gebhart/patrepeval huggingface dataset:
Engineering of head-mounted projective displays (2000)

Head-mounted projective displays (HMPD's) are a novel type of head-mounted display. A HMPD consists of a miniature projection lens mounted upon the user's head and retroreflective sheeting material placed strategically in the environment. First, the imaging concept of a HMPD is reviewed and its potential advantages and disadvantages are discussed. The design and a bench prototype implementation are then presented. Finally, the effects of retroreflective materials on the imaging properties and the optical properties of HMPD's are comprehensively investigated.
Amifostine, cisplatin, and vinblastine in metastatic non-small-cell lung cancer: a report of high response rates and prolonged survival. (1996)

ACV appears to be a highly active regimen in metastatic NSCLC. Acute toxicities were generally reversible and the data suggest that amifostine may protect against long-term renal insufficiency from cumulative doses of cisplatin. Although the sample size of this trial is small, the results are significantly encouraging to warrant confirmation in randomized multiinstitutional trials.
Whole body sweat collection in humans: an improved method with preliminary data on electrolyte content (1997)

Previous methods used to collect human sweat for electrolyte analysis have been criticized because they involve only regional sampling or because of methodological problems associated with whole body-washdown techniques. An improved method for collection of whole body sweat from exercising subjects is described. It involved construction of a plastic frame that supports a large plastic bag within which the subject exercises. The subject and the equipment are washed with distilled, deionized water before exercise begins. After exercise is completed, the subject and equipment are again washed with water containing a marker not present in sweat (ammonium sulfate). Total sweat loss is calculated from the change in body mass, and the volume of sweat not evaporated is calculated from dilution of the added marker. Recovery of added water was 102 +/- 2% (SD) of the added volume, and recovery of added electrolytes was 99 +/- 2% for sodium, 98 +/- 9% for potassium, and 101 +/- 4% for chloride. Repeated trials (n = 4) on five subjects to establish the reproducibility of the method gave a coefficient of variation of 17 +/- 5% for sodium, 23 +/- 6% for potassium, and 15 +/- 6% for chloride. These values include the biological variability between trials as well as the error within the method. The biological variability thus appears to be far greater than the methodological error. Normal values for the composition of sweat induced by exercise in a hot, humid environment in healthy young men and women were (in mM) 50.8 +/- 16.5 sodium, 4.8 +/- 1.6 potassium, 1.3 +/- 0.9 calcium, 0.5 +/- 0.5 magnesium, and 46.6 +/- 13.1 chloride.
Absorption spectroscopy in tissue-simulating materials: a theoretical and experimental study of photon paths (1995)

A diffusion model of noninvasive absorption spectroscopy was used to determine how the change in signal resulting from a point absorber depends on the position of that absorber relative to the source and detector. This is equivalent to calculating the relative probability that a photon will visit a certain location in tissue before its detection. Experimental mapping of the point-target response in tissue-simulating materials confirmed the accuracy of the model. For steady-state spectroscopy a simple relation was derived between the mean depth visited by detected photons, the source-detector separation, and the optical penetration depth. It was also demonstrated theoretically that combining a pulsed source with time-gated detection provides additional control over the spatial distribution of the photon-visit probability.
Design of multilayer extreme-ultraviolet mirrors for enhanced reflectivity (2000)

We show numerically that the reflectivity of multilayer extreme-UV (EUV) mirrors tuned for the 11-14-nm spectral region, for which the two-component, Mo/Be and Mo/Si multilayer systems with constant layer thickness are commonly used, can be enhanced significantly when we incorporate additional materials within the stack. The reflectivity performance of the quarter-wavelength multilayers can be enhanced further by global optimization procedures with which the layer thicknesses are varied for optimum performance. By incorporating additional materials of differing complex refractive indices-e.g., Rh, Ru, Sr, Pd, and RbCl-in various regions of the stack, we observed peak reflectivity enhancements of as much as ~5% for a single reflector compared with standard unoptimized stacks. We show that, in an EUV optical system with nine near-normal-incidence mirror surfaces, the optical throughput may be increased by a factor as great as 2. We also show that protective capping layers, in addition to protecting the mirrors from environmental attack, may serve to improve the reflectivity characteristics.
Stochastic Modeling of an Automated Guided Vehicle System With One Vehicle and a Closed-Loop Path (2008)

The use of automated guided vehicles (AGVs) in material-handling processes of manufacturing facilities and warehouses is becoming increasingly common. A critical drawback of an AGV is its prohibitively high cost. Cost considerations dictate an economic design of AGV systems. This paper presents an analytical model that uses a Markov chain approximation approach to evaluate the performance of the system with respect to costs and the risk associated with it. This model also allows the analytic optimization of the capacity of an AGV in a closed-loop multimachine stochastic system. We present numerical results with the Markov chain model which indicate that our model produces results comparable to a simulation model, but does so in a fraction of the computational time needed by the latter. This advantage of the analytical model becomes more pronounced in the context of optimization of the AGV's capacity which without an analytical approach would require numerous simulation runs at each point in the capacity space.
Node Representation Learning for Multiple Networks: The Case of Graph Alignment. (2018)

Recent advances in representation learning produce node embeddings that may be used successfully in many downstream tasks (e.g., link prediction), but do not generally extend beyond a single network. Motivated by the prevalence of multi-network problems, such as graph alignment, similarity, and transfer learning, we introduce an elegant and principled node embedding formulation, Cross-network Matrix Factorization or xNetMF, to effectively and efficiently learn embeddings from similarities based on the nodes' structural and attribute identities (if available), which are comparable across networks. Leveraging the Nystr\om method for low-rank approximation, we achieve significant reduction in space and time compared to the na\ive approach of directly factorizing the node similarity matrix, with xNetMF running up to 30x faster than existing representation learning methods. We study its effectiveness on the task of network alignment, and introduce REGAL (REpresentation-based Graph ALignment), the first method to use node representation learning for this task. Extensive experiments on a variety of challenging real-world networks with and without attributes show that REGAL outperforms existing network alignment methods by 20 to 30% in accuracy on average, uses attributes up to 40x faster, and scales to networks with millions of nodes each.
NVP-BEZ235, a Dual PI3K/mTOR Inhibitor, Prevents PI3K Signaling and Inhibits the Growth of Cancer Cells with Activating PI3K Mutations (2008)

Phosphatidylinositol-3-kinase (PI3K) pathway deregulation is a common event in human cancer, either through inactivation of the tumor suppressor phosphatase and tensin homologue deleted from chromosome 10 or activating mutations of p110-alpha. These hotspot mutations result in oncogenic activity of the enzyme and contribute to therapeutic resistance to the anti-HER2 antibody trastuzumab. The PI3K pathway is, therefore, an attractive target for cancer therapy. We have studied NVP-BEZ235, a dual inhibitor of the PI3K and the downstream mammalian target of rapamycin (mTOR). NVP-BEZ235 inhibited the activation of the downstream effectors Akt, S6 ribosomal protein, and 4EBP1 in breast cancer cells. The antiproliferative activity of NVP-BEZ235 was superior to the allosteric selective mTOR complex inhibitor everolimus in a panel of 21 cancer cell lines of different origin and mutation status. The described Akt activation due to mTOR inhibition was prevented by higher doses of NVP-BEZ235. NVP-BEZ235 reversed the hyperactivation of the PI3K/mTOR pathway caused by the oncogenic mutations of p110-alpha, E545K, and H1047R, and inhibited the proliferation of HER2-amplified BT474 cells exogenously expressing these mutations that render them resistant to trastuzumab. In trastuzumab-resistant BT474 H1047R breast cancer xenografts, NVP-BEZ235 inhibited PI3K signaling and had potent antitumor activity. In treated animals, there was complete inhibition of PI3K signaling in the skin at pharmacologically active doses, suggesting that skin may serve as surrogate tissue for pharmacodynamic studies. In summary, NVP-BEZ235 inhibits the PI3K/mTOR axis and results in antiproliferative and antitumoral activity in cancer cells with both wild-type and mutated p110-alpha.
High mobility, dual layer, c-axis aligned crystalline/amorphous IGZO thin film transistor (2015)

We demonstrate a dual layer IGZO thin film transistor (TFT) consisting of a 310 °C deposited c-axis aligned crystal (CAAC) 20 nm thick channel layer capped by a second, 30 nm thick, 260 °C deposited amorphous IGZO layer. The TFT exhibits a saturation field-effect mobility of ∼20 cm2/V s, exceeding the mobility of 50 nm thick single layer reference TFTs fabricated with either material. The deposition temperature of the second layer influences the mobility of the underlying transport layer. When the cap layer is deposited at room temperature (RT), the mobility in the 310 °C deposited CAAC layer is initially low (6.7 cm2/V s), but rises continuously with time over 58 days to 20.5 cm2/V s, i.e., to the same value as when the second layer is deposited at 260 °C. This observation indicates that the two layers equilibrate at RT with a time constant on the order of 5 × 106 s. An analysis based on diffusive transport indicates that the room temperature diffusivity must be of the order of 1 × 10−18 cm2 s−1 with an activation enthalpy EA < 0.2 eV for the mobility limiting species. The findings are consistent with a hypothesis that the amorphous layer deposited on top of the CAAC has a higher solubility for impurities and/or structural defects than the underlying nanocrystalline transport layer, and that the equilibration of the mobility limiting species is rate limited by hydrogen diffusion, whose known diffusivity fits these estimates.
Noncalcemic, Antiproliferative, Transcriptionally Active, 24-Fluorinated Hybrid Analogues of the Hormone 1α,25-Dihydroxyvitamin D3. Synthesis and Preliminary Biological Evaluation (1998)

Four new hybrid analogues of 1alpha,25-dihydroxyvitamin D3 (1) have been synthesized in a convergent manner by joining A-ring and C, D-ring fragments. Each hybrid analogue, having a noncalcemic 1-hydroxymethyl group and a potentiating 16-ene 24,24-difluorinated C,D-ring side chain, was designed to be lipophilic and inert toward 24-hydroxylase enzyme catabolism. Each hybrid analogue with 1beta, 3alpha-substituent stereochemistry (i.e., analogues 3b and 4b) showed a pharmacologically desirable combination of in vitro high antiproliferative activity in two different cell lines and high transcriptional activity with also low calcemic activity in vivo.
Protein Arrays: A Versatile Toolbox for Target Identification and Monitoring of Patient Immune Responses (2006)

Functional proteomics is a promising technique for the rational identification of novel therapeutic targets and biological markers. The studies of protein-protein interactions have been gained from the development of high-throughput technologies such as the yeast two-hybrid system, protein arrays, phage display, and systematic analysis of interaction maps for the prediction of protein functions. Because antibodies are used extensively as diagnostic and clinical tools, the characterization of their antigen specificity is of prime importance. Indeed, screening protein arrays with sera from patients with either cancer or autoimmune diseases would facilitate the identification of autoantibody signatures that can be used for diagnosis and/or prognosis of patients. The usefulness of multiplexed measurements lies not only in the ability to screen many individual marker candidates but also in evaluating the use of multiple markers in combination. Here, we review the advantage of protein and serum screening of peptides and cDNA repertoires displayed on phages as well as the fabrication of protein microarrays for probing immune responses in patients.
Maturation of the humoral autoimmune response to epitopes of GAD in preclinical childhood type 1 diabetes. (2000)

GAD is a major target of autoimmunity in preclinical type 1 diabetes. Here we examine the maturation of the humoral response to GAD epitopes sequentially from birth to diabetes onset or current follow-up in 29 GAD antibody (GADA)+ offspring of parents with diabetes from the BABYDIAB Study. Antibodies were measured against GAD65, GAD67, and GAD65/67 chimeras by radiobinding assay. In 28 of 29 offspring, the first GADAs contained reactivity against epitopes within GAD65 residues 96-444, suggesting that the middle GAD65 region is a primary target of GAD humoral autoimmunity. In 7 of these 28 offspring, initial antibody reactivity was against all epitope regions tested (middle GAD65, COOH-terminal GAD65 residues 445-585, NH2-terminal GAD65 residues 1-95, and GAD67); in 16 offspring, reactivity was to middle and COOH-terminal GAD65 epitopes, and in 5 offspring, reactivity was only to the middle GAD65 epitopes. The single offspring without middle GAD65 reactivity had antibodies to the NH2-terminal epitopes in the absence of all other islet autoimmunity. Subsequent GADA epitope spreading was frequent and seen in 10 of 15 offspring with informative follow-up samples. Spreading was mostly (eight cases) to NH2-terminal GAD65 epitopes. In two offspring, spreading to new epitopes was found when antibody titers to GAD65 and early epitopes were declining, suggesting determinant-specific regulation of the humoral response. None of the GADA reactivities nor any changes in reactivity over time were specifically associated with diabetes onset. The findings suggest that the humoral autoimmune response to GAD found in childhood is dynamic, is initially against epitopes within the middle portion of GAD65, and spreads to epitopes in other regions of GAD65 and GAD67.
Enzymatically Active Paraoxonase-1 Is Located at the External Membrane of Producing Cells and Released by a High Affinity, Saturable, Desorption Mechanism (2002)

Paraoxonase-1 (PON1) is a high density lipoprotein (HDL)-associated serum enzyme that protects low density lipoproteins from oxidative modifications. There is a relative lack of information on mechanisms implicated in PON1 release from cells. The present study focused on a model derived from stable transfection of CHO cells, to avoid co-secretion of apolipoprotein (apo) A-I and lipids, which could lead to formation of HDL-like complexes. Our results indicate that, in the absence of an appropriate acceptor, little PON1 is released. The results designate HDL as the predominant, physiological acceptor, whose efficiency is influenced by size and composition. Neither lipid-poor apoA-I or apoA-II nor low density lipoproteins could substitute for HDL. Protein-free phospholipid complexes promoted PON1 release. However, the presence of both apolipoprotein and phospholipid were necessary to promote release and stabilize the enzyme. Immunofluorescence studies demonstrated that PON1 was inserted into the external membrane of CHO cells, where it was enzymatically active. Accumulation of PON1 in the cell membrane was not influenced by the ability of the cell to co-secrete of apoA-I. Release appeared to involve desorption by HDL; human and reconstituted HDL promoted PON1 release in a saturable, high affinity manner (apparent affinity 1.59 +/- 0.3 microg of HDL protein/ml). Studies with PON1-transfected hepatocytes (HuH-7) revealed comparable structural features with the peptide located in a punctate pattern at the external membrane and enzymatically active. We hypothesize that release of PON1 involves a docking process whereby HDL transiently associate with the cell membrane and remove the peptide from the external membrane. The secretory process may be of importance for assuring the correct lipoprotein destination of PON1 and thus its functional efficiency.
Epitaxial Layers Grown with HCl Addition: A Comparison with the Standard Process (2006)

This DOI is not currently attached to any metadata records. DOIs can’t actually ever be deleted (they’re persistent), but sometimes our members create DOIs in error. We do have a process to approximate deletion which we follow only in rare cases where the DOI has been genuinely created in error, and most crucially, if the DOI has never been published anywhere online or in print and never otherwise distributed to or communicated with anyone (authors, readers, reviewers, etc.
Preliminary Results of the Combination of Bevacizumab and Weekly Paclitaxel in Advanced Melanoma (2008)

Our preliminary results suggest that the combination of bevacizumab and weekly paclitaxel is active and safe in patients with metastatic melanoma, warranting further investigation.
Dual-targeting anti-angiogenic cyclic peptides as potential drug leads for cancer therapy (2016)

Peptide analogues derived from bioactive hormones such as somatostatin or certain growth factors have great potential as angiogenesis inhibitors for cancer applications. In an attempt to combat emerging drug resistance many FDA-approved anti-angiogenesis therapies are co-administered with cytotoxic drugs as a combination therapy to target multiple signaling pathways of cancers. However, cancer therapies often encounter limiting factors such as high toxicities and side effects. Here, we combined two anti-angiogenic epitopes that act on different pathways of angiogenesis into a single non-toxic cyclic peptide framework, namely MCoTI-II (Momordica cochinchinensis trypsin inhibitor-II), and subsequently assessed the anti-angiogenic activity of the novel compound. We hypothesized that the combination of these two epitopes would elicit a synergistic effect by targeting different angiogenesis pathways and result in improved potency, compared to that of a single epitope. This novel approach has resulted in the development of a potent, non-toxic, stable and cyclic analogue with nanomolar potency inhibition in in vitro endothelial cell migration and in vivo chorioallantoic membrane angiogenesis assays. This is the first report to use the MCoTI-II framework to develop a 2-in-1 anti-angiogenic peptide, which has the potential to be used as a form of combination therapy for targeting a wide range of cancers.
Cytotoxic effects of the trifunctional bispecific antibody FBTA05 in ex-vivo cells of chronic lymphocytic leukaemia depend on immune-mediated mechanism (2011)

Monoclonal antibodies such as rituximab and alemtuzumab show considerable therapeutic efficacy in chronic lymphocytic leukaemia (CLL). Aiming to further improve antineoplastic efficacy, the trifunctional bispecific antibody FBTA05 was developed. FBTA05 is thought to function by simultaneously binding B cells and T cells by its variable regions and by recruiting FcγR-positive accessory immune cells by its intact Fc region. As it was previously shown that this antibody shows considerable cytotoxicity towards a spectrum of B-cell lymphoma cell lines, we here tested its potential efficacy ex vivo against malignant B-CLL cells. Therefore, we assessed the capacity of increasing concentrations of FBTA05 to bind to neoplastic cells, to induce cytotoxicity (comparing it with rituximab and alemtuzumab) and cytokine release. We evaluated the results with respect to the extent of CD20 expression, the effector:target cell ratio as well as with the patients' overall effector cell status. Thus, we show that, although FBTA05-elicited cytotoxicity was comparable with that induced by alemtuzumab, it considerably exceeded the antineoplastic effects of rituximab. Noteworthy, FBTA05 shows effective elimination of malignant B cells even if CD20 surface expression is low. Importantly, a high grade of cytotoxicity was associated with the induction of T-cell proliferation and the concomittant release of interferon-γ and interleukin-6, thus overcoming the detrimental effects of an unfavourable effector:target cell ratio. In conclusion, we here present novel evidence for the therapeutic efficacy of the trifunctional, bispecific antibody FBTA05 in CLL and provide evidence for the importance of immune-mediated mechanisms conveying the cytotoxic effects against malignant B lymphocytes.
A natural cytotoxic T cell response in a spontaneously regressing human melanoma targets a neoantigen resulting from a somatic point mutation (1999)

We have studied a case of human primary melanoma displaying the classical signs of a spontaneous regression in order to characterize potentially efficient anti-tumor T cell responses. In a previous series of experiments a unique TCR Vbeta16+ T cell was shown to be highly expanded at the tumor site. The corresponding clone was isolated in vitro and found to be a CD8+ cytotoxic T lymphocyte with a strong and selective cytolytic activity against the autologous tumor cell line. Here, we demonstrate that this predominant Vbeta16+ tumor-infiltrating lymphocyte recognizes a peptide encoded by a novel unconventional myosin class I gene. This peptide includes a mutation due to a single nucleotide substitution. The resulting Glu-->Lys replacement at position 911 of the coding sequence is critical to generate the recognized T cell epitope. These experiments demonstrate the existence of a natural tumor-specific cytolytic T cell response in a primary regressing human melanoma lesion.
Evidence for the multicentric origin of the sickle cell hemoglobin gene in Africa. (1984)

Previous studies of the Hpa I cleavage site-sickle cell hemoglobin gene linkage in various African populations suggested that the sickle gene arose independently more than once. In the present study we have performed restriction endonuclease haplotype analysis for the beta-globin-like gene cluster from four separate geographic areas in Africa, all of which possess the sickle gene. In Benin (Central West Africa) and Algeria (Arab North Africa) all chromosomes carrying the sickle gene possess an identical haplotype as defined by 11 different polymorphic restriction endonuclease sites within the 60-kilobase region of the beta-globin-like gene cluster. In the Central African Republic (Bantu-speaking Africa) and in Senegal (Atlantic West Africa) a very large proportion of the sickle gene chromosomes were associated with a haplotype specific for each country. Thus, three different haplotypes are shown to be associated with the sickle gene in Africa, and each is present at a very high frequency in geographically separate regions. Since the three haplotypes differ from each other by at least three sites residing both 5' and 3' to a putative hot spot for recombination, it is most likely that the sickle gene arose at least three times on separate preexisting chromosomal haplotypes. This may have implications for a better understanding of the variable nature of the expression of sickle cell anemia, because clinically relevant sequences (for example, gamma-globin gene regulatory sequences responsive to anemia) might be linked polymorphically to these haplotypes.