gebhart/patrepeval huggingface dataset:
Constitutively Active MuSK Is Clustered in the Absence of Agrin and Induces Ectopic Postsynaptic-Like Membranes in Skeletal Muscle Fibers (1999)

In skeletal muscle fibers, neural agrin can direct the accumulation of acetylcholine receptors (AChR) and transcription of AChR subunit genes from the subsynaptic nuclei. Although the receptor tyrosine kinase MuSK is required for AChR clustering, it is less clear whether MuSK regulates gene transcription. To elucidate the role of MuSK in these processes, we constructed a constitutively active MuSK receptor, MuSKneuTMuSK, taking advantage of the spontaneous homodimerization of the transmembrane domain of neuT, an oncogenic variant of the neu/erbB2 receptor. In the extrasynaptic region of innervated muscle fibers, MuSKneuTMuSK formed highly concentrated aggregates that colocalized with AChR clusters. Associated with MuSK-induced AChR clusters was a normal complement of synaptic proteins. Moreover, transcription of the AChR-epsilon subunit gene was increased, albeit via an indirect mechanism by MuSK-induced aggregation of erbB receptors and neuregulin. Although neural agrin was not required, the activity of MuSKneuTMuSK was nevertheless potentiated by ectopic expression of a muscle agrin isoform inactive in AChR clustering. To define the role of the kinase domain in the formation of a postsynaptic-like membrane, a second fusion receptor, neuneuTMuSK, which included the MuSK kinase but not the MuSK extracellular domain, was expressed. Significantly, neuneuTMuSK induced AChR clusters that colocalized with aggregates of endogenous MuSK. Taken together, it was concluded that the MuSK kinase domain is sufficient to initiate the recruitment of additional MuSK receptors, which then develop into highly concentrated aggregates by means of a positive feedback loop to induce a postsynaptic membrane in the absence of neural agrin.
Structural Investigation of Encapsulated Fluoride in Polyhedral Oligomeric Silsesquioxane Cages Using Ion Mobility Mass Spectrometry and Molecular Mechanics (2008)

A new series of encapsulated fluoride polyhedral oligomeric silsesquioxane (POSS) materials, [(CH3)4N+][F−@(R8Si8O12)], where R = vinyl, phenyl, styrenyl, trifluoropropyl, nonafluorohexyl, or tridecafluorooctyl, were synthesized by the reaction of tetramethylammonium fluoride with the R8Si8O12 POSS in tetrahydrofuran. Encapsulation of the fluoride was confirmed with 19F and 29Si NMR spectroscopy. Ion mobility and molecular modeling methods were used to investigate the gas phase conformational properties of these POSS. Theoretical calculations demonstrate that the binding energy of fluoride to the interior of the POSS cage ranges from 70 to 270 kcal/mol as a function of substituent. Sodiated positive ions of the form H+[F−@R8T8]Na+ (T = SiO3/2, R = styrenyl, phenyl, and vinyl) were examined by MALDI; ESI was used to study the negative ions F−@R8T8 (R = styrenyl, phenyl, vinyl, trifluoropropyl, and nonafluorohexyl). The ion mobilities of these species were measured and used to calculate collision cross sections. These cross sections were compared to X-ray crystal structures and theoretical cross sections obtained from molecular mechanics and dynamics calculations. Experimental cross sections were consistent with all of the known X-ray crystal structures (styrenyl, vinyl, and phenyl POSS species). The experimental cross sections also agreed with the calculated cross sections for each species. As a result of the compact nature of the POSS cages, each sample had only one stable conformation, and only one low-energy family of structures was found for each set of sample calculations.
Biological Concepts of Prolonged Neoadjuvant Treatment plus GM-CSF in Locally Advanced Tumors (2000)

Local treatment with surgery and radiotherapy gives unsatisfactory results in patients with locally advanced cancer. In many cases distant metastases appear shortly after the removal of the primary tumor. Selecting breast cancer as a model for locally advanced disease, we are extrapolating our findings to other solid tumors. Neoadjuvant chemotherapy has improved survival of these patients by downstaging the primary tumors allowing local treatment and early elimination of distant micrometastases. We recently reported in this journal on a study of 42 patients with locally advanced breast cancer (LABC) who received prolonged neoadjuvant chemotherapy of doxorubicin, cyclophosphamide, and GM-CSF prior to surgery and postoperative radiotherapy. These results were promising and prompted us to initiate an international randomized phase III study in which either six neoadjuvant cycles or three neoadjuvant cycles plus three adjuvant cycles are being compared. In LABC patients treated with six neoadjuvant chemoimmunotherapy cycles, we observed a significant rise in the dendritic cell content of the axillary tumor-draining lymph nodes after therapy, associated with an encouraging disease free survival and overall survival. We hypothesize that the prolonged presence of draining lymph nodes in combination with the repeated tumor antigen release, dendritic cell recruitment, and activation may account for the observed increased survival of LABC patients. Based on our findings and the results of preclinical studies, we hypothesize that it is more effective to administer chemotherapy in an extended neoadjuvant regimen, taking advantage of the concurrent biological and immunological processes in the primary tumor and its draining lymph nodes.
Plasma Levels of SDF-1 and Expression of SDF-1 Receptor on CD34+ Cells in Mobilized Peripheral Blood of Non-Hodgkin's Lymphoma Patients (2001)

CXCR4 is the receptor for the chemokine stromal derived factor-1 (SDF-1), is expressed on CD34+ cells, and has been implicated in the process of CD34+ cell migration and homing. We studied the mobilization of CD34/CXCR4 cells and the plasma levels of SDF-1 and flt3-ligand (flt3-L) in 36 non-Hodgkin's lymphoma patients receiving cyclophosphamide (Cy) plus G-CSF (arm A), Cy plus GM-CSF (arm B), or Cy plus GM-CSF followed by G-CSF (arm C) for peripheral blood stem cell (PBSC) mobilization and autotransplantation. We observed lower plasma levels of SDF-1 in PBSCs compared to premobilization bone marrow samples. The mean plasma SDF-1 levels were similar in PBSC collections in the three arms of the study. In contrast, SDF-1 levels in the apheresis collections of the "good mobilizers" (patients who collected a minimum of 2 x 10(6) CD34+ cells/kg in one to four PBSC collections) were significantly lower than the apheresis collections of the "poor mobilizers" (> or = 0.4 x 10(6) CD34+ cells/kg in the first two PBSC collections; 288 +/- 82 pg/ml versus 583 +/- 217 pg/ml; p = 0.0009). The mean percentage of CD34+ cells expressing CXCR4 in the apheresis collections was decreased in the PBSC collections compared with premobilization values from 28% to 19.4%. Furthermore, the percentage of CD34+ cells expressing CXCR4 in the good mobilizers was significantly lower compared with the poor mobilizers (14.7 +/- 2.1% versus 33.6 +/- 2.1%; p = 0.002). The good mobilizers had also significantly lower levels of flt3-L compared with the poor mobilizers (34 +/- 4 pg/ml versus 106 +/- 11 pg/ml; p = 0.006), Finally, the levels of flt3-L strongly correlated with SDF-1 levels (r = 0.8; p < 0.0001). We conclude: A) low plasma levels of SDF-1 and low expression of CXCR4 characterize patients with good mobilization outcome, and B) the levels of SDF-1 correlate with flt3-L, suggesting an association of these cytokines in mobilization of CD34+ cells.
Epitope mapping of 10 monoclonal antibodies against the pig analogue of human membrane cofactor protein (MCP) (1999)

Pig membrane cofactor protein (MCP; CD46) is a 50 000-60 000 MW glycoprotein that is expressed on a wide variety of cells, including erythrocytes. Pig MCP has cofactor activity for factor I-mediated cleavage of C3b and is an efficient regulator of the classical and alternative pathway of human and pig complement. A panel of 10 monoclonal antibodies (mAbs) was collected from two different laboratories; all of these mAbs were raised against pig leucocytes and all recognized the same complex banding pattern on sodium dodecyl sulphate-polyacrylamide gel electrophoresis (SDS-PAGE) of erythrocyte membranes. All were shown to be reactive with pig MCP and were divided into four groups of mutually competitive antibodies based on competition studies for membrane-bound MCP and for soluble MCP, the latter by surface plasmon resonance (SPR) analysis. The antigenic properties of membrane-bound and soluble MCP were similar, although some interesting differences were revealed. None of the 10 mAbs were cross-reactive with human MCP and only one showed cross-reactivity with leucocytes from a panel of large mammals - a weak cross-reactivity with a subset of dog leucocytes. All antibodies in one of the epitope groups and some in a second epitope group were able to block the functional activity of pig MCP, as measured by inhibition of MCP-catalysed C3 degradation by factor I.
Vision and control techniques for robotic visual tracking (2002)

Algorithms for robotic real-time visual tracking of arbitrary 3-D objects traveling at unknown velocities in a 2-D space are presented. The problem of visual tracking is formulated as a problem of combining control with computer vision. A mathematical formulation that is general enough to be extended to the problem of tracking 3-D objects in 3-D space is presented. The authors propose the use of sum-of-squared differences optical flow for the computation of the vector of discrete displacements each instant of time. These displacements can be fed either directly to a PI controller, a pole assignment controller, or a discrete steady-state Kalman filter. In the latter case, the Kalman filter calculates the estimated values of the system's states and exogenous disturbances, and a discrete LQG controller computes the desired motion of the robotic system. The outputs of the controllers are sent to a Cartesian robotic controller that drives the robot.< <ETX xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">&gt;</ETX>
The microRNA feedback regulation of p63 in cancer progression (2015)

The transcription factor p63 is a member of the p53 gene family that plays a complex role in cancer due to its involvement in epithelial differentiation, cell cycle arrest and apoptosis. MicroRNAs are a class of small, non-coding RNAs with an important regulatory role in various cellular processes, as well as in the development and progression of cancer. A number of microRNAs have been shown to function as transcriptional targets of p63. Conversely, microRNAs also can modulate the expression and activity of p63. However, the p63-microRNA regulatory circuit has not been addressed in depth so far. Here, computational genomic analysis was performed using miRtarBase, Targetscan, microRNA.ORG, DIANA-MICROT, RNA22-HSA and miRDB to analyze miRNA binding to the 3'UTR of p63. JASPAR (profile score threshold 80%) and TFSEARCH datasets were used to search transcriptional start sites for p53/p63 response elements. Remarkably, these data revealed 63 microRNAs that targeted p63. Furthermore, there were 39 microRNAs targeting p63 that were predicted to be regulated by p63. These analyses suggest a crosstalk between p63 and microRNAs. Here, we discuss the crosstalk between p63 and the microRNA network, and the role of their interactions in cancer.
Neurocognitive function (NCF) outcomes in patients with glioblastoma (GBM) enrolled in RTOG 0825. (2013)

2004 Background: RTOG 0825 evaluated overall survival (OS) and progression-free survival (PFS) differences in patients with newly diagnosed GBM treated with standard chemoradiation, maintenance temozolomide and placebo (Arm 1) or bevacizumab (Arm 2). While OS was equivalent, PFS was longer in Arm 2. Longitudinal NCF testing was performed to evaluate clinical benefit. Methods: NCF was evaluatedat baseline and while on study and progression free with the Hopkins Verbal Learning Test-Revised (HVLT-R), Trail Making Test (TMT) and Controlled Oral Word Association (COWA). Change in NCF from baseline was categorized using the reliable change index. Differences between treatment arms were compared at follow-up evaluations. Additionally, baseline (B) and early changes (EC) (B to week 10) in NCF were examined as prognostic factors. Results: 542 patients consented and 507 randomized patients participated, with test completion rates at weeks 0 (B), 10, 22, and 34 of 94-97, 69-73, 59-64, and 53-58%, respectively. Mean test performance at B was equivalent between arms and ranged from -0.8 to -4.8 SDs below healthy population norms with global NCF on a composite variable at -2.0 SDs. There were no statistically significant between arm differences in frequency of improvement through week 34. Decline on COWA (verbal measure of executive function) at week 34 relative to baseline was more common (16.1 vs 5.7%) in patients in Arm 1 (p&lt;0.05); whereas, there were trends for more decline in Arm 2 on a visuomotor measure of executive function (TMT B, p&lt; 0.06; 22.2 vs 35.4%). B performance and EC in global NCF, memory, executive function and processing speed were prognostic for OS. At B, global NCF was prognostic for PFS. EC in global NCF, memory and executive function were prognostic for PFS. Conclusions: There was a statistically significant difference in the frequency of decline on a verbal test of executive function at week 34 favoring Arm 2. However, this was not found at earlier time points and was not found on a visuomotor test of executive function. B and EC in NCF were prognostic for OS and PFS. Longitudinal modeling is ongoing to further evaluate the impact of treatment on patients’ NCF. Support: U10 CA21661, U10 CA37422 and Genentech, Inc. Clinical trial information: NCI-2009-01670.
HSV-1 Vector-Delivered FGF2 to the Retina Is Neuroprotective but Does Not Preserve Functional Responses (2001)

Fibroblast growth factor 2 (bFGF, FGF2) exhibits mitogenic, angiogenic, wound healing, and neuroprotective properties. Infusion of FGF2 in vivo to treat neurodegenerative disorders in animal models results in increased survival of damaged neurons, but these effects are transient. To test the feasibility of HSV vector-delivered FGF2 for neuroprotection, we inserted the FGF2 gene under the control of the HCMV immediate-early promoter into an attenuated avirulent HSV-1 vector. Transduction with FGF2/HSV-1 virus promoted survival of PC12 cells, induced differentiation of these cells to the neuronal phenotype in vitro, and protected PC12 neuronal cells from death induced by nerve growth factor withdrawal. The attenuated FGF2/HSV-1 virus was able to deliver and direct expression of the FGF2 gene in the eye. Delivery prior to light exposure in a rat model of retinal degeneration resulted in significant protection against photoreceptor loss. However, functional ERG responses were not detected. Treatment of normal eyes with the vector alone suppressed ERGs, which were only partially restored in eyes receiving the FGF2 vector. Thus, although the FGF2-HSV-1 virus induced preservation of cell and tissue structure, this was not sufficient to protect photoreceptor function. Fibroblast growth factor 2 (bFGF, FGF2) exhibits mitogenic, angiogenic, wound healing, and neuroprotective properties. Infusion of FGF2 in vivo to treat neurodegenerative disorders in animal models results in increased survival of damaged neurons, but these effects are transient. To test the feasibility of HSV vector-delivered FGF2 for neuroprotection, we inserted the FGF2 gene under the control of the HCMV immediate-early promoter into an attenuated avirulent HSV-1 vector. Transduction with FGF2/HSV-1 virus promoted survival of PC12 cells, induced differentiation of these cells to the neuronal phenotype in vitro, and protected PC12 neuronal cells from death induced by nerve growth factor withdrawal. The attenuated FGF2/HSV-1 virus was able to deliver and direct expression of the FGF2 gene in the eye. Delivery prior to light exposure in a rat model of retinal degeneration resulted in significant protection against photoreceptor loss. However, functional ERG responses were not detected. Treatment of normal eyes with the vector alone suppressed ERGs, which were only partially restored in eyes receiving the FGF2 vector. Thus, although the FGF2-HSV-1 virus induced preservation of cell and tissue structure, this was not sufficient to protect photoreceptor function.
Simultaneous Endocardial Mapping in the Human Left Ventricle Using a Noncontact Catheter (1998)

This noncontact mapping system accurately reconstructs endocardial unipolar electrograms from the human left ventricle. At M-E distances >34 mm, timing accuracy of reconstruction decreases.
Characterization of al-2, the phytoene synthase gene of Neurospora crassa. Cloning, sequence analysis, and photoregulation. (1994)

We have cloned the al-2 gene of Neurospora crassa and have analyzed its structure and regulation. The gene encodes a 603-residue polypeptide with a segment homologous to prokaryotic and other eukaryotic phytoene synthases. RNA measurements showed that the level of al-2 mRNA increased over 30-fold in photoinduced mycelia compared with dark-grown mycelia. This observation is consistent with the fact that carotenoid biosynthesis is induced by blue light during growth of N. crassa mycelia. The photoinduced increase in al-2 mRNA levels was not observed in two Neurospora mutants, wc-1 and wc-2, that are defective in all physiological photoresponses.
Adaptive Immunity to Infection (2001)

Panitumumab monotherapy efficacy in mCRC is confined to patients with WT KRAS tumors. KRAS status should be considered in selecting patients with mCRC as candidates for panitumumab monotherapy.
Comparison of sexual functioning in clinical and nonclinical populations using the Changes in Sexual Functioning Questionnaire (CSFQ). (1997)

The Changes in Sexual Functioning Questionnaire (CSFQ), a structured interview/questionnaire designed to measure illness- and medication-related effects on sexual functioning, is presented with initial evidence of its clinical usefulness in differentiating between those who have sexual dysfunction and those who have no dysfunction. Individuals from clinical and nonclinical samples completed the CSFQ. The sample groups were compared on mean scores on the CSFQ and its subscales. Comparative findings indicate that psychiatric patients diagnosed with a mood disorder have significantly lower sexual functioning when compared with nonpsychiatric outpatients, medical students, and psychiatry residents combined. The CSFQ is a useful measure for assessing medication- or illness-related effects on sexual functioning in a systematic way.
Critical care in 1996 (1996)

1996 President Society of Critical Care Medicine Presented, in part, at the 25th Educational and Scientific Symposium of the Society of Critical Care Medicine, New Orleans, LA, February 6, 1996. Address requests for reprints to: John W. Hoyt, MD, Department of Critical Care Medicine, St. Francis Medical Center, 408 45th Street, Pittsburgh, PA 15201-1115.
Phenotype associated with an R120X nonsense mutation in the RP2 gene in a Japanese family with X-linked retinitis pigmentosa (2001)

We examined a Japanese family with X-linked retinitis pigmentosa (RP) associated with a nonsense mutation, R120X, in the RP2 gene. The 26-year-old proband presented at the age of seven years with a two-year history of night blindness. Visual disability worsened with increasing age. At age 24, visual acuity was 0.08 in both eyes. Testing for refractive error indicated mild myopia. Visual fields showed bilateral-constriction to 10 degrees. He had central macular areolar sclerosis in both eyes. Two maternal uncles had vision of light perception to hand movement in their early forties together with dense bilateral cataracts. The ocular phenotype of this family with R120X was considered severe; reported phenotypes associated with this mutation have not been uniform.
Effect of Film Thickness on the Antifouling Performance of Poly(hydroxy-functional methacrylates) Grafted Surfaces (2011)

The development of nonfouling biomaterials to prevent nonspecific protein adsorption and cell/bacterial adhesion is critical for many biomedical applications, such as antithrombogenic implants and biosensors. In this work, we polymerize two types of hydroxy-functional methacrylates monomers of 2-hydroxyethyl methacrylate (HEMA) and hydroxypropyl methacrylate (HPMA) into polymer brushes on the gold substrate via surface-initiated atom transfer radical polymerization (SI-ATRP). We systematically examine the effect of the film thickness of polyHEMA and polyHPMA brushes on their antifouling performance in a wide range of biological media including single-protein solution, both diluted and undiluted human blood serum and plasma, and bacteria culture. Surface plasmon resonance (SPR) results show a strong correlation between antifouling property and film thickness. Too thin or too thick polymer brushes lead to large protein adsorption. Surfaces with the appropriate film thickness of ∼25-45 nm for polyHPMA and ∼20-45 nm for polyHEMA can achieve almost zero protein adsorption (<0.3 ng/cm(2)) from single-protein solution and diluted human blood plasma and serum. For undiluted human blood serum and plasma, polyHEMA brushes at a film thickness of ∼20-30 nm adsorb only ∼3.0 and ∼3.5 ng/cm(2) proteins, respectively, while polyHPMA brushes at a film thickness of ∼30 nm adsorb more proteins of ∼13.5 and ∼50.0 ng/cm(2), respectively. Moreover, both polyHEMA and polyHPMA brushes with optimal film thickness exhibit very low bacteria adhesion. The excellent antifouling ability and long-term stability of polyHEMA and polyHPMA brushes make them, especially for polyHEMA, effective and stable antifouling materials for usage in blood-contacting devices.
Identification of Positive and Negative Splicing Regulatory Elements within the Terminal tat-rev Exon of Human Immunodeficiency Virus Type 1 (1995)

The requirement of human immunodeficiency virus type 1 to generate numerous proteins from a single primary transcript is met largely by the use of suboptimal splicing to generate over 30 mRNAs. To ensure that appropriate quantities of each protein are produced, there must be a signal(s) that controls the efficiency with which any particular splice site in the RNA is used. To identify this control element(s) and to understand how it operates to generate the splicing pattern observed, we have initially focused on the control of splicing of the tat-rev intron, which spans the majority of the env open reading frame. Previous analysis indicated that a suboptimal branchpoint and polypyridimine tract in this intron contribute to its suboptimal splicing (A. Staffa and A. Cochrane, J. Virol. 68:3071-3079, 1994). In this report, we identify two additional elements within the 3'-terminal exon, an exon-splicing enhancer (ESE) and an exon splicing silencer (ESS), that modulate the overall efficiency with which the 3' tat-rev splice site is utilized. Both elements are capable of functioning independently of one another. Furthermore, while both the ESE and ESS can function in a heterologous context, the function of the ESS is extremely sensitive to the sequence context into which it is placed. In conclusion, it would appear that the presence of a suboptimal branchpoint and a polypyrimidine tract as well as the ESE and ESS operate together to yield the balanced splicing of the tat-rev intron observed in vivo.