gebhart/patrepeval huggingface dataset:
Serum surfactant proteins‐A and ‐D as biomarkers in idiopathic pulmonary fibrosis (2002)

Idiopathic pulmonary fibrosis (IPF) has a high mortality rate, and current therapies are only marginally effective. A serum biomarker that predicts clinical outcome would be useful to stage disease, indicate prognosis and the need for aggressive therapy, and help stratify patients for clinical trials. The goals of this study were to determine whether serum levels of surfactant protein-A (SP-A) or surfactant protein-D (SP-D) would distinguish between IPF and other types of interstitial lung disease and whether serum SP-A or SP-D levels predict outcome in patients with IPF. The authors found that serum SP-A and SP-D levels were significantly elevated in patients with IPF and systemic sclerosis compared to sarcoidosis, beryllium disease and normal controls, and that SP-D correlated with radiographic abnormalities in patients with IPF. In addition, the authors found that both serum SP-A and SP-D levels were highly predictive of survival in patients with IPF. This is the largest North American data set of surfactant protein measurements in idiopathic pulmonary fibrosis and the first report using multivariate analysis comparing serum surfactant proteins-A and -D to other commonly measured predictors of survival in idiopathic pulmonary fibrosis. Based on these results, the authors propose that serum surfactant proteins may prove to be useful biomarkers in patients with idiopathic pulmonary fibrosis.
Targeted Disruption of Bone Marrow Stromal Cell-Derived Gremlin1 Limits Multiple Myeloma Disease Progression In Vivo (2020)

In most instances, multiple myeloma (MM) plasma cells (PCs) are reliant on factors made by cells of the bone marrow (BM) stroma for their survival and growth. To date, the nature and cellular composition of the BM tumor microenvironment and the critical factors which drive tumor progression remain imprecisely defined. Our studies show that Gremlin1 (Grem1), a highly conserved protein, which is abundantly secreted by a subset of BM mesenchymal stromal cells, plays a critical role in MM disease development. Analysis of human and mouse BM stromal samples by quantitative PCR showed that <i>GREM1</i>/<i>Grem1</i> expression was significantly higher in the MM tumor-bearing cohorts compared to healthy controls (<i>p</i> < 0.05, Mann-Whitney test). Additionally, BM-stromal cells cultured with 5TGM1 MM PC line expressed significantly higher levels of <i>Grem1</i>, compared to stromal cells alone (<i>p</i> < 0.01, <i>t</i>-test), suggesting that MM PCs promote increased <i>Grem1</i> expression in stromal cells. Furthermore, the proliferation of 5TGM1 MM PCs was found to be significantly increased when co-cultured with <i>Grem1</i>-overexpressing stromal cells (<i>p</i> < 0.01, <i>t</i>-test). To examine the role of Grem1 in MM disease in vivo, we utilized the 5TGM1/KaLwRij mouse model of MM. Our studies showed that, compared to immunoglobulin G (IgG) control antibody-treated mice, mice treated with an anti-Grem1 neutralizing antibody had a decrease in MM tumor burden of up to 81.2% (<i>p</i> < 0.05, two-way ANOVA). The studies presented here demonstrate, for the first time, a novel positive feedback loop between MM PCs and BM stroma, and that inhibiting this vicious cycle with a neutralizing antibody can dramatically reduce tumor burden in a preclinical mouse model of MM.
Elevated Levels of Acute-Phase Proteins and Plasminogen Activator Inhibitor-1 Predict the Development of Type 2 Diabetes (2002)

Elevated serum levels of acute-phase proteins, indicating chronic subclinical inflammation, have been associated with cardiovascular disease as well as the insulin resistance syndrome. Chronic inflammation may also be a risk factor for developing type 2 diabetes. We studied the concentrations of C-reactive protein (CRP), fibrinogen, and plasminogen activator inhibitor-1 (PAI-1) in 1,047 nondiabetic subjects in relation to incident diabetes within 5 years in the Insulin Resistance Atherosclerosis Study. Subjects with diabetes at follow-up (n = 144) had higher baseline levels of fibrinogen (mean +/- SD; 287.8 +/- 58.8 vs. 275.1 +/- 56.0 mg/dl; P = 0.013) as well as of CRP (median [interquartile range]; 2.40 [1.29, 5.87] vs. 1.67 mg/l [0.75, 3.41]; P = 0.0001) and PAI-1 (24 [15, 37.5] vs. 16 ng/ml [9, 27]; P = 0.0001) than nonconverters. The odds ratio (OR) of converting to diabetes was significantly increased with increasing baseline concentrations of the inflammatory markers. In contrast to PAI-1, the association of CRP and fibrinogen with incident diabetes was significantly attenuated after adjustment for body fat (BMI or waist circumference) or insulin sensitivity (S(I)), as assessed by a frequently sampled intravenous glucose tolerance test. In a logistic regression model that included age, sex, ethnicity, clinical center, smoking, BMI, S(I), physical activity, and family history of diabetes, PAI-1 still remained significantly related to incident type 2 diabetes (OR [95% CI] for 1 SD increase: 1.61 [1.20-2.16]; P = 0.002). Chronic inflammation emerges as a new risk factor for the development of type 2 diabetes; PAI-1 predicts type 2 diabetes independent of insulin resistance and other known risk factors for diabetes.
Transcriptional analysis of product‐concentration driven changes in cellular programs of recombinant Clostridium acetobutylicumstrains (2003)

Antisense RNA (asRNA) downregulation alters protein expression without changing the regulation of gene expression. Downregulation of primary metabolic enzymes possibly combined with overexpression of other metabolic enzymes may result in profound changes in product formation, and this may alter the large-scale transcriptional program of the cells. DNA-array based large-scale transcriptional analysis has the potential to elucidate factors that control cellular fluxes even in the absence of proteome data. These themes are explored in the study of large-scale transcriptional analysis programs and the in vivo primary-metabolism fluxes of several related recombinant C. acetobutylicum strains: C. acetobutylicum ATCC 824(pSOS95del) (plasmid control; produces high levels of butanol snd acetone), 824(pCTFB1AS) (expresses antisense RNA against CoA transferase (ctfb1-asRNA); produces very low levels of butanol and acetone), and 824(pAADB1) (expresses ctfb1-asRNA and the alcohol-aldehyde dahydrogenase gene (aad); produce high alcohol and low acetone levels). DNA-array based transcriptional analysis revealed that the large changes in product concentrations (snd notably butanol concentration) due to ctfb1-asRNA expression alone and in combination with aad overexpression resulted in dramatic changes of the cellular transcriptome. Cluster analysis and gene expression patterns of established and putative operons involved in stress response, motility, sporulation, and fatty-acid biosynthesis indicate that these simple genetic changes dramatically alter the cellular programs of C. acetobutylicum. Comparison of gene expression and flux analysis data may point to possible flux-controling steps and suggest unknown regulatory mechanisms.
A new compression scheme for color-quantized images (2002)

An efficient compression scheme for color-quantized images based on progressive coding of color information has been developed. Instead of sorting color indexes into a linear list struc- ture, a binary-tree structure of color indexes is proposed. With this structure, the new algorithm can progressively recover an image from two colors to all of the colors contained in the original image, i.e., a lossless recovery is achieved. Experimental results showed that it can efficiently compress images in both lossy and lossless cases. Typically for color-quantized Lena image with 256 colors, the algorithm achieved 0.5 bpp below state-of-the-art lossless com- pression methods while preserving the efficient lossy compression. Such a compression scheme is very attractive to many applications that require the ability of fast browsing or progressive transmis- sion, and if necessary, to exactly recover the original image. Index Terms—Color-quantized images, data compression, index sorting, progressive refinement.
The case for design using the World Wide Web (1995)

Article Free Access Share on The case for design using the World Wide Web Authors: Mário J. Silva Computer Science Division, University of California, Berkeley, Berkeley, CA Computer Science Division, University of California, Berkeley, Berkeley, CAView Profile , Randy H. Katz Computer Science Division, University of California, Berkeley, Berkeley, CA Computer Science Division, University of California, Berkeley, Berkeley, CAView Profile Authors Info & Claims DAC '95: Proceedings of the 32nd annual ACM/IEEE Design Automation ConferenceJanuary 1995 Pages 579–585https://doi.org/10.1145/217474.217593Published:01 January 1995Publication History 17citation505DownloadsMetricsTotal Citations17Total Downloads505Last 12 Months9Last 6 weeks2 Get Citation AlertsNew Citation Alert added!This alert has been successfully added and will be sent to:You will be notified whenever a record that you have chosen has been cited.To manage your alert preferences, click on the button below.Manage my AlertsNew Citation Alert!Please log in to your account Save to BinderSave to BinderCreate a New BinderNameCancelCreateExport CitationPublisher SiteeReaderPDF
Type I interferon–mediated monogenic autoinflammation: The type I interferonopathies, a conceptual overview (2016)

Type I interferon is a potent substance. As such, the induction, transmission, and resolution of the type I interferon-mediated immune response are tightly regulated. As defined, the type I interferonopathies represent discrete examples of a disturbance of the homeostatic control of this system caused by Mendelian mutations. Considering the complexity of the interferon response, the identification of further monogenic diseases belonging to this disease grouping seems likely, with the recognition of type I interferonopathies becoming of increasing clinical importance as treatment options are developed based on an understanding of disease pathology and innate immune signaling. Definition of the type I interferonopathies indicates that autoinflammation can be both interferon and noninterferon related, and that a primary disturbance of the innate immune system can "spill over" into autoimmunity in some cases. Indeed, that several non-Mendelian disorders, most particularly systemic lupus erythematosus and dermatomyositis, are also characterized by an up-regulation of type I interferon signaling suggests the possibility that insights derived from this work will have relevance to a broader field of clinical medicine.
A Survey of Neurological Mutant Mice (1988)

The lipids of white matter and peripheral nerve from mutant mice with known myelin deficiencies were analyzed by one- and two-dimensional high-performance thin-layer chromatography and quantitated by densitometry. In optic nerve, the mutants jp/Y, jpmsd/Y, qk/qk, shi/shi and shimld/shimld, which have severe central nervous system (CNS) myelin deficiency, had a common pattern of lipid loss: cerebrosides and sulfatides (hydroxy and nonhydroxy forms) were generally reduced by 70-95% or more; most phospholipids were diminished by 15-55%, and cholesterol was reduced by 35-60%. Only in the CNS of jp/Y and jpmsd/Y did cholesterol ester accumulate. In peripheral nerve, the lipid composition varied markedly among these mutants. In jp/Y there was no change, while in jpmsd/Y there was a 5-15% loss among the phospholipids and cholesterol. Homozygous qk had reductions of 75-85% in the nonhydroxy forms of cerebroside and sulfatide, a 130% increase in hydroxy sulfatide, and a 55% loss of sphingomyelin. In shi/shi and shimld/shimld homozygotes, the glycolipids were altered by +/- 20%, most phospholipids and cholesterol were reduced by 5-15%, and sphingomyelin was reduced by 40%. Tr and TrJ showed 35-90% reductions in most lipid classes of the peripheral nervous system; CNS lipid composition was normal. Homozygous twi had a uniform loss of most lipid classes in both optic (generally 10-20%) and trigeminal nerves (generally 40-55%); cerebrosides did not accumulate in these tissues. dy/dy had a 10-20% reduction of cerebrosides in trigeminal nerve trunk. The CNS of dy homozygotes had 10-35% increases in specific classes of glycolipids and phospholipids, and in cholesterol. None of the mutants showed detectable levels of lysophospholipids or other unusual lipid species. The fractions of ethanolamine and choline phosphatides in the plasmalogen form were close to normal in all mutants.
Glucocorticoid‐induced leucine zipper is an endogenous antiinflammatory mediator in arthritis (2010)

Our findings indicate that GILZ functions as an endogenous inhibitor of chronic inflammation via effects on cytokine expression and suggest that local modulation of GILZ expression could be a beneficial therapeutic strategy.
Complexes containing activating transcription factor (ATF)/cAMP-responsive-element-binding protein (CREB) interact with the CCAAT/enhancer-binding protein (C/EBP)–ATF composite site to regulate Gadd153 expression during the stress response (1999)

Gadd153, also known as chop, encodes a member of the CCAAT/enhancer-binding protein (C/EBP) transcription factor family and is transcriptionally activated by cellular stress signals. We recently demonstrated that arsenite treatment of rat pheochromocytoma PC12 cells results in the biphasic induction of Gadd153 mRNA expression, controlled in part through binding of C/EBPbeta and two uncharacterized protein complexes to the C/EBP-ATF (activating transcription factor) composite site in the Gadd153 promoter. In this report, we identified components of these additional complexes as two ATF/CREB (cAMP-responsive-element-binding protein) transcription factors having differential binding activities dependent upon the time of arsenite exposure. During arsenite treatment of PC12 cells, we observed enhanced binding of ATF4 to the C/EBP-ATF site at 2 h as Gadd153 mRNA levels increased, and enhanced binding of ATF3 complexes at 6 h as Gadd153 expression declined. We further demonstrated that ATF4 activates, while ATF3 represses, Gadd153 promoter activity through the C/EBP-ATF site. ATF3 also repressed ATF4-mediated transactivation and arsenite-induced activation of the Gadd153 promoter. Our results suggest that numerous members of the ATF/CREB family are involved in the cellular stress response, and that regulation of stress-induced biphasic Gadd153 expression in PC12 cells involves the ordered, sequential binding of multiple transcription factor complexes to the C/EBP-ATF composite site.
Recruitment of HIV and Its Receptors to Dendritic Cell-T Cell Junctions (2003)

Monocyte-derived dendritic cells (MDDCs) can efficiently bind and transfer HIV infectivity without themselves becoming infected. Using live-cell microscopy, we found that HIV was recruited to sites of cell contact in MDDCs. Analysis of conjugates between MDDCs and T cells revealed that, in the absence of antigen-specific signaling, the HIV receptors CD4, CCR5, and CXCR4 on the T cell were recruited to the interface while the MDDCs concentrated HIV to the same region. We propose that contact between dendritic cells and T cells facilitates transmission of HIV by locally concentrating virus, receptor, and coreceptor during the formation of an infectious synapse.
Proxemic interaction (2010)

In the everyday world, much of what we do is dictated by how we interpret spatial relationships, or proxemics. What is surprising is how little proxemics are used to mediate people's interactions with surrounding digital devices. We imagine proxemic interaction as devices with fine-grained knowledge of nearby people and other devices -- their position, identity, movement, and orientation -- and how such knowledge can be exploited to design interaction techniques. In particular, we show how proxemics can: regulate implicit and explicit interaction; trigger such interactions by continuous movement or by movement of people and devices in and out of discrete proxemic regions; mediate simultaneous interaction of multiple people; and interpret and exploit people's directed attention to other people and objects. We illustrate these concepts through an interactive media player running on a vertical surface that reacts to the approach, identity, movement and orientation of people and their personal devices.
Hyperexcitable Substantia Nigra Dopamine Neurons inPINK1- andHtrA2/Omi-Deficient Mice (2010)

The electrophysiological properties of substantia nigra pars compacta (SNC) dopamine neurons can influence their susceptibility to degeneration in toxin-based models of Parkinson's disease (PD), suggesting that excitotoxic and/or hypoactive mechanisms may be engaged during the early stages of the disease. It is unclear, however, whether the electrophysiological properties of SNC dopamine neurons are affected by genetic susceptibility to PD. Here we show that deletion of PD-associated genes, PINK1 or HtrA2/Omi, leads to a functional reduction in the activity of small-conductance Ca(2+)-activated potassium channels. This reduction causes SNC dopamine neurons to fire action potentials in an irregular pattern and enhances burst firing in brain slices and in vivo. In contrast, PINK1 deletion does not affect firing regularity in ventral tegmental area dopamine neurons or substantia nigra pars reticulata GABAergic neurons. These findings suggest that changes in SNC dopamine neuron excitability may play a role in their selective vulnerability in PD.
Thermal stability of ohmic contacts between Ti and Se-passivated n-type Si(001) (2004)

The thermal stability of the interface between Ti and Se-passivated n-type Si(001) is investigated. As-deposited Ti contacts show ohmic characteristics. After annealing at temperatures from 200 °C to 480 °C in air, the Se-passivated samples are much more resistant to Schottky transition as compared to the bare samples. The bare samples turn to Schottky below 300 °C, whereas the passivated samples are ohmic all the way to 400 °C. A difference of over 100 °C is observed between the two types of samples. Schottky barrier heights are determined using capacitance–voltage and activation–energy methods. The bare samples reach a maximum barrier height of 0.39 eV as determined by activation–energy measurements, while the passivated samples maximize at 0.19 eV. We deduce that a monolayer of Se suppresses silicidation between Ti and Si by eliminating dangling bonds on Si(001).
A model of periodontitis in the rat: effect of lipopolysaccharide on bone resorption, osteoclast activity, and local peptidergic innervation (2004)

Intragingival injection of LPS in the rat provides an easily induced reproducible experimental model of periodontal inflammation that reiterates features of human disease.
Deep Penetration of a PDT Drug into Tumors by Noncovalent Drug-Gold Nanoparticle Conjugates (2011)

Efficient drug delivery to tumors is of ever-increasing importance. Single-visit diagnosis and treatment sessions are the goal of future theranostics. In this work, a noncovalent PDT cancer drug-gold nanoparticle (Au NP) conjugate system performed a rapid drug release and deep penetration of the drug into tumors within hours. The drug delivery mechanism of the PDT drug through Au NPs into tumors by passive accumulation was investigated via fluorescence imaging, elemental analysis, and histological staining. The pharmacokinetics of the conjugates over a 7-day test period showed rapid drug excretion, as monitored via the fluorescence of the drug in urine. Moreover, the biodistribution of Au NPs in this study period indicated clearance of the NPs from the mice. This study suggests that noncovalent delivery via Au NPs provides an attractive approach for cancer drugs to penetrate deep into the center of tumors.
Immunotherapy in a Natural Model of A&#946; Pathogenesis: The Aging Beagle (2009)

Alzheimer disease (AD) is the most common form of dementia in the elderly and the number of individuals developing the disease is rapidly rising. Interventions focused on reducing beta-amyloid (Abeta), a component of senile plaques within the AD brain offer a promising approach to prevent or slow disease progression. In this review, we describe the immune system and cognitive and neurobiological features of a natural model of human brain aging, the beagle. The immune system of dogs shares many features of the human immune system, including developmental and aging characteristics. Further, dogs naturally accumulate human sequence Abeta as they age, which coincides with declines in learning and memory. A longitudinal study (approximately 2 years) of the response of aged beagles to vaccination with fibrillar Abeta1-42 indicated that despite significant clearance of Abeta, there were limited benefits in cognitive function. However, there was evidence for maintenance of executive function over time. These results are strikingly similar to reports of human clinical immunotherapy trials. We propose that the canine model complements existing animal models and will be helpful in developing new vaccine approaches to slowing or preventing Abeta pathology that can be translated to human clinical trials.
Development of mucosal protection against the heat-stable enterotoxin (ST) of Escherichia coli by oral immunization with a genetic fusion delivered by a bacterial vector (1993)

An LT-B-ST (LT-B/ST) fusion peptide was constructed by genetically joining the 5' terminus of a synthetic gene coding for the heat-stable enterotoxin (ST) of Escherichia coli to the 3' terminus of the gene coding for the binding subunit of the heat-labile enterotoxin (LT-B) of E. coli. An eight-amino-acid, proline-containing linker was included between the LT-B and ST moieties. An aroA mutant of Salmonella dublin transformed with a plasmid carrying this genetic construct was shown to express a fusion peptide with antigenic determinants of both LT-B and ST. Mice were immunized orally with this strain or with a control strain expressing just LT-B from the same plasmid. Sera and mucosal secretions were obtained and analyzed for the presence of serum immunoglobulin G and mucosal immunoglobulin A that were able to recognize LT-B and ST by enzyme-linked immunosorbent assay (ELISA) and, more importantly, were able to neutralize native ST in the suckling mouse assay. Sera and mucosal secretions from animals immunized with the strain expressing the LT-B/ST fusion exhibited detectable ELISA reactivity against LT-B but not against native ST. However, even in the absence of detectable ELISA reactivity, both sera and mucosal secretions from these animals were able to neutralize the biological activity of native ST in the suckling mouse assay. These findings are important because they demonstrate the development of mucosal protection against ST by oral immunization with a genetic fusion delivered by a bacterial vector.