gebhart/patrepeval huggingface dataset:
Rev of human immunodeficiency virus and Rex of the human T-cell leukemia virus type I can counteract and mRNA downregulatory element of the transferrin receptor mRNA (1994)

Expression of the structural proteins of the human immunodeficiency virus type 1 (HIV-1), the human T-cell leukemia virus type I (HTLV-I), and of the transferrin receptor (TfR) mRNA depends on posttranscriptional regulatory mechanisms involving both positive and negative elements. In these systems the presence of elements decreasing mRNA expression have been demonstrated. The regulatory proteins (Rev, Rex or iron response element binding protein IRE-BP) antagonize the effects of the downregulatory elements by interacting directly with specific mRNA sites (Rev responsive element, RRE, Rex responsive element, RXRE, or iron responsive elements, IREs) resulting in stabilization and efficient expression of the corresponding mRNAs. To investigate whether this strategy involves common pathways of mRNA utilization, we have studied expression from hybrid mRNAs that contained these previously identified HIV-1 or TfR instability determinants and the binding sites of the regulatory proteins Rev, Rex and/or IRE-BP. Our results demonstrate that only low levels of these hybrid mRNAs accumulate in the absence of the positive regulatory factors Rev, Rex or IRE-BP. The presence of these factors counteracts the effect of heterologous downregulatory elements resulting in increased accumulation of the hybrid mRNAs. However, while Rev or Rex regulation also resulted in efficient protein expression, the IRE-BP only affected mRNA levels without significantly affecting protein expression, suggesting that the pathways of mRNA stabilization/expression are different in these systems.
Bioinspired bubble design for particle generation (2011)

In this study, we devise a method to generate homogeneous particles from a bubble suspension, with the capability to control loading and the structure of bubbles. Ideally, a process such as this would occur at the interface between daughter bubble formation (instant) and gaseous diffusion (gradual). Interestingly, the budding mechanism in micro-organisms is one that demonstrates features of the desired phenomena (although at a much slower rate), as viruses can eject and evolve structures from their membranes. With these natural concepts, a bubble's surface can also be made to serve as a platform for particle generation, which transfers significant elements from the initial bubble coating to the newly generated structures. Here, we illustrate this by preparing coated bubbles (approx. 150 µm in diameter) using a hydrophobic polymer, which may be comparable to naturally occurring bubble coatings (e.g. organic matter forming part of bubble coatings in the sea), and dye (which can demonstrate entrapment of smaller quantities of a desired moiety) and then observe particle generation (approx. 500 nm). The process, which may be driven by a polymerosome-forming mechanism, also illustrates how additional uniform sub-micrometre-scale structures may form from a bubble's surface, which may have also previously been attributed to gas diffusion. In addition, such methods of particle formation from a bubble structure, the incorporation of chemical or biological media via an in situ process and subsequent release technologies have several areas of interest across the broad scientific community.
Polycefin, a New Prototype of a Multifunctional Nanoconjugate Based on Poly(β-l-malic acid) for Drug Delivery (2006)

A new prototype of nanoconjugate, Polycefin, was synthesized for targeted delivery of antisense oligonucleotides and monoclonal antibodies to brain tumors. The macromolecular carrier contains: 1. biodegradable, nonimmunogenic, nontoxic beta-poly(L-malic acid) of microbial origin; 2. Morpholino antisense oligonucleotides targeting laminin alpha4 and beta1 chains of laminin-8, which is specifically overexpressed in glial brain tumors; 3. monoclonal anti-transferrin receptor antibody for specific tissue targeting; 4. oligonucleotide releasing disulfide units; 5. L-valine containing, pH-sensitive membrane disrupting unit(s), 6. protective poly(ethylene glycol); 7. a fluorescent dye (optional). Highly purified modules were conjugated directly with N-hydroxysuccinimidyl ester-activated beta-poly(L-malic acid) at pendant carboxyl groups or at thiol containing spacers via thioether and disulfide bonds. Products were chemically validated by physical, chemical, and functional tests. In vitro experiments using two human glioma cell lines U87MG and T98G demonstrated that Polycefin was delivered into the tumor cells by a receptor-mediated endocytosis mechanism and was able to inhibit the synthesis of laminin-8 alpha4 and beta1 chains at the same time. Inhibition of laminin-8 expression was in agreement with the designed endosomal membrane disruption and drug releasing activity. In vivo imaging showed the accumulation of intravenously injected Polycefin in brain tumor tissue via the antibody-targeted transferrin receptor-mediated endosomal pathway in addition to a less efficient mechanism known for high molecular mass biopolymers as enhanced permeability and retention effect. Polycefin was nontoxic to normal and tumor astrocytes in a wide range of concentrations, accumulated in brain tumor, and could be used for specific targeting of several biomarkers simultaneously.
Sunitinib: A newly approved small-molecule inhibitor ofangiogenesis (2006)

The advent of targeted therapies has allowed treatment to be directed at signaling pathways integral to tumor growth and survival. Sunitinib (SU11248, sunitinib malate; Pfizer Inc., New York, NY, USA) is a novel oral small-molecule multitargeted receptor tyrosine kinase inhibitor that has demonstrated direct antitumor activity and antiangiogenic action. It targets the vascular endothelial growth factor receptor (VEGFR), platelet derived growth factor receptor (PDGFR), stem-cell factor receptor and Fms-like tyrosine kinase receptor 3 receptor tyrosine-kinases. In January 2006, sunitinib malate was granted approval by the U.S. Food and Drug Administration for the treatment of gastrointestinal stromal tumor after disease progression on, or intolerance to, imatinib mesylate, as well as for the treatment of metastatic renal cell cancer. This review will discuss the development of sunitinib, particularly in acute myeloid leukemia, imatinib-resistant gastrointestinal stromal tumors and renal cell cancer. The review will also discuss ongoing trials with sunitinib in other malignancies such as neuroendocrine tumors and breast cancer, as well as its potential future development in combination therapy with other agents and in other malignancies.
Isolation and Characterization of Endophytic Colonizing Bacteria from Agronomic Crops and Prairie Plants (2002)

Endophytic bacteria reside within plant hosts without causing disease symptoms. In this study, 853 endophytic strains were isolated from aerial tissues of four agronomic crop species and 27 prairie plant species. We determined several phenotypic properties and found approximately equal numbers of gram-negative and gram-positive isolates. In a greenhouse study, 28 of 86 prairie plant endophytes were found to colonize their original hosts at 42 days postinoculation at levels of 3.5 to 7.7 log(10) CFU/g (fresh weight). More comprehensive colonization studies were conducted with 373 corn and sorghum endophytes. In growth room studies, none of the isolates displayed pathogenicity, and 69 of the strains were recovered from corn or sorghum seedlings at levels of 8.3 log(10) CFU/plant or higher. Host range greenhouse studies demonstrated that 26 of 29 endophytes were recoverable from at least one host other than corn and sorghum at levels of up to 5.8 log(10) CFU/g (fresh weight). Long-range dent corn greenhouse studies and field trials with 17 wild-type strains and 14 antibiotic-resistant mutants demonstrated bacterial persistence at significant average colonization levels ranging between 3.4 and 6.1 log(10) CFU/g (fresh weight) up to 78 days postinoculation. Three prairie and three agronomic endophytes exhibiting the most promising levels of colonization and an ability to persist were identified as Cellulomonas, Clavibacter, Curtobacterium, and Microbacterium isolates by 16S rRNA gene sequence, fatty acid, and carbon source utilization analyses. This study defines for the first time the endophytic nature of Microbacterium testaceum. These microorganisms may be useful for biocontrol and other applications.
Dosage-dependent over-expression of genes in the trisomic region of Ts1Cje mouse model for Down syndrome (2004)

Down syndrome (DS) is the most common chromosomally caused form of mental retardation and is caused by trisomy of chromosome 21. The over-expression of genes located on the trisomic region has been assumed to be responsible for the phenotypic abnormalities of DS, but this hypothesis has not been confirmed fully and the very existence of gene dosage effects has been called into question. We have therefore investigated global gene expression profiles in Ts1Cje, a mouse model for DS that displays learning deficits and has a segmental trisomy of chromosome 16 orthologous to a segment of human chromosome 21 spanning from Sod1 to Znf295. DNA microarray analyses of six Ts1Cje and six normal littermate (2N) mouse brains at postnatal day 0 with probe sets representing approximately 11,300 genes revealed that the number of expressed genes and their identities in Ts1Cje mice were almost same in 2N mice. Notably, the expression levels of most genes in the trisomic region were increased approximately 1.5-fold, and the top 24 most consistently over-expressed genes in the Ts1Cje mice were all located in the trisomic region. In contrast, the expression levels of genes on other chromosomes or the euploid region of chromosome 16 were largely the same (1.0-fold) in Ts1Cje and 2N mice. These results indicate that the genes in the trisomic region of Ts1Cje are over-expressed in a dosage-dependent manner and are implicated in the molecular pathogenesis of DS.
Oxidative Stress and HIV Infection: Target Pathways for Novel Therapies? (2008)

Oxidative stress is thought to play an important role in the progression of HIV infection. fact, it has been observed that perturbations in antioxidant defense systems, and consequently redox imbalance, are present in many tissues of HIV-infected patients. Moreover, there is clear evidence that oxidative stress may contribute to several aspects of HIV disease, including viral replication, inflammatory response and decreased immune cell proliferation. For this reason, the exogenous supply of antioxidants, as natural compounds and new-generation antioxidants that scavenge free radicals, might represent an important additional strategy for the treatment of HIV infection in the era after HAART therapy has been applied.
[A preliminary evaluation of alleviating damage due to scars postoperative in the area of the parotid gland]. (2004)

To estimate the methods of alleviating damage due to postoperative scars in the area of the parotid gland. 12 clinical cases was chosen which accepted operations in the area of the parotid gland, the method of minimally invasive suture was used in the operation and the remedy which can inhibit the hyperplasia of the scars was used after operation. 8 cases were without conspicuous scars, 4 had mild scars, no case was found with hyperplasia of scars. The influence of facial contour due to postoperative scars can be controlled by the above stated methods.
Ultra-low crosstalk, compact integrated optical crosspoint space switch arrays employing active InGaAsP-InP vertical waveguide couplers (2003)

An optical crosspoint switch array based on vertical waveguide couplers are experimentally demonstrated to have very low on-chip crosstalk level of <-60 dB and a ON-OFF contrast of >50 dB. The structure is also compact (250/spl times/250 /spl mu/m per input/output pair) and easily scalable.
Actively targeting solid tumours with thermoresponsive drug delivery systems that respond to mild hyperthermia (2013)

A diverse range of drug delivery vehicles have been developed to specifically target chemotherapeutics to solid tumours while avoiding systemic dose-limiting toxicity. Many of these active targeting strategies display limited efficacy because they rely on subtle differences in expression patterns between pathogenic tissue and healthy tissue. In contrast, drug delivery systems that exploit thermoresponsive behaviour allow a clinician to spatially and temporally control the accumulation and/or release of the toxic agents within tumour tissue by simply applying mild hyperthermia (defined as 39-43 °C) to the desired site. Although thermally sensitive materials comprise a significant portion of the literature on novel drug delivery systems, only a few systems have been methodically tuned to respond within this narrowly defined physiological temperature range in an in vivo environment. This review discusses the materials and strategies developed to control the primary tumour through the combined application of hyperthermia and chemotherapy.
Skin Penetration and Cellular Uptake of Amorphous Silica Nanoparticles with Variable Size, Surface Functionalization, and Colloidal Stability (2012)

In this study, the skin penetration and cellular uptake of amorphous silica particles with positive and negative surface charge and sizes ranging from 291 ± 9 to 42 ± 3 nm were investigated. Dynamic light scattering measurements and statistical analyses of transmission electron microscopy images were used to estimate the degree of particle aggregation, which was a key aspect to understanding the results of the in vitro cellular uptake experiments. Despite partial particle aggregation occurring after transfer in physiological media, particles were taken up by skin cells in a size-dependent manner. Functionalization of the particle surface with positively charged groups enhanced the in vitro cellular uptake. However, this positive effect was contrasted by the tendency of particles to form aggregates, leading to lower internalization ratios especially by primary skin cells. After topical application of nanoparticles on human skin explants with partially disrupted stratum corneum, only the 42 ± 3 nm particles were found to be associated with epidermal cells and especially dendritic cells, independent of their surface functionalization. Considering the wide use of nanomaterials in industries and the increasing interest for applications in pharmaceutics and cosmetics versus the large number of individuals with local or spread impairment of the skin barrier, e.g., patients with atopic dermatitis and chronic eczema, a careful dissection of nanoparticle-skin surface interactions is of high relevance to assess possible risks and potentials of intended and unintended particle exposure.
Comparison of racemic ketamine andS-ketamine in treatment-resistant major depression: Report of two cases (2008)

Recent studies with intravenous infusion of the NMDA receptor antagonist ketamine showed robust and rapid antidepressant effects within hours after treatment. Ketamine is a racemic mixture consisting of two enantiomers, R- and S-ketamine. In contrast to ketamine, S-ketamine is reported to be less prone to psychomimetic side effects, such as derealisation and hallucinations. In this report we describe the effect of ketamine and S-ketamine infusion therapy, respectively, in two patients with treatment-resistant major depression. Severity of depression was rated using the Hamilton Depression Rating Scale (HAMD) and the Beck Depression Inventory (BDI). While one patient did not respond to either treatment, in the other patient intravenous administration of ketamine as well as S-ketamine showed an antidepressant effect as assessed by a decrease in HAMD-21 and BDI at days 1 and 3 after infusion which faded until day 6. Both patients experienced psychomimetic side effects during ketamine infusion which were absent during treatment with S-ketamine. We conclude that S-ketamine might exert similar antidepressant effects as ketamine in drug-resistant depression but may be better tolerated by the patients.
Quantitation of the Tumor-Targeting Properties of Antibody Fragments Conjugated to Cell-Permeating HIV-1 TAT Peptides (2002)

Human monoclonal antibodies are promising agents for the development of more selective anticancer therapeutics. However, the tumor-targeting efficiency of most anticancer antibodies is severely limited by their poor penetration into the tumor mass. Recent studies have shown that a peptide derived from the HIV TAT protein could improve the distribution of cytoplasmic reporter proteins when administered systemically as fusion proteins or cross-linked chimeras. In this article, we tested by quantitative biodistribtution analysis whether conjugation to TAT peptides could improve the tumor targeting properties of scFv(L19)-Cys: an engineered human antibody fragment specific for the ED-B domain of fibronectin, a marker located in the modified extracellular matrix surrounding tumor neovasculature. Our results show that TAT peptides, consisting either of L-amino acids or D-amino acids, can efficiently transduce target cells when conjugated to fluorophores and/or antibody fragments, suggesting a receptor-independent cell entry mechanism. However, conjugation of scFv(L19)-Cys to TAT peptides resulted in a severely reduced tumor targeting performance compared to the unconjugated antibody, as measured in murine F9 teratocarcinoma-bearing mice, after intravenous injection of the radiolabeled antibody preparations. Our results outline the usefulness of TAT peptides for the efficient in vitro transduction of cells with globular proteins. In particular, the use of TAT peptides composed of D-amino acids may significantly reduce proteolytic degradation. At the same time, the poor biodistribution properties of antibody-TAT conjugates cast doubts over the applicability of this methodology for the delivery of biopharmaceuticals in vivo.
Characterization of Dicer-deficient murine embryonic stem cells (2005)

Dicer is an RNase III-family nuclease that initiates RNA interference (RNAi) and related phenomena by generation of the small RNAs that determine the specificity of these gene silencing pathways. We have previously shown that Dicer is essential for mammalian development, with Dicer-deficient mice dying at embryonic day 7.5 with a lack of detectable multipotent stem cells. To permit a more detailed investigation of the biological roles of Dicer, we have generated embryonic stem cell lines in which their single Dicer gene can be conditionally inactivated. As expected, Dicer loss compromises maturation of microRNAs and leads to a defect in gene silencing triggered by long dsRNAs. However, the absence of Dicer does not affect the ability of small interfering RNAs to repress gene expression. Of interest, Dicer loss does compromise the proliferation of ES cells, possibly rationalizing the phenotype previously observed in Dicer-null animals. Dicer loss also affects the abundance of transcripts from mammalian centromeres but does so without a pronounced affect on histone modification status at pericentric repeats or methylation of centromeric DNA. These studies provide a conditional model of RNAi deficiency in mammals that will permit the dissection of the biological roles of the RNAi machinery in cultured mammalian cells.
Construction of vectors with the pl5a replicon, kanamycin resistance, induciblelacZα and pUC18 or pUC19 multiple cloning sites (1990)

Journal Article Construction of vectors with the pl5a replicon, kanamycin resistance, inducible lacZα and pUC18 or pUC19 multiple cloning sites Get access Michael G. Jobling, Michael G. Jobling Department of Microbiology, Uniformed Services Universify of the Health Sciences4301 Jones Bridge Road, Bethesda, MD 20814–4799, USA Search for other works by this author on: Oxford Academic PubMed Google Scholar Randall K. Holmes Randall K. Holmes * Department of Microbiology, Uniformed Services Universify of the Health Sciences4301 Jones Bridge Road, Bethesda, MD 20814–4799, USA *To whom correspondence should be addressed Search for other works by this author on: Oxford Academic PubMed Google Scholar Nucleic Acids Research, Volume 18, Issue 17, 11 September 1990, Page 5315, https://doi.org/10.1093/nar/18.17.5315 Published: 11 September 1990 Article history Received: 17 July 1990 Published: 11 September 1990
A Full-Color Transparent Metal-Free Stacked Organic Light Emitting Device with Simplified Pixel Biasing (1999)

The integration of organic light-emitting diodes (OLEDs) into full-color flat-panel displays is a current research objective. Metal-free stacked OLEDs (MF-SOLEDs) are the latest development: a red, a blue, and a green subpixel, each of which is transparent to the light emitted by itself and the other subpixels, are stacked on top of each other. A MF-SOLED is described in which an insulating layer is interposed between the middle and top highly transparent subpixels, allowing the three subpixels to be referenced to a common ground and eliminating the differential drive schemes required in previous SOLEDs.
Dynamic contrast-enhanced MRI for prostate cancer localization (2009)

Radiotherapy dose escalation improves tumour control in prostate cancer but with increased toxicity. Boosting focal tumour only may allow dose escalation with acceptable toxicity. Intensity-modulated radiotherapy can deliver this, but visualization of the tumour remains limiting. CT or conventional MRI techniques are poor at localizing tumour, but dynamic contrast-enhanced MRI (DCE-MRI) may be superior. 18 patients with prostate cancer had T(2) weighted (T2W) and DCE-MRI prior to prostatectomy. The prostate was sectioned meticulously so as to achieve accurate correlation between imaging and pathology. The accuracy of DCE-MRI for cancer detection was calculated by a pixel-by-pixel correlation of quantitative DCE-MRI parameter maps and pathology. In addition, a radiologist interpreted the DCE-MRI and T2W images. The location of tumour on imaging was compared with histology, and the accuracy of DCE-MRI and T2W images was then compared. Pixel-by-pixel comparison of quantitative parameter maps showed a significant difference between the benign peripheral zone and tumour for the parameters K(trans), v(e) and k(ep). Calculation of areas under the receiver operating characteristic curve showed that the pharmacokinetic parameters were only "fair" discriminators between cancer and benign gland. Interpretation of DCE-MRI and T2W images by a radiologist showed DCE-MRI to be more sensitive than T2W images for tumour localization (50% vs 21%; p = 0.006) and similarly specific (85% vs 81%; p = 0.593). The superior sensitivity of DCE-MRI compared with T2W images, together with its high specificity, is arguably sufficient for its use in guiding radiotherapy boosts in prostate cancer.