gebhart/patrepeval huggingface dataset:
An Evaluation of a Non-contact Biomotion Sensor with Actimetry (2007)

Actimetry is a widely accepted technology for the diagnosis and monitoring of sleep disorders such as insomnia, circadian sleep/wake disturbance, and periodic leg movement. In this study we investigate a very sensitive non-contact biomotion sensor to measure actimetry and compare its performance to wrist-actimetry. A data corpus consisting of twenty subjects (ten normals, ten with sleep disorders) was collected in the unconstrained home environment with simultaneous non-contact sensor and ActiWatch actimetry recordings. The aggregated length of the data is 151 hours. The non-contact sensor signal was mapped to actimetry using 30 second epochs and the level of agreement with the ActiWatch actimetry determined. Across all twenty subjects, the sensitivity and specificity was 79% and 75% respectively. In addition, it was shown that the non-contact sensor can also measure breathing and breathing modulations. The results of this study indicate that the non-contact sensor may be a highly convenient alternative to wrist-actimetry as a diagnosis and screening tool for sleep studies. Furthermore, as the non-contact sensor measures breathing modulations, it can additionally be used to screen for respiratory disturbances in sleep caused by sleep apnea and COPD.
A Multi-Cancer Mesenchymal Transition Gene Expression Signature Is Associated with Prolonged Time to Recurrence in Glioblastoma (2012)

A stage-associated gene expression signature of coordinately expressed genes, including the transcription factor Slug (SNAI2) and other epithelial-mesenchymal transition (EMT) markers has been found present in samples from publicly available gene expression datasets in multiple cancer types, including nonepithelial cancers. The expression levels of the co-expressed genes vary in a continuous and coordinate manner across the samples, ranging from absence of expression to strong co-expression of all genes. These data suggest that tumor cells may pass through an EMT-like process of mesenchymal transition to varying degrees. Here we show that, in glioblastoma multiforme (GBM), this signature is associated with time to recurrence following initial treatment. By analyzing data from The Cancer Genome Atlas (TCGA), we found that GBM patients who responded to therapy and had long time to recurrence had low levels of the signature in their tumor samples (P = 3×10(-7)). We also found that the signature is strongly correlated in gliomas with the putative stem cell marker CD44, and is highly enriched among the differentially expressed genes in glioblastomas vs. lower grade gliomas. Our results suggest that long delay before tumor recurrence is associated with absence of the mesenchymal transition signature, raising the possibility that inhibiting this transition might improve the durability of therapy in glioma patients.
Allelic genealogy and human evolution. (1993)

Genetic variation at most loci examined in human populations indicates that the (effective) population size has been approximately 10(4) for the past 1 Myr and that individuals have been genetically united rather tightly. Also suggested is that the population size has never dropped to a few individuals, even in a single generation. These impose important requirements for the hypotheses for the origin of modern humans: a relatively large population size and frequent migration if populations were geographically subdivided. Any hypothesis that assumes a small number of founding individuals throughout the late Pleistocene can be rejected. Extraordinary polymorphism at some loci of the major histocompatibility complex (Mhc) rules out the past action of severe bottlenecks, or the so-called founder principle, which invokes only a small number of founding individuals when a new species emerges. This conclusion may be extended to the 35-Myr-old history of the human lineage, because some polymorphism at Mhc loci seems to have lasted that long. Furthermore, although the population structure prior to the late Pleistocene is less clear, owing to the insensitivity of Mhc alleles, even to low levels of migration, the nature of Mhc polymorphism suggests that the effective size of populations leading to humans was as large as 10(5). Hence, the effective population size of humans might have become somewhat smaller in most of the late Pleistocene. The reduction could be due either to the then adverse environment in the Old World and/or to the increased migration rate. It is also argued that population explosion fostered by the agriculture revolution has had significant effects on incorporating new alleles into human populations.
Preclinical Development of Ipilimumab and Nivolumab Combination Immunotherapy: Mouse Tumor Models, In Vitro Functional Studies, and Cynomolgus Macaque Toxicology (2016)

The monoclonal antibodies ipilimumab (anti-CTLA-4) and nivolumab (anti-PD-1) have shown remarkable antitumor activity in an increasing number of cancers. When combined, ipilimumab and nivolumab have demonstrated superior activity in patients with metastatic melanoma (CHECKMATE-067). Here we describe the preclinical development strategy that predicted these clinical results. Synergistic antitumor activity in mouse MC38 and CT26 colorectal tumor models was observed with concurrent, but not sequential CTLA-4 and PD-1 blockade. Significant antitumor activity was maintained using a fixed dose of anti-CTLA-4 antibody with decreasing doses of anti-PD-1 antibody in the MC38 model. Immunohistochemical and flow cytometric analyses confirmed that CD3+ T cells accumulated at the tumor margin and infiltrated the tumor mass in response to the combination therapy, resulting in favorable effector and regulatory T-cell ratios, increased pro-inflammatory cytokine secretion, and activation of tumor-specific T cells. Similarly, in vitro studies with combined ipilimumab and nivolumab showed enhanced cytokine secretion in superantigen stimulation of human peripheral blood lymphocytes and in mixed lymphocyte response assays. In a cynomolgus macaque toxicology study, dose-dependent immune-related gastrointestinal inflammation was observed with the combination therapy; this response had not been observed in previous single agent cynomolgus studies. Together, these in vitro assays and in vivo models comprise a preclinical strategy for the identification and development of highly effective antitumor combination immunotherapies.
['Lelystad agent'--the cause of abortus blauw (mystery swine disease)]. (1991)

An unidentified agent was isolated from samples of pigs affected with abortus blauw (also known as mystery swine disease). This agent, designated 'Lelystad agent', grows in cultures of pig lung macrophages. The agent was inoculated into eight pregnant sows which subsequently aborted or gave birth to weak or dead piglets. The agent was then isolated from these piglets, thus confirming that it is the causal agent of abortus blauw.
Role of c-Myc in intestinal tumorigenesis of the Apc min/+ mouse1 (2006)

The c-MYC oncogene plays an important role in tumorigenesis and is commonly highly expressed in gastrointestinal cancers. In colon cells, c-MYC is regulated by the adenomatous polyposis coli (Apc) tumor suppressor gene. Multiple intestinal neoplasia (ApcMin/+ or Min) mice are heterozygous for a truncating Apc mutation and serve as a model of familial adenomatous polyposis (FAP) disease. To study the role of c-Myc in the mutant Apc-mediated colon tumorigenesis, we have developed a transgenic mouse with the conditional deletion of the floxed c-Myc alleles in the intestinal crypts of ApcMin/+ mice (ApcMin/+; c-Mycfl/fl). The floxed c-Myc deletion was initiated via a Cre recombinase controlled by the intestine-specific transcriptional regulatory elements of the liver fatty acid-binding protein gene (Fabpl4xat-132). Fabpl4xat-132-mediated Cre expression and recombination resulted in a two-fold decrease in c-MYC protein expression with no effect on intestinal tract morphology. Small intestinal tumorigenesis was significantly suppressed throughout the small intestinal tract of ApcMin/+; c-Mycfl/fl mice compared to c-Myc wild type littermates. In ApcMin/+; c-Mycfl/fl mice, the intestinal apoptosis was higher in the areas of the small intestine with the decreased c-Myc protein expression (P=0.0016, compared to their littermates with the wild type c-Myc). Thus, conditional inactivation of c-Myc, mediated by Fabpl4xat-132-driven Cre-recombinase, suppresses Apc-dependent intestinal tumorigenesis in adult ApcMin/+ mice, without apparent effect on normal intestinal mucosa.
Porous titanium endosseous dental implants in rhesus monkeys: Microradiography and histological evaluation (1979)

Artificial tooth roots with porous surface coatings were fabricated by sintering spherical powder of titanium alloy to solid cylindrical cores. The tooth roots were implanted subgingivally in healed mandibular premolar extraction sites of fifteen Rhesus monkeys. Supracrestal abutments were screwed into pretapped holes in the superior aspect of the primary subgingival stage four to eight weeks after implantation of the root. Clinical evaluations were performed monthly. Ten animals were sacrificed for histological evaluation of the functioning free standing implants. Of twenty-nine implants placed, three were lost and four were rated failures on the basis of histological evaluation. Postmortem evaluations revealed bone growth into the porous surface coating of the primary stage of all the implants. The most characteristic features which could be used to describe differences in the implant histology were the buccal and lingual crestal bone heights measured in relation to the root porosity. Twelve of sixteen implants had crestal bone heights within one millimeter of the superior aspect of the root. Four other implants displayed excessive bone recession, revealing as much as one half of the root porosity supracrestally. The four implant failures could be related to unfavorable features of recipient bone sites. The results demonstrate that the bone growth into the porous surface coatings of artificial tooth roots is an efficacious method of dental implant fixation.
GMM-Based Entropy-Constrained Vector Quantization (2007)

In this paper, we present a scalable entropy-constrained vector quantizer based on Gaussian mixture models (GMMs), lattice quantization, and arithmetic coding. We assume that the source has a probability density function of a GMM. The scheme is based on a mixture component classifier, the Karhunen Loeve transform of the component, followed by a lattice quantization. The scalar elements of the quantized vector are entropy coded using a specially designed arithmetic coder. The proposed scheme has a computational complexity that is independent of rate, and quadratic with respect to vector dimension. The design is flexible and allows for adjusting the desired target rate on-the-fly. We evaluated the performance of the proposed scheme on speech-derived source vectors. It was demonstrated that the proposed scheme outperforms a fixed-rate GMM based vector quantizer, and performs closely to the theoretical optimum.
RNA-Seq of Tumor-Educated Platelets Enables Blood-Based Pan-Cancer, Multiclass, and Molecular Pathway Cancer Diagnostics (2015)

Tumor-educated blood platelets (TEPs) are implicated as central players in the systemic and local responses to tumor growth, thereby altering their RNA profile. We determined the diagnostic potential of TEPs by mRNA sequencing of 283 platelet samples. We distinguished 228 patients with localized and metastasized tumors from 55 healthy individuals with 96% accuracy. Across six different tumor types, the location of the primary tumor was correctly identified with 71% accuracy. Also, MET or HER2-positive, and mutant KRAS, EGFR, or PIK3CA tumors were accurately distinguished using surrogate TEP mRNA profiles. Our results indicate that blood platelets provide a valuable platform for pan-cancer, multiclass cancer, and companion diagnostics, possibly enabling clinical advances in blood-based "liquid biopsies".
Interleukin-6 Neutralization by Antibodies Immobilized at the Surface of Polymeric Nanoparticles as a Therapeutic Strategy for Arthritic Diseases (2018)

Arthritic diseases are disabling conditions affecting millions of patients worldwide. Pro-inflammatory cytokines, particularly interleukin-6 (IL-6), plays a crucial role in inflammation and cartilage destruction. Although the beneficial effects of antibody therapy, its efficacy is limited. Therefore, this work proposes the immobilization of antibodies at the surface of biodegradable polymeric nanoparticles (NPs) to capture and neutralize IL-6. Our system is intended to protect, extend and enhance the therapeutic efficacy after delivery. Chitosan-hyaluronic acid NPs are synthesized as a stable monodisperse population. After determining the maximum immobilization capacity (10 μg/mL), the capture ability was confirmed. Biological assays demonstrate the NPs cytocompatibility with human articular chondrocytes (hACs) and human macrophages. hACs stimulated with macrophage conditioned medium shows the beneficial role of IL-6 capture and neutralization. Biofunctionalized NPs exhibit a prolonged action and stronger efficacy than the free antibody. In conclusion, this system can be an effective and long lasting treatment for arthritic diseases.
HLA-E Surface Expression Depends on Binding of TAP-Dependent Peptides Derived from Certain HLA Class I Signal Sequences (1998)

Previous studies showed that HLA-E was expressed in lymphoblastoid cell line (LCL) 721.221 cells, but surface expression was lacking. To determine the signals controlling surface expression, we constructed a series of hybrid genes using complementary portions derived from the HLA-E and HLA-A2 genes. In this manner, a hybrid of HLA-E was identified, designated AEH, which differed from HLA-E by having the HLA-A2 signal sequence substituting for the HLA-E leader peptide. Transfection of LCL 721.221 cells with AEH induced HLA-E surface expression. Analysis of peptides bound to HLA-E revealed that a nonamer peptide derived from the A2 signal sequence was the predominant peptide bound. LCL 721.221 cells transfected with certain class I genes, including HLA-G, were also sufficient to promote peptide binding and HLA-E surface expression without increasing the level of HLA-E heavy chain synthesis. Peptides bound to HLA-E consisted of nine amino acids, with methionine at position 2 and leucine in the carboxyl-terminal position, and were nearly identical to the leader sequence-derived peptide previously shown to be a predominant peptide bound to the murine Qa-1 Ag. Signal peptides derived from certain HLA-B proteins with threonine in position 2 only marginally up-regulated HLA-E surface expression in .221 cells. An examination of HLA-E peptide binding in the TAP negative cell line .134 indicated that peptide binding to HLA-E was dependent on a functional TAP heterodimer regardless of whether peptide was available in cis, as in the AEH construct, or in trans, as in the class I transfectants of .221 cells.
Colour correction for panoramic imaging (2003)

This paper reports the problem of colour distortion in panoramic imaging. Particularly when image mosaicing is used for panoramic imaging, the images are captured under different lighting conditions and viewpoints. The paper analyses several linear approaches for their colour transform and mapping. A new approach of colour histogram based colour correction is provided, which is robust to image capturing conditions such as viewpoints and scaling. The procedure for the colour correction is introduced and implemented. The conclusions are derived after experimental tests.
Nanocomposites of Vapour Phase Deposited Teflon AF Containing Ni Clusters (2003)

Two component nanocomposites of polymer containing 3d transition metal clusters are of immense interest because of their potential future applications in magnetic high frequency or data storage media, in particular: However, nanoscale engineering of such airstable 3d clusters protected in polymer layers is a major technological challenge, given the readily reactive nature of such nanoparticles. In this invited paper, we introduce relatively simple vapour phase deposition as a powerful solvent free technique to prepare polymer nanocomposites containing 3d transition metal clusters. The different vapour phase production routes investigated show that the technique lends itself to the formation of metallic clusters of the appropriate size while reactions of the reactive Ni atoms with the growing Teflon AF matrix, contrary to common belief, do not take place. In addition to other results, a promising route of vapour phase tandem evaporation to produce nanoclusters of reactive Ni protected between the capping layers of Teflon AF is particularly presented. Independent control over homogeneously distributed particle size ( similar to 3 - 10 nm) is discussed, while increasing a cluster volume filling from similar to 1 to 20 % by following co-deposition to many sequential thermal evaporation of the two components. TEM electron diffraction investigations have shown that crystal structure of such nanoclusters to be fee, confirming the bulk Ni crystal parameters.
A gene transfer vector-cell line system for complete functional complementation of adenovirus early regions E1 and E4 (1996)

The improvements to adenovirus necessary for an optimal gene transfer vector include the removal of virus gene expression in transduced cells, increased transgene capacity, complete replication incompetence, and elimination of replication-competent virus that can be produced during the growth of first-generation adenovirus vectors. To achieve these aims, we have developed a vector-cell line system for complete functional complementation of both adenovirus early region 1 (E1) and E4. A library of cell lines that efficiently complement both E1 and E4 was constructed by transforming 293 cells with an inducible E4-ORF6 expression cassette. These 293-ORF6 cell lines were used to construct and propagate viruses with E1 and E4 deleted. While the construction and propagation of AdRSV beta gal.11 (an E1-/E4- vector engineered to contain a deletion of the entire E4 coding region) were possible in 293-ORF6 cells, the yield of purified virus was depressed approximately 30-fold compared with that of E1- vectors. The debilitation in AdRSV beta gal.11 vector growth was found to correlate with reduced fiber protein and mRNA accumulation. AdCFTR.11A, a modified E1-/E4- vector with a spacer sequence placed between late region 5 and the right inverted terminal repeat, efficiently expressed fiber and grew with the same kinetic profile and virus yield as did E1- vectors. Moreover, purified AdCFTR.11A yields were equivalent to E1- vector levels. Since no overlapping sequences exist in the E4 regions of E1-/E4- vectors and 293-ORF6 cell lines, replication-competent virus cannot be generated by homologous recombination. In addition, these second-generation E1-/E4- vectors have increased transgene capacity and have been rendered virus replication incompetent outside of the new complementing cell lines.
Serotype Distribution of Streptococcus pneumoniae Infections among Preschool Children in the United States, 1978-1994: Implications for Development of a Conjugate Vaccine (1995)

Conjugation of pneumococcal polysaccharide antigens to a protein carrier may improve protective immunity after vaccination of young children, an age group with high incidence of Streptococcus pneumoniae infection and poor immune responses to polysaccharide vaccines. To identify serotypes most commonly associated with infection in young children, pneumococcal isolates were serotyped from 3884 children < 6 years old (including 3007 < 2 years old) with pneumococcal bacteremia (n = 3169), meningitis (n = 401), or otitis media (n = 314). The isolates were submitted as part of a national surveillance during 1978-1994. Seven serotypes (14, 6B, 19F, 18C, 23F, 4, and 9V) accounted for 3045 isolates (78%). A conjugate pneumococcal vaccine protecting against these seven serotypes and serologically cross-reactive serotypes could potentially prevent 86% of bacteremia and 83% of meningitis but only 65% of otitis media cases. The proportion of isolates covered by such a vaccine increased from 78% to 87% during 1978-1994. Surveillance for pneumococcal serotypes causing infection is needed to detect shifts in serotype distribution over time.
Enzymatic properties of de novo-type mouse DNA (cytosine-5) methyltransferases (2001)

We have purified GST-fused recombinant mouse Dnmt3a and three isoforms of mouse Dnmt3b to near homogeneity. Dnmt3b3, an isoform of Dnmt3b, did not have DNA methylation activity. Dnmt3a, Dnmt3b1 or Dnmt3b2 showed similar activity toward poly(dG-dC)-poly(dG-dC) for measuring de novo methylation activity, and toward poly(dI-dC)-poly(dI-dC) for measuring total activity. This indicates that the enzymes are de novo-type DNA methyltransferases. The enzyme activity was inhibited by NaCl or KCl at concentrations >100 mM. The kinetic parameter, K(m)(AdoMet), for Dnmt3a, Dnmt3b1 and Dnmt3b2 was 0.4, 1.2 and 0.9 microM when poly(dI-dC)-poly(dI-dC) was used, and 0.3, 1.2 and 0.8 microM when poly(dG-dC)-poly(dG-dC) was used, respectively. The K(m)(DNA) values for Dnmt3a, Dnmt3b1 and Dnmt3b2 were 2.7, 1.3 and 1.5 microM when poly(dI-dC)-poly(dI-dC) was used, and 3.5, 1.0 and 0.9 microM when poly(dG-dC)-poly(dG-dC) was used, respectively. For the methylation specificity, Dnmt3a significantly methylated CpG >> CpA. On the other hand, Dnmt3b1 methylated CpG > CpT >/= CpA. Immuno-purified Dnmt3a, Myc-tagged and overexpressed in HEK 293T cells, methylated CpG >> CpA > CpT. Neither Dnmt3a nor Dnmt3b1 methylated the first cytosine of CpC.
Expression of the Thyroid Hormone Transporters Monocarboxylate Transporter-8 (SLC16A2) and Organic Ion Transporter-14 (SLCO1C1) at the Blood-Brain Barrier (2008)

Thyroid hormones require transport across cell membranes to carry out their biological functions. The importance of transport for thyroid hormone signaling was highlighted by the discovery that inactivating mutations in the human monocarboxylate transporter-8 (MCT8) (SLC16A2) cause severe psychomotor retardation due to thyroid hormone deficiency in the central nervous system. It has been reported that Mct8 expression in the mouse brain is restricted to neurons, leading to the model that organic ion transporter polypeptide-14 (OATP14, also known as OATP1C1/SLCO1C1) is the primary thyroid hormone transporter at the blood-brain barrier, whereas MCT8 mediates thyroid hormone uptake into neurons. In contrast to these reports, we report here that in addition to neuronal expression, MCT8 mRNA and protein are expressed in cerebral microvessels in human, mouse, and rat. In addition, OATP14 mRNA and protein are strongly enriched in mouse and rat cerebral microvessels but not in human microvessels. In rat, Mct8 and Oatp14 proteins localize to both the luminal and abluminal microvessel membranes. In human and rodent choroid plexus epithelial cells, MCT8 is concentrated on the epithelial cell apical surface and OATP14 localizes primarily to the basal-lateral surface. Mct8 and Oatp14 expression was also observed in mouse and rat tanycytes, which are thought to form a barrier between hypothalamic blood vessels and brain. These results raise the possibility that reduced thyroid hormone transport across the blood-brain barrier contributes to the neurological deficits observed in affected patients with MCT8 mutations. The high microvessel expression of OATP14 in rodent compared with human brain may contribute to the relatively mild phenotype observed in Mct8-null mice, in contrast to humans lacking functional MCT8.