gebhart/patrepeval huggingface dataset:
The transcription factor LMO2 is a robust marker of vascular endothelium and vascular neoplasms with rare exceptions (2008)

The transcription factor LMO2 is involved in vascular and hematopoietic development. Here we demonstrate that LMO2 is expressed nearly ubiquitously in native vascular endothelium including lymphatic endothelium. Rare exceptions include the vasculature of adult and fetal heart and the brain vasculature of older individuals, as well as hepatic sinusoidal endothelium. While LMO2 is expressed in the vasculature of a variety of carcinomas and non‐epithelial neoplasms, expression was rare in hepatocellular carcinomas (1/10) and was lacking in a subset of clear cell renal cell carcinomas (14/22). LMO2 was uniformly expressed in a variety of benign vascular (11/11) and lymphatic (5/5) neoplasms. LMO2 was also expressed in most vascular endothelium‐derived malignancies, including 11/11 non‐epithelioid angiosarcomas and 6/6 Kaposi sarcomas. Among epithelioid vascular malignancies, LMO2 expression was lacking in primary epithelioid vascular neoplasms of bone (1/4 positive) and pleura (0/3 positive), but was uniformly present in epithelioid vascular malignancies originating at other sites (9/9, p&lt;0.002 and chi value 12.8 for the three way comparison). In the context of diagnostic immunohistochemistry, LMO2 may be added to the arsenal of markers of vascular differentiation; in epithelioid vascular malignancies that lack LMO2, assessment for a primary site in bone or pleura may be indicated.
Epidural opiates: plasma and cerebrospinal fluid (CSF) pharmacokinetics of morphine, methadone and beta-endorphin (1981)

Max, Mitchell*,a; Inturrisi, C. E.b; Grabinski, P.*,b; Kaiko, R. F.b; Foley, K. M.a,b Author Information
11. Cobalt-Schiff Base Complexes: Preclinical Research and Potential Therapeutic Uses (2019)

The use of metals in medicine has grown impressively in recent years as a result of greatly advanced understanding of biologically active metal complexes and metal-containing proteins. One landmark in this area was the introduction of cisplatin and related derivatives as anticancer drugs. As the body of literature continues to expand, it is necessary to inspect sub-classes of this group with more acute detail. This chapter will review preclinical research of cobalt complexes coordinated by Schiff base ligands. Cobalt-Schiff base complexes have a wide variety of potential therapeutic functions, including as antimicrobials, anticancer agents, and inhibitors of protein aggregation. While providing a broad introduction to this class of agents, this chapter will pay particular attention to agents for which mechanisms of actions have been studied. Appropriate methods to assess activity of these complexes will be reviewed, and promising preclinical complexes in each of the following therapeutic areas will be highlighted: antimicrobial, antiviral, cancer therapy, and Alzheimer's disease.
Respiratory ATP synthesis: the new generation of mycobacterial drug targets? (2010)

Mycobacterium tuberculosis, the causative agent of tuberculosis, poses a global health challenge due to the emergence of drug-resistant strains. Recently, bacterial energy metabolism has come into focus as a promising new target pathway for the development of antimycobacterial drugs. This review summarizes our current knowledge on mycobacterial respiratory energy conversion, in particular, during the physiologically dormant state that is associated with latent or persistent tuberculosis infections. Targeting components of respiratory ATP production, such as type-2 NADH dehydrogenase or ATP synthase, is illustrated as an emerging strategy in the development of novel drugs.
Role of Ligand Protonation in Dihydrogen Evolution from a Pentamethylcyclopentadienyl Rhodium Catalyst (2017)

Recent work has shown that Cp*Rh(bpy) [Cp* = pentamethylcyclopentadienyl, bpy = 2,2'- bipyridine] undergoes endo protonation at the [Cp*] ligand in the presence of weak acid (Et<sub>3</sub>NH<sup>+</sup>; pK<sub>a</sub> = 18.8 in MeCN). Upon exposure to stronger acid (e.g., DMFH<sup>+</sup>; pK<sub>a</sub> = 6.1), hydrogen is evolved with unity yield. Here, we study the mechanisms by which this catalyst evolves dihydrogen using density functional theory (M06) with polarizable continuum solvation. The calculations show that the complex can be protonated by weak acid first at the metal center with a barrier of 3.2 kcal/mol; this proton then migrates to the ring to form the detected intermediate, a rhodium(I) compound bearing endo η<sup>4</sup>-Cp*H. Stronger acid is required to evolve hydrogen, which calculations show happens via a concerted mechanism. The acid approaches and protonates the metal, while the second proton simultaneously migrates from the ring with a barrier of ∼12 kcal/mol. Under strongly acidic conditions, we find that hydrogen evolution can proceed through a traditional metal-hydride species; protonation of the initial hydride to form an H-H bond occurs before migration of the hydride (in the form of a proton) to the [Cp*] ring (i.e., H-H bond formation is faster than hydride-proton tautomerization). This work demonstrates the role of acid strength in accessing different mechanisms of hydrogen evolution. Calculations also predict that modification of the bpy ligand by a variety of functional groups does not affect the preference for [Cp*] protonation, although the driving force for protonation changes. However, we predict that exchange of bpy for a bidentate phosphine ligand will stabilize a rhodium(III) hydride, reversing the preference for bound [Cp*H] found in all computed bpy derivatives and offering an appealing alternative ligand platform for future experimental and computational mechanistic studies of H<sub>2</sub> evolution.
Pathogene Mikroorganismen im Grund- und Trinkwasser (2003)

Mikroorganismen kommen natürlicherweise im Grund- und Trinkwasser vor. Kritisch wird es dann, wenn pathogene Keime im Trinkwasser auftreten. Das vorliegende Buch gibt einen umfassenden Einblick in den
Solution-Phase and Solid-Phase Syntheses of Enzyme Inhibitor RK-682 and Antibiotic Agglomerins (2005)

The enzyme inhibitor RK-682 (5R)-(+)-1 was prepared in solution and on a solid support from (2R)-glycerates in five steps and ca. 40% overall yield. Key steps were a ring-closing tandem addition-Wittig alkenation reaction of the respective protected or immobilized glycerates with the ylide Ph(3)PCCO and the 3-acylation of the tetronic acids thus obtained with palmitic acid. A similar route extended by a mesylation-elimination sequence led to antibiotic agglomerins A-C 2 featuring 3-acyl-5-methylidenetetronic acid structures.
Vortex phase masks of topological charge 4 and higher with diamond subwavelength gratings (2020)

High contrast imaging at small inner working angles can be achieved using a vector vortex coronagraph in the focal plane of the telescope providing a helical phase ramp with a singularity at its center. The form birefringence of full-diamond subwavelength gratings has proven to be well suited to manufacture such vortex phase masks for coronagraphic applications (Subwavelength Grating Vortex Coronagraph, SGVC). In the past years our group has developed and manufactured SGVCs of topological charge 2 (Annular Groove Phase Mask, AGPM) made of a concentric diamond subwavelength grating. For future applications including ELT-class telescopes in the near- to mid-infrared that will partly resolve nearby stars, it is however useful to increase the topological charge of the vortex. After shortly reviewing our previous attempts at optimizing the grating structure for SGVC of charge 4, we present the first laboratory results obtained with such devices. We then introduce and discuss more realistic simulations compared to prior studies using finite-difference time-domain methods. The quality of the simulation results obtained with the open source software MEEP for an AGPM is shown to be appropriate for developing and assessing the performance of future vortex phase masks. We therefore perform updated simulations for SGVC of charge 4 including various designs with straight and curved grating lines. We conclude with a perspective on the potential of metasurfaces and their applications to design novel vortex coronagraphs based on subwavelength structures.
Structural Aspects of 5‐methylthio‐1‐oxa‐6,6a δIV‐dithia‐2‐azapentalenes (2003)

Abstract Alkylation of 5‐[1‐hydroxyiminoalkyl]‐1,2‐dithiole‐3‐thiones using methyl iodide in the presence of sodium hydroxide gives derivatives which may be considered as being 5‐methylthio‐1‐oxa‐6,6a δ IV ‐dithia‐2‐azapentalenes with quantitative yields. The structure of oxadithiazapentalene attributed to the alkylation products is founded on X‐ray analysis and NMR and IR data.
Ferroelectric thin film microstructure development and related property enhancement (1994)

Abstract Factors that control phase evolution, microstructural development and ferroelectric domain assemblage are evaluated for chemically prepared lead zirconate titanate (PZT) thin films. Zirconium to titanium stoichiometry is shown to strongly influence microstructure. As Ti content increases, there is an apparent enhancement of the perovskite phase nucleation rate, grain size becomes smaller, and the amount of pyrochlore phase, if present, decreases. While the pyrochlore matrix microstructure for near morphotropic phase boundary composition thin films consists of two interpenetrating nanophases (pyrochlore and an amorphous phase); the pyrochlore microstructure for PZT 20/80 films deposited on MgO substrates is single phase and consists of 10 nm grains. Zirconium to titanium stoichiometry also has a substantial influence on process integration. Near morphotropic phase boundary films exhibit extensive reaction with underlying TiO2 diffusion barriers; conversely, there is no chemical reaction for identically processed PZT 20/80 thin films. We have attempted to directly correlate the optical quality of PZT thin films to the following microstructural features: 1) presence of a second phase, 2) domain orientation, and 3) nanometer surface morphology.
Emulating a Software Defined LTE Radio Access Network Towards 5G (2018)

This paper evaluates the performance of a Software Defined Network (SDN) and the respective OpenFlow (OF) protocol, when supporting a Long Term Evolution (LTE) Radio Access Network (RAN). The main objective is to understand the impact of the new Centralized Radio Access Network (C-RAN) architecture, using a SDN based LTE network (when compared to conventional LTE networks), in a solution towards Fifth Generation (5G) implementation. Several simulations were performed using the SDN emulator Mininet-Wifi platform, which was adapted to produce use cases regarding a SDN based LTE topology. This platform uses WiFi as radio technology. However, and since this is an open source platform, changes were introduced in order to include a LTE RAN parametrization based on LTE technology standards. The latency and throughput are the used Quality of Service (QoS) performance metrics. The throughput results led to spectral efficiency values close to each considered modulation maximum. The obtained average values of latency, 15.72, 16.17 and 16.50 ms for packets of 32, 1000 and 1500 bytes respectively, revealed to be lower than 20 ms, which is the LTE requirement established by 3GPP.
Abstract P2-05-21: The AKT-mTOR pathway as a potential organ-specific drug target signature of hepatic metastases from breast cancer (2016)

Abstract Background: The identification of organ-specific targetable signatures may help design more effective treatment for patients with metastatic breast cancer (MBC). We took a multi-OMIC approach to assess whether the AKT-mTOR pathway is globally activated during metastatic progression or whether it represents an organ-specific target. Methods: Snap frozen biopsies from 25 MBC patients enrolled in a prospective phase II trial were used. Sites of metastasis were classified as liver (n=8) and others (n=17), the latter including cutaneous, lung, lymph nodes, and intra-abdominal lesions. Signaling analysis of the 25 cases was performed using Reverse Phase Protein Microarray (RPPA) coupled with Laser Capture Microdissection. Activation of the AKT-mTOR pathway was quantified as phosphorylation of AKT (S473) and the mTOR target p70S6 (T389). Matched exome (WES) and RNASeq data were available for 17 of 25 patients, five with liver metastases. Sequencing data was processed using an in-house developed pipeline to identify somatic events including coding mutations, copy number alterations, gene fusions, and differential expression. Activation of the AKT-mTOR pathway and sequencing data were compared between hepatic and non-hepatic lesions using an integrated RPPA and genomic approach. Results: Among liver metastases, AKT was activated in 4 of the 8 (50.0%) patients, while 6 of the 8 cases (75.0%) showed activation of p70S6. Sequencing data revealed mutation of PIK3CA in 4 of the 5 liver metastases (80.0%). Three of the PIK3CA mutated specimens with catalytic domain mutations (codons 1023 and 147) demonstrated co-activation of AKT and p70S6, while the fourth case, containing a helical domain mutation (E542K), had activation of p70S6 only. The PIK3CA wild-type liver metastasis demonstrated low activation of AKT and p70S6. For non-hepatic metastases AKT was activated in 2 of the 17 cases (11.8%) and p70S6 in 5 of the 17 patients (29.4%). Discussion: Although these results need further validation, activation of the AKT-mTOR pathway appears to be a hepatic specific signature in MBC and could be used for the selection of targeted agents for hepatic lesions. Citation Format: Pierobon M, Wong S, Reeder A, Anthony SP, Robert NJ, Northfelt DW, Jahanzeb M, Vocila L, Wulfkuhle J, Dunetz B, Aldrich J, Byron S, Craig D, Liotta L, Petricoin EF, Carpten J. The AKT-mTOR pathway as a potential organ-specific drug target signature of hepatic metastases from breast cancer. [abstract]. In: Proceedings of the Thirty-Eighth Annual CTRC-AACR San Antonio Breast Cancer Symposium: 2015 Dec 8-12; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2016;76(4 Suppl):Abstract nr P2-05-21.
Current and emerging treatments and surgical interventions for Morquio A syndrome: a review (2012)

Patients with mucopolysaccharidosis type IVA (MPS IVA; Morquio A syndrome) have accumulation of the glycosaminoglycans, keratan sulfate, and chondroitin-6-sulfate, in bone and cartilage, causing systemic spondyloepiphyseal dysplasia. Features include lumbar gibbus, pectus carinatum, faring of the rib cage, marked short stature, cervical instability and stenosis, kyphoscoliosis, genu valgum, and laxity of joints. Generally, MPS IVA patients are wheelchair-bound as teenagers and do not survive beyond the second or third decade of life as a result of severe bone dysplasia, causing restrictive lung disease and airway narrowing, increasing potential for pneumonia and apnea; stenosis and instability of the upper cervical region; high risk during anesthesia administration due to narrowed airway as well as thoracoabdominal dysfunction; and surgical complications. Patients often need multiple surgical procedures, including cervical decompression and fusion, hip reconstruction and replacement, and femoral or tibial osteotomy, throughout their lifetime. Current measures to intervene in disease progression are largely palliative, and improved therapies are urgently needed. A clinical trial for enzyme replacement therapy (ERT) and an investigational trial for hematopoietic stem cell transplantation (HSCT) are underway. Whether sufficient enzyme will be delivered effectively to bone, especially cartilage (avascular region) to prevent the devastating skeletal dysplasias remains unclear. This review provides an overview of historical aspects of studies on MPS IVA, including clinical manifestations and pathogenesis of MPS IVA, orthopedic surgical interventions, and anesthetic care. It also describes perspectives on potential ERT, HSCT, and gene therapy.
Forefoot bending stiffness, running economy and kinematics during overground running (2016)

Previous research has shown that altering forefoot (FF) bending stiffness can enhance running economy; however, the mechanism behind the changes in running economy remains unknown. Therefore, the purpose of this study was to investigate the relationship between forefoot bending stiffness, running economy, and lower limb kinematics during overground running. Eighteen aerobically fit recreational male athletes performed overground running using a portable metabolic analysis system to measure oxygen consumption in two footwear conditions with different forefoot bending stiffness. Sagittal plane kinematic data of the metatarsophalangeal, ankle, and knee joints were recorded using a high-speed camera. On average, there was no difference in running economy when running in the Stiff shoe (O2 = 38.1 ± 5.4 mL/kg/min) compared to the Control shoe (O2 = 37.7 ± 5.8 mL/kg/min, p = 0.11). On an individual basis, 10 athletes (Responders) improved their running economy with increased FF bending stiffness (∆O2 = −2.9%), while eight athletes (Non-Responders) worsened or did not improve their running economy in a stiff shoe (∆O2 = +1.0%). In stiff footwear, Responders experienced kinematic changes at the ankle joint (decreased angular velocity) that likely resulted in decreased energy requirement for muscular contractions due to a presumed shift on their individual force–velocity relationship. The lack of improvement in running economy by the Non-Responders may be attributed to a presumed lack of a shift in the force–velocity relationship of the calf musculature. Instead, Non-Responders experienced kinematic changes (increased ankle plantarflexion during push phase with stiff footwear) that likely hindered their moment-generating capability potentially due to a shift on their individual force–length relationship. These findings represent important progress towards explaining inter-individual changes in running economy with different footwear bending stiffness.
Data from TRAP1 Regulates Proliferation, Mitochondrial Function, and Has Prognostic Significance in NSCLC (2023)

&lt;div&gt;Abstract&lt;p&gt;The TNF receptor-associated protein 1 (TRAP1) is a mitochondrial HSP that has been related to drug resistance and protection from apoptosis in colorectal and prostate cancer. Here, the effect of TRAP1 ablation on cell proliferation, survival, apoptosis, and mitochondrial function was determined in non–small cell lung cancer (NSCLC). In addition, the prognostic value of TRAP1 was evaluated in patients with NSCLC. These results demonstrate that TRAP1 knockdown reduces cell growth and clonogenic cell survival. Moreover, TRAP1 downregulation impairs mitochondrial functions such as ATP production and mitochondrial membrane potential as measured by TMRM (tetramethylrhodamine methylester) uptake, but it does not affect mitochondrial density or mitochondrial morphology. The effect of TRAP1 silencing on apoptosis, analyzed by flow cytometry and immunoblot expression (cleaved PARP, caspase-9, and caspase-3) was cell line and context dependent. Finally, the prognostic potential of TRAP1 expression in NSCLC was ascertained via immunohistochemical analysis which revealed that high TRAP1 expression was associated with increased risk of disease recurrence (univariate analysis, &lt;i&gt;P&lt;/i&gt; = 0.008; multivariate analysis, HR: 2.554; 95% confidence interval, 1.085–6.012; &lt;i&gt;P&lt;/i&gt; = 0.03). In conclusion, these results demonstrate that TRAP1 impacts the viability of NSCLC cells, and that its expression is prognostic in NSCLC.&lt;/p&gt;&lt;p&gt;&lt;b&gt;Implications:&lt;/b&gt; TRAP1 controls NSCLC proliferation, apoptosis, and mitochondrial function, and its status has prognostic potential in NSCLC. &lt;i&gt;Mol Cancer Res; 12(5); 660–9. ©2014 AACR&lt;/i&gt;.&lt;/p&gt;&lt;/div&gt;
Electrically Conductive Thin Films Prepared from Layer‐by‐Layer Assembly of Graphite Platelets (2009)

Abstract Layer‐by‐layer (LBL) assembly of carbon nanoparticles for low electrical contact resistance thin film applications is demonstrated. The nanoparticles consist of irregularly shaped graphite platelets, with acrylamide/ β β ‐methacryl‐oxyethyl‐trimethyl‐ammonium copolymer as the cationic binder. Nanoparticle zeta ( ζ ζ ) potential and thereby electrostatic interactions are varied by altering the pH of graphite suspension as well as that of the binder suspension. Film thickness as a function of zeta potential, immersion time, and the number of layers deposited is obtained using Monte Carlo simulation of the energy dispersive spectroscopy measurements. Multilayer film surface morphology is visualized via field‐emission scanning electron microscopy and atomic‐force microscopy. Thin film electrical properties are characterized using electrical contact resistance measurements. Graphite nanoparticles are found to self‐assemble onto gold substrates through two distinct yet overlapping mechanisms. The first mechanism is characterized by logarithmic carbon uptake with respect to the number of deposition cycles and slow clustering of nanoparticles on the gold surface. The second mechanism results from more rapid LBL nanoparticle assembly and is characterized by linear weight uptake with respect to the number of deposition cycles and a constant bilayer thickness of 15 to 21 nm. Thin‐film electrical contact resistance is found to be proportional to the thickness after equilibration of the bilayer structure. Measured values range from 1.6 mΩ cm −2 at 173 nm to 3.5 mΩ cm −2 at 276 nm. Coating volume resistivity is reduced when electrostatic interactions are enhanced during LBL assembly.
1,5‐Diamino‐2‐pentyne is both a substrate and inactivator of plant copper amine oxidases (2004)

1,5-diamino-2-pentyne (DAPY) was found to be a weak substrate of grass pea (Lathyrus sativus, GPAO) and sainfoin (Onobrychis viciifolia, OVAO) amine oxidases. Prolonged incubations, however, resulted in irreversible inhibition of both enzymes. For GPAO and OVAO, rates of inactivation of 0.1-0.3 min(-1) were determined, the apparent KI values (half-maximal inactivation) were of the order of 10(-5) m. DAPY was found to be a mechanism-based inhibitor of the enzymes because the substrate cadaverine significantly prevented irreversible inhibition. The N1-methyl and N5-methyl analogs of DAPY were tested with GPAO and were weaker inactivators (especially the N5-methyl) than DAPY. Prolonged incubations of GPAO or OVAO with DAPY resulted in the appearance of a yellow-brown chromophore (lambda(max) = 310-325 nm depending on the working buffer). Excitation at 310 nm was associated with emitted fluorescence with a maximum at 445 nm, suggestive of extended conjugation. After dialysis, the color intensity was substantially decreased, indicating the formation of a low molecular mass secondary product of turnover. The compound provided positive reactions with ninhydrin, 2-aminobenzaldehyde and Kovacs' reagents, suggesting the presence of an amino group and a nitrogen-containing heterocyclic structure. The secondary product was separated chromatographically and was found not to irreversibly inhibit GPAO. MS indicated an exact molecular mass (177.14 Da) and molecular formula (C10H15N3). Electrospray ionization- and MALDI-MS/MS analyses yielded fragment mass patterns consistent with the structure of a dihydropyridine derivative of DAPY. Finally, N-(2,3-dihydropyridinyl)-1,5-diamino-2-pentyne was identified by means of 1H- and 13C-NMR experiments. This structure suggests a lysine modification chemistry that could be responsible for the observed inactivation.