Miracle-dz/UniFAR-FTUs huggingface dataset:
DNA polymerase ɛ is required for coordinated and efficient chromosomal DNA replication in Xenopus egg extracts

DNA polymerase ɛ (Polɛ) is thought to be involved in DNA replication, repair, and cell-cycle checkpoint control in eukaryotic cells. Although the requirement of other replicative DNA polymerases, DNA polymerases α and δ (Polα and δ), for chromosomal DNA replication has been well documented by genetic and biochemical studies, the precise role, if any, of Polɛ in chromosomal DNA replication is still obscure. Here we show, with the use of a cell-free replication system with Xenopus egg extracts, that Xenopus Polɛ is indeed required for chromosomal DNA replication. In Polɛ-depleted extracts, the elongation step of chromosomal DNA replication is markedly impaired, resulting in significant reduction of the overall DNA synthesis as well as accumulation of small replication intermediates. Moreover, despite the decreased DNA synthesis, excess amounts of Polα are loaded onto the chromatin template in Polɛ-depleted extracts, indicative of the failure of proper assembly of DNA synthesis machinery at the fork. These findings strongly suggest that Polɛ, along with Polα and Polδ, is necessary for coordinated chromosomal DNA replication in eukaryotic cells.
Machine Learning Algorithms for b-Jet Tagging at the ATLAS Experiment

The separation of b-quark initiated jets from those coming from lighter quark flavors (b-tagging) is a fundamental tool for the ATLAS physics program at the CERN Large Hadron Collider. The most powerful b-tagging algorithms combine information from low-level taggers, exploiting reconstructed track and vertex information, into machine learning classifiers. The potential of modern deep learning techniques is explored using simulated events, and compared to that achievable from more traditional classifiers such as boosted decision trees.
Trisomy 8 in Philadelphia‐negative cells during imatinib therapy

Targeted therapy with imatinib selectively suppresses Philadelphia‐positive cells in chronic myeloid leukemia cells, with reappearance of apparently normal hemopoiesis in a considerable number of patients. Recently, clonal abnormalities have been observed in Philadelphia‐negative cells during imatinib therapy, the biologic and prognostic significance of which is actually unknown. A case of trisomy 8 occurring in Philadelphia‐negative cells, which was treated by bone marrow transplantation, is reported. Chromosomal abnormalities in Philadelphia‐negative cells do not seem to herald disease transformation, but the long‐term prognosis may be influenced by an increased incidence of myelodysplasia in younger patients. Am. J. Hematol. 77:88–89, 2004. © 2004 Wiley‐Liss, Inc.
Identification of Metal Ligands in theClostridium histolyticum ColH Collagenase

ABSTRACT A Clostridium histolyticum 116-kDa collagenase has an H415EXXH motif but not the third zinc ligand, as found in already characterized zinc metalloproteinases. To identify its catalytic site, we mutated the codons corresponding to the three conserved residues in the motif to other amino acid residues. The mutation affecting His415 or His419 abolished catalytic activity and zinc binding, while that affecting Glu416 did the former but not the latter. These results suggest that the motif forms the catalytic site. We also mutated the codons corresponding to other amino acid residues that are likely zinc ligands. The mutation affecting Glu447 decreased markedly both the enzymatic activity and the zinc content, while that affecting Glu446 or Glu451 had smaller effects on activity and zinc binding. These mutations caused a decrease inkcat but no significant change inKm. These results are consistent with the hypothesis that Glu447 is the third zinc ligand. The spacing of the three zinc ligands is the same in all known clostridial collagenases but not in other known gluzincins, indicating that they form a new gluzincin subfamily. The effects of mutations affecting Glu446 and Glu451 suggest that the two residues are also involved in catalysis, possibly through an interaction with the two zinc-binding histidine residues.
Wide-Area Traveling Wave Fault Location System Based on IEC61850

Existing traveling wave fault location systems employ the double-end method and do not make use of data from neighboring substations. If one of the data acquisition equipments at either end of a line fails to capture the fault transient, no fault location result can be obtained. A wide-area traveling wave fault location (WA-TWFL) system, which makes use of traveling wave data from various substations across the monitored network, is introduced. The WA-TWFL algorithm first identifies the area of the monitored network in which the source of the disturbance originated by analyzing the traveling wave propagation times using the extended double end method. Then, the faulty line, and the distance to fault, are determined using selected records from the identified area of the disturbance. This approach provides fault location reliability than the traditional TWFL algorithm. Traveling wave data models based on IEC61850, which supports open communication and interoperability between data acquisition equipment and the master station of the WA-TWFL, are also presented in this paper. The feasibility of the proposed algorithm is proved using traveling wave data from an actual fault on a power grid in China.
Safety and Efficacy of Durvalumab (MEDI4736), an Anti-Programmed Cell Death Ligand-1 Immune Checkpoint Inhibitor, in Patients With Advanced Urothelial Bladder Cancer.

PURPOSE To investigate the safety and efficacy of durvalumab, a human monoclonal antibody that binds programmed cell death ligand-1 (PD-L1), and the role of PD-L1 expression on clinical response in patients with advanced urothelial bladder cancer (UBC). METHODS A phase 1/2 multicenter, open-label study is being conducted in patients with inoperable or metastatic solid tumors. We report here the results from the UBC expansion cohort. Durvalumab (MEDI4736, 10 mg/kg every 2 weeks) was administered intravenously for up to 12 months. The primary end point was safety, and objective response rate (ORR, confirmed) was a key secondary end point. An exploratory analysis of pretreatment tumor biopsies led to defining PD-L1-positive as ≥ 25% of tumor cells or tumor-infiltrating immune cells expressing membrane PD-L1. RESULTS A total of 61 patients (40 PD-L1-positive, 21 PD-L1-negative), 93.4% of whom received one or more prior therapies for advanced disease, were treated (median duration of follow-up, 4.3 months). The most common treatment-related adverse events (AEs) of any grade were fatigue (13.1%), diarrhea (9.8%), and decreased appetite (8.2%). Grade 3 treatment-related AEs occurred in three patients (4.9%); there were no treatment-related grade 4 or 5 AEs. One treatment-related AE (acute kidney injury) resulted in treatment discontinuation. The ORR was 31.0% (95% CI, 17.6 to 47.1) in 42 response-evaluable patients, 46.4% (95% CI, 27.5 to 66.1) in the PD-L1-positive subgroup, and 0% (95% CI, 0.0 to 23.2) in the PD-L1-negative subgroup. Responses are ongoing in 12 of 13 responding patients, with median duration of response not yet reached (range, 4.1+ to 49.3+ weeks). CONCLUSION Durvalumab demonstrated a manageable safety profile and evidence of meaningful clinical activity in PD-L1-positive patients with UBC, many of whom were heavily pretreated.
Robust Query Processing (Dagstuhl Seminar 12321)

The 2012 Dagstuhl 12321 Workshop on Robust Query Processing, held from 5--10 August 2012, brought together researchers from both academia and industry to discuss various aspects of robustness in database management systems and ideas for future research. The Workshop was designed as a sequel to an earlier Workshop, Dagstuhl Workshop 10381, that studied a similar set of topics. In this article we summarize some of the main discussion topics of the 12321 Workshop, the results to date, and some open problems that remain.
Outcomes and prognostic factors after recurrence in children and adolescents with nonmetastatic rhabdomyosarcoma

Although > 90% of children with nonmetastatic rhabdomyosarcoma (RMS) achieve complete remission with current treatment, up to one‐third of them experience a recurrence. Survival rates are not always poor in patients who develop recurrences; thus, prognostic factors are needed to tailor salvage treatment.
Growth and production of laccases by the ligninolytic fungi, Pleurotus ostreatus and Botryosphaeria rhodina , cultured on basal medium containing the herbicide, Scepter® (imazaquin)

The herbicide, Scepter®, whose active principle is imazaquin, is commonly used in soybean farming to combat wide‐leaf weeds. The basidiomycete, Pleurotus ostreatus , and the ascomycete, Botryosphaeria rhodina , were evaluated for their growth and laccase production when cultured on basal media containing Scepter®. Both fungi could grow on the herbicide when cultivated in solid and submerged liquid culture in the presence of Scepter® at concentrations of 0–6% (v/v) for P. ostreatus , and up to 0–50% (v/v) for B. rhodina , and in each case produced laccases when assayed against ABTS [2,21‐azino‐bis(3‐ethylbenzthiazoline‐6‐sulfonic acid)] and 2,6‐dimethoxyphenol. P . ostreatus could tolerate up to 6% of Scepter® before it became toxic to the fungus, while in the case of B. rhodina , 50% (v/v) Scepter® was the highest amount that supported grow, and laccase activity was detectable up to 25% (v/v). An inverse relationship existed between the level of Scepter® in the culture medium that supported fungal growth and laccase production. Analysis of the results showed that the fungi studied presented different behaviour towards Scepter® in the culture environment. (© 2005 WILEY‐VCH Verlag GmbH & Co. KGaA, Weinheim)
Immune response to 19A serotype after immunization of 19F containing pneumococcal conjugate vaccine in Korean children aged 12-23 months

Purpose The purpose of this study was to evaluate the immune response to serotype 19A in children aged 12-23 months after immunization of the 19F containing 7-valent pneumococcal conjugate vaccine (PCV7). Methods Blood samples from a total of 45 subjects (age 12-23 months) were included in the study. Subjects were categorized according to immunization status into three groups as follows: 18 subjects with 3 primary doses and 1 booster dose of PCV7 (booster group), 21 subjects with 3 primary doses before 12 months of age (primary group), and 6 subjects with no vaccination history of PCV7 (control group). An ELISA and opsonophagocytic killing assay (OPKA) was done to evaluate the immune responses against serotypes 19F and 19A. Results According to the ELISA, all subjects had antibody titers ≥0.35 µg/mL for serotypes 19F and 19A in the booster and primary group and 83.0% and 66.7% in the control group, respectively. According to the OPKA, subjects with opsonic activity (≥20) against serotypes 19F and 19A were 100% and 61.1% of the subjects in the booster group and 66.7% and 19.0% in the primary group, respectively. No subjects in the control group had opsonic antibodies against both serotypes. Conclusion In conclusion, in children 12-23 months age who were previously vaccinated with PCV7, a cross-reactive immune response is elicited against serotype 19A after a primary series of 3 doses in a small proportion of subjects, and this response is amplified after booster vaccination.
The Effects of Perceived Destination Ability and Destination Brand Love on Tourists’ Loyalty to Post-Disaster Tourism Destinations: The Case of Korean Tourists to Japan

ABSTRACT This study explores the causal relationships between perceived destination ability, three dimensions of brand love (passionate love, emotional attachment, and self-brand integration), switching resistance loyalty, and behavioral loyalty. To test the proposed hypotheses, structural equation modeling was employed based on data from 417 Korean tourists traveling to Japan. The results show significant relationships between the study’s constructs. The results provide valuable insights into the extended model and have important managerial implications for Japan’s destination management organizers facing post-disaster situations.
Impossible Shadows and the Shadow Correspondence Problem

Shadows cast by objects contain potentially useful information about the location of these objects in the scene as well as their surface reflectance. However, before the visual system can use this information, it has to solve the shadow correspondence problem, that is to match the objects with their respective shadows. In the first experiment, it is shown that the estimate of the light source position is affected by a gradual luminance ramp added to the image. In the second experiment, it is shown that observers process impossible shadow images as if they ignored the local features of the objects. All together, the results suggest that the visual system solves the shadow correspondence problem by relying on a coarse representation of the scene.
Hoping for more: redeveloping U.S. public housing without marginalizing low-income residents?

Abstract Urban restructuring policies have uprooted residents and dismantled communities. Previous studies focus on housing redevelopment that minimizes the fraction of housing units left for poor residents and on interviewing residents only once the redevelopment has been announced. By contrast, this paper examines how residents over time experienced the HOPE VI redevelopment of the Orchard Park public housing project in Boston, which sought to preserve a low-income community. Using official records and a unique set of interviews with residents before and after redevelopment, we find marked declines in crime and increased residential satisfaction, which are attributed to changes in tenant composition. The redevelopment process reduced the total number of public housing units yet maintained the vast majority of housing for poor families while creating a new social mix. The findings suggest that to more fully capture the impacts of restructuring, existing theory must be expanded to consider who is displaced and how poverty is deconcentrated.
Large Scale Protein Identification in Intracellular Aquaporin-2 Vesicles from Renal Inner Medullary Collecting Duct*S

Vasopressin acts on renal collecting duct cells to stimulate translocation of aquaporin-2 (AQP2)-containing membrane vesicles from throughout the cytoplasm to the apical region. The vesicles fuse with the plasma membrane to increase water permeability. To identify the intracellular membrane compartments that contain AQP2, we carried out LC-MS/MS-based proteomic analysis of immunoisolated AQP2-containing intracellular vesicles from rat inner medullary collecting duct. Immunogold electron microscopy and immunoblotting confirmed heavy AQP2 labeling of immunoisolated vesicles. Vesicle proteins were separated by SDS-PAGE followed by in-gel trypsin digestion in consecutive gel slices and identification by LC-MS/MS. Identification of Rab GTPases 4, 5, 18, and 21 (associated with early endosomes); Rab7 (late endosomes); and Rab11 and Rab25 (recycling endosomes) indicate that a substantial fraction of intracellular AQP2 is present in endosomal compartments. In addition, several endosome-associated SNARE proteins were identified including syntaxin-7, syntaxin-12, syntaxin-13, Vti1a, vesicle-associated membrane protein 2, and vesicle-associated membrane protein 3. Rab3 was not found, however, either by mass spectrometry or immunoblotting, suggesting a relative lack of AQP2 in secretory vesicles. Additionally, we identified markers of the trans-Golgi network, components of the exocyst complex, and several motor proteins including myosin 1C, non-muscle myosins IIA and IIB, myosin VI, and myosin IXB. Beyond this, identification of multiple endoplasmic reticulum-resident proteins and ribosomal proteins indicated that a substantial fraction of intracellular AQP2 is present in rough endoplasmic reticulum. These results show that AQP2-containing vesicles are heterogeneous and that intracellular AQP2 resides chiefly in endosomes, trans-Golgi network, and rough endoplasmic reticulum.
Reducing to Independent Set Structure -- the Case of k-Internal Spanning Tree

The k-INTERNAL SPANNING TREE problem asks whether a certain graph G has a spanning tree with at least k internal vertices. Basing our work on the results presented in [Prieto and Sloper 2003], we show that there exists a set of reduction rules that modify an arbitrary spanning tree of a graph into a spanning tree with no induced edges between the leaves. Thus, the rules either produce a tree with many internal vertices, effectively deciding the problem, or they identify a large independent set, the leaves, in the graph. Having a large independent set is beneficial, because then the graph allows both 'crown decompositions' and path decompositions. We show how this crown decomposition can be used to obtain a O(k2) kernel for the k-INTERNAL SPANNING TREE problem, improving on the O(k3) kernel presented in [Prieto and Sloper 2003].
The impact of genetic variability on liver disease in the Hispanic/Latin-American population

Liver cirrhosis is within the top 10 causes of death in Latin-American countries and recent evidence suggests that Hispanics in the USA have a more aggressive course of many types of liver disease and show lower response to treatment of hepatitis C compared with other ethnic groups. Although environmental factors are very important, they do not appear to fully account for the observed ethnic differences in the incidence of cirrhosis and progression rates. Genome-wide association studies have been a powerful tool to identify genetic variants that directly confer susceptibility to liver disease. Here, we review the current knowledge on genetic variants associated with the most common types of liver disease that may contribute to ancestry-related differences in disease progression and mortality.
The allergen bronchoprovocation model: an important tool for the investigation of new asthma anti‐inflammatory therapies

Allergen bronchoprovocation tests have been used for more than two decades in the investigation of respiratory allergic diseases such as asthma and rhinitis. These bronchial challenges are now well standardized and can offer key information on the therapeutic potential of new agents and on their anti‐inflammatory effects on the airways. Both standard and low‐dose allergen provocations are safe when performed by experienced investigators and do not lead to persistent worsening of asthma or change in airway function. The evaluation of new therapeutic agents by these methods can also provide important information on the mechanisms of development and persistence of airway diseases.
Optical absorption spectra of human articular cartilage correlate with biomechanical properties, histological score and biochemical composition

This study investigates the relationship between the optical response of human articular cartilage in the visible (VIS) and near infrared (NIR) spectral range and its matrix properties. Full-thickness osteochondral cores (dia. = 16 mm, n = 50) were extracted from human cadaver knees (N = 13) at four anatomical locations and divided into quadrants. Absorption spectra were acquired in the spectral range 400–1100 nm from one quadrant. Reference biomechanical, biochemical composition, histological, and cartilage thickness measurements were obtained from two other quadrants. A multivariate statistical technique based on partial least squares (PLS) regression was then employed to investigate the correlation between the absorption spectra and tissue properties. Our results demonstrate that cartilage optical response correlates with its function, composition and morphology, as indicated by the significant relationship between spectral predicted and measured biomechanical (79.0% ⩽ R2 ⩽ 80.3%, p < 0.0001), biochemical (65.1% ⩽ R2 ⩽ 81.0%, p < 0.0001), and histological scores (Rmankin2 ? > = 83.3%, p < 0.0001) properties. Significant correlation was also obtained with the non-calcified cartilage thickness (Rthick2 ? > = 83.2%, p < 0.0001). We conclude that optical absorption of human cartilage in the VIS and NIR spectral range correlates with the overall tissue properties, thus providing knowledge that could facilitate development of systems for rapid assessment of tissue integrity.
Patterns of hematologic malignancies and solid tumors among 37,838 first‐degree relatives of 13,896 patients with multiple myeloma in Sweden

There are emerging data to suggest a role for genetic factors in the pathogenesis of multiple myeloma (MM). Based on small numbers, certain solid tumors have been reported to occur more frequently among blood relatives of patients with MM. Using population‐based data, we assessed risks for hematologic malignancies, monoclonal gammopathy of undetermined significance (MGUS), and solid tumors among first‐degree relatives of patients with MM. We included 13,896 patients with MM and 54,365 matched controls. Also we identified first‐degree relatives of patients with MM (n = 37,838) and controls (n = 151,068). Using a marginal survival model, we estimated relative risks (RRs) and 95% confidence intervals (CIs) for hematologic and solid tumors among family members of patients with MM and controls as measures of familial aggregation. Compared with relatives of controls, relatives of patients with MM had an increased risk of developing MM (RR = 2.1; 95% CI 1.6–2.9), MGUS (2.1; 1.5–3.1), acute lymphoblastic leukemia (ALL) (2.1; 1.0–4.2), any solid tumor (1.1; 1.0–1.1) and bladder cancer (1.3; 1.0–1.5). No significantly increased risk was found for other hematologic or solid malignancies. Our findings support a role for a shared susceptibility (genetic, environmental or both) that predisposes to MM, MGUS, ALL and bladder cancer. © 2009 UICC
Anthropology, knowledge-flows and global health

Abstract Global health programmes are damaged by blockages in the upward flow of information from localities and regional centres about realities of professional practice and about patients' lives and conditions of treatment. Power differentials between local actors and national or international decision-makers present further obstacles to effective action. Anthropological research and action, in its most effective current forms, make important contributions to these issues. This research often continues over the long term, intensively. It can be multi-sited, studying actors at local, national and international levels simultaneously. It studies the relative knowledge and power of impoverished patients and global decision-makers, all within a single frame. By doing so, anthropological research is capable of providing new and important insights on the diverse meanings of patient decision-making, informed consent, non-compliance, public health reporting, the building of political coalitions for health and many other issues.