gebhart/patrepeval huggingface dataset:
Botulinum neurotoxin type D enables cytosolic delivery of enzymatically active cargo proteins to neurones via unfolded translocation intermediates (2004)

Multi-domain bacterial protein toxins are being explored as potential carriers for targeted delivery of biomolecules. Previous approaches employing isolated receptor binding subunits disallow entry into the cytosol. Strategies in which catalytic domains are replaced with cargo molecules are presumably inefficient due to co-operation of domains during the endosomal translocation step. Here, we characterize a novel transport vehicle in which cargo proteins are attached to the amino terminus of the full-length botulinum neurotoxin type D (BoNT/D). The intrinsic enzymatic activity of the neurotoxin allowed quantification of the efficacy of cargo delivery to the cytosol. Dihydrofolate reductase and BoNT type A (BoNT/A) light chain (LC) were efficiently conveyed into the cytosol, whereas attachment of firefly luciferase or green fluorescent protein drastically reduced the toxicity. Luciferase and BoNT/A LC retained their catalytic activity as evidenced by luciferin conversion or SNAP-25 hydrolysis in the cytosol of synaptosomes, respectively. Conformationally stabilized dihydrofolate reductase as cargo considerably decreased the toxicity indicative for the requirement of partial unfolding of cargo protein and catalytic domain as prerequisite for efficient translocation across the endosomal membrane. Thus, enzymatically inactive clostridial neurotoxins may serve as effective, safe carriers for delivering proteins in functionally active form to the cytosol of neurones.
IBM Storage Tank—A heterogeneous scalable SAN file system (2003)

As the amount of data being stored in the open systems environment continues to grow, new paradigms for the attachment and management of data and the underlying storage of the data are emerging. One of the emerging technologies in this area is the storage area network (SAN). Using a SAN to connect large amounts of storage to large numbers of computers gives us the potential for new approaches to accessing, sharing, and managing our data and storage. However, existing operating systems and file systems are not built to exploit these new capabilities. IBM Storage Tank™ is a SAN-based distributed file system and storage management solution that enables many of the promises of SANs, including shared heterogeneous file access, centralized management, and enterprise-wide scalability. In addition, Storage Tank borrows policy-based storage and data management concepts from mainframe computers and makes them available in the open systems environment. This paper explores the goals of the Storage Tank project, the architecture used to achieve these goals, and the current and future plans for the technology.
Two distinct nodes of translational inhibition in the Integrated Stress Response (2017)

The Integrated Stress Response (ISR) refers to a signaling pathway initiated by stress-activated eIF2α kinases. Once activated, the pathway causes attenuation of global mRNA translation while also paradoxically inducing stress response gene expression. A detailed analysis of this pathway has helped us better understand how stressed cells coordinate gene expression at translational and transcriptional levels. The translational attenuation associated with this pathway has been largely attributed to the phosphorylation of the translational initiation factor eIF2α. However, independent studies are now pointing to a second translational regulation step involving a downstream ISR target, 4E-BP, in the inhibition of eIF4E and specifically cap-dependent translation. The activation of 4E-BP is consistent with previous reports implicating the roles of 4E-BP resistant, Internal Ribosome Entry Site (IRES) dependent translation in ISR active cells. In this review, we provide an overview of the translation inhibition mechanisms engaged by the ISR and how they impact the translation of stress response genes. [BMB Reports 2017; 50(11): 539-545].
Preserved IFN‐α production of circulating Vα24 NKT cells in primary lung cancer patients (2002)

Human Valpha24 NKT cells bearing an invariant Valpha24JalphaQ antigen receptor, the counterpart of murine Valpha14 NKT cells, are activated by a specific ligand, alpha-GalCer, in a CD1d-dependent manner. Here, we demonstrate decreased numbers of circulating Valpha24 NKT cells in patients with primary lung cancer compared to healthy volunteers. However, Valpha24 NKT cells and DCs from lung cancer patients were functionally normal, even in the presence of tumor. Furthermore, levels of Valpha24 NKT cells in surgically resected lung tissue appeared to be equivalent to those of Valpha14 NKT cells in the mouse lung. Levels of Valpha24 NKT cells in the tumor tissue itself were increased about 2.5 times. Administration of alpha-GalCer-pulsed DCs expanded Valpha14 NKT cells in the lung more than 10 times, and the increased levels were sustained for 1 week. This may explain the previous finding that alpha-GalCer-pulsed DCs exerted strong antitumor activity in mouse lung tumor metastatic models. The potential use of alpha-GalCer-pulsed DCs for immunotherapy aimed at activating endogenous Valpha24 NKT cells in the lung of cancer patients is discussed.
Cellular Basis of Skin Allograft Rejection: An In Vivo Model of Immune-Mediated Tissue Destruction (1992)

Rejection of transplanted tissue allografts results from T-cell recognition of histocompatibility antigens expressed by cells of the donor graft. This review focuses on the phenotype, specificity, and function of the T cells mediating rejection responses against skin allografts, and on the immune mechanisms by which host T cells are either activated or rendered non-responsive by cellular populations within the graft. We review the cellular basis for rejection responses across limited class-I and class-II major histocompatibility differences, as well as the specificity of the rejection response itself.
Novel Biodegradable Shape Memory Material Based on Partial Inclusion Complex Formation between α-Cyclodextrin and Poly(ϵ-caprolactone) (2008)

A novel shape memory material was prepared based on the formation of inclusion complexes between alpha-cyclodextrin (alpha-CD) and poly(epsilon-caprolactone) (PCL); the PCL-alpha-CD inclusion crystallites serve as a fixing phase, while free PCL crystallites serve as a reversible phase. The characteristics of the material were investigated and a mechanism for the shape memory behavior was proposed. This material showed good shape memory properties, with the recovery ratio exceeding 90% and the recovery time being less than 6 s at 90 degrees C. This PCL-alpha-CD partial inclusion complex lost about 50% (47.4 +/- 4.4%) weight within 45 days in presence of lipase, indicating its degradability. The shape memory and biodegradation properties of the well-designed polymer-alpha-CD complexes indicate great promise for this novel shape memory material.
Skyline with presorting (2004)

The skyline, or Pareto, operator selects those tuples that are not dominated by any others. Extending relational systems with the skyline operator would offer a basis for handling preference queries. Good algorithms are needed for skyline, however, to make this efficient in a relational setting. We propose a skyline algorithm, SFS, based on presorting that is general, for use with any skyline query, efficient, and well behaved in a relational setting.
ALDP expression in fibroblasts of patients with X‐linked adrenoleukodystrophy (1995)

The adrenoleukodystrophy gene encodes a peroxisomal integral membrane protein (ALDP) consisting of 745 amino acids with a molecular weight of 75kDa. ALDP expression was studied in fibroblasts from 24 male ALD patients from 17 unrelated ALD kindreds. In four kindreds an identical 2-base-pair deletion was found. We report the absence of ALDP in 12 kindreds carrying nonsense mutations, frame shifts or amino acid substitutions in the carboxy terminus of ALDP, together accounting for 71% of the ALD kindreds. ALDP was present in five kindreds (29%) with amino acid substitutions in the amino terminal half of the protein; in two of these kindreds ALDP was present although at a reduced level. The absence of truncated proteins suggests that the carboxy terminus has a function in the stabilization of ALDP.
Cache miss equations (1999)

With the ever-widening performance gap between processors and main memory, cache memory, which is used to bridge this gap, is becoming more and more significant. Caches work well for programs that exhibit sufficient locality. Other programs, however, have reference patterns that fail to exploit the cache, thereby suffering heavily from high memory latency. In order to get high cache efficiency and achieve good program performance, efficient memory accessing behavior is necessary. In fact, for many programs, program transformations or source-code changes can radically alter memory access patterns, significantly improving cache performance. Both hand-tuning and compiler optimization techniques are often used to transform codes to improve cache utilization. Unfortunately, cache conflicts are difficult to predict and estimate, precluding effective transformations. Hence, effective transformations require detailed knowledge about the frequency and causes of cache misses in the code. This article describes methods for generating and solving Cache Miss Equations (CMEs) that give a detailed representation of cache behavior, including conflict misses, in loop-oriented scientific code. Implemented within the SUIF compiler framework, our approach extends traditional compiler reuse analysis to generate linear Diophantine equations that summarize each loop's memory behavior. While solving these equations is in general difficult, we show that is also unnecessary, as mathematical techniques for manipulating Diophantine equations allow us to relatively easily compute and/or reduce the number of possible solutions, where each solution corresponds to a potential cache miss. The mathematical precision of CMEs allows us to find true optimal solutions for transformations such as blocking or padding. The generality of CMEs also allows us to reason about interactions between transformations applied in concert. The article also gives examples of their use to determine array padding and offset amounts that minimize cache misses, and to determine optimal blocking factors for tiled code. Overall, these equations represent an analysis framework that offers the generality and precision needed for detailed compiler optimizations.
Continuous Mesoporous Silica Films with Highly Ordered Large Pore Structures (1998)

The formation of continuous mesoporous silica films with large periodic cage and pore structures is reported here. The authors use low-cost commercially available triblock copolymers and poly(ethylene oxide) non-ionic surfactants as the structure-directing agents in conjunction with dip-coat processing. In the Figure a transmission electron microscope image of a calcined hexagonal mesoporous silica film is shown.
Gene Expression Analysis of Preinvasive and Invasive Cervical Squamous Cell Carcinomas Identifies HOXC10 as a Key Mediator of Invasion (2007)

If left untreated, a subset of high-grade squamous intraepithelial lesions (HSIL) of the cervix will progress to invasive squamous cell carcinomas (SCC). To identify genes whose differential expression is linked to cervical cancer progression, we compared gene expression in microdissected squamous epithelial samples from 10 normal cervices, 7 HSILs, and 21 SCCs using high-density oligonucleotide microarrays. We identified 171 distinct genes at least 1.5-fold up-regulated (and P < 0.001) in the SCCs relative to HSILs and normal cervix samples. Differential expression of a subset of these genes was confirmed by quantitative reverse transcription-PCR and immunohistochemical staining of cervical tissue samples. One of the genes up-regulated during progression, HOXC10, was selected for functional studies aimed at assessing its role in mediating invasive behavior of neoplastic squamous epithelial cells. Elevated HOXC10 expression was associated with increased invasiveness of human papillomavirus-immortalized keratinocytes and cervical cancer-derived cell lines in both in vitro and in vivo assays. Cervical cancer cells with high endogenous levels of HOXC10 were less invasive after short hairpin RNA-mediated knockdown of HOXC10 expression. Our findings support a key role for the HOXC10 homeobox protein in cervical cancer progression. Other genes with differential expression in invasive SCC versus HSIL may contribute to tumor progression or may be useful as markers for cancer diagnosis or progression risk.
The Ubiquitin Ligase Siah2 and the Hypoxia Response (2009)

Growing evidence indicates that ubiquitin ligases play a critical role in the hypoxia response. Among them, Siah2, a RING finger ligase, is an important regulator of pathways activated under hypoxia. Siah2 regulates prolyl hydroxylases PHD3 and 1 under oxygen concentration of 2% to 5%, thereby allowing accumulation of hypoxia-inducible factor (HIF)-1alpha, a master regulator of the hypoxia response within the range of physiological normoxic to mild hypoxic conditions. Growing evidence also indicates an important function for Siah2 in tumor development and progression based on pancreatic cancer, mammary tumor, and melanoma mouse models. This review summarizes our current understanding of Siah2 regulation and function with emphasis on hypoxia and tumorigenesis.
Comparative biology of the endocannabinoid system (2000)

In this review we discuss data showing that the endogenous cannabinoid system, represented by cannabinoid receptors, endogenous cannabinoid receptor ligands and enzymes for the biosynthesis and degradation of these ligands, is conserved throughout evolution from coelenterates to man. This signaling system has been suggested to play several roles in animals, including the regulation of cell development and growth, nervous functions, reproduction and feeding behavior. In this article, however, we shall describe with more detail the possible function of the endogenous cannabinoid system in the modulation of immune response in organisms from the lower to the higher levels of animal evolution.
Physicochemical properties of bile acids and their relationship to biological properties: an overview of the problem (1984)

The structure of the bile acid molecule is described and correlated with physiochemical properties of bile acids such as solubility, ionization, and micelle formation. Recent measurements of the critical micellar concentration (CMC) of a large number of bile acids indicate that the CMC is influenced by both side chain and nuclear structure. Bile acids with hydroxy substituents on both sides of the steroid nucleus are non-amphipathic and do not form micelles, and decreasing the length of the side chain causes an exponential increase in the CMC. Bile acid ionization, measured by titration in alcohol-water mixtures, is shown to be uninfluenced by nuclear substituents; the pKa of all unconjugated bile acids is about 5. Interactions of bile acid solutions with Ca2+ are discussed; recent work indicates that cholyl conjugates bind Ca2+ as monomers in solution. Model systems relevant to biological processes are classified, as are some of the physicochemical parameters of these systems. Biological processes involving bile acids are tabulated, and corresponding model systems are assigned to each. Some biological processes such as bile acid transport show marked species differences, suggesting that physicochemical parameters are insufficient to explain biological differences. It is recommended that the physical chemist study a variety of bile acids, that the biologist study a variety of species, and that both collaborate to attempt to factor out the extent to which physicochemical properties of bile acids can explain their biological properties.
A scheme for real-time channel establishment in wide-area networks (1990)

Multimedia communication involving digital audio and/or digital video has rather strict delay requirements. A real-time channel is defined as a simplex connection between a source and a destination characterized by parameters representing the performance requirements of the client. A study is made of the feasibility of providing real-time services on a packet-switched store-and-forward wide-area network with general topology. A description is given of a scheme for the establishment of channels with deterministic or statistical delay bounds, and the results of the simulation experiments run to evaluate it are presented. The results are judged encouraging: the approach satisfies the guarantees even in worst case situations, uses the network's resources to a fair extent, and efficiently handles channels with a variety of offered load and burstiness characteristics. Also, the packet transmission overhead is quite low, and the channel establishment overhead is small enough to be acceptable in most practical cases.< <ETX xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">&gt;</ETX>
Entity matching in heterogeneous databases: a distance-based decision model (2002)

The need to leverage the information contained in heterogeneous data sources has been widely documented. In order to accomplish this goal, an organization must resolve several types of heterogeneity problems that may exist across different data sources. We investigate one such problem called the entity heterogeneity problem. This problem arises when the same real-world entity type is represented using different identifiers in different applications. We propose a decision theoretic model to resolve the problem. Our model uses a distance-based measure to express the similarity between two entity instances. We have implemented the model, and our experimental results indicate that this is a viable approach in real-world situations.
Multimerization of Human Immunodeficiency Virus Type 1 Gag Promotes Its Localization to Barges, Raft-Like Membrane Microdomains (2001)

The Gag polyprotein of human immunodeficiency virus type 1 (HIV-1) organizes the assembly of nascent virions at the plasma membrane of infected cells. Here we demonstrate that a population of Gag is present in distinct raft-like membrane microdomains that we have termed "barges." Barges have a higher density than standard rafts, most likely due to the presence of oligomeric Gag-Gag assembly complexes. The regions of the Gag protein responsible for barge targeting were mapped by examining the flotation behavior of wild-type and mutant proteins on Optiprep density gradients. N-myristoylation of Gag was necessary for association with barges. Removal of the NC and p6 domains shifted much of the Gag from barges into typical raft fractions. These data are consistent with a model in which multimerization of myristoylated Gag proteins drives association of Gag oligomers into raft-like barges. The functional significance of barge association was revealed by several lines of evidence. First, Gag isolated from virus-like particles was almost entirely localized in barges. Moreover, a comparison of wild-type Gag with Fyn(10)Gag, a chimeric protein containing the N-terminal sequence of Fyn, revealed that Fyn(10)Gag exhibited increased affinity for barges and a two- to fourfold increase in particle production. These results imply that association of Gag with raft-like barge membrane microdomains plays an important role in the HIV-1 assembly process.
"Dip-Pen" Nanolithography (1999)

A direct-write "dip-pen" nanolithography (DPN) has been developed to deliver collections of molecules in a positive printing mode. An atomic force microscope (AFM) tip is used to write alkanethiols with 30-nanometer linewidth resolution on a gold thin film in a manner analogous to that of a dip pen. Molecules are delivered from the AFM tip to a solid substrate of interest via capillary transport, making DPN a potentially useful tool for creating and functionalizing nanoscale devices.
Dendritic Cell-Targeted Approaches to Modulate Immune Dysfunction in the Tumor Microenvironment (2013)

There has been enormous progress this past decade in the understanding of the biology of dendritic cells (DCs) along with increasing attention for the development of novel dendritic cell (DC)-based cancer therapies. However, the clinical impact of DC-based vaccines remains to be established. This limited success could be explained by suboptimal conditions for generating potent immunostimulatory DCs as well as immune suppression mediated by the tumor microenvironment (TME). Therefore, strategies that optimize the potency of DC vaccines along with newly described therapies that target the TME in order to overcome immune dysfunction may provide durable tumor-specific immunity. These novel interventions hold the most promise for successful cancer immunotherapies.
Interactive behaviors for bipedal articulated figures (1991)

We describe techniques for interactively controlling bipedal articulated figures through kinematic constraints. These constraints model certain behavioral tendencies which capture some of the characteristics of human-like movement, and give us control over such elements as the figures' balanced and stability. They operate in near real-time, so provide behavioral control for interactive manipulation. These constraints form the basis of an interactive motion-generation system that allows the active movement elements to be layered on top of the passive behavioral constraints.
Iterative blind deconvolution method and its applications (1988)

A simple iterative technique has been developed for blind deconvolution of two convolved functions. The method is described, and a number of results obtained from a computational implementation are presented. Some further possible applications are indicated.
Large-vocabulary speech recognition algorithms (2002)

By making the advances necessary to implement next-generation speech recognition applications, researchers could develop systems within a decade that match human performance levels.
Changes in Plasma Soluble CD26 and CD30 during Pregnancy: Markers of Th1/Th2 Balance? (2000)

The theory that the Th1 and Th2 cell ratio shifts towards Th2 dominance during pregnancy may improve fetal survival has gained support from recent studies. Also, the variation in the Th1/Th2 cell ratio is reportedly associated with intrauterine growth retardation and preeclampsia. On the basis of these findings, the analysis of the Th1/Th2 balance may be useful in predicting severe complications during pregnancy. However, simple methods for the analysis of Th1/Th2 balance are presently not available. Recently, it has been reported that regulation of CD26 cell surface expression correlates with the production of Th1-like cytokines. On the other hand, previous studies proposed that the sCD30 molecule is an activation marker useful for evaluation of a Th2 immune response. It is, therefore, possible that the analysis of the Th1/Th2 balance during pregnancy by measuring plasma sCD26 and sCD30 simultaneously is a simple and useful method. We herein demonstrate that combined analysis of sCD26 and sCD30 is a potent surrogate tool to evaluate the Th1/Th2 balance during pregnancy.