gebhart/patrepeval huggingface dataset:
Differences in the TGF-β1–Induced Profibrotic Response of Anterior and Posterior Corneal Keratocytes In Vitro (2010)

Purpose. To characterize phenotypic differences between anterior and posterior corneal keratocytes after stimulation with the profibrotic agent transforming growth factor-beta1 (TGF-beta1) in vitro. Methods. Sixteen corneas from healthy felines were obtained immediately after death. Lamellar dissection was performed to separate the anterior and posterior stroma at approximately 50% depth either manually (n = 2) or with a Moria microkeratome (300-mum head; n = 14). Cells from the anterior and posterior stroma were cultured separately but under identical conditions. Using immunohistochemistry and Western blot techniques, Ki-67 staining and relative expression of Thy-1, alpha smooth muscle actin (alpha-SMA), and fibronectin were assessed after stimulation with different TGF-beta1 concentrations. In addition, anterior and posterior cells cultured in different concentrations of TGF-beta1 were wounded with a razor blade, and the wound area and time to closure were determined. Results. Stimulation by all concentrations of TGF-beta1 increased the proportion of Ki-67-positive cells in anterior and posterior cell cultures, but this increase was noted earlier in posterior cells than in anterior cells. Increasing TGF-beta1 concentration also increased the relative expression of Thy-1, alpha-SMA, and fibronectin in anterior and posterior fibroblasts. However, anterior cells expressed these fibrotic markers at lower TGF-beta1 concentrations than did posterior keratocytes. After mechanical wounding, posterior cells closed the wound area faster than did anterior cells at all concentrations of TGF-beta1. Conclusions. The present experiments show that anterior and posterior corneal keratocytes exhibit different sensitivities to the profibrotic growth factor TGF-beta1. This heterogeneity of keratocyte response may impact wound closure after mechanical wounding.
Respiratory applications of in-vivo confocal endomicroscopy (2016)

International audience
Preclinical evaluation of 213Bi-/225Ac-labeled low-molecular-weight compounds for radiopharmaceutical therapy of prostate cancer (2020)

Prostate-specific membrane antigen (PSMA)-targeted radiopharmaceutical therapy is a new option for patients with advanced prostate cancer refractory to other treatments. Previously, we synthesized a β-particle-emitting low-molecular-weight compound, <sup>177</sup>Lu-L1 which demonstrated reduced off-target effects in a xenograft model of prostate cancer. Here, we leveraged that scaffold to synthesize α-particle-emitting analogs of L1, <sup>213</sup>Bi-L1 and <sup>225</sup>Ac-L1, to evaluate their safety and cell kill effect in PSMA-positive (+) xenograft models. <b>Methods:</b> The radiochemical synthesis, cell uptake, cell kill, and biodistribution of <sup>213</sup>Bi-L1 and <sup>225</sup>Ac-L1 were evaluated. The efficacy of <sup>225</sup>Ac-L1 was determined in human PSMA+ subcutaneous and micrometastatic models. Subacute toxicity at 8 wk and chronic toxicity at 1 y after administration were evaluated for <sup>225</sup>Ac-L1. The absorbed radiation dose of <sup>225</sup>Ac-L1 was determined using the biodistribution data and α-camera imaging. <b>Results:</b><sup>213</sup>Bi- and <sup>225</sup>Ac-L1 demonstrated specific cell uptake and cell kill in PSMA+ cells. The biodistribution of <sup>213</sup>Bi-L1 and <sup>225</sup>Ac-L1 revealed specific uptake of radioactivity within PSMA+ lesions. Treatment studies of <sup>225</sup>Ac-L1 demonstrated activity-dependent, specific inhibition of tumor growth in the PSMA+ flank tumor model. <sup>225</sup>Ac-L1 also showed an increased survival benefit in the micrometastatic model compared with <sup>177</sup>Lu-L1. Activity-escalated acute and chronic toxicity studies of <sup>225</sup>Ac-L1 revealed off-target radiotoxicity, mainly in kidneys and liver. The estimated maximum tolerated activity was about 1 MBq/kg. α-Camera imaging of <sup>225</sup>Ac-L1 revealed high renal cortical accumulation at 2 h followed by fast clearance at 24 h. <b>Conclusion:</b><sup>225</sup>Ac-L1 demonstrated activity-dependent efficacy with minimal treatment-related organ radiotoxicity. <sup>225</sup>Ac-L1 is a promising therapeutic for further clinical evaluation.
A Design of Home Network Security Protocol Using User Authentication and Access Control Technology (2008)

This paper designs and suggests a home network security protocol using user authentication and access control technology to prevent the threat by unauthorized users towards personal information and user asset in advance by providing the gradual authority to corresponding devices based on authorized information, after authorizing the users with a public key certificate. Also, the excellence of the protocol suggested in this paper can be confirmed by experimenting, comparing, and analyzing many categories such as number of computations and hash computation, quantity of sending out or receiving data, number of encryption, and the size of used keys while authenticating users in existing commercial products.
Transient spectroscopy of deep levels in thin semiconductor films (1990)

Characterization of deep levels in thin-film semiconductors by capacitive pulse transient spectroscopy has been analyzed and verified by measurement. Numerical calculations show that highly resistive thin films create a degradation of signal and possible sign inversion of the signal. Experiments on silicon on insulator and molecular beam epitaxy GaAs Schottky barrier capacitors verify the calculated signal deviation.
From pulmonary fibrosis to progressive pulmonary fibrosis: a lethal pathobiological jump (2021)

The month of September is Pulmonary Fibrosis Awareness Month. In this context, we would like to highlight the concept of progressive pulmonary fibrosis, a common denominator/phenotype of many interstitial lung diseases other than idiopathic pulmonary fibrosis, leading to clinical deterioration, decreased quality of life, and high mortality.
Interstitial radiation therapy for hepatic metastases: sonographic guidance for applicator placement (1986)

A new technique is reported for the treatment of hepatic metastases using sonography-directed percutaneous placement of a 14-gauge needle applicator and a high-intensity "remote afterloading" iridium-192 (Ir-192) source for interstitial radiation therapy. The results with six patients show that the procedure is easily performed, patient tolerance is good, and there is minimal disruption of the patient's lifestyle. Hospitalizations have been less than 24 hr. Partial response or stable disease in the liver was observed in all six patients. Tumoricidal doses up to 5000 rad (cGy) in a single treatment with durations from 7 to 41 min were achieved in small volumes (less than 25 cm3) with no clinically significant toxicity on follow-up evaluations from 2-6 months. The technique appears to ablate discrete metastatic tumor deposits in the liver.
Charge Trapping within UV and Vacuum UV Irradiated Low-k Porous Organosilicate Dielectrics (2010)

Vacuum ultraviolet VUV spectroscopy is used to determine the valence-band structure and location of defect states within the bandgap of porous organosilicate SiCOH dielectrics both before and after VUV and UV irradiation.SiCOH dielectrics have bandgap energies of about 9 eV.In addition, positive charge is trapped by defect states located 1 eV above the top of the SiCOH valence-band edge.These defect states can be populated or depopulated with electrons during UV and VUV irradiation, respectively.This is verified by measuring the magnitude and polarity of the trapped charge after VUV irradiation using two techniques: i capacitance vs voltage characteristics obtained with a mercury probe and ii surface-potential measurements obtained with a Kelvin probe.Both techniques show that the defect states are uncharged when occupied with electrons and positively charged when depleted of electrons.
A Concise, Selective Synthesis of the Polyketide Spacer Domain of a Potent Bryostatin Analogue (2003)

[reaction: see text] A concise, asymmetric synthesis of the polyketide spacer domain portion (C1-C13) of a highly potent bryostatin analogue was developed. The route utilizes asymmetric hydrogenation methodology to install the C3, C5, and C11 stereocenters, while a substrate directed syn reduction sets the C9 stereocenter. The spacer domain 1 is obtained in 10 steps with a 25% overall yield and is readily incorporated into the synthesis of 2.
Spatial admittance selection conditions for frictionless force-guided assembly of polyhedral parts in single principal contact (2006)

By judiciously selecting the admittance of a manipulator, the forces of contact that occur during assembly can be used to guide the parts to proper positioning. This paper identifies conditions for selecting the appropriate spatial admittance to achieve reliable force-guided assembly of polyhedral parts for cases in which a single feature (vertex, edge, or face) of one part contacts a single feature of the other, i.e., all single principal contact cases. These conditions ensure that the motion that results from frictionless contact always instantaneously reduces part misalignment. We show that, for bounded misalignments, if an admittance satisfies the misalignment-reducing conditions at a finite number of contact configurations, then the admittance will also satisfy the conditions at all intermediate configurations.
Functionalized, Vertically Super-Aligned Multiwalled Carbon Nanotubes for Potential Biomedical Applications (2020)

Currently, there is a lack of ultrasensitive diagnostic tool to detect some diseases such as ischemic stroke, thereby impacting effective and efficient intervention for such diseases at an embryonic stage. In addition to the lack of proper detection of the neurological diseases, there is also a challenge in the treatment of these diseases. Carbon nanotubes have a potential to be employed in solving the theragnostic challenges in those diseases. In this study, carbon nanotubes were successfully synthesized for potential application in the detection and treatment of the neurological diseases such as ischemic stroke. Vertically aligned multiwalled carbon nanotubes (VA-MWCNTs) were purified with HCl, carboxylated with H<sub>2</sub>SO<sub>4</sub>:HNO<sub>3</sub> (3:1) and acylated with SOCl<sub>2</sub> for use in potential targeting studies and for the design of a carbon-based electrode for possible application in the diagnosis of neurological diseases, including ischemic stroke. MWCNTs were washed, extracted from the filter membranes and dried in a vacuum oven at 60 °C for 24 h prior to functionalization and PEGylation. CNTs were characterized by SEM, TEM, OCA, DLS, CV and EIS. The HCl-treated CNT obtained showed an internal diameter, outer diameter and thickness of 8 nm, 34 nm and 75 µm, while these parameters for the H<sub>2</sub>SO<sub>4</sub>-HNO<sub>3</sub>-treated CNT were 8 nm, 23 nm and 41µm, respectively. PEGylated CNT demonstrated zeta potential, polydispersive index and particle size distribution of 6 mV, 0.41 and 98 nm, respectively. VA-MWCNTs from quartz tube were successfully purified, carboxylated, acylated and PEGylated for potential functionalization for use in targeting studies. For designing the carbon-based electrode, VA-MWCNTs on silicon wafer were successfully incorporated into epoxy resin for diagnostic applications. Functionalized MWCNTs were nontoxic towards PC-12 neuronal cells. In conclusion, vertically super-aligned MWCNTs have been successfully synthesized and functionalized for possible theragnostic biomedical applications in neurological disorders such as ischemic stroke.
Homodimerization of Retinoic Acid Receptor alpha through its Fusion Partners Underlies Pathogenesis of Acute Promyelocytic Leukemia. (2004)

Abstract In almost all cases of acute promyelocytic leukemia (APL), t(15;17)(q22;q12) fuses the promyelocytic leukemia (PML) gene with the retinoic acid receptor alpha (RARA) gene. In rare cases of APL, other genes are fused to RARA including PLZF, NPM, NuMA, and STAT5b. These chimeras are collectively referred to as X-RARA fusions. Common features of the X-RARα fusions include their ability to form dimers through the X domain proteins while retaining the ability to interact with rexinoid receptors (RXRs, the proteins with which RARα normally heterodimerizes). We previously created an artificial X-RARα: p50-RARα (a fusion of the dimerization interface of p50 NFκB with the portion of RARα found in naturally occurring X-RARα proteins). p50-RARα has effects similar to PML-RARα including (i) enhancing repression at retinoic acid response elements, due to impaired release of co-repressors at low levels of all-trans retinoic acid (ATRA), and (ii) inhibiting differentiation of myeloid cell lines. We generated transgenic mice expressing p50-RARα under the control of the MRP8 promoter. p50-RARα had a minimal effect on myelopoiesis and initiated myeloid leukemias at a rate of &amp;lt;5% in the first year of observation. Nevertheless, transduction of p50-RARA transgenic bone marrow with a retrovirus expressing an activated cytokine receptor (βcV449E) generated leukemias with features of APL including therapeutic responsiveness to ATRA. Complementing our work with the p50-RARA transgenic mice, retroviral co-transduction of normal bone marrow with βcV449E plus either p50-RARA or PML-RARA generated APL-like myeloid leukemias. Although retrovirally generated βc/p50-RARα and βc/PML-RARα leukemias were nearly identical, the PML fusion appeared associated with a subtle decrease in differentiation relative to the p50 fusion. In contrast to these X-RARα fusions, preliminary experiments suggest that RCRα (a homodimeric form of RARα in which the dimerization interface of RARα has been replaced by the dimerization domain of the homodimeric COUP-TF transcription factor) does not readily cooperate with βcV449E to cause leukemia. This finding lends support to the hypothesis that the decreased binding site selectivity of X-RARα fusions contributes to APL pathogenesis. Furthermore, we have generated a novel X-RARα fusion, F3-RARα, in which three copies of the F36M mutant of the Rapamycin-binding protein have been fused to RARα. This protein mimics the in vitro effects of PML-RARα on transcription &amp; differentiation, and de-dimerization of F3-RARα by rapamycin reverses these effects. Additional experiments in vivo with F3-RARα are expected to further confirm the importance of abnormal transcription factor dimerization in leukemia pathogenesis.
Antidoping programme and biological monitoring before and during the 2014 FIFA World Cup Brazil (2015)

Logistical issues linked to biological samples collection, and the overseas shipment during the World Cup did not impair the quality of the analyses, especially when used as the biological passport of football players.
Improving the Efficiency of Protein Conformation Prediction With Energy Landscape Modification (2009)

Since the native conformation or the natural shape of a protein largely determines its function, a prediction of protein conformation can shorten the process of drug discovery. This prediction is an optimization search to locate a configuration associated with the global minimum energy for the molecule. Due to the complexity of the multidimensional energy landscape, the prediction process can be extensive, which leads to very long simulation run times. For example, a high-resolution structure prediction algorithm [1] refining 20,000 to 30,000 models of several 49 to 88 residue long molecules takes about 150 CPU days per molecule. This paper presents the method of modified energy landscape (MEL) that improves the efficiency of the Broyden–Fletcher–Goldfarb–Shanno (BFGS) method by 12.8% on average, and more than 30% in some cases for a representative sample of cases. Since the efficiency improvement allows the probabilistic search to cover more areas of the energy landscape, locating the global minimum is more likely. Also, in a practical protein prediction running coarse refinements on more decoys is more preferable than comprehensively refining few decoys because of the low accuracy of energy functions. Therefore, the MEL can significantly improve the protein prediction simulation even though it yields less average score improvement. The MEL is implemented in a refinement protocol in Rosetta [2].
Parametric fluorescence in periodically poled silica fibers (1999)

We report the observation of quasiphase matched parametric fluorescence from a periodically poled silica fiber. A pair-photon production rate of more than 100 MHz around 1532 nm was achieved in second-order nonlinear gratings for 300 mW of pump power at 766 nm. These results are very promising for the realization of reliable all-fiber single-photon sources for quantum cryptography systems and metrology applications.
THERAPY OF ENDOCRINE DISEASE: Outcomes in patients with Cushing's disease undergoing transsphenoidal surgery: systematic review assessing criteria used to define remission and recurrence (2015)

The variety of methodologies used in clinical evaluation of TSS for Cushing's disease strongly support the call for standardization and optimization of studies to inform clinical practice and maximize patient outcomes. Clinically significant rates of failure of initial TSS highlight the need for effective second-line treatments.
Application of calibrated fMRI in Alzheimer's disease (2017)

Calibrated fMRI based on arterial spin-labeling (ASL) and blood oxygen-dependent contrast (BOLD), combined with periods of hypercapnia and hyperoxia, can provide information on cerebrovascular reactivity (CVR), resting blood flow (CBF), oxygen extraction fraction (OEF), and resting oxidative metabolism (CMRO<sub>2</sub>). Vascular and metabolic integrity are believed to be affected in Alzheimer's disease (AD), thus, the use of calibrated fMRI in AD may help understand the disease and monitor therapeutic responses in future clinical trials. In the present work, we applied a calibrated fMRI approach referred to as Quantitative O2 (QUO2) in a cohort of probable AD dementia and age-matched control participants. The resulting CBF, OEF and CMRO<sub>2</sub> values fell within the range from previous studies using positron emission tomography (PET) with <sup>15</sup>O labeling. Moreover, the typical parietotemporal pattern of hypoperfusion and hypometabolism in AD was observed, especially in the precuneus, a particularly vulnerable region. We detected no deficit in frontal CBF, nor in whole grey matter CVR, which supports the hypothesis that the effects observed were associated specifically with AD rather than generalized vascular disease. Some key pitfalls affecting both ASL and BOLD methods were encountered, such as prolonged arterial transit times (particularly in the occipital lobe), the presence of susceptibility artifacts obscuring medial temporal regions, and the challenges associated with the hypercapnic manipulation in AD patients and elderly participants. The present results are encouraging and demonstrate the promise of calibrated fMRI measurements as potential biomarkers in AD. Although CMRO<sub>2</sub> can be imaged with <sup>15</sup>O PET, the QUO2 method uses more widely available imaging infrastructure, avoids exposure to ionizing radiation, and integrates with other MRI-based measures of brain structure and function.
Pediatric-inspired intensified therapy of adult T-ALL reveals the favorable outcome of NOTCH1/FBXW7 mutations, but not of low ERG/BAALC expression: a GRAALL study (2011)

Despite recent progress in the understanding of acute lymphoblastic leukemia (T-ALL) oncogenesis, few markers are sufficiently frequent in large subgroups to allow their use in therapeutic stratification. Low ERG and BAALC expression (E/B(low)) and NOTCH1/FBXW7 (N/F) mutations have been proposed as powerful prognostic markers in large cohorts of adult T-ALL. We therefore compared the predictive prognostic value of N/F mutations versus E/B(low) in 232 adult T-ALLs enrolled in the LALA-94 and Group for Research on Adult Acute Lymphoblastic Leukemia (GRAALL) protocols. The outcome of T-ALLs treated in the pediatric-inspired GRAALL trials was significantly superior to the LALA-94 trial. Overall, 43% and 69% of adult T-ALL patients were classified as E/B(low) and N/F mutated, respectively. Strikingly, the good prognosis of N/F mutated patients was stronger in more intensively treated, pediatric-inspired GRAALL patients. The E/B expression level did not influence the prognosis in any subgroup. N/F mutation status and the GRAALL trial were the only 2 independent factors that correlated with longer overall survival by multivariate analysis. This study demonstrates that the N/F mutational status and treatment protocol are major outcome determinants for adults with T-ALL, the benefit of pediatric inspired protocols being essentially restricted to the N/F mutated subgroup.
Z-pinch driven fusion energy (2000)

The Z machine at Sandia National Laboratories (SNL) is the most powerful multi-module synchronized pulsed-power accelerator in the world. Rapid development of z-pinch loads on Z has led to outstanding progress in the last few years, resulting in radiative powers of up to 280 TW in 4 ns and a total radiated x-ray energy of 1.8 MJ. The present goal is to demonstrate single-shot, high-yield fusion capsules. Pulsed power is a robust and inexpensive technology, which should be well suited for Inertial Fusion Energy, but a rep-rated capability is needed. Recent developments have led to a viable conceptual approach for a rep-rated z-pinch power plant for IFE. This concept exploits the advantages of going to high yield (a few GJ) at low rep-rate ({approximately} 0.1 Hz), and using a Recyclable Transmission Line (RTL) to provide the necessary standoff between the fusion target and the power plant chamber. In this approach, a portion of the transmission line near the capsule is replaced after each shot. The RTL should be constructed of materials that can easily be separated from the liquid coolant stream and refabricated for a subsequent shots. One possibility is that most of the RTL is formed by casting FLiBe, a salt composed of fluorine, lithium, and beryllium, which is an attractive choice for the reactor coolant, with chemically compatible lead or tin on the surface to provide conductivity. The authors estimate that fusion yields greater than 1 GJ will be required for efficient generation of electricity. Calculations indicate that the first wall will have an acceptable lifetime with these high yields if blast mitigation techniques are used. Furthermore, yields above 5 GJ may allow the use of a compact blanket direct conversion scheme.
4-Acyl-1-(4-aminoalkoxyphenyl)-2-ketopiperazines as a Novel Class of Non-Brain-Penetrant Histamine H3 Receptor Antagonists (2007)

A series of ketopiperazines were prepared and evaluated for their activity as histamine H 3 antagonists. From investigation of the tertiary basic center in the aminopropyloxyphenyl template, the 2( R)-methylpyrrolidine was identified as the most potent amine. In the more rigid piperidineoxyphenyl template the N-cyclobutyl group was the most potent amine. The 4-fluorobenzyol, 4-cyanobenzoyl, and 2,4-difluorobenzoyl groups provided good pharmacokinetic profiles for the various amides. The PSA and log D values of these compounds suggested low brain penetration. The compounds had very high selectivity over other receptors and did not inhibit hepatic cytochrome P450, indicating low drug-drug interaction potential. Compound 22i was identified as the best compound of this series based on its overall profile of high potency, selectivity, low brain penetration, lack of CYP450 inhibition, high oral bioavailability, and pharmacokinetic properties.