gebhart/patrepeval huggingface dataset:
Acoustic Standing Wave Manipulation of Particles and Cells in Microfluidic Chips (2009)

The rise of MEMS and µTAS techniques has created a whole new family of microfluidic devices for a wide range of chemical and biomedical analyses to be performed on small Lab-on-a-chip platforms. The operations often include small samples of particle or cell suspensions on which separation, mixing, trapping or sorting is performed. External fields and forces are used for these operations, and this thesis is specifically focused the development of ultrasonic standing wave technology and the use of acoustic force fields to perform bioanalytical unit operations. The combination of acoustic standing waves and the laminar flow in microfluidics has proven to be well suited for performing particle and cell separation. The fundamental acoustic separator used in this thesis consists of a microfluidic flow channel with a three way flow splitter (trifurcation) in the end of the channel. An acoustic standing wave field is applied to the main flow channel by attaching the transducer underneath the chip. The acoustic standing wave is however obtained perpendicular to the axial propagation of the wave field and the direction of the flow. The half wavelength resonance affects rigid particles or cells driving them into the acoustic pressure node while liquid spheres having other density and compressibility properties may move to the pressure antinode. This enables acoustic separation of different particle types. Blood has proven to be very suitable for acoustic cell manipulation. An application where lipid particles can be removed acoustically from shed blood from open heart surgery is demonstrated. An application for acoustic plasmapheresis is also shown where high quality blood plasma is generated. Different separator designs, device material, and the influence of the separation channel cross-section design are also investigated.
In vivo and in vitro characterization of antalarmin, a nonpeptide corticotropin-releasing hormone (CRH) receptor antagonist: suppression of pituitary ACTH release and peripheral inflammation. (1996)

Corticotropin-releasing hormone (CRH) secreted from the hypothalamus is the major regulator of pituitary ACTH release and consequent glucocorticoid secretion. CRH secreted in the periphery also acts as a proinflammatory modulator. CRH receptors (CRH-R1, R2alpha, R2beta) exhibit a specific tissue distribution. Antalarmin, a novel pyrrolopyrimidine compound, displaced 12SI-oCRH binding in rat pituitary, frontal cortex and cerebellum, but not heart, consistent with antagonism at the CRHR1 receptor. In vivo antalarmnin (20 mg/kg body wt.) significantly inhibited CRH-stimulated ACTH release and carageenin-induced subcutaneous inflammation in rats. Antalarmin, or its analogs, hold therapeutic promise in disorders with putative CRH hypersecretion, such as melancholic depression and inflammatory disorders.
T Cell Activation Antigen, CD26, as a Cofactor for Entry of HIV in CD4 + Cells (1993)

The CD4 molecule is essential for binding HIV particles, but is not sufficient for efficient viral entry and infection. The cofactor was shown to be dipeptidyl peptidase IV (DPP IV), also known as CD26. This serine protease cleaves its substrates at specific motifs; such motifs area also highly conserved in the V3 loops of HIV-1, HIV-2, and related simian isolates. Entry of HIV-1 or HIV-2 into T lymphoblastoid and monocytoid cell lines was inhibited by a specific monoclonal antibody against DPP IV or specific peptide inhibitors of this protease. Coexpression of human CD4 and CD26 in murine NIH 3T3 cells rendered them permissive to infection by HIV-1 and HIV-2. These observations could provide the basis for developing simple and specific inhibitors of HIV and open a possibility for vaccine development.
Expression of normal and novel glucokinase mRNAs in anterior pituitary and islet cells (1991)

The glucose-phosphorylating enzyme glucokinase likely plays an important role in regulating glucose-stimulated insulin secretion from the islets of Langerhans and has previously been thought to be expressed only in that tissue and in liver. In this study, we demonstrate high levels of glucokinase mRNA in the anterior pituitary cell line AtT20ins, which has been engineered to secrete correctly processed insulin, as well as in primary anterior pituitary tissue. Unlike islet or liver cells, expression of glucokinase mRNA in anterior pituitary cells was not accompanied by expression of the high Km glucose transporter (GLUT-2) mRNA. The glucokinase transcript in anterior pituitary cells was similar in size to islet glucokinase mRNA, which has a unique, elongated 5'-end relative to the liver glucokinase message. Amplification and sequence analysis of the glucokinase mRNA expressed in islets, RIN1046-38 cells, and anterior pituitary cells confirmed that the glucokinase transcripts in these cell types contain the same 5'-sequence. In addition, a novel alternative transcript was identified that contains a 52-nucleotide deletion and that predicts a 58-amino acid peptide as a result of a frame shift. Both the deleted and undeleted transcripts were found in islets, RIN cells, and AtT20ins cells, whereas only the deleted product was identified in primary anterior pituitary tissue. An antibody prepared against a peptide found at the N terminus of the islet isoform of glucokinase easily detected a protein with a size predicted by the undeleted transcript in extracts prepared from islets, RIN1046-38 cells, and AtT20ins cells. Since both the glucokinase protein and mRNA are naturally expressed in AtT20ins and RIN1046-38 cells, we compared the effect of varying concentrations of glucose on insulin secretion from the two lines. Insulin secretion from RIN1046-38 cells was stimulated by glucose in a dose-dependent manner over the range 0-2.5 mM, where it reached a maximum. AtT20ins cells, in contrast, exhibited no response to glucose at any concentration tested, despite the fact that insulin secretion from both cell lines was stimulated by incubation with dibutyryl cAMP. We conclude that glucokinase expression in AtT20ins cells may be necessary, but is not sufficient to confer glucose-stimulated insulin secretion.
Extra- and Intracellular pH in the Brain during Seizures and in the Recovery Period following the Arrest of Seizure Activity (1985)

The objective of the study was to estimate changes in extracellular pH (pHe) and intracellular pH (pHi) during seizures and in the recovery period following the arrest of seizure activity. Seizures of 5- and 20-min duration were induced in rats by fluorothyl added to the insufflated gas mixture, and recovery for 5, 15, and 45 min was instituted by withdrawal of the fluorothyl supply following 20 min of continuous seizures. Changes in pHe were measured by double-barreled, liquid ion-exchange pH microelectrodes, and in pHi by the CO2 method, following estimation of tissue PCO2 and extracellular fluid (ECF) volume. The animals were either normoxic or rendered moderately hypoxic (arterial PO2 40-50 mm Hg). Upon induction of seizures in normoxic animals, pHe decreased by a mean of 0.36 unit, the values being identical at 5 and 20 min. In moderate hypoxia, seizures sustained for 20 min were accompanied by a further fall in pHe (mean decrease 0.51 unit). The changes in pHe seemed mainly to reflect the nonionic diffusion of lactic acid from cells to the ECF (tissue lactate levels approximately 10 and 15 mumol g-1 during seizures in normoxic and hypoxic animals, respectively). However, the gradual fall in pHe attributable able to lactic acid production was preceded by rapid acidification, sometimes exceeding the steady-state values subsequently attained. This acidification was interpreted to reflect spreading depression and fast transcellular Na+/H+ exchange. Following cessation of seizure discharge, pHe normalized at a surprisingly slow rate, with some acidosis persisting even after 45 min. The difference between cerebrovenous and arterial PCO2 was reduced during seizures and increased in the recovery period, probably reflecting alterations in the blood flow/metabolic rate coupling. Impedance changes were slight, indicating only minor changes in ECF volume. Changes in pHi after 5 min of seizures ranged from 0.20 (normoxic animals) to 0.32 (hypoxic animals) unit, the pHi values after 20 min being 0.07-0.08 unit higher. The results suggest the regulation of pHi during ongoing seizures. Upon arrest of seizure activity, pHi rapidly increased to normal and subsequently to supranormal values. Postepileptic intracellular alkalosis occurred at a time when pHe was still reduced and in spite of the fact that tissue lactate values had not normalized. It is concluded that the rapid normalization of pHi and overt alkalosis were caused by the simultaneously occurring oxidation of lactate, with the removal of a stoichiometrical amount of H+, and the extrusion of H+ from cells, possibly via a Na+/H+ exchanger, the latter probably delaying normalization of pHe.
Selective Estrogen Receptor Modulator (SERM) Lasofoxifene Forms Reactive Quinones Similar to Estradiol (2012)

The bioactivation of both endogenous and equine estrogens to electrophilic quinoid metabolites has been postulated as a contributing factor in carcinogenic initiation and/or promotion in hormone sensitive tissues. Bearing structural resemblance to estrogens, extensive studies have shown that many selective estrogen receptor modulators (SERMs) are subject to similar bioactivation pathways. Lasofoxifene (LAS), a third generation SERM which has completed phase III clinical trials for the prevention and treatment of osteoporosis, is currently approved in the European Union for this indication. Previously, Prakash et al. (Drug Metab. Dispos. (2008) 36, 1218-1226) reported that similar to estradiol, two catechol regioisomers of LAS are formed as primary oxidative metabolites, accounting for roughly half of the total LAS metabolism. However, the potential for further oxidation of these catechols to electrophilic o-quinones has not been reported. In the present study, LAS was synthesized and its oxidative metabolism investigated in vitro under various conditions. Incubation of LAS with tyrosinase, human liver microsomes, or rat liver microsomes in the presence of GSH as a trapping reagent resulted in the formation of two mono-GSH and two di-GSH catechol conjugates which were characterized by liquid chromatography-tandem mass spectrometry (LC-MS/MS). Similar conjugates were also detected in incubations with P450 3A4, P450 2D6, and P450 1B1 supersomes. Interestingly, these conjugates were also detected as major metabolites when compared to competing detoxification pathways such as glucuronidation and methylation. The 7-hydroxylasofoxifene (7-OHLAS) catechol regioisomer was also synthesized and oxidized either chemically or enzymatically to an o-quinone that was shown to form depurinating adducts with DNA. Collectively, these data show that analogous to estrogens, LAS is oxidized to catechols and o-quinones which could potentially contribute to in vivo toxicity for this SERM.
Direct printing of polymer microstructures on flat and spherical surfaces using a letterpress technique (2002)

We have developed a letterpress technique capable of printing polymer films with micrometer scale feature sizes onto flat or spherically shaped nonporous substrates. This printing technique deposits polymer only in desired regions thereby eliminating subsequent developing and subtraction steps. Flat or curved printing plates, which are fabricated from either rigid or deformable materials, are used to transfer thin molten polymer films onto flat target substrates. By deforming the printing plates into a spherical shape, it is also possible to print patterned films onto the concave side of a spherically deformed target substrate. These printed films serve as good resists for both wet chemical etching and reactive ion etching. Interferometric measurements of the polymer film thickness are used to probe physical mechanisms affecting printing instabilities, pattern fidelity, and edge resolution. Our experimental study indicates that this letterpress technique may prove suitable for high-throughput device fabrication involving large-area microelectronics.
Acid-catalysed rearrangements of trans- and cis-1-acetoxy-3,4-epoxypentane and 1-acetoxy-4,5-epoxyhexane (1973)

Acid-catalysed rearrangement of trans- and cis-1-acetoxy-3,4-cpoxypentanes and 1-acetoxy-4,5-epoxyhexanes give cis- and trans-2-methyl-3-acetoxytetrahydrofuran and threo- and erythro-2-(1-acetoxyethyl)tetrahydrofuran respectively with retention of configuration at the epoxide carbon atoms; the mechanism is consistent with the intermediary of orthoesters.
Expression of a coriander desaturase results in petroselinic acid production in transgenic tobacco. (1992)

Little is known about the metabolic origin of petroselinic acid (18:1 delta 6cis), the principal fatty acid of the seed oil of most Umbelliferae, Araliaceae, and Garryaceae species. To examine the possibility that petroselinic acid is the product of an acyl-acyl carrier protein (ACP) desaturase, Western blots of coriander and other Umbelliferae seed extracts were probed with antibodies against the delta 9-stearoyl-ACP desaturase of avocado. In these extracts, proteins of 39 and 36 kDa were detected. Of these, only the 36-kDa peptide was specific to tissues which synthesize petroselinic acid. A cDNA encoding the 36-kDa peptide was isolated from a coriander endosperm cDNA library, placed under control of the cauliflower mosaic virus 35S promoter, and introduced into tobacco by Agrobacterium tumefaciens-mediated transformation. Expression of this cDNA in transgenic tobacco callus was accompanied by the accumulation of petroselinic acid and delta 4-hexadecenoic acid, both of which were absent from control callus. These results demonstrate the involvement of a 36-kDa putative acyl-ACP desaturase in the biosynthetic pathway of petroselinic acid and the ability to produce fatty acids of unusual structure in transgenic plants by the expression of the gene for this desaturase.
Synthesis of Organic Dye-Impregnated Silica Shell-Coated Iron Oxide Nanoparticles by a New Method (2008)

A new method for preparing magnetic iron oxide nanoparticles coated by organic dye-doped silica shell was developed in this article. Iron oxide nanoparticles were first coated with dye-impregnated silica shell by the hydrolysis of hexadecyltrimethoxysilane (HTMOS) which produced a hydrophobic core for the entrapment of organic dye molecules. Then, the particles were coated with a hydrophilic shell by the hydrolysis of tetraethylorthosilicate (TEOS), which enabled water dispersal of the resulting nanoparticles. The final product was characterized by X-ray diffraction, transmission electron microscopy, Fourier transform infrared spectroscopy, photoluminescence spectroscopy, and vibration sample magnetometer. All the characterization results proved the final samples possessed magnetic and fluorescent properties simultaneously. And this new multifunctional nanomaterial possessed high photostability and minimal dye leakage.
Cannabinoid CB2 Receptor as a New Phototherapy Target for the Inhibition of Tumor Growth (2014)

The success of targeted cancer therapy largely relies upon the selection of target and the development of efficient therapeutic agents that specifically bind to the target. In the current study, we chose a cannabinoid CB2 receptor (CB2R) as a new target and used a CB2R-targeted photosensitizer, IR700DX-mbc94, for phototherapy treatment. IR700DX-mbc94 was prepared by conjugating a photosensitizer, IR700DX, to mbc94, whose binding specificity to CB2R has been previously demonstrated. We found that phototherapy treatment using IR700DX-mbc94 greatly inhibited the growth of CB2R positive tumors but not CB2R negative tumors. In addition, phototherapy treatment with nontargeted IR700DX did not show significant therapeutic effect. Similarly, treatment with IR700DX-mbc94 without light irradiation or light irradiation without the photosensitizer showed no tumor-inhibitory effect. Taken together, IR700DX-mbc94 is a promising phototherapy agent with high target-specificity. Moreover, CB2R appears to have great potential as a phototherapeutic target for cancer treatment.
Telomerase Activity in Benign and Malignant Thyroid Tumors (1997)

Thyroid nodules are found in 5% to 10% of the population. While these nodules carry only a 5% to 10% risk of malignancy, tests that complement fine-needle aspiration (FNA) cytology in preoperative diagnosis and risk stratification are lacking. Telomerase is a ribonucleoprotein polymerase with activity found in many malignant tissues, but absent from most normal adult tissue. In this study, we have investigated telomerase activity in 24 thyroid tumors, 14 matched adjacent thyroid tissues, and 3 chronic thyroiditis tissue samples. Using a telomeric repeat amplification protocol (TRAP) assay on frozen tissue, telomerase activity was detected in 11 of 20 thyroid carcinomas, including 10 of 14 papillary carcinomas and a Hurthle cell carcinoma. Telomerase activity was not detected in 4 benign adenomas, 3 follicular carcinomas, or a single case each of medullary and anaplastic thyroid carcinoma. Telomerase activity was detected in 3 of 14 samples of adjacent thyroid tissue from patients with thyroid tumors. Interestingly, all 3 cases of adjacent thyroid tissue that tested positive had a moderate to marked degree of chronic inflammation. In addition, 3 of 3 samples from chronic thyroiditis specimens tested positive for telomerase activity. When tumor invasiveness (vascular and/or capsular) was compared with telomerase activity in papillary carcinomas, only 1 of 4 telomerase-negative tumors was invasive, while 6 of 10 of telomerase-positive tumors were invasive. Moreover, 6 of 7 invasive papillary carcinomas had telomerase activity. In summary, this is the first report of telomerase activity in thyroid tissue and nodules. This activity was detected in a large percentage of papillary thyroid carcinomas, but not benign adenomas, follicular carcinomas, or most normal thyroid tissue. Telomerase activity may also correlate with tumor invasiveness. Further studies will focus on larger numbers of tumors, metastatic tissue, and undifferentiated carcinomas, as well as application of this assay to products from fine-needle aspirates as a potential diagnostic and prognostic marker in thyroid neoplasms.
Efficient In Vitro vectorial transport of a fluorescent conjugated bile acid analogue by polarized hepatic hybrid WIF-B and WIF-B9 cells (1998)

Efficient transport of bile acids, a typical characteristic of hepatocytes, is partially lost in most hepatoma cell lines and in normal hepatocytes after some days in culture. We have tested whether the polarized rat hepatoma-human fibroblast hybrid WIF (hybrids between W138 and Fao cells) cells previously obtained by our group were able to perform vectorial transport of the fluorescent bile acid derivative cholylglycylamidofluorescein (CGamF) towards the bile canaliculi (BC). Four different WIF clones were analyzed. All were well polarized, as shown by the formation of spherical and even tubular BC-like structures and by the restricted localization at the BC, visualized by immunofluorescence, of the apical membrane marker HA4, a possible bile acid carrier. WIF-B and its subclone WIF-B9 were found to accumulate CGamF in 65% to 75% of their BC. This transport was time, temperature, and partly sodium dependent and was inhibited by coincubation with the parental natural bile salt cholylglycine. Dinitrophenyl glutathione, a substrate of the canalicular multispecific organic anion transporter, did not inhibit CGamF canalicular secretion, whereas it greatly impaired the canalicular secretion of a non-bile acid organic anion, fluorescein, generated intracellularly from fluorescein diacetate. Confocal microscopy confirmed the presence of CGamF in the cytoplasm, supporting a transcellular route from medium to BC. In contrast, two other polarized clones exhibited a poor ability (WIF 12-6) or no ability (WIF12-1 TGdelta) to vectorially transport CGamE In conclusion, WIF-B and WIF-B9 exhibit not only structural but also functional polarity, at least as far as vectorial organic anion transport is concerned.
Histoire de la Volkskunde. Tentative d’une approche a l’usage des français (1987)

Volkskunde, non seulement le nom mais la chose elle-même sont typiquement allemands, originaires plus précisément d’Europe centrale, mais c’est en allemand qu’ils ont pris forme d’abord. Cela est lié à l’histoire politique de l’Europe centrale et, par conséquent, à l’histoire de ses idées et mouvements intellectuels depuis le milieu du xviiie siècle. A la France moderne, Etat national centralisé, ayant depuis le xviie siècle une identité culturelle hégémonique institutionnalisée, s’opposait e...
L-Glutaminase: Suppression of Lymphocyte Blastogenic Responses in vitro (1971)

Continuous exposure to 0.1 international unit or more of Escherichia coli L-glutaminase inhibited responses of human lymphocytes to phytohemagglutinin, streptolysin O, and allogeneic leukocytes. Inhibition was completety reversed by removing the enzyme from the culture or adding L-glutamine but not L-asparagine. Cytoxicity did not occur. L-Glutaminase should be immunosuppressive in vivo.
Cancer Gene Therapy Using a Replication-Competent Herpes Simplex Virus Type 1 Vector (1998)

The inherent cytotoxicity of hrR3 replication effectively destroys colon carcinoma cells in vitro and in vivo. This cytotoxicity is not enhanced in vivo by the addition of ganciclovir. In the future, more efficacious and selective HSV 1 vectors may be useful in the treatment of cancer.
Use of near infrared spectroscopy to identify traumatic intracranial hemotomas (1997)

Delayed intracranial hematomas are an important treatable cause of secondary brain injury in patients with head trauma. Early identification and treatment of these mass lesions, which appear or enlarge after the initial CT scan, may improve neurological outcome. Serial examinations using near-infrared spectroscopy (NIRS) to detect the development of delayed hematomas were performed in 305 patients. The difference in optical density (DOD) at 760 nm between the normal and the hematoma side was measured on admission and then serially during the first 3 to 5 days after injury. On admission, the DOD was highly predictive of the initial findings on CT scan. Patients with an epidural, subdural, or intracerebral hematoma had significantly greater DOD in the involved brain region than patients with diffuse brain injury. For the extracerebral hematomas, the DOD was significantly related to the size of the hematoma (r2=0.55 and 0.77 for subdural and epidural hematomas, respectively). Fifty-nine (19%) of the patients developed some type of late hematoma: there was an intracerebral hematoma in 29 patients, an extracerebral hematoma in 7 patients, and a postoperative hematoma in 23 patients. Thirty-three of the late hematomas were large enough to require surgical evacuation. The hematomas appeared between 2 and 72 h after admission. In 55 of the 59 patients, an increase in the DOD to >0.10 occurred prior to an increase in intracranial pressure or a change in the neurological examination. Early diagnosis using NIRS may allow early treatment and reduce secondary injury caused by delayed hematomas.