gebhart/patrepeval huggingface dataset:
Molecular cloning, sequencing and expression of the mRNA encoding human Cdx1 and Cdx2 homeobox. Down-regulation of Cdx1 and Cdx2 mRNA expression during colorectal carcinogenesis (1997)

Defining the molecular mechanisms involved in cancer formation and progression is still a major challenge in colorectal-cancer research. Our strategy was to characterize genes whose expression is altered during colorectal carcinogenesis. To this end, the phenotype of a colorectal tumour was previously established by partial sequencing of a large number of its transcripts and the genes of interest were selected by differential screening on high-density filters with mRNA of colorectal cancer and normal adjacent mucosa. Fifty-one clones were found over-expressed and 23 were underexpressed in the colorectal-cancer tissues of the 5 analyzed patients. Among the latter, clones 6G2 and 32D6 were found of particular interest, since they had significant homology with several homeodomain-containing genes. The highest degree of similarity was with the murine Cdx1 for 6G2, and with the murine Cdx2 and hamster Cdx3 for 32D6. Using a RT-PCR approach, complete sequence of both types of homeobox-containing cDNA was obtained. The amino-acid sequence of the human Cdx1 is 85% identical to the mouse protein, and human Cdx2 has 94% identity with the mouse Cdx2 and hamster Cdx3. Tissue-distribution analysis of Cdx1 and Cdx2 mRNA showed that both transcripts were specifically expressed in small intestine, in colon and rectum. Twelve tissue samples from colorectal adenocarcinomas and the corresponding normal mucosa were analyzed by Northern blot. Expression of the 2 types of mRNA was either reduced or absent in 10 of them. Several colon-cancer cell lines were also analyzed. Cdx2 mRNA was absent from LS174T cells and Cdx1 mRNA was absent in PF11, TC7 and SW480 cells; none was detected in HT29 cells. It was concluded that decrease in human Cdx1 and/or Cdx2 expression is associated with colorectal tumorigenesis.
Functional Anatomy of Complement Factor H (2013)

Factor H (FH) is a soluble regulator of the proteolytic cascade at the core of the evolutionarily ancient vertebrate complement system. Although FH consists of a single chain of similar protein modules, it has a demanding job description. Its chief role is to prevent complement-mediated injury to healthy host cells and tissues. This entails recognition of molecular patterns on host surfaces combined with control of one of nature's most dangerous examples of a positive-feedback loop. In this way, FH modulates, where and when needed, an amplification process that otherwise exponentially escalates the production of the pro-inflammatory, pro-phagocytic, and pro-cytolytic cleavage products of complement proteins C3 and C5. Mutations and single-nucleotide polymorphisms in the FH gene and autoantibodies against FH predispose individuals to diseases, including age-related macular degeneration, dense-deposit disease, and atypical hemolytic uremic syndrome. Moreover, deletions or variations of genes for FH-related proteins also influence the risk of disease. Numerous pathogens hijack FH and use it for self-defense. As reviewed herein, a molecular understanding of FH function is emerging. While its functional oligomeric status remains uncertain, progress has been achieved in characterizing its three-dimensional architecture and, to a lesser extent, its intermodular flexibility. Models are proposed, based on the reconciliation of older data with a wealth of recent evidence, in which a latent circulating form of FH is activated by its principal target, C3b tethered to a self-surface. Such models suggest hypotheses linking sequence variations to pathophysiology, but improved, more quantitative, functional assays and rigorous data analysis are required to test these ideas.
Multiple Heme Oxygenase Family Members Contribute to the Biosynthesis of the Phytochrome Chromophore in Arabidopsis (2006)

The oxidative cleavage of heme by heme oxygenases (HOs) to form biliverdin IXalpha (BV) is the committed step in the biosynthesis of the phytochrome (phy) chromophore and thus essential for proper photomorphogenesis in plants. Arabidopsis (Arabidopsis thaliana) contains four possible HO genes (HY1, HO2-4). Genetic analysis of the HY1 locus showed previously that it is the major source of BV with hy1 mutant plants displaying long hypocotyls and decreased chlorophyll accumulation consistent with a substantial deficiency in photochemically active phys. More recent analysis of HO2 suggested that it also plays a role in phy assembly and photomorphogenesis but the ho2 mutant phenotype is more subtle than that of hy1 mutants. Here, we define the functions of HO3 and HO4 in Arabidopsis. Like HY1, the HO3 and HO4 proteins have the capacity to synthesize BV from heme. Through a phenotypic analysis of T-DNA insertion mutants affecting HO3 and HO4 in combination with mutants affecting HY1 or HO2, we demonstrate that both of the encoded proteins also have roles in photomorphogenesis, especially in the absence of HY1. Disruption of HO3 and HO4 in the hy1 background further desensitizes seedlings to red and far-red light and accelerates flowering time, with the triple mutant strongly resembling seedlings deficient in the synthesis of multiple phy apoproteins. The hy1/ho3/ho4 mutant can be rescued phenotypically and for the accumulation of holo-phy by feeding seedlings BV. Taken together, we conclude that multiple members of the Arabidopsis HO family are important for synthesizing the bilin chromophore used to assemble photochemically active phys.
Overexpression of calreticulin increases the Ca2+ capacity of rapidly exchanging Ca2+ stores and reveals aspects of their lumenal microenvironment and function. (1995)

A molecularly tagged form of calreticulin (CR), a low affinity-high capacity Ca2+ binding protein that resides in the ER lumen, was transiently transfected into HeLa cells to specifically modify the Ca2+ buffering capacity of the intracellular Ca2+ stores. Fluorescence and confocal microscope immunocytochemistry revealed the tagged protein to be expressed by over 40% of the cells and to overlap in its distribution the endogenous CR yielding a delicate cytoplasmic network, i.e., the typical pattern of ER. In contrast, no signal was observed associated with the plasmalemma (marked by ConA) and within the nucleus. One- and two-dimensional Western blots revealed the transfected to exceed the endogenous CR of approximately 3.5-fold and to maintain its Ca2+ binding ability, whereas the expression of other ER proteins was unchanged. Ca2+ homeostasis in the transfected cells was investigated by three parallel approaches: (a) 45Ca equilibrium loading of cell populations; (b) [Ca2+]c measurement with fura-2 followed by quantitative immunocytochemistry of single cells and iii) [Ca2+]c measurement of cell population upon cotransfection with the Ca(2+)-sensitive photoprotein, aequorin. The three approaches revealed different aspects of Ca2+ homeostasis, yielding results which were largely complementary. In particular, the following conclusions were established: (a) both endogenous and transfected CR participate in Ca2+ buffering within the IP3-sensitive, rapidly exchanging, Ca2+ stores; the other pools of the cells were in contrast unaffected by CR transfection; (b) the Ca2+ capacity of the stores is not the main limiting factor of individual IP3-mediated Ca2+ release responses triggered by receptor agonists; (c) in control cells, the contribution of CR to Ca2+ buffering within the IP3-sensitive stores accounts for approximately 45% of the total, the rest being probably contributed by the other lumenal (and also membrane) Ca2+ binding proteins; (d) the free [Ca2+] within the lumen of the IP3-sensitive stores, revealed by the degree of Ca2+ binding to the transfected CR protein, amounts to values in (or approaching) the millimolar range; and (e) Ca2+ influx across the plasmalemma activated by depletion of the stores is directly dependent on the lumenal [Ca2+].
Oral Administration of Gemcitabine in Patients with Refractory Tumors: A Clinical and Pharmacologic Study (2008)

Systemic exposure to oral gemcitabine was low due to extensive first-pass metabolism to dFdU. Moderate toxicity combined with hints of activity warrant further investigation of the concept of prolonged exposure to gemcitabine.
Longitudinal Assessment of Serum Free Testosterone Concentration Predicts Memory Performance and Cognitive Status in Elderly Men (2002)

Circulating testosterone (T) levels have behavioral and neurological effects in both human and nonhuman species. Both T concentrations and neuropsychological function decrease substantially with age in men. The purpose of this prospective, longitudinal study was to investigate the relationships between age-associated decreases in endogenous serum T and free T concentrations and declines in neuropsychological performance. Participants were volunteers from the Baltimore Longitudinal Study of Aging, aged 50-91 yr at baseline T assessment. Four hundred seven men were followed for an average of 10 yr, with assessments of multiple cognitive domains and contemporaneous determination of serum total T, SHBG, and a free T index (FTI). We administered neuropsychological tests of verbal and visual memory, mental status, visuomotor scanning and attention, verbal knowledge/language, visuospatial ability, and depressive symptomatology. Higher FTI was associated with better scores on visual and verbal memory, visuospatial functioning, and visuomotor scanning and a reduced rate of longitudinal decline in visual memory. Men classified as hypogonadal had significantly lower scores on measures of memory and visuospatial performance and a faster rate of decline in visual memory. No relations between total T or the FTI and measures of verbal knowledge, mental status, or depressive symptoms were observed. These results suggest a possible beneficial relationship between circulating free T concentrations and specific domains of cognitive performance in older men.
Suppression of angiogenesis by lentiviral delivery of PEX, a noncatalytic fragment of matrix metalloproteinase 2 (2000)

Modulation of the balance between pro- and antiangiogenic factors holds great promise for the treatment of a broad spectrum of human disease ranging from ischemic heart disease to cancer. This requires both the identification of angiogenic regulators and their efficient delivery to target organs. Here, we demonstrate the use of a noncatalytic fragment of matrix metalloproteinase 2 (termed PEX) delivered by lentiviral vectors in different angiogenesis models. Transduction of human endothelial cells with PEX virus suppressed endothelial invasion and formation of capillary-like structures without affecting chemotaxis in vitro. Lentiviral delivery of PEX blocked basic fibroblast growth factor-induced matrix metalloproteinase 2 activation and angiogenesis on chicken chorioallantoic membranes. PEX expression also inhibited tumor-induced angiogenesis and tumor growth in a nude mouse model. Thus, our study shows that lentiviral vectors can deliver sufficient quantities of antiangiogenic substances to achieve therapeutic effects in vivo.
Joint Asynchronous Congestion Control and Distributed Scheduling for Multi-Hop Wireless Networks (2006)

We consider a multi-hop wireless network shared by many users. For an interference model that only constrains a node to either transmit or receive at a time, but not both, we propose an architecture for fair resource allocation that consists of a distributed scheduling algorithm operating in conjunction with an asynchronous congestion control algorithm. We show that the proposed joint congestion control and scheduling algorithm supports at least one-third of the throughput supportable by any other algorithm, including centralized algorithms.
Global equity markets : technological, competitive, and regulatory challenges (1994)

Explains the full scope of the changes and challenges within the global equities market. Noted regulators, scholars, and other professionals assess the current state of major and emerging global securities markets and the forces that influence them.
Prognostic Associations of Activated Mitogen-Activated Protein Kinase and Akt Pathways in Glioblastoma (2006)

p-MAPK and activated members of the Akt pathway are markers of outcome in glioblastoma. Elevated expression of p-MAPK is associated with increased radiation resistance and represents an independent prognostic factor in these tumors.
Phenethylthiazolylthiourea (PETT) Compounds as a New Class of HIV-1 Reverse Transcriptase Inhibitors. 2. Synthesis and Further Structure−Activity Relationship Studies of PETT Analogs (1996)

Phenylethylthiazolylthiourea (PETT) derivatives have been identified as a new series of non-nucleoside inhibitors of HIV-1 RT. Structure-activity relationship studies of this class of compounds resulted in the identification of N-[2-(2-pyridyl)ethyl]-N'-[2-(5-bromopyridyl)]-thiourea hydrochloride (trovirdine; LY300046.HCl) as a highly potent anti-HIV-1 agent. Trovirdine is currently in phase one clinical trials for potential use in the treatment of AIDS. Extension of these structure-activity relationship studies to identify additional compounds in this series with improved properties is ongoing. A part of this work is described here. Replacement of the two aromatic moieties of the PETT compounds by various substituted or unsubstituted heteroaromatic rings was investigated. In addition, the effects of multiple substitution in the phenyl ring were also studied. The antiviral activities were determined on wild-type and constructed mutants of HIV-1 RT and on wild-type HIV-1 and mutant viruses derived thereof, Ile100 and Cys181, in cell culture assays. Some selected compounds were determined on double-mutant viruses, HIV-1 (Ile 100/Asn103) and HIV-1 (Ile100/Cys181). A number of highly potent analogs were synthesized. These compounds displayed IC50's against wild-type RT between 0.6 and 5 nM. In cell culture, these agents inhibited wild-type HIV-1 with ED50's between 1 and 5 nM in MT-4 cells. In addition, these derivatives inhibited mutant HIV-1 RT (Ile 100) with IC50's between 20 and 50 nM and mutant HIV-1 RT (Cys 181) with IC50's between 4 and 10 nM, and in cell culture they inhibited mutant HIV-1 (Ile100) with ED50's between 9 and 100 nM and mutant HIV-1 (Cys181) with ED50's between 3 and 20 nM.
Identification and purification of a single-stranded-DNA-specific exonuclease encoded by the recJ gene of Escherichia coli. (1989)

The Escherichia coli recJ gene product was overproduced using a plasmid that carries the recJ gene downstream of a strong regulatable promoter and a strong ribosome-binding site. Overexpression of recJ produced a concomitant increase in the levels of single-stranded-DNA-specific nuclease activity present in crude cell extracts. This nuclease activity was purified to homogeneity and found to reside in a 60-kDa polypeptide. This polypeptide was induced with recJ overexpression and had the size and N-terminal amino acid sequence identical to the predicted RecJ protein sequence. The RecJ nuclease degraded linear single-stranded DNA but did not have exonuclease activity on linear double-stranded substrates or endonuclease activity on either single-stranded or double-stranded substrates. The RecJ exonuclease had greater activity on duplex DNA molecules with 5'-rather than 3'-single-stranded tails.
Low-Power Wireless Micromanometer System for Acute and Chronic Bladder-Pressure Monitoring (2010)

This letter describes the design, fabrication, and testing of a wireless bladder-pressure-sensing system for chronic, point-of-care applications, such as urodynamics or closed-loop neuromodulation. The system consists of a miniature implantable device and an external RF receiver and wireless battery charger. The implant is small enough to be cystoscopically implanted within the bladder wall, where it is securely held and shielded from the urine stream. The implant consists of a custom application-specific integrated circuit (ASIC), a pressure transducer, a rechargeable battery, and wireless telemetry and recharging antennas. The ASIC includes instrumentation, wireless transmission, and power-management circuitry, and on an average draws less than 9 μA from the 3.6-V battery. The battery charge can be wirelessly replenished with daily 6-h recharge periods that can occur during the periods of sleep. Acute in vivo evaluation of the pressure-sensing system in canine models has demonstrated that the system can accurately capture lumen pressure from a submucosal implant location.
Transcriptional Activation of a Constitutive Heterochromatic Domain of the Human Genome in Response to Heat Shock (2003)

Heat shock triggers the assembly of nuclear stress bodies that contain heat shock factor 1 and a subset of RNA processing factors. These structures are formed on the pericentromeric heterochromatic regions of specific human chromosomes, among which chromosome 9. In this article we show that these heterochromatic domains are characterized by an epigenetic status typical of euchromatic regions. Similarly to transcriptionally competent portions of the genome, stress bodies are, in fact, enriched in acetylated histone H4. Acetylation peaks at 6 h of recovery from heat shock. Moreover, heterochromatin markers, such as HP1 and histone H3 methylated on lysine 9, are excluded from these nuclear districts. In addition, heat shock triggers the transient accumulation of RNA molecules, heterogeneous in size, containing the subclass of satellite III sequences found in the pericentromeric heterochromatin of chromosome 9. This is the first report of a transcriptional activation of a constitutive heterochromatic portion of the genome in response to stress stimuli.
Performance of Commercial Cultures in Fluid Milk Applications (1996)

Six Lactobacillus acidophilus, 5 Bifidobacterium, and 6 Streptococcus thermophilus strains were studied for characteristics that are important to activity and stability in unfermented fluid milk products. Speciation, strain relatedness, frozen concentrate stability, bile sensitivity, and lactase activity were evaluated. The microbiological stability of a culture-containing fluid milk product was also determined. Two of the bifidobacteria cultures contained >1 strain. Some strains were shown to be closely related or identical by pulsed-field gel electrophoresis of fragmented chromosomal DNA. Selective media that distinguished among all 3 added genera were identified. All lactobacilli and most of the bifidobacteria were resistant to bile concentrations varying from 1 to 3%, and all streptococci were sensitive to bile. Lactase activities were highest for S. thermophilus strains, supporting use of this species in fluid milk and dairy products to aid in the digestion of lactose by consumers. The experimental product evaluated in this study contained 10 7 cfu/ml of both L. acidophilus and Bifidobacterium spp. and 5 x 10 7 cfu/ml of S. thermophilus. Lactic, but not psychrotrophic, populations were fairly stable during storage. The results suggest that milk formulated with high concentrations of three different genera of probiotic bacteria can be manufactured with commercial strains.
Heavy-tailed on/off source behavior and self-similar traffic (2002)

Traffic measurement studies suggest that the self-similarity observed in packet traffic arises from aggregating individual sources which behave in an on/off manner with heavy-tailed sojourn times in one or both of the states. We investigate the connection between general on/off behavior, self-similarity and queueing performance. We use chaotic maps to model general on/off behavior with combinations of heavy tailed and light tailed sojourn time behavior. We present results which show that chaotic maps which capture the heavy-tailed sojourn time behavior in the off and/or on states generate traffic that is asymptotically self-similar. However, the resulting queue length distribution decays as a power law with the heavy on source, and as an exponential with the light on source, even though both processes exhibit identical l/f noise behavior. To resolve this apparent paradox, we consider aggregates of on and off sources, and show that the nature of the on period is less consequential, and in both instances the aggregate appears to converge to fractional Brownian motion (FBM). The queueing behavior is heavy in both cases, corresponding to the "stretched exponential" form predicted by FBM models. This indicates that differences in the single source case arise due to the impacts of higher order statistics, which become less significant as sources are aggregated. Convergence to FBM is observed to be slower with light on sources. Our results indicate that in assessing the impact of long range dependence on performance, the potential impacts of other factors, such as higher-order statistics, must also be considered. Our analysis indicates conditions under which long-range dependence can dominate queueing performance in fast packet and SS7 networks, and with variable bit rate (VBR) video applications.
Interactive effects of nitric oxide and the p53 tumor suppressor gene in carcinogenesis and tumor progression (1997)

The tumor suppressor gene product p53 plays an important role in the cellular response to DNA damage. DNA damage can lead to p53-mediated growth arrest and apoptosis. High concentrations of nitric oxide (NO) and NO metabolites such as peroxynitrite and NO2 cause DNA damage and have been shown to be mutagenic. Furthermore, NO induces p53 accumulation and, as part of a feedback loop, p53 mediates transcriptional transrepression of inducible nitric oxide synthase. Recent studies have shown increased expression and activity of nitric oxide synthase isoforms in human cancer. NO has both genotoxic and angiogenic properties, so that increased NO production may select mutant p53 cells and contribute to human carcinogenesis and tumor progression.
Inverse scattering for frequency-scanned full-field optical coherence tomography (2007)

Full-field optical coherence tomography (OCT) is able to image an entire en face plane of scatterers simultaneously, but typically the focus is scanned through the volume to acquire three-dimensional structure. By solving the inverse scattering problem for full-field OCT, we show it is possible to computationally reconstruct a three-dimensional volume while the focus is fixed at one plane inside the sample. While a low-numerical-aperture (NA) OCT system can tolerate defocus because the depth of field is large, for high NA it is critical to correct for defocus. By deriving a solution to the inverse scattering problem for full-field OCT, we propose and simulate an algorithm that recovers object structure both inside and outside the depth of field, so that even for high NA the focus can be fixed at a particular plane within the sample without compromising resolution away from the focal plane.