inhibition in BRAF(V600)-mutated melanoma and the impressive durability but relatively low rate of response achieved with immune checkpoint blockade is striking. Preclinical data on potential synergies between CTLA-4/PD-1/PD-L1 inhibition and MAPK-targeted therapy is emerging, and combined immune checkpoint blockade and MAPK inhibition are being explored in clinical trials. Other promising approaches to increase the number of patients with melanoma who benefit from durable responses with immune checkpoint blockade include concurrent or sequenced CTLA-4 and PD-1/PD-L1 inhibition and combination with other immunotherapeutic strategies. Clin Cancer Res; 19(19); 5300-9. ©2013 AACR.
Fiber phase conjugators for high-power lasers (1998)

Using stimulated Brillouin-scattering (SBS) in glass fibers as phase-conjugating process, the field of application of SBS phase-conjugators can be expanded, because fibers offer a decreased power threshold and a stable behavior even at high input powers. We have developed phase conjugators consisting of multimode fused silica fibers in standard or tapered geometry with core diameters between 25 and 400 &mu;m. Such fiber phase conjugators were characterized for different lengths in respect of the phase conjugating parameters like threshold, reflectivity, and fidelity. Dependencies of all SBS parameters on the fiber length and on the coherence length of the input beams were determined. Such optimized fiber phase conjugators operate with more than 50% reflectivity, 93% fidelity, and less than 200 W threshold in the spectral range from IR down to the UV. A depolarization of SBS pulses could be reduced to less than 0.3% by proper configuration of the fiber. High power densities of more than 1 GW/cm<SUP>2</SUP> do not damage our fiber phase conjugators, because the absorption of the fiber materials used is very low. Furthermore, fiber phase conjugators are harmless to the environment and beat the performance of dangerous liquid or high pressure gas SBS- cells used in high power lasers up to now in all concerns. High economic benefits can be expected due to the popular fiber materials used from the glass fiber technology.
Estrogen-Mediated Endothelial Progenitor Cell Biology and Kinetics For Physiological Postnatal Vasculogenesis (2007)

Estrogen has been demonstrated to promote therapeutic reendothelialization after vascular injury by bone marrow (BM)-derived endothelial progenitor cell (EPC) mobilization and phenotypic modulation. We investigated the primary hypothesis that estrogen regulates physiological postnatal vasculogenesis by modulating bioactivity of BM-derived EPCs through the estrogen receptor (ER), in cyclic hormonally regulated endometrial neovascularization. Cultured human EPCs from peripheral blood mononuclear cells (PB-MNCs) disclosed consistent gene expression of ER alpha as well as downregulated gene expressions of ER beta. Under the physiological concentrations of estrogen (17beta-estradiol, E2), proliferation and migration were stimulated, whereas apoptosis was inhibited on day 7 cultured EPCs. These estrogen-induced activities were blocked by the receptor antagonist, ICI182,780 (ICI). In BM transplanted (BMT) mice with ovariectomy (OVX) from transgenic mice overexpressing beta-galactosidase (lacZ) regulated by an endothelial specific Tie-2 promoter (Tie-2/lacZ/BM), the uterus demonstrated a significant increase in BM-derived EPCs (lacZ expressing cells) incorporated into neovasculatures detected by CD31 immunohistochemistry after E2 administration. The BM-derived EPCs that were incorporated into the uterus dominantly expressed ER alpha, rather than ER beta in BMT mice from BM of transgenic mice overexpressing EGFP regulated by Tie-2 promoter with OVX (Tie-2/EGFP/BMT/OVX) by ERs fluorescence immunohistochemistry. An in vitro assay for colony forming activity as well as flow cytometry for CD133, CD34, KDR, and VE-cadherin, using human PB-MNCs at 5 stages of the female menstrual-cycle (early-proliferative, pre-ovulatory, post-ovulatory, mid-luteal, late-luteal), revealed cycle-specific regulation of EPC kinetics. These findings demonstrate that physiological postnatal vasculogenesis involves cyclic, E2-regulated bioactivity of BM-derived EPCs, predominantly through the ER alpha.
CEDA: Control-flow Error Detection through Assertions (2006)

This paper presents an efficient software technique, control flow error detection through assertions (CEDA), for online detection of control flow errors. Extra instructions are automatically embedded into the program at compile time to continuously update run-time signatures and to compare them against pre-assigned values. The novel method of computing run-time signatures results in a huge reduction in the performance overhead, as well as the ability to deal with complex programs and the capability to detect subtle control flow errors. The widely used C compiler, GCC, has been modified to implement CEDA, and the SPEC benchmark programs were used as the target to compare with earlier techniques. Fault injection experiments were used to evaluate the fault detection capabilities. Based on a new comparison metric, method efficiency, which takes into account both error coverage and performance overhead, CEDA is found to be much better than previously proposed methods
Can Stroke Cause Neurodegenerative Dementia? (2011)

Stroke and dementia have typically been housed in different taxonomies. They are considered to be exemplars of very different forms of brain injury: stroke as an acute vascular injury and dementia as a progressive degenerative disease. Yet there is definite overlap between the two conditions: stroke increases the likelihood of developing dementia. Recent work has confirmed that vascular risk factors such as diabetes and hypertension predispose to dementia. However, in the absence of any clear findings of a direct pathway from stroke to degenerative dementia, the separation has persisted. In this review, we summarize the evidence relating to whether stroke can initiate or promote degenerative dementia and, in particular, Alzheimer's disease. The evidence comes from autopsy studies, from brain imaging studies, from studies of patients with symptomatic stroke and from studies in CADASIL. A number of studies have demonstrated that stroke can lead to changes in brain volume and cognitive performance, although generally of a different profile to the atrophy and cognitive decline seen in Alzheimer's disease. Much of the evidence is circumstantial, and does little to support a claim that stroke triggers neurodegenerative dementia. The question, then, remains open. None of the studies reviewed included the necessary longitudinal follow-up of stroke patients incorporating cognitive assessment, imaging and pathology. Given the high prevalence and substantial burden of dementia, there is much to be gained from identifying prognostic markers and it remains an exciting idea that we might be able to identify a subgroup of stroke patients who are at high risk.
Comparison of Esophageal Pressure with Pulse Transit Time as a Measure of Respiratory Effort for Scoring Obstructive Nonapneic Respiratory Events (2000)

Obstructive nonapneic respiratory events (ONAREs) are much more difficult to detect and classify than apneas unless sensitive measures of respiratory effort and airflow are employed. The aim of this study was to compare two measures of respiratory effort, esophageal pressure monitoring (Pes) and pulse transit time (PTT), for scoring of ONAREs by visual analysis. Nine men (age 49 +/- 10 yr) with mild to moderate sleep apnea syndrome (AHI of 25.1 +/- 10. 8/h) were studied and 340 ONAREs (hypopneas and upper airway resistance episodes) were randomly selected for scoring by two experienced observers. Each observer blindly scored each ONARE twice (once with Pes and once with PTT) with a concurrent pneumotachography trace available for airflow quantification. This permitted the respiratory events scored with PTT to be compared with those scored with Pes, and in addition interobserver variability could be assessed for each signal. Even though standard criteria were used for scoring, there was significant interobserver variability for both Pes (29.7%) and PTT (37.1%). Taking those events for which there was agreement between the observers, PTT had a sensitivity of 79.9% and a positive predictive value of 91.2% (using Pes as the gold standard). In those ONAREs for which there was agreement between the two observers there was a larger percentage reduction in airflow compared to ONAREs that did not concur (51 versus 30.3%, p < 0.001), a larger increase in respiratory effort as assessed by PTT (slope of PTT: 23.1 versus 14. 3 arbitrary units, p < 0.01), and a higher incidence in autonomic microarousals detected with PTT (90 versus 45% of ONAREs, p < 0.006). Subtle respiratory events are more difficult to detect than apneas or frank hypopneas. When comparing PTT with esophageal pressure in detecting those events the sensitivity of PTT is good but limited when the reduction in airflow, the increase in respiratory effort, or the arousal reaction is the less clear. However, PTT appears to be a good noninvasive alternative to Pes in the detection of nonapneic obstructive respiratory events, and its ability to detect autonomic arousal gives this physiological signal added clinical usefulness.
Adult Spinal Cord Stem Cells Generate Neurons after Transplantation in the Adult Dentate Gyrus (2000)

The adult rat spinal cord contains cells that can proliferate and differentiate into astrocytes and oligodendroglia in situ. Using clonal and subclonal analyses we demonstrate that, in contrast to progenitors isolated from the adult mouse spinal cord with a combination of growth factors, progenitors isolated from the adult rat spinal cord using basic fibroblast growth factor alone display stem cell properties as defined by their multipotentiality and self-renewal. Clonal cultures derived from single founder cells generate neurons, astrocytes, and oligodendrocytes, confirming the multipotent nature of the parent cell. Subcloning analysis showed that after serial passaging, recloning, and expansion, these cells retained multipotentiality, indicating that they are self-renewing. Transplantation of an in vitro-expanded clonal population of cells into the adult rat spinal cord resulted in their differentiation into glial cells only. However, after heterotopic transplantation into the hippocampus, transplanted cells that integrated in the granular cell layer differentiated into cells characteristic of this region, whereas engraftment into other hippocampal regions resulted in the differentiation of cells with astroglial and oligodendroglial phenotypes. The data indicate that clonally expanded, multipotent adult progenitor cells from a non-neurogenic region are not lineage-restricted to their developmental origin but can generate region-specific neurons in vivo when exposed to the appropriate environmental cues.
A MEMS-based Air Flow Sensor with a Free-standing Micro-cantilever Structure (2007)

This paper presents a micro-scale air flow sensor based on a free-standingcantilever structure. In the fabrication process, MEMS techniques are used to deposit asilicon nitride layer on a silicon wafer. A platinum layer is deposited on the silicon nitridelayer to form a piezoresistor, and the resulting structure is then etched to create afreestanding micro-cantilever. When an air flow passes over the surface of the cantileverbeam, the beam deflects in the downward direction, resulting in a small variation in theresistance of the piezoelectric layer. The air flow velocity is determined by measuring thechange in resistance using an external LCR meter. The experimental results indicate that theflow sensor has a high sensitivity (0.0284 ω/ms<sup>-1</sup>), a high velocity measurement limit (45ms<sup>-1</sup>) and a rapid response time (0.53 s).
Elevated expression of TGF‐β1 in head and neck cancer–associated fibroblasts (2004)

Head and neck cancers are characterized by a vigorous desmoplastic response, but the contribution of stromal-derived growth factors to the tumor microenvironment is poorly understood. We evaluated the expression of stromal growth factor expression in head and neck squamous cell carcinoma (HNSCC) in normal and tumor-associated stromal cells. Stromal tissue was isolated from epithelial cells with laser capture microdissection (LCMD) and analyzed by cDNA array for the expression of TGFalpha, TGF-beta1, HGF, PDGF-alpha, IGFII, bFGF, aFGF, VEGFC, and VEGF. Primary fibroblasts were isolated in vitro from HNSCC tumors, adjacent histologically normal mucosa, and skin in vitro. Fibroblast populations were assessed for TGF-beta1 expression by ELISA and luciferase reporter assay to assess protein expression. We identified TGF-beta1 and IGFII overexpression in normal and tumor-associated stromal cells; however, only TGF-beta1 was significantly overexpressed (3.4-fold) in tumor-associated stroma. Assessment of carcinoma-associated fibroblasts (CAFs), normal dermal fibroblasts (NDFs), and normal mucosal fibroblasts (NMFs) in propagated fibroblasts demonstrated persistently elevated levels of TGF-beta1 in CAFs compared to NMF and NDF populations. Elevated levels of TGF-beta1 were identified in the stromal compartment of HNSCC tumors compared to normal mucosa by immunohistochemical analysis. These results suggest that TGF-beta1 mRNA and protein is specifically upregulated in CAFs in vitro and in vivo.
Determination of leucocyte antibody binding capacity (ABC): the need for standardization (1998)

The flow cytometric determination of antigen density, or cellular antibody binding capacity, is now an accepted technique for the characterization of cells in health and disease. In HIV infection, for example, antigen density changes in CD38 expression may be an important indicator of disease progression. Our experience of using one such method, Quantum Simply Cellular, which measures antibody binding capacity (ABC), has highlighted several technical factors which can affect the results. We report the influence of pH, incubation temperature and time, antibody fluorochrome and titre, as well as lysing reagent (FACS Lysing Solution v. Ortho-mune Lysing Reagent) on the ABC of anti-CD3, CD4 and CD8 of normal lymphocytes. In addition, the effect of single, double or triple-staining was assessed. The results indicate that the ABC values are influenced by all the variables studied. The pH range tested (6.0-9.0) demonstrated that pH 7.4 gave maximal binding. Furthermore, temperature also influenced the pH of the two lysing solutions, and thus potentially the ABC. Antibody concentration, fluorochrome and staining technique are also important factors with an observed difference of up to 458,855 ABC between the various fluorochromes. In addition a maximal difference of 130,119 ABC was observed between single and triple staining techniques. In conclusion, if antigen quantification is to be used in the clinical setting, an internationally standardized method is required to ensure the reproducibility of results from centre to centre. Our data suggests that single staining, using fluorescein isothiocynate (FITC) conjugated antibodies with all reagents at pH 7.4 + 0.1, with incubation and lysing carried out at 20 + 1 degrees C, could be used as a 'benchmark' method for ABC determination using the QSC system.
Asymmetric multilevel outphasing architecture for multi-standard transmitters (2009)

We describe a new outphasing transmitter architecture in which the supply voltage for each PA can switch among multiple levels. It is based on a new asymmetric multilevel outphasing (AMO) modulation technique which increases overall efficiency over a much wider output power range than the standard LINC system while maintaining high linearity. For demonstration, the overall transmitter is simulated in a 65 nm CMOS process with HSUPA and WLAN signals. The simulation results show an efficiency improvement from 17.7% to 40.7% for HSUPA at 25.3 dBm output power and from 11.3% to 35.5% for WLAN 802.11g at 22.8 dBm while still meeting system linearity requirements.
Recombinant polyepitope vaccines for the delivery of multiple CD8 cytotoxic T cell epitopes (1996)

Development of epitope-based CD8 alpha beta CTL vaccines requires effective strategies for codelivery of large numbers of individual epitopes. We have designed an artificial "polyepitope" protein containing 10 contiguous minimal CTL epitopes, which were restricted by five MHC alleles and derived from five viruses, a parasite, and a tumor model. A recombinant vaccinia virus coding for this protein was capable of inducing MHC-restricted primary CTL responses to all 10 epitopes. Mice immunized with this recombinant vaccinia showed protection against murine cytomegalovirus, Sendai virus, and a tumor model. This simple generic approach to multiepitope delivery should find application in CTL-based vaccine design.
Pulmonary and Systemic Oxidant/Antioxidant Imbalance in Chronic Obstructive Pulmonary Disease (2005)

An imbalance between oxidants and antioxidants is considered to play a role in the pathogenesis of chronic obstructive pulmonary disease (COPD). There is considerable evidence that an increased oxidative burden occurs in the lungs of patients with this disorder, and this may be involved in many of the pathogenic processes, such as direct injury to lung cells, mucus hypersecretion, inactivation of antiproteases, and enhancing lung inflammation through activation of redox-sensitive transcription factors. COPD is now recognized to have multiple systemic consequences, such as weight loss and skeletal muscle dysfunction. Moreover, it is appreciated that oxidative stress extends beyond the lung and may, through similar oxidative stress mechanisms as those in the lung, contribute to several of the systemic manifestations in COPD.
Demethylation of the FOXP3 gene in human melanoma cells precludes the use of this epigenetic mark for quantification of Tregs in unseparated melanoma samples (2011)

The human suppressive T cells that stably express transcription factor FOXP3, or regulatory T cells (Tregs), are thought to suppress antitumor immune responses. The most specific marker for human Tregs is the demethylation of CpG dinucleotides located in the first intron of FOXP3 (FOXP3i1). FOXP3i1 is completely methylated in other hematopoietic cells, including nonsuppressive T cells that transiently express FOXP3 after activation. Previously, we and others reported estimations of the frequency of Tregs in the blood of melanoma patients using a FOXP3i1 methylation-specific qPCR assay. Here, we attempted to quantify Tregs inside tumor samples using this assay. However, we found demethylated FOXP3i1 sequences in the melanoma cells themselves. This demethylation was not associated with substantial FOXP3 mRNA or protein expression, even though the demethylation extended to the promoter and terminal regions of the gene in some melanoma cells. Our results imply that analyzing Treg frequencies by quantification of demethylated FOXP3i1 will require that tumor-infiltrating T cells be separated from melanoma cells.
Temperature-sensitive yeast mutants defective in mitochondrial inheritance. (1990)

The distribution of mitochondria to daughter cells is an essential feature of mitotic cell growth, yet the molecular mechanisms facilitating this mitochondrial inheritance are unknown. We have isolated mutants of Saccharomyces cerevisiae that are temperature-sensitive for the transfer of mitochondria into a growing bud. Two of these mutants contain single, recessive, nuclear mutations, mdm1 and mdm2, that cause temperature-sensitive growth and aberrant mitochondrial distribution at the nonpermissive temperature. The absence of mitochondria from the buds of mutant cells was confirmed by indirect immunofluorescence microscopy and by transmission electron microscopy. The mdm1 lesion also retards nuclear division and prevents the transfer of nuclei into the buds. Cells containing the mdm2 mutation grown at the nonpermissive temperature sequentially form multiple buds, each receiving a nucleus but no mitochondria. Neither mdm1 or mdm2 affects the transfer of vacuolar material into the buds or causes apparent changes in the tubulin- or actin-based cytoskeletons. The mdm1 and mdm2 mutations are cell-cycle specific, displaying an execution point in late G1 or early S phase.
Effects of α-MSH on ischemia/reperfusion injury in the rat sciatic nerve (2012)

The results confirm that pre-treatment with α-MSH after ischemia protected the peripheral nerves against I/R injury.
A genetic polymorphism of a human urinary mucin (1983)

We report here a novel genetically determined polymorphism of a human urinary mucin which is demonstrable by the separation technique of SDS polyacrylamide gel electrophoresis, followed by detection with radio-iodinated lectins. The mucins are demonstrable using various lectins but the polymorphism is most easily recognized using peanut agglutinin and we therefore propose to designate this new genetic locus PUM (peanut-reactive urinary mucin). Four common alleles have been identified and an autosomal codominant mode of inheritance has been found in the families studied so far.
-Autolink- A Tool for the Automatic and Semi-Automatic Test Generation. (1997)

Due to increasing interest in validation and test generation tools, Telelogic AB, Malmo, and the Institute for Telematics of the University of Lubeck have started a research and development project which aims at bringing new test generation facilities to the Tau tool set. For that purpose, a software component is developed which supports the automatic and semi-automatic generation of TTCN test suites based on SDL specifications and MSC test cases. The project follows a pragmatic approach and is driven by practical experience. Autolink is currently used by the Project Team 100 at the European Telecommunications Standardisation Institute (ETSI), where it has to prove its usefulness in everyday work. 1 Introduction Autolink is part of Tau, a commercial product by Telelogic AB, Malmo. Tau combines the two well-known tool sets SDT and ITEX. It provides tools for the formal design, implementation and testing of communicating systems software. In particular, it supports the use of the speci...