gebhart/patrepeval huggingface dataset:
Urinary Podocyte Loss Is a More Specific Marker of Ongoing Glomerular Damage than Proteinuria (2005)

Podocyte loss contributes to the development of glomerulosclerosis. Although podocyte detachment has been recognized as a new mechanism of podocyte loss in glomerular diseases, its time course and relationship to disease activity are not known. Urinary excretion of viable podocytes was quantified in two models of transient glomerular injury, i.e., rats with puromycin aminonucleoside-induced nephrosis (PAN) and mesangioproliferative nephropathy (anti-Thy 1.1 nephritis model), as well as in a model of continuous glomerular injury, i.e., hypertensive nephropathy (5/6-nephrectomy model), and in aging rats. The number of glomerular Wilm's tumor (WT)-1-positive podocytes and the glomerular expression of cell-cycle proteins in vivo were assessed. Urinary podocyte loss occurred in both primary (PAN) and secondary (anti-Thy 1.1 nephritis) in parallel to the onset of proteinuria. However, subsequently proteinuria persisted despite remission of podocyturia. In continuous glomerular injury, i.e., after 5/6-nephrectomy, podocyturia paralleled the course of proteinuria and of systemic hypertension, whereas no podocyturia became detectable during normal aging (up to 12 mo). Despite podocyte detachment of varying degrees, no decrease in glomerular podocyte counts (i.e., WT-1 positive nuclei) was noted in either disease model. Podocyturia in the PAN and anti-Thy 1.1 nephritis model was preceded by entry of glomerular podocytes into the cell cycle, i.e., cyclin D1, cdc2, and/or proliferating cell nuclear antigen (PCNA) expression. Podocyturia is a widespread phenomenon in glomerular disease and not simply a reflection of proteinuria because it is limited to phases of ongoing glomerular injury. The data suggest that podocyturia may become a more sensitive means to assess the activity of glomerular damage than proteinuria.
Visual Genome: Connecting Language and Vision Using Crowdsourced Dense Image Annotations (2017)

Despite progress in perceptual tasks such as image classification, computers still perform poorly on cognitive tasks such as image description and question answering. Cognition is core to tasks that involve not just recognizing, but reasoning about our visual world. However, models used to tackle the rich content in images for cognitive tasks are still being trained using the same datasets designed for perceptual tasks. To achieve success at cognitive tasks, models need to understand the interactions and relationships between objects in an image. When asked “What vehicle is the person riding?”, computers will need to identify the objects in an image as well as the relationships riding(man, carriage) and pulling(horse, carriage) to answer correctly that “the person is riding a horse-drawn carriage.” In this paper, we present the Visual Genome dataset to enable the modeling of such relationships. We collect dense annotations of objects, attributes, and relationships within each image to learn these models. Specifically, our dataset contains over 108K images where each image has an average of $$35$$ objects, $$26$$ attributes, and $$21$$ pairwise relationships between objects. We canonicalize the objects, attributes, relationships, and noun phrases in region descriptions and questions answer pairs to WordNet synsets. Together, these annotations represent the densest and largest dataset of image descriptions, objects, attributes, relationships, and question answer pairs.
Oxidation of Thiols to Disulfides Using Silica Chloride as a Heterogeneous Catalyst (2006)

Abstract Silica chloride is used as a selective and effective heterogeneous catalyst for the rapid conversion of thiols to disulfides with quantitative yields in a very short period of time.
Cyclin D1 overexpression in hepatocellular carcinoma (2001)

Our results suggest that cyclin D1 overexpression may be an early event in hepatocarcinogenesis and that it plays a role in tumor differentiation. In addition, cyclin D1 expression is not correlated with tumor cell proliferation in HCCs.
Structures of the transcriptional regulator BgaR, a lactose sensor. (2019)

The structure of BgaR, a transcriptional regulator of the lactose operon in Clostridium perfringens, has been solved by SAD phasing using a mercury derivative. BgaR is an exquisite sensor of lactose, with a binding affinity in the low-micromolar range. This sensor and regulator has been captured bound to lactose and to lactulose as well as in a nominal apo form, and was compared with AraC, another saccharide-binding transcriptional regulator. It is shown that the saccharides bind in the N-terminal region of a jelly-roll fold, but that part of the saccharide is exposed to bulk solvent. This differs from the classical AraC saccharide-binding site, which is mostly sequestered from the bulk solvent. The structures of BgaR bound to lactose and to lactulose highlight how specific and nonspecific interactions lead to a higher binding affinity of BgaR for lactose compared with lactulose. Moreover, solving multiple structures of BgaR in different space groups, both bound to saccharides and unbound, verified that the dimer interface along a C-terminal helix is similar to the dimer interface observed in AraC.
Small molecule targeting Cdc42–intersectin interaction disrupts Golgi organization and suppresses cell motility (2013)

Signaling through the Rho family of small GTPases has been intensely investigated for its crucial roles in a wide variety of human diseases. Although RhoA and Rac1 signaling pathways are frequently exploited with the aid of effective small molecule modulators, studies of the Cdc42 subclass have lagged because of a lack of such means. We have applied high-throughput in silico screening and identified compounds that are able to fit into the surface groove of Cdc42, which is critical for guanine nucleotide exchange factor binding. Based on the interaction between Cdc42 and intersectin (ITSN), a specific Cdc42 guanine nucleotide exchange factor, we discovered compounds that rendered ITSN-like interactions in the binding pocket. By using in vitro binding and imaging as well as biochemical and cell-based assays, we demonstrated that ZCL278 has emerged as a selective Cdc42 small molecule modulator that directly binds to Cdc42 and inhibits its functions. In Swiss 3T3 fibroblast cultures, ZCL278 abolished microspike formation and disrupted GM130-docked Golgi structures, two of the most prominent Cdc42-mediated subcellular events. ZCL278 reduces the perinuclear accumulation of active Cdc42 in contrast to NSC23766, a selective Rac inhibitor. ZCL278 suppresses Cdc42-mediated neuronal branching and growth cone dynamics as well as actin-based motility and migration in a metastatic prostate cancer cell line (i.e., PC-3) without disrupting cell viability. Thus, ZCL278 is a small molecule that specifically targets Cdc42-ITSN interaction and inhibits Cdc42-mediated cellular processes, thus providing a powerful tool for research of Cdc42 subclass of Rho GTPases in human pathogenesis, such as those of cancer and neurological disorders.
Interferometric Synthetic Aperture Microscopy: Computed Imaging for Scanned Coherent Microscopy (2008)

Three-dimensional image formation in microscopy is greatly enhanced by the use of computed imaging techniques. In particular, Interferometric Synthetic Aperture Microscopy (ISAM) allows the removal of out-of-focus blur in broadband, coherent microscopy. Earlier methods, such as optical coherence tomography (OCT), utilize interferometric ranging, but do not apply computed imaging methods and therefore must scan the focal depth to acquire extended volumetric images. ISAM removes the need to scan the focus by allowing volumetric image reconstruction from data collected at a single focal depth. ISAM signal processing techniques are similar to the Fourier migration methods of seismology and the Fourier reconstruction methods of Synthetic Aperture Radar (SAR). In this article ISAM is described and the close ties between ISAM and SAR are explored. ISAM and a simple strip-map SAR system are placed in a common mathematical framework and compared to OCT and radar respectively. This article is intended to serve as a review of ISAM, and will be especially useful to readers with a background in SAR.
Tumor necrosis factor in the serum of patients with systemic lupus erythematosus (1989)

In view of recent data demonstrating defective production of tumor necrosis factor alpha (TNF cachectin) in murine autoimmune lupus nephritis, we studied the serum levels of TNF in 22 patients with systemic lupus erythematosus (SLE), using a specific radioimmunoassay. Patients with SLE had either normal or slightly elevated levels of TNF when compared with healthy control subjects. All 5 SLE patients with concomitant infections had elevated levels of TNF; those with systemic bacterial infection had markedly raised levels (median 260 pg/ml; normal less than 40). These results show that SLE in humans is not associated with a depressed level of circulating TNF, and that in SLE patients with infection, the level of TNF in the circulation increases in a manner similar to that in other subjects.
High‐Density Lipoprotein Nanoparticles Deliver RNAi to Endothelial Cells to Inhibit Angiogenesis (2014)

Systemic delivery of therapeutic nucleic acids to target cells and tissues outside of the liver remains a major challenge. We synthesized a biomimetic high density lipoprotein nanoparticle (HDL NP) for delivery of a cholesteryl modified therapeutic nucleic acid (RNAi) to vascular endothelial cells, a cell type naturally targeted by HDL. HDL NPs adsorb cholesteryl modified oligonucleotides and protect them from nuclease degradation. As proof of principle, we delivered RNAi targeting vascular endothelial growth factor receptor 2 (<i>VEGFR2</i>) to endothelial cells to effectively silence target mRNA and protein expression <i>in vitro.</i> In addition, data show that treatment strongly attenuated <i>in vivo</i> neovascularization measured using a standard angiogenesis assay and in hypervascular tumor allografts where a striking reduction in tumor growth was observed. For effective delivery, HDL NPs required the expression of the cell surface protein scavenger receptor type-B1 (SR-B1). No toxicity of HDL NPs was measured <i>in vitro</i> or after <i>in vivo</i> administration. Thus, by using a biomimetic approach to nucleic acid delivery, data demonstrate that systemically administered RNAi-HDL NPs target SR-B1 expressing endothelial cells to deliver functional anti-angiogenic RNAi as a potential treatment of cancer and other neo-vascular diseases.
Gene inactivation of Na+/H+ exchanger isoform 1 attenuates apoptosis and mitochondrial damage following transient focal cerebral ischemia (2008)

We investigated mechanisms underlying the Na+/H+ exchanger isoform 1 (NHE1)-mediated neuronal damage in transient focal ischemia. Physiological parameters, body and tympanic temperatures, and regional cerebral blood flow during 30 min of middle cerebral artery occlusion were similar in wild-type NHE1 (NHE1+/+) and NHE1 heterozygous (NHE1+/-) mice. NHE1+/+ mice developed infarct volume of 57.3 +/- 8.8 mm(3) at 24 h reperfusion (Rp), which progressed to 86.1 +/- 10.0 mm(3) at 72 h Rp. This delayed cell death was preceded by release of mitochondrial cytochrome c (Cyt. C), nuclear translocation of apoptosis-inducing factor (AIF), activation of caspase-3, and TUNEL-positive staining and chromatin condensation in the ipsilateral hemispheres of NHE1+/+ brains. In contrast, NHE1+/- mice had a significantly smaller infarct volume and improved neurological function. A similar neuroprotection was obtained with NHE1 inhibitor HOE 642. The number of apoptotic cells, release of AIF and Cyt. C or levels of active caspase-3 was significantly reduced in NHE1+/- brains. These data imply that NHE1 activity may contribute to ischemic apoptosis. Ischemic brains did not exhibit changes of NHE1 protein expression. In contrast, up-regulation of NHE1 expression was found in NHE1+/+ neurons after in vitro ischemia. These data suggest that NHE1 activation following cerebral ischemia contributes to mitochondrial damage and ischemic apoptosis.
Consistent and Selective Expression of the Discoidin Domain Receptor-1 Tyrosine Kinase in Human Brain Tumors (2000)

ABSTRACT OBJECTIVE Few molecular targets are both consistently and selectively expressed in a majority of central nervous system (CNS) neoplasms. Receptor tyrosine kinases have been implicated in brain tumor oncogenesis. We previously isolated one such receptor, discoidin domain receptor-1 (DDR1), from high-grade pediatric brain tumors. Here, we analyze the cellular origin and distribution of DDR1 expression in human brain tumors and its expression in tumor cells relative to surrounding brain. METHODS By use of a digoxigenin-labeled DDR1 riboprobe, we investigated the expression of DDR1 messenger ribonucleic acid in a prospective series of 30 resected human primary and metastatic brain neoplasms, nonneoplastic human brain, and mouse embryonic brain, as well as a mouse glioblastoma model, by in situ hybridization. RESULTS All the high-grade primary brain and metastatic brain tumors showed unequivocal, intense DDR1 expression within the majority of tumor cells, whereas expression was not observed in hyperplastic tumor blood vessels, normal brain blood vessels, inflammatory cells, or in the normal brain tissue that surrounded the tumor. Receptor expression was limited to tumor cells located within solid tumor tissue. Overall, 27 of 29 resected CNS tumors exhibited tumor cell-specific DDR1 expression, whereas one specimen composed of isolated glioblastoma cells within invaded brain parenchyma showed no detectable staining for this receptor. DDR1 was also expressed preferentially in the ventricular zone (a region of highly proliferating precursor cells) of mice at embryonic Day 15.5. CONCLUSION We found that DDR1 is consistently expressed in all high-grade brain neoplasms studied and is selective for tumor cells in the specimens analyzed. The expression of DDR1 by tumor cells of CNS neoplasms and by primitive cells of the embryonic ventricular zone suggests that DDR1 is a potentially useful marker of tumor cells within the CNS.
Efficient near-infrared up-conversion photoluminescence in carbon nanotubes (2015)

Photoluminescence phenomena normally obey Stokes' law of luminescence according to which the emitted photon energy is typically lower than its excitation counterparts. Here we show that carbon nanotubes break this rule under one-photon excitation conditions. We found that the carbon nanotubes exhibit efficient near-infrared photoluminescence upon photoexcitation even at an energy lying >100-200 meV below that of the emission at room temperature. This apparently anomalous phenomenon is attributed to efficient one-phonon-assisted up-conversion processes resulting from unique excited-state dynamics emerging in an individual carbon nanotube with accidentally or intentionally embedded localized states. These findings may open new doors for energy harvesting, optoelectronics and deep-tissue photoluminescence imaging in the near-infrared optical range.
Melatonin Agonist Tasimelteon (VEC-162) for Transient Insomnia After Sleep-Time Shift: Two Randomized Controlled Multicentre Trials (2009)

Substantial evidence suggests that exogenous melatonin and melatonin agonists promote sleep and entrain endogenous circadian rhythms. Two previous meta-analyses evaluated the efficacy of melatonin treatment in patients with secondary sleep disorders or circadian rhythm sleep disorders and reached opposite conclusions on efficacy. This study presents the results of 2 randomized, double-blind, placebo-controlled, parallel-group trials, which evaluated tasimelteon (VEC-162), a novel melatonin agonist, in a model of transient insomnia induced by a 5-hour advance in the sleep–wake schedule. The investigators hypothesized that the melatonin agonist would reduce the sleep disruption produced by transient insomnia and readjust circadian rhythms. The study subjects in the phase II study were 39 healthy individuals who were randomized to receive either tasimelteon (in doses of 10 [n = 9], 20 [n = 8], 50 [n = 7], or 100 mg [n = 7]) or placebo (n = 8) 30 minute before bedtime. The plasma melatonin concentration was measured for circadian phase assessment. The study subjects in the phase III study were 411 healthy individuals who were randomized to receive either tasimelteon (20 [n = 100], 50 [n = 102], or 100 mg [n = 106]) or placebo (n = 103) 30 minute before bedtime. Changes in sleep patterns were assessed by polysomnography in the phase II and III studies with prespecified primary efficacy outcomes. Safety was assessed by daily queries about adverse events and physical examinations. In the phase II study, compared with placebo, tasimelteon increased sleep efficiency and duration, and reduced sleep latency and latency to persistent sleep. There was a dose-dependent shift in plasma melatonin to an earlier hour associated with treatment. In addition to improvements in sleep latency, efficiency, duration, and latency to persistent sleep, treated-individuals in the phase III study had reduced wake after sleep onset (improved sleep maintenance). The frequency and severity of adverse events were low and similar among all treatment groups. These findings indicate that tasimelteon improves sleep initiation and maintenance simultaneously with a shift in endogenous circadian rhythms and has therapeutic potential for transient insomnia associated with circadian rhythm sleep disorders.
Efficient Learning of Sparse Representations with an Energy-Based Model (2007)

We describe a novel unsupervised method for learning sparse, overcomplete features. The model uses a linear encoder, and a linear decoder preceded by a sparsifying non-linearity that turns a code vector into a quasi-binary sparse code vector. Given an input, the optimal code minimizes the distance between the output of the decoder and the input patch while being as similar as possible to the encoder output. Learning proceeds in a two-phase EM-like fashion: (1) compute the minimum-energy code vector, (2) adjust the parameters of the encoder and decoder so as to decrease the energy. The model produces stroke detectors when trained on handwritten numerals, and Gabor-like filters when trained on natural image patches. Inference and learning are very fast, requiring no preprocessing, and no expensive sampling. Using the proposed unsupervised method to initialize the first layer of a convolutional network, we achieved an error rate slightly lower than the best reported result on the MNIST dataset. Finally, an extension of the method is described to learn topographical filter maps.
Calibration of a laser galvanometric scanning system by adapting a camera model (2009)

We propose a new calibration method for a laser galvanometric scanning (LGS) system by adapting the camera model to model the LGS system. The similarity between the camera system and the LGS system has been investigated and exploited. The distortion parameters are acquired by solving a nonlinear least squares problem of 12 coefficients using the Levenberg-Marquardt algorithm. The efficiency of the calibration is improved. Experiments are conducted to verify the proposed model.
Graphic codes for computer holography (1995)

Several aspects of graphic codes of computer-generated holograms are discussed. This is in contrast to the algorithmic studies that have dominated research in the field of computer holography in recent years. We study the graphic cells of binary cell-oriented holograms under the aspects of specificfabrication and performance problems such as the pen-width problem and zero-order scattering. Asresult, we present experiments with new or modified cell structures that avoid some of these problems.
Efficient code generation for automatic parallelization and optimization (2004)

Supercompilers look for the best execution order of the statement instances in the most compute intensive kernels. It has been extensively shown that the polyhedral model provides convenient abstractions to find and perform the useful program transformations. Nevertheless, the current polyhedral code generation algorithms lack for flexibility by adressing mainly unimodular or at least invertible transformation functions. Moreover, their complexity is challenging for large problems (with many statements). In this paper, we discuss a general transformation framework able to deal with non-unimodular, non-invertible functions. A completed and improved version of one of the best algorithms known so far is presented to actually perform the code generation. Experimental evidence proves the ability of our framework to handle real-life problems.
Preparation, Reactivity and Peptide Labelling Properties of (η6‐Arene)ruthenium(II) Complexes with Pendant Carboxylate Groups (2003)

Abstract (η 6 ‐Arene)ruthenium( II ) complexes of the type [{[η 6 ‐C 6 H 5 (CH 2 ) n COOH]Ru(µ‐Cl)Cl} 2 ] ( 2a , n = 1; 3 , n = 3) with tethered carboxylate groups can be obtained by dehydrogenation of the appropriate cyclohexadiene with RuCl 3 ·3H 2 O. Formation of a κ O ‐coordinated chelate in weakly acidic solution is observed by means of a 1 H NMR titration for both [{η 6 ‐C 6 H 5 (CH 2 ) 3 COOH}Ru(aq)](OTf) 2 ( 3a′ ) and [{η 6 ‐C 6 H 5 (CH 2 ) 3 COOH}Ru(phen)(aq)](OTf) 2 ( 5′ ). Sandwich complexes of the type [{η 6 ‐C 6 H 5 (CH 2 ) 3 COOH}Ru(η 6 ‐amino acid)](OTf) 2 [amino acid = AcpheOH ( 6 ), ActyrOEt ( 7 ), ActrpOH ( 8 )] can be prepared by treating [{η 6 ‐C 6 H 5 (CH 2 ) 3 COOH}Ru(acetone) 3 ](OTf) 2 with the appropriate aromatic bioligand in CF 3 COOH ( 6 / 8 ) or CH 2 Cl 2 ( 7 ). Chemospecific η 6 ‐labelling of the C ‐terminal indole function is observed for the peptide HphetrpOH in the analogous complex 9 . Quantitative formation of 8 can also be achieved in aqueous solution in the presence of a 3:1 excess of the {η 6 ‐C 6 H 5 (CH 2 ) 3 COOH}Ru II fragment. This can also be employed for the N ‐terminal labelling of amino acids and peptides in its sandwich complex [(η 6 ‐C 6 Me 6 )Ru{η 6 ‐C 6 H 5 (CH 2 ) 3 COOH}](OTf) 2 ( 10 ). Coupling reactions by the carbodiimide method with EDC afford water‐stable complexes of the type [(η 6 ‐C 6 Me 6 )Ru{η 6 ‐C 6 H 5 (CH 2 ) 3 C(O)R}](OTf) 2 [R = trpOMe ( 11 ), pheOMe ( 12 ), glyglyOEt ( 13 )] in good yields. X‐ray structures of [(η 6 ‐C 6 H 5 CH 2 COOC 2 H 5 )RuCl(phen)](OTf) ( 4b′ ) and 10 are reported. (© Wiley‐VCH Verlag GmbH &amp; Co. KGaA, 69451 Weinheim, Germany, 2003)
Kinetics of thrombopoiesis (1968)

Measurements of megakaryocyte number, volume, nuclear number, and cytoplasmic granulation were compared in animals with induced thrombocytosis, normal platelet counts, and induced thrombocytopenia for 4- and 10-day periods. Thrombopoiesis, as measured by megakaryocytic mass and (35)S incorporation into platelets, appeared to be regulated by the demand for circulating platelets. In addition, two mechanisms were operative in the alteration of thrombopoiesis. The first mechanism involved the regulation of endomitosis in the immature megakaryocytes which in turn determined the subsequent volume of platelet-producing cytoplasm. The second mechanism regulated the number of megakaryocytes formed from the precursor, "stem cell," compartment.