gebhart/patrepeval huggingface dataset:
Polychlorinated biphenyls, cytochrome P450 1A1, and breast cancer risk in the Nurses' Health Study. (2002)

There is concern that exposures to the environmental chemicals polychlorinated biphenyls (PCBs) may contribute to breast cancer risk. An individual's susceptibility to the effects of PCBs may be partially determined by polymorphisms in the gene encoding the biotransformation enzyme cytochrome P450 1A1 (CYP1A1). PCB exposure induces CYP1A1 activity, and PCBs themselves or other xenobiotics can be metabolized to carcinogenic intermediates in the presence of the variant genotype. A previous case-control study provided evidence of an interaction between high exposures to PCBs and the CYP1A1-exon 7 polymorphism (the A to G transition at nucleotide 4889), leading to a significant increase in postmenopausal breast cancer risk. We examined the interaction of PCBs with the CYP1A1-MspI (the T to C transition at nucleotide 6235) and exon 7 polymorphisms among 367 breast cancer case-control pairs (293 postmenopausal pairs) in the Nurses' Health Study. Although there was no independent association of either the CYP1A1 variants or PCBs with breast cancer risk, the relative risk among the postmenopausal women with plasma PCB levels in the highest third of the distribution in the control group and at least one exon 7 variant allele compared with women who were homozygous for the wild-type allele and who had PCB levels in the lowest third was 2.78 (95% confidence interval, 0.99-7.82). The majority of studies have concluded that exposure to PCBs is unlikely to be a major cause of breast cancer, but these findings indicate that further studies of genetically susceptible populations are warranted.
Endoplasmic Reticulum Stress and the Unfolded Protein Response in Exocrine Pancreas Physiology and Pancreatitis (2015)

The endoplasmic reticulum (ER) plays a pivotal role in cellular homeostasis as it is the site of translation, folding and covalent modification of proteins either destined for secretion or expressed on the surface of other organelles and the plasma membrane. The cytoplasmic surface of the ER membrane is also the primary site of triglyceride, phospholipid and sterol synthesis and therefore, is a hub of membrane synthesis and cellular metabolism. Many studies have established the ER as a major site of intracellular Ca storage essential for hormone/neurotransmitter signaling. More recent work has also begun to identify unexpected functions of the ER in diverse cellular processes including mitochondrial fission, endosomal dynamics and autophagy.
The effects of age on dopamine receptors measured by positron tomography in the living human brain (1984)

C-11 n-methylspiperone has been used to measure dopamine (D2) receptors in the caudate and putamen of 30 normal persons. In vitro studies in rodent brain revealed a high affinity for dopamine (D2) receptors and five fold less for serotonin (S2) receptors. In vivo drug competition studies in rodents demonstrated that 90% of striatal binding is to dopamine receptors. In the frontal cortex, the majority of receptor binding is to serotonin receptors. Thirty normal volunteers aged 19 to 73 years were screened for normality by medical, neurological and neuropsychological examinations. Positron tomography was performed serially for 2 hours after injection. In 10 subjects there was good agreement between activity in arterial samples and that in venous samples from a heated hand. Binding in the dopamine rich caudate and putamen progressively increased while binding in the dopamine poor cerebellum decreased. The dopamine receptor density was estimated by the ratio of the caudate-to-cerebellar mean counts/pixel (Ca/Cb) and putamen-to-cerebellar mean counts/pixel (Pu/Cb). The ratios (Ca/Cb, Pu/Cb) increased linearly with time (r>0.95) for each subject. There was a decrease (Ca/Cb) with age (0.8%/yr) that could be approximated with a linear fit: (Ca/Cb = -.02 age + 3.92, r=.6). For the 21 males alone, the decreasemore » was (1.1%/yr, r=.7 , p <.01), while for the 9 females there was no significant decrease with age. Similar findings were noted in the putamen. This decline in dopamine receptor density with age has been reported in rodent and human autopsy studies, but never before in the living human brain.« less
Synthesis of the carbobicyclic substructure of CP-225,917 and CP-263,114 (1997)

The bridgehead alkenic ketones 22a and 22b, representing the carbobicyclic substructure of the squalene synthase and farnesyl transferase inhibitors CP-225,917 (1) and CP-263,114 (23), have been synthesized from the 7-norbornenone acetal 8, using an anionic oxy-Cope rearrangement of 21a and 21b in the key step; the synthesis serves as a test of a potential route to both natural products.
Effect of prebiotic (fructooligosaccharide) on uremic toxins of chronic kidney disease patients: a randomized controlled trial (2018)

Our result suggests the potential of FOS in reducing serum total and free PCS in nondiabetic NDD-CKD patients.
Development of MBE-grown HgCdTe 64 x 64 FPA for long-wavelength IR detection (1993)

The HgCdTe (MCT) 64 X 64 focal plane array (FPA) for long wavelength infrared (LWIR) detection was developed, using MCT epilayers grown by molecular beam epitaxy (MBE). The n-on-p photodiode array has a cutoff wavelength of 10.7 micrometers . The readout circuit, with off focal plane integration capacitance, was designed for 77 K operation. These components were fabricated independently and were hybridized. The 97.8% operability was obtained. Photodiode characteristics for each pixel were measured directly. Mean R$o)A value of 1.9 (Omega) (DOT) cm<SUP>2</SUP> and quantum efficiency of 0.3 were obtained. Using an infrared camera system with nonuniformity correction function, the infrared image was successfully demonstrated. An NETD (noise equivalent temperature difference) value of 0.117 K was attained with an F/2.5 optical lens under the 300 K background condition.
High Serum Interleukin-6 Levels Correlate with a Shorter Failure-Free Survival in Indolent Lymphoma (1998)

Interleukin-6 (IL-6) is a potent immunomodulatory cytokine that may have pathogenetic and prognostic significance in a number of disorders. The objective of this study was to examine the correlation between serum IL-6 levels and phenotypic characteristics, as well as failure-free survival of patients with low-grade non-Hodgkin's lymphomas (NHL). Using a sensitive enzyme-linked immunoabsorbent assay (ELISA), we measured IL-6 in frozen sera from 55 healthy controls and in the pre-treatment frozen sera from 100 low-grade lymphoma patients who were enrolled on protocols at MD Anderson Cancer Center. Serum IL-6 levels were correlated with clinical and laboratory features at diagnosis and with failure-free survival.
Semantic Vector Encoding and Similarity Search Using Fulltext Search\n Engines (2017)

Vector representations and vector space modeling (VSM) play a central role in\nmodern machine learning. We propose a novel approach to `vector similarity\nsearching' over dense semantic representations of words and documents that can\nbe deployed on top of traditional inverted-index-based fulltext engines, taking\nadvantage of their robustness, stability, scalability and ubiquity.\n We show that this approach allows the indexing and querying of dense vectors\nin text domains. This opens up exciting avenues for major efficiency gains,\nalong with simpler deployment, scaling and monitoring.\n The end result is a fast and scalable vector database with a tunable\ntrade-off between vector search performance and quality, backed by a standard\nfulltext engine such as Elasticsearch.\n We empirically demonstrate its querying performance and quality by applying\nthis solution to the task of semantic searching over a dense vector\nrepresentation of the entire English Wikipedia.\n
Induction of myocardial hypertrophy after coronary ligation in rats decreases ventricular dilatation and improves systolic function. (1991)

Induction of myocardial hypertrophy with an inhibitor of long-chain fatty acid oxidation retarded the process of LV dilatation and produced beneficial effects on systolic function after large myocardial infarction. These data support the hypothesis that inadequate hypertrophy of residual myocardium after infarction may contribute to LV dilatation and the development of congestive heart failure.
G Protein-Coupled Receptor Pharmacogenetics (2008)

Common G protein-coupled receptor (GPCR) gene variants that encode receptor proteins with a distinct sequence may alter drug efficacy without always resulting in a disease phenotype. GPCR genetic loci harbor numerous variants, such as DNA insertions or deletions and single-nucleotide polymorphisms that alter GPCR expression and function, thereby contributing to interindividual differences in disease susceptibility/progression and drug responses. In this chapter, these pharmacogenetic phenomena are reviewed with respect to a limited sampling of GPCR systems, including the beta(2)-adrenergic receptors, the cysteinyl leukotriene receptors, and the calcium-sensing receptor. In each example, the nature of the disruption to receptor function that results from each variant is discussed with respect to the regulation of gene expression, expression on cell surface (affected by receptor trafficking, dimerization, desensitization/downregulation), or perturbation of receptor function (by altering ligand binding, G protein coupling, and receptor constitutive activity). Despite the breadth of pharmacogenetic knowledge available, assessment for genetic variants is only occasionally applied to drug development projects involving pharmacogenomics or to optimizing the clinical use of GPCR drugs. The continued effort by the basic science of pharmacogenetics may draw the attention of drug discovery projects and clinicians alike to the utility of personalized pharmacogenomics as a means to optimize novel GPCR drug targets.
Effect of nonlinear flow on DNAPL migration in a rough‐walled fracture (2008)

Experiments were carried out to investigate the influence of the groundwater flow regime on dense nonaqueous phase liquid (DNAPL) migration in a rough‐walled fracture. Hydraulic and DNAPL migration experiments were performed at Reynolds numbers ranging from 0 to 60.8. Nonlinear groundwater flow occurred in the fracture from Reynolds number of approximately 10. Different migration paths taken by DNAPL were observed between linear and nonlinear flow regimes. Experiments were quantitatively analyzed using the modified invasion percolation (MIP) model, which was found to be attributed to the inertial force of flowing groundwater. The MIP model was reformulated to incorporate the effect of inertia to predict the DNAPL migration path in a rough‐walled fracture. The model data provided a good match to the experimentally determined DNAPL migration. The studies indicated that DNAPL migration depended on the groundwater flow regime, which needs to be considered in order to better understand DNAPL migration in rock fractures.
Uranyl ion complexation by medium and large homooxacalixarenes: from mono- to poly-uranate complexes (2001)

Crystal structures of dioxouranium(VI) complexes of three homooxacalix[n]arenes (n = 4, 6 or 8) have shown the possibility to complex metal moieties of variable nuclearity, depending upon the number of phenolic groups and ether links they contain. p-tert-Butyltetrahomodioxacalix[6]arene embraces a single uranyl unit through tetraphenoxide coordination as commonly observed in calixarene complexes, whereas p-methyloctahomotetraoxacalix[4]arene binds a doubly bridged binuclear species coordinated to both phenoxide and ether oxygen donors, while the large p-tert-butyloctahomotetraoxacalix[8]arene binds a unique tetrauranate cluster containing both double and single oxygen bridges between uranium atoms and involving only phenoxide-oxygen coordination to the macrocycle. An additional crystal structure determination on the triethylammonium complex of the singly deprotonated homooxacalix[6]arene enables some comments to be made on the effects of coordination on the macrocycle conformation. The relation between the nuclearity of the uranyl complexes with ligands in the calixarene/homooxacalixarene family and the size of the ligands is discussed.
Efficacy and safety of sustained-delivery fluocinolone acetonide intravitreal implant in patients with chronic diabetic macular edema insufficiently responsive to available therapies: a real-life study (2016)

This prospective study confirms the efficacy of the FAc implant in DME patients insufficiently responsive to laser and anti-VEGF. Moreover, with a careful patient selection, our safety results would support an earlier use of FAc in the DME treatment pathway.
Case report: whole exome sequencing of primary cardiac angiosarcoma highlights potential for targeted therapies (2017)

Mutations in KDR have been reported previously in angiosarcomas. Previous studies also demonstrated that KDR mutants with constitutive KDR activation could be inhibited with specific KDR inhibitors in vitro. Thus, patients harboring activating KDR mutations could be candidates for treatment with KDR-specific inhibitors.
Assay Validation (2016)

Biomolecular screening is now a crucial component of the drug discovery process, and this glossary will be of use to practitioners in the field of screening and to those who interact with the screening community. The glossary contains definitions related to various aspects of the screening process such as assay types, data handling, and relevant technologies. Many of the terms used in this discipline are not covered by existing glossaries, and where they are, the definitions are often not appropriate for this field. Where appropriate, this document provides new or modified definitions to better reflect the new context. The field of biomolecular screening is multidisciplinary in nature, and this glossary, containing authoritative definitions, will be useful not only for regular practitioners, but also for those who make use of data generated during the screening process.
3D Printed Neural Regeneration Devices (2019)

Neural regeneration devices interface with the nervous system and can provide flexibility in material choice, implantation without the need for additional surgeries, and the ability to serve as guides augmented with physical, biological (e.g., cellular), and biochemical functionalities. Given the complexity and challenges associated with neural regeneration, a 3D printing approach to the design and manufacturing of neural devices could provide next-generation opportunities for advanced neural regeneration via the production of anatomically accurate geometries, spatial distributions of cellular components, and incorporation of therapeutic biomolecules. A 3D printing-based approach offers compatibility with 3D scanning, computer modeling, choice of input material, and increasing control over hierarchical integration. Therefore, a 3D printed implantable platform could ultimately be used to prepare novel biomimetic scaffolds and model complex tissue architectures for clinical implants in order to treat neurological diseases and injuries. Further, the flexibility and specificity offered by 3D printed <i>in vitro</i> platforms have the potential to be a significant foundational breakthrough with broad research implications in cell signaling and drug screening for personalized healthcare. This progress report examines recent advances in 3D printing strategies for neural regeneration as well as insight into how these approaches can be improved in future studies.
Methamphetamine Causes Microglial Activation in the Brains of Human Abusers (2008)

Methamphetamine is a popular addictive drug whose use is associated with multiple neuropsychiatric adverse events and toxic to the dopaminergic and serotonergic systems of the brain. Methamphetamine-induced neuropathology is associated with increased expression of microglial cells that are thought to participate in either pro-toxic or protective mechanisms in the brain. Although reactive microgliosis has been observed in animal models of methamphetamine neurotoxicity, no study has reported on the status of microglial activation in human methamphetamine abusers. The present study reports on 12 abstinent methamphetamine abusers and 12 age-, gender-, and education-matched control subjects who underwent positron emission tomography using a radiotracer for activated microglia, [(11)C](R)-(1-[2-chlorophenyl]-N-methyl-N-[1-methylpropyl]-3-isoquinoline carboxamide) ([(11)C](R)-PK11195). Compartment analysis was used to estimate quantitative levels of binding potentials of [(11)C](R)-PK11195 in brain regions with dopaminergic and/or serotonergic innervation. The mean levels of [(11)C](R)-PK11195 binding were higher in methamphetamine abusers than those in control subjects in all brain regions (>250% higher; p < 0.01 for all). In addition, the binding levels in the midbrain, striatum, thalamus, and orbitofrontal and insular cortices (p < 0.05) correlated inversely with the duration of methamphetamine abstinence. These results suggest that chronic self-administration of methamphetamine can cause reactive microgliosis in the brains of human methamphetamine abusers, a level of activation that appears to subside over longer periods of abstinence.
Injury-induced activation of ERK 1/2 in the sciatic nerve of healthy and diabetic rats (2010)

Phosphorylation of extracellular-signal-regulated kinase 1/2 (p-ERK 1/2) was investigated by immunohistochemistry at 30 min, 1 h, and 48 h after nerve transection in the sciatic nerve of healthy and diabetic [streptozotocin (STZ)-induced diabetes mellitus and BioBreeding (BB; i.e. DR.lyp/lyp or BBDP)] rats. Transection injury increased the intensity of p-ERK 1/2 in nerve stumps at all time points. Staining was confined to Schwann cells with occasional faint staining in single axons. In diabetic rats, a lower intensity of p-ERK 1/2 was found at 1 and 48 h in the distal and proximal nerve stumps compared with healthy rats. STZ-induced diabetic rats were not different from BB rats. p-ERK 1/2 is activated differentially in Schwann cells after nerve injury in diabetic rats, whereas activation in STZ-induced diabetic rats did not differ from BB rats.
Ornithobacterium rhinotracheale: A review (1999)

Ornithobacterium rhinotracheale is a relatively recently discovered bacterium of the rRNA superfamily V. It is of worldwide distribution in commercial poultry, in which it is associated with respiratory diseases, and it is also found in wild birds. Airsacculitis and pneumonia are the most common features of infection with O. rhinotracheale. These signs can be induced by aerosol in intra-tracheal or intra-thoracic administration of the organism, and can be aggravated by other factors, such as respiratory viruses, bacteria or climatic conditions. Osteitis, meningitis and joint-infections, which can be induced by intravenous application, have been associated with O. rhinotracheale, but it remains uncertain whether the organism should be regarded as a primary pathogen. The infection can be transmitted horizontally by aerosol, as well as vertically through eggs, which probably accounts for its rapid and worldwide spread. Although O. rhinotracheale is difficult to identify, some commercial identification systems have been found to be suitable, although the media used in such systems will not always support its growth. A PCR assay was also found to be suitable for identification purposes. Twelve serotypes can be distinguished within the species O. rhinotracheale, of which serotype A is the most prevalent. Genetic investigation has revealed that more species or subspecies probably exist within the genus Ornithobacterium. Therapeutic treatment of the disease can be difficult because acquired resistance against the regular antibiotics is very common within the genus. Vaccination with autogenous inactivated vaccines has been successful in reducing clinical signs, but success depends on the adjuvant used. Only potent oil adjuvants are effective in young birds with maternal antibodies, but the use of these adjuvants is known to induce some local reactions. Live vaccination is feasible, but up to now, no avirulent strains of O. rhinotracheale have been found. Vaccination of broiler breeders induced protection against experimental infection of the progeny to at least 3 weeks of age.
Investigating programmable floating-gate digital-to-analog converter as single element or element arrays (2003)

This approach analogous to the classical scaled transistor DAC techniques, where we scale our transistors by programming each transistor's floating-gate charge instead of adjusting W/L ratios. The programable DAC allows great accuracy by eliminating any device mismatch that would otherwise impact a DACs performance. We investigate the feasibility of this approach by making experimental measurements from fabricated floating-gate DAC circuits. The resulting structure requires minimal IC area, since it only uses a minimum or nearly minimum size transistor and a capacitor per bit of resolution.
Pre‐exposure to Subtoxic Levels Prevents Kainic Acid Lesions in Organotypic Hippocampal Slice Cultures: Effects of Kainic Acid on Parvalbumin‐immunoreactive Neurons and Expression of Heat Shock Protein 72 Following the Induction of Tolerance (1996)

The effects of kainic acid on the survival of principal neurons and parvalbumin-immunoreactive (PARV-IR) neurons, and on the expression of heat shock protein 72 immunoreactivity (HSP72-IR) were investigated in organotypic hippocampal slice cultures. Untreated cultures displayed an organotypic organization and the development and morphology of PARV-IR neurons in the hippocampus paralleled that reported to occur in vivo, with the exception of the hilar region of the dentate gyrus which exhibited a marked lack of PARV-IR neurons. No constitutive expression of HSP72 was found in untreated cultures. The lesion of CA3 neurons and the reduction in numbers of PARV-IR neurons in both CA3 and CA1 after chronic exposure to 5 microM kainic acid were similar to those reported to occur in vivo. Exposure to 1 microM doses of kainic acid resulted in a widespread appearance of HSP72-IR and the induction of tolerance to a previously toxic dose of kainic acid. These results suggest the presence of endogenous neuroprotective mechanisms, activated by a stress response which induces HSP72, and is reminiscent of the induced tolerance reported to occur after a mild ischaemic insult.