gebhart/patrepeval huggingface dataset:
Differential niche and Wnt requirements during acute myeloid leukemia progression (2011)

Hematopoietic stem cells (HSCs) engage in complex bidirectional signals with the hematopoietic microenvironment (HM), and there is emerging evidence that leukemia stem cells (LSCs) may use similar interactions. Using a syngeneic retroviral model of MLL-AF9 induced acute myeloid leukemia (AML), we have identified 2 different stages of leukemia progression, propagated by "pre-LSCs" and established leukemia (LSCs) and compared the homing properties of these distinctive entities to that of normal HSCs. The homing and microlocalization of pre-LSCs was most similar to long-term HSCs and was dependent on cell-intrinsic Wnt signaling. In contrast, the homing of established LSCs was most similar to that of committed myeloid progenitors and distinct from HSCs. Although osteoblast-derived Dickkopf-1, a potent Wnt inhibitor known to impair HSC function, dramatically impaired normal HSC localization within the bone marrow, it did not affect pre-LSCs, LSC homing, or AML development. Mechanistically, cell-intrinsic Wnt activation was observed in human and murine AML samples, explaining the independence of MLL-AF9 LSCs from niche-derived Wnt signals. These data identify differential engagement of HM associated with leukemic progression and identify an LSC niche that is physically distinct and independent of the constraints of Wnt signaling that apply to normal HSCs.
The effect of prestorage irradiation red cell survival on posttransfusion (1992)

Transfusion-associated graft-versus-host disease (TA-GVHD) may occur whenever immunologically competent allogeneic lymphocytes are transfused to an immunocompromised recipient. Irradiation of blood components eliminates the risk of TA-GVHD but may damage the cellular elements in the transfused component, particularly if the cells are stored for prolonged periods in the irradiated state. To study the effect of irradiation on long-term storage of red cells, AS-1 red cells from eight normal subjects were prepared on two occasions. On one occasion, the units were stored as standard AS-1 red cells for 42 days at 4 degrees C; on the other, they were exposed to 3000 cGy radiation within 4 hours of collection and then were stored as AS-1 red cells for 42 days at 4 degrees C. The donations were at least 12 weeks apart. Irradiated units demonstrated significant elevations in poststorage plasma hemoglobin (Hb) (623 +/- 206 vs. 429 +/- 194 g/dL [6230 +/- 2060 vs. 4290 +/- 1940 g/L], p less than 0.02) and plasma potassium (78 +/- 4 vs. 43 +/- 9 mEq/L [78 +/- 4 vs. 43 +/- 9 mmol/L], p less than 0.01) and significant decreases in red cell ATP (1.9 +/- 0.2 vs. 2.1 +/- 0.3 microM/g Hb, p less than 0.04) and 24-hour posttransfusion red cell recovery (68.5 vs. 78.4%, p less than 0.02), as compared to nonirradiated units. It can be concluded that irradiation with 3000 cGy damages red cells and that long-term storage in the irradiated state may enhance this damage. Red cells should not be stored for 42 days after irradiation with 3000 cGy.
Preparation and Tumor Cell Uptake of Poly(N-isopropylacrylamide) Folate Conjugates (2002)

Folate conjugates (PNIPAM-NH-FA) of a copolymer of N-isopropylacrylamide (NIPAM) and amino-N'-ethylenedioxy-bis(ethylacrylamide) were prepared by an efficient synthesis leading to random grafting, via a short dioxyethylene spacer, of approximately 7 folic acid residues per macromolecule. The chemical composition of the copolymer was characterized by (1)H NMR and UV/vis spectroscopy. A fluorophore-labeled folate PNIPAM conjugate was tested by in vitro assays performed with cultured KB-31 cells overexpressing the folate receptor. The cellular uptake of the copolymer was found to be temperature dependent and was competitively decreased by free folic acid, indicating that the polymer uptake is mediated specifically by the folate receptor. Hydrophobically modified folate conjugates of NIPAM, amino-N'-ethylenedioxy-bis(ethylacrylamide) copolymers, bearing a small number of n-octadecyl groups were prepared following a modified synthetic procedure for use in future studies of FA-targeted liposomes.
Xom: a Xenopus homeobox gene that mediates the early effects of BMP-4 (1996)

Bone morphogenetic protein-4 (BMP-4) is thought to play an important role in early Xenopus development by acting as a "ventralizing factor' and as an epidermal determinant: local inhibition of BMP-4 function in whole embryos causes the formation of an additional dorsal axis, and inhibition of BMP-4 function in isolated ectodermal cells causes the formation of neural tissue. In this paper we describe a homeobox-containing gene whose expression pattern is similar to that of BMP-4, whose expression requires BMP-4 signalling and which, when over-expressed, causes a phenotype similar to that caused by over-expression of BMP-4. We suggest that this gene, which we call Xom, acts downstream of BMP-4 to mediate its effects.
Toward dependency-aware live virtual machine migration (2009)

The most powerful characteristic of any machine virtualization technology is its ability to adapt to both its underlying infrastructure and the applications it supports. Possibly the most dynamic feature of machine virtualization is the ability to migrate live virtual machines between physical hosts in order to optimize performance or avoid catastrophic events. Unfortunately, the need for live migration increases during times when resources are most scarce. For example, load-balancing is only necessary when load is significantly unbalanced and impending downtime often causes many virtual machines to seek new hosts simultaneously. It is imperative that live migration mechanisms be as fast and efficient as possible in order for virtualization to provide dynamic load balancing, zero-downtime scheduled maintenance, and automatic failover during unscheduled downtime.
A game theoretical approach to evaluate cooperation enforcement mechanisms in mobile ad hoc networks (2003)

Abstract. This paper focuses on the formal assessment of the properties of cooperation enforcement mechanisms used to detect and prevent selfish behavior of nodes forming a mobile ad hoc network. Taking as a reference the CORE mechanism introduced in [9], we present two alternative approaches based on game theory that provide a powerful analytical method to study cooperation between self-interested players. We demonstrate that the formation of large coalitions of cooperating nodes is possible only when a mechanism like CORE is implemented in each node. Game theory also provides further insight to features of CORE such as the convergence speed to a cooperative behavior. 1.
Microcirculation in Sepsis: New Perspectives (2013)

Microcirculatory dysfunction has been recently recognized as a key pathophysiologic process in the evolution of sepsis. In the present review, we discuss fundamental aspects of microcirculatory abnormalities during septic shock, including pathogenic mechanisms, technological assessment, clinical correlates and potential therapies. The most important function of the microcirculation is the regulation and distribution of flow within the different organs. In septic shock, microcirculatory dysfunction may arise as a result of several factors such as endothelial dysfunction, leukocyte-endothelium interactions, coagulation and inflammatory disorders, hemorheologic abnormalities, and functional shunting. Severity and persistence of these microcirculatory abnormalities are associated with bad prognosis and are not necessarily predicted by systemic variables. The introduction of bedside techniques that allow evaluation of the microcirculation into clinical practice has opened up a new field of functional hemodynamic monitoring. Recent data suggest that microcirculatory abnormalities can be staged in severity. Some microcirculatory indices are more accurately related to morbidity and mortality, and thus a definition of clinically relevant microcirculatory abnormalities is feasible. On the other hand, although several systemic variables do not predict microcirculatory status, high norepinephrine (NE) requirements and hyperlactatemia are associated with a much higher prevalence of relevant microcirculatory derangements. Therefore, severe septic shock patients could represent a more precise target for interventions, particularly in microcirculation-oriented clinical trials. Clinical research has identified various therapeutic approaches that are successful in modifying the microcirculation. Future research must determine whether some of these approaches are successful in improving outcome of critically ill patients by recruiting the microcirculation.
Monoclonal Antibodies for B-Cell Lymphomas: Rituximab and Beyond (2007)

The year 2007 marks the 10th anniversary of approval by the U.S. Food and Drug Adminstration of the first monoclonal antibody for the treatment of cancer. Rituximab, an anti-CD20 chimeric monoclonal antibody, was approved for the treatment of patients with relapsed/refractory low-grade B-cell non-Hodgkin lymphomas. From an immunologic perspective, this therapeutic indication provided the long-elusive validation of immunotherapy as the fourth modality of treatment for patients with cancer. From a clinical perspective, it was hard to imagine then that this nonchemotherapeutic approach would dramatically impact the management of patients with almost every type of B-cell malignancy and that it would even find a place as a therapeutic option for patients with non-malignant disorders. Although thousands of patients have been treated worldwide with rituximab, there is still debate regarding its mechanism(s) of action. The demonstration that a number of patients do not benefit with this treatment and that no cures have been achieved with single-agent rituximab prompted several investigators to identify those barriers limiting the efficacy of this monoclonal antibody. Here, we summarize what we have learned in the past 10 years about rituximab efficacy and its mechanisms of action and resistance. We also discuss the new generation of monoclonal antibodies, the development of which has been spurred by the widespread success of anti-CD20 MAb therapy.
Self-alignment of optical fibers with optical quality end-polished silicon rib waveguides using wet chemical micromachining techniques (1999)

This paper presents a new cost-effective method for self-aligning optical fibers on silicon platforms and for achieving optical quality end-polished silicon-on-insulator (SOI) rib waveguide devices using wet chemical micromachining techniques. Through accurate alignment to the [011] plane of the [100] device layer of a SOI wafer, rib waveguide devices with self-alignment features are fabricated with the ends of each waveguide wet etched and concurrently polished providing an optical quality facet or fiber-to-waveguide interface. Eliminating the need to saw cut and then mechanically polish the ends of fabricated devices, the overall fabrication process is simplified whilst also providing an integrated optic fiber alignment capability at the ends of the fabricated waveguide devices with an alignment accuracy limited by fiber size tolerance. Experimental measurements were carried out to verify the optical quality of the waveguide facets formed using this new technique which proved excess facet losses of practically unmeasurable quantities.
The chemical origin of enhanced signals from tip-enhanced Raman detection of functionalized nanoparticles (2013)

Here we present results that investigate the origins of signals observed in tip-enhanced Raman (TERS) measurements of functionalized nanoparticles. Surface enhanced Raman scattering (SERS) is known to give the largest enhancements in gap junctions. Similarly, gap-mode TERS also produces significant enhancements. The methodology developed here provides gap-mode like enhancements in TERS measurements without the need for a metal surface. Using a combination of aggregated nanoparticle SERS and TERS detection of functionalized nanoparticles, we assess the chemical origins of the observed peaks and show that molecules outside of gap junctions are also enhanced using our methodology. Our experiments use biotin and streptavidin as a model system for protein-ligand binding. Different size functionalized nanoparticles (20, 50, 80 nm) show changes in intensity in both SERS and TERS measurements. SERS measurements indicate that streptavidin has a larger Raman cross-section than biotin and is preferentially observed. The specific streptavidin peaks observed by TERS vary depending on whether streptavidin is attached to the nanoparticle and located in the gap or bound to the substrate surface. This methodology suggests a route to enhancing TERS signals associated with protein receptors in biological systems that cannot be isolated to a metallic surface.
Object recognition by fast hypothesis generation and reasoning about object interactions (1996)

We present a two-step approach for recognizing multiple 3-D objects in single 2-D images. In the first step, hypotheses of object instances are generated using a memory-based technique. This technique relies on an array, which is computed off-line, that associates a large number of object poses with corresponding image features. During actual recognition, the array serves as a discrete approximation of the inverse projection function, and each image feature returns a set of poses that are accumulated by a generalized Hough transform. In the second step, the configuration of hypotheses that best interprets the image is calculated using a Bayesian network. The network represents both visual effects, such as the creation and occlusion of image features, and physical constraints, such as object interference.
RNA interference improves motor and neuropathological abnormalities in a Huntington's disease mouse model (2005)

Huntington's disease (HD) is a fatal, dominant neurogenetic disorder. HD results from polyglutamine repeat expansion (CAG codon, Q) in exon 1 of HD, conferring a toxic gain of function on the protein huntingtin (htt). Currently, no preventative treatment exists for HD. RNA interference (RNAi) has emerged as a potential therapeutic tool for treating dominant diseases by directly reducing disease gene expression. Here, we show that RNAi directed against mutant human htt reduced htt mRNA and protein expression in cell culture and in HD mouse brain. Importantly, htt gene silencing improved behavioral and neuropathological abnormalities associated with HD. Our data provide support for the further development of RNAi for HD therapy.
Ein glucosespezifischer molekularer Fluoreszenzsensor (1994)

Geringe D ‐Fructose‐ und D ‐Galactosekonzentrationen stören den Nachweis von D ‐Glucose mit dem Fluoreszenzindikator 1 nicht. Die Diboronsäure 1 ist einfach zu synthetisieren und bildet eine spaltenförmige Struktur, in de Monosaccharide mit unterschiedlicher Selektivität gebunden werden können. Die Zucker‐Diboronsäure‐1 :1‐Komplexe lassen sich durch ihre Fluoreszenz gut nachweisen. magnified image
Partitioned ROBDDs—a compact, canonical and efficiently manipulable representation for Boolean functions (1996)

We present a new representation for Boolean functions called Partitioned ROBDDs. In this representation we divide the Boolean space into 'k' partitions and represent a function over each partition as a separate ROBDD. We show that partitioned-ROBDDs are canonical and can be efficiently manipulated. Further they can be exponentially more compact than monolithic ROBDDs and even free BDDs. Moreover, at any given time, only one partition needs to be manipulated which further increases the space efficiency. In addition to showing the utility of partitioned-ROBDDs on special classes of functions, we provide automatic techniques for their construction. We show that for large circuits our techniques are more efficient in space as well as time over monolithic ROBDDs. Using these techniques, some complex industrial circuits could be verified for the first time.
CD22 Ligand Binding Regulates Normal and Malignant B Lymphocyte Survival In Vivo (2006)

The CD22 extracellular domain regulates B lymphocyte function by interacting with alpha2,6-linked sialic acid-bearing ligands. To understand how CD22 ligand interactions affect B cell function in vivo, mouse anti-mouse CD22 mAbs were generated that inhibit CD22 ligand binding to varying degrees. Remarkably, mAbs which blocked CD22 ligand binding accelerated mature B cell turnover by 2- to 4-fold in blood, spleen, and lymph nodes. CD22 ligand-blocking mAbs also inhibited the survival of adoptively transferred normal (73-88%) and malignant (90%) B cells in vivo. Moreover, mAbs that bound CD22 ligand binding domains induced significant CD22 internalization, depleted marginal zone B cells (82-99%), and reduced mature recirculating B cell numbers by 75-85%. The CD22 mAb effects were independent of complement and FcRs, and the CD22 mAbs had minimal effects in CD22AA mice that express mutated CD22 that is not capable of ligand binding. These data demonstrate that inhibition of CD22 ligand binding can disrupt normal and malignant B cell survival in vivo and suggest a novel mechanism of action for therapeutics targeting CD22 ligand binding domains.
Diabodies: Molecular engineering and therapeutic applications (2009)

Bispecific antibodies are capable of interacting with two different antigens and when selected properly, can redirect cytotoxic effector cells to tumor cells for effective killing. These antibodies are therefore of great interest in the research and development of cancer treatment. Over the last two decades, many different bispecific antibody-derived molecular formats have been described, among which diabodies represent an important class of engineered molecules that possess tumor-targeting function. Since diabodies were first introduced in the early 1990s, extensive efforts have been made to optimize their physicochemical and key functional properties, as well as to provide in vivo proof of concept of their antitumor efficacy in animal models. With the clinical validation of the T-cell-retargeting mechanism for cancer therapy currently in place, there is renewed interest in this bispecific class of biologic molecules, with additional novel formats being described in recent years. Even with the remaining challenges of the manufacturing yields and drug-like properties, diabodies and their derivatives remain viable therapeutic modalities that warrant further consideration and development.
A Framework for Fine-Granular Computational-Complexity Scalable Motion Estimation (2005)

This paper presents a novel motion estimation (ME) framework that offers fine-granular computational-complexity scalability. In the proposed framework, the ME process is first partitioned into multiple search passes. A priority function is used to represent the distortion reduction efficiency of each pass. According to the predicted priority of each macroblock (MB), computational resources are then allocated effectively in a progressive way to achieve fine-granular computational-complexity scalability. Experiments show that our proposed scheme achieves progressively improved performance over a wide range of computational capabilities.
Interferon-α in systemic lupus erythematosus (2004)

Purpose of review To describe the lines of evidence supporting a significant role for interferon-α (IFNα) in the pathogenesis of systemic lupus erythematosus (SLE) and to propose potential mechanisms by which IFNα contributes to the autoimmunity and immune dysfunction of SLE. Recent findings Long-standing data indicating elevated levels of IFNα in the circulation of patients with SLE have recently been supplemented by reports from clinical practice, gene expression data, analysis of patient cells studied ex vivo, and studies of mechanisms of induction of IFNα production to provide complementary data strongly supporting a pathogenic role for IFNα in SLE. Recombinant IFNα, when administered as a therapy to patients with malignancy or hepatitis infection, can induce SLE. IFNα-regulated genes are highly expressed in SLE peripheral blood cells compared with cells from control subjects. Functional alterations of SLE mononuclear cells have been attributed to effects of IFNα. In addition, immune complexes bearing lupus autoantibodies and RNA or DNA have been shown to induce IFNα production. Finally, progress in understanding the role of Toll-like receptors (TLR) in the activation of the innate immune response has suggested potential mechanisms by which adjuvant-like factors act through TLR to induce IFNα as well as effective processing of self-antigens, resulting in activation of an adaptive immune response directed against self, as well as cytokine-mediated immune dysfunction. Summary Substantial evidence supports a significant role for IFNα in the pathogenesis of lupus. The IFNα pathway represents a promising target for therapeutic intervention in patients with SLE.
Paper Spray for Direct Analysis of Complex Mixtures Using Mass Spectrometry (2010)

Complex mixtures can be ionized directly from paper for quantitative mass spectrometric analysis of trace components. Prior separations are an option. Detailed facts of importance to specialist readers are published as ”Supporting Information”. Such documents are peer-reviewed, but not copy-edited or typeset. They are made available as submitted by the authors. Please note: The publisher is not responsible for the content or functionality of any supporting information supplied by the authors. Any queries (other than missing content) should be directed to the corresponding author for the article.
Mycobacteriocidal Action of Exogenous Nitric Oxide (1999)

We tested the hypothesis that exposure of extracellular Mycobacterium tuberculosis to low concentrations (< 100 ppm) of nitric oxide (NO) for short periods (24 h or less) will result in microbial killing. We observed that NO had both dose- and time-dependent cidal effects that were very significant by two-way analysis of variance (F ratios of 13.4 [P < 0.001] and 98.1 [P < 0.0001], respectively). Conceivably, extracellular bacilli in patients with pulmonary tuberculosis might be vulnerable to exogenous NO.
On Estimation of a Probability Density Function and Mode (1962)

Abstract : Given a sequence of independent identically distributed random variables with a common probability density function, the problem of the estimation of a probability density function and of determining the mode of a probability function are discussed. Only estimates which are consistent and asymptotically normal are constructed. (Author)
Using the Boneh-Franklin and Boneh-Boyen Identity-Based Encryption Algorithms with the Cryptographic Message Syntax (CMS) (2009)

This document describes the conventions for using the Boneh-Franklin (BF) and Boneh-Boyen (BB1) identity-based encryption algorithms in the Cryptographic Message Syntax (CMS) to encrypt content-encryption keys. Object identifiers and the convention for encoding a recipient's identity are also defined.