Determination of Pathways for Oxygen Binding to Human Hemoglobin A

The role of His(E7) in ligand binding to HbA was re-examined in view of discrepancies between early kinetic studies and recent structure determinations. Replacing His(E7) with Gly, Leu, Phe, and Trp causes 20- to 500-fold increases in the rates of O2 dissociation from both subunits, and FfIR spectra reveal a shift in the C-O stretching frequency peak from 1950 cm-1 to -1970 cm-1 for apolar mutations, indicating loss of a positive electrostatic field next to bound ligands. Thus, the native His(E7) side chain forms a strong hydrogen bond (- -8 kJ/mol) with bound 02 in both HbA subunits. Increasing the size of the E7 residue from Gly to Trp monotonically decreases the rate constants for CO, 02 and NO association to HbA. Substituting His(E7) with Trp also slows down opening and closing of the E7 gate. Ligand binding to the Trp(E7) subunits is markedly biphasic due to a competition between very fast recombination to an open conformer and relaxation of the indole side chain to closed or blocked forms. Crystal structures of Hb and Mb Trp(E7) mutants provide structural models for these closed and blocked conformers. In the closed state, the indole side chain fills both the E7 channel and the distal pocket, inhibiting binding to iron from any direction. In the blocked state, Trp(E7) is located in the solvent interface but still blocks entry into the E7 channel. The bimolecular rate constants for CO binding to the closed and blocked states are 0.08 IlMIS- l and 0.7IlM-1S-1, respectively, which are -100 and -lO-fold slower than average wildtype parameter (-7 IlM-1s-1). Filling potential alternative ligand pathways with xenon does not affect the rate or fraction of ligand escape from either HbA subunit. In contrast, reducing the volume of the distal pocket by space-filling mutations at the BlO, Ell and GS positions dramatically affects both geminate recombination and bimolecular ligand binding. Taken together, these results demonstrate that the E7 channel is the major pathway for ligand entry and escape in HbA and that previously proposed ligand migration routes involving Xe cavities are not functionally significant

The Importance of Conference Proceedings in Research Evaluation: A Methodology for Assessing Conference Impact

Conferences are an essential tool for scientific communication. In disciplines such as Computer Science the majority of original research results are published in conference proceedings. In this study, we have analyzed the role of conference proceedings in various disciplines and propose an alternative approach to research evaluation based on conference proceedings sources indexed in Scopus and Scimago Journal Rank (SJR). This allows one to categorize conference proceedings in quartiles Q1–Q4 by analogy with SJR journal quartiles. Out of 171 conference proceedings sources analyzed, 38 conference proceedings in Engineering (45% of the list) and 23 in Computer Science (32% of the list) have an SJR level corresponding to the first quartile journals in these areas, which emphasizes the exceptional importance of conferences in these disciplines The comparison of this bibliometric-driven ranking with the expert-driven CORE ranking in Computer Science showed a 62% overlap, as well as a significant average rank correlation of the category distribution. © 2022, Springer Nature Switzerland AG

Statistical model and method for analyzing AI conference rankings: China vs USA

Artificial Intelligence (AI) is a rapidly developing field of research that attracts significant funding from both the state and industry players. Such interest is driven by a wide range of AI technology applications in many fields. Since many AI research topics relate to computer science, where a significant share of research results are published in conference proceedings, the same applies to AI. The world leaders in artificial intelligence research are China and the United States. The authors conducted a comparative analysis of the bibliometric indicators of AI conference papers from these two countries based on Scopus data. The analysis aimed to identify conferences that receive above-average citation rates and suggest publication strategies for authors from these countries to participate in conferences that are likely to provide better dissemination of their research results. The results showed that, although Chinese researchers publish more AI papers than those from the United States, US conference papers are cited more frequently. The authors also conducted a correlation analysis of the MNCS index, which revealed no high correlation between MNCS USA vs. MNCS China, MNCS China/MNCS USA vs. MSAR, and MNCS China/MNCS USA vs. CORE ranking indicators.Merit, Expertise and Measuremen

Predictive Task Monitoring for Business Processes

Information sources providing real-time status of physical objects have drastically increased in recent times. So far, research in business process monitoring has mainly focused on checking the completion of tasks. However, the availability of real-time information allows for a more detailed tracking of individual business tasks. This paper describes a framework for controlling the safe execution of tasks and signalling possible misbehaviours at runtime. It outlines a real use case on smart logistics and the preliminary results of its application.European Union FP7/2007-2013 / 318275 (GET Service

Predictive Monitoring of Business Processes

Modern information systems that support complex business processes generally maintain significant amounts of process execution data, particularly records of events corresponding to the execution of activities (event logs). In this paper, we present an approach to analyze such event logs in order to predictively monitor business goals during business process execution. At any point during an execution of a process, the user can define business goals in the form of linear temporal logic rules. When an activity is being executed, the framework identifies input data values that are more (or less) likely to lead to the achievement of each business goal. Unlike reactive compliance monitoring approaches that detect violations only after they have occurred, our predictive monitoring approach provides early advice so that users can steer ongoing process executions towards the achievement of business goals. In other words, violations are predicted (and potentially prevented) rather than merely detected. The approach has been implemented in the ProM process mining toolset and validated on a real-life log pertaining to the treatment of cancer patients in a large hospital

Spherically symmetric scalar field collapse in any dimension

We describe a formalism and numerical approach for studying spherically symmetric scalar field collapse for arbitrary spacetime dimension d and cosmological constant Lambda. The presciption uses a double null formalism, and is based on field redefinitions first used to simplify the field equations in generic two-dimensional dilaton gravity. The formalism is used to construct code in which d and Lambda are input parameters. The code reproduces known results in d = 4 and d = 6 with Lambda = 0. We present new results for d = 5 with zero and negative Lambda.Comment: 16 pages, 6 figures, typos corrected, presentational changes, PRD in pres

Modified general relativity as a model for quantum gravitational collapse

We study a class of Hamiltonian deformations of the massless Einstein-Klein-Gordon system in spherical symmetry for which the Dirac constraint algebra closes. The system may be regarded as providing effective equations for quantum gravitational collapse. Guided by the observation that scalar field fluxes do not follow metric null directions due to the deformation, we find that the equations take a simple form in characteristic coordinates. We analyse these equations by a unique combination of numerical methods and find that Choptuik's mass scaling law is modified by a mass gap as well as jagged oscillations. Furthermore, the results are universal with respect to different initial data profiles and robust under changes of the deformation.Comment: 22 pages, 4 figure

On Field Theory Thermalization from Gravitational Collapse

Motivated by its field theory interpretation, we study gravitational collapse of a minimally coupled massless scalar field in Einstein gravity with a negative cosmological constant. After demonstrating the accuracy of the numerical algorithm for the questions we are interested in, we investigate various aspects of the apparent horizon formation. In particular, we study the time and radius of the apparent horizon formed as functions of the initial Gaussian profile for the scalar field. We comment on several aspects of the dual field theory picture.Comment: 31 pages, 17 figures; V2 Some figures corrected, minor revision. arXiv admin note: substantial text overlap with arXiv:1106.233

Role of Heme Pocket Water in Allosteric Regulation of Ligand Reactivity in Human Hemoglobin

Water molecules can enter the heme pocket after the escape of ligand from myoglobins and hemoglobins, hydrogen bond with the distal histidine, and introduce steric barriers to ligand rebinding. The photodissociated CO complexes of human hemoglobin and its isolated α and β chains were subjected to spectrokinetic analysis of the effect of heme hydration on ligand rebinding. A strong coupling was observed between heme hydration and quaternary state. This coupling may contribute significantly to the 20–60-fold difference between the R- and T-state bimolecular CO binding rate constants and thus to the modulation of ligand reactivity that is the hallmark of hemoglobin allostery. Heme hydration proceeded over the course of several kinetic phases in the tetramer, including the R to T quaternary transition. An initial 150 ns hydration phase increased the R-state distal pocket water occupancy, n(w)(R), to a level similar to that of the isolated α (~60%) and β (~10%) chains, resulting in a modest barrier to ligand binding. A subsequent phase, concurrent with the first step of the R → T transition, further increased the level of heme hydration, increasing the barrier. The final phase, concurrent with the final step of the allosteric transition, brought the water occupancy of the T-state tetramer, n(w)(T), even higher and close to full occupancy in both the α and β subunits (~90%). This hydration level could present an even larger barrier to ligand binding and contribute significantly to the lower iron reactivity of the T state toward CO

Data Sharing and Research on Peer Review: A Call to Action

While recent surveys show that most stakeholders recognise the importance of peer review to the publication process, there is a lack of systematic research on the topic. In a period of hyper-competition for resources, with perverse incentives that lead to academic capitalism and a \u201cpublish or perish\u201d mentality, the lack of robust and cumulative research on approaches, models and practices of peer review can slow down efforts towards fostering research integrity and the credibility of scholarly communication. A major challenge in studying peer review systematically is the lack of available data. While data sharing in scientific research has made relevant progress in certain fields, the lack of infrastructures to promote the sharing of peer review data among publishers, journals and academic scholars, the challenges posed by privacy and data protection legislation, and the perceived lack of incentives for publishers, learned societies and journals to share data, have all hampered efforts in this important domain. While public authorities, learned societies and publishers may face different priorities, incentives and obstacles regarding data sharing, the time has come to call to action all stakeholders who play a part in this field. In this paper, we argue that an infrastructure for data sharing is needed to stimulate independent, collaborative, public research on peer review and we suggest measures and initiatives to set up a collaborative effort towards this goal