gebhart/patrepeval huggingface dataset:
PDMS–glass serpentine microchannel chip for time domain PCR with bubble suppression in sample injection (2007)

This paper reports on the development of a low-cost microreactor (10 µl) biochip for DNA polymerase chain reaction (PCR). The microbiochip (20 mm × 28 mm) is a hybrid type that is composed of a polydimethylsiloxane (PDMS) layer with a serpentine microchannel (360 µm × 100 µm) chamber and glass substrate integrated with a microheater and thermal microsensor. Because of the hydrophobic chip surface, bubbles are usually created during sample loading in the PMDS-based microchip. These bubbles disrupt the stable biochemical reaction. An improved microreactor chamber was designed using microfluidic simulation. The reactor has a rounded-corner serpentine channel architecture, which enables stable injection into the hydrophobic surface using only a micropipette. The reactor temperature needed for the PCR reaction is controlled within ±0.5 °C by the LabVIEW software proportional-integrative-derivative (PID) controller. PCR analyses of the sex-determining Y chromosome (SRY) gene and mouse GAPDH gene were successfully performed in less than 54 min by the fabricated microreactor chip.
PI3K inhibition potentiates Bcl‐2‐dependent apoptosis in renal carcinoma cells (2013)

Inhibitors of PI3-K/Akt are currently being assessed clinically in patients with advanced RCC. Identification of therapeutic strategies that might enhance the efficacy of PI3-K/Akt inhibitors is therefore of great interest. As PI3-K inhibition would be expected to have many pro-apoptotic effects, we hypothesized that there may be unique synergy between PI3-K inhibitors and BH3-mimetics. Towards this end, we assessed the combination of the PI3K inhibitor LY 294002 and the Bcl-2 family inhibitor ABT-737 in RCC cell lines. We found that the combinatorial treatment with these agents led to a significant increase in PARP cleavage and cell death in all RCC cell lines. The synergized cell death was correlated with decreased levels of Mcl-1 and XIAP, and increased levels in Bim, and appears critically dependent upon the activation of caspase 3 and 8. The enhanced lethality observed with the combination also appears dependent upon the regulation of XIAP, Mcl-1 and Bim levels. Our results suggest that the combination of PI3-K inhibitors with BH3-mimetics may be a viable therapeutic strategy in RCC.
Specification and implementation of exceptions in workflow management systems (1999)

Although workflow management systems are most applicable when an organization follows standard business processes and routines, any of these processes faces the need for handling exceptions, i.e., asynchronous and anomalous situations that fall outside the normal control flow. In this paper we concentrate upon anomalous situtations that, although unusual, are part of the semantics of workflow applications, and should be specified and monitored coherently; in most real-life applications, such exceptions affect a significant fraction of workflow cases. However, very few workflow management systems are integrated with a highly expressive language for specifying this kind of exception and with a system component capable of handling it. We present Chimera-Exc, a language for the specification of exceptions for workflows based on detached active rules, and then describe the architecture of a system, called FAR, that implements Chimera-Exc and integrates it with a commercial workflow management system and database server. We discuss the main issues that were solved by our implementation, and report on the performance of FAR. We also discuss design criteria for exceptions in light of the formal properties of their execution. Finally, we focus on the portability of FAR on its unbundling to a generic architecture with detached active rules.
Mutations in RAB39B in individuals with intellectual disability, autism spectrum disorder, and macrocephaly (2017)

Penetrance for ASD is high among males but more variable among females with <i>RAB39B</i> mutations. A critical role for this gene in brain development and function is demonstrated.
Proof without prejudice: use of the Kolmogorov-Smirnov test for the analysis of histograms from flow systems and other sources. (1977)

In this paper the Kolmogorov-Smirnov statistical test for the analysis of histograms is presented. The test is discussed for both the two-sample case (comparing fn1(X) to fn2 (X)) and the one-sample case (comparing fn1 (X) to f(X)). Presentation of the specific algorithmic steps involved is done through development of an example where the data are from an experiment discussed elsewhere in this issue. It is shown that the two histograms examined come from two different parent populations at the 99.9% confidence level.
Characterization of pertussis toxin analogs containing mutations in B-oligomer subunits (1993)

The S2, S3, and S4 subunit genes of pertussis toxin (PT) from Bordetella pertussis were subjected to site-directed mutagenesis, and the resultant PT analogs were assayed for altered biological properties. PT analogs S2(T91,R92,N93) delta and S2(Y102A,Y103A) exhibited reduced binding to fetuin. Several PT analogs with mutations in the S2, S3, or S4 subunit showed reduced in vitro toxicity, as measured in the Chinese hamster ovary (CHO) cell clustering assay. In particular, PT analogs S3(Y82A) and S3(I91,Y92,K93) delta retained 10% or less residual toxicity. These mutants also exhibited significantly lower mitogenic and hemagglutinating activities and reduced in vivo activities, as measured by the histamine sensitization and leukocytosis assays. The S4(K54A,K57A) PT analog had significantly reduced CHO cell clustering activity, though other biological activities remained unaffected. PT analogs S1(E129G)/S3(Y82A) and S1(E129G)/S3(I91,Y92,K93) delta displayed a cumulative effect of the S1 and S3 mutations for both in vitro and in vivo toxic activities. These PT analogs, as well as S1(R9K,E129G)/S3(K82A) and S1(R9K,E129G)/S3(I91,Y92,K93) delta, still expressed an epitope which elicits a neutralizing antitoxin antibody and were protective in the mouse intracerebral challenge test. Recombinant pertussis vaccines based on PT analogs with detoxifying mutations in multiple subunits may thus represent the next generation of improved whooping cough vaccines.
Laser lipolysis: an update. (2011)

Laser lipolysis is now a commonly used and accepted modality for removal of unwanted fatty tissue. Since its United States Food and Drug Administration (FDA) approval in October of 2006,1 studies have continued to corroborate early clinical observations of decreased adiposity, shorter recovery times, and improved skin tightening. Throughout the last five years, we have discovered that laser lipolysis liquefies fatty tissue, coagulates small blood vessels, induces collagenesis with remodeling, and promotes tissue tightening.2–6

Despite these findings, some clinicians have been reluctant to accept laser lipolysis citing longer procedural times, increased risk of adverse reactions, and lack of evidence supporting superiority over traditional liposuction. On the other hand, surgeons already familiar with laser technology may more enthusiastically embrace laser lipolysis as an adjunctive tool to satisfy the growing demand for minimally invasive technologies that enhance body sculpting and skin tightening without disfiguring scars.

Sasaki et al7 document that many experimental and histological publications have reported that external application of laser energies, including 1064nm and 1320nm wavelengths, and radiofrequency devices increase fibroblast numbers, stimulate new collagen, and augment tissue tightening and elasticity. Low level laser therapy and cryolipolysis are additional newer modalities purporting lipolysis and collagenesis externally. Until further optimization of these devices occurs, and penetration and absorption through the skin is efficiently achieved, internal application of laser energy may be the most effective method of reducing fatty tissue and enhancing skin tightening.

The objectives of this article are to 1) discuss the progression of laser lipolysis as it pertains to the controversial skin-tightening debate, 2) discuss the latest understanding regarding the mechanism of action, 3) review the advantages and disadvantages of laser lipolysis, 4) discuss how to optimize outcomes and avoid pitfalls such as thermal injury, 5) highlight emerging uses for laser lipolysis, and 6) conclude with alternative modalities and how they may stack up against laser lipolysis.
Concise Review: Human Umbilical Cord Stroma with Regard to the Source of Fetus-Derived Stem Cells (2007)

Human umbilical cord (UC) has been a tissue of increasing interest in recent years. Many groups have shown the stem cell potency of stromal cells isolated from the human UC mesenchymal tissue, namely, Wharton's jelly. Since UC is a postnatal organ discarded after birth, the collection of cells does not require an invasive procedure with ethical concerns. Stromal cells, as the dominant cells of this fetus-derived tissue, possess multipotent properties between embryonic stem cells and adult stem cells. They bear a relatively higher proliferation rate and self-renewal capacity. Although they share common surface markers with bone marrow-derived MSCs, they also express certain embryonic stem cell markers, albeit in low levels. Without any spontaneous differentiation, they can be successfully differentiated into mature adipocytes, osteoblasts, chondrocytes, skeletal myocytes, cardiomyocytes, neurons, and endothelial cells. While causing no immunorejection reaction, they effectively function in vivo as dopaminergic neurons, myocytes, and endothelial cells. Given these characteristics, particularly the plasticity and developmental flexibility, UC stromal cells are now considered an alternative source of stem cells and deserve to be examined in long-term clinical trials. This review first aims to document the published findings so far regarding the nature of human UC stroma with special emphasis on the spatial distribution and functional structure of stromal cells and matrix, which serves as a niche for residing cells, and, secondly, to assess the in vitro and in vivo experiments in which differential stem cell potencies were evaluated.
Using EM to Classify Text from Labeled and Unlabeled Documents (1998)

Abstract : This paper shows that the accuracy of learned text classifiers can be improved by augmenting a small number of labeled training documents with a large pool of unlabeled documents. This is significant because in many important text classification problems obtaining classification labels is expensive, while large quantities of unlabeled documents are readily available. We present a theoretical argument showing that, under common assumptions, unlabeled data contain information about the target function. We then introduce an algorithm for learning from labeled and unlabeled text, based on the combination of Expectation-Maximization with a naive Bayes classifier. The algorithm first trains a classifier using the available labeled documents, and probabilistically labels the unlabeled documents. It then trains a new classifier using the labels for all the documents, and iterates. Experimental results, obtained using text from three different real-world tasks, show that the use of unlabeled data reduces classification error by up to 30%.
Available human feeder cells for the maintenance of human embryonic stem cells (2004)

Mouse embryonic fibroblasts (MEFs) have been previously used as feeder cells to support the growth of human embryonic stem cells (hESCs). In this study, human adult uterine endometrial cells (hUECs), human adult breast parenchymal cells (hBPCs) and embryonic fibroblasts (hEFs) were tested as feeder cells for supporting the growth of hESCs to prevent the possibility of contamination from animal feeder cells. Cultured hUECs, hBPCs and hEFs were mitotically inactivated and then plated. hESCs (Miz-hES1, NIH registered) initially established on mouse feeder layers were transferred onto each human feeder layer and split every 5 days. The morphology, expression of specific markers and differentiation capacity of hESCs adapted on each human feeder layer were examined. On hUEC, hBPC and hEF feeder layers, hESCs proliferated for more than 90, 50 and 80 passages respectively. Human feeder-based hESCs were positive for stage-specific embryonic antigen (SSEA)-3 and -4, and Apase; they also showed similar differentiation capacity to MEF-based hESCs, as assessed by the formation of teratomas and expression of tissue-specific markers. However, hESCs cultured on hUEC and hEF feeders were slightly thinner and flatter than MEF- or hBPC-based hESCs. Our results suggest that, like MEF feeder layers, human feeder layers can support the proliferation of hESCs without differentiation. Human feeder cells have the advantage of supporting more passages than when MEFs are used as feeder cells, because hESCs can be uniformly maintained in the undifferentiated stage until they pass through senescence. hESCs established and/or maintained under stable xeno-free culture conditions will be helpful to cell-based therapy.
Microstructural Organization of Three-Phase Polydimethylsiloxane-Based Segmented Polyurethanes (2007)

Microphase separation is investigated for segmented polyurethane copolymers synthesized from 4,4'-methylenediphenyl diisocyanate and 1,4-butanediol as the hard segments and poly(hexamethylene oxide diol) and hydroxyl-terminated polydimethylsiloxane as soft segments. The neat PDMS-based diol exhibits two segmental relaxations corresponding to the principal repeating unit, Si(CH3)2O, and to the hydroxyl end-group segments. When incorporated in the polyurethanes, the siloxane units form their own phase, while the end-group segments are mixed with the second macrodiol and some short hard segment sequences. This is demonstrated by the results of dynamic mechanical analysis and wide-angle X-ray diffraction experiments. The microdomain morphology was characterized principally by small-angle X-ray scattering, and the scattering data were analyzed with a pseudo-two-phase model as well as a modified three-phase core−shell model.
Run-time scheduling and execution of loops on message passing machines (1990)

We examine the effectiveness of optimizations aimed to allowing distributed machine to efficiently compute inner loops over globally defined data structures. Our optimizations are specifically targeted toward loops in which some array references are made through a level of indirection. Unstructured mesh codes and sparse matrix solvers are examplese of programs with kernels of this sort. Experimental data that quantify the performance obtainable using the methods discussed here are included.
The tumor-targeting immunocytokine F16-IL2 in combination with doxorubicin: dose escalation in patients with advanced solid tumors and expansion into patients with metastatic breast cancer (2015)

A phase Ib/II trial was performed to evaluate safety, tolerability, recommended dose (RD) and efficacy of F16-IL2, a recombinant antibody-cytokine fusion protein, in combination with doxorubicin in patients with solid tumors (phase Ib) and metastatic breast cancer (phase II). Six patient cohorts with progressive solid tumors (n = 19) received escalating doses of F16-IL2 [5-25 Million International Units (MIU) of IL2 equivalent dose] in combination with escalating doses of doxorubicin (0-25 mg/m(2)) on day 1, 8 and 15 every 4 weeks. Subsequently, patients with metastatic breast cancer (n = 10) received the drug combination at the RD. Clinical data and laboratory findings were analyzed for safety, tolerability, and activity. F16-IL2 could be administered up to 25 MIU, in combination with the RD of doxorubicin (25 mg/m(2)). No human anti-fusion protein antibodies (HAFA) response was detected. Pharmacokinetics of F16-IL2 was dose-dependent over the tested range, with half-lives of ca. 13 and ca. 8 hours for cohorts dosed at lower and higher levels, respectively. Toxicities were controllable and reversible, with no combination treatment-related death. After 8 weeks, 57% and 67% disease control rates were observed for Phase I and II, respectively (decreasing to 43% and 33% after 12 weeks), considering 14 and 9 patients evaluable for efficacy. One patient experienced a long lasting partial response (45 weeks), still on-going at exit of study. F16-IL2 can be safely and repeatedly administered at the RD of 25 MIU in combination with 25 mg/m(2) doxorubicin; its safety and activity are currently being investigated in combination with other chemotherapeutics, in order to establish optimal therapy settings.
A single-package solution for wireless transceivers (1999)

Although a single-chip solution seems to be ultimate goal for the design of wireless transceivers, there are many reasons to believe that this approach is not feasible for high performance applications. Especially the RF front-ends of these transceivers require components that are difficult to combine into one single chip. As an alternative we propose a single-package solution that contains different components that are interconnected with a multi-chip module (MCM) interconnect technology. By implementing passive front-end components directly into this interconnect technology, instead of using external commercial components, a cost-effective realization of the front-end can be obtained with a higher performance or a lower power consumption.
Prodrugs and site-specific drug delivery (1980)

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTProdrugs and site-specific drug deliveryValentino J. Stella and Kenneth J. HimmelsteinCite this: J. Med. Chem. 1980, 23, 12, 1275–1282Publication Date (Print):December 1, 1980Publication History Published online1 May 2002Published inissue 1 December 1980https://pubs.acs.org/doi/10.1021/jm00186a001https://doi.org/10.1021/jm00186a001research-articleACS PublicationsRequest reuse permissionsArticle Views862Altmetric-Citations107LEARN ABOUT THESE METRICSArticle Views are the COUNTER-compliant sum of full text article downloads since November 2008 (both PDF and HTML) across all institutions and individuals. These metrics are regularly updated to reflect usage leading up to the last few days.Citations are the number of other articles citing this article, calculated by Crossref and updated daily. Find more information about Crossref citation counts.The Altmetric Attention Score is a quantitative measure of the attention that a research article has received online. Clicking on the donut icon will load a page at altmetric.com with additional details about the score and the social media presence for the given article. Find more information on the Altmetric Attention Score and how the score is calculated. Share Add toView InAdd Full Text with ReferenceAdd Description ExportRISCitationCitation and abstractCitation and referencesMore Options Share onFacebookTwitterWechatLinked InRedditEmail Other access optionsGet e-Alertsclose Get e-Alerts
Coupling of carriers injection and charges distribution in Schottky barrier charge-trapping memories using source-side electrons programming (2014)

This study elucidates the coupling of Schottky barriers and trapped charges involved in the source-side electrons programming and two-bit/cell reading of the Schottky barrier charge-trapping cells. Two-dimensional numerical iterations were employed to examine the distribution of electron injections and trapped charges, and to discuss the differences of physical mechanisms between the Schottky barrier and conventional cells. In the Schottky barrier cells, both the conduction and injection of electron carriers depend on the Schottky source barrier lowering. The source-side trapped charges alter the source-side lateral field distribution, reducing the maximum of the lateral electric field, and moving the subsequent injections away from the source edge. The distribution of total trapped-charges is considerably wider than that of the initial injection. However, because of source-side conduction, the excellent screening of second-bit effect is beneficial to operate the NOR-type multibit/cell charge-trapping memories.
Regulatory Effect of Cinnamaldehyde on Monocyte/Macrophage-Mediated Inflammatory Responses (2010)

Cinnamaldehyde (CA) has been known to exhibit anti-inflammatory and anticancer effects. Although numerous pharmacological effects have been demonstrated, regulatory effect of CA on the functional activation of monocytes and macrophages has not been fully elucidated yet. To evaluate its monocyte/macrophage-mediated immune responses, macrophages activated by lipopolysaccharide (LPS), and monocytes treated with proaggregative antibodies, and extracellular matrix protein fibronectin were employed. CA was able to suppress both the production of nitric oxide (NO) and upregulation of surface levels of costimulatory molecules (CD80 and CD69) and pattern recognition receptors (toll-like receptor 2 (TLR2) and complement receptor (CR3)). In addition, CA also blocked cell-cell adhesion induced by the activation of CD29 and CD43 but not cell-fibronectin adhesion. Immunoblotting analysis suggested that CA inhibition was due to the inhibition of phosphoinositide-3-kinase (PI3K) and phosphoinositide-dependent kinase (PDK)1 as well as nuclear factor-(NF-) kappaB activation. In particular, thiol compounds with sulphydryl group, L-cysteine and dithiothreitol (DTT), strongly abrogated CA-mediated NO production and NF-kappaB activation. Therefore, our results suggest that CA can act as a strong regulator of monocyte/macrophage-mediated immune responses by thiolation of target cysteine residues in PI3K or PDK1.
Macrophage inflammatory protein 1 modulates macrophage function (1992)

Macrophage inflammatory protein 1 (MIP 1), initially purified from the conditioned medium of endotoxin-stimulated macrophages, is a low m.w. heparin-binding protein doublet comprising two peptides, MIP 1 alpha and MIP 1 beta. Although native doublet MIP 1 has previously been shown to exert pyrogenic, mitogenic, and proinflammatory effects on other cell types, its actions on its cell of origin, the macrophage, have not been well catalogued. Our study reports several aspects of macrophage function that are modulated by MIP 1. MIP 1 was not directly cytotoxic for WEHI tumor cells, but MIP 1-treated macrophage exhibited enhanced antibody-independent macrophage cytotoxicity for tumor targets. MIP 1 treatment stimulated proliferation of mature tissue macrophages, and this effect was enhanced upon costimulations with either CSF-1 or granulocyte-macrophage-CSF. Thioglycollate-elicited peritoneal exudate macrophages incubated with native doublet MIP 1-secreted bioactive TNF and IL-6, as well as immunoreactive IL-1 alpha, and these effects were enhanced significantly when the cells were costimulated with IFN-gamma. Purified preparations of the recombinantly derived MIP 1 alpha peptide alone stimulated the secretion of TNF, IL-1 alpha, and IL-6 by peritoneal macrophages, but MIP 1 beta did not. In fact, as little as eightfold excess MIP 1 beta blocked TNF-induction by MIP 1 alpha to a significant degree. By contrast to these apparent "macrophage activating" properties of MIP 1, the cytokine failed to trigger the macrophage oxidative burst, or to up-regulate the expression of Ia on the macrophage surface. Taken together, these data reveal that MIP 1 peptides act as autocrine modulators of their cells of origin, and raise the possibility that MIP 1 peptides may play a role in modulating macrophage responses to inflammatory stimuli in vivo.