gebhart/patrepeval huggingface dataset:
A simple specific pattern of chromosomal aberrations at early stages of head and neck squamous cell carcinomas: PIK3CA but not p63 gene as a likely target of 3q26-qter gains. (2001)

Low-grade head and neck squamous cell carcinomas without lymph node involvement or distant metastasis (N(0)M(0)) were screened for chromosomal imbalances by comparative genomic hybridization (CGH). pT(1-2) tumors contain a low number of aberrations (average number, 4.3; 15 cases), in contrast to pT(3) tumors (average number, 11.8; 6 cases), and exhibit a specific CGH pattern, affecting three chromosomes: partial or total 3q gain and/or 3p loss (73% of cases), 8q gain (47%), and 11q13 gain (27%). Thus, these changes represent early events in the pathogenesis of low-grade tumors. Cytogenetic exploration of chromosome 3 aberrations in head and neck cell lines suggests that the formation of an isochromosome 3q is one intermediate mechanism leading to 3p losses and/or 3q gains. On the long arm of chromosome 3, most of tumors exhibit low-level gains of large segments, involving systematically the 3q26-qter area, but with two alternative smallest region overlaps at 3q26 and 3q28-qter. We decided to refine the mapping of 3q26-qter gains by using fluorescence in situ hybridization on tumor nuclei, with clones containing two outstanding positional and functional candidate genes, PIK3CA and p63, located respectively at 3q26 and at 3q28. Although PIK3CA or p63 were preferentially gained in few cases (4 of 45), both genes were over-represented in 27 of 45 low-grade N(0)M(0) carcinomas analyzed by CGH or fluorescence in situ hybridization. To evaluate the relative contribution of PIK3CA and p63 in the pathogenesis of head and neck carcinomas displaying a 3q gain, we measured their respective transcription levels in tumors with previously determined gene copy number. DNp63, the predominant p63 transcript, is overexpressed in tumors compared with normal tissues, but its expression level is independent to gene copy number. In contrast, a significant PIK3CA overexpression is associated with increased gene dosage. These results indicate that PIK3CA, contrary to DNp63, may participate to the progression of head and neck tumors consequent to a low-level 3q over-representation. Interestingly, survival analysis using CGH suggested, in accordance with previous data, that 3q26 gain, the locus of PIK3CA, could predict clinical outcome for early disease tumors. This prompts us to pursue 3q26 (or PIK3CA) prognostic evaluation in a larger population of head and neck squamous cell carcinomas.
Macromolecular-scale resolution in biological fluorescence microscopy (2006)

We demonstrate far-field fluorescence microscopy with a focal-plane resolution of 15-20 nm in biological samples. The 10- to 12-fold multilateral increase in resolution below the diffraction barrier has been enabled by the elimination of molecular triplet state excitation as a major source of photobleaching of a number of dyes in stimulated emission depletion microscopy. Allowing for relaxation of the triplet state between subsequent excitation-depletion cycles yields an up to 30-fold increase in total fluorescence signal as compared with reported stimulated emission depletion illumination schemes. Moreover, it enables the reduction of the effective focal spot area by up to approximately 140-fold below that given by diffraction. Triplet-state relaxation can be realized either by reducing the repetition rate of pulsed lasers or by increasing the scanning speed such that the build-up of the triplet state is effectively prevented. This resolution in immunofluorescence imaging is evidenced by revealing nanoscale protein patterns on endosomes, the punctuated structures of intermediate filaments in neurons, and nuclear protein speckles in mammalian cells with conventional optics. The reported performance of diffraction-unlimited fluorescence microscopy opens up a pathway for addressing fundamental problems in the life sciences.
The human immunoglobulin x locus. Characterization of the duplicated A regions (1992)

The central regions of the kappa locus, the so-called A regions, have been fully characterized on cosmid and phage lambda clones. The regions, which are parts of the C kappa-proximal and -distal copies of the locus and are, therefore, called Ap and Ad regions, comprise about 140 kb each and contain together 30 V kappa genes and pseudogenes. The A regions have been linked on their 5' sides to the O regions and on their 3' sides to the L regions. Chromosomal walking has eliminated a previous gap in the Ap region. Detailed restriction maps of the Ap and Ad regions and the sequences of 9 V kappa genes are reported. Four events, which have occurred in evolution probably after the duplication of the A region, were identified: the insertion of an Alu element in Ad; the insertion of part of a LINE element in Ap; the deletion of a 17.5-kb fragment including one V kappa gene from Ap; the sequence divergence of duplicated V kappa gene regions which ranges among the five pairs studied here from 0 to 14 bp per kb and converted two genes to pseudogenes while their duplicates stayed functional. An analysis of the A regions of the lymphoid cell lines RPMI 6140 and GM607 confirmed the previous finding that the V kappa-J kappa rearrangement in these cell lines had occurred by deletion and inversion mechanisms, respectively. Thus, the structural data contribute to the understanding of the evolution and the functioning of the A regions of the kappa locus.
Phase I studies of recombinant interferon-gamma. (1990)

A phase I study of the effects of intravenous administration of interferon-gamma on 31 patients was performed. The effects of dose, schedule, and chronic administration were studied. In the first phase of the study, a dose range of 0.01-500 MU/m2 (0.0002-25 mg/m2) was tested and we found the maximum tolerated dose to be 400 MU/m2; the dose-limiting toxicity with this preparation was hypotension. In the second phase, three different schedules of administration were tested. There were no significant differences in toxicity between a 20 min, a 4 h, or a 24 h infusion of 60 MU/m2 (3 mg/m2). In the third phase, patients received chronic administration of either 1 or 30 MU/m2. Patients given 30 MU/m2 twice a week for 4 weeks showed more symptoms--fever, nausea, and orthostasis--than those treated with 1 MU/m2. No significant changes were seen in natural killer cell activity, antibody-dependent complement cytotoxicity, or monocyte cytotoxicity at any dose. Maximal stimulation of 2',5'-oligodenylate synthetase occurred at low doses (12 MU/m2). Depressed bone marrow colony formation for CFU-GM, BFU-E, and CFU-GEMM in vivo was noted. No objective antitumor responses were noted. This preparation of recombinant interferon-gamma can be given in doses as high as 400 MU/m2. Chronic administration would appear to be limited to 30 MU/m2. However, lower doses may give maximal biologic responses. These studies provide further information on the biologic effects of a wide dose range and a variety of schedules of recombinant interferon-gamma.
High‐level expression of active HIV‐1 integrase from a synthetic gene in human cells (2000)

A synthetic gene encoding for HIV‐1 integrase was designed to circumvent the intrinsic instability and the repressor elements present in the wild‐type gene. High‐level expression of HIV‐1 integrase was obtained in various human cell lines independently of viral accessory proteins. A human 293T cell line was selected that stably expresses HIV‐1 integrase and has growth kinetics comparable to the parental cell line. The enzyme was localized in the nucleus and remained stably associated with the chromosomes during mitosis. Lentiviral vector particles carrying the inactivating D64V mutation in the integrase gene were capable of stably transducing 293T cells when complemented in the producer cells with integrase expressed from the synthetic gene. When the cell line that stably expresses integrase was infected with the defective viral particles, complementation of integrase activity was detected as well. Expression of active HIV‐1 integrase in human cells will facilitate the study of the interplay between host and viral factors during integration.—Cherepanov, P., Pluymers, W., Claeys, A., Proost, P., De Clercq, E., Debyser, Z. High‐level expression of active HIV‐1 integrase from a synthetic gene in human cells. FASEB J. 14, 1389–1399 (2000)
A flow cytometric assay of CD34‐positive cell populations in the bone marrow (1994)

CD34+ BM cells form a heterogenous population of primitive stem cells and more mature progenitors committed to different lineages of differentiation. By combining CD45 expression with SSC, it is possible to separate immature cells from more differentiated BM cells, and, by three-colour flow cytometry, analyse the antigens expressed in various subsets of cells. In this paper we show that in the normal BM at least four distinct CD34+ cell populations can be identified by their different patterns of CD45 expression and SSC. The most immature CD34+ cell population (0.1% of the BM cellularity) lacked all signs of lineage commitment and was CD45RA negative and only weakly CD45 positive. With increasing expression of the CD45 antigens, a second CD34+ population (0.2% of the BM cellularity) was formed expressing mainly primitive lymphatic antigens. However, 30% of the cells co-expressed B-cell line antigens and myeloid antigens. Cells committed to the myeloid cell line lost B-cell line antigens, gained CD45 antigen expression and SSC and formed two CD34+ cell populations (0.2% and 0.1% of the BM cellularity, respectively) differing only with respect to the pattern of myeloid antigen expression and SSC characteristics. Similarly, differentiation along the lymphatic pathway implicated down-regulation of myeloid antigens, loss of the stem cell antigen and immature lymphatic antigens and gain of CD45 expression and mature lymphatic antigens.
Delayed tyrosine phosphorylation and nuclear expression of STAT1 following antigen receptor stimulation of B lymphocytes (1996)

The regulation of the STAT1 alpha transcription factor was assessed during B cell activation induced by cross-linking the surface IgM Ag receptor. Surface Ig ligation or pharmacologic stimulation with PMA and ionomycin resulted in the delayed (2-3 h after stimulation) nuclear appearance of tyrosine-phosphorylated STAT1 alpha, in contrast to the rapid induction that follows cytokine treatment. Nuclear expression of phosphorylated STAT1 alpha was abrogated by co-incubation of anti-Ig-treated B cells with the protein synthesis inhibitor cycloheximide (CHX), with the protein kinase inhibitor H-7, or with the immunosuppressive drug rapamycin. Tyrosine-phosphorylated STAT1 alpha was found to be recruited to the STAT binding site of the IFN regulatory factor-1 (IRF-1) gene promoter only after 2 to 3 h, and this association was also inhibitable by CHX and rapamycin. The arrival of STAT1 alpha coincided with attenuation of anti-Ig-induced STAT-binding activity specific for the IRF-1 promoter site, and both rapamycin and CHX treatment counteracted the loss of this activity. Furthermore, basal transcription of the endogenous IRF-1 gene was decreased as a result of anti-Ig treatment, and this effect of anti-Ig was blocked by co-incubation with rapamycin. Thus, STAT1 alpha plays a dynamic role in the composition of IRF-1 promoter-specific DNA binding complexes stimulated by B cell Ag receptor ligation, and nuclear expression of phosphorylated STAT1 alpha is regulated in a unique fashion by Ag receptor engagement. In addition, surface Ig cross-linking imparts negative regulatory control of IRF-1 gene expression, possibly through activation of STAT1 alpha.
Transdermal Testosterone Therapy in the Treatment of Male Hypogonadism* (1988)

Five hypogonadal men were treated with transdermal testosterone therapy, using a testosterone patch applied to the scrotal skin. Daily application of the patch, which contained 10 mg testosterone, produced an increase in serum testosterone concentrations from a pretreatment value of 45 +/- 12 (+/- SE; 1.5 +/- 0.4) to 436 +/- 80 ng/dL (15.1 +/- 2.8 nmol/L; P less than 0.001) after 4 weeks of treatment. Normal serum testosterone concentrations were achieved in all men after 6-8 weeks of therapy and were maintained during continued long term therapy for 9-12 months with a patch containing 15 mg testosterone. All men reported a subjective increase in libido and sexual function during therapy, and three men preferred it to testosterone injections. The serum testosterone and estradiol levels did not rise above the normal adult male range at any time during therapy. However, elevated serum dihydrotestosterone (DHT) concentrations occurred during treatment; the pretreatment DHT concentration was 95 +/- 3 ng/dL (3.3 +/- 0.1 nmol/L), and it increased to 228 +/- 40 ng/dL (7.8 +/- 1.4 nmol/L) after 4 weeks of treatment and remained elevated thereafter. The individual mean DHT to testosterone ratio increased from a pretreatment value of 0.2 (range, 0.1-0.3) to 0.6 (range, 0.4-0.7) after 2 weeks of therapy and remained high thereafter. Comparison of the serum DHT levels in patients during therapy with those in normal men who had similar testosterone concentrations [531 +/- 62 vs. 566 +/- 72 ng/dL (18.4 +/- 2.1 vs. 19.6 +/- 2.5 nmol/L); P greater than 0.05] revealed that the mean serum DHT concentration was significantly higher in the patients [315 +/- 69 vs. 87 +/- 6 ng/dL (10.8 +/- 2.4 vs. 2.9 +/- 0.2 nmol/L); P less than 0.001], as was the mean DHT to testosterone ratio [0.6 (range, 0.25- 1.1) vs. 0.16 (range, 0.09- 0.24); P less than 0.001]. The high serum DHT levels presumably were due to increased metabolism of testosterone to DHT by the 5 alpha-reductase in the scrotal skin. Serum 3 alpha-androstanediol glucuronide levels were not elevated in the patients. We conclude that transdermal testosterone therapy is an effective long term treatment for hypogonadism in men. It is, however, associated with high serum DHT levels, whose potential long term effects on the prostate and other tissues need to be investigated.
Cilk (1995)

Cilk (pronounced “silk”) is a C-based runtime system for multi-threaded parallel programming. In this paper, we document the efficiency of the Cilk work-stealing scheduler, both empirically and analytically. We show that on real and synthetic applications, the “work” and “critical path” of a Cilk computation can be used to accurately model performance. Consequently, a Cilk programmer can focus on reducing the work and critical path of his computation, insulated from load balancing and other runtime scheduling issues. We also prove that for the class of “fully strict” (well-structured) programs, the Cilk scheduler achieves space, time and communication bounds all within a constant factor of optimal. The Cilk runtime system currently runs on the Connection Machine CM5 MPP, the Intel Paragon MPP, the Silicon Graphics Power Challenge SMP, and the MIT Phish network of workstations. Applications written in Cilk include protein folding, graphic rendering, backtrack search, and the *Socrates chess program, which won third prize in the 1994 ACM International Computer Chess Championship.
Fluorescent Sensors for Organophosphorus Nerve Agent Mimics (2006)

We present a small molecule sensor that provides an optical response to the presence of an organophosphorus (OP)-containing nerve agent mimic. The design contains three key features: a primary alcohol, a tertiary amine in close proximity to the alcohol, and a fluorescent group used as the optical readout. In the sensor's rest state, the lone pair of electrons of the basic amine quenches the fluorescence of the nearby fluorophore through photoinduced electron transfer (PET). Exposure to an OP nerve agent mimic triggers phosphorylation of the primary alcohol followed rapidly by an intramolecular substitution reaction as the amine displaces the created phosphate. The quaternized ammonium salt produced by this cyclization reaction no longer possesses a lone pair of electrons, and a fluorescence readout is observed as the nonradiative PET quenching pathway of the fluorophore is shut down.
Expression of Neural Stem Cell Surface Marker CD133 in Balloon Cells of Human Focal Cortical Dysplasia (2005)

These results show that balloon cells are heterogeneous cell populations expressing cell-surface markers for pluripotential stem cells and proteins for multipotent progenitors, or immature neurons/glia. The presence of stem cell/progenitor markers in the balloon cells could be due to a persistent postnatal neurogenesis or early embryonic insult that resulted in arrest of proliferation/differentiation at their early stages. Additionally, the coexpression of Bcl-2 in CD133-positive balloon cells suggests that a resistance to programmed cell death may be involved in the pathogenesis of cortical dysplasia.
Acetazolamide Testing of Cerebral Vasodilator Capacity Provokes “Vascular” But Not Tension Headaches (1996)

Cerebrovascular capacitance was tested by measuring local cerebral blood flow (LCBF) by xenon-contrasted CT scanning before and after the oral administration of 14.3 mg/kg of acetazolamide among 45 subjects including 15 age-matched controls without history of headache, 20 migraineurs with and without aura, 3 patients with cluster headache, and 7 patients with tension-type headache. Percentage increases of LCBF were measured in 10 regions located throughout both hemispheres. Laterality indices for asymmetric LCBF increases were calculated. Local cerebral blood flow in cortical gray matter increased 5.9% in controls, 9.9% in patients with tension headaches, but 18.6% in both migraine and cluster headache patients; significantly greater LCBF increases than among controls or among patients with tension headaches (P < 0.05). Increases in LCBF were significantly asymmetric among migraine and cluster patients and provoked typical unilateral vascular headaches which responded to sumatriptan. Maximal asymmetric LCBF increases also corresponded to the reported side of the induced headaches confirming their vascular pathogenesis. Patients with tension headaches and controls without history of headache did not develop head pain after acetazolamide.
Sequential Hepatogenic Transdifferentiation of Adipose Tissue-Derived Stem Cells: Relevance of Different Extracellular Signaling Molecules, Transcription Factors Involved, and Expression of New Key Marker Genes (2009)

Adipose tissue contains a mesenchymal stem cell (MSC) population known as adipose-derived stem cells (ASCs) capable of differentiating into different cell types. Our aim was to induce hepatic transdifferentiation of ASCs by sequential exposure to several combinations of cytokines, growth factors, and hormones. The most efficient hepatogenic protocol includes fibroblastic growth factors (FGF) 2 and 4 and epidermal growth factor (EGF) (step 1), hepatocyte growth factor (HGF), FGF2, FGF4, and nicotinamide (Nic) (step 2), and oncostatin M (OSM), dexamethasone (Dex), and insulin-tranferrin-selenium (step 3). This protocol activated transcription factors [GATA6, Hex, CCAAT/enhancer binding protein alpha and beta (CEBPalpha and beta), peroxisome proliferator-activated receptor-gamma, coactivator 1 alpha (PGC1alpha), and hepatocyte nuclear factor 4 alpha (HNF4alpha)], which promoted a characteristic hepatic phenotype, as assessed by new informative markers for the step-by-step hepatic transdifferentiation of hMSC [early markers: albumin (ALB), alpha-2-macroglobuline (alpha2M), complement protein C3 (C3), and selenoprotein P1 (SEPP1); late markers: cytochrome P450 3A4 (CYP3A4), apolipoprotein E (APOE), acyl-CoA synthetase long-chain family member 1 (ACSL1), and angiotensin II receptor, type 1 (AGTR1)]. The loss of adipose adult stem cell phenotype was detected by losing expression of Thy1 and inhibitor of DNA binding 3 (Id3). The reexpression of phosphoenolpyruvate corboxykinase (PEPCK), apolipoprotein C3 (APOCIII), aldolase B (ALDOB), and cytochrome P450 1A2 (CYP1A2) was achieved by transduction with a recombinant adenovirus for HNF4alpha and finally hepatic functionality was also assessed by analyzing specific biochemical markers. We conclude that ASCs could represent an alternative tool in clinical therapy for liver dysfunction and regenerative medicine.
Summary of Travel Trends 2001 National Household Travel Survey (2005)

air-quality impacts of various policies. To address these data needs, the U.S. Department of Transportation (USDOT) initiated an effort in 1969 to collect detailed data on personal travel. The 1969 survey was the first Nationwide Personal Transportation Survey (NPTS). The survey was conducted again in 1977, 1983, 1990, 1995, and 2001. Data on daily travel were collected in 1969, 1977, 1983, 1990 and 1995. In 2001, the survey was renamed the National Household Travel Survey (NHTS) and it collected both daily and long-distance trips. The 2001 survey was sponsored by three USDOT agencies: Federal Highway Administration (FHWA), Bureau of Transportation Statistics (BTS), and National Highway Traffic Safety Administration (NHTSA). The primary objective of the survey was to collect trip-based data on the nature and characteristics of personal travel so that the relationships between the characteristics of personal travel and the demographics of the traveler can be established. Commercial and institutional travel were not part of the survey. Due to the survey's design, data in the NHTS survey series were not recommended for estimating travel statistics for categories smaller than the combination of Census division (e.g., New England, Middle Atlantic, and Pacific), MSA size, and the availability of rail. Extrapolating NHTS data within small geographic areas could risk developing and subsequently using unreliable estimates. For example, if a planning agency in City X of State Y estimates travel rates and other travel characteristics based on survey data collected from NHTS sample households that were located in City X of State Y, then the agency could risk developing and using unreliable estimates for their planning process. Typically, this limitation significantly increases as the size of an area decreases. That said, the NHTS contains a wealth of information that could allow statistical inferences about small geographic areas, with a pre-determined level of statistical certainty. The question then becomes whether a method can be developed that integrates the NHTS data and other data to estimate key travel characteristics for small geographic areas such as Census tract and transportation analysis zone, and whether this method can outperform other, competing methods.
Depletion of TDP 43 overrides the need for exonic and intronic splicing enhancers in the human apoA-II gene (2005)

Exon 3 of the human apolipoprotein A-II (apoA-II) gene is efficiently included in the mRNA although its acceptor site is significantly weak because of a peculiar (GU)16 tract instead of a canonical polypyrimidine tract within the intron 2/exon 3 junction. Our previous studies demonstrated that the SR proteins ASF/SF2 and SC35 bind specifically an exonic splicing enhancer (ESE) within exon 3 and promote exon 3 splicing. In the present study, we show that the ESE is necessary only in the proper context. In addition, we have characterized two novel sequences in the flanking introns that modulate apoA-II exon 3 splicing. There is a G-rich element in intron 2 that interacts with hnRNPH1 and inhibits exon 3 splicing. The second is a purine rich region in intron 3 that binds SRp40 and SRp55 and promotes exon 3 inclusion in mRNA. We have also found that the (GU) repeats in the apoA-II context bind the splicing factor TDP-43 and interfere with exon 3 definition. Significantly, blocking of TDP-43 expression by small interfering RNA overrides the need for all the other cis-acting elements making exon 3 inclusion constitutive even in the presence of disrupted exonic and intronic enhancers. Altogether, our results suggest that exonic and intronic enhancers have evolved to balance the negative effects of the two silencers located in intron 2 and hence rescue the constitutive exon 3 inclusion in apoA-II mRNA.