gebhart/patrepeval huggingface dataset:
Adipocyte (Pro)Renin-Receptor Deficiency Induces Lipodystrophy, Liver Steatosis and Increases Blood Pressure in Male Mice (2016)

Adipose tissue dysfunction related to obesity is overwhelmingly associated with increased risk of developing cardiovascular diseases. In the setting of obesity, (pro)renin receptor (PRR) is increased in adipose tissue of mice. We sought to determine the physiological consequences of adipocyte-PRR deficiency using adiponectin-Cre mice. We report a unique model of adipocyte-PRR-deficient mice (PRR(Adi/Y)) with almost no detectable white adipose tissues. As a consequence, the livers of PRR(Adi/Y) mice were enlarged and demonstrated a marked accumulation of lipids. Adipocyte-specific deficiency of PRR increased systolic blood pressure and the concentration of soluble PRR in plasma. To determine whether adipocyte-PRR was involved in the development of obesity-induced hypertension, mice were fed a low-fat or a high-fat diet for 16 weeks. Adipocyte-PRR-deficient mice were resistant to diet-induced obesity. Both high-fat- and low-fat-fed PRR(Adi/Y) mice had elevated insulin levels. Interestingly, adipocyte-PRR deficiency improved glucose tolerance in high-fat-fed PRR(Adi/Y) mice. In response to feeding either low-fat or high-fat diets, systolic blood pressure was greater in PRR(Adi/Y) mice than in control mice. High-fat feeding elevated soluble PRR concentration in control and PRR(Adi/Y) mice. In vitro knockdown of PRR by siRNA significantly decreased mRNA abundance of PPARγ (peroxisome proliferator-activated receptor gamma), suggesting an important role for PRR in adipogenesis. Our data indicate that adipocyte-PRR is involved in lipid homeostasis and glucose and insulin homeostasis, and that soluble PRR may be a predictor of metabolic disturbances and play a role in systolic blood pressure regulation.
Importance of Glass Transition Temperature in Accelerated Stability Testing of Amorphous Solids: Case Study Using a Lyophilized Aspirin Formulation (1996)

During the development and formulation screening for a lyophilized dosage form, one of the most important characteristic of the amorphous lyophilized solid that is usually not considered is its glass transition temperature. The knowledge of Tg for various formulations becomes especially important during the initial stages of formulation development, when formulation screening is done predominantly by monitoring the stability of various formulations under accelerated conditions (i.e. high temperature and humidity) and extrapolating their stability to the storage temperature. This extrapolation assumes that reaction mechanism does not change with temperature and that the reaction obeys Arrhenius kinetics. 1 Added to the complexity that reaction mechanisms may inherently be temperature dependent, any physical change (e.g. due to glass transition) in the dosage form can further complicate the data interpretation and may render the information from high-temperature studies useless. As a consequence, it is likely that several incorrect decisions may be made during the formulation screening and development.
Alu‐mediated large deletion of the CDSN gene as a cause of peeling skin disease (2013)

Peeling skin disease (PSD) is an autosomal recessive skin disorder caused by mutations in CDSN and is characterized by superficial peeling of the upper epidermis. Corneodesmosin (CDSN) is a major component of corneodesmosomes that plays an important role in maintaining epidermis integrity. Herein, we report a patient with PSD caused by a novel homozygous large deletion in the 6p21.3 region encompassing the CDSN gene, which abrogates CDSN expression. Several genes including C6orf15, PSORS1C1, PSORS1C2, CCHCR1, and TCF19 were also deleted, however, the patient showed only clinical features typical of PSD. The deletion size was 59.1 kb. Analysis of the sequence surrounding the breakpoint showed that both telomeric and centromeric breakpoints existed within Alu-S sequences that were oriented in opposite directions. These results suggest an Alu-mediated recombination event as the mechanism underlying the deletion in our patient.
Condensed Tannins in Adhesives (1989)

Sequential extraction of the bark of most species of conifers and deciduous trees, using water or polar organic solvents followed by aqueous alkali, yields two fractions of polymeric polyphenols, respectively referred to as condensed tannins and phenolic acids. These materials react with formaldehyde or phenol-formaldehyde prepolymers to make suitable resins for cold-setting waterproof adhesives for wood lamination or thermosets for exterior-grade plywood. Commercial production of bark extracts from western hemlock, Douglas-fir, and redwood in North America found limited application for adhesives during the period 1955-1975. Wattle (Acacia mearnsii) bark tannins, produced in South Africa, are currently used in adhesive formulations. The availability of large quantities of pine bark residues from pulping operations in the Americas, Australia, and New Zealand located near waferboard, plywood, and wood-laminating producers who consume substantial amounts of phenolic adhesives suggests that the time is ripe for production of bark-based adhesives. Lower cost, higher yield isolation techniques, in particular, may still be needed for this objective to become a commercial reality.
Discovery of direct inhibitors of Keap1–Nrf2 protein–protein interaction as potential therapeutic and preventive agents (2015)

The Keap1-Nrf2-ARE pathway is an important antioxidant defense mechanism that protects cells from oxidative stress and the Keap1-Nrf2 protein-protein interaction (PPI) has become an important drug target to upregulate the expression of ARE-controlled cytoprotective oxidative stress response enzymes in the development of therapeutic and preventive agents for a number of diseases and conditions. However, most known Nrf2 activators/ARE inducers are indirect inhibitors of Keap1-Nrf2 PPI and they are electrophilic species that act by modifying the sulfhydryl groups of Keap1׳s cysteine residues. The electrophilicity of these indirect inhibitors may cause "off-target" side effects by reacting with cysteine residues of other important cellular proteins. Efforts have recently been focused on the development of direct inhibitors of Keap1-Nrf2 PPI. This article reviews these recent research efforts including the development of high throughput screening assays, the discovery of peptide and small molecule direct inhibitors, and the biophysical characterization of the binding of these inhibitors to the target Keap1 Kelch domain protein. These non-covalent direct inhibitors of Keap1-Nrf2 PPI could potentially be developed into effective therapeutic or preventive agents for a variety of diseases and conditions.
FUTEBOL Control Framework: Enabling Optical-Wireless Convergence (2019)

Large-scale testing and performance evaluation of network services is complex and involves multiple network domains (e.g., optical and wireless networks, cloud services). The H2020 EU-Brazil FUTEBOL project has deployed geographically distributed testbeds that enable the experimentation and validation of new protocols that spread over both optical and wireless networks. In this article, we describe a control framework that allows experimenters to slice, reserve, and control optical, wireless, and cloud resources in a coordinated manner. Our control framework employs network orchestrators, which cope with the heterogeneity of both wireless and optical communications. We illustrate the features of and evaluate our solution through an experiment that supports cross-domain resource orchestration and automatic service scaling.
Flexible Communication and Control Protocol for Injectable Neuromuscular Interfaces (2007)

BION2 is a system based on injectable neuromuscular implants whose main goal is to restore the functional movement of paralyzed limbs. To achieve this objective, the functional requirements of the implanted interfaces include not only stimulation but also integrated sensors in order to detect patient intention, to provide servocontrol of muscle activation and to sense posture to inform more global motor planning and coordination. The technical constraints for managing the system include the efficient use of forward and reverse telemetry channels with limited capacity, minimization of adverse consequences from errors in data transmission or intermittent loss of power to the implants, and ability to adjust stimulation rates and phases to achieve efficient fine control of muscle force while minimizing fatigue. This paper describes a communication and control architecture with several novel features that address these requirements.
Age-Dependent Attenuation of the Decrease of C Fibers by Capsaicin and Its Effects on Responses to Nociceptive Stimuli (1992)

The effects of subcutaneous treatment of mice 10, 15, or 20 days (young) or 30 or 60 days (adult) of age with capsaicin on development of unmyelinated (C) fibers in the L4 dorsal roots were examined. The responses of the mice 2-4 months later to thermal (hot plate; 55 degrees C) and neurogenic plasma extravasative (chemogenic nociception) stimuli were evaluated. Capsaicin treatment 10 days after birth affected development of myelinated fibers significantly (7.9% reduction). Capsaicin treatment 10, 15, 20, and 30 days after birth reduced the number of C fibers 11.0-51.7% and even treatment 60 days after birth caused a significant decrease (10.0%) in the mean number of C fibers. The destruction of C fibers by capsaicin was attenuated during development, but individual differences in the reduction of C fibers were observed on and after 15 days of life and seemed to become more marked over time. Neurogenic plasma extravasation related to primary sensory neurons was decreased by capsaicin, irrespective of the time of treatment. In parallel with reduction of C fibers, hot-plate latency was increased significantly by treatment of young animals with capsaicin. These results suggest that the effect of capsaicin on thermal nociception is age-dependent and is correlated with decrease of C fibers. However, a marked increase in hot-plate latency did not always correspond to a marked decrease of C fibers. In contrast, the reduction of plasma extravasation was not age-dependent: Reduced extravasation of dye persisted during development.(ABSTRACT TRUNCATED AT 250 WORDS)
An evaluation of molecular weight distribution in high pressure polyethylene (1958)

Abstract A particular kind of plot has been used, yielding graphs tending toward straight lines, to compare the fractionation and viscometry data of eight high pressure polyethylene samples with the distribution formula deduced by Beasley. These graphs are equivalent, except for an additive constant in the abscissas, to the log‐log plots of intrinsic viscosity versus molecular weights. In this way an evaluation of the distribution parameters defined by Beasley can be obtained for all the investigated samples. By means of these parameters and the absolute determination of the (number‐)average molecular weight of a single sample, an evaluation of all the molecular weights and of their distribution in the given samples has been proposed. Within the limits of experimental uncertainty of the measurements of high pressure polyethylene in diluted solutions, these results are in some agreement with the experimental findings of other authors.
A Fault Tolerance Protocol with Fast Fault Recovery (2007)

Fault tolerance is an important issue for large machines with tens or hundreds of thousands of processors. Checkpoint-based methods, currently used on most machines, rollback all processors to previous checkpoints after a crash. This wastes a significant amount of computation as all processors have to redo all the computation from that checkpoint onwards. In addition, recovery time is bound by the time between the last checkpoint and the crash. Protocols based on message logging avoid the problem of rolling back all processors to their earlier state. However, the recovery time of existing message logging protocols is no smaller than the time between the last checkpoint and crash. We present a fault tolerance protocol, in this paper, that provides fast restarts by using the ideas of message logging and object-based processor virtualization. We evaluate our implementation of the protocol in the Charm++/adaptive MPI runtime system. We show that our protocol provides fast restarts and, for many applications, has low fault-free overhead.
Investigation of the synthesis and analgesic activity of 1‐substituted 4‐(propananilido)perhydroazepines (1992)

Abstract Methods are explored to enhance the efficiency and versatility of the synthesis of the 1‐substituted 4‐(propananilido)perhydroazepine analgesics. The modified synthesis begins with ring expansion of 1‐carbethoxy‐4‐piperidinone 3 with ethyl diazoacetate and boron trifluoride to yield 1,5‐biscarbethoxyperhydroazepin‐4‐one 4 . Selective hydrolysis of 4 followed by decarboxylation provides 1‐carbethoxyperhydroazepin‐4‐one 6 . Reductive amination of 6 with aniline affords the 4‐anilino intermediate 7 which is treated with propionic anhydride to give 1‐carbethoxy‐4‐(propananilido)perhydroazepine 18 . Selective cleavage of the 1‐carbethoxy group of 18 was accomplished with trimethylsilyliodide to yield the versatile intermediate 4‐(propananilido)‐perhydroazepine 19. Treatment of 19 with styrene oxide afforded the 1‐[2‐(1‐hydroxy‐1‐phenyl)ethyl] derivative 1c which, in the tail‐flick assay, displays greater analgesic potential than previously reported members of this series.
[Dysphagia as the only manifestation of inclusion body myositis]. (1994)

We report a 72-year-old woman with dysphagia as the only manifestation of inclusion body myositis (IBM). Although electrophysiological examination revealed subclinical abnormalities in limb muscles, dysphagia was the only symptom 4 years after the onset of the disease. Muscle biopsy showed rimmed vacuoles and cytoplasmic inclusions together with lymphocytic inflammation. IBM must be included in the differential diagnosis of isolated dysphagia.
P09.57 Clinical trials of VAL-083 in patients with chemoresistant glioblastoma (2017)

Glioblastoma (GBM) is the most common CNS tumor. Patients with recurrent GBM have few treatment options and dismal prognosis. O6-methylguanine-DNA-methyltransferase (MGMT) is correlated with resistance to standard of care treatment with temozolomide and poor patient outcomes. Dianhydrogalactitol (VAL-083) is a bi-functional alkylating agent with a distinct mechanism-of-action differentiating it from other alkylating agents used in the treatment of GBM and other CNS tumors. VAL-083 readily crosses the blood-brain barrier and accumulates in brain tumor tissue. VAL-083 has demonstrated MGMT-independent cytotoxicity in multiple GBM cell-lines and cancer stem cells and is able to overcome TMZ-resistance in vitro demonstrating a different mechanism of action. In multiple prior NCI-sponsored clinical trials VAL-083 showed promise against CNS tumors. We recently concluded a phase I/II clinical trial studying VAL-083 in recurrent GBM patients failing temozolomide and bevacizumab, and data suggests a potential for VAL-083 to offer clinically meaningful survival benefits in patients who have failed or are unlikely to respond to currently available chemotherapeutic regimens. In the phase I portion of the trial, VAL-083, 40 mg/m2/day x 3 every 21 days was well-tolerated and this dose was selected for study in the phase II expansion phase. We are initiating multiple clinical trials targeting adult patients with chemoresistant GBM due to MGMT expression. Enrollment is anticipated to be initiated in early 2017. These trials include i) a pivotal, randomized Phase 3 study measuring survival outcome compared to “physician’s choice” control, which, if successful, would serve as the basis for a New Drug Application (NDA) submission for VAL-083. The control arm will consist of a limited number of salvage chemotherapies currently utilized in bevacizumab-failed GBM. ii) A single-arm, biomarker-driven, Phase 2 study to determine if treatment of MGMT-unmethylated recurrent GBM with VAL-083 improves overall survival at 9 months, compared to historical control in bevacizumab-naïve patients (clinicaltrials.gov identifier: NCT02717962). iii) A single arm Phase 2 study to confirm the tolerability of DelMar’s dosing regimen in combination with radiotherapy and to explore the activity of VAL-083 in newly diagnosed MGMT-unmethylated GBM patients whose tumors are known to express high MGMT levels. The results of these studies may support a new treatment paradigm in chemotherapeutic regimens for the treatment of GBM. Enrollment updates and study design details will be presented at the meeting.
Auditory processing of coherent and incoherent frequency modulation (1999)

When two elements of a visual array move coherently, there is a strong tendency to group them perceptually. This has prompted several authors to suggest that acoustic frequency components which undergo coherent FM should be perceptually fused, and that those which are modulated incoherently should be segregated. This paper will review the mounting body of evidence demonstrating that, once a number of co-varying cues are controlled for, the auditory system is insensitive to the difference between coherent and incoherent FM. Such cues include the greater inharmonicity, smaller swings in average frequency, and more salient distortion products which can occur with incoherent compared to coherent modulation. In addition, new evidence will be presented showing that listeners can be more sensitive to one form of incoherent FM than to another: Opposite-direction quasi-linear frequency sweeps imposed on two carriers are more detectable when the frequency of the lower component decreases and that of the higher component increases than vice versa. This occurs even though the frequency sweeps imposed on the individual components are equally detectable when those components are presented in isolation, and even though within-channel interactions are masked by noise.
Modeling spatial relation in skin lesion images by the graph walk kernel (2010)

Early skin cancer detection with the help of dermoscopic images is becoming more and more important. Previous methods generally ignored the spatial relation of the pixels or regions inside the lesion. We propose to employ a graph representation of the skin lesion to model the spatial relation. We then use the graph walk kernel, a similarity measure between two graphs, to build a classifier based on support vector machines for melanoma detection. In experiments, we compare the sensitivities and specificities of models with and without spatial information. Experimental results show that the model with spatial information performs the best in both sensitivity and specificity. Statistical test indicates that the improvement is significant.
Bone Marrow Stromal Stem Cells in Tissue Engineering and Regenerative Medicine (2016)

Bone marrow stromal stem cells (BMSCs) are adult multipotent cells, which have the potential to differentiate into cell types of mesodermal origin, namely osteocytes, adipocytes, and chondrocytes. Due to their accessibility and expansion potential, BMSCs have historically held therapeutic promise in tissue engineering and regenerative medicine applications. More recently, it has been demonstrated that not only can bone marrow stromal stem cells directly participate in tissue regeneration, but they also have the capacity to migrate to distant sites of tissue injury, where they can participate in tissue repair either directly through their differentiation or indirectly through paracrine mechanisms. Additionally, they can elicit various immunomodulatory signals, which can attenuate the inflammatory and immune responses. As such, bone marrow stromal stem cells have been explored clinically for treatment of a wide variety of different conditions including bone defects, graft-vs.-host disease, cardiovascular diseases, autoimmune diseases, diabetes, neurological diseases, and liver and kidney diseases. This review provides an overview of current clinical applications of bone marrow stromal stem cells and discusses their therapeutic properties, while also addressing limitations of their use. PubMed, Ovid, and Google Scholar online databases were searched using several keywords, including "stem cells", "tissue engineering", tissue regeneration" and "clinical trials". Additionally, Clinical trials.gov was used to locate completed clinical trials using bone marrow derived stem cells.
ChemInform Abstract: SYNTHESIS AND STRUCTURE OF A SEVEN‐COORDINATE MOLYBDENUM CARBONYL FLUORIDE DERIVATIVE: (ET4N)(MO(CO)2(S2CNET2)2F) (1985)

Abstract Ausgehend von den Hexacarbonylen (I) wird über die Carbonyliodide (III) und (IV) wie aufgezeigt eine verbesserte Darstellungsmethode für die Mo(II)‐ und W(II)‐dithiocarbamate (VI) demonstriert.
High‐throughput screening and small animal models, where are we? (2010)

Current high‐throughput screening methods for drug discovery rely on the existence of targets. Moreover, most of the hits generated during screenings turn out to be invalid after further testing in animal models. To by‐pass these limitations, efforts are now being made to screen chemical libraries on whole animals. One of the most commonly used animal model in biology is the murine model Mus musculus . However, its cost limit its use in large‐scale therapeutic screening. In contrast, the nematode Caenorhabditis elegans , the fruit fly Drosophila melanogaster , and the fish Danio rerio are gaining momentum as screening tools. These organisms combine genetic amenability, low cost and culture conditions that are compatible with large‐scale screens. Their main advantage is to allow high‐throughput screening in a whole‐animal context. Moreover, their use is not dependent on the prior identification of a target and permits the selection of compounds with an improved safety profile. This review surveys the versatility of these animal models for drug discovery and discuss the options available at this day.
Physiopathology of Circulating Immunoreactive Somatostatin in Man (1988)

The hypothalamic hormone somatostatin has also been found in numerous other organs throughout the body; circulating immunoreactive somatostatin (IRS) in man is most likely of gastrointestinal origin, where much greater amounts of the peptide are found than in the central nervous system. In a series of clinical protocols carried out over the last few years, we have observed an increase in the plasma IRS with age and a rise in its response (stimulated either by insulin-induced hypoglycaemia or by food) in hyperchlorhydria (i.e. duodenal ulcer) and in functional or acute organic diseases of the colon. We observed a decrease in circulating IRS stimulation in situations characterized by achlorhydria (pernicious anemia, surgical vagotomy, diabetic autonomic neuropathy, or during Cimetidine administration). Additionally, hypersomatostatinaemia was detected in diabetic ketoacidosis, where a direct correlation was observed between plasma IRS and free fatty acids. As far as the metabolism of IRS in man, not only the liver but also the rest of the splanchnic area not only secretes but also metabolizes this peptide. These results suggest that in man, plasma IRS is under vagal control and varies parallely to the secretion of gastric acid; since this peptide is known to influence many gastrointestinal functions, a physiological role for this circulating IRS concentration is a feasible possibility.
Caregiving and infant behavior in day care and in homes. (1979)

Social interaction and play behavior were compared in community-based day care and at home for 2 matched groups of 18-mo-olds (30 Ss). Adult-infant, infant-peer, and infant-toy interaction were time sampled. More adult-infant play, tactile contact, and reciprocal smiling were found in day care. More