gebhart/patrepeval huggingface dataset:
Torturing databases for fun and profit (2014)

Programmers use databases when they want a high level of reliability. Specifically, they want the sophisticated ACID (atomicity, consistency, isolation, and durability) protection modern databases provide. However, the ACID properties are far from trivial to provide, particularly when high performance must be achieved. This leads to complex and error-prone code--even at a low defect rate of one bug per thousand lines, the millions of lines of code in a commercial OLTP database can harbor thousands of bugs.Here we propose a method to expose and diagnose violations of the ACID properties. We focus on an ostensibly easy case: power faults. Our framework includes workloads to exercise the ACID guarantees, a record/replay subsystem to allow the controlled injection of simulated power faults, a ranking algorithm to prioritize where to fault based on our experience, and a multi-layer tracer to diagnose root causes. Using our framework, we study 8 widely-used databases, ranging from open-source key-value stores to high-end commercial OLTP servers. Surprisingly, all 8 databases exhibit erroneous behavior. For the open-source databases, we are able to diagnose the root causes using our tracer, and for the proprietary commercial databases we can reproducibly induce data loss.
Purification of germline stem cells from adult mammalian ovaries: a step closer towards control of the female biological clock? (2009)

For decades it was believed that a non-renewable pool of oocyte-containing follicles is established in female mammals at birth. This cornerstone of reproductive biology was challenged 5 years ago by a study reporting on the presence of mitotically-active germ cells in juvenile and adult mouse ovaries. Additional findings presented in this study and others that followed further suggested that mammals retain the capacity to generate oocytes during adulthood; however, isolation of oocyte-producing germline stem cells (GSC) as unequivocal proof of their existence remained elusive. This piece of information now appears to have been provided by Ji Wu and colleagues. In addition to showing that proliferative germ cells resembling male spermatogonial stem cells can be purified from neonatal or adult mouse ovaries and maintained in vitro for months, transplantation studies demonstrated that these cells generate oocytes in ovaries of chemotherapy-sterilized recipients that fertilize and produce viable offspring. Although these findings do not establish that oogenesis occurs in adult females under physiological conditions, they strongly support the existence of GSC in adult mouse ovaries. If equivalent cells can be found in human ovaries, stem cell-based rejuvenation of the oocyte reserve in ovaries on the verge of failure may one day be realized.
Optimizing T-cell receptor gene therapy for hematologic malignancies (2016)

Recent advances in genetic engineering have enabled the delivery of clinical trials using patient T cells redirected to recognize tumor-associated antigens. The most dramatic results have been seen with T cells engineered to express a chimeric antigen receptor (CAR) specific for CD19, a differentiation antigen expressed in B cells and B lineage malignancies. We propose that antigen expression in nonmalignant cells may contribute to the efficacy of T-cell therapy by maintaining effector function and promoting memory. Although CAR recognition is limited to cell surface structures, T-cell receptors (TCRs) can recognize intracellular proteins. This not only expands the range of tumor-associated self-antigens that are amenable for T-cell therapy, but also allows TCR targeting of the cancer mutagenome. We will highlight biological bottlenecks that potentially limit mutation-specific T-cell therapy and may require high-avidity TCRs that are capable of activating effector function when the concentrations of mutant peptides are low. Unexpectedly, modified TCRs with artificially high affinities function poorly in response to low concentration of cognate peptide but pose an increased safety risk as they may respond optimally to cross-reactive peptides. Recent gene-editing tools, such as transcription activator-like effector nucleases and clustered regularly interspaced short palindromic repeats, provide a platform to delete endogenous TCR and HLA genes, which removes alloreactivity and decreases immunogenicity of third-party T cells. This represents an important step toward generic off-the-shelf T-cell products that may be used in the future for the treatment of large numbers of patients.
Vivo-Morpholinos: A Non-Peptide Transporter Delivers Morpholinos into a Wide Array of Mouse Tissues (2008)

We have developed a new transporter structure that provides effective delivery of Morpholino antisense oligomers into a wide variety of tissues in living mice. This transporter comprises a dendritic structure assembled around a triazine core which serves to position eight guanidinium head groups in a conformation effective to penetrate cell membranes. This transporter structure is conjugated to a Morpholino oligomer to form a delivery-enabled product referred to as a Vivo-Morpholino. Vivo-Morpholinos are shown to effectively enter and function within cultured cells in the presence of 100% serum using a rigorous positive test system based on correction of a defined splicing error in a pre-messenger RNA. In addition, Vivo-Morpholinos are demonstrated to enter into a wide variety of tissues in a similar positive test system in transgenic mice, as evidenced by correction of the targeted splicing error in all tissues assessed, including near-complete splice correction in the small intestine, colon, stomach, liver kidney, and a number of muscles. Finally, Vivo-Morpholinos, which target the exon-skipping of exon 23 harboring a premature termination codon in the mdx mouse model, effectively restore the reading frame of dystrophin and restore expression of a functional dystrophin protein.
Alginate Lyase Promotes Diffusion of Aminoglycosides through the Extracellular Polysaccharide of MucoidPseudomonas aeruginosa (1998)

We demonstrated that a 2% suspension of Pseudomonas aeruginosa alginate completely blocked the diffusion of gentamicin and tobramycin, but not that of carbenicillin, illustrating how alginate production can help protect P. aeruginosa growing within alginate microcolonies in patients with cystic fibrosis (CF) from the effects of aminoglycosides. This aminoglycoside diffusion barrier was degraded with a semipurified preparation of P. aeruginosa alginate lyase, suggesting that this enzyme deserves consideration as an adjunctive agent for CF patients colonized by mucoid strains of P. aeruginosa.
Genetic and biochemical characterizations of Zika virus NS2A protein (2019)

Zika virus (ZIKV) can cause devastating congenital Zika syndromes in pregnant women and Guillain-Barre syndrome in adults. Understanding the molecular mechanism of ZIKV replication is essential for antiviral and vaccine development. Here we report the structural and functional characterization of ZIKV NS2A protein. Biochemical structural probing suggests that ZIKV NS2A has a single segment that traverses the ER membrane and six segments that peripherally associate with the ER membrane. Functional analysis has defined distinct NS2A residues essential for viral RNA synthesis or virion assembly. Only the virion assembly-defective mutants, but not the RNA synthesis-defective mutants, could be rescued through trans complementation with a wide-type NS2A protein. These results suggest that the NS2A molecules in virion assembly complex could be recruited in trans, whereas the NS2A molecules in viral replication complex must be recruited in cis. Together with previous results, we propose a flavivirus assembly model where NS2A plays a central role in modulating viral structural and nonstructural proteins as well as genomic RNA during virion assembly.
Expression of interleukin‐21 receptor in epidermis from patients with systemic sclerosis (2005)

The up-regulation of IL-21R in keratinocytes indicates that, similar to fibroblasts and endothelial cells, the expression pattern is altered in SSc. Moreover, the expression of IL-21R appears to be independent of key cytokines that are operant in SSc.
iTRAQ-Facilitated Proteomic Analysis of Human Prostate Cancer Cells Identifies Proteins Associated with Progression (2008)

The unpredictable behavior of prostate cancer presents a major clinical challenge during patient management. In order to gain an insight into the molecular mechanisms associated with prostate cancer progression, we employed the shot-gun proteomic approach of isobaric tags for relative and absolute quantitation (iTRAQ), followed by 2D-LC-MS/MS, using the poorly metastatic LNCaP cell line and its highly metastatic variant LNCaP-LN3 cell line as a model. A total number of 280 unique proteins were identified (> or =95% confidence), and relative expression data was obtained for 176 of these. Ten proteins were found to be significantly up-regulated (> or =1.50 fold), while 4 proteins were significantly down-regulated (> or = -1.50 fold), in LNCaP-LN3 cells. Differential expression of brain creatine kinase (CKBB), soluble catechol-O-methyltransferase (S-COMT), tumor rejection antigen (gp96), and glucose regulated protein, 78 kDa (grp78), was confirmed by Western blotting or independent 2D-PAGE analysis. Additionally, iTRAQ analysis identified absence of the lactate dehydrogenase-B (LDH-B) subunit in LNCaP-LN3 cells, confirming our published data. The clinical relevance of gp96 was assessed by immunohistochemistry using prostate tissues from benign ( n = 95), malignant ( n = 66), and metastatic cases ( n = 3). Benign epithelium showed absent/weak gp96 expression in the basal cells, in contrast to the moderate/strong expression seen in malignant epithelium. Furthermore, there was a statistically significant difference in the intensity of gp96 expression between benign and malignant cases ( p < 0.0005, Mann-Whitney U). Our study is the first to report the application of iTRAQ technology and its potential for the global proteomic profiling of prostate cancer cells, including the identification of absent protein expression.
CD39 Expression Defines Cell Exhaustion in Tumor-Infiltrating CD8+ T Cells (2017)

The ability of CD8<sup>+</sup> T lymphocytes to eliminate tumors is limited by their ability to engender an immunosuppressive microenvironment. Here we describe a subset of tumor-infiltrating CD8<sup>+</sup> T cells marked by high expression of the immunosuppressive ATP ecto-nucleotidase CD39. The frequency of CD39<sup>high</sup>CD8<sup>+</sup> T cells increased with tumor growth but was absent in lymphoid organs. Tumor-infiltrating CD8<sup>+</sup> T cells with high CD39 expression exhibited features of exhaustion, such as reduced production of TNF and IL2 and expression of coinhibitory receptors. Exhausted CD39<sup>+</sup>CD8<sup>+</sup> T cells from mice hydrolyzed extracellular ATP, confirming that CD39 is enzymatically active. Furthermore, exhausted CD39<sup>+</sup>CD8<sup>+</sup> T cells inhibited IFNγ production by responder CD8<sup>+</sup> T cells. In specimens from breast cancer and melanoma patients, CD39<sup>+</sup>CD8<sup>+</sup> T cells were present within tumors and invaded or metastatic lymph nodes, but were barely detectable within noninvaded lymph nodes and absent in peripheral blood. These cells exhibited an exhausted phenotype with impaired production of IFNγ, TNF, IL2, and high expression of coinhibitory receptors. Although T-cell receptor engagement was sufficient to induce CD39 on human CD8<sup>+</sup> T cells, exposure to IL6 and IL27 promoted CD39 expression on stimulated CD8<sup>+</sup> T cells from human or murine sources. Our findings show how the tumor microenvironment drives the acquisition of CD39 as an immune regulatory molecule on CD8<sup>+</sup> T cells, with implications for defining a biomarker of T-cell dysfunction and a target for immunotherapeutic intervention.<b>Significance:</b> The tumor microenvironment elicits a subset of functionally exhausted CD8<sup>+</sup> T cells by creating conditions that induce cell surface expression of CD39, an immunosuppressive molecule that can be therapeutically targeted to restore effector T-cell function. <i>Cancer Res; 78(1); 115-28. ©2017 AACR</i>.
Air Atmosphere Annealing Effects on LSO:Ce Crystal (2010)

Cerium-doped lutetium oxyorthosilicate Lu <sub xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">2</sub> SiO <sub xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">5</sub> :Ce crystal is a well-known scintillator with an excellent figure-of-merit. In this paper, air annealing was used to further improve its scintillation properties. The samples cut from Czochralski grown Lu <sub xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">2</sub> SiO <sub xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">5</sub> :Ce crystals were annealed in air atmosphere at 1400°C for 10 h. Based on the analysis of the difference in the crystal's spectra (such as absorption, emission, and thermoluminescence) obtained before and after annealing, we investigate the nature of the observed effects. To investigate the annealing effects on the valence state of cerium ion, synchrotron radiation was used in this work as an energy source to measure the X-ray absorption near edge spectroscopy of cerium ions. It is supposed that annealing in air atmosphere helps to reduce the content of deep traps, which possibly include oxygen vacancy, lower the intensity of afterglow, shorten the decay time of afterglow, and increase the luminescence intensity of Ce2 (6-oxygen-coordinated). However, this may also cause cerium ion to be oxidized to +4 charge state, which may introduce an additional nonradiative trap center, thereby weakening luminescence.
The use of irradiated‐crosslinked human collagen membrane in guided tissue regeneration (1992)

Irradiated glutaraldehyde-crosslinked human collagen membrane was evaluated for its effects on new attachment formation in clinical trials, using the principle of guided tissue regeneration (GTR). 19 adult periodontitis patients with 52 matched bilateral periodontal defects received scaling and polishing with oral hygiene instruction. The bilateral periodontal defects were treated by reflecting a flap with collagen membrane (test) or flap reflection alone (control). Plaque (P1I) and gingival index (GI) scorings, probing pocket depth (PPD) and probing attachment level (PAL) along with classification of furcation involvement (FI) and bony defects were made at pre- and post surgery (6 weeks, 3 and 6 months). Improvement of P1I and GI scores was seen in both test and control sites following the surgical therapy. Reductions in PPD and PAL were significantly (p less than 0.001) more pronounced at 6 months in the test sites compared to the controls. The 2 Class I furcations in the graft-treated teeth showed complete resolution, while the corresponding furcations in the control teeth showed incomplete closure. The use of human collagen membrane based on the GTR technique for treatment of human periodontal defects provided greater gain of clinical attachment than when flap surgery alone was undertaken.
Lysis of ovarian cancer cells by human lymphocytes redirected with a chimeric gene composed of an antibody variable region and the Fc receptor gamma chain. (1993)

To expand the spectrum of recognition of effector lymphocytes and to redirect them towards predefined targets, we have altered the specificity of human tumor-infiltrating lymphocytes (TIL) through stable modification with chimeric receptor genes consisting of single-chain antibody variable regions linked to the gamma subunit common to the immunoglobulin (Ig)G and IgE Fc receptors. Using either hapten or ovarian carcinoma-specific monoclonal antibodies, we constructed chimeric receptor genes and retrovirally introduced them into CD8+ TIL. Redirected TIL specifically lysed trinitrophenyl-labeled Daudi or a human ovarian carcinoma cell line (IGROV-1), and secreted granulocyte/macrophage colony-stimulating factor upon stimulation with the appropriate antigen. This strategy may allow new approaches towards the adoptive immunotherapy of cancer in humans.
In situ estimation of acoustic impedance on the surfaces of realistic interiors: An inverse approach (2007)

In situ measurement of acoustic impedance is traditionally performed using pairs of microphones located close to the test surface. However, this method becomes troublesome if inaccessible complex-shaped surfaces, such as those in a real room, are considered. To overcome this problem, a method to estimate the normal acoustic impedance on the interior surfaces of a room is proposed. As input data, the algorithm takes: (1) The 3-D shape of the room; (2) the strength of the sound source; and (3) a set of sound pressures measured at random locations in the interior sound field. The estimation of the acoustic impedance at each surface is achieved via the solution of an inverse problem, which arises from the boundary-element method applied to the discretized interior boundaries of the room. Unfortunately, the solutions of this kind of problems are known to be unstable and sensitive to noise, due to a rank-deficient linear system. Dealing with such a system is avoided in the proposed method by formulating an iterative optimization approach, which is shown to be more robust to noise. Previous work has reported examples with numerical simulations. This paper goes further and presents results obtained with real data from experiments.
Delayed Cytoprotection after Enhancement ofSod2(MnSOD) Gene Expression in SA-NH Mouse Sarcoma Cells Exposed to WR-1065, the Active Metabolite of Amifostine (2002)

SA-NH mouse sarcoma cells were grown to confluence and then exposed to either 40 microM or 4 mM of WR-1065, i.e. the active thiol form of amifostine, for 30 min and then washed. Total RNA and protein were isolated at various times up to 24 h after exposure. Both concentrations of WR-1065 were equally effective in affecting Sod2 (also known as MnSOD) gene expression and protein levels. Northern blot analysis using a mouse cDNA probe revealed three Sod2 transcripts of 1, 4 and 6 kb. Expression of both the 4- and 6-kb transcripts increased by 20 and 60%, respectively, and remained elevated over a period of 4 to 20 h. Sod2 protein levels, as determined by Western blot analysis, increased 15-fold over background control levels over the same interval. Sod2 protein was evaluated using activity gels and was found to be active. SA-NH cells were irradiated with X rays either in the presence of 40 microM or 4 mM WR-1065 or 24 h later after its removal, when Sod2 protein levels were most elevated. No protection was observed for cells irradiated in the presence of 40 microM WR-1065. In contrast, survival after a dose of 2 Gy was elevated 1.27-, 1.14- and 1.20-fold in SA-NH cells irradiated in the presence of 4 mM WR-1065 or 24 h after exposure of the cells to 40 microM and 4 mM WR-1065, respectively. The increased survival levels observed 24 h after exposure to WR-1065 represents a delayed radioprotective effect of WR-1065 and corresponds to the time at which Sod2 protein levels are most elevated. These data demonstrate a novel mechanism for radioprotection by WR-1065 and suggest a new potential concern regarding the issue of tumor protection.
Endothelial cell behavior after denudation injury is modulated by transforming growth factor-beta1 and fibronectin. (1989)

Endothelial denudation injury after endarterectomy, autologous and synthetic grafting and balloon angioplasty leads to exposure of thrombogenic vessel wall material and may elicit an atherogenic response in the media of the affected vessels in which complete reendothelialization may not occur. While the role(s) of extracellular matrix composition and organization in this process are only incompletely understood, it is widely accepted that endothelial cells respond to matrix components in specific, complex fashions. In this report we demonstrate that large vessel endothelial cell migration is affected by the surrounding matrix and the soluble factor, transforming growth factor-beta1, which may mediate its effects, in part, by modulating endothelial cell matrix synthesis. Specifically, large vessel endothelial cell migration is decreased on a fibronectin substratum and in the presence of transforming growth factor-beta1, which increases fibronectin mRNA and protein accumulation in culture. Inhibition of sheet migration is also elicited by the addition of soluble fibronectin to the cultures. These in vitro findings are consistent with our in vivo findings of increased staining of fibronectin luminally and in the intima in the chronically deendothelialized region of a balloon catheter denuded carotid artery. Thus, reendothelialization after iatrogenic and natural injury appears to be a complex process which can be modulated by the underlying matrix and soluble factors, which may themselves modulate the matrix synthesis of local vascular cells.
The B-cell epitope of the monoclonal anti-factor VIII antibody ESH8 characterized by peptide array analysis (2008)

* Current address: PT-DLR – Umwelt, Kultur, Nachhaltigkeit, Heinrich-Konen-Str. 1, 53227 Bonn, Germany
Sample Number and Denaturation Time Are Crucial for the Accuracy of Capillary-Based LightCyclers (2007)

Carousel position-dependent effects on capillary-based LightCycler instruments have been described by Wilhelm et al. (1) and Zuna et al.(2). Both studies found such positional effects to depend on small temperature differences in the thermal chamber of the LightCycler that lead to variable DNA melting efficiencies when amplifying genomic DNA targets with high melting temperatures. These temperature inhomogeneities lead to carousel position-dependent differences in primer binding efficiency and thus to different cycles over threshold (Ct). Both authors postulated that such positional effects would disappear with the instrument’s software version 3.5 that allows constant rotation of the carousel, leveling off possible temperature inhomogeneities in the thermal chamber.

However, even when the use of software version 3.5 provided constant carousel rotation, we observed positional effects when amplifying a region of the SNRPN gene in an assay containing 26 reactions (performed on a LightCycler 1.2). Similar effects were observed with the ATP7B gene and the LightCycler Control Kit (Roche), and the effect was even stronger on a LightCycler 1.1 instrument. Position effects were also observed when only 10 reactions were performed. Of special concern is that the …