gebhart/patrepeval huggingface dataset:
Local Analgesia with Opioid Drugs (1995)

These data suggest the presence of peripheral opioid receptors that are involved in the clinical perception of pain. This is a radical change in our traditional thinking of opioid pharmacology and pain management. Most clinicians have been taught that opioids work through the central nervous system. These new data depart from this traditionally held view of an exclusively central site of action. Further data, specifically, additional dose-response data with varying amounts of morphine, additional studies in pain syndromes other than knee arthroscopy, and the development and pharmacology of orally active opioid compounds that do not cross the central nervous system, are necessary to confirm and expand the present findings. The possibility of providing opioid pain relief free of central nervous system adverse effects is an exciting prospect. Additional studies of topical opioid preparations also would be of interest.
5.2 GHz Self-Powered Lock and Roll Radio using VCO Injection-Locking and On-Chip Antennas (2006)

A novel integrated transceiver suitable for short range wireless applications such as RFID tagging or the transmission of data from medical sensors is presented. The circuit is unique in that it is virtually completely integrated, making use of on-chip antennas, and self-powered by a thin film ultracapacitor and solar cell stacked on top of the chip. Both the transmitter and receiver consist of PLLs which initially lock VCOs, and then allow them to "roll" in order to transmit and receive the signal. The VCO in the receiver is injection-locked by the incoming signal. The current design has a communication range of 4.5 cm which can be increased at the expense of the bit rate or increased power consumption in the receiver
Fine-Structure Mapping of Meiosis-Specific Double-Strand DNA Breaks at a Recombination Hotspot Associated with an Insertion of Telomeric Sequences Upstream of the His4 Locus in Yeast (2020)

Meiotic recombination in Saccharomyces cerevisiae is initiated by double-strand DNA breaks (DSBs). Using two approaches, we mapped the position of DSBs associated with a recombination hotspot created by insertion of telomeric sequences into the region upstream of HIS4. We found that the breaks have no obvious sequence specificity and localize to a region of ~50 bp adjacent to the telomeric insertion. By mapping the breaks and by studies of the exonuclease III sensitivity of the broken ends, we conclude that most of the broken DNA molecules have blunt ends with 3'-hydroxyl groups.
Hyperthermic intraperitoneal chemotherapy: Rationale and technique (2010)

The combination of complete cytoreductive surgery and perioperative intraperitoneal chemotherapy provides the only chance for long-term survival for selected patients diagnosed with a variety of peritoneal neoplasms, either primary or secondary to digestive or gynecologic malignancy. Hyperthermic intraperitoneal chemotherapy (HIPEC) delivered in the operating room once the cytoreductive surgical procedure is finalized, constitutes the most common form of administration of perioperative intraperitoneal chemotherapy. This may be complemented in some instances with early postoperative intraperitoneal chemotherapy (EPIC). HIPEC combines the pharmacokinetic advantage inherent to the intracavitary delivery of certain cytotoxic drugs, which results in regional dose intensification, with the direct cytotoxic effect of hyperthermia. Hyperthermia exhibits a selective cell-killing effect in malignant cells by itself, potentiates the cytotoxic effect of certain chemotherapy agents and enhances the tissue penetration of the administered drug. The chemotherapeutic agents employed in HIPEC need to have a cell cycle nonspecific mechanism of action and should ideally show a heat-synergistic cytotoxic effect. Delivery of HIPEC requires an apparatus that heats and circulates the chemotherapeutic solution so that a stable temperature is maintained in the peritoneal cavity during the procedure. An open abdomen (Coliseum) or closed abdomen technique may be used, with no significant differences in efficacy proven to date. Specific technical training and a solid knowledge of regional chemotherapy management are required. Concerns about safety of the procedure for operating room personnel are expected but are manageable if universal precautions and standard chemotherapy handling procedures are used. Different HIPEC drug regimens and dosages are currently in use. A tendency for concurrent intravenous chemotherapy administration (bidirectional chemotherapy, so-called "HIPEC plus") has been observed in recent years, with the aim to further enhance the cytotoxic potential of HIPEC. Future trials to ascertain the ideal HIPEC regimen in different diseases and to evaluate the efficacy of new drugs or drug combinations in this context are warranted.
Effects of Li+, K+, and Ba2+ Cations on the ORR at Model and High Surface Area Pt and Au Surfaces in Alkaline Solutions (2011)

This Letter reveals new findings on the influence of noncovalent interactions on the electrochemical interface. Using surface X-ray scattering, we demonstrate that the barium cations are located at 3.4 Å away from the surface, suggesting that they are partially hydrated, though not adsorbed at the surface. The effect of the cation on the oxygen reduction reaction (ORR) ranges from significant (Pt) to little (Au), depending on the nature of the metal and cation. Finally, we show that these results, as obtained on well-defined single-crystal surfaces, correlate well with observations on high surface area nanoparticle catalysts.
Fast slow folding of an outer membrane porin (2022)

In comparison to globular proteins, the spontaneous folding and insertion of β-barrel membrane proteins are surprisingly slow, typically occurring on the order of minutes. Using single-molecule Förster resonance energy transfer to report on the folding of fluorescently labeled outer membrane protein G we measured the real-time insertion of a β-barrel membrane protein from an unfolded state. Folding events were rare and fast (<20 ms), occurring immediately upon arrival at the membrane. This combination of infrequent, but rapid, folding resolves this apparent dichotomy between slow ensemble kinetics and the typical timescales of biomolecular folding.
Hydrogen bonded supramolecular assemblies based on neutral square-planar palladium(ii) complexes (2007)

An isomeric series of seven, square-planar, neutral dichloropalladium(II) complexes cis-PdCl2{P,P-C6H3N(CH2PPh2)2(CO2H)(OH)} 2a–2g have been synthesised in high yields (70–99%) from PdCl2(cod) (cod = cycloocta-1,5-diene) and the appropriate ligands C6H3N(CH2PPh2)2(CO2H)–(OH) 1a–1g in CH2Cl2. The new ditertiary phosphine C6H3N(CH2PPh2)2(3-CO2H)(4-CO2H) 3, bearing two remote carboxylic acid groups on the N-arene backbone, was prepared by condensation of H2NC6H3(3-CO2H)(4-CO2H) with 2 equiv. of Ph2PCH2OH in MeOH. The palladium(II) complex cis-{P,P-PdCl2C6H3N(CH2PPh2)2(3-CO2H)(4-CO2H)} 4 was synthesised in an analogous fashion to 2a–2g. Solution NMR (31P{1H}, 1H), FT-IR, ms and microanalytical data are in full agreement with the proposed structures. Single crystal X-ray studies confirm that, in each case, compounds 2a–2e and 4 are square-planar with normal Pd–P [range 2.2255(11)–2.2529(5) Å]/Pd–Cl [range 2.3292(14)–2.3640(16) Å] bond lengths and P–Pd–P [range 91.586(18)–97.25(4)°] bond angles. These studies also demonstrate the importance of predisposition, with respect to the –N(CH2PPh2)2, –CO2H and –OH (or a second –CO2H as in 4) functionalities around the benzene core, and the choice of recrystallisation solvent used with regards to the supramolecular structures observed here for the palladium(II) complexes 2a–2e and 4. Hence in 2a·MeOH, intermolecular O–H⋯Cl hydrogen bonding associates two molecules into a dimer pair with the formation of a 20-membered ring. Two different hydrogen bonded motifs are observed in 2b·0.5Et2O namely an intermolecular O–H⋯O dimer pair and a 1-D polymeric chain through bifurcated O–H⋯Cl hydrogen bonding. Both 2c·MeOH and 2d·CHCl3 have 1-D chain structures using intermolecular O–H⋯Cl hydrogen bonding between neighbouring molecules (for 2d·CHCl3) or a combination of O–H⋯O (with a MeOH solvent) and O–H⋯Cl hydrogen bonding (for 2c·MeOH). The structures of 2e·CHCl3 and 2a·CHCl3 have similar features in common namely a classic H-bonded head-to-tail arrangement of carboxylic acid groups between molecules and additional intermolecular O–H⋯Cl H-bonds giving rise to ladder structures. Each ring is either 38- (for 2e·CHCl3) or 34-membered (for 2a·CHCl3) in size. In 4·2.5MeOH dimers are connected via MeOH solvates to give a 2-D infinite H-bonded network. The X-ray structures of 4·3DMSO, 2e·2DMSO and 2a·DMSO have also been determined. Whilst 4·3DMSO and 2e·2DMSO form discrete structures, 2a·DMSO forms a 1-D chain through O–H⋯Cl hydrogen bonding. The Pd⋯Pd contacts for all these palladium(II) complexes lie clearly within the non bonding range [7.35–20.69 Å].
Structure Development of the Interphase between Drying Cellulose Materials Revealed by In Situ Grazing-Incidence Small-Angle X-ray Scattering (2021)

The nano- to microscale structures at the interface between materials can define the macroscopic material properties. These structures are extremely difficult to investigate for complex material systems, such as cellulose-rich materials. The development of new model cellulose materials and measuring techniques has opened new possibilities to resolve this problem. We present a straightforward approach combining micro-focusing grazing-incidence small-angle X-ray scattering and atomic force microscopy (AFM) to investigate the structural rearrangements of cellulose/cellulose interfaces in situ during drying. Based on the results, we propose that molecular interdiffusion and structural rearrangement play a major role in the development of the properties of the cellulose/cellulose interphase; this model is representative of the development of the properties of joint/contact points between macroscopic cellulose fibers.
Recent advances in nanotherapeutics for the treatment and prevention of acute kidney injury (2020)

Acute kidney injury (AKI) is a serious kidney disease without specific medications currently except for expensive dialysis treatment. Some potential drugs are limited due to their high hydrophobicity, poor <i>in vivo</i> stability, low bioavailability and possible adverse effects. Besides, kidney-targeted drugs are not common and small molecules are cleared too quickly to achieve effective drug concentrations in injured kidneys. These problems limit the development of pharmacological therapy for AKI. Nanotherapeutics based on nanotechnology have been proved to be an emerging and promising treatment strategy for AKI, which may solve the pharmacological therapy dilemma. More and more nanotherapeutics with different physicochemical properties are developed to efficiently deliver drugs, increase accumulation and control release of drugs in injury kidneys and also directly as effective antioxidants. Here, we discuss the recent nanotherapeutics applied in the treatment and prevention of AKI with improved effectiveness and few side effects.
TBCRC 022: Phase II trial of neratinib for patients (Pts) with human epidermal growth factor receptor 2 (HER2+) breast cancer and brain metastases (BCBM). (2014)

528 Background: Evidence-based treatments for metastatic, HER2+ breast cancer to the central nervous system (CNS) are limited. Neratinib is an irreversible inhibitor of erbB1, HER2, and erbB4 with promising activity in HER2+ disease. Preclinical evidence suggests it may cross the blood brain barrier. We evaluated neratinib in pts with HER2+ BCBM in a multicenter, phase II open label trial. We report the results of cohort 1 here. Methods: Pts with measurable BCMC (>/= 1 cm in longest dimension) who progressed after receipt of local CNS therapy were eligible. Pts received neratinib 240 mg orally once daily over 28 day cycles. Brain MRI and non-CNS imaging were obtained at baseline and every two cycles. Circulating tumor cell collections and neurocognitive evaluations were performed serially. The primary endpoint was composite CNS objective response rate (ORR). CNS ORR required all of the following: >/=50% reduction in volumetric sum of target CNS lesions, no progression of non-target lesions, no new lesions, no escalating steroids, no progressive neurologic signs/symptoms, and no non-CNS progression by RECIST 1.1. If patients progressed outside the CNS, the addition of trastuzumab was offered. We used a two-stage design to distinguish between ORR 6% vs 20% (responses in >/=1/18 pts to enter 2ndstage; responses in >/=5/40 pts to be promising). Results: 40 pts were enrolled between 2/12-6/13; median age was 51. Most pts (80%) had received 2+ lines of therapy for metastatic disease, 85% had prior lapatinib, and 75% had prior WBRT. As of 1/10/14, 0 patients remain on protocol therapy and 22 patients have died. Three women experienced a response (CNS ORR=7.5%; 95% CI 2-27%). The median number of cycles received was 2 (range 1-15+); 6 women (15%) received 6+ cycles of therapy. The most common grade 3+ event was diarrhea (25%); this event decreased after an amendment mandated 2 mg loperamide prophylaxis once daily during cycle 1 (33% grade 3+ diarrhea pre-prophylaxis vs. 21% post-prophylaxis). Conclusions: Neratinib is associated with a low CNS ORR in pts with BCBM but provided durable disease control in some pts. Updated results will be presented at the meeting. Clinical trial information: NCT01494662.
A Highly Selective Fluorescent Sensor for Distinguishing Cadmium from Zinc Ions Based on a Quinoline Platform (2012)

A fluorescent sensor, N-(quinolin-8-yl)-2-(quinolin-8-yloxy)acetamide (HL), based on 8-aminoquinoline and 8-hydroxyquinoline platforms has been synthesized. This sensor displays high selectivity and sensitive fluorescence enhancement to Cd(2+) in ethanol. Moreover, sensor HL can distinguish Cd(2+) from Zn(2+) via two different sensing mechanisms (photoinduced electron transfer for Cd(2+); internal charge transfer for Zn(2+)). The composition of the complex Cd(2+)/HL or Zn(2+)/L(-) has been found to be 1:1, based on the fluorescence/absorption titration and further confirmed by X-ray crystallography.
Postprandial NMR-Based Metabolic Exchanges Reflect Impaired Phenotypic Flexibility across Splanchnic Organs in the Obese Yucatan Mini-Pig (2020)

The postprandial period represents one of the most challenging phenomena in whole-body metabolism, and it can be used as a unique window to evaluate the phenotypic flexibility of an individual in response to a given meal, which can be done by measuring the resilience of the metabolome. However, this exploration of the metabolism has never been applied to the arteriovenous (AV) exploration of organs metabolism. Here, we applied an AV metabolomics strategy to evaluate the postprandial flexibility across the liver and the intestine of mini-pigs subjected to a high fat-high sucrose (HFHS) diet for 2 months. We identified for the first time a postprandial signature associated to the insulin resistance and obesity outcomes, and we showed that the splanchnic postprandial metabolome was considerably affected by the meal and the obesity condition. Most of the changes induced by obesity were observed in the exchanges across the liver, where the metabolism was reorganized to maintain whole body glucose homeostasis by routing glucose formed de novo from a large variety of substrates into glycogen. Furthermore, metabolites related to lipid handling and energy metabolism showed a blunted postprandial response in the obese animals across organs. Finally, some of our results reflect a loss of flexibility in response to the HFHS meal challenge in unsuspected metabolic pathways that must be further explored as potential new events involved in early obesity and the onset of insulin resistance.
Associations of ω-3 Fatty Acids With Interstitial Lung Disease and Lung Imaging Abnormalities Among Adults (2020)

Docosahexaenoic acid (DHA), an ω-3 polyunsaturated fatty acid, attenuates interstitial lung disease (ILD) in experimental models, but human studies are lacking. We examined associations of circulating levels of DHA and other polyunsaturated fatty acids with hospitalization and death due to ILD over 12 years in the Multi-Ethnic Study of Atherosclerosis (MESA; n = 6,573). We examined cross-sectional associations with CT lung abnormalities in MESA (2000-2012; n = 6,541), the Framingham Heart Study (2005-2011; n = 3,917), and the Age, Gene/Environment Susceptibility-Reykjavik Study (AGES-Reykjavik) (2002-2006; n = 1,106). Polyunsaturated fatty acid levels were determined from fasting blood samples and extracted from plasma phospholipids (MESA and AGES-Reykjavik) or red blood cell membranes (Framingham Heart Study). Higher DHA levels were associated with a lower risk of hospitalization due to ILD (per standard-deviation increment, adjusted rate ratio = 0.69, 95% confidence interval (CI): 0.48, 0.99) and a lower rate of death due to ILD (per standard-deviation increment, adjusted hazard ratio = 0.68, 95% CI: 0.47, 0.98). Higher DHA was associated with fewer interstitial lung abnormalities on computed tomography (per natural log increment, pooled adjusted odds ratio = 0.65, 95% CI: 0.46, 0.91). Higher DHA levels were associated with a lower risk of hospitalization and death due to ILD and fewer lung abnormalities on computed tomography in a meta-analysis of data from population-based cohort studies.
Differential Expression of IL-17RC Isoforms in Androgen-Dependent and Androgen-Independent Prostate Cancers (2007)

IL-17RC (interleukin-17 receptor-like) gene codes for a transmembrane protein, the full length of which inhibits apoptosis in prostate cancer cells. IL-17RC gene transcribes over a dozen different splice variants of mRNA. However, it is not known whether there are relevant protein isoforms. Here we report that different IL-17RC protein isoforms were detected by two different antibodies. The isoform as detected byanti-IL-17RC intracellular domain antibodies (anti-ICD) was expressed at higher levels in androgen-independent prostate cancer cell lines (PC3 and DU145) than in androgen-dependent prostatic cell lines (RWPE-1, pRNS-1-1, MLC-SV40, and LNCaP). In contrast, several isoforms as detected by anti-IL-17RC extracellular domain antibodies (anti-ECD) were expressed at significantly higher levels in androgen-dependent prostatic cell lines than in androgen-independent ones. Furthermore, immunohistochemical staining of prostate tissue microarrays showed that IL-17RC protein expression was significantly higher in androgen-independent prostate cancers than in androgen-dependent ones when anti-ICD was used, whereas the trend was reversed using anti-ECD. These observations provide evidence that IL-17RC protein isoforms are differentially expressed in prostatic cells and cancer tissues and may play a negative or positive role in the initiation and progression of prostate cancer.
The Role of Ubiquitination and Sumoylation in Diabetic Nephropathy (2014)

Diabetic nephropathy (DN) is a common and characteristic microvascular complication of diabetes; the mechanisms that cause DN have not been clarified, and the epigenetic mechanism was promised in the pathology of DN. Furthermore, ubiquitination and small ubiquitin-like modifier (SUMO) were involved in the progression of DN. MG132, as a ubiquitin proteasome, could improve renal injury by regulating several signaling pathways, such as NF- κ B, TGF- β , Nrf2-oxidative stress, and MAPK. In this review, we summarize how ubiquitination and sumoylation may contribute to the pathology of DN, which may be a potential treatment strategy of DN.
ChemInform Abstract: A PRELIMINARY INVESTIGATION FOR AN ALUMINUM/ALUMINUM CHLORIDE‐SODIUM CHLORIDE/IRON SULFIDE (FES2) SECONDARY CELL (1980)

Abstract Die Entladungskurven, Stromausb.
Annual decline in forced expiratory volume and airway inflammatory cells and mediators in a general population-based sample (2019)

In this cohort of presumably healthy subjects, we found no associations between sputum inflammatory cells or mediators and dFEV<sub>1</sub> during 10 years of follow-up.
The creative work of large ensembles (2017)

Preparing large ensembles for performance involves musical, social, logistical and financial challenges of a kind seldom encountered in other forms of collective music-making. The conventional approach to meeting the challenges that arise during rehearsal is to appoint a single musical overseer, usually a conductor, whose ostensible role in musical preparation is to directly influence the musicians while working towards the creation of a musical product to be delivered in later performances. Rehearsal leadership, viewed from this perspective, moves predominantly in one direction, from conductor to ensemble. But such a perspective oversimplifies the conductor’s relationship with the ensemble, the relationships between the musicians, and the strategies that the latter must employ when working in large ensembles. Conceptualizing the ensemble as a complex system of interrelated components, where leadership and creative agency are distributed and developed through rehearsal to achieve what audiences assume to be a unified whole, yields new understanding of the work of large ensembles. This chapter examines these components of the creative process in orchestral and choral rehearsal and performance, the internal and external forces shaping and constraining that process, and the approaches that individual musicians and conductors could adopt in response to the changing contexts in which such creativity might be manifested.
Medical Bioremediation: A Concept Moving Toward Reality (2009)

Abstract A major driver of aging is catabolic insufficiency, the inability of our bodies to break down certain substances that accumulate slowly throughout the life span. Even though substance buildup is harmless while we are young, by old age the accumulations can reach a toxic threshold and cause disease. This includes some of the most prevalent diseases in old age-atherosclerosis and macular degeneration. Atherosclerosis is associated with the buildup of cholesterol and its oxidized derivatives (particularly 7-ketocholesterol) in the artery wall. Age-related macular degeneration is associated with carotenoid lipofuscin, primarily the pyridinium bisretinoid A2E. Medical bioremediation is the concept of reversing the substance accumulations by using enzymes from foreign species to break down the substances into forms that relieve the disease-related effect. We report on an enzyme discovery project to survey the availability of microorganisms and enzymes with these abilities. We found that such microorganisms and enzymes exist. We identified numerous bacteria having the ability to transform cholesterol and 7-ketocholesterol. Most of these species initiate the breakdown by same reaction mechanism as cholesterol oxidase, and we have used this enzyme directly to reduce the toxicity of 7-ketocholesterol, the major toxic oxysterol, to cultured human cells. We also discovered that soil fungi, plants, and some bacteria possess peroxidase and carotenoid cleavage oxygenase enzymes that effectively destroy with varied degrees of efficiency and selectivity the carotenoid lipofuscin found in macular degeneration.