gebhart/patrepeval huggingface dataset:
Accelerated HF-rTMS in treatment-resistant unipolar depression: Insights from subgenual anterior cingulate functional connectivity (2014)

Strong rsFC anti-correlation between the sgACC and parts of the left prefrontal cortex could be indicative of a beneficial outcome. Accelerated HF-rTMS treatment designs have the potential to acutely adjust deregulated sgACC neuronal networks in TRD patients.
Laser capture microdissection: beyond functional genomics to proteomics. (2000)

Proteomics will drive biology and medicine beyond genomics, and can have a profound impact on molecular diagnostics. The posttranslational modifications of cellular proteins that govern physiology and become deranged in disease cannot be accurately portrayed by gene expression alone. Consequently, new technology is being developed to discover, and quantitatively monitor, proteomic changes that are associated with disease etiology and progression. In the past, proteomic technologies were restricted to tumor cell lines or homogenized bulk tissue specimens. This source material may not accurately reflect molecular events taking place in the specific cells of the tissue itself. This article describes a completely new class of proteomic-based approaches aimed at the identification and investigation of protein markers in the actual histologically defined cell populations that are immersed in heterogeneous diseased tissue. It is envisioned that these investigations will eventually lead to novel diagnostic, prognostic, or therapeutic markers that can be applied to monitor therapeutic toxicity or efficacy.
Small Interfering RNA Targeting Heme Oxygenase-1 Enhances Ischemia-Reperfusion-induced Lung Apoptosis (2004)

Heme oxygenase-1 (HO-1) is emerging as an important cytoprotective enzyme system in a variety of injury models. To optimize future therapeutic applications of HO-1, it is necessary to delineate the precise functions and mechanisms as well as modes of externally regulating HO-1 expression. Investigations have been limited by difficulties with the generation of HO-1 null mice and the lack of specific HO-1 inhibitors. Lung ischemia-reperfusion (I-R) injury is the inciting event in acute lung failure following transplantation, surgery, and shock. To study the function of HO-1 in I-R-induced lung injury, we designed small interfering RNA (siRNA) sequences that effectively suppress HO-1 expression both in vitro and in vivo in an organ-specific manner. In this study we show that there is enhanced apoptosis, via increased Fas expression and caspase 3 activity, in the presence of HO-1 siRNA in endothelial cells and mouse lung during I-R injury, whereas HO-1 overexpression attenuates apoptosis. To the best of our knowledge, we are the first to demonstrate that lung-specific siRNA delivery can be achieved by intranasal administration without the need for viral vectors or transfection agents in vivo, thereby obviating potential concerns for toxicity if siRNA technology is to have clinical application in the future.
Functional Upregulation of the Vascular Endothelial Growth Factor Receptor KDR by Hypoxia (1996)

These data indicate that hypoxia stimulates VEGF-dependent signaling not only by upregulation of VEGF ligand but also by functional upregulation of a specific signaling receptor. Therefore, these data provide evidence that the endothelium plays an active role in hypoxia-induced angiogenesis.
A New Family of Enantiomerically Pure Smectic C* Liquid Crystals with a Bridged Chiral Biphenyl Core (1998)

The synthesis of enantiomerically pure bridged biphenyl compounds, (−)-(R)-3,9-bis(4-(dodecyloxy)benzoyloxy)-5,7-dihydro-1,11-dimethyldibenzo[c,e]thiepine, 13, and (−)-(R)-3,9-bis(4-(dodecyloxy)benzoyloxy)-5,7-dihydro-1,11-dimethyldibenzo[c,e]-thiepin dioxide, 14, is described. This is the first report of smectic C* mesophases with a rigid twisted biphenyl core and axial chirality.
Quantitative phase imaging using actively stabilized phase-shifting low-coherence interferometry (2004)

We describe a quantitative phase-imaging interferometer in which phase shifting and noise cancellation are performed by an active feedback loop using a reference laser. Depth gating via low-coherence light allows phase measurement from weakly reflecting biological samples. We demonstrate phase images from a test structure and living cells.
Light field rendering (1996)

Article Free Access Share on Light field rendering Authors: Marc Levoy Computer Science Department, Stanford University, Gates Computer Science Building 3B, Stanford University Stanford, CA Computer Science Department, Stanford University, Gates Computer Science Building 3B, Stanford University Stanford, CAView Profile , Pat Hanrahan Computer Science Department, Stanford University, Gates Computer Science Building 3B, Stanford University Stanford, CA Computer Science Department, Stanford University, Gates Computer Science Building 3B, Stanford University Stanford, CAView Profile Authors Info & Claims SIGGRAPH '96: Proceedings of the 23rd annual conference on Computer graphics and interactive techniquesAugust 1996 Pages 31–42https://doi.org/10.1145/237170.237199Online:01 August 1996Publication History 2,352citation10,366DownloadsMetricsTotal Citations2,352Total Downloads10,366Last 12 Months729Last 6 weeks129 Get Citation AlertsNew Citation Alert added!This alert has been successfully added and will be sent to:You will be notified whenever a record that you have chosen has been cited.To manage your alert preferences, click on the button below.Manage my AlertsNew Citation Alert!Please log in to your account Save to BinderSave to BinderCreate a New BinderNameCancelCreateExport CitationPublisher SiteeReaderPDF
Directed Self-assembly of Topcoat-free, Integration-friendly High-^|^chi; Block Copolymers (2014)

To extend the scaling beyond the most widely used poly(styrene-b-methyl methacrylate) (PS-b-PMMA), organic high-χ block copolymers (BCPs) were developed. Vertically oriented BCP domains were obtained by simple coat and bake process without application of an additional layer of a topcoat material. In addition, process-friendly conditions including low bake temperature (< 200 °C) and short bake time (≤ 5 min) provided a simple scheme to integrate these high-χ block copolymers to standard lithography process and pre-patterns defined by 193i lithography. Successful demonstration of directed self-assembly of these high-χ block copolymers on 193i-defined guiding pre-patterns offers a simple route to access well-aligned perpendicular lamellae and cylinders with a pitch less than 20 nm.
High-Throughput Proteomics:  A Flexible and Efficient Pipeline for Protein Production (2002)

Many studies that aim to characterize the proteome require the production of pure protein in a high-throughput format. We have developed a system for high-throughput subcloning, protein expression and purification that is simple, fast, and inexpensive. We utilized ligation-independent cloning with a custom-designed vector and developed an expression screen to test multiple parameters for optimal protein production in E. coli. A 96-well format purification protocol that produced microgram quantities of pure protein was also developed.
The Tight Junction Proteins Claudin-1, -6, and -9 Are Entry Cofactors for Hepatitis C Virus (2008)

Hepatitis C virus (HCV) is a major cause of liver disease in humans. The CD81 tetraspanin is necessary but not sufficient for HCV penetration into hepatocytes, and it was recently reported that the tight junction protein claudin-1 is a critical HCV entry cofactor. Here, we confirm the role of claudin-1 in HCV entry. In addition, we show that claudin-6 and claudin-9 expressed in CD81(+) cells also enable the entry of HCV pseudoparticles derived from six of the major genotypes. Whereas claudin-1, -6, and -9 function equally well as entry cofactors in endothelial cells, claudin-1 is more efficient in hepatoma cells. This suggests that additional cellular factors modulate the ability of claudins to function as HCV entry cofactors. Our work has generated novel and essential means to investigate the mechanism of HCV penetration into hepatocytes and the role of the claudin protein family in HCV dissemination, replication, and pathogenesis.
Replication of rep-cap Genes Is Essential for the High-Efficiency Production of Recombinant AAV (1997)

Adenoassociated virus (AAV) has been developed as a vector for gene transfer because of its advantageous features: it is nonpathogenic, naturally replication-defective; it infects growth-arrested cells, and can transfer the therapeutic gene without co-delivery of any viral genes. However, a major obstacle in conducting systematic studies of AAV-mediated gene transfer in animal models is the difficulty of obtaining large quantities of recombinant virus. Recent development of AAV packaging cell lines has simplified the procedure of producing recombinant AAV (rAAV). However, the efficacy of producing large quantities of rAAV with these cell lines is yet to be demonstrated. In this study we have analyzed the difference between the replication of wild-type AAV and the production of rAAV. Using a combined single-plasmid system that carries both an AAV vector and the rep-cap genes, we have demonstrated that the AAV vector replicates to high number of copies whereas the rep-cap sequences remain unamplified in the virus-producing cells, When the copy number of rep-cap genes was increased by varying the vector/rep-cap ratio in the transfection mixture, the titer of rAAV increased proportionally. Thus, the titer of rAAV is limited by the low copy number of the rep-cap genes that results in an insufficient expression of the Rep and Cap proteins. We have also shown that generation of double-stranded replicating form of the vector DNA is accompanied by an amplified transgene expression. We propose that the increased gene expression from the accumulating double-stranded viral DNA is likely to be the mechanism by which wild-type AAV produces a large number of particles necessary to package the self-replicating AAV genomes. We conclude that mimicking this amplified expression of rep-cap genes may provide the key to produce high titers of rAAV.
Carbon‐11 labelling of MADAM in two different positions: a highly selective PET radioligand for the serotonin transporter (2001)

Abstract Imaging by scintigraphy the serotonin transporter (5‐HTT) in the living human brain would be of great value in research on the pathophysiology and treatment of neuropsychiatric disorders such as depression. For that reason, and in order to obtain a selective radiotracer applicable to PET, we report here the carbon‐11 labelling of a selective 5‐HTT radioligand: N , N ‐dimethyl‐2‐(2‐amino‐4‐methylphenylthio)benzylamine or MADAM in two different positions: [ p ‐ 11 C‐methyl]MADAM and [ N ‐ 11 C‐methyl]MADAM. The synthesis of Bu 3 Sn‐ADAM and N ‐dimethyl‐MADAM is described. [ p ‐ 11 C‐methyl]MADAM was obtained by a Stille coupling reaction between Bu 3 Sn‐ADAM and [ 11 C]methyl iodide using palladium (0) as a catalyst without (Ia) or with copper chloride as a co‐catalyst (Ib). [ N ‐ 11 C‐methyl]MADAM was obtained by an N ‐methylation reaction between N ‐demethyl‐MADAM and [ 11 C]methyl iodide (II). The carbon‐11 incorporation yield in [ p ‐ 11 C‐methyl]MADAM was 10–30% (Ia and Ib) and in [ N ‐ 11 C‐methyl]MADAM was 75‐80% (II). The final product in each case was obtained in 30 min total synthesis time, including HPLC purification and with &gt;99% radiochemical purity. Copyright © 2001 John Wiley &amp; Sons, Ltd.
2-Aminothiazole as a Novel Kinase Inhibitor Template. Structure−Activity Relationship Studies toward the Discovery of N -(2-Chloro-6-methylphenyl)-2-[[6-[4-(2-hydroxyethyl)-1- piperazinyl)]-2-methyl-4-pyrimidinyl]amino)]-1,3-thiazole-5-carboxamide (Dasatinib, BMS-354825) as a Potent pan -Src Kinase Inhibitor (2006)

2-aminothiazole (1) was discovered as a novel Src family kinase inhibitor template through screening of our internal compound collection. Optimization through successive structure-activity relationship iterations identified analogs 2 (Dasatinib, BMS-354825) and 12m as pan-Src inhibitors with nanomolar to subnanomolar potencies in biochemical and cellular assays. Molecular modeling was used to construct a putative binding model for Lck inhibition by this class of compounds. The framework of key hydrogen-bond interactions proposed by this model was in agreement with the subsequent, published crystal structure of 2 bound to structurally similar Abl kinase. The oral efficacy of this class of inhibitors was demonstrated with 12m in inhibiting the proinflammatory cytokine IL-2 ex vivo in mice (ED50 approximately 5 mg/kg) and in reducing TNF levels in an acute murine model of inflammation (90% inhibition in LPS-induced TNFalpha production when dosed orally at 60 mg/kg, 2 h prior to LPS administration). The oral efficacy of 12m was further demonstrated in a chronic model of adjuvant arthritis in rats with established disease when administered orally at 0.3 and 3 mg/kg twice daily. Dasatinib (2) is currently in clinical trials for the treatment of chronic myelogenous leukemia.
Cell Death in the Thin Films of Bursting Bubbles (1992)

A sparged gas bubble floating at the liquid interface has a liquid film which drains and thins until the film spontaneously ruptures at a point. This causes rapid retraction of the film, forming a rim of collected fluid. This rim moves at a constant velocity of about 3 m/s and any cells in the bubble film are rapidly accelerated to this velocity in the moving rim. Half of the surface energy originally in the thin film is converted to kinetic energy of the rim, while the rest is dissipated in this rim. The rate of energy dissipation per mass of rim fluid is approximately 9000 m2/s3, which corresponds to a Kolmogorov eddy size of 3.2 microns in fully developed turbulence or a shear stress of 95 N/m2 in laminar flow. Either of these limiting cases presents an environment in which rapid cell death would be expected. Experiments with Sf-9 insect cells suggest that the cell concentration in these thin films is 0.6 times the bulk liquid concentration and that about 20% of these cells are killed when the film ruptures. An equation based on this mechanism accurately predicts the death rate.
Conformational mimicry: Synthesis and solution conformation of a cyclic somatostatin hexapeptide containing a tetrazole cis amide bond surrogate (1995)

Potent, cyclic hexapeptide analogues of somatostatin are generally believed to adopt some common secondary structural features: a II' beta turn at one end of the cycle, and a type VI turn with a cis amide bond at the other. A proposed cis amide surrogate, the 1,5-disubstituted tetrazole, has been placed into a cyclic hexapeptide analog of somatostatin in order to constrain the putative cis amide bond. The final cyclization was done by either chemical or enzymatic means. The product, cyclo(Ala6-Tyr7-D-Trp8-Lys9-Val10-Phe11-psi[CN4] ), was found to have 83% of the activity of somatostatin. Solution nmr analysis in DMSO/water revealed that the backbone as well as side chain chi1 and chi2 were well ordered. Relaxation matrix methods were used to extract distance restraints from the nuclear Overhauser effect spectroscopy data set, and these were used in a systematic search of torsional space to identify structures consistent with the nmr data. Restrained minimizations of these structures using a number of different force fields produced structures having the expected beta II' turn at D-Trp8-Lys9 and a beta VIa turn in the Phe11-psi[CN4]-Ala6 portion of the molecule. The similarity of the minimized structures to those previously reported for cyclic hexapeptide analogues of somatostatin confirms the similarity of the tetrazole geometry to that of the cis amide in solution.
Amine‐Functionalized Polyacrylamide for Labeling and Crosslinking Purposes (2007)

Abstract Free radical copolymerization of acrylamide with N ‐(3‐aminopropyl)‐methacrylamide yields water‐soluble polymers with randomly distributed pendent nucleophilic amine moieties. The copolymerization parameters were determined to be r 1 = 0.49 and r 2 = 0.85. A procedure which allows controlling the degree of functionalization and the molecular weight is described in detail. Copolymers with low amounts of functional groups were used to synthesize polymers with fluoresceine or rhodamine side groups as fluorescence labels. Furthermore, reaction of the amine moieties of the copolymers with glutaraldehyde under suitable conditions provides a way to generate polymer networks via random crosslinking of existent chains in a semi‐dilute solution. magnified image
Fibronectin receptors of phagocytes. Characterization of the Arg-Gly-Asp binding proteins of human monocytes and polymorphonuclear leukocytes. (1988)

We have defined the cell surface molecules of human monocytes and PMN that bind to the chymotryptic cell binding domain of Fn and to a synthetic peptide, KYAVTGRGDS, based on the sequence of Fn, by affinity chromatography. Monocytes express two receptors that differ in their affinity for CBD-Sepharose and peptide-Sepharose, but that both recognize the RGD sequence. Only a single receptor is purified from PMN, which resembles the monocyte surface molecule that binds to peptide-Sepharose. These receptors are not part of the Mac-1, LFA-1, p(150,95) family, but do have homology to the platelet Fn receptor, gpIIb/IIIa. Interestingly, the antigenic crossreactivity between gpIIb/IIIa and the phagocyte receptors purified on peptide-Sepharose is largely in the beta chain of the receptors. The alpha chains appear to be distinct, based on molecular weight, antigenic analysis, and ligand specificity. This receptor also seems to be the surface molecule on monocytes that is critical for phagocytosis enhancement by Fn. Thus, we have defined the phagocyte Fn receptor that transduces the signal for increased phagocytosis by monocytes; it may be a third member of a family of adhesion molecules that includes the gpIIb/IIIa of platelets and the vitronectin receptor of fibroblasts.
Effect of furosemide on calcium and magnesium transport in the rat nephron (1981)

Superficial tubules were perfused in vivo to determine the effect of intraluminal furosemide on electrolyte transport in the loop of Henle and distal tubule of the rat with special reference to calcium and magnesium reabsorption. in vivo perfusion of single tubules allowed us the opportunity to investigate separate electrolyte transfers with altering the corticomedullary concentration gradient within the kidney. Intraluminal furosemide (3 X 10(-6) and 3 X 10(-5) M) resulted in proportionately greater calcium and magnesium inhibition relative to sodium and chloride in Henle's loop. Furosemide had little effect on transport function within the perfused superficial distal tubule. Distal calcium and magnesium reabsorption was dependent on their respective deliveries to this segment. Parathyroid hormone increased fractional calcium and magnesium reabsorption in Henle's loop and the distal tubule in the presence of intraluminal furosemide. These results are consistent with a luminal effect of furosemide in the loop of Henle that inhibits calcium and magnesium transport to a greater degree than sodium chloride. Intraluminal ethacrynic acid (10(-4) M) or its cysteine complex had no effect on electrolyte transport in the perfused rat nephron.
Classification of human lung carcinomas by mRNA expression profiling reveals distinct adenocarcinoma subclasses (2001)

We have generated a molecular taxonomy of lung carcinoma, the leading cause of cancer death in the United States and worldwide. Using oligonucleotide microarrays, we analyzed mRNA expression levels corresponding to 12,600 transcript sequences in 186 lung tumor samples, including 139 adenocarcinomas resected from the lung. Hierarchical and probabilistic clustering of expression data defined distinct subclasses of lung adenocarcinoma. Among these were tumors with high relative expression of neuroendocrine genes and of type II pneumocyte genes, respectively. Retrospective analysis revealed a less favorable outcome for the adenocarcinomas with neuroendocrine gene expression. The diagnostic potential of expression profiling is emphasized by its ability to discriminate primary lung adenocarcinomas from metastases of extra-pulmonary origin. These results suggest that integration of expression profile data with clinical parameters could aid in diagnosis of lung cancer patients.
Influence of Disulfide Density and Molecular Weight on Disulfide Cross-Linked Polyethylenimine as Gene Vectors (2009)

Disulfide cross-linked polyethylenimines (PEI(X)-SS(Y), where X refers to the molecular weight of raw PEI, and Y refers to the thiolation degree) were prepared in two steps: First, thiol groups were introduced on a raw polyethylenimine (PEI) by the amine-induced ring-opening reaction of thiirane. Second, thiol groups were oxidized by DMSO to form the disulfide cross-links. The cross-linked PEI(800)-SS(Y) polymers with a moderate thiolation degree (PEI(800)-SS(2.6,) PEI(800)-SS(3.5), and PEI(800)-SS(4.5)) could form compact polyplexes with a size of 200-300 nm at an adequate N/P ratio. In contrast, those with a too low or too high thiolation degree (Y below 2.6 or above 4.5) formed much looser polyplexes with a size above 600 nm. The polyplexes of PEI(X)-SS(3.0-4.0) series (X = 800, 1800, and 25,000) formed small particles with a size below 400 nm at a wide range of N/P ratios. Efficiency of the cross-linked PEIs as gene vectors was evaluated in vitro by transfection of pGL3 to HeLa, COS7, 293T, and CHO cells. The efficiency is disulfide content and molecular weight dependent. The PEI(800)-SS(Y) series with an adequate thiolation degree between 2.6 and 4.5 have relatively lower cytotoxicity and higher gene transfection efficiency than 25 KDa PEI. The polymers with very low or very high thiolation degrees were unable to form compact polyplexes and had very poor transfection efficiency. A suitable molecular weight of raw PEI is also essential to obtain a highly efficient disulfide cross-linked PEI gene vector. Among the three raw PEIs of different molecular weights tested (800 Da, 1800 Da, and 25 KDa), the cross-linked polymer prepared from 800 Da PEI that has the lowest molecular weight gave the best results.
Antidiabetic Screening of Commercial Botanical Products in 3T3-L1 Adipocytes and db/db Mice (2010)

Numerous botanicals are purported to improve glucose metabolism and diabetic risk factors with varying degrees of supportive evidence. We investigated 203 commercially available botanical products representing 90 unique botanical species for effects on lipogenic activity in differentiating 3T3-L1 adipocytes. Anti-inflammatory activity of 21 of these products was further assessed in tumor necrosis factor alpha (TNFalpha)-stimulated, mature 3T3-L1 adipocytes. From these results, rho-isoalpha acids, Acacia nilotica bark, fennel, and wasabi were tested in the db/db mouse model. Fifty-nine percent of the 90 unique botanicals increased adipogenesis as did the standard troglitazone relative to the solvent controls. Botanical species with the greatest percentage of positive products were Centella asiatica, Panax quinquefolius, and Phyllanthus amarus at 100%, Vitis vinifera at 80%, Humulus lupulus at 71%, Aloe barbadensis at 66%, and Momordica charantia, Phaseolus vulgaris, and Punica granatum at 60%. All 21 subset samples inhibited TNFalpha-stimulated free fatty acid release and attenuated TNFalpha inhibition of adiponectin secretion. Both rho-isoalpha acids and A. nilotica reduced nonfasting glucose in the db/db mouse model, whereas A. nilotica also decreased nonfasting insulin levels. A post hoc analysis of the screening results indicated that the positive predictive value of the lipogenesis assay alone was 72%, while adding the criterion of a positive response in the anti-inflammatory assays increased this figure to 82%. Moreover, this large-scale evaluation demonstrates that antidiabetic, in vitro efficacy of botanicals is more a function of manufacturing or quality control differences than the presence of marker compounds and further underscores the need to develop functional as well as analytical bases for standardization of dietary supplements.