gebhart/patrepeval huggingface dataset:
Angiogenesis and Lymphangiogenesis in Tumors: Insights from Intravital Microscopy (2002)

A solid tumor is an organ-like structure composed ofcancer cells and host stromal cells, embedded in an extracellular matrix and bathed in interstitial fluid (Jain et al.2002). These cells are nourished by blood vessels madeup of vascular endothelial cells. In addition to supplyingnutrients and removing waste products, these blood vessels serve as a conduit for the spread of cancer cells to distal sites (hematogenic metastases) (Carmeliet and Jain2000). A second vascular system associated with solid tumors is made up of lymphatic endothelial cells. In addition to absorbing excess interstitial fluid and macromolecules to maintain homeostasis, the lymphatic systemserves as a conduit for host immune cells and cancer cellsto reach the draining lymph nodes ( Alitalo and Carmeliet2002; Jain and Fenton 2002). Thus, blocking the formation and function of these two vascular systems has thepotential to arrest tumor growth and metastasis (Folkman2000)...
Repeated voltage biasing improves unit recordings by reducing resistive tissue impedances (2005)

Reactive tissue encapsulation of chronically implanted microelectrode probes can preclude long-term recording of extracellular action potentials. We investigated an intervention strategy for functionally encapsulated microelectrode sites. This method, known as "rejuvenation," involved applying a +1.5 V dc bias to an iridium site for 4 s. Previous studies have demonstrated that rejuvenation resulted in higher signal-to-noise ratios (SNRs) by decreasing noise levels, and reduced 1-kHz site impedances by decreasing the tissue interface resistances. In this study, we have investigated: 1) the duration of a single-voltage bias session and 2) the efficacy of multiple sessions. These questions were addressed through electrophysiological recordings, cyclic voltammetry, and modeling the electrode-tissue interface via an equivalent circuit model fit to impedance spectroscopy data. In the six implants studied, we found SNRs improved for 1-7 days with a peak typically occurring within 24 h of the voltage bias. Root-mean square (RMS) noise of the extracellular recordings decreased for 1-2 days, which paralleled a similar decrease in the adsorbed tissue resistance (Ren) from the model. Implants whose SNR effects lasted more than a day showed stabilized reductions in the extracellular tissue resistance (Rex) and cellular membrane area (Am). Subsequent stimulus sessions were found to drop neural tissue parameters consistently to levels observed immediately after surgery. In most cases, these changes did parallel an improvement in SNR. These findings suggest that rejuvenation may be a useful intervention strategy to prolong the lifetime of chronically implanted microelectrodes.
Nongenomic Activation of the Calcium Message System by Vitamin D Metabolites in Osteoblast-like Cells (1990)

1,25-dihydroxycholecalciferol (1,25(OH)2D3) rapidly affects calcium (Ca2+) transport in several cell systems, suggesting physiological actions independent of genomic activation. To test this hypothesis, we studied immediate to early effects (0.5-300 sec) of 1,25(OH)2D3 on cytosolic Ca2+ [Ca2+]i in single osteogenic sarcoma ROS 17/2.8 cells loaded with fura-2. An acute rise in [Ca2+]i was observed in 40% of the cells following addition of 1,25(OH)2D3, with a threshold concentration of 10(-11) M. In most cases, the [Ca2+]i rise was transient, with return to baseline within 1 min; less frequently a more prolonged effect was observed, with variable recovery times. 25-hydroxycholecalciferol (25(OH)D3) reproduced the effect of 1,25(OH)2D3 on [Ca2+]i, with equal potency and similar responses, whereas 24,25-dihydroxycholecalciferol, 1 alpha-hydroxycholecalciferol, and 22 oxa-1,25(OH)2D3 were not effective. 1,25(OH)2D3 also increased [Ca2+]i in ROS 24/1 cells, which are defective of receptors for the vitamin D metabolites. At high doses (10(-8)-10(-7) M) of 1,25(OH)2D3 the [Ca2+]i rise in ROS 17/2.8 cells was due to both influx of extracellular Ca2+ and release of Ca2+ from intracellular stores, as the effect was only partially inhibited by Ca2(+)-channel blockade by nifedipine. At low doses (10(-9)-10(-10) M), the effect was entirely dependent on extracellular Ca2+. 1,25(OH)2D3 also increased the production of inositol 1,4,5 trisphosphate (Ins(1, 4, 5)P3) and diacylglycerol, at a threshold dose of 10(-9) M, indicating activation of phospholipase C (PLC). In two thirds of the cells studied, a second addition of 1,25(OH)2D3 within 5 min to cells prestimulated with equimolar doses of the vitamin D metabolite resulted in a [Ca2+]i transient of higher amplitude than the first, a phenomenon occurring at all doses of the hormone, and associated with production of Ins(1, 4, 5)P3. This response amplification was not produced by 25(OH)D3, and pretreatment with 1 alpha(OH)D3 did not significantly enhance 1,25(OH)2D3-induced production of Ins(1, 4, 5)P3. In conclusion, activation of the Ca2+ message system by vitamin D metabolites is a rapid, nongenomic effect; 1,25(OH)2D3 specifically activates both PLC and dihydropyridine-sensitive Ca2+ channels, and "primes" the cells to respond with an enhanced [Ca2+]i rise to a subsequent homologous stimulation; the presence of both the 1 alpha and 25 hydroxyl groups is necessary to express the full hormonal action of vitamin D on [Ca2+]i.
Identification of novel loci affecting entry of Salmonella enteritidis into eukaryotic cells (1992)

There are an estimated 2 million cases of salmonellosis in the United States every year. Unlike the incidence of many infectious diseases, the incidence of salmonellosis in the United States and other developed countries has been rising steadily over the past 30 years, and the disease now accounts for 10 to 15% of all cases of acute gastroenteritis in the United States. The infecting organism is ingested and must traverse the intestinal epithelium to reach its preferred site for multiplication, the reticuloendothelial system. Despite several recent studies, the genetic basis of the invasion process is poorly understood. An emerging theme from these studies is that wild-type Salmonella organisms probably have several chromosomal loci that are required for the most efficient level of invasion. In this study, we have identified and characterized 13 TnphoA insertion mutants of Salmonella enteritidis CDC5 that exhibit altered invasion phenotypes. The mutants were identified by screening a bank of TnphoA insertions in S. enteritidis CDC5str for their invasion phenotype in three tissue culture cell lines (HEp-2, CHO, and MDCK). These 13 mutants were separated into six classes based on their invasive phenotypes in the tissue culture cell lines. Several mutants were defective for entry of some cell lines but not for others, while two mutants (SM6 and SM7) were defective for entry into all three tissue culture cell lines. This suggests that Salmonella spp. may express more than one invasion pathway. Southern analysis and chromosomal mapping indicated that as many as nine chromosomal loci may contribute to the invasion phenotype. It is becoming clear that the invasive phenotype of Salmonella spp. is multifactorial and more complex than that of some other invasive members of the family Enterobacteriaceae.
RET/PTC oncogene activation is an early event in thyroid carcinogenesis. (1995)

RET/PTC oncogene activation occurs in about 20% of human thyroid papillary carcinomas. However, it is not known yet whether it is an early or late event in the process of thyroid carcinogenesis. Here we demonstrate, by using a combined immunohistochemical and reverse transcriptase-polymerase chain reaction based approach, that RET/PTC activation is present in 11 out of 26 occult thyroid papillary carcinomas analysed. Therefore, we conclude that it represents an early event in the process of thyroid cell transformation.
폴란드민속문학에 대한 고찰 (2002)

폴란드는 체코 그리고 슬로바키아와 함께 서슬라브 세계에 속한다. 서슬라브민족들은 일찍부터 서유럽으로부터 기독교와 라틴문자를 받아들였다. 따라서 그들의 문화는 서유럽에 가깝다. 966년에 카톨릭을 받아들인 이후 폴란드사람들은 유럽인들 가운데에서도 매우 독실한 카톨릭교도로서 유명하다. 하지만 아쉽게도 카톨릭은 폴란드민속의 상당 부분을 미신이라 하여 파괴하고...
Structural Versatility of Anion−π Interactions in Halide Salts with Pentafluorophenyl Substituted Cations (2008)

A series of pentafluorophenyl substituted ammonium, iminium, amidinium, and phosphonium halides are presented which show extensive anion-pi interactions. Hereby, the well-known anion-donor-pi-acceptor as well as "eta6" anion-pi-complex type interactions are observed. The latter is supported by fixation of the anion on top of the aromatic system through hydrogen bonding. This arrangement was investigated by theoretical methods showing a highly attractive anion-pi interaction. In addition an eta2-type coordination of the anions to only two C-atoms of the electron-deficient ring system is described.
Rotating Shiftwork Schedules: Can We Enhance Physician Adaptation to Night Shifts? (1997)

Although the experimental intervention was successfully implemented, it failed to significantly improve attending physicians' sleep, performance, or mood on night shifts. A decrease in speed of intubation, vigilance reaction times, and subjective alertness was evident each time the physicians rotated through the night shift. These findings plus the limited sleep across all conditions and shifts suggest that circadian-mediated disruptions of waking neurobehavioral functions and sleep deprivation are problems in EPs.
Pharmacokinetics and Safety of S/GSK1349572, a Next-Generation HIV Integrase Inhibitor, in Healthy Volunteers (2009)

S/GSK1349572 is a novel integrase inhibitor with potent in vitro anti-HIV activity, an in vitro resistance profile different from those of other integrase inhibitors, and favorable preclinical safety and pharmacokinetics (PK). Randomized, double-blind, placebo-controlled single-dose and multiple-dose, dose escalation studies evaluated the PK, safety, and tolerability of S/GSK1349572 for healthy subjects. In the single-dose study, two cohorts of 10 subjects each (8 active, 2 receiving placebo) received suspension doses of 2, 5, 10, 25, 50, and 100 mg in an alternating panel design. In the multiple-dose study, three cohorts of 10 subjects each (8 active, 2 receiving placebo) received suspension doses of 10, 25, and 50 mg once daily for 10 days. A cytochrome P450 3A (CYP3A) substudy with midazolam was conducted with the 25-mg dose. Laboratory testing, vital signs, electrocardiograms (ECGs), and PK sampling were performed at regular intervals. S/GSK1349572 was well tolerated. Most adverse events (AEs) were mild, with a few moderate AEs reported. Headache was the most common AE. No clinically significant laboratory trends or ECG changes were noted. PK was linear over the dosage range studied. The steady-state geometric mean area under the concentration-time curve over a dosing interval (AUC(0-tau)) and maximum concentration of the drug in plasma (C(max)) ranged from 16.7 microg.h/ml (coefficient of variation [CV], 15%) and 1.5 microg/ml (CV, 24%) at a 10-mg dose to 76.8 microg.h/ml (CV, 19%) and 6.2 microg/ml (CV, 15%) at a 50-mg dose, respectively. The geometric mean steady-state concentration at the end of the dosing interval (C(tau)) with a 50-mg dose was 1.6 microg/ml, approximately 25-fold higher than the protein-adjusted 90% inhibitory concentration (0.064 microg/ml). The half-life was approximately 15 h. S/GSK1349572 had no impact on midazolam exposure, indicating that it does not modulate CYP3A activity. The PK profile suggests that once-daily, low milligram doses will achieve therapeutic concentrations.
Hydrophilic CdSe−ZnS Core−Shell Quantum Dots with Reactive Functional Groups on Their Surface (2010)

We synthesized macromolecular ligands for CdSe-ZnS core-shell quantum dots incorporating multiple thiol groups, poly(ethylene glycol) chains, and either carboxylic acids or primary amines along a common poly(methacrylate) backbone. The thiol groups encourage the adsorption of these macromolecular constructs on the ZnS shell of the nanoparticles, and the poly(ethylene glycol) chains impose hydrophilic character on the resulting assemblies. Indeed, the coated quantum dots are readily soluble in water and are stable under these conditions for months over a broad pH range (4.0-12.0) and even in the presence of large salt concentrations. In addition, these nanoparticles have relatively small hydrodynamic diameters (17-30 nm) and good quantum yields (0.3-0.4). Furthermore, the pendant carboxylic acids or primary amines of the macromolecular ligands can be exploited to modify the quantum dots after the adsorption of the polymers on their surface. For example, boron dipyrromethene dyes can be connected to the hydrophilic quantum dots on the basis of amide bond formation to encourage the transfer of energy from the luminescent CdSe core to the organic dyes. Our hydrophilic nanoparticles can also cross the membrane of Chinese hamster ovarian cells and accumulate in the cytosol with limited nuclear localization. Moreover, the internalized quantum dots are not cytotoxic and have essentially no influence on cell viability. Thus, our strategy for the preparation of biocompatible quantum dots can evolve into the development of valuable luminescent probes with nanoscaled dimensions and optimal photophysical properties for a diversity of biomedical applications.
Molecular Interactions of Cyclam and Bicyclam Non-peptide Antagonists with the CXCR4 Chemokine Receptor (2001)

The non-peptide CXCR4 receptor antagonist AMD3100, which is a potent blocker of human immunodeficiency virus cell entry, is a symmetrical bicyclam composed of two identical 1,4,8,11-tetraazacyclotetradecane (cyclam) moieties connected by a relatively rigid phenylenebismethylene linker. Based on the known strong propensity of the cyclam moiety to bind carboxylic acid groups, receptor mutagenesis identified Asp(171) and Asp(262), located in transmembrane domain (TM) IV and TM-VI, respectively, at each end of the main ligand-binding crevice of the CXCR4 receptor, as being essential for the ability of AMD3100 to block the binding of the chemokine ligand stromal cell-derived factor (SDF)-1alpha as well as the binding of the receptor antibody 12G5. The free cyclam moiety had no effect on 12G5 binding, but blocked SDF-1alpha binding with an affinity of 3 microm through interaction with Asp(171). The effect on SDF-1alpha binding of a series of bicyclam analogs with variable chemical linkers was found to rely either only on Asp(171), i.e. the bicyclams acted as the isolated cyclam, or on both Asp(171) and Asp(262), i.e. they acted as AMD3100, depending on the length and the chemical nature of the linker between the two cyclam moieties. A positive correlation was found between the dependence of these compounds on Asp(262) for binding and their potency as anti-human immunodeficiency virus agents. It is concluded that AMD3100 acts on the CXCR4 receptor through binding to Asp(171) in TM-IV and Asp(262) in TM-VI with each of its cyclam moieties, and it is suggested that part of its function is associated with a conformational constraint imposed upon the receptor by the connecting phenylenebismethylene linker.
Antidepressant Effect of Combined Ketamine and Electroconvulsive Therapy on Patients With Major Depressive Disorder: A Randomized Trial (2015)

This study could not show the effect of Ketamine on depression recovery in a 2-week follow-up period. Nevertheless, Ketamine may provide a better cognitive performance in patients under ECT.
Novel RGD lipopeptides for the targeting of liposomes to integrin-expressing endothelial and melanoma cells (2004)

RGD peptides targeting alphav-integrins are promising ligands for the generation of vascular targeting agents. We isolated from phage display RGD motif libraries novel high-affinity cyclic RGD peptides by selection on either endothelial or melanoma cells. Although the starting sequences contained only two cysteine residues flanking the RGD motif, several of the isolated peptides possessed four cysteine residues. A high-affinity peptide (RGD10) constrained by only one disulfide bond was used to generate novel lipopeptides composed of a lipid anchor, a short flexible spacer and the peptide ligand conjugated to the spacer end. Incorporation of RGD10 lipopeptides into liposomes resulted in specific and efficient binding of the liposomes to integrin-expressing cells. In vivo experiments applying doxorubicin-loaded RGD10 liposomes in a C26 colon carcinoma mouse model demonstrated improved efficacy compared with free doxorubicin and untargeted liposomes.
Antidiabetogenic action of glucagon‐like peptide‐1 related to administration relative to meal intake in subjects with type 2 diabetes (2001)

GLP-1 reduced postprandial hyperglycaemia in subjects with type 2 diabetes regardless of administration at the onset of meal intake or at 30 or 60 min after start of meal intake, although the mechanism of the antidiabetogenic action of GLP-1 depended on administration versus meal intake. Thus, when administered at the start of a meal, GLP-1 was antidiabetogenic mainly through retarding gastric emptying, whereas when given at 30 or 60 min after meal ingestion, changes in islet hormone secretion seem to be predominant.
Genetic immunization with the free human chorionic gonadotropin beta subunit elicits cytotoxic T lymphocyte responses and protects against tumor formation in mice. (1997)

The free beta subunit of human chorionic gonadotropin (hCG beta) is produced and secreted by human lung, bladder, and pancreatic tumors. We attempted to generate cytotoxic T lymphocytes (CTL) with activity against free hCG beta-producing tumors by genetic immunization using a construct containing a beta subunit expressing cDNA. To assess CTL activity in vivo, a cloned syngeneic SP2/O myeloma call line was established that constitutively expresses the free hCG beta protein. Inoculation of this cell line into BALB/c mice produced large tumors within 2 weeks. However, mice immunized with the free hCG beta expression construct demonstrated a marked reduction of tumor size and weight compared with animals immunized with mock DNA ("empty" plasmid). Indeed, 30% of immunized mice were tumor-free after 3 months and thus considered long-term survivors. Inhibition of tumor growth was strongly associated with the level of CTL activity present in CD8+ cells derived from the spleen. In addition, immunized mice developed high titer anti-hCG beta antibodies that neutralized the biologic effects of the intact hCG glycoprotein hormone on its cellular receptor as well. These results illustrate that substantial cellular and humoral immune responses to the free hCG beta subunit may be generated by DNA immunization. This study thus presents a potential approach to inhibiting growth of human tumor cells that produce and secrete the free hCG beta protein.
Visible Light Photocatalysis of [2+2] Styrene Cycloadditions by Energy Transfer (2012)

Hip to be square: Styrenes participate in [2+2] cycloadditions upon irradiation with visible light in the presence of an iridium(III) polypyridyl complex. In contrast to previous reports of visible light photoredox catalysis, the mechanism of this process involves photosensitization by energy transfer and not electron transfer.
[A study on the distribution of metastases at autopsy in 70 patients with ovarian cancer]. (1994)

A total of 6,457 autopsy protocols were reviewed to identify 70 women who died of ovarian cancer. 1. Epithelial tumors were the most common tumor (74%). Twenty% were germ cell tumors. There were two cases each of sarcoma and stromal cell tumors. 2. The patients with germ cell tumors were younger than those with epithelial tumors. The duration of the epithelial tumor disease was longer than that of germ cell tumor. 3. The most common mechanism of death was carcinomatosis (69%). Eight of 70 patients (11%) had respiratory failure. One case of subacute cor pulmonale was due to tumor embolization. One case had a rupture of the portal vein. 4. The peritoneum was most frequently involved in every tumor (87%). The liver was the second most frequent site (73%). Other frequent metastatic sites included the lungs (44%), and spleen (47%). Lymph nodes including the paraaortic, pelvic and mesenteric were also very frequent metastatic sites. 5. CDDP containing regimens were used in 33 cases (47%). FAMT regimen was the second most common treatment (15.7%). Another common treatment is whole abdominal radiotherapy (14%). The patients treated with the CDDP containing regimen had a significantly longer survival time (23.4 months) than those treated with FAMT (19.2 months) and others (13.6 months). 6. For metastasis to the lungs, spleen and mesenteric lymph nodes the patients treated with the CDDP containing regimen were more numerous than those treated without CDDP. For metastasis to the kidneys, the patients treated without CDDP were more numerous than those treated with CDDP containing regimens.(ABSTRACT TRUNCATED AT 250 WORDS)
Effects of formaldehyde fixation on protein secondary structure: a calorimetric and infrared spectroscopic investigation. (1991)

We investigated the effects of formaldehyde fixation on the secondary structure of isolated proteins (bovine serum albumin, ribonuclease A, and hemoglobin) using high-sensitivity differential scanning calorimetry and Fourier transform infrared spectroscopy. Whereas thermograms obtained by scanning calorimetry on unfixed purified proteins demonstrated denaturation transitions in the 70-90 degrees C temperature range, the thermograms showed no denaturation transitions in this temperature range when the proteins had been placed in formaldehyde solutions. Thus, fixation destroyed the denaturation transition of bovine serum albumin, ribonuclease A, and hemoglobin. Infrared spectra obtained on the unfixed and fixed proteins were essentially identical. This demonstrates that the "fixed" proteins retain the secondary structure present before fixation. We therefore conclude that the cross-linking of proteins that occurs in the process of formaldehyde fixation "locks in" the secondary structure of these protein molecules.
Direct conversion of glucose to 5-(hydroxymethyl)furfural in ionic liquids with lanthanide catalysts (2010)

The direct conversion of glucose to 5-(hydroxymethyl)furfural (HMF) in ionic liquids with lanthanide catalysts was examined in search of a possibly more environmentally feasible process not involving chromium. The highest HMF yield was obtained with ytterbium chloride or triflate together with alkylimidazolium chlorides. Notably, a higher reactivity was observed when the hydrophobicity of the imidazolium cation was increased, in contrast to analogous chromium catalyst systems. This indicates a different reaction mechanism for the lanthanides than for the chromium catalyst systems.
Uncommon Side Effects Associated with Olanzapine (2003)

Olanzapine (Zyprexa) is one of the novel atypical antipsychotics that act as a serotonin-dopamine receptor antagonist. Its use is increasing in frequency among psychiatrists to treat both the positive and negative symptoms of schizophrenia. It is also becoming a commonly prescribed antipsychotic because of its low association with dystonia and other extrapyramidal side effects. More commonly, sedation, weight gain, and transient, non-dose-dependent, symptomatic elevations in liver enzymes are seen with the use of this drug [1] [2] [3].
Clinical inhibition of CYP2D6‐catalysed metabolism by the antianginal agent perhexiline (2004)

Perhexiline significantly inhibits CYP2D6-catalysed metabolism in angina patients. The plasma cis-OH-perhexiline/perhexiline ratio may help to both phenotype patients and predict those in whom perhexiline may be most likely to cause clinically significant metabolic inhibition.