gebhart/patrepeval huggingface dataset:
Effects of endogenous fluorescence from ex vivo human facial skin specimens in the pharmacokinetic study of a topical minocycline gel using two-photon excitation fluorescence (2PEF) and fluorescence lifetime imaging microscopy (FLIM) (Conference Presentation) (2018)

The safety and efficacy of an investigational topical minocycline gel (BPX-01) has recently been studied in a Phase 2b trial for the treatment of acne vulgaris. As part of the drug development process, there was a need to determine if minocycline was delivered to the target tissue compartments, including the epidermis, hair follicle, and the sebaceous gland. While it was easier to demonstrate delivery on an ex vivo human skin model with an infinite dose, it was initially challenging to verify low-dose delivery with conventional fluorescence microscopy due to the high autofluorescence inherent to human skin. An integrating sphere screening approach was implemented along with conventional fluorescence microscopy to quantitatively and qualitatively assess endogenous fluorescence concurrently from numerous human facial skin specimens. Donor tissues were cut into 50-µm frozen sections, mounted onto microscope slides, and positioned on an inverted fluorescence microscope, sandwiched between the microscope’s 40x high NA objective lens and an external integrating sphere. The tissue sections were illuminated with UV excitation centered at 386 nm. For the first time, it was found that random samples from >40 human facial skin donors produced at least 5× differential in measurable autofluorescence. This observation has significant implications for the use of 2PEF microscopy and FLIM to visualize/quantify drug distribution; the endogenous autofluorescence may limit the detectability of the minocycline signature. Our studies indicated that a single daily dose of BPX-01 was detected in low autofluorescence skin specimens with FLIM, thus validating a novel imaging modality for future pharmacokinetic studies.
Integrated Optical Sensors (2012)

We review important progress made in the field of integrated optical sensors in 2011. This paper focuses on key aspects of integrated sensors, including new detection mechanism developments, integration progress, and efforts toward resolving the challenges associated with surface functionalization and analyte transport.
Sustainable, fire‐resistant phthalonitrile‐based glass fiber composites (2018)

ABSTRACT The sustainable resveratrol‐based phthalonitrile was used in the preparation of E‐glass fiber‐reinforced phthalonitrile composite panels fabricated by hot pressed prepreg consolidation with bis[4‐(3‐aminophenoxy)phenyl]sulfone ( m ‐BAPS) as the curing additive. This amorphous monomer exhibited excellent viscosities at temperatures below 200 °C, which is applicable to standard processing conditions. Rheometric measurements were used to evaluate the cure of the composite as a function of the postcure conditions. The composite retains &gt;95% of its room temperature storage modulus up to 450 °C based on these postcuring parameters. More importantly, flammability performance of the composite—which was determined in terms of ignitability, heat release, and mass loss rate—excels over other state‐of‐the‐art polymer/glass composites. Even under the most extreme heat fluxes (e.g., 100 kW⋅m −2 ), the composite performs exceptionally well suggesting that resveratrol‐based phthalonitrile composites can be used in fire‐resistant applications. Published 2018. † J. Polym. Sci., Part A: Polym. Chem. 2018 , 56 , 1128–1132
Phase I clinical trial combining imatinib mesylate and IL-2 in refractory cancer patients (2013)

Imatinib mesylate (IM) is a small molecule inhibitor of protein tyrosine kinases. In addition to its direct effect on malignant cells, it has been suggested IM may activate of natural killer (NK) cells, hence exerting immunomodulatory functions. In preclinical settings, improved antitumor responses have been observed when IM and interleukin-2 (IL-2), a cytokine that enhances NK cells functions, were combined. The goals of this study were to determine the maximum tolerated dose (MTD) of IL-2 combined with IM at a constant dose of 400 mg, the pharmacokinetics of IM and IL-2, as well as toxicity and clinical efficacy of this immunotherapeutic regimen in patients affected by advanced tumors. The treatment consisted in 50 mg/day cyclophosphamide from 21 d before the initiation of IM throughout the first IM cycle (from D-21 to D14), 400 mg/day IM for 14 d (D1 to D14) combined with escalating doses of IL-2 (3, 6, 9 and 12 MIU/day) from days 10 to 14. This treatment was administered at three week intervals to 17 patients. Common side effects of the combination were mild to moderate, including fever, chills, fatigue, nausea and hepatic enzyme elevation. IL-2 dose level II, 6 MIU/day, was determined as the MTD with the following dose-limiting toxicities: systemic capillary leak syndrome, fatigue and anorexia. Pharmacokinetic studies revealed that the area under the curve and the maximum concentration of IM and its main metabolite CGP74588 increased significantly when IM was concomitantly administered with IL-2. In contrast, IM did not modulate IL-2 pharmacokinetics. No objective responses were observed. The best response obtained was stable disease in 8/17 (median duration: 12 weeks). Finally, IL-2 augmented the impregnation of IM and its metabolite. The combination of IM (400 mg/day) and IL-2 (6 MIU/day) in tumors that express IM targets warrants further investigation.
Management of shoulder stiffness following rotator cuff repair: a systematic review and meta-analysis (2023)

The purpose was to systematically review and synthesize the literature on treatment modalities for shoulder stiffness following rotator cuff repair (RCR) and investigate which modality provides the greatest postoperative range of motion (ROM). A search was performed on PubMed, Embase, and Cochrane. Clinical case series and comparative studies that report pre- and posttreatment ROM of shoulder stiffness following RCR were included. Studies that exclusively assess idiopathic frozen shoulder or primary shoulder stiffness were excluded. Five eligible studies that reported on a total of 177 patients who underwent treatment for shoulder stiffness following RCR were included. The ranges of postoperative ROM following arthroscopic capsular release were 158°-166° for active forward elevation (AFE) and 53°-59° for external rotation (ER). The ranges of postoperative ROM following infiltration were 146°-163° for AFE and 34°-35° for ER. The ranges of postoperative ROM following rehabilitation were 166° for AFE and 62° for ER. For AFE, 4 studies (5 data sets) were eligible for meta-analysis, which indicated better AFE when treated with a mean difference (MD) of 5.10° with no heterogeneity (I<sup>2</sup> = 0%, CI, 0.83-9.38). For ER, 3 studies (4 data sets) were eligible for meta-analysis, which indicated better ER without treatment with an MD of 4.59° with no heterogeneity (I<sup>2</sup> = 0%, CI, -7.04 to -2.13). For the treatment of shoulder stiffness following RCR, all included treatments improved the ROM, resulting in comparable AFE and ER compared to the comparative group. Among the treatment modalities, arthroscopic capsular release granted the greatest posttreatment AFE, while rehabilitation granted the greatest posttreatment ER.
Effect of Oral Aluminium Hydroxide on Iron Absorption from Iron(III)-hydroxide Polymaltose Complex in Patients with Iron Deficiency Anemia (2011)

The study was carried out as an open-label, laboratory-blind, single-dose, randomized, two-period crossover, isotope efficacy study. Twenty-two patients with iron-deficiency anemia were enrolled in the study. The study consisted of two treatment phases of 15 days each, including blood sample measurements for Fe-59 activity. The 2 treatments were given orally. Treatment A was Fe-59 labeled iron(III) -hydroxide polymaltose complex (IPC, Maltofer<sup>©</sup>), equivalent to 100 mg elemental iron given orally, and Treatment B consisted of Treatment A combined with 600 mg aluminium hydroxide (CAS 21645-51-2) (10 ml). No differences between the two treatment groups with regard to the erythrocyte uptake were found, and thus IPC can be used with aluminium hydroxide, if necessary.
Effect of CO2 and H2O on the synthesis of single‐walled CNTs (2006)

Abstract Two different floating catalyst synthesis methods were used to investigate the effect of CO 2 and H 2 O vapor on the growth of single‐walled carbon nanotubes (CNTs). As a carbon source and catalyst material, carbon monoxide and iron nanoparticles were used. The catalyst particles were prepared by evaporation from a resistively heated iron wire (hot wire generator) and by thermal decomposition of ferrocene vapor. The essential role of CO 2 and H 2 O in the CNT formation was demonstrated. The addition of small amounts of CO 2 and H 2 O vapor in the reactor resulted in an increase in CNT length. Also, the CO 2 introduction was found to decrease the minimum temperature of the CNT synthesis from 890 °C to below 600 °C. (© 2006 WILEY‐VCH Verlag GmbH &amp; Co. KGaA, Weinheim)
Synthesen von Pyrethroidsäuren (1981)

Abstract Im letzten Jahrzehnt wurde die Chemie der Insektizide durch neue Cyclopropancarbonsäureester spezifischer Struktur erweitert, die in ihrer Wirkung die bis dahin bekannten Insektizide aus anderen Stoffklassen und auch die natürlichen Vorbilder aus der Gruppe der Pyrethrum‐Inhaltsstoffe bei weitem übertreffen. Diese Entdeckung hat eine Fülle vielfältiger synthetischer Arbeiten ausgelöst. Um selektive Synthesemethoden für komplizierte Kleinringe zu entwickeln, wurde ein umfangreiches Repertoire des synthetisch arbeitenden Chemikers aktiviert: So nutzt eine großtechnisch ausgeübte Synthese dieser Verbindungen sigmatrope Umlagerung, radikalische Addition und nucleophilen Ringschluß mit Carbanionen. Besondere Aktualität gewinnen diese neuen industriellen Synthesen durch die Anwendung stereospezifischer und enantioselektiver Methoden.
Nano-patterning using an embedded particle monolayer as an etch mask (2004)

A new nano-fabrication technique using a self-assembled nano-particle monolayer as an etch mask is presented. We developed the embedded particle monolayer (EPM) method that forms a homogeneous particle monolayer over a large area. A periodic nano-cone pattern was fabricated by transferring the pattern of the particle monolayer onto the substrate. The nano-fabrication method developed here expected to be a useful tool for producing devices that require a periodic structure of nanometer scale such as a moth-eye antireflection surfaces [ 1], two-dimensional gratings, patterned magnetic media, and so on.
The Methanothermobacter thermautotrophicus MCM Helicase Is Active as a Hexameric Ring (2008)

The minichromosome maintenance (MCM) complex is thought to function as the replicative helicase in archaea and eukarya. The structure of the single MCM protein homologue from the archaeon Methanothermobacter thermautotrophicus is not yet clear, and hexameric, heptameric, octameric, and dodecameric structures, open rings, and filamentous structures have been reported. Using a combination of biochemical and structural analysis, it is shown here that the M. thermautotrophicus MCM helicase is active as a hexamer.
Biosensors: Electrical Biomolecule Detection Using Nanopatterned Silicon via Block Copolymer Lithography (Small 2/2014) (2014)

The electrical biomolecule detection of nanopatterned silicon channels fabricated by block copolymer (BCP) lithography is demonstrated by S. O. Kim, K. J. Lee, and co-workers on page 337. The nanomesh patterned silicon biosensor achieves excellent sensitivity and stability for detecting streptavidin and avidin proteins. This work offers new opportunities for biomedical applications such as clinical diagnoses, biological studies, and lab-on-a-chip technologies enabled by inherently-scalable BCP lithography.
APIM-peptide targeting PCNA improves the efficacy of docetaxel treatment in the TRAMP mouse model of prostate cancer (2018)

Docetaxel is the chemotherapeutic choice for metastatic hormone-refractory prostate cancer, however, it only marginally improves the survival rate. The purpose of the present study was to examine if a peptide targeting the cellular scaffold protein PCNA could improve docetaxel's efficacy. We found that docetaxel given in combination with a cell penetrating peptide containing the AlkB homolog 2 PCNA interacting motif (APIM-peptide), reduced the prostate volume and limited prostate cancer regrowth <i>in vivo</i> in the immunocompetent transgenic adenocarcinoma model of prostate cancer (TRAMP). In accordance with this, we found that the APIM-peptide enhanced the efficacy of docetaxel <i>in vitro</i>. Gene expression analysis on prostate cancer cell lines indicated that the combination of docetaxel and APIM-peptide alters expression of genes involved in cellular signaling, apoptosis, and prostate cancer development. These changes were not detected in single agent treated cells. Our results suggest that targeting PCNA and thereby affecting multiple cellular pathways simultaneously has the potential to improve docetaxel therapy of advanced prostate cancer.
A HomozygousNme7Mutation Is Associated withSitus Inversus Totalis (2016)

We investigated the cause of situs inversus totalis (SIT) in two siblings from a consanguineous family. Genotyping and whole-exome analysis revealed a homozygous change in NME7, resulting in deletion of an exon causing an in-frame deletion of 34 amino acids located in the second NDK domain of the protein and segregated with the defective lateralization in the family. NME7 is an important developmental gene, and NME7 protein is a component of the γ-tubulin ring complex. This mutation is predicted to affect the interaction of NME7 protein with this complex as it deletes the amino acids crucial for the binding. SIT associated with homozygous deletion in our patients is in line with Nme7(-/-) mutant mice phenotypes consisting of congenital hydrocephalus and SIT, indicating a novel human laterality patterning role for NME7. Further cases are required to elaborate the full human phenotype associated with NME7 mutations.
Structure of the human smoothened receptor bound to an antitumour agent (2020)

The smoothened (SMO) receptor, a key signal transducer in the Hedgehog (Hh) signaling pathway is both responsible for the maintenance of normal embryonic development and implicated in carcinogenesis. The SMO receptor is classified as a class Frizzled (class F) G protein-coupled receptor (GPCR), although the canonical Hh signaling pathway involves the transcription factor Gli and the sequence similarity with class A GPCRs is less than 10%. Here we report the crystal structure at 2.5 Å resolution of the transmembrane domain of the human SMO receptor bound to the small molecule antagonist LY2940680. Although the SMO receptor shares the seven transmembrane helical (7TM) fold, most conserved motifs for class A GPCRs are absent, and the structure reveals an unusually complex arrangement of long extracellular loops stabilized by four disulfide bonds. The ligand binds at the extracellular end of the 7TM bundle and forms extensive contacts with the loops.
The Research Organ at the Fraunhofer IBP in Stuttgart (2012)

At the Fraunhofer IBP in Stuttgart a research organ has been built for scientists. Its transparency and unique design allows the demonstration of research results, the investigation of technical and sound problems in organ building as well as the audible testing of sound ideas. Some of the special design features are: The wind system can be switched from traditional to innovative design. Newly developed swell shutters which allow a better dynamic of the sound are mounted in the swell organ. The dimensioning of pipes and wind systems was conducted by means of scaling software developed within the context of European research projects. One wind chest of a division can be exchanged to allow the testing of valves and pipe layouts. In order to test newly designed stops a blind slider is available. There are several blind grooves to analyze the effect of wind flow, of resonances in the grooves and of different outlet holes on the pipe sound. The blowers are driven by a frequency converter for continuous adjustment of wind pressures. The motion of a beating and a free reed can be visualized by means of a stroboscope installed. Some of the research results will be demonstrated.
Network Virtualization and Network Hypervisors (2022)

Abstract Modern communication networks have to deal with dynamically changing requirements of emerging applications. In order to support such heterogeneous requirements on the same substrate network, concepts for network abstraction and network programmability are essential to offer applications that individually tailored views on the network. Network virtualization is the basic concept to provide an abstraction of a substrate network that can be offered to a network application provider. Here, a network hypervisor realizes the level of indirection between substrate network and virtual network(s). Additional programmability can be offered through the concept of Software‐Defined Networking (SDN). SDN provides a network abstraction based on a centralized view on a network to program individual features such as forwarding rules inside a network. This chapter gives an overview of the networking concept of network virtualization as the example of the virtualization of SDN‐based networks. The combination of network virtualization and Software‐Defined Networking provides full network abstraction and adaptability. We detail the basic features of a network hypervisor, abstraction and isolation, and provide the example of FlowVisor as a prominent network hypervisor example in the state of the art.
Multilayer graphene/ITO transparent n‐electrodes for high‐efficiency III‐nitride light‐emitting diodes (2015)

Multilayer graphene (MLG)/ITO transparent n‐electrodes for high‐efficiency III‐nitride light‐emitting diodes (LEDs) were fabricated. MLG was grown on Ni/SiO 2 /Si substrates using a chemical vapor deposition method and transferred to the ITO transparent n‐electrodes of the LEDs. The properties were analyzed by electroluminescence measurements, Raman spectroscopy, and radiant intensity–current testing. The external quantum efficiency (EQE) was enhanced greatly by the MLG/ITO dual layers as transparent n‐electrodes in LEDs. The EQE and radiant intensity at an injection current of 200 mA of the LEDs with the MLG/ITO transparent n‐electrodes were improved by 33 and 32%, respectively, which was attributed to the improved light extraction through the transparent ITO n‐electrodes as well as the enhanced current spreading by the MLG on the ITO layer. The high transmittance and outstanding current spreading of the MLG/ITO transparent n‐electrodes have great potential for advanced transparent conducting n‐electrodes in optoelectronic devices.
Die Zukunft der Partikelreplikation in nicht benetzenden Templaten (PRINT) (2013)

Abstract Die Partikelreplikation in nicht benetzenden Templaten (PRINT) ist ein kontinuierliches, hochauflösendes Roll‐to‐Roll‐Abgussverfahren zur Herstellung von präzise definierten Mikro‐ und Nanopartikeln. Die Technik greift Lithographietechniken aus der Mikroelektronikindustrie auf und kombiniert diese mit den Roll‐to‐Roll‐Verfahren der Photofilmindustrie. Das Resultat ist eine exzellente und in dieser Form beispiellose Steuerung von Größe, Form, chemischer Zusammensetzung, Beladung, Modul und Oberflächeneigenschaften der Partikel. Zudem ist PRINT mit der GMP (Good Manufacturing Practice) kompatibel und daher auch für die großtechnische Partikelherstellung geeignet. In diesem Kurzaufsatz beschreiben wir unsere neuesten Arbeiten zur Anwendung der PRINT‐Technologie in den Bio‐ und Materialwissenschaften.
Small Molecule Receptor Protein Tyrosine Phosphatase γ (RPTPγ) Ligands That Inhibit Phosphatase Activity via Perturbation of the Tryptophan–Proline–Aspartate (WPD) Loop (2011)

Protein tyrosine phosphatases (PTPs) catalyze the dephosphorylation of tyrosine residues, a process that involves a conserved tryptophan-proline-aspartate (WPD) loop in catalysis. In previously determined structures of PTPs, the WPD-loop has been observed in either an "open" conformation or a "closed" conformation. In the current work, X-ray structures of the catalytic domain of receptor-like protein tyrosine phosphatase γ (RPTPγ) revealed a ligand-induced "superopen" conformation not previously reported for PTPs. In the superopen conformation, the ligand acts as an apparent competitive inhibitor and binds in a small hydrophobic pocket adjacent to, but distinct from, the active site. In the open and closed WPD-loop conformations of RPTPγ, the side chain of Trp1026 partially occupies this pocket. In the superopen conformation, Trp1026 is displaced allowing a 3,4-dichlorobenzyl substituent to occupy this site. The bound ligand prevents closure of the WPD-loop over the active site and disrupts the catalytic cycle of the enzyme.
Pellicular Particles with Spherical Carbon Cores and Porous Nanodiamond/Polymer Shells for Reversed-Phase HPLC (2011)

A new stationary phase for reversed-phase high performance liquid chromatography (RP HPLC) was created by coating spherical 3 μm carbon core particles in a layer-by-layer (LbL) fashion with poly(allylamine) (PAAm) and nanodiamond. Unfunctionalized core carbon particles were characterized by scanning electron microscopy (SEM), X-ray photoelectron spectroscopy (XPS), time-of-flight secondary ion mass spectrometry (ToF-SIMS), and Raman spectroscopy. After LbL of PAAm and nanodiamond, which yields ca. 4 μm core–shell particles, the particles were simultaneously functionalized and cross-linked using a mixture of 1,2-epoxyoctadecane and 1,2,7,8-diepoxyoctane to obtain a mechanically stable C18/C8 bonded outer layer. Core–shell particles were characterized by SEM, and their surface area, pore diameter, and volume were determined using the Brunauer–Emmett–Teller (BET) method. Short stainless steel columns (30 × 4.6 mm i.d.) were packed and the corresponding van Deemter plots obtained. The Supporting Information contains a MATLAB program used to fit the van Deemter data. The retentions of a suite of analytes were investigated on a conventional HPLC at various organic solvent compositions, pH values of mobile phases, including extreme pH values, and column temperatures. At 60 °C, a chromatogram of 2,6-diisopropylphenol showed 71 500 plates/m (N/m). Chromatograms obtained under acidic conditions (pH 2.7) of a mixture of acetaminophen, diazepam, and 2,6-diisopropylphenol and a mixture of phenol, 4-methylphenol, 2-chlorophenol, 4-chlorophenol, 4-bromophenol, and 1-tert-butyl-4-methylphenol are presented. Retention of amitriptyline, cholesterol, and diazinon at temperatures ranging from 35 to 80 °C and at pH 11.3 is reported. A series of five basic drugs was also separated at this pH. The stationary phase exhibits considerable hydrolytic stability at high pH (11.3) and even pH 13 over extended periods of time. An analysis run on a UHPLC with a “sandwich” injection appeared to reduce extra column band broadening and gave best efficiencies of 110 000–120 000 N/m.
Wavelet-based multiresolution stereo vision (2003)

An efficient wavelet-based multiresolution approach to the stereo vision problem is presented. A cost function is defined and iteratively minimized. The minimization is performed on the image representation in wavelet space. We employ the theory of representation of operators in spaces spanned by scaling functions and thereby take advantage of a simplified approximation of differentiation. Examples illustrate the advantages afforded by the application of our algorithm over correlation-based methods.