gebhart/patrepeval huggingface dataset:
The Potential of Adipose-Derived Adult Stem Cells as a Source of Neuronal Progenitor Cells (2005)

Adipose-derived adult stem cells are a population of mesenchymal stem cells extracted from discarded adipose tissue. Many have reported the differentiation of adipose-derived stem cells into chondrocytes, myocytes, osteoblasts, and, most recently, neural progenitor cells. This article covers the current state of the potential of the differentiation of adipose-derived stem cells into neuronal cells and an overview of their potential as adult stem therapies for neurological disorders. It has been reported that adipose-derived stem cells are capable of undergoing neuronal differentiation using protocols similar to that of Woodbury et al., which reported the differentiation of bone marrow stromal cells specifically into neurons. However, the transdifferentiation of bone marrow stromal cells into neuronal cells has recently fallen under intense criticism, which will likely place the plasticity of adipose-derived stem cells under scrutiny as well. To date, no group has produced evidence that adipose-derived stem cells are capable of differentiating to mature, functional neuronal cells in vitro. However, recent in vivo studies with adipose-derived stem cells are promising.
Therapeutic vaccines for chronic diseases: successes and technical challenges (2011)

Chronic, non-communicable diseases are the major cause of death and disability worldwide and have replaced infectious diseases as the major burden of society in large parts of the world. Despite the complexity of chronic diseases, relatively few predisposing risk factors have been identified by the World Health Organization. Those include smoking, alcohol abuse, obesity, high cholesterol and high blood pressure as the cause of many of these chronic conditions. Here, we discuss several examples of vaccines that target these risk factors with the aim of preventing the associated diseases and some of the challenges they face.
Degradation of Overexpressed Wild-type and Mutant Uricase Proteins in Cultured Cells (1999)

Wild-type and mutated urate oxidase (UO) proteins were overexpressed in Cos-1 and HEK293 cells and were analyzed by Western blotting and several morphological methods. By immunoelectron microscopy, wild-type UO formed large aggregates in the cytoplasm and nucleoplasm and exhibited a crystalloid structure. Mutated UO (UOdC), from which 28 amino acids, including peroxisomal targeting signal at the C-terminus, were deleted, formed dispersed aggregates in the cytoplasm and nucleus. Chimeric UO (MUOdC), which was made by addition of the mitochondrial targeting signal of serine:pyruvate/glyoxylate aminotransferase to the N-terminus of UOdC, attached to ER to form a complicated MUOdC-ER complex. These three structures were immunostained for ubiquitin- and p32-subunits of proteasomes. Western blotting showed strong signal for UO and UOdC but very weak signal for MUOdC. The results suggest that overexpressed UO and UOdC accumulate in the cells because their synthesis rate is higher than the degradation rate, whereas MUOdC forming a complex with ER is degraded very rapidly. The ubiquitin-proteasome pathway may be involved in the degradation of these proteins.
Complement Factor H Antibodies from Lung Cancer Patients Induce Complement-Dependent Lysis of Tumor Cells, Suggesting a Novel Immunotherapeutic Strategy (2015)

Characterization of the humoral immune response in selected patients with cancer who uniformly do well may lead to the development of novel therapeutic strategies. We have previously shown an association between patients with early-stage nonmetastatic lung cancer and autoantibodies to complement factor H (CFH). CFH protects normal and tumor cells from destruction by the alternative complement pathway by inactivating C3b, a protein that is essential for formation of a lytic complex on the cell surface. Here, we show that CFH autoantibodies in lung cancer patients recognize a conformationally distinct form of CFH in vitro, are IgG3 subclass, and epitope map to a crucial functional domain of CFH known to interact with C3b. Purified CFH autoantibodies inhibited binding of CFH to A549 lung tumor cells, increased C3b deposition, and caused complement-dependent tumor cell lysis. This work demonstrates that CFH autoantibodies isolated from patients with lung cancer can kill tumor cells in vitro, suggesting that they may perform this function in vivo as well. Development of specific antibodies to the conformationally distinct epitope of CFH may lead to a useful biologic therapy for lung cancer.
Dynamic Antibody Specificities and Virion Concentrations in Circulating Immune Complexes in Acute to Chronic HIV-1 Infection (2011)

Understanding the interactions between human immunodeficiency virus type 1 (HIV-1) virions and antibodies (Ab) produced during acute HIV-1 infection (AHI) is critical for defining antibody antiviral capabilities. Antibodies that bind virions may prevent transmission by neutralization of virus or mechanically prevent HIV-1 migration through mucosal layers. In this study, we quantified circulating HIV-1 virion-immune complexes (ICs), present in approximately 90% of AHI subjects, and compared the levels and antibody specificity to those in chronic infection. Circulating HIV-1 virions coated with IgG (immune complexes) were in significantly lower levels relative to the viral load in acute infection than in chronic HIV-1 infection. The specificities of the antibodies in the immune complexes differed between acute and chronic infection (anti-gp41 Ab in acute infection and anti-gp120 in chronic infection), potentially suggesting different roles in immunopathogenesis for complexes arising at different stages of infection. We also determined the ability of circulating IgG from AHI to bind infectious versus noninfectious virions. Similar to a nonneutralizing anti-gp41 monoclonal antibody (MAb), purified plasma IgG from acute HIV-1 subjects bound both infectious and noninfectious virions. This was in contrast to the neutralizing antibody 2G12 MAb that bound predominantly infectious virions. Moreover, the initial antibody response captured acute HIV-1 virions without selection for different HIV-1 envelope sequences. In total, this study demonstrates that the composition of immune complexes are dynamic over the course of HIV-1 infection and are comprised initially of antibodies that nonselectively opsonize both infectious and noninfectious virions, likely contributing to the lack of efficacy of the antibody response during acute infection.
Epidermal Growth Factor Tethered to β-Tricalcium Phosphate Bone Scaffolds via a High-Affinity Binding Peptide Enhances Survival of Human Mesenchymal Stem Cells/Multipotent Stromal Cells in an Immune-Competent Parafascial Implantation Assay in Mice (2016)

Stem cells are limited as tissue replacements owing to rapid death induced in the hostile wound environment. It has been found that restricting epidermal growth factor (EGF) receptor signaling to the membrane provides a survival advantage. This report elucidates a method to tether EGF to bone induction material to improve the survival of mesenchymal stem cells/multipotent stromal cells in vivo.
Evaluation of the Effect of Betapropiolactone/Ultraviolet Irradiation (BPL/UV) Treatment of Source Plasma on Hepatitis Transmission by Factor IX Complex in Chimpanzees (1980)

Summary To evaluate the safety of a β-Propiolactone/Ultraviolet (BPL/UV), irradiated Factor IX complex preparation we inoculated 8 chimpanzees with 25 units Factor IX/Kilo from a pool of 5 production lots which had been treated in this manner. These lots were derived from approximately 1,000 donors. Animals were followed with weekly tests for hepatitis B serologic markers and transaminases, and biweekly liver biopsies, for 6 months. No evidence of transmission of hepatitis B, or non-A, non-B viruses was observed. To further evaluate the BPL/UV procedure a plasma pool was intentionally contaminated with hepatitis B virus and one half of the pool treated with BPL/UV. Factor IX complex was isolated from the treated and untreated pools and each was inoculated into 4 chimpanzees. The Factor IX derived from untreated plasma infected all four animals with an average incubation period of 10.5 weeks, whereas that prepared from BPL/UV treated plasma infected only one of four animals with an incubation period of 21 weeks. These results were interpreted as suggesting that BPL/UV can inactivate approximately 99.9% of hepatitis B virus infectivity.
Oncogene cooperation in tumor maintenance and tumor recurrence in mouse mammary tumors induced by Myc and mutant Kras (2008)

Most, if not all, cancers are composed of cells in which more than one gene has a cancer-promoting mutation. Although recent evidence has shown the benefits of therapies targeting a single mutant protein, little attention has been given to situations in which experimental tumors are induced by multiple cooperating oncogenes. Using combinations of doxycycline-inducible and constitutive Myc and mutant Kras transgenes expressed in mouse mammary glands, we show that tumors induced by the cooperative actions of two oncogenes remain dependent on the activity of a single oncogene. Deinduction of either oncogene individually, or both oncogenes simultaneously, led to partial or complete tumor regression. Prolonged remission followed deinduction of Kras(G12D) in the context of continued Myc expression, deinduction of a MYC transgene with continued expression of mutant Kras produced modest effects on life extension, whereas simultaneous deinduction of both MYC and Kras(G12D) transgenes further improved survival. Disease relapse after deinduction of both oncogenes was associated with reactivation of both oncogenic transgenes in all recurrent tumors, often in conjunction with secondary somatic mutations in the tetracycline transactivator transgene, MMTV-rtTA, rendering gene expression doxycycline-independent. These results demonstrate that tumor viability is maintained by each gene in a combination of oncogenes and that targeted approaches will also benefit from combination therapies.
Temperature measurements during ultrasound hyperthermia (1989)

In this study the ultrasonic field distortions and the temperature measurement errors caused by temperature sensing probes were investigated. It was found that probes with diameters equal to or greater than 1/2 of the square root of the wavelength (lambda) scatter and reflect the waves, and thus distort the field significantly. Smaller probes down to lambda 1/2/5 in diameter had a detectable effect which was very local and, therefore, will probably not have a significant effect on the overall temperature distribution. When the temperature measurement errors were studied, even the smallest probes showed some self-heating artifact and its magnitude depended on the probe size, material, structure, orientation, and the operating frequency. This error was small with most of the nonultrasound absorbing probes (such as bare wires or stainless steel needle probes), but significant with plastic shielded thermocouples. The energy absorption associated with plastic coated probes can be reduced by orienting the probe parallel to the beam, by scanning the focus in such a manner that the focus is not passing on the sensor, and by inserting the probe in a stainless steel catheter. The temperature measurement error can also be reduced by covering the plastic probe with a high- (or low-) acoustical impedance material around the sensor. This would scatter the sound around the probe, thus preventing energy absorption in the plastic. This arrangement can preserve the desirable properties of plastic probes (mainly flexibility, strength, and electrical isolation from the patient) while at the same time allowing fairly absorption artifact free measurements.
Mosquitoes smell and avoid the insect repellent DEET (2008)

The insect repellent DEET is effective against a variety of medically important pests, but its mode of action still draws considerable debate. The widely accepted hypothesis that DEET interferes with the detection of lactic acid has been challenged by demonstrated DEET-induced repellency in the absence of lactic acid. The most recent hypothesis suggests that DEET masks or jams the olfactory system by attenuating electrophysiological responses to 1-octen-3-ol. Our research shows that mosquitoes smell DEET directly and avoid it. We performed single-unit recordings from all functional ORNs on the antenna and maxillary palps of Culex quinquefasciatus and found an ORN in a short trichoid sensillum responding to DEET in a dose-dependent manner. The same ORN responded with higher sensitivity to terpenoid compounds. SPME and GC analysis showed that odorants were trapped in conventional stimulus cartridges upon addition of a DEET-impregnated filter paper strip thus leading to the observed reduced electrophysiological responses, as reported elsewhere. With a new stimulus delivery method releasing equal amounts of 1-octen-3-ol alone or in combination with DEET we found no difference in neuronal responses. When applied to human skin, DEET altered the chemical profile of emanations by a "fixative" effect that may also contribute to repellency. However, the main mode of action is the direct detection of DEET as indicated by the evidence that mosquitoes are endowed with DEET-detecting ORNs and corroborated by behavioral bioassays. In a sugar-feeding assay, both female and male mosquitoes avoided DEET. In addition, mosquitoes responding only to physical stimuli avoided DEET.
High-Resolution Satellite Imagery Mapping of the Surface Rupture and Slip Distribution of the Mw 7.8, 14 November 2001 Kokoxili Earthquake, Kunlun Fault, Northern Tibet, China (2005)

International audience
Estimating the output gap in real time: A factor model approach (2008)

An approximate dynamic factor model can substantially improve the reliability of real time output gap estimates. The model extracts a common component from macroeconomic indicators, which reduces errors in the gap due to data revisions. The model's ability to handle the unbalanced arrival of data, also yields favorable nowcasting properties and thus starting conditions for the filtering of data into trend and deviations from trend. Combined with the method of augmenting data with forecasts prior to filtering, this greatly reduces the end-of-sample imprecision in the gap estimate. The increased precision has economic significance for real time policy decisions.
CMOS active pixel image sensor with simple floating gate pixels (1995)

A new pixel structure using a simple floating gate (SFG) has been proposed. The pixel consists of a coupling capacitor, a photogate, a barrier gate and a MOS transistor. It features complete reset that results in no kTC noise and no image lag, high blooming overload protection, nondestructive readout (NDRO), and CMOS compatibility. Its basic operation has been confirmed with a 32(H)/spl times/27(V) pixel area array. Since the pixel structure is relatively simple, small pixel size is feasible.< <ETX xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">&gt;</ETX>
Clustering of highly homologous sequences to reduce the size of large protein databases (2001)

We present a fast and flexible program for clustering large protein databases at different sequence identity levels. It takes less than 2 h for the all-against-all sequence comparison and clustering of the non-redundant protein database of over 560,000 sequences on a high-end PC. The output database, including only the representative sequences, can be used for more efficient and sensitive database searches.
Discovery of a Small-Molecule Degrader of Bromodomain and Extra-Terminal (BET) Proteins with Picomolar Cellular Potencies and Capable of Achieving Tumor Regression (2017)

The bromodomain and extra-terminal (BET) family proteins, consisting of BRD2, BRD3, BRD4, and testis-specific BRDT members, are epigenetic "readers" and play a key role in the regulation of gene transcription. BET proteins are considered to be attractive therapeutic targets for cancer and other human diseases. Recently, heterobifunctional small-molecule BET degraders have been designed based upon the proteolysis targeting chimera (PROTAC) concept to induce BET protein degradation. Herein, we present our design, synthesis, and evaluation of a new class of PROTAC BET degraders. One of the most promising compounds, 23, effectively degrades BRD4 protein at concentrations as low as 30 pM in the RS4;11 leukemia cell line, achieves an IC<sub>50</sub> value of 51 pM in inhibition of RS4;11 cell growth and induces rapid tumor regression in vivo against RS4;11 xenograft tumors. These data establish that compound 23 (BETd-260/ZBC260) is a highly potent and efficacious BET degrader.
Platelet‐Derived Growth Factor (PDGF) Gene Delivery for Application in Periodontal Tissue Engineering (2001)

These findings demonstrate that gene delivery of platelet-derived growth factor stimulates cementoblast activity that is sustained above that of rhPDGF-AA application. The use of gene therapy as a mode of growth factor delivery offers a novel approach to periodontal tissue engineering.
Two-component regulatory systems can interact to process multiple environmental signals (1996)

The PhoP/PhoQ two-component system of Salmonella typhimurium governs transcription of some 25 loci in response to the extracellular concentration of Mg2+. We have now identified one of these loci as pmrCAB, which codes for a two-component system that mediates resistance to the antibiotic polymyxin B. Transcription of seven of 25 PhoP-activated loci was dependent on a functional PmrA protein, the response regulator of the PmrA/PmrB system. Expression of the PmrA-dependent loci was induced by either Mg2+ limitation or mild acidification, whereas transcription of a PmrA-independent gene was activated by Mg2+ limitation but not acid pH. Induction of PmrA-activated genes by Mg2 limitation required the PhoP and PhoQ proteins. In contrast, the acid-mediated activation of PmrA-regulated genes occurred in strains that were missing either one of these proteins. Transcriptional regulation by a cascade of two-component systems allows pathogenic bacteria to express their virulence determinants in response to a broader spectrum of environmental cues.
Altered peptide ligand vaccination with Flt3 ligand expanded dendritic cells for tumor immunotherapy (2001)

Most tumor-associated antigens represent self-proteins and as a result are poorly immunogenic due to immune tolerance. Here we show that tolerance to carcinoembryonic antigen (CEA), which is overexpressed by the majority of lethal malignancies, can be reversed by immunization with a CEA-derived peptide. This peptide was altered to make it a more potent T cell antigen and loaded onto dendritic cells (DCs) for delivery as a cellular vaccine. Although DCs are rare in the blood, we found that treatment of advanced cancer patients with Flt3 ligand, a hematopoietic growth factor, expanded DCs 20-fold in vivo. Immunization with these antigen-loaded DCs induced CD8 cytotoxic T lymphocytes that recognized tumor cells expressing endogenous CEA. Staining with peptide-MHC tetramers demonstrated the expansion of CD8 T cells that recognize both the native and altered epitopes and possess an effector cytotoxic T lymphocyte phenotype (CD45RA(+)CD27(-)CCR7(-)). After vaccination, two of 12 patients experienced dramatic tumor regression, one patient had a mixed response, and two had stable disease. Clinical response correlated with the expansion of CD8 tetramer(+) T cells, confirming the role of CD8 T cells in this treatment strategy.
Cimetidine therapy in nonsteroidal anti-inflammatory drug gastropathy. Double-blind long-term evaluation. (1987)

To assess the efficacy of cimetidine in treating and preventing gastric mucosal lesions associated with nonsteroidal anti-inflammatory drug (NSAID) therapy (NSAID gastropathy), we endoscopically studied 104 patients taking NSAIDs for a variety of rheumatic diseases. Fifty-six percent (22/43) of patients randomized to cimetidine 300 mg four times a day and 52% (22/42) of those randomized to placebo showed progression of endoscopic lesions during the eight-week short-term phase. Thirty-nine patients whose endoscopic lesions improved were then randomized to a ten-month maintenance regimen of either cimetidine 400 mg at bedtime or placebo. Fifty percent (7/14) of placebo-treated and 42% (5/12) of cimetidine-treated patients showed progression of lesions during the maintenance phase. The failure of cimetidine to offer any significant benefit under these protocol conditions reflects the fundamental difference in pathophysiologic features between classic acid-mediated ulcer disease and NSAID gastropathy.
Ibrutinib and idelalisib synergistically target BCR-controlled adhesion in MCL and CLL: a rationale for combination therapy (2015)

To the editor:

Most B-cell malignancies are dependent upon signaling by the B-cell receptor (BCR) and other growth and survival signals provided by the tumor microenvironment. Two recently US Food and Drug Administration–approved drugs that target the BCR signalosome, the Bruton tyrosine kinase (
The Modified Yen Model (2010)

Asphaltenes, the most aromatic of the heaviest components of crude oil, are critical to all aspects of petroleum use, including production, transportation, refining, upgrading, and heavy-end use in paving and coating materials. As such, efficiency in these diverse disciplines mandates proper chemical accounting of structure−function relations of crude oils and asphaltenes, the vision of petroleomics (Asphaltenes, Heavy Oils and Petroleomics; Mullins, O. C., Sheu, E. Y., Hammami, A., Marshall, A. G., Eds.; Springer: New York, 2007). Indeed, the molecular characterization of asphaltenes is required as well as the detailed understanding of the hierarchical colloidal structures of asphaltenes and petroleum. With great prescience, Professor Teh Fu Yen and co-workers proposed a hierarchical model of asphaltenes to account for many of their characteristics known at that time (Dickie, J. P.; Yen, T. F. Macrostrucutres of asphaltic fractions by various instrumental methods. Anal. Chem. 1967, 39, 1847−1852). This model is rightfully known as the Yen model. Nevertheless, at the time the Yen model was formulated, there were many order-of-magnitude uncertainties in asphaltene science that precluded establishing structure−function relations and causality, thereby rendering the Yen model somewhat phenomenological. Petroleum science has advanced greatly in recent years enabling development of a much more specific model yet still based on precepts of the Yen model; we call this the “modified Yen model”. The modified Yen model is shown to account for wide ranging, myriad properties of asphaltenes, including their dynamics. In addition, the modified Yen model has even proven successful for understanding interfacial phenomena involving asphaltenes. Moreover, the modified Yen model accounts for fundamental observations in oil reservoirs and is now propelling significantly improved efficiency in oil production. The modified Yen model is a simple, yet powerful construct that provides the foundation to test future developments in asphaltene and petroleum science; refinement of the modified Yen model is an expected outcome of this process.