gebhart/patrepeval huggingface dataset:
Nanoscale Cellular Changes in Field Carcinogenesis Detected by Partial Wave Spectroscopy (2009)

Understanding alteration of cell morphology in disease has been hampered by the diffraction-limited resolution of optical microscopy (>200 nm). We recently developed an optical microscopy technique, partial wave spectroscopy (PWS), which is capable of quantifying statistical properties of cell structure at the nanoscale. Here we use PWS to show for the first time the increase in the disorder strength of the nanoscale architecture not only in tumor cells but also in the microscopically normal-appearing cells outside of the tumor. Although genetic and epigenetic alterations have been previously observed in the field of carcinogenesis, these cells were considered morphologically normal. Our data show organ-wide alteration in cell nanoarchitecture. This seems to be a general event in carcinogenesis, which is supported by our data in three types of cancer: colon, pancreatic, and lung. These results have important implications in that PWS can be used as a new method to identify patients harboring malignant or premalignant tumors by interrogating easily accessible tissue sites distant from the location of the lesion.
New developments in the treatment of opioid‐induced gastrointestinal symptoms (2018)

Chronic pain affects a large part of the global population, leading to an increase of opioid use. Opioid-induced constipation (OIC), a highly prevalent adverse effect of opioid use, has a major impact on patients' quality of life. Thanks to the introduction of new drugs for chronic constipation, which can also be used in OIC, and the development of peripherally acting mu-opioid receptor blockers, specifically for use in OIC, therapeutic options have seen major development. This review summarises current and emerging treatment options for OIC based on an extensive bibliographical search. Efficacy data for laxatives, lubiprostone, prucalopride, linaclotide, oxycodone/naloxone combinations, methylnaltrexone, alvimopan, naloxegol, naldemedine, axelopran, and bevenopran in OIC are summarised.
Edge-based blur kernel estimation using patch priors (2013)

Blind image deconvolution, i.e., estimating a blur kernel k and a latent image x from an input blurred image y, is a severely ill-posed problem. In this paper we introduce a new patch-based strategy for kernel estimation in blind deconvolution. Our approach estimates a “trusted” subset of x by imposing a patch prior specifically tailored towards modeling the appearance of image edge and corner primitives. To choose proper patch priors we examine both statistical priors learned from a natural image dataset and a simple patch prior from synthetic structures. Based on the patch priors, we iteratively recover the partial latent image x and the blur kernel k. A comprehensive evaluation shows that our approach achieves state-of-the-art results for uniformly blurred images.
Nanofabrication by DNA self-assembly (2009)

Molecular self-assembly strategies involve the formation of nanometer scale objects and materials in the absence of significant external control. One increasingly popular self-assembly approach makes use of the unique properties of deoxyribonucleic acid (DNA) including its diminutive size and high capacity for information storage. For many applications, DNA stands alone as the top choice for the programmable construction of supramolecular materials due to its specific and well-understood base-pairing interactions. In this review, we will discuss recent advances in the fabrication of materials via DNA based self-assembly.
<title>Head-mounted display using a holographic optical element</title> (1998)

We will discuss the prototype of Head Mounted Display using Holographic Optical Element in this paper. It is obvious that a single HOE can record the multiple optical images by the characteristic in itself, that is angular selectivity and wavelength selectivity. Therefore, it is very easy to understand the HOE has the function which can separate the stereoscopic images onto the left and right eyes, like as the conventional HMD. In this report, we propose the prototype of HMD using a single HOE, and we will extract the problem in application of the real industrial field, especially manufacturing and designing. Consequently, we proved that the HMD using Lippmann hologram has the potentiality of miniaturization, lightening, wide field of vision. This HMD can be suitable in the Virtual Reality field. But it is necessary to adjust the pupil distance and the incident angle of conjugate beam precisely.
Comparative studies of different cryopreservation methods for mesenchymal stem cells derived from human fetal liver (2010)

Fetal stem cells possess some intriguing characteristics, which delineate them as promising cellular therapeutics. They are less immunogenic, at lower stage of differentiation and have higher potential for repopulation and migration. Furthermore, the fetal stem cells secrete a set of cytokines and growth factors, which stimulate the regeneration of the recipient tissue. The present study indicated that the adhesive fraction of human fetal liver cells possessed the morphological characteristics of mesenchymal stem cells, as well as potential to differentiate into adipocyte and osteoblast lineages. The immunophenotypic analysis showed that the cells expressed CD13, CD73, CD90 and CD105 (typical for mesenchymal stem cells) and lacked the haematopoietic lineage markers CD34 and CD45. Addressing the issue of the low-temperature storage of the human fetal liver cells, four different methods for cryopreservation were assessed: conventional slow freezing, program freezing and two vitrification protocols. The obtained results demonstrated that the cells were cryotolerant and maintained their properties and differentiation potential after thawing. Program freezing showed to be the most efficient method for cryopreservation of the investigated cells.
Determination of tumor‐related factors of influence on the uptake of the monoclonal antibody 323/A3 in experimental human ovarian cancer (1997)

The epithelial glycoprotein 40 (EGP40) is an important target in the clinic for radioimmunolocalization and monoclonal antibody (MAb)-mediated therapy of cancer. We determined which tumor-related factors (including antigen distribution and density, vascularization and perfusion) were involved in the uptake of the anti-EGP40 MAb 323/A3 in 4 different human ovarian cancer xenografts grown s.c. in nude mice. The reactivity pattern of 323/A3 in all xenografts in vitro was similar and showed a strong and homogeneous distribution of the EGP40 antigen. FMa xenografts, however, showed the highest uptake of 323/A3 in vivo, which was 5.5-, 6.2- and 10.0-fold higher than that in OVCAR-3, Ov.Pe and Ov.Sh xenografts, respectively. FMa xenografts contained 2.1- to 3.5-fold more antigen per gram protein when compared with the antigen content of the other xenografts. FMa and Ov.Sh xenografts demonstrated a better vascularization pattern, whereas Ov.Pe and OVCAR-3 xenografts were moderately to poorly vascularized. FMa xenografts were also better perfused, as was shown by a 1.6- to 1.8-fold higher uptake of the 99mTc-labeled blood flow marker hexamethylpropyleneamine oxime (HMPAO). The tumor uptake of the non-specific MAb E48 was 2.2- to 11.2-fold lower when compared with that of 323/A3, but the sequence of uptake was similar (FMa > OVCAR-3 = Ov.Pe > Ov.Sh), indicating the lowest extravasation of MAbs in Ov.Sh xenograft tissue. Since both the antigen content and the perfusion appeared to be important factors of influence on the tumor uptake of 323/A3, attempts were made to manipulate these determinants to improve the tumor uptake. Neither γ-interferon nor 5-fluorouracil were able to increase EGP40 expression in human ovarian cancer cells in vitro. Treatment of tumor-bearing mice with the calcium-antagonist flunarizine did not result in an improved perfusion, although a slight increase in the initial tumor uptake of 323/A3 was observed in Ov.Sh-bearing mice. Our results illustrate the relative contribution of various tumorrelated factors that determine the usefulness of a MAb for imaging and therapy of cancer. Int. J. Cancer 71:237–245, 1997. © 1997 Wiley-Liss, Inc.
GaN homoepitaxy on freestanding (1100) oriented GaN substrates (2002)

We report homoepitaxial GaN growth on freestanding (11̄00) oriented (M-plane GaN) substrates using low-pressure metalorganic chemical vapor deposition. Scanning electron microscopy, atomic-force microscopy, and photoluminescence were used to study the influence of growth conditions such as the V/III molar ratio and temperature on the surface morphology and optical properties of the epilayers. Optimized growth conditions led to high quality (11̄00) oriented GaN epilayers with a smooth surface morphology and strong band-edge emission. These layers also exhibited strong room temperature stimulated emission under high intensity pulsed optical pumping. Since for III-N materials the (11̄00) crystal orientation is free from piezoelectric or spontaneous polarization electric fields, our work forms the basis for developing high performance III-N optoelectronic devices.
Mutant and Wild Type Human α-Synucleins Assemble into Elongated Filaments with Distinct Morphologies in Vitro (1999)

alpha-Synuclein is a soluble presynaptic protein which is pathologically redistributed within intracellular lesions characteristic of several neurodegenerative diseases. Here we demonstrate that wild type and two mutant forms of alpha-synuclein linked to familial Parkinson's disease (Ala30 --> Pro and Ala53 --> Thr) self-aggregate and assemble into 10-19-nm-wide filaments with distinct morphologies under defined in vitro conditions. Immunogold labeling demonstrates that the central region of all these filaments are more robustly labeled than the N-terminal or C-terminal regions, suggesting that the latter regions are buried within the filaments. Since in vitro generated alpha-synuclein filaments resemble the major ultrastructural elements of authentic Lewy bodies that are hallmark lesions of Parkinson's disease, we propose that self-aggregating alpha-synuclein is the major subunit protein of these filamentous lesions.
Huntingtons Disease (1986)

HUNTINGTON'S disease is an autosomal dominant disorder that usually begins in mid-life and is characterized by a progression of involuntary choreiform movements, psychological change, and dementia.1 George Huntington and his father and grandfather first studied the illness in families in East Hampton, Long Island, New York. The ancestry of some cases has been traced to immigrants from Bures, England, in 1649.2 , 3 Other evidence also suggests that the disease is of European origin; cases in South Africa have been traced to Dutch settlers who emigrated there in 1658,4 and cases in Tasmania have been traced to ancestors from Somerset, England.3 These . . .
Interleukin-2 druggability is modulated by global conformational transitions controlled by a helical capping switch (2020)

Interleukin-2 (IL-2) is a small α-helical cytokine that regulates immune cell homeostasis through its recruitment to a high-affinity heterotrimeric receptor complex (IL-2Rα/IL-2Rβ/γ<sub>c</sub>). IL-2 has been shown to have therapeutic efficacy for immune diseases by preferentially expanding distinct T cell compartments, and several regulatory T cell (T<sub>reg</sub>)-biasing anti-IL-2 antibodies have been developed for combination therapies. The conformational plasticity of IL-2 plays an important role in its biological actions by modulating the strength of receptor and drug interactions. Through an NMR analysis of milliseconds-timescale dynamics of free mouse IL-2 (mIL-2), we identify a global transition to a sparse conformation which is regulated by an α-helical capping "switch" at the loop between the A and B helices (AB loop). Binding to either an anti-mouse IL-2 monoclonal antibody (mAb) or a small molecule inhibitor near the loop induces a measurable response at the core of the structure, while locking the switch to a single conformation through a designed point mutation leads to a global quenching of core dynamics accompanied by a pronounced effect in mAb binding. By elucidating key details of the long-range allosteric communication between the receptor binding surfaces and the core of the IL-2 structure, our results offer a direct blueprint for designing precision therapeutics targeting a continuum of conformational states.
Analysis and Design Optimization of Diode Front-End Rectifier Passive Components for Voltage Source Inverters (2008)

<para xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink"> This paper presents a systematic design optimization approach for inductors and capacitors in diode front-end rectifiers for voltage source inverters. Analytical relationships between various design variables, operating conditions, and performance and physical constraints are established under nominal, overload, and inrush conditions. A new method to analytically calculate the inrush current is developed considering the nonlinear characteristics of the inductor core materials. A design optimization program based on the established analytical relationships and a genetic algorithm is developed. Examples show that the optimization process can lead to a smaller/lower cost inductor and capacitor design. Experiments are conducted to verify key analytical relationships and the optimized design. </para>
Quantification of circulating cell‐free DNA in the plasma of cancer patients during radiation therapy (2008)

Cell-free plasma DNA is elevated in cancer patients and decreases in response to effective treatments. Consequently, these nucleic acids have potential as new tumor markers. In our current study, we investigated whether the plasma DNA concentrations in patients with cancer are altered during the course of radiation therapy. To first determine the origin of cell-free plasma DNA, plasma samples from mice bearing transplanted human tumors were analyzed for human-specific and mouse-specific cell-free DNA. Human-specific DNA was detectable only in plasma from tumor-bearing mice. However, mouse-specific plasma DNA was significantly higher in tumor-bearing mice than in normal mice, suggesting that cell-free plasma DNA originated from both tumor and normal cells. We measured the total cell-free plasma DNA levels by quantitative polymerase chain reaction in 15 cancer patients undergoing radiation therapy and compared these values with healthy control subjects. The cancer patients showed higher pretreatment plasma DNA concentrations than the healthy controls. Eleven of these patients showed a transient increase of up to eightfold in their cell-free plasma DNA concentrations during the first or second week of radiation therapy, followed by decreasing concentrations toward the end of treatment. In two other cancer patients, the cell-free plasma DNA concentrations only decreased over the course of the treatment. The total cell-free plasma DNA levels in cancer patients thus show dynamic changes associated with the progression of radiation therapy. Additional prospective studies will be required to elucidate the potential clinical utility and biological implications of dynamic changes in cell-free plasma DNA during radiation therapy.
Pretreatment Psychosocial Variables as Predictors of Outcomes Following Lumbar Surgery and Spinal Cord Stimulation: A Systematic Review and Literature Synthesis (2009)

At present, while there is insufficient empirical evidence that psychological screening before surgery or device implantation helps to improve treatment outcomes, the current literature suggests that psychological factors such as somatization, depression, anxiety, and poor coping, are important predictors of poor outcome. More research is needed to show if early identification and treatment of these factors through psychological screening will enhance treatment outcome.
Location of open reading frames coding for equine herpesvirus type-1 glycoproteins with homology to gE and gI of herpes simplex virus. (1991)

The DNA fragments representing the entire short unique region and part of the repeat sequences of the equine herpesvirus type-1 genome were cloned into plasmid vectors. The approximate positions of the junctions between the short unique region and the inverted repeats were then located by restriction endonuclease mapping. Two open reading frames coding for potential glycoproteins have been identified within the short unique region, using DNA sequence analysis. The predicted amino acid sequences of these open reading frames had extensive homology to the herpes simplex virus glycoproteins gE and gI and the related glycoproteins of pseudorabies virus and varicella-zoster virus.
Immunological variants of the aerobactin-cloacin DF13 outer membrane protein receptor IutA among enteric bacteria (1994)

Mouse monoclonal antibodies (MAbs) were generated against a 76-kDa IutA receptor of pathogenic avian Escherichia coli 15972. Six of the eight IutA-specific MAbs isolated (AB1 to AB6) were shown to be directed toward membrane-exposed conformational epitopes, although they did not interfere with the uptake of ferric aerobactin and cloacin DF13 as assessed by competition experiments with purified ligands. The two remaining IutA MAbs (AB9 and AB10) recognized linear epitopes buried in the IutA molecule. The panel of IutA MAbs was used to characterize IutA variants occurring in strains of E. coli, Klebsiella pneumoniae, Enterobacter spp., and Shigella spp., resulting in the identification of four immunological groups of IutAs. MAb AB9 defined an epitope conserved in all IutA variants. In addition, the panel of IutA MAbs served to identify the presence of IutA in wild-type bacteria grown in the presence of diphenylamine to reduce the expression of O-specific polysaccharide.
Dendritic Cell-Derived Exosomes Promote Natural Killer Cell Activation and Proliferation: A Role for NKG2D Ligands and IL-15Rα (2009)

Dendritic cell (DC) derived-exosomes (Dex) are nanomeric vesicles harboring functional MHC/peptide complexes promoting T cell-dependent tumor rejection. In the first Phase I trial using peptide-pulsed Dex, the observation of clinical regressions in the absence of T cell responses prompted the search for alternate effector mechanisms. Mouse studies unraveled the bioactivity of Dex on NK cells. Indeed, Dex promoted an IL-15Ralpha- and NKG2D-dependent NK cell proliferation and activation respectively, resulting in anti-metastatic effects mediated by NK1.1(+) cells. In humans, Dex express functional IL-15Ralpha which allow proliferation and IFNgamma secretion by NK cells. In contrast to immature DC, human Dex harbor NKG2D ligands on their surface leading to a direct engagement of NKG2D and NK cell activation ex vivo. In our phase I clinical trial, we highlight the capacity of Dex based-vaccines to restore the number and NKG2D-dependent function of NK cells in 7/14 patients. Altogether, these data provide a mechanistic explanation on how Dex may stimulate non MHC restricted-anti-tumor effectors and induce tumor regression in vivo.
Neuraminidase-Inhibiting Antibody Is a Correlate of Cross-Protection against Lethal H5N1 Influenza Virus in Ferrets Immunized with Seasonal Influenza Vaccine (2013)

In preparing for the threat of a pandemic of avian H5N1 influenza virus, we need to consider the significant delay (4 to 6 months) necessary to produce a strain-matched vaccine. As some degree of cross-reactivity between seasonal influenza vaccines and H5N1 virus has been reported, this was further explored in the ferret model to determine the targets of protective immunity. Ferrets were vaccinated with two intramuscular inoculations of trivalent inactivated split influenza vaccine or subcomponent vaccines, with and without adjuvant, and later challenged with a lethal dose of A/Vietnam/1203/2004 (H5N1) influenza virus. We confirmed that vaccination with seasonal influenza vaccine afforded partial protection against lethal H5N1 challenge and showed that use of either AlPO(4) or Iscomatrix adjuvant with the vaccine resulted in complete protection against disease and death. The protection was due exclusively to the H1N1 vaccine component, and although the hemagglutinin contributed to protection, the dominant protective response was targeted toward the neuraminidase (NA) and correlated with sialic acid cleavage-inhibiting antibody titers. Purified heterologous NA formulated with Iscomatrix adjuvant was also protective. These results suggest that adjuvanted seasonal trivalent vaccine could be used as an interim measure to decrease morbidity and mortality from H5N1 prior to the availability of a specific vaccine. The data also highlight that an inducer of cross-protective immunity is the NA, a protein whose levels are not normally monitored in vaccines and whose capacity to induce immunity in recipients is not normally assessed.
Surface microarchitectural design in biomedical applications:In vivo analysis of tissue ingrowth in excimer laser-directed micropored scaffold for cardiovascular tissue engineering (2000)

A micropatterned microporous segmented polyurethane film (20 x 12 mm in size, 30 micrometer thick) with four regions was prepared by excimer laser microprocessing to provide an in vivo model of transmural tissue ingrowth in an open cell-structured scaffold specially designed for cardiovascular tissue engineering. Three microporous regions had the same circular micropores (30 micrometer diameter) but different pore density arrangements (percentage of total pore area against unit area was 0.3%, 1.1%, and 4.5%), and the other region remained nonporous. The covered stent, prepared by wrapping the regionally different density-microporous film on an expandable metallic stent (approximately 3.1 mm in diameter), was delivered to the luminal surface of canine common carotid arteries and placed after expansion of the stent to a diameter of approximately 8 mm using a balloon catheter. At 4 weeks of implantation, all the covered stents (n = 10) were patent. The luminal surfaces of the covered stents were almost confluently endothelialized both in nonporous and microporous regions. Histological examination showed that the neointimal wall was formed by tissue ingrowth from host through micropores (transmural) and anastomotic sites. Thrombus formation occurred frequently in the lowest density porous region and nonporous region. With an increase in pore density, the thickness of the neointimal wall decreased. This study demonstrated how the micropore density of implanted devices influences tissue ingrowth in arterial implantation.
The transcriptional coactivator PGC-1α mediates exercise-induced angiogenesis in skeletal muscle (2009)

Peripheral arterial disease (PAD) affects 5 million people in the US and is the primary cause of limb amputations. Exercise remains the single best intervention for PAD, in part thought to be mediated by increases in capillary density. How exercise triggers angiogenesis is not known. PPARgamma coactivator (PGC)-1alpha is a potent transcriptional co-activator that regulates oxidative metabolism in a variety of tissues. We show here that PGC-1alpha mediates exercise-induced angiogenesis. Voluntary exercise induced robust angiogenesis in mouse skeletal muscle. Mice lacking PGC-1alpha in skeletal muscle failed to increase capillary density in response to exercise. Exercise strongly induced expression of PGC-1alpha from an alternate promoter. The induction of PGC-1alpha depended on beta-adrenergic signaling. beta-adrenergic stimulation also induced a broad program of angiogenic factors, including vascular endothelial growth factor (VEGF). This induction required PGC-1alpha. The orphan nuclear receptor ERRalpha mediated the induction of VEGF by PGC-1alpha, and mice lacking ERRalpha also failed to increase vascular density after exercise. These data demonstrate that beta-adrenergic stimulation of a PGC-1alpha/ERRalpha/VEGF axis mediates exercise-induced angiogenesis in skeletal muscle.