gebhart/patrepeval huggingface dataset:
Fasting in α1-antitrypsin deficient liver: consultative activation of autophagy (2002)

Antitrypsin (α 1 -AT) deficiency causes severe liver injury in a subgroup of patients. Liver injury is thought to be caused by retention of a polymerized mutant α 1 -ATZ molecule in the endoplasmic reticulum (ER) of hepatocytes and is associated with an intense autophagic response. However, there is limited information about what physiologic stressors might influence liver injury. In this study, we examined the effect of fasting in the PiZ mouse model of α 1 -AT deficiency, because fasting is a well-characterized physiological stressor and a known stimulus for autophagy. Results show that there is a marked increase in fat accumulation and in α 1 -AT-containing globules in the liver of the PiZ mouse induced by fasting. Although fasting induced a marked autophagic response in wild-type mice, the autophagic response was already activated in PiZ mice and did not further increase with fasting. PiZ mice also had a significantly decreased tolerance for prolonged fasting compared with wild-type mice (PiZ mice 0% survival of 72-h fast; wild-type 100% survivial). These results demonstrate an altered response to stress in the α 1 -AT-deficient liver, including inability to further increase an activated autophagic response, a developmental state-specific increase in α 1 -AT-containing globules, and increased mortality.
Sharing MLM's: an experiment between Columbia-Presbyterian and LDS Hospital. (1993)

The use of Arden syntax for development of shareable medical logic modules (MLM's) has developed as an ASTM standard. To test the feasibility of sharing MLM's between institutions a study was conducted between Columbia-Presbyterian Medical Center and LDS Hospital. In this study seven MLM's clinically executing at Columbia-Presbyterian were used to test the sharing potential of the Arden syntax. The study was limited to measuring the modifications necessary to make executable at LDS Hospital the shared MLM's. Because of the site specific nature of the data variables, multiple modifications were required. Three classes of modifications were necessary. The simplest involved only data variable mappings. The other classes required either minor modifications to the logic or relatively major modifications. Over 50% of the modifications were in the minor or major classes. While the sharing of decision logic was possible and facilitated by the use of the MLM's at the two sites, the absence of standard medical vocabularies limited the utility of the MLM as a mechanism for directly sharing medical knowledge.
A dominant negative mutant of PG13 suppresses transcription from a cauliflower mosaic virus 35S truncated promoter in transgenic tobacco plants. (1994)

TGA1a and PG13 constitute a family of tobacco basic leucine zipper (bZIP) proteins that bind to activating sequence-1 (as-1), which is one of the multiple regulatory cis elements of the cauliflower mosaic virus (CaMV) 35S promoter. After truncation of the CaMV 35S promoter down to position -90 (CaMV 35S [-90] promoter), transcription stringently depends on the presence of as-1, which is recognized by nuclear DNA binding proteins called ASF-1. The role of the TGA1a/PG13 bZIP family in the formation of ASF-1 and in transcriptional activation of the CaMV 35S (-90) promoter has not yet been demonstrated in vivo. We constructed transgenic tobacco plants expressing a mutant of potato PG13, which lacks its wild-type DNA binding domain. This mutant acts as a trans-dominant inhibitor of ASF-1 formation and of expression from the CaMV 35S (-90) promoter, showing that PG13 can specifically interact with proteins necessary for these processes. Although we did not observe any other obvious phenotypic changes, these transgenic plants are a potentially valuable tool in identifying whether TGA1a and PG13 are involved in controlling promoters encoded in the plant genome.
PHENIX: building new software for automated crystallographic structure determination (2002)

Structural genomics seeks to expand rapidly the number of protein structures in order to extract the maximum amount of information from genomic sequence databases. The advent of several large-scale projects worldwide leads to many new challenges in the field of crystallographic macromolecular structure determination. A novel software package called PHENIX (Python-based Hierarchical ENvironment for Integrated Xtallography) is therefore being developed. This new software will provide the necessary algorithms to proceed from reduced intensity data to a refined molecular model and to facilitate structure solution for both the novice and expert crystallographer.
Three-Dimensional, Flexible Nanoscale Field-Effect Transistors as Localized Bioprobes (2010)

Nanoelectronic devices offer substantial potential for interrogating biological systems, although nearly all work has focused on planar device designs. We have overcome this limitation through synthetic integration of a nanoscale field-effect transistor (nanoFET) device at the tip of an acute-angle kinked silicon nanowire, where nanoscale connections are made by the arms of the kinked nanostructure, and remote multilayer interconnects allow three-dimensional (3D) probe presentation. The acute-angle probe geometry was designed and synthesized by controlling cis versus trans crystal conformations between adjacent kinks, and the nanoFET was localized through modulation doping. 3D nanoFET probes exhibited conductance and sensitivity in aqueous solution, independent of large mechanical deflections, and demonstrated high pH sensitivity. Additionally, 3D nanoprobes modified with phospholipid bilayers can enter single cells to allow robust recording of intracellular potentials.
Label-Free Vibrational Spectroscopic Imaging of Neuronal Membrane Potential (2017)

Detecting membrane potentials is critical for understanding how neuronal networks process information. We report a vibrational spectroscopic signature of neuronal membrane potentials identified through hyperspectral stimulated Raman scattering (SRS) imaging of patched primary neurons. High-speed SRS imaging allowed direct visualization of puff-induced depolarization of multiple neurons in mouse brain slices, confirmed by simultaneous calcium imaging. The observed signature, partially dependent on sodium ion influx, is interpreted as ion interactions on the CH<sub>3</sub> Fermi resonance peak in proteins. By implementing a dual-SRS balanced detection scheme, we detected single action potentials in electrically stimulated neurons. These results collectively demonstrate the potential of sensing neuronal activities at multiple sites with a label-free vibrational microscope.
Hash routing for collections of shared Web caches (1997)

Shared Web caches, also referred to as proxy Web servers, allow multiple clients to quickly access a pool of popular Web pages. An organization that provides shared caching to its Web clients will typically have a collection of shared caches rather than just one. For collections of shared caches, it is desirable to coordinate the caches so that all cached pages in the collection are shared among the organization's clients. In this article we investigate two classes of protocols for coordinating a collection of shared caches: the ICP protocol, which has caches ping each other to locate a cached object; and the hash routing protocols, which place objects in the shared caches as a function of the objects' URLs. Our contribution is twofold. First, we compare the performance of the protocols with respect to cache-server overhead and object retrieval latency; for a collection of shared caches, our analysis shows that the hash-routing schemes have significant performance advantages over ICP for both of the performance metrics. The existing hash-routing protocols assume that the cache servers are homogeneous in storage capacity and processing capability, even though most collections of cache servers are vastly heterogeneous. Our second contribution is to extend a robust hash-routing scheme so that it balances requests among the caches according to any desired distribution; the extended hash-routing scheme is robust in the face of cache failures, is tunable for heterogeneous caches, and can have significant performance advantages over ICP.
P3‐021: Dexmedetomidine induces tau hyperphosphorylation in the mouse hippocampus (2012)

In Alzheimer's disease and other neurodegenerative tauopathies, the microtubule-associated protein tau can undergo aberrant phosphorylation, potentially leading to its aggregation and the development of neurofibrillary pathology. Anesthetics can induce tau hyperphosphorylation through a mechanism involving the inhibition of protein phosphatase 2A activity by anesthesia-induced hypothermia. However, we recently demonstrated that the commonly used anesthetic propofol induces tau hyperphosphorylation in the absence of hypothermia. The aim of this study was to determine the impact of normothermic administration of dexmedetomidine, a commonly used sedative-analgesic agent, on tau phosphorylation in vivo. Following institutional approval, male C57BL6/J mice (8–10 week old) received either dexmedetomidine (Dex) 300 Î¼g/kg or 0.9% saline (control) i.p. The Dex-treated mice were sacrificed 30 min (n=6) and 2h (n=6) following treatment and control (n=6) mice were sacrificed at 30 min (0.5h). Hippocampal tissue was immediately harvested at the end of the study, and levels tau phosphorylated (p-tau) at the AT8 (pSer 202/pThr 205), CP13 (pSer 202), and PHF-1 (pSer 396/pSer 404) phosphoepitopes, as well as total tau were determined using SDS-PAGE followed by immunoblotting. The mechanism of tau hyperphosphorylation was dissected by screening for the activation pattern of an extensive panel of tau kinases and phosphatases. Statistical comparisons were made using analysis of variance with Newman-Keuls post hoc test applied when appropriate. Data are expressed as mean ± SD and p < 0.05 was considered statistically significant. Dex produced significant increases in hippocampal p-tau levels at the AT8, CP13, and PHF-1 phosphoepitopes 30 min (0.5h) following treatment (Fig. 1). Interestingly, at 2h post-Dex, a significant increase in p-tau was observed at all three phosphoepitopes despite recovery from anesthesia. No significant changes in total-tau levels were observed following Dex administration. Kinase activation could not explain the increase in p-tau levels; however, significant decreases in demethylation levels of the catalytic subunit of protein phosphastase 2A (PP2A-C) and the A subunit of PP2A (PP2A-A) paralleled the p-tau increase. These data indicate that Dex directly induces tau hyperphosphorylation in the mouse hippocampus. This effect persists after the recovery from anesthesia and may involve the deregulation of PP2A. The impact of this anesthetic exposure on neurofibrillary pathology warrants further investigation.
BINOL:  A Versatile Chiral Reagent (2005)

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTADDITION / CORRECTIONThis article has been corrected. View the notice.BINOL: A Versatile Chiral ReagentJean Michel BrunelView Author Information Laboratoire SESNAB, IMRN INRA 1111, Faculté des Sciences et Techniques de St Jérôme, Université Paul Cézanne, Aix-Marseille, Avenue Escadrille Normandie Niémen, 13397 Marseille Cedex 20, France Cite this: Chem. Rev. 2005, 105, 3, 857–898Publication Date (Web):February 12, 2005Publication History Received14 July 2004Published online12 February 2005Published inissue 1 March 2005https://pubs.acs.org/doi/10.1021/cr040079ghttps://doi.org/10.1021/cr040079gresearch-articleACS PublicationsCopyright © 2005 American Chemical SocietyRequest reuse permissionsArticle Views19651Altmetric-Citations877LEARN 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 SUBJECTS:Aldehydes,Catalysts,Cyclization,Lewis acids,Stereoselectivity Get e-Alerts
UGT1A1*28 Genotype and Irinotecan-Induced Neutropenia: Dose Matters (2007)

The Food and Drug Administration and Pfizer changed the package insert for irinotecan to include a patient's UGT1A1*28 genotype as a risk factor for severe neutropenia on the basis of the findings of four pharmacogenetic studies, which found that irinotecan-treated patients who were homozygous for the UGT1A1*28 allele had a greater risk of hematologic toxic effects than patients who had one or two copies of the wild-type allele (UGT1A1*1). Findings of subsequent irinotecan pharmacogenetic studies have been inconsistent. In a meta-analysis, we reviewed data presented in nine studies that included a total of 10 sets of patients (for a total of 821 patients) and assessed the association of irinotecan dose with the risk of irinotecan-related hematologic toxicities (grade III-IV) for patients with a UGT1A1*28/*28 genotype. The risk of toxicity was higher among patients with a UGT1A1*28/*28 genotype than among those with a UGT1A1*1/*1 or UGT1A1*1/*28 genotype at both medium (odds ratio [OR] = 3.22, 95% confidence interval [CI] = 1.52 to 6.81; P = .008) and high (OR = 27.8, 95% CI = 4.0 to 195; P = .005) doses of irinotecan. However, risk was similar at lower doses (OR = 1.80, 95% CI = 0.37 to 8.84; P = .41). Low doses of irinotecan (100-125 mg/m2) are in the commonly used therapeutic range. The risk of experiencing irinotecan-induced hematologic toxicity for patients with a UGT1A1*28/*28 genotype thus appears to be a function of the dose of irinotecan administered.
Changes in cytokinins and cytokinin oxidase activity in developing maize kernels and the effects of exogenous cytokinin on kernel development (1995)

Temporal changes in cytokinin levels, mitotic activity and cytokinin oxidase activity were determined within kernels at the same stage of physiological development in single ears of field-grown maize (Zea mays L.). Cytokinins were qualitatively and quantitatively characterized by immunoaffinity chromatography, high-performance liquid chromatography (HPLC) and radioimmunoassay (RIA). Zeatin (Z), zeatin riboside (ZR) and isopentenyladenosine (iPA) all reached their maximum concentrations 9 days after pollination (DAP). The mitotic activity within the endosperm also peaked at 9 DAP. Cytokinin oxidase was present in kernels at basal levels from 3-6 DAP, then increased substantially through 10 DAP. Comparison of oxidase activity in kernels which are maturing normally and those which will abort, revealed major differences. In aborting apical kernels, the enzyme activity remained at basal levels from 4-10 DAP and only increased slightly trough 15 DAP. In median kernels, which develop normally, oxidase activity increased significantly by 5 DAP and reached a peak 4-fold higher than the basal level by 9 DAP. The differences in cytokinin oxidase activity between kernels which are maturing normally and those which will abort was so pronounced that cytokinin oxidase levels can be considered an indicator of normal kernel development. Stem infusion of benzylaminopurine (BA), but not Z or ZR, into intact plants at pollination increased the kernel number per ear at maturity by up to 30% and in some cases the total kernel weight per ear. The increase was due to a reduction in apical kernel abortion
Integrin alpha 6: A novel therapeutic target in esophageal squamous cell carcinoma (2013)

Esophageal squamous cell carcinoma (ESCC), the most common subtype of esophageal cancer in East Asian countries, is a devastating disease characterized by distinctly high incidence and mortality rates. Our previous expression profile analysis showed that integrin alpha 6 (ITGA6) is highly expressed in ESCC tissues. To validate cell surface expression of ITGA6 as a novel target in ESCC, we investigated ITGA6 expression in tumor tissue samples and cell lines of ESCC and found that ITGA6 was upregulated in these cells. In vitro knockdown of ITGA6 in ESCC cells resulted in inhibition of cell proliferation, invasion and colony formation. In addition, we demonstrated that ITGA6 associates with integrin beta 4 (ITGB4), and that this heterodimer complex is upregulated in both ESCC tissues and cell lines. Moreover, our biodistribution results in an ESCC xenograft model indicated that ITGA6 is a possible target for antibody-related diagnostic and therapeutic modalities in ESCC. Thus, our findings suggest that ITGA6 plays an important role in tumorigenesis in ESCC and represents a potential therapeutic target in the treatment of ESCC.
A Branch and Bound Algorithm for Cyclic Scheduling of Timed Petri Nets (2013)

A timed Petri net (TPN) has been widely used for modeling, scheduling, and analyzing discrete event dynamic systems. This study examines cyclic scheduling problems of a TPN to minimize the cycle time especially for automated manufacturing systems. Appropriate token routing at each conflict place can make a TPN repeat an identical firing sequence. We propose a systematic procedure to transform a TPN with such cyclic token routing into an equivalent timed event graph (TEG) for which the cycle time and firing schedules can be evaluated by a linear programming (LP). Based on the transformation procedure, we develop an efficient branch and bound algorithm to solve the scheduling problem. A partial solution is defined as a partial token route that has only a subset of token routes for determining the complete schedule. The lower bound of a partial solution is determined by the cycle time of a TEG that has the partial token route. The cycle time of a TEG with an additional token route for a new partial solution is computed by a dual-simplex algorithm which avoids solving the LP completely again. A dynamic branching strategy that prevents unnecessary branching for the scheduling decision is also proposed. We demonstrate the computational efficiency through intensive experiments of cluster tools and robotic flow shops. Note to Practitioners-There are many systems which repeat an identical task sequence such as manufacturing systems, transportation systems, and robotic systems. Maximizing the throughput of such a system by optimizing the cyclic task sequence, which is called a cyclic scheduling problem, has been an important problem. In order to deal with cyclic scheduling problems, this paper uses a timed Petri net (TPN) which is a graphical modeling tool for discrete event dynamic systems. As the size of TPN model increases, the computational complexity of the cyclic scheduling problem exponentially increases due to the combinatorial nature of sequencing problems. Therefore, an efficient algorithm for optimal cyclic scheduling of TPNs is needed. This study proposes an efficient branch and bound algorithm which is kind of a tree search algorithm. Several important techniques are developed. First, a transformation procedure from a TPN to timed event graph is developed. Second, an efficient branching rule which reduces the size of the search tree is proposed. Third, the lower bound which evaluates the cycle time of each node in the search tree is suggested. We verify the efficiency of the algorithm through the experiments on manufacturing systems such as a cluster tool and a robotic flow shop.
Recombinant bispecific antibodies for cellular cancer immunotherapy. (2007)

Bispecific antibodies recognizing two different antigens present on different cells have been developed for cellular cancer therapy in which cytotoxic effector cells are recruited to tumor cells. Initial studies with bispecific antibodies have not reached satisfactory clinical endpoints, mainly due to low efficacy, Fc-mediated side effects and immunogenicity. This has resulted in a declining interest in bispecific antibodies for cancer therapy. However, growing knowledge in effector cell biology and the implementation of antibody engineering technologies has led to a revival and the development of novel or improved strategies. Various recombinant bispecific antibodies have demonstrated efficacy in vitro andin vivo, with the first recombinant antibody molecule currently in clinical trials for the treatment of B-cell malignancies.
Repurposing EGFR Inhibitor Utility in Colorectal Cancer in Mutant APC and TP53 Subpopulations (2019)

These findings, if further validated through clinical trials, could also expand the utility of EGFRi therapies that are currently underutilized.
Obtaining material identification with cosmic ray radiography (2012)

The passage of muons through matter is dominated by the Coulomb interaction with electrons and nuclei in the matter. The muon interaction with the electrons leads to continuous energy loss and stopping of the muons. The muon interaction with nuclei leads to angular diffusion. Using both stopped muons and angle diffusion interactions allows us to determine density and identify materials. Here we demonstrate material identification using data taken at Los Alamos with a particle tracker built from a set of sealed drift tubes with commercial electronics and software, the Mini Muon Tracker (MMT).
Heterogeneous Breakpoints on the Immunoglobulin Genes Are Involved in Fusion with the 5′ Region of BCL2 in B‐Cell Tumors (2001)

The 5' flanking region of the BCL2 gene (5'-BCL2) is a breakpoint cluster of rearrangements with immunoglobulin genes (IGs). In contrast to t(14;18)(q32;q21) affecting the 3' region of BCL2, 5'-BCL2 can fuse to not only the heavy chain gene (IGH), but also two light chain gene (IGL) loci. We report here cloning and sequencing of a total of eleven 5'-BCL2 / IGs junctional areas of B-cell tumors, which were amplified by long-distance polymerase chain reaction-based assays. The breakpoints on 5'-BCL2 were distributed from 378 to 2312 bp upstream of the translational initiation site and, reflecting the alteration of regulatory sequences of BCL2, 5'-BCL2 / IGs-positive cells showed markedly higher levels of BCL2 expression than those of t(14;18)-positive cells. In contrast, the breakpoints on the IGs were variable. Two 5'-BCL2 / IGH and two 5'-BCL2 / IGLkappa junctions occurred 5' of the joining (J) segments, suggesting operation of an erroneous variable (V) / diversity (D) / J and V / J rearrangement mechanism. However, two other 5'-BCL2 / IGH junctions affected switch regions, and the kappa-deleting element, which is located 24 kb downstream of the constant region of IGLkappa, followed the 5'-BCL2 in another case. One 5'-BCL2 / IGLkappa and two 5'-BCL2 / IGLlambda junctions involved intronic regions where the normal recombination process does not occur. In the remaining one case, the 5'-BCL2 fused 3' of a Vlambda gene that was upstream of another Vlambda / Jlambda complex carrying a non-producing configuration, indicating that the receptor editing mechanism was likely involved in this rearrangement. Our study revealed heterogeneous anatomy of the 5'-BCL2 / IGs fusion gene leading to transcriptional activation of BCL2, and suggested that the mechanisms underlying the formation of this particular oncogene / IGs recombination are not identical to those of t(14;18).