gebhart/patrepeval huggingface dataset:
Development of an effective gene delivery system: a study of complexes composed of a peptide-based amphiphilic DNA compaction agent and phospholipid (2001)

We recently described a basic technology to efficiently combine compacted DNA with phospholipids and hydrophobic peptides, to produce homogenous complexes that are completely resistant to nuclease. We have developed this technology further to form gene delivery complexes that transfect cells effectively in vitro. In addition to plasmid DNA, the complexes contained two basic components: (i) a DNA compacting peptide (-CGKKKFKLKH), either conjugated to lipid or extended to contain (WLPLPWGW-) and (ii) either phosphatidylethanolamine or phosphatidylcholine. Complexes containing a 5.5-fold charge equivalence (peptide charge/DNA charge) of WLPLPWGWCGKKKFKLKH and 5 nmol dimyristoleoylphosphatidylethanolamine/microg DNA produced the highest luciferase gene expression, exceeding 1 x 10(9) relative light units/s/mg protein (>3 microg luciferase per mg protein). These complexes transfected OVCAR-3, COS-7 and HeLa cells at either similar or superior levels when compared to polyethylenimine or lipofectamine complexes. With green fluorescent protein reporter gene, >50% of HeLa cells were positive 30 h after addition of these complexes. Furthermore, these optimal complexes were the least sensitive to pre-treatment of cells with chloroquine, indicating efficient endosomal escape. Our results indicated that self-assembling complexes of plasmid DNA, amphiphilic peptide and phosphatidylethanolamine are highly effective non-viral gene delivery systems.
RUNX proteins desensitize multiple myeloma to lenalidomide via protecting IKZFs from degradation (2019)

Ikaros family zinc finger protein 1 and 3 (IKZF1 and IKZF3) are transcription factors that promote multiple myeloma (MM) proliferation. The immunomodulatory imide drug (IMiD) lenalidomide promotes myeloma cell death via Cereblon (CRBN)-dependent ubiquitylation and proteasome-dependent degradation of IKZF1 and IKZF3. Although IMiDs have been used as first-line drugs for MM, the overall survival of refractory MM patients remains poor and demands the identification of novel agents to potentiate the therapeutic effect of IMiDs. Using an unbiased screen based on mass spectrometry, we identified the Runt-related transcription factor 1 and 3 (RUNX1 and RUNX3) as interactors of IKZF1 and IKZF3. Interaction with RUNX1 and RUNX3 inhibits CRBN-dependent binding, ubiquitylation, and degradation of IKZF1 and IKZF3 upon lenalidomide treatment. Inhibition of RUNXs, via genetic ablation or a small molecule (AI-10-104), results in sensitization of myeloma cell lines and primary tumors to lenalidomide. Thus, RUNX inhibition represents a valuable therapeutic opportunity to potentiate IMiDs therapy for the treatment of multiple myeloma.
Signal epidetection in third-harmonic generation microscopy of turbid media (2007)

Third-harmonic generation (THG) imaging of thick samples or large organisms requires TH light to be epicollected through the focusing objective. In this study we first estimate the amount of backward-to-forward TH radiation created by an isolated object as a function of size and spatial frequencies in the object. Theory and model experiments indicate that no significant signal can be epidetected from a (biological) dielectric structure embedded in a transparent medium. In contrast, backward emission is observed from metal nanoparticles where THG is partly a surface effect. We then address the case of an object embedded in a turbid medium. Experiments and Monte Carlo simulations show that epidetection is possible when the absorption mean free path of harmonic light in the medium exceeds its reduced scattering length, and that epicollection efficiency critically depends on the microscope field-of-view even at shallow depths, because backscattered light is essentially diffusive. These observations provide guidelines for optimizing epidetection in third-harmonic, second-harmonic, or CARS imaging of thick tissues.
Multiprotein complexes that link dislocation, ubiquitination, and extraction of misfolded proteins from the endoplasmic reticulum membrane (2005)

Polypeptides that fail to pass quality control in the endoplasmic reticulum (ER) are dislocated from the ER membrane to the cytosol where they are degraded by the proteasome. Derlin-1, a member of a family of proteins that bears homology to yeast Der1p, was identified as a factor that is required for the human cytomegalovirus US11-mediated dislocation of class I MHC heavy chains from the ER membrane to the cytosol. Derlin-1 acts in concert with the AAA ATPase p97 to remove dislocation substrate proteins from the ER membrane, but it is unknown whether other factors aid Derlin-1 in its function. Mammalian genomes encode two additional, related proteins (Derlin-2 and Derlin-3). The similarity of the mammalian Derlin-2 and Derlin-3 proteins to yeast Der1p suggested that these as-yet-uncharacterized Derlins also may play a role in ER protein degradation. We demonstrate here that Derlin-2 is an ER-resident protein that, similar to Derlin-1, participates in the degradation of proteins from the ER. Furthermore, we show that Derlin-2 forms a robust multiprotein complex with the p97 AAA ATPase as well as the mammalian orthologs of the yeast Hrd1p/Hrd3p ubiquitin-ligase complex. The data presented here define a set of interactions between proteins involved in dislocation of misfolded polypeptides from the ER.
Safety, pharmacodynamics, and pharmacokinetics of single doses of BAY 59-7939, an oral, direct factor Xa inhibitor (2005)

BAY 59--7939 was well tolerated with predictable pharmacodynamics and pharmacokinetics across a wide range of doses in healthy male subjects. BAY 59--7939 was shown to be an effective and specific factor Xa inhibitor.
Preparation of Hydrophobic Drugs Cyclodextrin Complex by Lyophilization Monophase Solution (2006)

A novel method was evaluated for preparation of hydrophobic drugs cyclodextrin (CD) complex in this study. To obtain sterilized drug-CD complex lyophilized powder for injection or other purpose, the CD solution in water and the hydrophobic drug in tertiary butyl alcohol (TBA) were mixed in a suitable volume ratio, filtered through 0.22 microm millpores, and subsequently freeze-dried. A high drug concentration was obtained in the co-solvent due to the good solvency of TBA, which is miscible with water in any proportion, for hydrophobic drugs. Moreover, TBA could be removed rapidly and completely by freeze-drying because of its high vapor pressure and high melting point. The chemical stability of some labile active compounds was also improved in TBA-water co-solvent. Based on the data from differential scanning calormetry (DSC) and X-ray diffractometry (XRD), drug was amorphous in freeze-dried complex. The fourier transform infrared spectra indicated drug-CD interaction was present in drug-CD complex. An enhanced dissolution rate was also obtained in drug-CD complex. These results proved drug-CD complex had been formed after this technique. Thus, this report provided a simple, efficient, and economic technique for preparation of hydrophobic drugs CD complex, which may be useful practically in modifying hydrophobic drugs physicochemical properties and improving their absorption and pharmacodynamics.
A physiological camera shake model for image stabilization systems (2011)

In order to design and validate optimal motion compensation controller algorithms for optical image stabilization, trustworthy hand tremor models are needed. This paper presents an accurate camera shake model derived from both medical and digital photography observations. It successfully reproduces subjective observations made about the shape and time evolution of hand tremor-induced motion blur patterns. Our model is compared to the simpler random-walk and straight-line-walk models as well as previously reported experiments. It paves the way towards accurate deblurring and optimal image stabilization algorithms by providing realistic motion blur point spread function matrices. To our best knowledge it is the first model in which both spectral and statistical characteristics fit several ground truths from literature.
Endogenous Telomerase Reverse Transcriptase N-Terminal Tagging Affects Human Telomerase Function at Telomeres In Vivo (2016)

Telomerase action at telomeres is essential for the immortal phenotype of stem cells and the aberrant proliferative potential of cancer cells. Insufficient telomere maintenance can cause stem cell and tissue failure syndromes, while increased telomerase levels are associated with tumorigenesis. Both pathologies can arise from only small perturbation of telomerase function. To analyze telomerase at its low endogenous expression level, we genetically engineered human pluripotent stem cells (hPSCs) to express various N-terminal fusion proteins of the telomerase reverse transcriptase from its endogenous locus. Using this approach, we found that these modifications can perturb telomerase function in hPSCs and cancer cells, resulting in telomere length defects. Biochemical analysis suggests that this defect is multileveled, including changes in expression and activity. These findings highlight the unknown complexity of telomerase structural requirements for expression and function in vivo.
MOLECULAR GENETICS OF YEAST MATING TYPE (1982)

INTRODUCTION Heterothallism .. Homothallism .. The Discovery of Homothallism . Scope of Review .
Treatment of Stretch Marks with the 585-nm Flashlamp-pumped Pulsed Dye Laser (1996)

Treatment with the 585-nm pulsed dye laser at low energy densities was shown to improve the appearance of striae. Apparent increased dermal elastin was also observed 8 weeks posttherapy and possibly contributed to the improvement seen in the study patients.
Axillary, subclavian, and brachiocephalic vein obstruction. (1977)

The consequences of occlusion of a major upper extremity vein were evaluated in eight patients with effort thrombosis, ten with thrombosis secondary to intimal injury, six with extrinsic compression, and one hypercoagulable patient, all of whom were followed for an average of 4 years. Twenty-two patients had venography, which confirmed the diagnosis but often failed to define the proximal extent of obstruction. Thirteen patients had noninvasive hemodynamic studies which did not corroborate chronic morbidity, but which were valuable in assessing the effect os specific therapy. Twelve patients were treated with anticoagulants, and six had operative removal or bypass of the obstruction. Three patients had pulmonary emboli; two embolized while on anticoagulants and both died. Swelling, pain, prominent veins, and easy fatigability of the affected extremity were the late sequelae of occlusion. Chronic morbidity was more dependent on etiology than on initial treatment. Thrombosis secondary to intimal injury caused no persistent symptoms, whether treated with anticoagulants or not. Effort thrombosis was intermediate: three fourths complained that their affected arm tired easily and half had prominent veins or persistent swelling. All of those with obstruction secondary to extrinsic compression had easy fatigability. The majority also had concomitant swelling, pain, and prominent collaterals. Operative treatment produced objective improvement in venous outflow but often was unsuccessful in relieving symptoms, particularly in patients with obstruction from extrinsic compression.
Evolutionary Medicine: From Dwarf Model Systems to Healthy Centenarians? (2003)

Restriction of the number of calories consumed extends longevity in many organisms. In rodents, caloric restriction decreases the levels of plasma glucose and insulin-like growth factor I (IGF-1) and postpones or attenuates cancer, immunosenescence, and inflammation without irreversible side effects. In organisms ranging from yeast to mice, mutations in glucose or IGF-I-like signaling pathways extend life-span but also cause glycogen or fat accumulation and dwarfism. This information suggests a new category of drugs that could prevent or postpone diseases of aging with few adverse effects.
Automatic extraction of web data records containing user-generated content (2010)

In this paper, we are concerned with the problem of automatically extracting web data records that contain user-generated content (UGC). In previous work, web data records are usually assumed to be well-formed with a limited amount of UGC, and thus can be extracted by testing repetitive structure similarity. However, when a web data record includes a large portion of free-format UGC, the similarity test between records may fail, which in turn results in lower performance. In our work, we find that certain domain constraints (e.g., post-date) can be used to design better similarity measures capable of circumventing the influence of UGC. In addition, we also use anchor points provided by the domain constraints to improve the extraction process, which ends in an algorithm called MiBAT (Mining data records Based on Anchor Trees). We conduct extensive experiments on a dataset consisting of forum thread pages which are collected from 307 sites that cover 219 different forum software packages. Our approach achieves a precision of 98.9% and a recall of 97.3% with respect to post record extraction. On page level, it perfectly handles 91.7% of pages without extracting any wrong posts or missing any golden posts. We also apply our approach to comment extraction and achieve good results as well.
Signal monitoring system for wireless network operation and management (2002)

In the last few years, various types of wireless networks have become available and cost-effective for commercial applications. In order to become a real alternative to traditional wireline telecommunications, wireless networks should provide competitive quality, reliability and availability of service. These requirements imply a need for a wireless fault management system with features similar to those incorporated in wireline counterparts. Despite a significant need for fault management in wireless networks, there has been almost no such proposals nor deployments. Existing wireless fault management systems provide management of mobile switching centers (MSG), rarely of base stations. Traditionally, base stations measure signal quality, and send alarms to a network management center (NMC) if some of the signal parameters are out of allowed range. This solution has been proven to be insufficient since it is possible to detect the signal quality at a base station's site, not at a subscriber's site. The proposed overlay signal monitoring system collects various signal parameters at a subscriber's site, determines if these parameters are within the allowed range of values, and generates an alarm if it is not the case. The NMC receives alarms and handles them as in wireline networks. This paper describes elements of the signal monitoring system, and how it detects and locates base station failures, signal degradation, co-channel and adjacent channel interference in a network. A mechanism for alarm generation and reporting is also described, as well as the interface between the signal monitoring system and existing network management center.
Apigenin inhibited migration and invasion of human ovarian cancer A2780 cells through focal adhesion kinase (2008)

Apigenin, a common dietary flavonoid, has been found to have antitumor properties and therefore poses special interest for the development of chemopreventive and/or chemotherapeutic agent for cancers. Here, we demonstrate that apigenin inhibits expression of focal adhesion kinase (FAK) and migration and invasion of human ovarian cancer A2780 cells. FAK is a non-receptor protein tyrosine kinase downstream of integrins and growth factors. It plays an important role in migration and invasion of cancer cells. We found that apigenin inhibited adhesion, migration and invasion of A2780 cells. Apigenin attenuated FAK expression through reducing its protein stability. FAK plays a critical role in migration and invasion of A2780 cells. Overexpression of FAK could reverse A2780 cell migration and invasion inhibited by apigenin. The in vivo experiments showed that apigenin inhibited spontaneous metastasis of A2780 cells implanted onto the ovary of nude mice. Our results provide a new insight into the mechanisms that apigenin inhibits ovarian cancers. These results suggest that molecular targeting of FAK by apigenin might be a useful strategy for chemoprevention and/or chemotherapeutics of ovarian cancers.
Control of the Shape of Liquid Lenses on a Modified Gold Surface Using an Applied Electrical Potential across a Self-Assembled Monolayer (1995)

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTControl of the Shape of Liquid Lenses on a Modified Gold Surface Using an Applied Electrical Potential across a Self-Assembled MonolayerChristopher B. Gorman, Hans A. Biebuyck, and George M. WhitesidesCite this: Langmuir 1995, 11, 6, 2242–2246Publication Date (Print):June 1, 1995Publication History Published online1 May 2002Published inissue 1 June 1995https://pubs.acs.org/doi/10.1021/la00006a063https://doi.org/10.1021/la00006a063research-articleACS PublicationsRequest reuse permissionsArticle Views912Altmetric-Citations108LEARN ABOUT THESE METRICSArticle Views are the COUNTER-compliant sum of full text article downloads since November 2008 (both PDF and HTML) across all institutions and individuals. These metrics are regularly updated to reflect usage leading up to the last few days.Citations are the number of other articles citing this article, calculated by Crossref and updated daily. Find more information about Crossref citation counts.The Altmetric Attention Score is a quantitative measure of the attention that a research article has received online. Clicking on the donut icon will load a page at altmetric.com with additional details about the score and the social media presence for the given article. Find more information on the Altmetric Attention Score and how the score is calculated. Share Add toView InAdd Full Text with ReferenceAdd Description ExportRISCitationCitation and abstractCitation and referencesMore Options Share onFacebookTwitterWechatLinked InRedditEmail Other access optionsGet e-Alertsclose Get e-Alerts
BiP and Immunoglobulin Light Chain Cooperate to Control the Folding of Heavy Chain and Ensure the Fidelity of Immunoglobulin Assembly (1999)

The immunoglobulin (Ig) molecule is composed of two identical heavy chains and two identical light chains (H2L2). Transport of this heteromeric complex is dependent on the correct assembly of the component parts, which is controlled, in part, by the association of incompletely assembled Ig heavy chains with the endoplasmic reticulum (ER) chaperone, BiP. Although other heavy chain-constant domains interact transiently with BiP, in the absence of light chain synthesis, BiP binds stably to the first constant domain (CH1) of the heavy chain, causing it to be retained in the ER. Using a simplified two-domain Ig heavy chain (VH-CH1), we have determined why BiP remains bound to free heavy chains and how light chains facilitate their transport. We found that in the absence of light chain expression, the CH1 domain neither folds nor forms its intradomain disulfide bond and therefore remains a substrate for BiP. In vivo, light chains are required to facilitate both the folding of the CH1 domain and the release of BiP. In contrast, the addition of ATP to isolated BiP-heavy chain complexes in vitro causes the release of BiP and allows the CH1 domain to fold in the absence of light chains. Therefore, light chains are not intrinsically essential for CH1 domain folding, but play a critical role in removing BiP from the CH1 domain, thereby allowing it to fold and Ig assembly to proceed. These data suggest that the assembly of multimeric protein complexes in the ER is not strictly dependent on the proper folding of individual subunits; rather, assembly can drive the complete folding of protein subunits.
Gene Expression Profiling of the Forming Atrioventricular Node Using a Novel Tbx3 -Based Node-Specific Transgenic Reporter (2009)

The atrioventricular (AV) node is a recurrent source of potentially life-threatening arrhythmias. Nevertheless, limited data are available on its developmental control or molecular phenotype. We used a novel AV nodal myocardium-specific reporter mouse to gain insight into the gene programs determining the formation and phenotype of the developing AV node. In this reporter, green fluorescent protein (GFP) expression was driven by a 160-kbp bacterial artificial chromosome with Tbx3 and flanking sequences. GFP was selectively active in the AV canal of embryos and AV node of adults, whereas the Tbx3-positive AV bundle and sinus node were devoid of GFP, demonstrating that distinct regulatory sequences and pathways control expression in the components of the conduction system. Fluorescent AV nodal and complementary Nppa-positive chamber myocardial cell populations of embryonic day 10.5 embryos and of embryonic day 17.5 fetuses were purified using fluorescence-activated cell sorting, and their expression profiles were assessed by genome-wide microarray analysis, providing valuable information concerning their molecular identities. We constructed a comprehensive list of sodium, calcium, and potassium channel genes specific for developing nodal or chamber myocardium. Furthermore, the data revealed that the AV node and the chamber (working) myocardium phenotypes diverge during development but that the functional gene classes characterizing both subtypes are maintained. One of the repertoires identified in the AV node-specific gene profiles consists of multiple neurotrophic factors and semaphorins, not yet appreciated to play a role in nodal development, revealing shared characteristics between nodal and nervous system development.
Bimodal Viral Vectors andIn VivoImaging Reveal the Fate of Human Neural Stem Cells in Experimental Glioma Model (2008)

Transplantation of genetically engineered cells into the CNS offers immense potential for the treatment of several neurological disorders. Monitoring expression levels of transgenes and following changes in cell function and distribution over time is critical in assessing therapeutic efficacy of such cells in vivo. We have engineered lentiviral vectors bearing fusions between different combinations of fluorescent and bioluminescent marker proteins and used bioluminescence imaging and intravital-scanning microscopy in real time to study the fate of human neural stem cells (hNSCs) at a cellular resolution in glioma-bearing brains in vivo. Using Renilla luciferase (Rluc)-DsRed2 or GFP-Rluc-expressing malignant human glioma model, transduced hNSCs were shown to migrate extensively toward gliomas, with hNSCs populating gliomas at 10 d after transplantation. Furthermore, transduced hNSCs survived longer in mice with gliomas than in normal brain, but did not modulate glioma progression in vivo. These studies demonstrate the utility of bimodal viral vectors and real-time imaging in evaluating fate of NSCs in diseased models and thus provide a platform for accelerating cell-based therapies for CNS disorders.