gebhart/patrepeval huggingface dataset:
Localization of PDZD7 to the Stereocilia Ankle-Link Associates this Scaffolding Protein with the Usher Syndrome Protein Network (2012)

Usher syndrome is the leading cause of genetic deaf-blindness. Monoallelic mutations in PDZD7 increase the severity of Usher type II syndrome caused by mutations in USH2A and GPR98, which respectively encode usherin and GPR98. PDZ domain-containing 7 protein (PDZD7) is a paralog of the scaffolding proteins harmonin and whirlin, which are implicated in Usher type 1 and type 2 syndromes. While usherin and GPR98 have been reported to form hair cell stereocilia ankle-links, harmonin localizes to the stereocilia upper tip-link density and whirlin localizes to both tip and ankle-link regions. Here, we used mass spectrometry to show that PDZD7 is expressed in chick stereocilia at a comparable molecular abundance to GPR98. We also show by immunofluorescence and by overexpression of tagged proteins in rat and mouse hair cells that PDZD7 localizes to the ankle-link region, overlapping with usherin, whirlin, and GPR98. Finally, we show in LLC-PK1 cells that cytosolic domains of usherin and GPR98 can bind to both whirlin and PDZD7. These observations are consistent with PDZD7 being a modifier and candidate gene for USH2, and suggest that PDZD7 is a second scaffolding component of the ankle-link complex.
Maintenance therapy for metastatic non-small-cell lung cancer &ndash; the role of pemetrexed (2010)

Over the last several years, we have greatly enhanced our understanding of tumor biology and have now integrated novel and molecular-targeted therapies into front-line treatment for locally advanced and metastatic non-small-cell lung cancer (NSCLC). Despite all the recent advances, the improvement in survival outcomes for these patients has been measured in weeks compared to historical controls. Clinical researchers continue to search for the silver bullet that will allow oncologists to treat lung cancer as a chronic illness and prolong life well beyond the statistical barrier of 1 year for these patients. In that vein, maintenance therapy is emerging as a new treatment option in the metastatic setting. However, there is much controversy over the validity and cost-effectiveness of this modality. Recently, a phase III trial of pemetrexed maintenance versus best supportive care in the setting of metastatic NSCLC following non-progression after 4 cycles of platinum-based doublet therapy showed significant survival outcomes of the treatment group. This article will review the current available treatment options in metastatic NSCLC, including maintenance regimens, with particular attention paid to the recent pemetrexed study.
On approaching wideband capacity using multitone FSK (2005)

In the wideband limit, certain types of "flash" signaling, such as flash frequency-shift keying (FSK), achieve the capacity of multipath fading channels. It is not clear, however, whether these asymptotic results translate into insights for practical fading channels in the finite-bandwidth, power-limited regime. It is known that, for flash FSK, the size of the input alphabet grows slowly with increasing bandwidth, leading to very high-peak power per tone. Thus, for flash FSK, the codeword probability of error decays very slowly with bandwidth and feasible rates approach the wideband capacity limit extremely slowly. Without contradicting the above results, our results in this paper point to a more optimistic outlook, from the point of view of error exponents and achievable rates, for the applicability of flash techniques in practical scenarios. We consider multitone FSK (MFSK), which has the same asymptotic capacity-achieving property as flash FSK in the wideband limit, but allows a larger input alphabet size with the same bandwidth. First, we show, using an error exponent approach, that multitone FSK allows lower peak power per tone than flash FSK. Next, we present the capacity of single-tone and two-tone FSK schemes with hard-decision detection at finite bandwidths. For typical channel parameters, the capacities are close to the wideband capacity limit.
Characterization of the murine Mpl proto-oncogene, a member of the hematopoietic cytokine receptor family: molecular cloning, chromosomal location and evidence for a function in cell growth. (1993)

The v-mpl oncogene transduced in the myeloproliferative leukemia virus (MPLV) encodes a truncated form of a putative receptor protein that belongs to the cytokine receptor superfamily. We previously reported the cloning of complete human c-MPL cDNA. In the present report, we show that the murine Mpl proto-oncogene is located at the D-band of murine chromosome 4, in a region in synteny with human chromosome 1p34, where MPL was previously located. RNA blot analysis of murine hematopoietic tissues and cells lines indicated that Mpl is expressed in immature hematopoietic precursor cells. Molecular cloning of murine proto-oncogene c-Mpl cDNAs is also reported. Two cDNA species were isolated. One potentially encodes a transmembrane protein. The extracellular domain of this protein has two repeats of the cytokine receptor domain common to all members of this receptor family. The cytoplasmic domain has no protein kinase or phosphatase motifs, but does contain a sequence that has been shown to be essential for the transmission of a growth signal in several other members of the family. Comparison of murine and human putative proteins indicated that they shared 81% amino acid identity, the most conserved region being the cytoplasmic domain (91% identity). The other Mpl cDNA clones potentially encode a soluble form of this receptor chain. A chimeric receptor containing the extracellular domain of the granulocyte colony-stimulating factor (G-CSF) receptor fused to the transmembrane and cytoplasmic domains of Mpl was able to induce G-CSF responsiveness when transfected into the interleukin 3 (IL-3)-dependent cell line BAF/BO3. This demonstrated that the cytoplasmic Mpl domain is most probably implicated in proliferative signal transduction.
Analysis of the corrective forces exerted by a dynamic derotation brace (DDB) (2011)

Tightening the brace's straps always produces a significant force increase, independent of the body posture and the curve type. Also there are some body postures which significantly modify the exerted force. The body posture of maximum inspiration for thoracolumbar curves and, additionally, prone and lying left for thoracic curves.
Modulation of hepatic lipoprotein synthesis and secretion by taxifolin, a plant flavonoid (2000)

In the present study, the effects of taxifolin, a plant flavonoid, on lipid, apolipoprotein B (apoB), and apolipoprotein A-I (apoA-I) synthesis and secretion were determined in HepG2 cells. Pretreatment of cells with (+/-)-taxifolin led to an inhibition of cholesterol synthesis in a dose- and time-dependent manner, with an 86 +/- 3% inhibition at 200 microM observed within 24 h. As to the mechanism underlying this inhibitory effect, taxifolin was shown to inhibit the activity of HMG-CoA reductase by 47 +/- 7%. In addition, cellular cholesterol esterification, and triacylglycerol and phospholipid syntheses, were also significantly suppressed in the presence of taxifolin. ApoA-I and apoB synthesis and secretion were then studied by pulse-chase experiments. ApoA-I secretion was found to increase by 36 +/- 10%. In contrast, an average reduction of 61 +/- 8% in labeled apoB in the medium was apparent with taxifolin. This effect on secretion appeared not to be exerted at the transcriptional level. Rather, the effect on apoB secretion was found to be exerted in the early stages of apoB degradation and to be sensitive to dithiothreitol (DTT) and insensitive to N-acetyl-leucyl-leucyl-norleucinal, suggesting a proteolytic pathway involving a DTT-sensitive protease. Fractionation of secreted apoB revealed a slight shift in the distribution of secreted apoB-containing lipoproteins. Cholesteryl ester, rather than triacylglycerol, was shown to be the lipid that primarily regulated apoB secretion. In summary, our data suggest that taxifolin decreases hepatic lipid synthesis with a concomitant decrease and increase in apoB and apoA-I secretion, respectively.
Effect of bacterial lectin on acceleration of fat cell lipolysis at in vitro diode laser treatment using encapsulated ICG (2012)

The influence of bacterial lectin on photochemically induced fat cell lipolysis was studied. Resulting capsules were tested for ICG absorption by optical spectra measurements. To separate released and encapsulated ICG supernatant was removed and capsules were redispered in pure deionized water. Supernatant and capsule suspension spectra were measured separately. It was also found that pretreatment of tissue by lectin leads to acceleration of lipolysis at photochemical treatment. The data obtained can be used to enhance efficiency of photochemical therapy.
Oxaliplatin induces mitotic catastrophe and apoptosis in esophageal cancer cells (2007)

The platinum-based chemotherapeutic agent oxaliplatin displays a wide range of antitumor activities. However, the underlying molecular responses to oxaliplatin in esophageal cancer remain largely unknown. In the present study, we investigated the effect of oxaliplatin on two esophageal cancer cell lines, squamous cell carcinoma (TE3) and adenocarcinoma (TE7). Following cell-cycle arrest at G(2) phase after oxaliplatin treatment, TE3 cells died via apoptosis and TE7 cells died via mitotic catastrophe. Survivin was inhibited more in TE7 cells compared with TE3 cells, but inhibition of survivin using small interfering RNA induced mitotic catastrophe in both cell lines. Further investigations indicated that survivin promoter activity was also inhibited by oxaliplatin. Among mitotic catastrophe-associated proteins, 14-3-3 sigma was decreased in TE7 cells; no evident changes were observed for aurora kinases. Oxaliplatin-induced apoptosis in the TE3 cells was caspase dependent. However, downregulation of Bad, Bid, Puma, and Noxa, lack of cytochrome c release, and limited loss of mitochondrial membrane potential in early phase indicated possible initiation by pathways other than the mitochondrial pathway. Mechanistic studies showed that downregulation of survivin by oxaliplatin in TE7 cells was partially due to the proteasome-mediated protein degradation pathway and partially due to the downregulation of Sp1 transcription factor. Similar results were obtained for another gastric adenocarcinoma cell line, MKN45, in which survivin was previously shown to be inhibited by oxaliplatin. These data indicate that survivin may be a key target for oxaliplatin. The ability of oxaliplatin to induce different modes of cell death may contribute to its efficacy in esophageal cancer.
Common-path low-coherence interferometry fiber-optic sensor guided microincision (2011)

We propose and demonstrate a common-path low-coherence interferometry (CP-LCI) fiber-optic sensor guided precise microincision. The method tracks the target surface and compensates the tool-to-surface relative motion with better than ± 5 μm resolution using a precision micromotor connected to the tool tip. A single-fiber distance probe integrated microdissector was used to perform an accurate 100 μm incision into the surface of an Intralipid phantom. The CP-LCI guided incision quality in terms of depth was evaluated afterwards using three-dimensional Fourier-domain optical coherence tomography imaging, which showed significant improvement of incision accuracy compared to free-hand-only operations.
Dicarboxylic acid transport in Escherichia coli K12: involvement of a binding protein in the translocation of dicarboxylic acids across the outer membrane of the cell envelope (1979)

We have previously found that the dicarboxylate transport system in Escherichia coli K12 is an active transport system and that at least one binding protein and two cytoplasmic membrane transport components are involved in the uptake of dicarboxylic acids. Recently, through surface labelling studies, some dicarboxylate binding proteins were found to be exposed on the cell surface. In the present paper, we demonstrate that the dicarboxylate transport component located in the outer membrane can be inactivated by two different kinds of nonpenetrating inhibitors, viz. proteases, and diazosulfanilic acid. These inhibitors seem to act on the dicarboxylate binding protein. By adding this protein to inactivated cells or to transport-negative mutants, we have succeeded in reconstituting the dicarboxylate transport system. These findings suggest that the dicarboxylate binding protein found on the cell surface plays an essential role in the translocation of dicarboxylic acids across the outer membrane.
Mice Lacking Histone Deacetylase 6 Have Hyperacetylated Tubulin but Are Viable and Develop Normally (2008)

Posttranslational modifications play important roles in regulating protein structure and function. Histone deacetylase 6 (HDAC6) is a mostly cytoplasmic class II HDAC, which has a unique structure with two catalytic domains and a domain binding ubiquitin with high affinity. This enzyme was recently identified as a multisubstrate protein deacetylase that can act on acetylated histone tails, alpha-tubulin and Hsp90. To investigate the in vivo functions of HDAC6 and the relevance of tubulin acetylation/deacetylation, we targeted the HDAC6 gene by homologous recombination in embryonic stem cells and generated knockout mice. HDAC6-deficient mice are viable and fertile and show hyperacetylated tubulin in most tissues. The highest level of expression of HDAC6 is seen in the testis, yet development and function of this organ are normal in the absence of HDAC6. Likewise, lymphoid development is normal, but the immune response is moderately affected. Furthermore, the lack of HDAC6 results in a small increase in cancellous bone mineral density, indicating that this deacetylase plays a minor role in bone biology. HDAC6-deficient mouse embryonic fibroblasts show apparently normal microtubule organization and stability and also show increased Hsp90 acetylation correlating with impaired Hsp90 function. Collectively, these data demonstrate that mice survive well without HDAC6 and that tubulin hyperacetylation is not detrimental to normal mammalian development.
Multichannel analysis of surface waves (1999)

Abstract The frequency-dependent properties of Rayleigh-type surface waves can be utilized for imaging and characterizing the shallow subsurface. Most surface-wave analysis relies on the accurate calculation of phase velocities for the horizontally traveling fundamental-mode Rayleigh wave acquired by stepping out a pair of receivers at intervals based on calculated ground roll wavelengths. Interference by coherent source-generated noise inhibits the reliability of shear-wave velocities determined through inversion of the whole wave field. Among these nonplanar, nonfundamental-mode Rayleigh waves (noise) are body waves, scattered and nonsource-generated surface waves, and higher-mode surface waves. The degree to which each of these types of noise contaminates the dispersion curve and, ultimately, the inverted shear-wave velocity profile is dependent on frequency as well as distance from the source. Multichannel recording permits effective identification and isolation of noise according to distinctive trace-to-trace coherency in arrival time and amplitude. An added advantage is the speed and redundancy of the measurement process. Decomposition of a multichannel record into a time variable-frequency format, similar to an uncorrelated Vibroseis record, permits analysis and display of each frequency component in a unique and continuous format. Coherent noise contamination can then be examined and its effects appraised in both frequency and offset space. Separation of frequency components permits real-time maximization of the S/N ratio during acquisition and subsequent processing steps. Linear separation of each ground roll frequency component allows calculation of phase velocities by simply measuring the linear slope of each frequency component. Breaks in coherent surface-wave arrivals, observable on the decomposed record, can be compensated for during acquisition and processing. Multichannel recording permits single-measurement surveying of a broad depth range, high levels of redundancy with a single field configuration, and the ability to adjust the offset, effectively reducing random or nonlinear noise introduced during recording. A multichannel shot gather decomposed into a swept-frequency record allows the fast generation of an accurate dispersion curve. The accuracy of dispersion curves determined using this method is proven through field comparisons of the inverted shear-wave velocity (v s ) profile with a downhole v s profile.
Multiple field strength in vivo T1 and T2 for cerebrospinal fluid protons (1986)

To estimate the feasibility of measuring in vivo CSF protein, oxygen, or other solutes through their effect on proton relaxation times, the T1 and T2 of CSF protons has been measured within the human lateral ventricles. T1 was measured at 6.25, 25.4, and 60.1 MHz with a two-point method. T2 was measured at 6.25 and 25.4 MHz using the CPMG sequence to acquire 8 echo images. The T1 was 4.3 s with no evidence of field dependence. The T2 was 2 s. Although these values approach those for water at the same temperature it is possible that the T1 is influenced by the normal oxygen concentration. Calculations based on the relaxivity of dissolved protein indicate that the use of these methods for the detection of elevated levels of CSF protein would be less sensitive than existing methods.
Reperfusion Differentially Induces Caspase-3 Activation in Ischemic Core and Penumbra After Stroke in Immature Brain (2003)

In the neonate, caspase-3 activation is likely to contribute substantially to cell death not only in the penumbra but also in the core after ischemia with reperfusion. Furthermore, persistent perfusion deficits result in less caspase-3 activation and appear to favor caspase-independent injury.
Hippocampal synaptic plasticity and NMDA receptors: a role in information storage? (1990)

There has recently been renewed interest in the idea that alterations in synaptic efficacy may be the neural basis of information storage. Particular attention has been focused upon long-term potentiation (LTP), a long-lasting, but experimentally induced synaptic change whose physiological properties point to it being a candidate memory mechanism. However, considerations of storage capacity and the possibility of concomitant activity-dependent synaptic depression make it unlikely that individual learning experiences will give rise to gross changes in field potentials similar to those that occur in LTP, even if learning and LTP utilize common neural mechanisms. One way of investigating the functional significance of LTP is to use selective antagonists of those excitatory amino acid receptors whose activation is essential for its induction. This paper discusses various design requirements for such experiments and reviews work indicating that the N-methyl-D-aspartate receptor antagonist AP5 causes a behaviourally selective learning impairment having certain common features to the behavioural profile seen after hippocampal lesions. Two new studies are described whose results show that AP5 has no effect upon the retrieval of previously established memories, and that the dose-response profile of the impairment of spatial learning occurs across a range of extracellular concentrations in hippocampus for which receptor selectivity exists. These experiments show that activation of NMDA receptors is essential for certain kinds of learning.
o-Fluoroazobenzenes as Readily Synthesized Photoswitches Offering Nearly Quantitative Two-Way Isomerization with Visible Light (2012)

Azobenzene functionalized with ortho-fluorine atoms has a lower energy of the n-orbital of the Z-isomer, resulting in a separation of the E and Z isomers' n→π* absorption bands. Introducing para-substituents allows for further tuning of the absorption spectra of o-fluoroazobenzenes. In particular, electron-withdrawing ester groups give rise to a 50 nm separation of the n→π* transitions. Green and blue light can therefore be used to induce E→Z and Z→E isomerizations, respectively. The o-fluoroazobenzene scaffold is readily synthesized and can be inserted into larger structures via its aryl termini. These new azobenzene derivatives can be switched in both ways with high photoconversions, and their Z-isomers display a remarkably long thermal half-life.
Fibroblast growth factors: An epigenetic mechanism of broad spectrum resistance to anticancer drugs (2000)

Based on the observation that removal of tumors from metastatic organs reversed their chemoresistance, we hypothesized that chemoresistance is induced by extracellular factors in tumor-bearing organs. By comparing chemosensitivity and proteins in different tumors (primary vs. metastases) and different culture systems (tumor fragment histocultures vs. monolayer cultures derived from the same tumor), we found elevated levels of acidic (aFGF) and basic (bFGF) fibroblast growth factors in the conditioned medium (CM) of solid and metastatic tumors. These CM induced broad spectrum resistance to drugs with diverse structures and action mechanisms (paclitaxel, doxorubicin, 5-fluorouracil). Inhibition of bFGF by mAb and its removal by immunoprecipitation resulted in complete reversal of the CM-induced chemoresistance, whereas inhibition/removal of aFGF resulted in partial reversal. Using CM that had been depleted of aFGF and/or bFGF and subsequently reconstituted with respective human recombinant proteins, we found that bFGF but not aFGF induced chemoresistance whereas aFGF amplified the bFGF effect. aFGF and bFGF fully accounted for the CM effect, indicating these proteins as the underlying mechanism of the chemoresistance. The FGF-induced resistance was not due to reduced intracellular drug accumulation or altered cell proliferation. We further showed that an inhibitor of aFGF/bFGF (suramin) enhanced the in vitro and in vivo activity of chemotherapy, resulting in shrinkage and eradication of well established human lung metastases in mice without enhancing toxicity. These results indicate elevated levels of extracellular aFGF/bFGF as an epigenetic mechanism by which cancer cells elude cytotoxic insult by chemotherapy, and provide a basis for designing new treatment strategies.
MUC1-C Oncoprotein Regulates Glycolysis and Pyruvate Kinase m2 Activity in Cancer Cells (2011)

Aerobic glycolysis in cancer cells is regulated by multiple effectors that include Akt and pyruvate kinase M2 (PKM2). Mucin 1 (MUC1) is a heterodimeric glycoprotein that is aberrantly overexpressed by human breast and other carcinomas. Here we show that transformation of rat fibroblasts by the oncogenic MUC1-C subunit is associated with Akt-mediated increases in glucose uptake and lactate production, consistent with the stimulation of glycolysis. The results also demonstrate that the MUC1-C cytoplasmic domain binds directly to PKM2 at the B- and C-domains. Interaction between the MUC1-C cytoplasmic domain Cys-3 and the PKM2 C-domain Cys-474 was found to stimulate PKM2 activity. Conversely, epidermal growth factor receptor (EGFR)-mediated phosphorylation of the MUC1-C cytoplasmic domain on Tyr-46 conferred binding to PKM2 Lys-433 and inhibited PKM2 activity. In human breast cancer cells, silencing MUC1-C was associated with decreases in glucose uptake and lactate production, confirming involvement of MUC1-C in the regulation of glycolysis. In addition, EGFR-mediated phosphorylation of MUC1-C in breast cancer cells was associated with decreases in PKM2 activity. These findings indicate that the MUC1-C subunit regulates glycolysis and that this response is conferred in part by PKM2. Thus, the overexpression of MUC1-C oncoprotein in diverse human carcinomas could be of importance to the Warburg effect of aerobic glycolysis.