gebhart/patrepeval huggingface dataset:
Inhibition of capillary endothelial cell growth by pericytes and smooth muscle cells. (1987)

Morphological studies of developing capillaries and observations of alterations in capillaries associated with pathologic neovascularization indicate that pericytes may act as suppressors of endothelial cell (EC) growth. We have developed systems that enable us to investigate this possibility in vitro. Two models were used: a co-culture system that allowed direct contact between pericytes and ECs and a co-culture system that prevented physical contact but allowed diffusion of soluble factors. For these studies, co-cultures were established between bovine capillary ECs and the following growth-arrested cells (hereafter referred to as modulating cells): pericytes, smooth muscle cells (SMCs), fibroblasts, epithelial cells, and 3T3 cells. The modulating cell type was growth arrested by treatment with mitomycin C before co-culture with ECs. In experiments where cells were co-cultured directly, the effect of co-culture on EC growth was determined by comparing the mean number of cells in the co-cultures to the mean for each cell type (EC and modulating cell) cultured separately. Since pericytes and other modulating cells were growth arrested, any cell number change in co-cultures was due to EC growth. In the co-cultures, pericytes inhibited all EC proliferation throughout the 14-d time course; similar levels of EC inhibition were observed in SMC-EC co-cultures. Co-culture of ECs with fibroblasts, epithelial cells, and 3T3 cells significantly stimulated EC growth over the same time course (30-192% as compared to EC cultured alone). To determine if cell contact was required for inhibition, cells were co-cultured using Millicell chambers (Millipore Corp., Bedford, MA), which separated the cell types by 1-2 mm but allowed the exchange of diffusible materials. There was no inhibition of EC proliferation by pericytes or SMCs in this co-culture system. The influence of the cell ratios on observed inhibition was assessed by co-culturing the cells at EC/pericyte ratios of 1:1, 2:1, 5:1, 10:1, and 20:1. Comparable levels of EC inhibition were observed at ratios from 1:1 to 10:1. When the cells were co-cultured at a ratio of 20 ECs to 1 pericyte, inhibition of EC growth at 3 d was similar to that observed at other ratios. However, at higher ratios, the inhibition diminished so that by the end of the time course the co-cultured ECs were growing at the same rate as the controls. These results suggest that pericytes and SMCs can modulate EC growth by a mechanism that requires contact or proximity. We postulate that similar interactions may operate to modulate vascular growth in vivo.
Mediation of Subacute Anthracycline Cardiotoxicity in Rabbits by Cardiac Histamine Release (1983)

We tested the hypothesis that cardiac histamine release mediates subacute doxorubicin (DXR) cardiotoxicity in rabbits. New Zealand white rabbits given DXR 20 mg/kg i.v. over 30 min developed myocardial damage 24 h later that was similar to that observed in humans. In isolated heart preparations, DXR produced dose-related cardiac histamine release at DXR concentrations of 1, 5, and 25 micrograms/ml given as 1-min exposures. Prior exposure of isolated hearts to 10 microM cromolyn sodium completely prevented histamine release from 5 micrograms/ml DXR. Pretreatment of animals with cromolyn produced significant protection against DXR-mediated subacute cardiotoxicity. We conclude that the release of cardiac histamine may be involved in the pathogenesis of anthracycline cardiotoxicity.
Wax-deficient anther1 Is Involved in Cuticle and Wax Production in Rice Anther Walls and Is Required for Pollen Development (2006)

In vegetative leaf tissues, cuticles including cuticular waxes are important for protection against nonstomatal water loss and pathogen infection as well as for adaptations to environmental stress. However, their roles in the anther wall are rarely studied. The innermost layer of the anther wall (the tapetum) is essential for generating male gametes. Here, we report the characterization of a T-DNA insertional mutant in the Wax-deficient anther1 (Wda1) gene of rice (Oryza sativa), which shows significant defects in the biosynthesis of very-long-chain fatty acids in both layers. This gene is strongly expressed in the epidermal cells of anthers. Scanning electron microscopy analyses showed that epicuticular wax crystals were absent in the outer layer of the anther and that microspore development was severely retarded and finally disrupted as a result of defective pollen exine formation in the mutant anthers. These biochemical and developmental defects in tapetum found in wda1 mutants are earlier events than those in other male-sterile mutants, which showed defects of lipidic molecules in exine. Our findings provide new insights into the biochemical and developmental aspects of the role of waxes in microspore exine development in the tapetum as well as the role of epicuticular waxes in anther expansion.
T-cell lines from 2 patients with adenosine deaminase (ADA) deficiency showed the restoration of ADA activity resulted from the reversion of an inherited mutation (2001)

Inherited deficiency of adenosine deaminase (ADA) results in one of the autosomal recessive forms of severe combined immunodeficiency. This report discusses 2 patients with ADA deficiency from different families, in whom a possible reverse mutation had occurred. The novel mutations were identified in the ADA gene from the patients, and both their parents were revealed to be carriers. Unexpectedly, established patient T-cell lines, not B-cell lines, showed half-normal levels of ADA enzyme activity. Reevaluation of the mutations in these T-cell lines indicated that one of the inherited ADA gene mutations was reverted in both patients. At least one of the patients seemed to possess the revertant cells in vivo; however, the mutant cells might have overcome the revertant after receiving ADA enzyme replacement therapy. These findings may have significant implications regarding the prospects for stem cell gene therapy for ADA deficiency.
Accumulation of a recombinant immunotoxin in a tumor in vivo: fewer than 1000 molecules per cell are sufficient for complete responses. (1998)

Recombinant immunotoxins have been shown to cure human tumor xenografts in mice, but their biodistribution to both tumors and normal organs has not been reported. Anti-Tac(Fv)-PE38 is a single-chain recombinant immunotoxin composed of the variable heavy and light domains of the anti-Tac monoclonal antibody that reacts with the primate interleukin 2 (IL2) receptor alpha subunit (IL2R alpha or CD25) fused to a truncated form of Pseudomonas exotoxin (PE). 125I-labeled anti-Tac(Fv)-PE38 was given i.v. to immunodeficient mice each bearing two A431 tumors, one that expresses IL2R alpha (ATAC-4) and one that does not (A431, parental). A single i.v. dose of 4 microg/mouse caused complete regression of the IL2R alpha + tumor. At 6 h, over 6% of the injected dose/g was found in the ATAC-4 tumor, and 2% was in the A431 tumor. Uptake in the ATAC-4 tumor was higher than in any other tissue. Sections of tumor examined by autoradiography indicated that anti-Tac(Fv)-PE38 was distributed throughout the entire tumor, with some portions having higher uptake than others. By subtracting uptake in tumors without receptor (A431) from uptake in receptor-containing tumors (ATAC-4), we calculated that at least 400 molecules/cell specifically bound to IL2R alpha-positive tumor cells at 90 min and 750 molecules/cell bound at 360 min. This is similar to the 400-870 molecules/cell required for >99.9% killing of ATAC-4 cells growing as a monolayer. The results show that solid tumors in mice can be eradicated like cells in tissue culture, and that delivery of less than 1000 molecules/cell is sufficient to cause complete tumor regressions.
Micro-Electrospray: Zeptomole/attomole per microliter sensitivity for peptides (1994)

The micro-electrospray ionization source has been optimized for the specific analysis of neuropeptides such as neurotensin and methionine enkephalin. The source has the option of integrating nanoliter flow-rate desalting and preconcentration techniques into the micro-electrospray spray needle, eliminating post-column dead volumes. For neurotensin, the most sensitive neuropeptide analyzed thus far in this work, the injection of 10 μL of a solution containing 320 zeptomolesy/gmL gave an [M + 3H](+3) ion at m/z 558.4 with S/N of > 8∶1. The MS/MS analysis of this peptide for the fragment ion at m/z 578.9 gave a S/N > 20∶1 for a solution containing 32 attomoles/μL.
The nucleotide sequences of the rbsD, rbsA, and rbsC genes of Escherichia coli K12. (1986)

The nucleotide sequences of rbsD, rbsA, and rbsC have been determined. These genes encode components of the high affinity ribose transport system in Escherichia coli, and together with the sequences of rbsB (Groarke, J.M., Mahoney, W.C., Hope, J.N., Furlong, C.E., Robb, F.T., Zalkin, H., and Hermodson, M.A. (1983) J. Biol. Chem. 258, 12952-12956) and rbsK (Hope, J.N., Bell, A.W., Hermodson, M.A., and Groarke, J.M. (1986) J. Biol. Chem. 261, 7663-7668), they complete the nucleotide sequence of the first five genes of the rbs operon. Nuclease S1 mapping places the transcriptional start site for the operon 29 base pairs upstream from the most likely translational start site for rbsD. The open reading frames of rbsD, rbsA, and rbsC encode proteins of 139, 501, and 321 amino acid residues, respectively. The character of the proteins varies widely, from very hydrophilic for the rbsA product to exceedingly hydrophobic for the rbsC product. The intercistronic spaces between the three genes are very short, with the stop codons of the upstream genes overlapping the ribosome-binding sites of the downstream genes. This may imply translational control of expression of these genes, the products of which presumably form a membrane-bound transport complex.
Using the photoinduced reversible refractive-index change of an azobenzene co-polymer to reconfigure an optical Bragg grating (2010)

A photoactive material has been synthesised in which azobenzene units are attached to a methyl methacrylate/2-hydroxyethyl methacrylate co-polymer and shows repeated photoresponsive switching upon irradiation at 365 nm and 254 nm with long term thermal stability. In combination with a direct UV-written silica-on-silicon Bragg grating, this has been used to fabricate a prototype optical device which undergoes reversible refractive index changes at telecom wavelengths. The 63 GHz tuning response demonstrated by this device has potential applicability for reconfigurable dispersion compensation for use in optical networks.
ChemInform Abstract: SYNTHESE VON 3‐(AMIDINOPHENYL)‐ALANINEN UND 3‐(AMIDINOPHENYL)‐MILCHSAEUREN (1974)

Abstract Aus den Cyanbenzylbromiden (I) und den Malonesterderivaten (II) werden die Verbindungen (III) hergestellt und mit Methanol und Chlorwasserstoff in die ImidoesteF hydrochloride (V) übergeführt.
2,5‘-Disubstituted Adenosine Derivatives:  Evaluation of Selectivity and Efficacy for the Adenosine A1, A2A, and A3 Receptor (2001)

Novel 2,5'-disubstituted adenosine derivatives were synthesized in good overall yields starting from commercially available guanosine. Binding affinities were determined for rat adenosine A(1) and A(2A) receptors and human A(3) receptors. E(max) values were determined for the stimulation or inhibition of cAMP production in CHO cells expressing human adenosine A(2A) (EC(50) values as well) or A(3) receptors, respectively. The compounds displayed affinities in the nanomolar range for both the adenosine A(2A) and A(3) receptor, without substantial preference for either receptor. The derivatives with a 2-(1-hexynyl) group had the highest affinities for both receptors; compound 4 (2-(1-hexynyl)adenosine) had the highest affinity for the adenosine A(2A) receptor with a K(i) value of 6 nM (A(3)/A(2A) selectivity ratio of approximately 3), whereas compound 37 (2-(1-hexynyl)-5'-S-methyl-5'-thioadenosine) had the highest affinity for the adenosine A(3) receptor with a K(i) value of 15 nM (A(2A)/A(3) selectivity ratio of 4). In general, compounds with a relatively small 5'-S-alkyl-5'-thio substituent (methyl-5'-thio) displayed the highest affinities for both the adenosine A(2A) and A(3) receptor; the larger ones (n- or i-propyl-5'-thio) increased the selectivity for the adenosine A(3) receptor. The novel compounds were also evaluated in cAMP assays for their (partial) agonistic behavior. Overall, the disubstituted derivatives behaved as partial agonists for both the adenosine A(2A) and A(3) receptor. The compounds showed somewhat higher intrinsic activities on the adenosine A(2A) receptor than on the A(3) receptor. Compounds 37, 40 and 45, 48, with either a 5'-S-methyl-5'-thio or a 5'-S-i-propyl-5'-thio substituent had the lowest intrinsic activities on the adenosine A(2A) receptor. For the A(3) receptor, compounds 34, 35, 38, 39, and 46, 47, with a 5'-S-ethyl-5'-thio or a 5'-S-n-propyl-5'-thio substituent had the lowest intrinsic activities.
Electrophysiological mapping for the implantation of deep brain stimulators for Parkinson's disease and tremor (2006)

The vast majority of centers use electrophysiological mapping techniques to finalize target selection during the implantation of deep brain stimulation (DBS) leads for the treatment of Parkinson's disease and tremor. This review discusses the techniques used for physiological mapping and addresses the questions of how various mapping strategies modify target selection and outcome following subthalamic nucleus (STN), globus pallidus internus (GPi), and ventralis intermedius (Vim) deep brain stimulation. Mapping strategies vary greatly across centers, but can be broadly categorized into those that use microelectrode or semimicroelectrode techniques to optimize position prior to implantation and macrostimulation through a macroelectrode or the DBS lead, and those that rely solely on macrostimulation and its threshold for clinical effects (benefits and side effects). Microelectrode criteria for implantation into the STN or GPi include length of the nucleus recorded, presence of movement-responsive neurons, and/or distance from the borders with adjacent structures. However, the threshold for the production of clinical benefits relative to side effects is, in most centers, the final, and sometimes only, determinant of DBS electrode position. Macrostimulation techniques for mapping, the utility of microelectrode mapping is reflected in its modification of electrode position in 17% to 87% of patients undergoing STN DBS, with average target adjustments of 1 to 4 mm. Nevertheless, with the absence of class I data, and in consideration of the large number of variables that impact clinical outcome, it is not possible to conclude that one technique is superior to the other in so far as motor Unified Parkinson's Disease Rating Scale outcome is concerned. Moreover, mapping technique is only one out of many variables that determine the outcome. The increase in surgical risk of intracranial hemorrhage correlated to the number of microelectrode trajectories must be considered against the risk of suboptimal benefits related to omission of this technique.
Tibialis Posterior Muscle (1992)

The posterior aspect of 51 embalmed cadaver legs in 50 cadavers was dissected to establish the prevalence of a separate compartment for the tibialis posterior muscle (TP). All dissections revealed the presence of a superficial and a deep posterior compartment. No distinct fascial septum separated the TP from the flexor digitorum longus (FDL) and flexor hallucis longus (FHL). We conclude that the TP does not commonly rest within its own osseofascial compartment and thus does not require isolated decompression for acute compartment syndrome of the leg. An incidental observation, frequently overlooked in the anatomy literature, was a supplemental tendon of origin of the FDL. In addition to the classically described tibial origin, several cadavers exhibited a proximal fibular tendon of origin for the FDL. One cadaver demonstrated the FDL to have an extensive fibular origin that completely covered the TP, forming a myotendinous fifth compartment. We feel that the variable fibular origin can explain the chronic exertional compartment syndrome of the TP described previously by Davey et al. and serves as a basis for a minor alteration in our fasciotomy technique.
Cell phone intervention to improve adherence: Cystic fibrosis care team, patient, and parent perspectives (2010)

The current study provided some support from key stakeholders for this intervention to improve adherence in adolescents with CF. Next steps include a multi-center trial of the efficacy and safety of CFFONE.
Promoter of the gene for the multifunctional protein disulfide isomerase polypeptide. Functional significance of the six CCAAT boxes and other promoter elements. (1992)

Protein disulfide isomerase (PDI) is a highly unusual multifunctional polypeptide that is identical to the beta-subunit of prolyl 4-hydroxylase, a cellular thyroid hormone-binding protein and a subunit of the microsomal triglyceride transfer protein complex, and very similar to a polypeptide functioning in vitro as a glycosylation site binding protein of oligosaccharyl transferase. The human PDI gene possesses several putative transcriptional control elements, including the highly unusual presence of six CCAAT boxes between -108 and -378 of the 5'-flanking region. We report here on a promoter analysis of this gene. Eleven PDI promoter elements recognized by DNA-binding proteins present in HeLa cell and HT-1080 cell nuclear extracts were identified by DNase I footprinting analysis within the first 630 nucleotides of the 5'-flanking region. Interestingly, these included all six CCAAT elements. Functional 5' deletion analysis suggested that only two or three of the CCAAT elements may contribute significantly to the promoter activity in HeLa cells. Mutations introduced into each of the CCAAT boxes separately indicated, however, that all six appear to contribute to the promoter strength, the largest decreases (approximately 50%) being seen with mutations in the second or fifth CCAAT box. These data thus suggested that efficient expression of the multifunctional PDI polypeptide is secured by multiple CCAAT elements, some of which appear to be functionally redundant. The 5' deletion analysis further suggested that a region between -623 and -518 may contain additional positively and negatively acting elements.
Targeted Therapeutic Strategies for Fetal Hemoglobin Induction (2011)

Increased levels of fetal hemoglobin (HbF) can ameliorate the severity of the β-hemoglobin disorders, sickle cell disease (SCD) and β-thalassemia, which are major sources of morbidity and mortality worldwide. As a result, there has been a longstanding interest in developing therapeutic approaches for inducing HbF. For more than 3 decades, the majority of HbF inducers developed were based on empiric observations and have had limited success. Recently, human genetic approaches have provided insight into previously unappreciated regulators of the fetal-to-adult hemoglobin switch and HbF silencing, revealing molecular targets to induce HbF. This article reviews these developments and discusses how molecules including BCL11A, KLF1, MYB, SOX6, miRNAs 15a and 16-1, and histone deacetylase 1 and 2 (HDAC1/2) could be important targets for HbF induction in humans. The current understanding of how these molecules function and the benefits and drawbacks of each of these potential therapeutic targets are also examined. The identification of these regulators of HbF expression is extremely promising and suggests that rationally designed approaches targeting the very mechanisms mediating this switching process could lead to better, less toxic, and more effective strategies for HbF induction.
Chemistry, mechanism and clinical status of antisense oligonucleotides and duplex RNAs (2017)

RNA plays a central role in the expression of all genes. Because any sequence within RNA can be recognized by complementary base pairing, synthetic oligonucleotides and oligonucleotide mimics offer a general strategy for controlling processes that affect disease. The two primary antisense approaches for regulating expression through recognition of cellular RNAs are single-stranded antisense oligonucleotides and duplex RNAs. This review will discuss the chemical modifications and molecular mechanisms that make synthetic nucleic acid drugs possible. Lessons learned from recent clinical trials will be summarized. Ongoing clinical trials are likely to decisively test the adequacy of our current generation of antisense nucleic acid technologies and highlight areas where more basic research is needed.
A Quasi-Dense Approach to Surface Reconstruction from Uncalibrated Iages (2005)

This paper proposes a quasi-dense approach to 3D surface model acquisition from uncalibrated images. Firstly, correspondence information and geometry are computed based on new quasi-dense point features that are re-sampled sub-pixel points from a disparity map. The quasi-dense approach gives more robust and accurate geometry estimations than the standard sparseapproach. The robustness is measured as the success rate of full automatic geometry estimation with all involved parameters fixed. The accuracy is measured by a fast gauge-free uncertainty estimation algorithm. The quasi-dense approach also works for more largely separated images than the sparse approach, therefore requires fewer images for modeling. More importantly, the quasi-dense approach delivers a high density of reconstructed 3D points on which a surface representation can be reconstructed. This fills the gap of insufficiency of the sparse approach for surface reconstruction, essential for modeling and visualization applications. Secondly, surface reconstruction methods from the given quasi-dense geometry are also developed. The algorithm optimizes new unified functionals integrating both 3D quasi-dense points and 2D image information including silhouettes. Combining both 3D data and 2D images is more robust than the existing methods using only 2D information or only 3D data. An efficient bounded regularization method is proposed to implement the surface evolution by level-set methods. Its properties are discussed and proved for some cases. As a whole, a complete automatic and practical system of 3D modeling from raw images captured by hand-held cameras to surface representation is proposed. Extensive experiments demonstrate the superior performance of the quasi-dense approach with respect to the standard sparse approach in robustness, accuracy, and applicability.
Comparison of Pre- versus Post-incision Administration of Intrathecal Bupivacaine and Intrathecal Morphine in a Rat Model of Postoperative Pain (1997)

Early reduction in pain behaviors either by pre- or postincision management had no impact on subsequent measures of hyperalgesia in this model. These results agree with a number of clinical studies and suggest that incisional pain may be initiated and maintained differently than pain in other models.
ALD precursor chemistry : Evolution and future challenges (1999)

The requirements of ALD precursors differ from those of CVD concerning thermal stability, adsorption on the surface, and reactions towards each other In the first ALD experiments in the 70s clements (Zn, Cd, S), metal halides and non-metal hydrides (H 2 O, H 2 S) were used. In the 80s the selection of precursors widened to metal complexes (alkoxides, β-diketonates) and simple organometallics (alkyl compounds). In the 90s both new metal (Cp-compounds, alkylamides) as well as non-metal precursors (H 2 O 2 , O 3 , hydrazine) have been introduced. A characteristic feature of ALD is that surface groups play an important role as reactive sites for the next precursor pulse. The development of ALD precursors is limited by the small number of groups working in the field. It seems, however, that the precuror development is diverged and tailored molecules are designed for each process.