gebhart/patrepeval huggingface dataset:
Evaluation of Cost Estimation Metrics: Towards a Unified Terminology (2013)

Cost overrun of software projects is major cause of their failures. In order to facilitate accurate software cost estimation, there are several metrics, tools and datasets. In this paper, we evaluate and compare different metrics and datasets in terms of similarities and differences of involved software attributes. These metrics forecast project cost estimations based on different software attributes. Some of these metrics are public and standard while others are only employed in a particular metric tool/dataset. Sixteen public cost estimation datasets are collected and analyzed. Different perspectives are used to compare and classify those datasets. Tools for feature selection and classification are used to find the most important attributes in cost estimation datasets toward the goal of effort prediction. In order to have better estimation it is needed to correlate cost estimation from different resources, which requires a unified standard for software cost estimation metric tools and datasets. It is pertinent that a common cost estimation model may not work for each project due to diverse project size, application areas etc. We suggest having a standardized terminology of project attributes used for cost estimation. This would improve cost estimation as multiple metrics could be applied on a project without much additional effort.
Mesothelin Expression in Pancreatic Mucinous Cysts (2014)

Our findings suggest that MLSN can be used as a marker of neoplastic transformation of epithelial cells in pancreatic mucinous cysts. The findings can help identify neoplastic mucinous epithelium.
Molecular Evidence of Adenosine Deaminase Linking Adenosine A2A Receptor and CD26 Proteins (2018)

Adenosine is an endogenous purine nucleoside that acts in all living systems as a homeostatic network regulator through many pathways, which are adenosine receptor (AR)-dependent and -independent. From a metabolic point of view, adenosine deaminase (ADA) is an essential protein in the regulation of the total intracellular and extracellular adenosine in a tissue. In addition to its cytosolic localization, ADA is also expressed as an ecto-enzyme on the surface of different cells. Dipeptidyl peptidase IV (CD26) and some ARs act as binding proteins for extracellular ADA in humans. Since CD26 and ARs interact with ADA at opposite sites, we have investigated if ADA can function as a cell-to-cell communication molecule by bridging the anchoring molecules CD26 and A<sub>2A</sub>R present on the surfaces of the interacting cells. By combining site-directed mutagenesis of ADA amino acids involved in binding to A<sub>2A</sub>R and a modification of the bioluminescence resonance energy transfer (BRET) technique that allows detection of interactions between two proteins expressed in different cell populations with low steric hindrance (NanoBRET), we show direct evidence of the specific formation of trimeric complexes CD26-ADA-A<sub>2A</sub>R involving two cells. By dynamic mass redistribution assays and ligand binding experiments, we also demonstrate that A<sub>2A</sub>R-NanoLuc fusion proteins are functional. The existence of this ternary complex is in good agreement with the hypothesis that ADA could bridge T-cells (expressing CD26) and dendritic cells (expressing A<sub>2A</sub>R). This is a new metabolic function for ecto-ADA that, being a single chain protein, it has been considered as an example of moonlighting protein, because it performs more than one functional role (as a catalyst, a costimulator, an allosteric modulator and a cell-to-cell connector) without partitioning these functions in different subunits.
Molecular defect in coagulation factor XFriuli results from a substitution of serine for proline at position 343 (1991)

Our previous findings suggested that coagulation factor XFriuli could be functionally defective owing to a point mutation in the portion of the factor X gene coding for the fully activated heavy chain. To verify the existence of this postulated change, we analyzed all eight exons of the normal and Friuli factor X gene. Each exon was amplified from genomic DNA using the polymerase chain reaction and cloned into the plasmid pUC19. The amplified DNA inserts were subjected to direct sequencing by the dideoxy chain termination method with forward and reverse oligonucleotide sequencing primers. A point mutation (C to T transition at nucleotide position 19,297) that results in coding for serine (TCC) in place of proline (CCC) at amino acid position 343 was found. This substitution involves a highly conserved proline residue oriented spatially close to both the cleavage site of the zymogen and the active site of the enzyme and explains the previous observations of discrete biochemical and functional differences between factor XFriuli and normal factor X. The mutation abolished an HgiCI restriction site present in the normal factor X gene, and this change constitutes the basis for a convenient method for screening individuals carrying this molecular defect. Proline343 is in conserved region 5 of the serine protease superfamily to which factor X belongs and is part of a 14- residue L*****P******C motif that occurs in at least 16 other enzymes. Computer analysis suggests that the motif may be an essential aspect of conformational features important to functional properties of factor X as well as other serine proteases.
Impact of Mutations in the Coreceptor Binding Site on Human Immunodeficiency Virus Type 1 Fusion, Infection, and Entry Inhibitor Sensitivity (2004)

An increasingly large number of antiviral agents that prevent entry of human immunodeficiency virus (HIV) into cells are in preclinical and clinical development. The envelope (Env) protein of HIV is the major viral determinant that affects sensitivity to these compounds. To understand how changes in Env can impact entry inhibitor sensitivity, we introduced six mutations into the conserved coreceptor binding site of the R5 HIV-1 strain YU-2 and measured the effect of these changes on CD4 and coreceptor binding, membrane fusion levels and rates, virus infection, and sensitivity to the fusion inhibitors enfuvirtide (T-20) and T-1249, the CCR5 inhibitor TAK-779, and an antibody to CD4. The mutations had little effect on CD4 binding but reduced CCR5 binding to various extents. In general, reductions in coreceptor binding efficiency resulted in slower fusion kinetics and increased sensitivity to TAK-779 and enfuvirtide. In addition, low CCR5 binding usually reduced overall fusion and infection levels. However, one mutation adjacent to the bridging sheet beta21 strand, P438A, had little effect on fusion activity, fusion rate, infectivity, or sensitivity to enfuvirtide or T-1249 despite causing a marked reduction in CCR5 binding and a significant increase in TAK-779 sensitivity. Thus, our findings indicate that changes in the coreceptor binding site of Env can modulate its fusion activity, infectivity, and entry inhibitor sensitivity by multiple mechanisms and suggest that reductions in coreceptor binding do not always result in prolonged fusion kinetics and increased sensitivity to enfuvirtide.
Racemic marinopyrrole B by total synthesis (2012)

The first synthesis of marinopyrrole B, which is highly active against methicillin-resistant Staphylococcus aureus, is described. The route involved constructing a pyrrole ring on the nitrogen of a 3-bromo-4,5-dichloropyrrole by N-alkylation with a special Michael acceptor having an allylic leaving group; the second pyrrole ring was then formed by a Paal-Knorr reaction.
TAK1 Regulates Reactive Oxygen Species and Cell Death in Keratinocytes, Which Is Essential for Skin Integrity (2008)

Mice with a keratinocyte-specific deletion of Tak1 exhibit severe skin inflammation due to hypersensitivity to tumor necrosis factor (TNF) killing. Here we have examined the mechanisms underlying this hypersensitivity. We found that TAK1 deficiency up-regulates reactive oxygen species (ROS) resulting in cell death upon TNF or oxidative stress challenge. Because blockade of NF-kappaB did not increase ROS or did not sensitize cells to oxidative stress in keratinocytes TAK1 regulates ROS mainly through the mechanisms other than those mediated by NF-kappaB. We found that c-Jun was decreased in TAK1-deficient keratinocytes and that ectopic expression of c-Jun could partially inhibit TNF-induced increase of ROS and cell death. Finally, we show that, in an in vivo setting, the antioxidant treatment could reduce an inflammatory condition in keratinocyte-specific Tak1 deletion mice. Thus, TAK1 regulates ROS partially through c-Jun, which is important for preventing ROS-induced skin inflammation.
An Altered Peptide Ligand Specifically Inhibits Th2 Cytokine Synthesis by Abrogating TCR Signaling (1999)

Altered peptide ligands (APL) can modify T cell effector function by their diversity in binding to the TCR or MHC class II-presenting molecules. The capacity to inhibit Th2 cytokine production by allergen-specific T cells would contribute to combating allergic inflammation. The presence of APL generated by Ala-substitutions in a synthetic dodeca-peptide spanning an immunodominant epitope of bee venom phospholipase A2 (PLA) was investigated in human T cells. Four of five substituted peptides reduced proliferation, IL-4, and IFN-gamma production by cloned PLA-specific Th0 cells proportionately. However, one APL, PLA-F82A, inhibited IL-4 but had no effect on IFN-gamma production. This uncoupling of IL-4 from IFN-gamma production was also observed on immunogenic restimulation of the cloned T cells pre-exposed to the APL/APCs. It appeared to result from lower affinity of binding to MHC class II by the APL compared with the native peptide. The APL also inhibited IL-4 production by polyclonal T cells. In consequence of the change in cytokine secretion, the production of IgG4 in vitro increased by PLA-F82A stimulation, compared with the native peptide. Exposure of the cloned T cells to either the APL or the native peptide, in the absence of professional APC, induced anergy such that proliferation and production of IL-4, IL-5, and IL-13 was abrogated on immunogenic rechallenge. Defective T cell activation appeared to result from alterations in transmembrane signaling through the TCR, specifically to lack of tyrosine phosphorylation of the tyrosine kinase, ZAP-70.
The extracellular domain of the Epstein-Barr virus BZLF2 protein binds the HLA-DR beta chain and inhibits antigen presentation (1996)

The Epstein-Barr virus BZLF2 gene encodes a glycoprotein that associates with gH and gL and facilitates the infection of B lymphocytes. In order to determine whether the BZLF2 protein recognizes a B-cell-specific surface antigen, a soluble protein containing the extracellular portion of the BZLF2 protein linked to the Fc portion of human immunoglobulin G1 (BZLF2.Fc) was expressed from mammalian cells. BZLF2.Fc was used in an expression cloning system and found to bind to a beta-chain allele of the HLA-DR locus of the class II major histocompatibility complex (MHC). Analysis of amino- and carboxy-terminal deletion mutants of the BZLF2.Fc protein indicated that the first 90 amino acids of BZLF2.Fc are not required for HLA-DR beta-chain recognition. Site-directed mutagenesis of an HLA-DR beta-chain cDNA and subsequent immunoprecipitation of expressed mutant beta-chain proteins using BZLF2.Fc indicated that the beta1 domain, which participates in the formation of peptide binding pockets, is required for BZLF2.Fc recognition. The addition of BZLF2.Fc to sensitized peripheral blood mononuclear cells in vitro abolished their proliferative response to antigen and inhibited cytokine-dependent cytotoxic T-cell generation in mixed lymphocyte cultures. Flow-cytometric analysis of Akata cells induced to express late Epstein-Barr virus antigens indicated that expression of BZLF2 did not result in reduced surface expression levels of MHC class II. The ability of BZLF2.Fc to bind to the HLA-DR beta chain suggests that the BZLF2 protein may interact with MHC class II on the surfaces of B cells.
Microscopy ambient ionization top-down mass spectrometry reveals developmental patterning (2013)

There is immense cellular and molecular heterogeneity in biological systems. Here, we demonstrate the utility of integrating an inverted light microscope with an ambient ionization source, nanospray electrospray desorption ionization, attached to a high-resolution mass spectrometer to characterize the molecular composition of mouse spinal cords. We detected a broad range of molecules, including peptides and proteins, as well as metabolites such as lipids, sugars, and other small molecules, including S-adenosyl methionine and glutathione, through top-down MS. Top-down analysis revealed variation in the expression of Hb, including the transition from fetal to adult Hb and heterogeneity in Hb subunits consistent with the genetic diversity of the mouse models. Similarly, temporal changes to actin-sequestering proteins β-thymosins during development were observed. These results demonstrate that interfacing microscopy with ambient ionization provides the means to perform targeted in situ ambient top-down mass spectral analysis to study the pattern of proteins, lipids, and sugars in biologically heterogeneous samples.
Apnea Detection based on Respiratory Signal Classification (2013)

Obstructive sleep apnea (OSA) is the most common form of different types of sleep-related breathing disorders. It is characterized by repetitive cessations of respiratory flow during sleep, which occurs due to a collapse of the upper respiratory airway. OSA is majorly undiagnosed due to the inconvenient Polysomnography (PSG) testing procedure at sleep labs. This paper introduces an automated approach towards identifying the presence of sleep apnea based on the acoustic signal of respiration. The characterization of breathing sound was carried by Voice Activity Detection (VAD) algorithm, which is used to measure the energy of the acoustic respiratory signal during breath and breath hold. The performance of our classification algorithm is tested on real respiratory signals and the experimental results show that the VAD is useful as a predictive tool for the segmentation of breath into sound and silence segments. Moreover, the system we developed can be used as a basis for future development of a tool for OSA screening.
Bone Loss in the Distal Anterior Femur After Total Knee Arthroplasty (1990)

Bone loss in the distal anterior femur in asymptomatic total knee arthroplasty (TKA) patients has been noted roentgenographically and during revision surgery. A retrospective roentgenographic review of 147 TKA cases was carried out to document bone loss. The influence that the mode of fixation (porous coated and cemented) and the implant design have on bone loss was examined. The time of onset and the progression of bone loss were studied. Bone loss occurred in the distal anterior femur in the majority of cases reviewed (68%). The prevalence of bone loss was independent of the mode of fixation and the implant design. By qualitative observation, roentgenographically detectable bone loss occurred within the first postoperative year and did not progress further. Previously three-dimensional finite element analysis demonstrated that the replacement of the bearing surface of the femur with a stiff metallic implant reduces the stress in the distal anterior femur by at least one order of magnitude. It is therefore speculated that the observed bone loss results from stress shielding. The apparent lack of progression may reflect the development of a new remodeling equilibrium under the altered stress conditions. The bone loss in the distal anterior femur described has not been implicated as a source of failure. However, since the bone strength in the femoral region is compromised as it becomes osteopenic, bone failure may occur with longer periods of cyclic loading. Furthermore, as a result of bone loss, revision arthroplasty may be more difficult.
Bioorthogonal Chemistry: Fishing for Selectivity in a Sea of Functionality (2009)

The study of biomolecules in their native environments is a challenging task because of the vast complexity of cellular systems. Technologies developed in the last few years for the selective modification of biological species in living systems have yielded new insights into cellular processes. Key to these new techniques are bioorthogonal chemical reactions, whose components must react rapidly and selectively with each other under physiological conditions in the presence of the plethora of functionality necessary to sustain life. Herein we describe the bioorthogonal chemical reactions developed to date and how they can be used to study biomolecules.
Frequency and phenotype of peripheral blood Th17 cells in ankylosing spondylitis and rheumatoid arthritis (2009)

The frequencies of IL-17-positive and IL-22-positive CD4+ T cells were increased in PBMCs from patients with AS and patients with RA, resulting in secretion of higher quantities of IL-17 by PBMCs following stimulation. These data support the hypothesis that Th17 cells, particularly when present in excess of IL-10-producing cells, are involved in the pathogenesis of inflammatory arthritis.
Phosphorylation of Bad at Thr-201 by JNK1 Promotes Glycolysis through Activation of Phosphofructokinase-1 (2008)

The mitogen-activated protein kinase JNK1 suppresses interleukin-3 withdrawal-induced cell death through phosphorylation of the BH3-only pro-apoptotic Bcl-2 family protein Bad at Thr-201. It is unknown whether JNK1 regulates glycolysis, an important metabolic process that is involved in cell survival, and if so, whether the regulation depends on Thr-201 phosphorylation of Bad. Here we report that phosphorylation of Bad by JNK1 is required for glycolysis through activation of phosphofructokinase-1 (PFK-1), one of the key enzymes that catalyze glycolysis. Genetic disruption of Jnk1 alleles or silencing of Jnk1 by small interfering RNA abrogates glycolysis induced by growth/survival factors such as serum or interleukin-3. Proteomic analysis identifies PFK-1 as a novel Bad-associated protein. Although the interaction between PFK-1 and Bad is independent of JNK1, Thr-201 phosphorylation of Bad by JNK1 is required for PFK-1 activation. Thus, our results provide a novel molecular mechanism by which JNK1 promotes glycolysis for cell survival.
elastix: A Toolbox for Intensity-Based Medical Image Registration (2009)

Medical image registration is an important task in medical image processing. It refers to the process of aligning data sets, possibly from different modalities (e.g., magnetic resonance and computed tomography), different time points (e.g., follow-up scans), and/or different subjects (in case of population studies). A large number of methods for image registration are described in the literature. Unfortunately, there is not one method that works for all applications. We have therefore developed elastix, a publicly available computer program for intensity-based medical image registration. The software consists of a collection of algorithms that are commonly used to solve medical image registration problems. The modular design of elastix allows the user to quickly configure, test, and compare different registration methods for a specific application. The command-line interface enables automated processing of large numbers of data sets, by means of scripting. The usage of elastix for comparing different registration methods is illustrated with three example experiments, in which individual components of the registration method are varied.
High-aspect ratio nanochannel formation by single femtosecond laser pulses (2010)

Single femtosecond pulsed laser damage can be confined radially to regions smaller than the focus spot size due to the highly nonlinear mechanisms for energy absorption and ablation in transparent dielectrics. Along the propagation axis, however, we show that channels can be machined much deeper than the Rayleigh range of the laser focus. Using focused ion beam cross sections and acetate imprints, we analyze these channels and show that spherical aberration is not the primary source for this elongated damage, which is likely caused by microscale filamentation.
A Bridging Framework for Universal Interoperability in Pervasive Systems (2006)

We explore the design patterns and architectural tradeoffs for achieving interoperability across communication middleware platforms, and describe uMiddle, a bridging framework for universal interoperability that enables seamless device interaction over diverse platforms. The proliferation of middleware platforms that cater to specific devices has created isolated islands of devices with no uniform protocol for interoperability across these islands. This void makes it difficult to rapidly prototype pervasive computing applications spanning a wide variety of devices. We discuss the design space of architectural solutions that can address this void, and detail the trade-offs that must be faced when trying to achieve cross-platform interoperability. uMiddle is a framework for achieving such interoperability, and serves as a powerful platform for creating applications that are independent of specific underlying communication platforms.
CD4+ T Cell-derived Novel Peptide Thp5 Induces Interleukin-4 Production in CD4+ T Cells to Direct T Helper 2 Cell Differentiation (2011)

The differentiation of naïve CD4(+) T cells into T helper 2 (Th2) cells requires production of the cytokine IL-4 in the local microenvironment. It is evident that naïve/quiescently activated CD4(+) T cells produce the IL-4 that drives Th2 cell differentiation. Because early production of IL-4 in naïve T cells leads to preferential Th2 cell differentiation, this process needs to be tightly regulated so as to avoid catastrophic and misdirected Th2 cell differentiation. Here, we show that Thp5, a novel peptide with structural similarity to vasoactive intestinal peptide, regulates production of early IL-4 in newly activated CD4(+) T cells. Induction of IL-4 in CD4(+) T cells by Thp5 is independent of the transcription factor STAT6 but dependent on ERK1/2 signaling. Furthermore, cytokines (IL-12 and TGF-β) that promote the differentiation of Th1 or Th17 cells inhibit Thp5 induction, thus suppressing Th2 cell differentiation. We further showed that Thp5 enhances Th2 responses and exacerbates allergic airway inflammation in mice. Taken together, our findings reveal that early activated CD4(+) T cells produce Thp5, which plays a critical role as a molecular switch in the differentiation of Th cells, biasing the response toward the Th2 cell phenotype.