gebhart/patrepeval huggingface dataset:
Protein Kinase A Phosphorylation of the Ryanodine Receptor Does Not Affect Calcium Sparks in Mouse Ventricular Myocytes (2002)

Ryanodine receptor (RyR) phosphorylation by protein kinase A (PKA) may be important in modulating resting sarcoplasmic reticulum (SR) Ca2+ release, especially in heart failure. However, clear cellular data on PKA-dependent modulation of cardiac RyRs is limited because of difficulty in distinguishing between PKA effects on RyR, phospholamban (PLB), and Ca2+ current. To clarify this, we measured resting Ca2+ sparks in streptolysin-O permeabilized ventricular myocytes from wild-type (WT) and PLB knockout (PLB-KO) mice and transgenic mice expressing only double-mutant PLB (PLB-DM) that lacks the regulatory phosphorylation sites (S16A/T17A). In WT myocytes, cAMP dramatically increased Ca2+ spark frequency (CaSpF) by 2- and 3-fold when [Ca2+] was clamped at 50 and 10 nmol/L (and the SR Ca2+ content also rose by 40% and 50%). However, in PLB-KO and PLB-DM, neither CaSpF nor SR Ca2+ load was changed by the addition of 10 micromol/L cAMP (even with phosphatase inhibition). PKA activation also increased Ca2+ spark amplitude, duration, and width in WT, but not in PLB-KO or PLB-DM. RyR phosphorylation was confirmed by measurements of 32P incorporation on immunoprecipitated RyR. In intact resting myocytes, PKA activation increased CaSpF 2.8-fold in WT, but not in PLB-KO, confirming results in permeabilized myocytes. We conclude that the PKA-dependent increase in myocyte CaSpF and size is entirely attributable to PLB phosphorylation and consequent enhanced SR Ca2+ load. PKA does not seem to have any appreciable effect on resting RyR function in these ventricular myocytes. Moreover, the data provide compelling evidence that elevated intra-SR [Ca2+] increases RyR gating independent of cytosolic [Ca2+] (which was clamped).
Pharmacokinetics of tablet huperzine A in six volunteers. (1995)

Hup-A was absorbed rapidly, distributed widely in the body, and eliminated at a moderate rate.
Both immunity and hyperresponsiveness to Pneumocystis carinii result from transfer of CD4+ but not CD8+ T cells into severe combined immunodeficiency mice. (1992)

The opportunistic pathogen Pneumocystis carinii (Pc) is considered to be the leading cause of morbidity in patients with AIDS. It is important, therefore, to determine the immunological mechanisms of resistance to Pc. We have taken advantage of the lack of both T and B lymphocytes in severe combined immunodeficiency (scid) mice to determine the critical factors in resistance to spontaneously acquired Pc pneumonia. Using adoptive transfer of unfractionated or fractionated lymphocyte subsets or hyperimmune serum from congenic normal donors, we have demonstrated that effective immunity to Pc results from the action of CD4+ but not CD8+ T cells (in the absence of antibody) or from humoral immunity (in the absence of T cells). However, responses of CD4+ T cells (but not antibody) to already well-established burdens of Pc are often accompanied by a fatal hyperinflammatory reaction. The activity of CD4+ T cells against Pc thus illustrates a broadly applicable principle that T cell immunity represents a critical balance between consequences beneficial and harmful to the host.
MESOTHELIN IS A MALIGNANT FACTOR AND THERAPEUTIC VACCINE TARGET FOR PANCREATIC CANCER (2007)

Background: Mesotheline (MSLN) is a GPI-linked glycoprotein, which is overexpressed in several cancer types including mesothelioma, ovarian cancer, and pancreatic cancer, but very little or no expression of MSLN is seen in normal tissues and other cancer types. In this study, we investigated the expression and functions of MSLN in human pancreatic cancer cells, and further determined the effect and mechanism of chimeric virus-like particle (VLP)-hMSLN as a potent candidate for vaccine and immune therapy for pancreatic cancer. Methods: The expression of MSLN in human pancreatic cancer cell lines, HPDE cells, clinical specimens of human pancreatic adenocarcinoma were determined by real-time RT-PCR and Western blot. MSLN stable overexpression and silencing cells were selected in MIA PaCa-2, and BxPC-3 cells using retrovirus vectors. In vitro cell proliferation, migration, and cell cycle were performed by MTS, modified Boyden chamber assay, and flow cytometry analysis, respectively. In vivo tumor growth was performed in subcutaneous and orthotopic nude mice model. C57BL/6J mice were used for vaccine study with VLP-hMSLN. MSLN-specific T cells and Abs were assessed by ELISPOT and ELISA, respectively. Results: The MSLN expression was significantly increased in all four pancreatic cancer cell lines tested, compared with that in HPDE cells (p < 0.05). In 18 of 21 clinical pancreatic carcinoma samples, MSLN was found to be substantially over-expressed compared with the surrounding normal tissues (p < 0.05). Forced expression of MSLN boosts tumor cell proliferation, and migration in vitro by 90% and 300% compared with the vector control cells (p < 0.05), and contributes to tumor progression in nude mouse xenograft model through activation of the STAT3 pathway. Silencing of MSLN decreased cell proliferation, and migration in pancreatic cancer cells by 50% and 70% compared with the vector control cells (p < 0.05), and ablated tumor progression in vivo. Immunization with chimeric VLP which contains surface protein MSLN (VLP-hMSLN) significantly inhibited tumor progression inC57BL/6J mice. The increases in MSLN-specific antibodies and T-cell responses and the decrease in regulatory T cells correlated with reduced tumor progression and prolonged survival. Conclusions: This study revealed novel functions of MSLN and suggested a new therapeutic vaccine strategy whereby MSLN is targeted to control pancreatic cancer progression.
Implants as drug delivery devices for the treatment of eye diseases (2010)

The treatment of diseases affecting the posterior segment of the eye is limited by the difficulty in transporting effective doses of drugs to the vitreous, retina, and choroid. Topically applied drugs are poorly absorbed due to the low permeability of the external ocular tissues and tearing. The blood-retina barrier limits drug diffusion from the systemic blood to the posterior segment, thus high doses of drug are needed to maintain therapeutic levels. In addition, systemic side effects are common. Intraocular injections could be an alternative, but the fast flowing blood supply in this region, associated with rapid clearance rates, causes drug concentration to quickly fall below therapeutic levels. To obtain therapeutic levels over longer time periods, polymeric sustained-drug release systems implanted within the vitreous are being studied for the treatment of vitreoretinal disorders. These systems are prepared using different kinds of biodegradable or non-biodegradable polymers. This review aims to demonstrate the main characteristics of these drug delivery implants and their potential for clinical application.
Functional characterization of four novel PAX8 mutations causing congenital hypothyroidism: new evidence for haploinsufficiency as a disease mechanism (2012)

D46fs is the first PAX8 mutation with confirmed protein instability. Our clinical and in vitro findings together suggest that pure PAX8 haploinsufficiency can cause CH in humans.
PiggyBac Transposon Mutagenesis: A Tool for Cancer Gene Discovery in Mice (2010)

Transposons are mobile DNA segments that can disrupt gene function by inserting in or near genes. Here, we show that insertional mutagenesis by the PiggyBac transposon can be used for cancer gene discovery in mice. PiggyBac transposition in genetically engineered transposon-transposase mice induced cancers whose type (hematopoietic versus solid) and latency were dependent on the regulatory elements introduced into transposons. Analysis of 63 hematopoietic tumors revealed that PiggyBac is capable of genome-wide mutagenesis. The PiggyBac screen uncovered many cancer genes not identified in previous retroviral or Sleeping Beauty transposon screens, including Spic, which encodes a PU.1-related transcription factor, and Hdac7, a histone deacetylase gene. PiggyBac and Sleeping Beauty have different integration preferences. To maximize the utility of the tool, we engineered 21 mouse lines to be compatible with both transposon systems in constitutive, tissue- or temporal-specific mutagenesis. Mice with different transposon types, copy numbers, and chromosomal locations support wide applicability.
Expression of Trop2 Cell Surface Glycoprotein in Normal and Tumor Tissues (2011)

Trop2 is a cell-surface glycoprotein reported to be overexpressed in various types of adenocarcinomas with minimal expression in normal tissues. Recent findings that Trop2 expression correlates with tumor aggressiveness have increased interest in Trop2 as a potential target for cancer immunotherapy. The goal of this study was to extensively evaluate Trop2 expression at the transcript and protein levels in normal and tumor tissues. It was determined that Trop2 is overexpressed on some carcinomas relative to the corresponding normal tissue. However, in human and mouse, Trop2 is highly expressed at both the transcript and protein levels on several essential normal tissues. The findings suggest that the development of therapeutic agents to target Trop2 may require strategies that target Trop2 on malignant tissues in order to minimize potential toxicities to essential normal tissues that also express high levels of Trop2.
1H-1-Benzazepines. The reactions of laevulinic acid and β-benzoylpropionic acid with aniline and methoxyanilines (1978)

Treatment of laevulinic acid with aniline yields 5-methyl-2,3-dihydro- 1H-1-benzazepin-2-one and 5-(2-methyl-5-oxo-1-phenylpyrrolidin-2-yl)-4- oxo-N-phenylpentanamide In contrast, the reaction between ß- benzoylpropionic acid and aniline yields 4-(2-oxo-1,5-diphenyl-2,3- dihydropyrrol-3-ylidene)-N,4-diphenylbutanamide, whose structure is confirmed by an independent synthesis. The yield of the latter type of reaction is enhanced if p-methoxyaniline is used, whereas the desired benzazepine is obtained if m-methoxyaniline is utilized. For example, the reaction between ß-benzoyl-propionic acid and m-methoxyaniline yields 8-methoxy-5-phenyl-2,3-dihydro-1H-1-benzazepine-2-one as the major cyclized product.
Visual Tracking Synchronization as a Metric for Concussion Screening (2010)

Our goal was to determine whether performance variability during predictive visual tracking can provide a screening measure for mild traumatic brain injury (mTBI). Seventeen subjects with chronic postconcussive syndrome and 9 healthy control subjects were included in this study. Eye movements were recorded with video-oculography as the subject visually tracked a target that moved through a circular trajectory. We compared the variability of gaze positional errors relative to the target with the microstructural integrity of white matter tracts as measured by the fractional anisotropy (FA) parameter of diffusion tensor imaging. Gaze error variability was significantly correlated with the mean FA values of the right anterior corona radiata (ACR) and the left superior cerebellar peduncle, tracts that support spatial processing and sustenance of attention, and the genu of the corpus callosum. Because the ACR and the genu are among the most frequently damaged white matter tracts in mTBI, the correlations imply that gaze error variability during visual tracking may provide a useful screening tool for mTBI. Gaze error variability was also significantly correlated with attention and working memory measures in neurocognitive testing; thus, measurement of visual tracking performance is promising as a fast and practical screening tool for mTBI.
Recurrent Dense Deposit Disease After Renal Transplantation: An Emerging Role for Complementary Therapies (2012)

Dense deposit disease is a rare glomerulonephritis caused by uncontrolled stimulation of the alternative complement pathway. Allograft survival after kidney transplantation is significantly reduced by the high rate of disease recurrence. No therapeutic interventions have consistently improved outcomes for patients with primary or recurrent disease. This is the first reported case of recurrent dense deposit disease being managed with eculizumab. Within 4 weeks of renal transplantation, deteriorating graft function and increasing proteinuria were evident. A transplant biopsy confirmed the diagnosis of recurrent dense deposit disease. Eculizumab was considered after the failure of corticosteroid, rituximab and plasmapheresis to attenuate the rate of decline in allograft function. There was a marked clinical and biochemical response following the administration of eculizumab. This case provides the first evidence that eculizumab may have a place in the management of crescentic dense deposit disease. More information is necessary to clarify the effectiveness and role of eculizumab in dense deposit disease but the response in this patient was encouraging. The results of clinical trials of eculizumab in this condition are eagerly awaited.
Effect of Clostridium difficile enterotoxin A on ultrastructure of Chinese hamster ovary cells (1989)

Electron microscopical immunocytochemistry and light microscopy were used to study the effect of Clostridium difficile enterotoxin A (EA) on cultured Chinese hamster ovary (CHO) cells. At 4 degrees C, immunocytochemically detected EA was randomly distributed along the plasma membrane; when cells were subsequently transferred to 37 degrees C, the EA moved into coated pits and coated vesicles within 2 min. Within 2 h of incubation at 37 degrees C with EA, the perinuclear cytoplasm of the CHO cells became highly refractile, and in 4 h, most of the cells were round; however, the majority of rounded cells excluded erythrosin B while remaining firmly attached to the culture dish plastic. When EA was removed from the cultured cells within 2 h, the cells returned to a normal morphology and formed a confluent monolayer. The nuclei of rounded cells were irregularly shaped; cytoplasmic intermediate filaments were collapsed toward the nucleus. Long bundles of parallel, 11-nm-diameter filaments appeared in the nuclei after 3 h of incubation with EA and disappeared by the fourth hour of incubation. Intoxicated cells did not undergo mitosis. Thus, EA was internalized, at least in part, by receptor-mediated endocytosis and subsequently affected the nuclei of CHO cells.
The benefits of event (2000)

A prerequisite of energy-aware scheduling is precise knowledge of any activity inside the computer system. Embedded hardware monitors (e.g., processor performance counters) have proved to offer valuable information in the field of performance analysis. The same approach can be applied to investigate the energy usage patterns of individual threads. We use information about active hardware units (e.g., integer/floating-point unit, cache/memory interface) gathered by event counters to establish a thread-specific energy accounting. The evaluation shows that the correlation of events and energy values provides the necessary information for energy-aware scheduling policies.Our approach to OS-directed power management adds the energy usage pattern to the runtime context of a thread. Depending on the field of application we present two scenarios that benefit from applying energy usage patterns: Workstations with passive cooling on the one hand and battery-powered mobile systems on the other hand.Energy-aware scheduling evaluates the energy usage of each thread and throttles the system activity so that the scheduling goal is achieved. In workstations we throttle the system if the average energy use exceeds a predefined power-dissipation capacity. This makes a compact, noiseless and affordable system design possible that meets sporadic yet high demands in computing power. Nowadays, more and more mobile systems offer the features of reducible clock speed and dynamic voltage scaling. Energy-aware scheduling can employ these features to yield a longer battery life by slowing down low-priority threads while preserving a certain quality of service.
Inhibition of human glioblastoma cell adhesion and invasion by 4-(4'-hydroxylphenyl)-amino-6,7-dimethoxyquinazoline (WHI-P131) and 4-(3'-bromo-4'-hydroxylphenyl)-amino-6,7-dimethoxyquinazoline (WHI-P154). (1998)

Glioblastoma multiforme is a highly invasive primary brain tumor with a disappointingly high local recurrence rate and mortality despite intensive multimodality treatment programs. Therefore, new agents that are capable of inhibiting the infiltration of normal brain parenchyma by glioblastoma cells are urgently needed. Here, we show that the novel quinazoline derivatives 4-(4'-hydroxylphenyl)-amino-6,7-dimethoxyquinazoline (WHI-P131) and 4-(3'-bromo-4'hydroxylphenyl)-amino-6,7-dimethoxyquinazoline (WHI-P154) are potent inhibitors of glioblastoma cell adhesion and migration. Specifically, both compounds inhibited at micromolar concentrations: (a) integrin-mediated glioblastoma cell adhesion to the extracellular matrix proteins laminin, type IV collagen, and fibronectin; (b) integrin-independent epidermal growth factor-induced adhesion of glioblastoma cells to poly-L-lysine-coated tissue culture plates; (c) fetal bovine serum-induced polymerization of actin and actin stress fiber formation as well epidermal growth factor-stimulated formation of focal adhesion plaques in serum-starved glioblastoma cells; and most importantly, (d) glioblastoma cell migration in in vitro assays of tumor cell invasiveness using tumor cell spheroids and/or Matrigel-coated Boyden chambers. Further preclinical development of WHI-P131 and WHI-P154 may provide the basis for the design of more effective adjuvant chemotherapy programs for glioblastoma multiforme.
Significant correlation of monocyte chemoattractant protein-1 expression with neovascularization and progression of breast carcinoma (2001)

The results of this study suggest that MCP-1 may play key roles in macrophage recruitment, in the expression of angiogenic factors, and in the activation of matrix metalloproteinases in patients with breast carcinoma.
Carbazole functionalized luminescent silver(i), gold(i) and gold(iii)–N-heterocyclic carbene complexes: a new synthetic disproportionation approach towards Au(i)–NHC to provide Au(iii)–NHC (2012)

Synthetic, structural and photophysical properties of carbazole functionalized novel procarbenic species 1-(methyl/picolyl)-3-(N-ethylcarbazolyl)-1H benzimidazoliumhexaflurophosphate (1 and 2) and their N-heterocyclic carbene (NHC) complexes of Ag(I) (3 and 4), Au(I) (5 and 6) and Au(III) (7 and 8) are described. According to the solid-state structures, a linear coordination geometry of Ag(I)–NHC (4) and Au(I)–NHC (6) has been established by X-ray diffraction studies; whereas the Au(III)–NHC complex (7) adopts the square planar geometry. The Au(III)–NHC (7 and 8) complexes have been synthesized from Au(I)–NHC (5 and 6) by capitalizing on a novel disproportionation protocol. Furthermore, the Au–Ccarbene bonds in complexes 7 and 8 are inert towards changes in the oxidation state of the metal atom. All the proligands (1 and 2) and complexes (3–8) are luminescent at room temperature.
Release of the neuronal glycoprotein ICAM‐5 in serum after hypoxic‐ischemic injury (2000)

Intercellular adhesion molecule (ICAM)-5 (telencephalin) is unique among the ICAMs, because it is only expressed in somatodendritic membranes of telencephalic neurons. To investigate the fate of ICAM-5 during focal brain injury, we induced hypoxia-ischemia (HI) damage in adult mice by right common carotid artery ligation followed by hypoxia. ICAM-5 was detectable in serum within a 48-hour window after HI injury. In HI brain, dendritic ICAM-5 immunoreactivity was abolished, but it was present in the neuropil and soma of hippocampal pyramidal, dentate granule, and some cortical and striatal neurons. After HI injury, levels of ICAM-5 protein and messenger RNA initially increased, and ICAM-5 messenger RNA expression then decreased, although protein levels continued to increase. Because HI injury induces microglial activation with increases in CD11a/CD18 (lymphocyte function antigen [LFA]-1) counterreceptors to ICAM-5, we investigated whether modulation of interactions between LFA-1 receptors and brain ICAM-5 during HI injury are associated with changes in levels of serum ICAM-5. Intracerebroventricular administration of lipopolysaccharide to activate microglia before HI injury resulted in elevated serum ICAM-5 levels compared with those in mice with only HI injury. Pretreatment with anti-LFA-1 antibodies before HI injury or LFA-1 receptor knockout mice with HI injury had markedly reduced levels of serum ICAM-5. Lipopolysaccharide levels increased, whereas LFA-1 receptor blockade or LFA-1 knockout decreased HI injury in the first 12 hours. These data suggest that during the necrotic phase of HI injury, serum ICAM-5 may be a potential marker for somatodendritic neuronal damage. Ann Neurol 2000;48:590–602
Towards a Multi-hypothesis Road Representation for Automated Driving (2015)

The process of perception inevitably involves uncertainty. In the field of automated driving, however, uncertainty about the roadway -- and especially about the understanding of the roadway -- is yet mostly neglected. In this paper it is argued that this uncertainty should be represented and considered in the process of behavior generation. A road representation capable of representing multiple hypotheses about the roadway is presented. The representation language allows to express where and how hypotheses differ and to infer this information in an efficient way. The focus of this paper is on the qualitative representation of uncertainty.