gebhart/patrepeval huggingface dataset:
A unique palindromic element mediates gamma interferon induction of mig gene expression. (1994)

To define the molecular mechanisms involved in the action of gamma interferon (IFN-gamma), we have analyzed the transcriptional regulation of the mig (monokine induced by gamma interferon) gene, a member of the platelet factor 4-interleukin-8 cytokine family that is expressed in murine macrophages specifically in response to IFN-gamma. Analysis of mig/CAT chimeric constructs transiently transfected into the RAW 264.7 mouse monocytic cell line revealed a unique IFN-gamma-responsive element (gamma RE-1). The sequence of this cis regulatory element defined by deletion analysis contains an imperfect inverted repeat extending 27 bp. Examination of mig/CAT constructs with mutations in gamma RE-1 revealed that the palindromic positions in the element were essential for activity. Consistent with its function as an enhancer, a single copy of gamma RE-1 conferred IFN-gamma inducibility to a heterologous (herpes simplex virus thymidine kinase) promoter. Exonuclease III protection assays demonstrated symmetrical protection of a mig promoter fragment centered about the gamma RE-1 palindromic sequence. Using the gel electrophoretic mobility shift assay, we identified a factor (gamma RF-1) present in nuclear extracts prepared from IFN-gamma-stimulated RAW 264.7 cells which binds to gamma RE-1. The activation of gamma RF-1 occurred rapidly (within 1 min) in response to IFN-gamma and was independent of protein synthesis. Similar to the expression of mig mRNA, the formation of gamma RF-1 was selectively induced by IFN-gamma and not IFN-alpha. The regulation of gene expression through gamma RF-1 and gamma RE-1 may explain the preferential activation of a subset of interferon-inducible genes by IFN-gamma.
GITRL-armed Delta-24-RGD oncolytic adenovirus prolongs survival and induces anti-glioma immune memory (2019)

GITRL-armed Delta-24-RGD treatment results in an antigen-restricted antitumor memory, an enhanced anti-glioma effect, and the generation of central immune memory. Our results strongly indicate that this strategy represents a vertical advance in virotherapy designed to treat patients with malignant brain tumors.
Biphasic Dose Response in Low Level Light Therapy – an Update (2011)

Low-level laser (light) therapy (LLLT) has been known since 1967 but still remains controversial due to incomplete understanding of the basic mechanisms and the selection of inappropriate dosimetric parameters that led to negative studies. The biphasic dose-response or Arndt-Schulz curve in LLLT has been shown both in vitro studies and in animal experiments. This review will provide an update to our previous (Huang et al. 2009) coverage of this topic. In vitro mediators of LLLT such as adenosine triphosphate (ATP) and mitochondrial membrane potential show biphasic patterns, while others such as mitochondrial reactive oxygen species show a triphasic dose-response with two distinct peaks. The Janus nature of reactive oxygen species (ROS) that may act as a beneficial signaling molecule at low concentrations and a harmful cytotoxic agent at high concentrations, may partly explain the observed responses in vivo. Transcranial LLLT for traumatic brain injury (TBI) in mice shows a distinct biphasic pattern with peaks in beneficial neurological effects observed when the number of treatments is varied, and when the energy density of an individual treatment is varied. Further understanding of the extent to which biphasic dose responses apply in LLLT will be necessary to optimize clinical treatments.
Quantitative Dynamic Stratigraphy (1990)

State-of-the-science summary of computer modeling techniques of the earth's subsurface as applied to groundwater, petroleum or hazardous waste management.
Patient‐specific Surgical Simulation (2007)

Technological innovations of the twentieth century have provided medicine and surgery with new tools for education and therapy definition. Thus, by combining Medical Imaging and Virtual Reality, patient-specific applications providing preoperative surgical simulation have become possible.
BPTree: an $\ell_2$ heavy hitters algorithm using constant memory (2016)

The task of finding heavy hitters is one of the best known and well studied problems in the area of data streams. One is given a list $i_1,i_2,\ldots,i_m\in[n]$ and the goal is to identify the items among $[n]$ that appear frequently in the list. In sub-polynomial space, the strongest guarantee available is the $\ell_2$ guarantee, which requires finding all items that occur at least $ε\|f\|_2$ times in the stream, where the vector $f\in\mathbb{R}^n$ is the count histogram of the stream with $i$th coordinate equal to the number of times~$i$ appears $f_i:=\#\{j\in[m]:i_j=i\}$. The first algorithm to achieve the $\ell_2$ guarantee was the CountSketch of [CCF04], which requires $O(ε^{-2}\log n)$ words of memory and $O(\log n)$ update time and is known to be space-optimal if the stream allows for deletions. The recent work of [BCIW16] gave an improved algorithm for insertion-only streams, using only $O(ε^{-2}\logε^{-1}\log\log n)$ words of memory. In this work, we give an algorithm \bptree for $\ell_2$ heavy hitters in insertion-only streams that achieves $O(ε^{-2}\logε^{-1})$ words of memory and $O(\logε^{-1})$ update time, which is the optimal dependence on $n$ and $m$. In addition, we describe an algorithm for tracking $\|f\|_2$ at all times with $O(ε^{-2})$ memory and update time. Our analyses rely on bounding the expected supremum of a Bernoulli process involving Rademachers with limited independence, which we accomplish via a Dudley-like chaining argument that may have applications elsewhere.
Remnant lipoproteins are related to intima-media thickness of the carotid artery independently of LDL cholesterol and plasma triglycerides (2001)

Remnants of triglyceride-rich lipoproteins (TRL) have been implicated in the early development of atherosclerosis. We tested this hypothesis by quantifying the plasma concentration of remnant-like particle cholesterol (RLP-C) in a cohort of healthy 50-year-old men in whom the common carotid artery intima-media thickness (CCA-IMT) was assessed by B-mode ultrasound as a surrogate marker for atherosclerosis. The subjects were given a fat-rich meal to study the generation of RLP-C during postprandial lipemia. Fasting plasma RLP-C and other major fasting plasma lipids and lipoproteins were determined twice, and the mean RLP-C concentration was strongly correlated with CCA-IMT (r = 0.32, P = 0.002). In addition, low density lipoprotein (LDL) cholesterol (r = 0.25, P = 0.01) and plasma triglycerides (r = 0.20, P = 0.05) were significantly related to CCA-IMT. Multivariate analyses showed a triglyceride-independent contribution of RLP-C to CCA-IMT. After fat intake, the median plasma RLP-C concentration was doubled after 3 h. The increase was strongly related to the postprandial generation of TRL apolipoprotein (apo)B-48, and large (S(f) 60;-400) TRL apoB-100. The association with CCA-IMT was somewhat stronger for the 3-h RLP-C level than for the fasting RLP-C concentration [r = 0.27, P < 0.01 (3 h) compared with r = 0.22, P < 0.05 (0 h)]. We conclude that the plasma concentration of RLP-C is related to CCA-IMT, independent of plasma triglycerides and LDL cholesterol, in a healthy middle-aged male population. - Karpe, F., S. Boquist, R. Tang, G. M. Bond, U. de Faire, and A. Hamsten. Remnant lipoproteins are related to intima-media thickness of the carotid artery independently of LDL cholesterol and plasma triglycerides. J. Lipid Res. 2001. 42: 17;-21.
Capillary Array Electrophoresis-MALDI Mass Spectrometry Using a Vacuum Deposition Interface (2001)

We previously introduced a vacuum deposition interface for matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI/TOF MS) on a moving surface (e.g., quartz wheel, Mylar tape, metal target). In our present work, the approach has been extended to demonstrate parallel analysis for multiple on-line infusion MALDI MS and capillary array electrophoresis (CAE)-MALDI MS. In the infusion mode, individual peptide samples were simultaneously deposited on a Mylar tape cartridge using an array of eight capillaries, yielding eight parallel traces. For CAE-MALDI/TOF MS, the same number of separation capillaries were coupled with an array of eight infusion capillaries using a common liquid junction, containing matrix solution. A fast-scanning mirror was employed to traverse the beam of the desorption laser across the Mylar tape to probe one trace at a time. The positions of the eight sample traces formed on the tape were automatically determined, and all samples were analyzed in rapid sequence using a kilohertz repetition rate laser and a high-throughput data acquisition system. The instrumentation was operated with CAE MS for high-throughput analysis without compromising data quality. The principles of parallel separation-vacuum deposition should be generally applicable to MALDI/TOF MS analysis for proteomics and other areas where separation and high throughput are required.
Targeting RING domains of Mdm2–MdmX E3 complex activates apoptotic arm of the p53 pathway in leukemia/lymphoma cells (2015)

Reactivation of tumor-suppressor p53 for targeted cancer therapy is an attractive strategy for cancers bearing wild-type (WT) p53. Targeting the Mdm2-p53 interface or MdmX ((MDM4), mouse double minute 4)-p53 interface or both has been a focus in the field. However, targeting the E3 ligase activity of Mdm2-MdmX really interesting new gene (RING)-RING interaction as a novel anticancer strategy has never been explored. In this report, we describe the identification and characterization of small molecule inhibitors targeting Mdm2-MdmX RING-RING interaction as a new class of E3 ligase inhibitors. With a fluorescence resonance energy transfer-based E3 activity assay in high-throughput screening of a chemical library, we identified inhibitors (designated as MMRis (Mdm2-MdmX RING domain inhibitors)) that specifically inhibit Mdm2-MdmX E3 ligase activity toward Mdm2 and p53 substrates. MMRi6 and its analog MMRi64 are capable of disrupting Mdm2-MdmX interactions in vitro and activating p53 in cells. In leukemia cells, MMRi64 potently induces downregulation of Mdm2 and MdmX. In contrast to Nutlin3a, MMRi64 only induces the expression of pro-apoptotic gene PUMA (p53 upregulated modulator of apoptosis) with minimal induction of growth-arresting gene p21. Consequently, MMRi64 selectively induces the apoptotic arm of the p53 pathway in leukemia/lymphoma cells. Owing to the distinct mechanisms of action of MMRi64 and Nutlin3a, their combination synergistically induces p53 and apoptosis. Taken together, this study reveals that Mdm2-MdmX has a critical role in apoptotic response of the p53 pathway and MMRi64 may serve as a new pharmacological tool for p53 studies and a platform for cancer drug development.
Feeding Healthy Beagles Medium-Chain Triglycerides, Fish Oil, and Carnitine Offsets Age-Related Changes in Serum Fatty Acids and Carnitine Metabolites (2012)

The purpose of this study was to determine if feeding dogs medium-chain triglycerides (MCT), fish oil, and L-carnitine enriched foods offsets age-associated changes in serum fatty acids (FA) and carnitine metabolites. Forty-one healthy Beagles, mean age 9.9 years (range 3.1 to 14.8), were fed control or one of two treatment foods for 6 months. All foods were complete and balanced and met the nutrient requirements for adult dogs, and had similar concentrations of moisture, protein, and fat (approx. 7.4%, 14.0%, and 18.1%, respectively). The treatment diets both contained added L-carnitine (300 mg/kg) and 0.6% (treatment food 1) or 1.5% (treatment food 2) added fish oil. Treatment food 2 also had increased MCT from coconut oil, added corn oil, and reduced animal fat. Composition of serum FA was determined by gas chromatography of FA methyl esters. Metabolomic profiles of serum samples were determined from extracted supernatants that were split and run on GC/MS and LC/MS/MS platforms, for identification and relative quantification of small metabolites. Body composition was determined by dual energy x-ray absorptiometry. Among dog groups, there was no change in total-lean-body weight, or in serum total protein and serum albumin concentrations, based on time or dietary treatment. Serum concentrations of carnitine metabolites were decreased in geriatric (>7 years) vs. mature adult (≤ 7 years) dogs, and supplementation with L-carnitine attenuated the effects of aging. The ratio of PUFA to SFA was significantly greater in mature dogs at baseline (P ≤ 0.05). Serum concentrations of eicosapentaenoic and docosahexaenoic FA increased in a dose-dependent manner. Dogs consuming treatment food 2 also had increased serum concentrations of lauric and myristic FA, and decreased concentrations of SFA, MUFA, and arachidonate (all P ≤ 0.05) and their PUFA to SFA ratio increased. In summary, dietary MCT, fish oil, and L-carnitine counterbalanced the effects of aging on circulating concentrations of these compounds.
Characterization of 248nm Deep Ultraviolet (DUV) Photoresist after Ion Implantation (2009)

The elemental and structural changes of 248nm DUV photoresist induced by arsenic implantation with high dose and different acceleration energies were studied. For this purpose different analytical techniques were combined. An investigation of the capabilities of the Micro Raman Spectroscopy for analysis of ion implanted photoresist (II-PR) revealed that the method is unreliable for the characterization of II-PR since it induces a modification of the top crust layer. Moreover, alternative methods were used for characterization of the crust. The crust structure was indentified as cross-linked PR by Solid State Nuclear Magnetic Resonance. No experimental evidence for presence of amorphous carbon was found. Furthermore, the elemental composition and mechanical properties of the crust as a function of the implant energy were discussed as a measure for the cross-linking density. Finally, the dopant role in the cross-link process was considered.
Anion-Controlled Redox Process in a Cross-linked Polyviologen Film toward Electrochemical Anion Recognition (2000)

The highly selective recognition of halide ions by a cross-linked polyviologen film was demonstrated electrochemically. The film was prepared on an electrode by electropolymerization of a branched monomer with three polymerizable groups, 1,3,5-tris(4‘-cyanopyridinio-1‘-methyl)-2,4,6-trimethylbenzene tribromide, to form a highly cross-linked polyviologen, through successive reductive coupling of the cyanopyridinium moieties. The highly cross-linked structure is built up by the formed viologen skeleton, incorporating the electrolyte anion used as the template to fabricate a kind of cavity structure complementary in size to the electrolyte anion, called anion-imprinted electropolymerization. The resulting cross-linked polyviologen film exhibits highly selective anion recognition in the redox process. The anion-controlled redox process was investigated quantitatively by multilateral analyses with cyclic voltammetry, potential-step chronoamperometry, and electrochemical quartz crystal microbalance measurement coupled with visible absorption spectrophotometry. A highly selective size exclusion effect by the cavity structure fabricated in the anion-imprinted electropolymerization was demonstrated in the redox process of the viologen moiety in different kinds of aqueous electrolytic solutions. From the systematic study of the anion size recognition using a series of halide ions, not only the precisely fabricated cavity structure but also the anion diffusion dynamics in the cavities successfully running are suggested.
Latency Performance of SOAP Implementations (2003)

This paper presents an experimental evaluation of the latency performance of several implementations of Simple Object Access Protocol (SOAP) operating over HTTP, and compares these results with the performance Of JavaRMI, CORBA, HTTP, and with the TCP setup time. SOAP is an XML based protocol that supports RPC and message semantics. While SOAP has been designed as an interoperable business-to-business protocol usable over the Internet, we believe that applications will also use SOAP for interactive web applications running within an intranet. The objective of this paper is to identify the sources of inefficiency in the current implementations of SOAP and discuss changes that can improve their performance. SOAP implementations studied include Microsoft SOAP Toolkit, the SOAP: Lite Perl module, and Apache SOAP.
Mapping the Binding Site of Melanocortin 4 Receptor Agonists:  A Hydrophobic Pocket Formed by I3.28(125), I3.32(129), and I7.42(291) Is Critical for Receptor Activation (2006)

The melanocortin 4 receptor is involved in the control of the feeding behavior and energy homeostasis. It is regulated by internal agonist (alpha-MSH) and antagonists (Agouti). Peptide agonists bind in a beta-turn conformation that organizes the characteristic message sequence (His-L/DPhe-Arg-Trp) in an optimal arrangement for binding and activation of the receptor. Our goal is to determine the most likely binding modes of peptide and small molecule agonists to use this information to guide our structure-based drug design efforts. Previous studies have identified some residues that are likely to be involved in peptide agonist binding, giving an initial estimate of the main contacts between peptides and receptor. However, a more detailed description of the orientation of the peptide in a beta-turn conformation in the binding site, as well as of the small molecule agonists, and it is commonalities with the peptide agonist binding modes is necessary to serve as the basis for structure-based drug design. In the current study we combine site-directed mutagenesis with molecular modeling studies to determine the most likely binding mode of peptide and small molecule agonists, and we found that Y6.58(268), Y7.38(287), I3.28(125), I3.32(129), and I7.42(291) also line the binding site and are likely to have direct contacts with the MC4R agonists. Of particular interest are residues I3.28(125), I3.32(129), and I7.42(291), which form a hydrophobic pocket where I7.42(291), on top of the NPXXY motif, is likely to act as a new rotamer switch implicated in the activation of the receptor.
Relational Neural Expectation Maximization: Unsupervised Discovery of Objects and their Interactions (2018)

Common-sense physical reasoning is an essential ingredient for any intelligent agent operating in the real-world. For example, it can be used to simulate the environment, or to infer the state of parts of the world that are currently unobserved. In order to match real-world conditions this causal knowledge must be learned without access to supervised data. To address this problem we present a novel method that learns to discover objects and model their physical interactions from raw visual images in a purely \emph{unsupervised} fashion. It incorporates prior knowledge about the compositional nature of human perception to factor interactions between object-pairs and learn efficiently. On videos of bouncing balls we show the superior modelling capabilities of our method compared to other unsupervised neural approaches that do not incorporate such prior knowledge. We demonstrate its ability to handle occlusion and show that it can extrapolate learned knowledge to scenes with different numbers of objects.
Chemically Modified Amino Acids in Copper Proteins That Bind or Activate Dioxygen The author acknowledges the Royal Society (London) for a University Research Fellowship. (2001)

Changing mechanisms: More than half of the known classes of copper oxidase contain a chemically modified amino acid within their active site. Recent experiments by Klinman et al. on the biogenesis of one of these, topaquinone (TPQ; see scheme), have shown that this occurs by a different mechanism from that observed for the aqueous aerobic synthesis of hydroxybenzoquinones in vitro.
The role of superantigens in human diseases (1995)

Many of the infections caused by group A streptococci and Staphylococcus aureus depend upon these organisms' ability to produce exotoxins. Pyrogenic toxin superantigens, a large family of serologically distinct, three-dimensional, structure-related proteins, are an example of such exotoxins. Pyrogenic toxin superantigens cause illnesses such as toxic shock syndromes and scarlet fever and have been strongly implicated in Kawasaki syndrome, arthritis, guttate psoriasis, and atopic dermatitis. Many, if not all, of the toxins' effects are caused by their alteration of the immune system cells, leading to CD4+ T-lymphocyte and macrophage activation.
Release-control structure for post-process release of a micromachined cantilever (2002)

This paper presents a cost-effective method of obtaining intact, released oxide/poly cantilever beams (using bulk micromachining), within the constraints of simple post-processing of a standard CMOS fabrication process. Extensions to the basic cantilever are used to prevent the main oxide/poly beam from bending upwards until the main cantilever is completely released from the Si beneath. The cantilever and extensions are designed based on etch anisotropy in TMAH 25 wt% at 80/spl deg/C. The connection tether angles are designed to be at an angle where the underetch rate of the etchant is greatest.
Disc Space Preparation in Transforaminal Lumbar Interbody Fusion: A Comparison of Minimally Invasive and Open Approaches (2014)

When performed by a surgeon experienced with MIS TLIF, MIS and open approaches are similar in regard to the adequacy of disc space preparation. The least amount of disc by percentage is removed from the posterior contralateral quadrant regardless of the approach; surgeons should pay particular attention to this anatomic location during the discectomy portion of the procedure to minimize the likelihood of pseudarthrosis.
Label-Retaining Cells in the Rat Pancreas (2003)

Islets of Langerhans are micro-organs scattered throughout the pancreas that contain insulin-producing cells, called beta-cells. Although new light has been recently shed on beta-cell development, information on the phenotype and location of beta-stem cells remains scarce. Here, we provide evidence that beta-stem cells are slow-cycling cells located within and around the islets of Langerhans. First, using a bromodeoxyuridine (BrdU) pulse/chase approach, we detected BrdU-retaining cells in vivo in the islet area of rat pancreata. These cells were negative for endocrine markers but expressed Pdx1, a marker for pancreatic stem cells. Next, using an in vitro model that mimicked endocrine cell development, we found that BrdU-retaining cells were capable of differentiating into beta-cells. Taken together, these observations demonstrate that BrdU retention is a property of beta-stem cells.
Gestural Mappings:towards the creation of a three dimensional composition environment (2011)

The creation of the UPIC system by Iannis Xenakis [6, pp.331-335] marked a highly evocative period in his compositional career in synthesizing and exploring directly, physical drawings and gestures. Since that date, few gestural based compositional tools have been created and explored by composers of contemporary Instrumental, Electronic or Acousmatic music. In the last couple of years society has seen the commercial sale of several inexpensive gestural based controllers for video game systems that allow the exploration and mapping of physical movements onto DSP (Digital Signal Processing). It has been documented for many years that more sensitive computer interfaces is one of the most important fields of research [3, p.209], however, few have used such hardware in a serious compositional sense. This initial investigation into the control of DSP and synthesis using physical movements and gestures is part of the ongoing research of the author into the creation of a fully dynamic three-dimensional composition environment.