gebhart/patrepeval huggingface dataset:
5-Hydroxymethylcytosine – the elusive epigenetic mark in mammalian DNA (2012)

Over the past decade, epigenetic phenomena claimed a central role in cell regulatory processes and proved to be important factors for understanding complex human diseases. One of the best understood epigenetic mechanisms is DNA methylation. In the mammalian genome, cytosines (C) were long known to exist in two functional states: unmethylated or methylated at the 5-position of the pyrimidine ring (5mC). Recent studies of genomic DNA from the human and mouse brain, neurons and from mouse embryonic stem cells found that a substantial fraction of 5mC in CpG dinucleotides is converted to 5-hydroxymethyl-cytosine (hmC) by the action of 2-oxoglutarate- and Fe(ii)-dependent oxygenases of the TET family. These findings provided important clues in a long elusive mechanism of active DNA demethylation and bolstered a fresh wave of studies in the area of epigenetic regulation in mammals. This review is dedicated to critical assessment of the most popular techniques with respect to their suitability for analysis of hmC in mammalian genomes. It also discusses the most recent data on biochemical and chemical aspects of the formation and further conversion of this nucleobase in DNA and its possible biological roles in cell differentiation, embryogenesis and brain function.
An ultra low power, high performance Medical Implant Communication System (MICS) transceiver for implantable devices (2006)

A 402-405 MHz MICS band transceiver has been developed for implantable medical applications. The transceiver offers exceptionally low power consumption whilst providing a high data rate. The circuit features a unique ultra low power wakeup system enabling an average sleep current of less than 250 nA. The transmit and receive current is less than 5 mA when operating at a data rate of up to 800 kbps. System integration is high and only 3 external components (crystal and 2 decoupling capacitors) and a matching network are required. The transceiver can also operate in the 433 MHz ISM band. The key system design features and performance of this transceiver are presented in this paper.
Compact Modeling of CMOS Devices (2013)

The history of MOSFET modeling for extreme environments is interwoven in the development of SPICE itself. SPICE, as its name implies, was designed as a Simulation Program with Integrated Circuit Emphasis, with transistors being the primary active device employed on such ICs. Depending upon the phenomena to be modeled, either model characterization, model augmentation, or a combination of both may be applied. CMOS devices are commonly fabricated in both bulk and SOI forms in minimum features sizes varying from 0.5 µm or greater all the way down to 32 nm and below in traditional silicon and compound technologies and hybrids. As the most widely used structure in integrated circuits design, the modeling, characterization, and simulation of the MOSFET have grown into a field all its own. Modeling of MOSFET devices in CMOS technologies, whether they be traditional bulk processes or be SOI technologies, requires working with complex models consisting of decades of research into device physics and efficient modeling techniques.
Single and Dual Amino Acid Substitutions in TCR CDRs Can Enhance Antigen-Specific T Cell Functions (2008)

Single and dual amino acid substitution variants were generated in the TCR CDRs of three TCRs that recognize tumor-associated Ags. Substitutions that enhance the reactivity of TCR gene-modified T cells to the cognate Ag complex were identified using a rapid RNA-based transfection system. The screening of a panel of variants of the 1G4 TCR, that recognizes a peptide corresponding to amino acid residues 157-165 of the human cancer testis Ag NY-ESO-1 (SLLMWITQC) in the context of the HLA-A*02 class I allele, resulted in the identification of single and dual CDR3alpha and CDR2beta amino acid substitutions that dramatically enhanced the specific recognition of NY-ESO-1(+)/HLA-A*02(+) tumor cell lines by TCR gene-modified CD4(+) T cells. Within this group of improved TCRs, a dual substitution in the 1G4 TCR CDR3alpha chain was identified that enhanced Ag-specific reactivity in gene-modified CD4(+) and CD8(+) T cells. Separate experiments on two distinct TCRs that recognize the MART-1 27-35 (AAGIGILTV) peptide/HLA-A*02 Ag complex characterized single amino acid substitutions in both TCRs that enhanced CD4(+) T cell Ag-specific reactivity. These results indicate that simple TCR substitution variants that enhance T cell function can be identified by rapid transfection and assay techniques, providing the means for generating potent Ag complex-specific TCR genes for use in the study of T cell interactions and in T cell adoptive immunotherapy.
Using the shuttle, Mir and ISS for operating micro-gravity engineering research laboratories (2001)

Maturing space technologies to operational readiness is an expensive and time-consuming process. New technologies must climb technology readiness levels involving simulation, ground tests, and flight tests before they are considered mature enough to serve critical roles in operational missions. In particular, technologies pertaining to dynamics and controls are key to the successful coordination of numerous subsystems and therefore require maturation in a systems context where all aspects of operation can be verified. Unfortunately, computer simulation seldom captures all of the fine detail, and potential for detrimental interaction, that hardware implementations ensure. Ground-based component and systems-level tests often lack access to the representative on-orbit environment. Systems-level flight tests, while essential to achieving high levels of technology readiness, are expensive and somewhat conservative due to the risk that a failure in the test might pose to the technology's success. As a result, there is a need for a development step between ground and flight test that exploits the International Space Station as a laboratory environment for maturing high risk, yet high payoff technologies in a representative and risk tolerant micro-gravity environment. This paper details design guidelines and lessons learned through MIT's development and operation of five micro-gravity dynamics and controls laboratories and how they are impacting the design of two future laboratories on the International Space Station.
MN Protein Immunolocalization in Uterine Cervix Carcinoma With Glandular Differentiation: A Clinicopathologic Study of a New Cancer-specific Biomarker (1995)

MN protein is the product of the newly described endogenous MN gene that is expressed in the tumorigenic phenotype of HeLa X fibroblast somatic cell hybrids. MN protein has carbonic anhydrase and putative DNA binding activity. With the exception of gastric mucosa, MN protein is expressed in neoplasia, particularly uterine cervix carcinoma, but not in benign tissue. This investigation examined the pathogenetic and prognostic significance of MN-protein immunoreactivity in uterine cervix carcinoma with glandular differentiation. Paraffin sections from 77 cervix carcinomas with glandular differentiations including 36 pure adenocarcinomas and 41 adenosquamous carcinomas were immunostained with anti-MN-protein (M-75 monoclonal proprietary; Ciba Corning Diagnostics, Alameda, CA). A total of 64.9% of cervix carcinomas with glandular differentiation exhibit MN-protein immunoreactivity localized to plasma membranes, cytoplasm, and some nuclei of neoplastic cells only, but not in adjacent benign tissue. The MN-protein staining intensity and distribution was as follows: 37.7% strong diffuse (≥ 50% cells positive), 19.5% strong focal (&lt; 50% cells positive), and weak (7.8%). Immunoreactivity occurred in both squamous and glandular areas of adenosquamous carcinomas and was unrelated to histopathologic features. Follow-up information was available on 67 patients: 31 exhibited recurrent disease (7 pelvic, 14 distant, and 10 both) at 1–144 months (mean 37, median 14), and 36 were disease-free at 12–216 months (mean 67, median 44.5). MN-protein immunoreactivity (all positives, both standard diffuse and strong focal, or standard diffuse only) exhibited no association with clinical outcome. Recurrent disease was associated with nuclear grade ( P &lt; .001), lymphatic invasion ( P &lt; .005), size on clinical examination or pathologic evaluation ( P &lt; .005), pelvic lymph node involvement ( P &lt; .05), and clinical stage ( P &lt; .05). MN-protein immunoreactivity did not correlate with these features and did not help predict which patients would develop recurrence in the good prognosis groups. Our data show that expression of MN-protein is associated with cervix carcinoma with glandular differentiation carcinogenesis. MN-protein immunolocalization may have a diagnostic role in confirming cervix carcinoma with glandular differentiation in histologically challenging cases.
Conventional and Power Spectrum Analysis of the Effects of Zolpidem on Sleep EEG in Patients with Chronic Primary Insomnia (2000)

In agreement with previous findings obtained in patients with chronic primary insomnia, zolpidem significantly improved sleep induction and maintenance. Moreover, zolpidem increased power density in the 0.25-1.0 Hz band during short-term and intermediate-term treatment. Nevertheless, other frequency bands in the delta range showed a relative decrease which was not statistically significant.
Computational Method to Predict Mitochondrially Imported Proteins and their Targeting Sequences (1996)

Most of the proteins that are used in mitochondria are imported through the double membrane of the organelle. The information that guides the protein to mitochondria is contained in its sequence and structure, although no direct evidence can be obtained. In this article, discriminant analysis has been performed with 47 parameters and a large set of mitochondrial proteins extracted from the SwissProt database. A computational method that facilitates the analysis and objective prediction of mitochondrially imported proteins has been developed. If only the amino acid sequence is considered, 75-97% of the mitochondrial proteins studied have been predicted to be imported into mitochondria. Moreover, the existence of mitochondrial-targeting sequences is predicted in 76-94% of the analyzed mitochondrial precursor proteins. As a practical application, the number of unknown yeast open reading frames that might be mitochondrial proteins has been predicted, which revealed that many of them are clustered.
Involvement of Lipid Rafts of Rabbit Red Blood Cells in Morphological Changes Induced by Methylated .BETA.-Cyclodextrins (2009)

Lipid rafts on cell membranes have heterogeneity such as cholesterol-rich microdomains and sphingolipids-rich microdomains. We previously reported that beta-cyclodextrin (beta-CyD) induced morphological changes of red blood cells (RBC) from discocyte to stomatocyte, possibly due to extraction of cholesterol from cholesterol-rich lipid rafts of RBC membranes. In this study, the effects of methyl-beta-cyclodextrin (M-beta-CyD) and 2,6-di-O-methyl-beta-cyclodextrin (DM-beta-CyD) on lipid rafts and morphological changes in rabbit RBC (RRBC) were examined, compared to those of beta-CyD. In sharp contrast to beta-CyD, M-beta-CyD and DM-beta-CyD induced morphological changes of RRBC from discocyte to echinocyte. At pre-hemolytic concentrations of beta-CyDs, M-beta-CyD and DM-beta-CyD strongly released cholesterol from cholesterol-rich lipid rafts, compared to beta-CyD. Meanwhile, the lowering effects of DM-beta-CyD on fluorescent sphingomyelin analogue in sphingolipids-rich lipid rafts were more potent than those of beta-CyD and M-beta-CyD. The magnitude of the abilities of M-beta-CyD and DM-beta-CyD to extract membrane constituents was higher than that of beta-CyD, consistent with that of hemolytic activity. Furthermore, DM-beta-CyD and M-beta-CyD, not beta-CyD, lowered the amount of proteins in cholesterol-rich lipid rafts of RRBC. These results suggest that higher hemolytic activity and morphological changes from discocyte to echinocyte in RRBC induced by M-beta-CyD and DM-beta-CyD may be due to the extraction of both cholesterol and proteins from cholesterol-rich lipid rafts of RRBC, although DM-beta-CyD may interact with sphingolipids-rich lipid rafts on RRBC membranes only slightly.
Verbesina zaragosana (Asteraceae, Heliantheae), a new species from Nuevo Leon, Mexico (1992)

A new species, Verbesina zaragosana B. Turner, is described from southiem Nuevo Leon where it occurs on gypsum substrates. It is closely related to the gjrpsophilic endemic V. hintonionim B. Turner, but is readily distinguished by having larger leaves with an ashy white, densely tomentose vestiture on both surfaces (vs. sparsely to moderately pubescent with stout terete hairs, each hair arising from an enlarged based complex of ceils).
The Implications of Risk for Client Project Management (1994)

Investment in all kinds of engineering projects is subject to ever-increasing uncertainty, making appraisal and reappraisal of financial risk an essential aspect of project management. In this paper, the author draws on extensive research in the UK to present risk management as a positive process and team effort. An active role for the client is advocated in all stages of project development.
PHD-an automatic mail server for protein secondary structure prediction (1994)

By the middle of 1993, > 30,000 protein sequences has been listed. For 1000 of these, the three-dimensional (tertiary) structure has been experimentally solved. Another 7000 can be modelled by homology. For the remaining 21,000 sequences, secondary structure prediction provides a rough estimate of structural features. Predictions in three states range between 35% (random) and 88% (homology modelling) overall accuracy. Using information about evolutionary conservation as contained in multiple sequence alignments, the secondary structure of 4700 protein sequences was predicted by the automatic e-mail server PHD. For proteins with at least one known homologue, the method has an expected overall three-state accuracy of 71.4% for proteins with at least one known homologue (evaluated on 126 unique protein chains).
Instrument-quality digital camera that transitioned to low-cost high-volume production (2002)

MOSAD(copyright), Multiplexed OverSample Analog to Digital conversion, is a low power on focal plane analog to digital, A/D, process that places an oversample A/D at each pixel site. Two full custom designs for a visible light staring array were developed with this approach. One design approach uses a silicon photo diode in combination with photo gates at the pixel and the other approach uses an all photo gate sensor for detection. Both arrays were designed with a 320x240 format with the pixels placed on 16 micron centers. The system includes the camera assembly, driver interface assembly, a frame grabber board with integrated decimator and Windows 2000 compatible software for real time image display. The camera includes the sensor, either photo gate or photo diode, mounted on a PC card with support electronics. A custom lens mount attaches the camera to C or CS mount lens. Testing was done with a Tamron 13VM2812 CCTV CS mount lens. Both an RS644 and an RS422 parallel interface card assembly was developed to attach to the frame grabber board. The final iteration cameras were tested at the Amain facility and pictures were taken. At 400 samples per second, measured on chip power consumption is under 10 milliwatts. Noise measurements at sample rates from 400 samples per second to 1,600 samples per second were taken for both parts. The photo diode worked and produced images but it had a sense amplifier problem that prevented adequate noise measurement. At 28 times oversample, the photo gate achieved typical 9 to 11 bits signal to noise with best case measured at 13 bits. Nonuniformity variation was below the noise floor.
SSD: Smooth Signed Distance Surface Reconstruction (2011)

Abstract We introduce a new variational formulation for the problem of reconstructing a watertight surface defined by an implicit equation, from a finite set of oriented points; a problem which has attracted a lot of attention for more than two decades. As in the Poisson Surface Reconstruction approach, discretizations of the continuous formulation reduce to the solution of sparse linear systems of equations. But rather than forcing the implicit function to approximate the indicator function of the volume bounded by the implicit surface, in our formulation the implicit function is forced to be a smooth approximation of the signed distance function to the surface. Since an indicator function is discontinuous, its gradient does not exist exactly where it needs to be compared with the normal vector data. The smooth signed distance has approximate unit slope in the neighborhood of the data points. As a result, the normal vector data can be incorporated directly into the energy function without implicit function smoothing. In addition, rather than first extending the oriented points to a vector field within the bounding volume, and then approximating the vector field by a gradient field in the least squares sense, here the vector field is constrained to be the gradient of the implicit function, and a single variational problem is solved directly in one step. The formulation allows for a number of different efficient discretizations, reduces to a finite least squares problem for all linearly parameterized families of functions, and does not require boundary conditions. The resulting algorithms are significantly simpler and easier to implement, and produce results of quality comparable with state‐of‐the‐art algorithms. An efficient implementation based on a primal‐graph octree‐based hybrid finite element‐finite difference discretization, and the Dual Marching Cubes isosurface extraction algorithm, is shown to produce high quality crack‐free adaptive manifold polygon meshes.
Biodegradable electrospun patch containing cell adhesion or antimicrobial compounds for trachea repair in vivo (2019)

Difficulty breathing due to tracheal stenosis (i.e. narrowed airway) diminishes the quality of life and can potentially be life-threatening. Tracheal stenosis can be caused by congenital anomalies, external trauma, infection, intubation-related injury, and tumors. Common treatment methods for tracheal stenosis requiring surgical intervention include end-to-end anastomosis, slide tracheoplasty and/or laryngotracheal reconstruction. Although the current methods have demonstrated promise for treatment of tracheal stenosis, a clear need exists for the development of new biomaterials that can hold the trachea open after the stenosed region has been surgically opened, and that can support healing without the need to harvest autologous tissue from the patient. The current study therefore evaluated the use of electrospun nanofiber scaffolds encapsulating 3D-printed PCL rings to patch induced defects in rabbit tracheas. The nanofibers were a blend of polycaprolactone (PCL) and polylactide-co-caprolactone (PLCL), and encapsulated either the cell adhesion peptide, RGD, or antimicrobial compound, ceragenin-131 (CSA). Blank PCL/PLCL and PCL were employed as control groups. Electrospun patches were evaluated in a rabbit tracheal defect model for 12 weeks, which demonstrated re-epithelialization of the luminal side of the defect. No significant difference in lumen volume was observed for the PCL/PLCL patches compared to the uninjured positive control. Only the RGD group did not lead to a significant decrease in the minimum cross-sectional area compared to the uninjured positive control. CSA reduced bacteria growth in vitro, but did not add clear value in vivo. Adequate tissue in-growth into the patches and minimal tissue overgrowth was observed inside the patch material. Areas of future investigation include tuning the material degradation time to balance cell adhesion and structural integrity.
Exploiting T cell receptor genes for cancer immunotherapy (2004)

Adoptive antigen-specific immunotherapy is an attractive concept for the treatment of cancer because it does not require immunocompetence of patients, and the specificity of transferred lymphocytes can be targeted against tumour-associated antigens that are poorly immunogenic and thus fail to effectively trigger autologous T cell responses. As the isolation and in vitro expansion of antigen-specific lymphocytes is difficult, 'conventional' adoptive T cell therapy can only be carried out in specialized centres in small numbers of patients. However, T cell receptor (TCR) genes isolated from antigen-specific T cells can be exploited as generic therapeutic molecules for 'unconventional' antigen-specific immunotherapy. Retroviral TCR gene transfer into patient T cells can readily produce populations of antigen-specific lymphocytes after a single round of polyclonal T cell stimulation. TCR gene modified lymphocytes are functionally competent in vitro, and can have therapeutic efficacy in murine models in vivo. TCR gene expression is stable and modified lymphocytes can develop into memory T cells. Introduction of TCR genes into CD8(+) and CD4(+) lymphocytes provides an opportunity to use the same TCR specificity to produce antigen-specific killer and helper T lymphocytes. Thus, TCR gene therapy provides an attractive strategy to develop antigen-specific immunotherapy with autologous lymphocytes as a generic treatment option.
Blocking of the PD‐1/PD‐L1 Interaction by a D‐Peptide Antagonist for Cancer Immunotherapy (2015)

Abstract Blockade of the protein–protein interaction between the transmembrane protein programmed cell death protein 1 (PD‐1) and its ligand PD‐L1 has emerged as a promising immunotherapy for treating cancers. Using the technology of mirror‐image phage display, we developed the first hydrolysis‐resistant D ‐peptide antagonists to target the PD‐1/PD‐L1 pathway. The optimized compound D PPA‐1 could bind PD‐L1 at an affinity of 0.51 μ M in vitro. A blockade assay at the cellular level and tumor‐bearing mice experiments indicated that D PPA‐1 could also effectively disrupt the PD‐1/PD‐L1 interaction in vivo. Thus D ‐peptide antagonists may provide novel low‐molecular‐weight drug candidates for cancer immunotherapy.
Regulatory effects of cell density on the binding of transforming growth factor beta, epidermal growth factor, platelet-derived growth factor, and fibroblast growth factor. (1988)

The work described in this paper demonstrates that the cellular binding of transforming growth factor beta, epidermal growth factor, platelet-derived growth factor, and fibroblast growth factor is reduced as cell density is increased. The reduction in transforming growth factor beta binding was observed in five different cell lines. Examination of several of the cell lines, under conditions where transforming growth factor beta binding is reduced, revealed that epidermal growth factor binding, platelet-derived growth factor binding, and fibroblast growth factor binding are also reduced. In the case of NRK-49F cells, the reduction in transforming growth factor beta binding results from a decrease in the number of high-affinity receptors and not from a change in receptor affinity. Similarly, it was determined that the reduction in epidermal growth factor binding is due to a selective reduction in the high-affinity receptors for epidermal growth factor. Overall, the data suggest that the effect of cell density on growth factor binding, which we refer to as density-induced down regulation of growth factor receptors, differs both from down regulation induced by a specific growth factor and from receptor transmodulation.