gebhart/patrepeval huggingface dataset:
Inhibition of PDGF BB stimulated DNA synthesis in rat aortic vascular smooth muscle cells by the expression of a truncated PDGFβ receptor (1993)

Rat aortic vascular smooth muscle cells (VSMCs) were transfected with a vector encoding a truncated human PDGF beta receptor or the full-length human PDGF beta receptor. Cells stably expressing the truncated human PDGF beta receptor or the full-length human PDGF beta receptor were selected and the effect of PDGF BB on DNA synthesis in these cells was studied. Cells expressing the full-length PDGF beta receptor entered DNA synthesis normally, however, cells expressing the truncated PDGF beta receptor failed to enter DNA synthesis in response to PDGF BB. These data show that the mitogenic response of rat aortic vascular smooth muscle cells to PDGF BB can be inhibited by the expression of a truncated PDGF beta receptor.
Identification of interleukin‐7 as a candidate disease mediator in spondylarthritis (2008)

In the present study, both known and unsuspected candidate mediators of SpA pathogenesis were identified, including IL-7. The specific overexpression of IL-7 at sites of peripheral synovitis in SpA suggests that further functional investigations of the role of this cytokine in SpA pathogenesis are warranted.
In vivo evaluation of 188Re‐labeled alpha‐melanocyte stimulating hormone peptide analogs for melanoma therapy (2002)

The purpose of our study was to optimize melanoma tumor uptake of 188Re-CCMSH and reduce its nonspecific kidney retention. Nephrotoxicity is often a serious problem associated with targeted radiotherapy, therefore, increasing the tumor/kidney uptake ratio of 188Re-CCMSH is crucial for optimizing its therapeutic efficacy. Structural modification of the peptide and amino acid co-infusion were investigated as strategies to improve the tumor/kidney uptake ratio of 188Re-CCMSH. The substitution of Lys11 with Arg11 was examined to determine if removal of lysine from the peptide would improve kidney clearance without sacrificing tumor uptake. The pharmacokinetics of 188Re-CCMSH and 188Re-(Arg(11))CCMSH were determined in B16/F1 murine melanoma-bearing C57 mice. Tumor uptake values of (188)Re-CCMSH and 188Re-(Arg(11))CCMSH were 15.03 +/- 5.20% ID/g and 20.44 +/- 1.91% ID/g at 1 hr postinjection and 1.94 +/- 0.47% ID/g and 3.50 +/- 2.32% ID/g at 24 hr postinjection. Renal retention of 188Re-(Arg(11))CCMSH was 11.79 +/- 1.29 ID/g and 3.67 +/- 0.51 ID/g at 1 hr and 4 hr postinjection, which was a greater than 50% reduction compared to 188Re-CCMSH. The Arg for Lys substitution in 188Re-(Arg(11))CCMSH resulted in improved tumor uptake and reduced kidney retention. Renal retention of both 188Re-CCMSH and 188Re-(Arg(11))CCMSH were significantly reduced by co-injection of 20 mg of L-lysine, L-arginine and a combination of L-lysine:L-arginine. Tumor/kidney uptake values for 188Re-CCMSH and 188Re-(Arg(11))CCMSH were maximally reduced by 52.9% and 46.3%, respectively. However, even with amino acid co-injection, the tumor/kidney ratio of 188Re-CCMSH was lower than that of 188Re-(Arg(11))CCMSH. Improved tumor uptake and reduced kidney retention of 188Re-(Arg(11))CCMSH will facilitate targeted irradiation of melanoma tumors while minimizing the dose to the kidneys.
Effects of thyroid hormone administration on skeletal muscle mitochondria (1975)

The effects of thyroid hormone administration on the levels of a number of mitochondrial markers were measured in skeletal muscle and liver of normal rats. Injection of 18 mug of L-thyroxine (T4) per 100 g body wt every 4th day for 3 wk had no effect on the concentrations of cytochrome c, on citrate synthase activity, or on respiratory capacity of skeletal muscle. Injection of 200 mug of L-triiodothyronine (T3) daily for 5 days, or feeding 23 mg T4 and 7 mg T3/kg of diet for 2 wk, resulted in thyrotoxicosis and large increases in the activity of hepatic alpha-glycerophosphate dehydrogenase and other mitochondrial markers; however, the levels of activity of mitochondrial marker enzymes in gastrocnemius and quadriceps muscles were not significantly changed. Only when rats were fed 3 mg T4 and 1 mg T3/kg diet for a 6-wk period did we observe an increase in skeletal muscle mitochondrial markers. Thus, thyroxine treatment must be sufficiently prolonged if it is to be used as a tool for studying skeletal muscle mitochondrial biogenesis.
Effects of nucleic acid local structure and magnesium ions on minus-strand transfer mediated by the nucleic acid chaperone activity of HIV-1 nucleocapsid protein (2007)

HIV-1 nucleocapsid protein (NC) is a nucleic acid chaperone, which is required for highly specific and efficient reverse transcription. Here, we demonstrate that local structure of acceptor RNA at a potential nucleation site, rather than overall thermodynamic stability, is a critical determinant for the minus-strand transfer step (annealing of acceptor RNA to (-) strong-stop DNA followed by reverse transcriptase (RT)-catalyzed DNA extension). In our system, destabilization of a stem-loop structure at the 5' end of the transactivation response element (TAR) in a 70-nt RNA acceptor (RNA 70) appears to be the major nucleation pathway. Using a mutational approach, we show that when the acceptor has a weak local structure, NC has little or no effect. In this case, the efficiencies of both annealing and strand transfer reactions are similar. However, when NC is required to destabilize local structure in acceptor RNA, the efficiency of annealing is significantly higher than that of strand transfer. Consistent with this result, we find that Mg2+ (required for RT activity) inhibits NC-catalyzed annealing. This suggests that Mg2+ competes with NC for binding to the nucleic acid substrates. Collectively, our findings provide new insights into the mechanism of NC-dependent and -independent minus-strand transfer.
Dual Adeno-Associated Virus Vectors Result in Efficient In Vitro and In Vivo Expression of an Oversized Gene, MYO7A (2014)

Usher syndrome 1B (USH1B) is a severe, autosomal recessive, deaf-blind disorder caused by mutations in myosin 7A (MYO7A). Patients are born profoundly deaf and exhibit progressive loss of vision starting in their first decade. MYO7A is expressed in human photoreceptors and retinal pigment epithelium, but disease pathology begins in photoreceptors, highlighting the need to develop a gene replacement strategy that effectively targets this cell type. For its safety and efficacy in clinical trials and ability to transduce postmitotic photoreceptors, we have focused on developing a clinically applicable adeno-associated virus (AAV) platform for delivering full-length MYO7A cDNA (∼6.7 kb). Packaging of full-length MYO7A cDNA in AAV produces vectors with heterogeneous, fragmented genomes ("fAAV") capable of reconstituting full-length cDNA postinfection. We previously showed that fAAV vectors effectively delivered full-length MYO7A in vitro and in vivo. However, fAAV vectors are relatively inefficient and their heterogeneous genomes preclude definitive characterization, a drawback for clinical translatability. The aim of this study was to overcome these limitations by creating dual-AAV-vector platforms for USH1B with defined genomes. Human MYO7A was cloned in AAV vector pairs, each containing genomes <5 kb and intact inverted terminal repeats. One vector contained a promoter and 5' portion of the cDNA and the partner vector contained a 3' portion and polyadenylation signal. "Simple overlap" vectors share a central part of the MYO7A cDNA sequence. "Trans-splicing" and "hybrid" vectors utilize splice donor and acceptor sites with and without an additional central recombinogenic sequence, respectively. Vector pairs expressed full-length MYO7A in vitro and in vivo with equal or higher efficiency than fAAV, with a hybrid platform being most efficient. Importantly, analysis of MYO7A mRNA derived from each dual-vector platform revealed 100% fidelity to the predicted sequence. Our results suggest that dual AAV vectors with defined genetic payloads are a potential treatment option for USH1B.
Aperture sharing between low-background infrared sensors and ladar sensors (2002)

The sharing of a common aperture for both ladar pulse transmission and reception; and passive sensor surveillance, acquisition, and tracking, presents many unique challenges. Performance assessments based on fielded optical systems of this type are few. Our particular application (the BMDO Advanced Sensor Technology Program-ASTP for enhanced theater missile defense capability) calls for the sharing of common optics between a MWIR and LWIR, relatively low-background passive sensor, and a ladar for which the operational wavelength has not been selected. This paper describes the advantages and technical challenges associated with our shared optics application, reviews the state of the art in this area, and derives constraints on system designs. Briefly, we find that the shared aperture approach enjoys the obvious advantages of reduced size and weight, and simplifies handover of targets from the passive sensor to the ladar sensor. These advantages must be traded against potential passive sensor performance degradation in the areas of reduced duty cycle, increased noise floor, and reduced sensitivity.
Heterologous overexpression of Glomerella cingulata FAD-dependent glucose dehydrogenase in Escherichia coli and Pichia pastoris (2011)

The heterologous expression of active GDH was greatly favoured in the eukaryotic host. The efficient expression in P. pastoris facilitates the production of genetically engineered GDH variants for electrochemical-, physiological- and structural studies.
Delayed metabolism of human brain natriuretic peptide reflects resistance to neutral endopeptidase (2000)

Metabolism of natriuretic peptides is regulated by two degradative pathways: uptake by the clearance receptor (natriuretic peptide receptor C--NPR-C) and hydrolysis by neutral endopeptidase (NEP). Affinity studies favour a dominant role of NPR-C in hormone degradation in several species but do not account for the efficacy of NEP inhibitors in vivo, nor the uniquely prolonged half life (t((1/2))) of human brain natriuretic peptide (hBNP). Postulating that (1) delayed metabolism of hBNP reflects resistance to NEP and (2) interactions between NPR-C and NEP increase enzyme activity, we have used purified ovine and human NEP, plus ovine lung plasma membranes to study the relative importance of receptor and enzyme pathways. We have also related the findings to hormone metabolism in vivo. Binding affinities of atrial natriuretic peptide (ANP), hBNP and ovine BNP (oBNP) to oNPR-C were similar (K(d)=8-16 pM). In contrast, unlike ANP and oBNP, hBNP was not significantly degraded by purified oNEP or plasma membranes. Despite similar (and high) affinity of oNPR-C for oBNP and hBNP, the t((1/2)) of hBNP (12.7 min) was more than fourfold that of oBNP (2.6 min). Although we found no evidence for receptor-enzyme interaction, our results show that the delayed metabolism of hBNP reflects resistance to NEP. These findings have important implications for future treatment strategies in human disease.
2‐Hydroxyisocaproyl‐CoA dehydratase and its activator from Clostridium difficile (2004)

The hadBC and hadI genes from Clostridium difficile were functionally expressed in Escherichia coli and shown to encode the novel 2-hydroxyisocaproyl-CoA dehydratase HadBC and its activator HadI. The activated enzyme catalyses the dehydration of (R)-2-hydroxyisocaproyl-CoA to isocaprenoyl-CoA in the pathway of leucine fermentation. The extremely oxygen-sensitive homodimeric activator as well as the heterodimeric dehydratase, contain iron and inorganic sulfur; besides varying amounts of zinc, other metal ions, particularly molybdenum, were not detected in the dehydratase. The reduced activator transfers one electron to the dehydratase concomitant with hydrolysis of ATP, a process similar to that observed with the unrelated nitrogenase. The thus activated dehydratase was separated from the activator and ATP; it catalyzed about 10(4) dehydration turnovers until the enzyme became inactive. Adding activator, ATP, MgCl(2), dithionite and dithioerythritol reactivated the enzyme. This is the first demonstration with a 2-hydroxyacyl-CoA dehydratase that the catalytic electron is recycled after each turnover. In agreement with this observation, only substoichiometric amounts of activator (dehydratase/activator = 10 mol/mol) were required to generate full activity.
Induction of Rapid Atherogenesis by Perivascular Carotid Collar Placement in Apolipoprotein E–Deficient and Low-Density Lipoprotein Receptor–Deficient Mice (2001)

We propose that this model of collar-induced acceleration of carotid atherogenesis is of hemodynamic cause. It may serve as a substrate for sequential mechanistic studies concerned with the underlying cause and pathogenesis of atherosclerosis. The rapidity of lesion development will also aid the efficient screening of new potentially antiatherogenic chemical entities and the evaluation of therapies with limited duration of effectiveness, such as adenoviral gene therapy.
Genetic modification of T cells for cancer therapy. (2005)

The use of immune cells with restricted specificities for the treatment of cancer is a rapidly emerging area of clinical research. Chimeric receptors composed of the single-chain variable domain of murine antibodies and human signaling molecules are a promising tool to redirect the specificity of autologous or allogeneic immune cells. The success of this approach depends on the identification of target molecules expressed preferentially on cancer cells. Moreover, appropriate primary and secondary stimuli must be delivered to generate vigorous and durable immune responses. Since cancer cells often lack ligands for key co-stimulatory molecules, the addition of molecules such as CD28 or 4-1BB to the chimeric receptors can significantly improve their function. Studies in vitro and in animal models indicate that immune cells expressing chimeric receptors can have remarkable anti-cancer activity, while experimental and clinical data indicate that long-term persistence of adoptively transferred cells is feasible. Therefore, testing of this approach in clinical trials is warranted. We here review the principles and methodologies for designing chimeric receptors and delivering them into immune cells, as well as some of the potential complications associated with this form of cell therapy.
Glycoprotein Ibα Receptor Instability Is Associated with Loss of Quality in Platelets Produced in Culture (2010)

The development of culture processes for hematopoietic progenitors could lead to the development of a complementary source of platelets for therapeutic purposes. However, functional characterization of culture-derived platelets remains limited, which raises some uncertainties about the quality of platelets produced in vitro. The aim of this study was to define the proportion of functional platelets produced in cord blood CD34+ cell cultures. Toward this, the morphological and functional properties of culture-derived platelet-like particles (PLPs) were critically compared to that of blood platelets. Flow cytometry combined with transmission electron microscopy analyses revealed that PLPs formed a more heterogeneous population of platelets at a different stage of maturation than blood platelets. The majority of PLPs harbored the fibrinogen receptor αIIbβ3, but a significant proportion failed to maintain glycoprotein (GP)Ibα surface expression, a component of the vWF receptor essential for platelet functions. Importantly, GPIbα extracellular expression correlated closely with platelet function, as the GPIIb+ GPIbα+ PLP subfraction responded normally to agonist stimulation as evidenced by α-granule release, adhesion, spreading, and aggregation. In contrast, the GPIIb+ GPIbα⁻ subfraction was unresponsive in most functional assays and appeared to be metabolically inactive. The present study confirms that functional platelets can be generated in cord blood CD34+ cell cultures, though these are highly susceptible to ectodomain shedding of receptors associated with loss of function. Optimization of culture conditions to prevent these deleterious effects and to homogenize PLPs is necessary to improve the quality and yields of culture-derived platelets before they can be recognized as a suitable complementary source for therapeutic purposes.
A Review of Quantitative Studies of Adherence to Mental Health Clinical Practice Guidelines (2002)

Mental health clinical practice guidelines have proliferated, but there is little evidence regarding the degree to which they are actually implemented in clinical practice. The goal of this study was to locate and review all peer-reviewed reports published through 2000 that provide quantitative information on rates of adherence to specific mental health guidelines. A literature search yielded 41 pertinent studies. These studies were of three types: 26 were cross-sectional investigations performed after the release of guidelines, six were conducted before and after release of guidelines without any specific intervention (pre/post), and nine involved a controlled trial of a specific intervention. Only 37% were conducted in the mental health specialty sector. Adequate adherence was found in 27% of the cross-sectional and pre/post studies but in 67% of the controlled trials. Successful interventions tended to be complex, involving system redesign or additional resources. Only six of 13 investigations (46%) that also measured patient outcome found that better outcome was associated with greater guideline adherence. Several studies showed that after cessation of interventions, adherence rates returned to preintervention levels. Thus, evidence indicates that guideline adherence is not high without specific intervention, but that certain interventions (typically multifaceted and resource-intensive ones) improve adherence. However, the public health challenge is to design and implement interventions that are sustainable in general clinical practice.
Targeting endothelium and its dynamic caveolae for tissue-specific transcytosisin vivo: A pathway to overcome cell barriers to drug and gene delivery (2002)

Site-directed pharmacodelivery is a desirable but elusive goal. Endothelium and epithelium create formidable barriers to endogenous molecules as well as targeted therapies in vivo. Caveolae provide a possible, yet unproven, transcellular pathway to overcome such barriers. By using an antibody- and subfractionation-based strategy, we generated a monoclonal antibody specific for lung caveolae (TX3.833) that targets rat lungs after i.v. injection (up to 89% of dose in 30 min). Unlike control antibodies (nonbinding or to lipid rafts), TX3.833 targets lung caveolae that bud to form free vesicles for selective and quantal transendothelial transport to underlying tissue cells in vivo. Rapid sequential transcytosis can occur to the alveolar air space via epithelial caveolae. Conjugation to TX3.833 increases drug delivery to the lung up to 172-fold and achieves rapid, localized bioefficacy. We conclude that: (i) molecular heterogeneity of the endothelium and its caveolae permits vascular targeting to achieve theoretical expectations of tissue-specific delivery and bioefficacy; (ii) caveolae can mediate selective transcytosis in vivo; and (iii) targeting caveolae may provide a tissue-specific pathway for overcoming key cell barriers to many drug and gene therapies in vivo.
Molecular Characterization of Seven Chinese Isolates of Infectious Bursal Disease Virus: Classical, Very Virulent, and Variant Strains (1998)

Seven infectious bursal disease virus (IBDV) strains isolated from China have been characterized in this study, including a classical strain CJ801, an attenuated strain GZ911, a variant strain GZ902, and four very virulent strains G9201, G9302, F9502, and HK46. With the use of reverse transcription-polymerase chain reaction, the full-length VP2 genes were amplified and the hypervariable regions were sequenced. Protein sequences of the hypervariable region (a.a. 143-382) of the field isolates confirmed their identities. CJ801 has the highest identity to the classical strains STC and 52/70. GZ902 has the highest identity to the American variant strains A, E, and GLS, and they share unique amino acid residue at positions 249K and 254S, which are not present in standard serotype 1 strains. Attenuated strain GZ911, like other cell culture-adapted strains, has substitutions at positions 279(D to N) and 284 (A to T) as well as in the serine-rich heptapeptide region. Hence, these substitutions may take an important role in the reduced virulence of these strains. The four very virulent strains have the highest identity to the European very virulent strain UK661 and Japanese strain OKYM. These strains share unique amino acid residues at positions 222A, 256I, and 294I, which are not present in other less virulent strains. The very virulent strains isolated in Guangdong (G9201, G9303) and Fujian (F9502) Provinces have one to five amino acid substitutions at the two hydrophilic domains of VP2 comparing with UK661 and OKYM, indicating that new very virulent strains are evolving. Phylogenetic analysis suggests that Chinese very virulent IBDVs and European very virulent strains are derived from similar origin.
The role of human papillomaviruses in human cancers (2002)

Of the more than 100 different human papillomavirus types (HPVs), the "high-risk" HPVs are associated with the vast majority of cervical carcinoma, and a pathologically distinct group of oropharyngeal tumors. In addition, other HPVs are associated with cutaneous tumors, in particular epidermodysplasia verruciformis and non-melanoma skin cancers. In general, HPV-associated cancers arise from a single accidental integration event of the viral genome into a host cell chromosome. Integration is a terminal event for the viral life cycle. Even though integration does not occur at specific chromosomal hot spots in the human genome, it follows a consistent pattern with respect to the viral genome, and expression of the HPV E6 and E7 genes is consistently retained. The normal function of E6 and E7 is to establish and maintain a cellular milieu that allows for viral genome replication. E6 and E7 target important cellular growth regulatory circuits among them the p53 and retinoblastoma tumor suppressors, respectively. Uncontrolled expression of the E6 and E7 proteins, as a consequence of viral integration is paramount to the establishment and maintenance of the tumorigenic state. In addition, expression of E6 and E7 increases genomic instability of the host cell thus accelerating malignant progression. Taken together, there is compelling molecular and epidemiological evidence in support of an oncogenic function of certain HPVs.
Dual-band strip-sleeve monopole for handheld telephones (1999)

A dual-frequency strip-sleeve monopole antenna for mobile handheld units has been designed that operates in both frequency bands allocated for wireless communication. The bandwidth of the antenna is 19.3 and 11.2% for AMPS and PCS bands, respectively with VSWR≤2. These bandwidths are practically unchanged in the proximity of the user's head. Relevant characteristics of the designed antenna have been analyzed with and without the presence of the user's head using the finite-difference time-domain (FDTD) method. The resultant deposition of the microwave power in the user's head, called the specific absorption rate (SAR), has also been calculated. ©1999 John Wiley & Sons, Inc. Microwave Opt Technol Lett 21: 79–82, 1999.
Blankett Slate: Australian Style (2010)

The fashion scene in Australia is explored. Australian boutiques are investigated to find out what works and what does not. Balmain the Paris fashion house seems to be the most popular.