gebhart/patrepeval huggingface dataset:
Systematic analysis and prediction of genes associated with disorders on chromosome X (2022)

Abstract Disease gene discovery on chromosome (chr) X is challenging owing to its unique modes of inheritance. We undertook a systematic analysis of human chrX genes. We observe a higher proportion of disorder-associated genes and an enrichment of genes involved in cognition, language, and seizures on chrX compared to autosomes. We analyze gene constraints, exon and promoter conservation, expression and paralogues, and report 127 genes sharing one or more attributes with known chrX disorder genes. Using a neural network trained to distinguish disease-associated from dispensable genes, we classify 235 genes, including 121 of the 127, as having high probability of being disease-associated. We provide evidence of an excess of variants in predicted genes in existing databases. Finally, we report damaging variants in CDK16 and TRPC5 in patients with intellectual disability or autism spectrum disorders. This study predicts large-scale gene-disease associations that could be used for prioritization of X-linked pathogenic variants.
Multilayers of hydrogels loaded with microparticles: a fast and simple approach for microarray manufacturing (2009)

We present a novel and simple approach towards the creation of arrays of biomolecules for the multiplexed detection of biological interactions. Microarrays were obtained by cutting stacked layers of biofunctionalized polystyrene particle layers embedded in a permeable agarose matrix. Microparticles were therefore the vehicles for biorecognition. The three-dimensional constructs were obtained by consecutive dipping steps in a pre-gel solution. Our strategy enables the rapid manufacturing of a large number of array copies in a flexible manner and without any specialized instrumentation. Model binding assays for the detection of rabbit and mouse IgG were performed as a proof of concept using a fluorescence microscope for read-out. The limits of detection were in the low picomolar range for the sandwich assay while 1 IgG out of 50,000 background proteins could be detected in a reverse phase assay. Thus, without any assay optimization, sensitivities comparable to the ones usually observed for standard fluorescence-based assays were achieved with the particle/hydrogel array.
Fundamental studies on cationic polymerization. III. Extension of mechanism studies to homogenous systems (1963)

Abstract Fundamental studies of the cationic polymerizations of isobutylene has been extended to the n ‐pentane and carbon disulfide systems. The kinetic equation for the n ‐pentane system is more complex than for other solvent systems because simplifying assumptions (which were possible for methyl chloride, ethyl chloride, and vinyl chloride) do not appear to be valid here. However, in all systems studied, the molecular weight of the polymer is determined principally by two competing chain breaking processes; namely, chain transfer from polymer to monomer and chain transfer or termination involving the solvent. The solvent reaction is important in polar solvents, especially at higher temperatures (e.g. −35°C.) but is much less important in either n ‐pentane or carbon disulfide systems.
Trityl mass-tags for encoding in combinatorial oligonucleotide synthesis (1999)

Combinatorial libraries of oligonucleotides on beads were synthesised by a split-and-mix strategy using 5'-DMTr- or 5'-Fmoc- nucleoside phosphoramidites. Trityl moieties with different masses were used to encode for the bases coupled at each step in the synthesis of oligonucleotides selected by hybridisation from the libraries. Tags orthogonal to the nucleotides added were produced by coupling amines of different MW to an activated carboxyl group(s) on the trityl moiety. Tags can be released from the support by laser irradiation and measured directly by TOF without matrix. Alternatively, they may be released by an acidic treatment and then analysed by (MA)LDI-TOF.
Innentitelbild: Nachhaltiger Eisen‐Photokatalysator auf Holzbasis für vielfältige Anwendungen mit Sonnenlicht: Wasseraufbereitung und radikalische Photopolymerisation (Angew. Chem. 27/2023) (2023)

Ein nachhaltiger Photokatalysator aus Eisenoxid und modifiziertem Lignin forciert die Materialsynthese in eine grünere Richtung und erledigt die Aufgabe mit der Reinigung von Abwasser unter Verwendung von Sonnenlicht als natürlicher photonischer Quelle. Monomere, die an der radikalischen Photopolymerisation teilnehmen, genießen diese wunderbaren Reaktionsbedingungen. Der robuste Photokatalysator ermöglicht insbesondere die Wiederverwendung in mehreren Reaktionszyklen zur Abwasserreinigung, wie Bernd Strehmel, Zhijun Chen et al. in ihrem Forschungsartikel erläutern (e202301242).
GA201, a novel humanized, glycoengineered EGFR antibody with enhanced ADCC and superior in vivo efficacy in xenograft models (2008)

AACR Annual Meeting-- Apr 12-16, 2008; San Diego, CA

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The epidermal growth factor receptor (EGFR, HER1) is a clinically validated target for unconjugated antibodies in the treatment of cancer. It is over-expressed in a large variety of tumors for example in non-small cell lung cancer (NSCLC), head and neck, colorectal, gastric, pancreatic, renal cell, breast and prostate cancer as well as in gliomas. One anti-EGFR antibody, cetuximab, is already approved for the treatment of refractory metastatic colorectal cancer (mCRC) and of locally advanced and recurrent head and neck cancer. A second EGFR antibody, panitumumab has also been approved for mCRC. Several more EGFR antibodies are currently in clinical development. Response rates and times to progression with these drugs are modest (e.g., 11% and 1.5 months for cetuximab alone and 23 % and 4.1 months in combination with chemotherapy in mCRC) which means there is a significant need to improve on these results. Anti-EGFR antibodies can work via various mechanisms including: (1) blocking of ligand (EGF, TGF-α, epiregulin, amphiregulin and additional EGF-like ligands) binding to the receptor, (2) blocking of homo- and heterodimerization among HER family members (HER 1-4), (3) receptor downregulation, and (4) immune effector functions such as antibody-dependent cellular cytotoxicity (ADCC). Mechanisms 1 to 3 lead to inhibition of EGFR phosphorylation and of downstream signaling, leading to inhibition of tumor cell growth, VEGF secretion, tumor cell migration, and resistance to apoptosis, while ADCC is a mechanism of direct target cell killing by immune effector cells (e.g., NK cells, macrophages) triggered upon cross-linking of Fc receptors. GA201 is a novel humanized and glycoengineered IgG1 antibody which targets EGFR. Similar to cetuximab, its mechanism of action involves high affinity binding to EGFR, which subsequently results in ligand binding and heterodimerization blockade preventing receptor phosphorylation. This leads to inhibition of cell growth, tumor cell migration, VEGF secretion and resistance to apoptosis. However, a unique feature of GA201 that differentiates it from other EGFR antibodies, including cetuximab, is its ability to bind to human FcgRIIIa on immune effector cells with a 50-fold higher affinity than standard, IgG1 antibodies, a property conferred by the engineered glycosylation of the antibody Fc region. Consequently, GA201 exhibits superior potency and efficacy in ADCC, as shown in vitro using different EGFR expressing cell lines and in its Fc mediated anti-tumor effect in a murine models compared to other anti-EGFR Abs. The enhanced ADCC capability renders GA201 a promising new therapy compared to the other anti-EGFR MAbs on the market and currently in clinical development for the treatment of solid tumors.
Tunable planar polymer Bragg gratings having exceptionally low polarization sensitivity (2003)

We report fabrication of planar polymer Bragg gratings that can be thermally tuned 20 nm with very low polarization sensitivity, (λ/sub TE/-λ/sub TM/)<±>/0.05 nm, throughout the tuning range. Polarization sensitivity in a planar film is caused by an anisotropic effective refractive index in the film typically resulting from strain. Strain in polymer Bragg gratings is caused by the photopolymerization and the thermal annealing processes utilized for the grating fabrication. For the case of polymer Bragg gratings, we show for the first time that fabrication-induced strain can be nearly eliminated by laser etching parallel trenches into the polymer layers on each side of the grating. The improvement in polarization sensitivity depends strongly on the trench separation, the thermal annealing process, and the grating tuning method.
Early afterdepolarizations in a model of cardiac cells (1992)

Using a single Beeler-Reuter patch, we demonstrate that oscillatory responses of transmembrane potential can be simulated in the absence of a constant current stimulus by applying physiologically reasonable parametric variations to the model. Our results indicate that 1) the principal active elements of this periodicity could be limited to the Ca <sup xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">+2</sup> kinetics, with the K <sup xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">+</sup> kinetics playing a passive role, 2) these oscillations are capable of triggering sequences of entrained action potentials in a neighboring cell, and 3) partial K <sup xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">+</sup> blockade can facilitate activation in the neighboring cell.
Low temperature plasma for tunable resonant attenuation (2016)

A cold-plasma-based technique for tuning an evanescent-mode cavity resonator is introduced and studied experimentally for the first time in this paper. The technique involves a plasma jet that constitutes a variable resistance integrated in the cavity. The electron density and consequently the electromagnetic properties of plasma, including its resistivity, are controlled by varying the magnitude of the sinusoidal excitation voltage. The transmission coefficient of the two-port fabricated resonator at 2.735 GHz exhibits 11 dB tunability when the magnitude of the 20-kHz plasma-excitation voltage increases from zero to 5.26 kV (peak-to-peak). The resonator's quality factor varies in the acceptable range of 684-342 for these conditions. The measured and simulated results reveal that this approach may become a promising tuning technology particularly in demanding applications where conventional solid-state techniques are ineffective due to temperature, power, or linearity limitations.
Computer extracted features related to the spatial arrangement of tumor-infiltrating lymphocytes predict overall survival in epithelial ovarian cancer (2020)

The presence of tumor-infiltrating lymphocytes (TILs) is correlated with outcome and prognosis in epithelial ovarian cancer (EOC). In this study, automated image analysis was used to analyze the association between overall survival (OS) and TIL spatial arrangement and density in a multi-site cohort of 102 EOC patients who received adjuvant chemotherapy following debulking surgery. Features of the spatial arrangement of TILs (SpaTIL) were used to quantify the spatial co-localization of TILs and tumor cells on digitized pathology slides of the malignant neoplasm of excised specimens. A multivariable Cox regression model of SpaTIL features was fit on the n<sub>1</sub> = 51 patient training set and was evaluated in the n<sub>2</sub> = 51 patient validation set. The SpaTIL signature was significantly associated with OS, both in the training set (hazard ratio (HR) = 2.81, 95% confidence interval (CI) = 1.33 − 5.92, and p = 0.003) and the validation set (HR = 2.06, 95% CI = 1.04 − 4.07, and p = 0.008). In addition, fusing our spaTIL risk score and the clinical staging further improved the results of the predictive model (HR = 4.045, 95% CI = 4.11−5.41, and p = 0.0002 in the validation set) and outperformed clinical staging alone. This finding illustrates that a spaTIL risk score is not only able to predict OS independent of clinical data, but also offers prognostic value complementary to current clinical standard-of-care. Patients with longer survival times had significantly higher heterogeneity of non-TIL cluster area, while shorter time survivors had mostly same-sized, evenly-distributed non-TIL clusters and smaller average TIL cluster area. These findings suggest that dispersion of TILs throughout the tumor is associated with better treatment response to post-treatment adjuvant chemotherapy, and therefore longer survival time.
Proceedings of the 2016 ACM on Cloud Computing Security Workshop (2016)

It is our great pleasure to welcome you to the 8th ACM Cloud Computing Security Workshop (CCSW). Since its inception, CCSW has been a forum for bringing together researchers and practitioners to discuss technological advances bearing on the security of compute clouds, their tenants, and the larger Internet community. This year's workshop continues in this tradition. Submissions were evaluated by a program committee of 28 experts in the field, resulting in the selection of 8 full papers (from 23 submitted) and 2 short papers (from 4 submitted) after a roughly one-month review process and online discussion. In addition, the workshop hosted invited lectures by Dr. Michael Waidner from the Fraunhofer SIT and Technische Universität Darmstadt, and Mr. Luciano Franceschina from Teralytics.
The drm game (2007)

In this paper we cast DRM in a setting that allows us to model a number of current approaches as games. The DRM game is partitioned into two subgames, one that considers the game associated with content acquisition, and a second that considers how a consumer uses the content, along with a vendor's response to this usage. Examples are provided in order to demonstrate how these subgames correspond to real situations associated with content industries, and the conditions under which Nash equilibria will exist. These subgames form the primary stage of a repeated game that models a number of important long-term interactions between consumers and vendors. We analyze current strategies that attempt to influence the outcome of the repeated game, and we also consider a new type of architectural infrastructure that makes novel use of a trust authority in order to create a suitable environment for constructing DRM games that may prove useful in the future.
Production in Eukaryotic Cells and Characterization of Four Hybrids of Tissue-Type and Urokinase-Type Plasminogen Activators (1989)

To investigate the structure-function relationship in tissue-type plasminogen activator (t-PA) and urokinase-type plasminogen activator (u-PA), four hybrid sequences were amplified and overexpressed in a mouse myeloma cell line. The following constructs were made starting from cDNA encoding human t-PA and u-PA: (i) a hybrid in which amino acids (AA) 1-262 of the A-chain of t-PA is fused to AA 139-411 of the B-chain of u-PA; (ii) a hybrid in which the kringle 2 region of t-PA (AA 173-262) is inserted between amino acids 130 and 139 of u-PA; (iii) hybrid #2 having amino acids 1 to 10 deleted and replaced by the finger region of t-PA (AA 1-50); and (iv) a chimera in which the finger region of t-PA is followed by amino acids 10-411 of u-PA and where the lysine residues at positions 135 and 136 of u-PA are replaced by glutamines. These four hybrids were efficiently secreted into the culture medium as single-chain polypeptides of the expected molecular weights and had fully functional catalytic activity. Replacement of the A-chain of u-PA by that of t-PA leads to increased fibrin binding, whereas additions of finger and kringle domains do not. These data suggest that structural domains in serine proteases may not fold and/or function autonomously.
Enantioconvergent production of (R)‐1‐phenyl‐1,2‐ethanediol from styrene oxide by combining the Solanum tuberosum and an evolved Agrobacterium radiobacter AD1 epoxide hydrolases (2006)

Soluble epoxide hydrolase (EH) from the potato Solanum tuberosum and an evolved EH of the bacterium Agrobacterium radiobacter AD1, EchA-I219F, were purified for the enantioconvergent hydrolysis of racemic styrene oxide into the single product (R)-1-phenyl-1,2-ethanediol, which is an important intermediate for pharmaceuticals. EchA-I219F has enhanced enantioselectivity (enantiomeric ratio of 91 based on products) for converting (R)-styrene oxide to (R)-1-phenyl-1,2-ethanediol (2.0 +/- 0.2 micromol/min/mg), and the potato EH converts (S)-styrene oxide primarily to the same enantiomer, (R)-1-phenyl-1,2-ethanediol (22 +/- 1 micromol/min/mg), with an enantiomeric ratio of 40 +/- 17 (based on substrates). By mixing these two purified enzymes, inexpensive racemic styrene oxide (5 mM) was converted at 100% yield to 98% enantiomeric excess (R)-1-phenyl-1,2-ethanediol at 4.7 +/- 0.7 micromol/min/mg. Hence, at least 99% of substrate is converted into a single stereospecific product at a rapid rate.
Minimally Invasive Total Knee Arthroplasty Meets Computer Navigation (2009)

Learning Objectives Understand minimally invasive approaches to total knee arthroplasty Understand the new technologic advances in performing total knee arthroplasty Understand the importance of surgical technique in performing total knee arthroplasty
Constrained segmentation of complex models for image-based texture editing (2004)

We present a constrained segmentation method for the partitioning of complex textured 3D models. Our method automatically identifies large regions of reduced metric distortion suitable for texture mapping. The boundaries of the regions conform to salient features of the model and respect user-imposed constraints. We illustrate the application of this method to virtual paint restoration through image-based texture editing.
New Technologies for Printed Material's Advanced Value in the Production Printing Market (2011)

RICOH Pro C901 was launched in the late last year. It was successor of Pro C900 which was launched in the late 2008 and has gotten favorable reviews.Pro C901 has newly chosen RICOH original chemical toners called &#x201C;PxP (polyester x polymerization)&#x201D; and achieved near&#x2013;offset, high image quality. Pro C901 is also focused on being used in production printing market. And we have given priority to making printed materials valuable.In this report as the technologies for enhancing the printed materials, we will introduce the designing for stable image quality and the designing for UV varnish coating.
Polymerization of olefins with zirconocene catalysts using methylaluminoxane modified with hydroquinone as cocatalyst (1996)

Abstract Methylaluminoxane (MAO) was reacted with a small quantity of p ‐hydroquinone to obtain a modified MAO insoluble in toluene. Ethylene and propylene homo‐ and copolymerization were conducted with zirconocene using the modified MAO as cocatalyst both in the presence and absence of triisobutylaluminium. It was found that the modified MAO alone cannot activate the zirconocene catalyst, whereas polymers with high molecular weights are obtained when combined with triisobutylaluminium. The catalytic activity is markedly dependent on the mole ratio of p ‐hydroquinone to MAO as well as the amount of triisobutyl‐aluminium.
Characterization of AlInGaN-based 405nm distributed feedback laser diodes (2008)

The first-order AlInGaN 405 nm distributed feed-back (DFB) laser diodes were grown on the low dislocation freestanding GaN substrates by a metal organic chemical vapor deposition method. The first-order diffractive grating whose period was 80 nm was formed into an n-type cladding layer. The fine tooth shape grating was obtained by the EB lithography and the dry etching. No additional threading dislocation could be found at the regrowth interface. As a result, we succeeded in demonstrating the first-order AlInGaN based 405 nm DFB laser diodes under cw operation. The threshold current and the slope efficiency were 22 mA and 1.44 W/A under continuous wave operation at 25 &deg;C, respectively. The single longitudinal mode emission was maintained up to an output power of 60 mW. The fundamental transverse mode operation with a single longitudinal mode was observed in the temperature range from 15 &deg;C to 85 &deg;C at an output power of 30 mW. The lifetime was estimated to be 4000 h by the lifetime test which was carried out under the condition of a constant output power of 30mW at 25 &deg;C for 1000 h. The single longitudinal mode emission was maintained for the life tested DFB laser diodes.
Advances in the Characterization of the T-Cell Response to Human Herpesvirus-6 (2018)

Human herpesvirus (HHV) 6 is thought to remain clinically latent in most individuals after primary infection and to reactivate to cause disease in persons with severe immunosuppression. In allogeneic hematopoietic stem cell transplant recipients, reactivation of HHV-6 species B is a considerable cause of morbidity and mortality. HHV-6B reactivation is the most frequent cause of infectious meningoencephalitis in this setting and has been associated with a variety of other complications such as graft rejection and acute graft versus host disease. This has inspired efforts to develop HHV-6-targeted immunotherapies. Basic knowledge of HHV-6-specific adaptive immunity is crucial for these endeavors, but remains incomplete. Many studies have focused on specific HHV-6 antigens extrapolated from research on human cytomegalovirus, a genetically related betaherpesvirus. Challenges to the study of HHV-6-specific T-cell immunity include the very low frequency of HHV-6-specific memory T cells in chronically infected humans, the large genome size of HHV-6, and the lack of an animal model. This review will focus on emerging techniques and methodological improvements that are beginning to overcome these barriers. Population-prevalent antigens are now becoming clear for the CD4+ T-cell response, while definition and ranking of CD8+ T-cell antigens and epitopes is at an earlier stage. This review will discuss current knowledge of the T-cell response to HHV-6, new research approaches, and translation to clinical practice.
Anti‐cyclic citrullinated peptide but not rheumatoid factor is associated with ultrasound‐detected bone erosion among rheumatoid arthritis patients with at least moderate disease activity (2020)

The association of anti-CCP and RF with joint damage appears to differ in RA. Among patients with at least moderate disease activity (DAS28 ≥ 3.2), anti-CCP-but not RF-is associated with joint damage, being moderately correlated with ultrasound-detected bone erosion.
C-type lectin-like receptor (CLEC)-2, the ligand of podoplanin, induces morphological changes in podocytes (2022)

Abstract Podoplanin (PDPN) is intensely expressed on the podocyte membrane in an evolutionally conserved manner. CLEC-2, the endogenous ligand of PDPN, is highly expressed in platelets and also exists in a soluble form in plasma. Normally, podocytes are sequestered from CLEC-2, but when the glomerular barrier is injured, podocytes gain access to CLEC-2. We tested the effects of CLEC-2 in podocytes in vitro and in vivo. Cultured podocytes treated with Fc-CLEC-2 demonstrated that CLEC-2 induced the dephosphorylation of moesin, which we found to be the major ERM in cultured podocytes. Podocytes treated with Fc-CLEC-2 also showed the dissociation of F-actin filaments from PDPN, F-actin degradation, detachment, and round morphology. Next, we perfused normal mouse kidney in vivo with FLAG-CLEC-2. CLEC-2 induced dephosphorylation of ezrin and widening of the foot processes of podocytes. Platelets were detected by immunostaining for CD41 in the urine of mice with podocyte injury, indicating that podocytes can encounter platelets when glomeruli are injured. Collectively, these observations suggest that when platelets leak through the injured glomeruli, CLEC-2 from the platelets acts on PDPN in podocytes and induces morphological change and detachment, which may further aggravate podocyte injury. Thus, PDPN on podocytes may work as a leaked-platelet sensor.