This paper presents a comparison of a graph-based genetic algorithm (GB-GA) and machine learning (ML) results for the optimization of log
values with a constraint for synthetic accessibility and ...shows that the GA is as good as or better than the ML approaches for this particular property. The molecules found by the GB-GA bear little resemblance to the molecules used to construct the initial mating pool, indicating that the GB-GA approach can traverse a relatively large distance in chemical space using relatively few (50) generations. The paper also introduces a new non-ML graph-based generative model (GB-GM) that can be parameterized using very small data sets and combined with a Monte Carlo tree search (MCTS) algorithm. The results are comparable to previously published results (
, 2017,
, 972-976) using a recurrent neural network (RNN) generative model, and the GB-GM-based method is several orders of magnitude faster. The MCTS results seem more dependent on the composition of the training set than the GA approach for this particular property. Our results suggest that the performance of new ML-based generative models should be compared to that of more traditional, and often simpler, approaches such a GA.
This protocol shows how to obtain a detailed glycan compositional and structural profile from purified glycoproteins or protein mixtures, and it can be used to distinguish different isobaric glycan ...isomers. Glycoproteins are immobilized on PVDF membranes before the N-glycans are enzymatically released by PNGase F, isolated and reduced. Subsequently, O-glycans are chemically released from the same protein spot by reductive β-elimination. After desalting with cation exchange microcolumns, the glycans are separated and analyzed by porous graphitized carbon liquid chromatography-electrospray ionization tandem mass spectrometry (LC-ESI-MS/MS). Optionally, the glycans can be treated with sialidases or other specific exoglycosidases to yield more detailed structural information. The sample preparation takes approximately 4 d, with a heavier workload on days 2 and 3, and a lighter load on days 1 and 4. The time for data interpretation depends on the complexity of the samples analyzed. This method can be used in conjunction with the analysis of enriched glycopeptides by capillary/nanoLC-ESI-MS/MS, which together provide detailed information regarding the site heterogeneity of glycosylation.
We identified policy implications of organizational behavior and human resource management (OBHRM) research based on reviewing 4,026 articles in 10 journals (2010–2019). We found that policy ...implications are underutilized and not part of OBHRM's zeitgeist because only 1.5% of articles (i.e., n = 61) included them, suggesting that OBHRM risks becoming societally irrelevant. Societal irrelevance may result in lower perceived value-added, less prestige and status compared to other fields that do offer implications for policy, and less support regarding research funding. However, we see potential for OBHRM research to make meaningful contributions to policy-making in the future because we uncovered several areas that do offer some policy implications, such as labor relations, leadership, training and development, justice and fairness, and diversity and inclusion. We offer a dual theory–policy research agenda focused on (a) designing empirical studies with policy-making goals in mind; (b) converting existing exploratory and explanatory research to prescriptive and normative research; (c) deriving policies from bodies of research rather than individual studies; and (d) creating policies based on integrating theories, fields, and levels of analysis. We hope our article will be a catalyst for the creation and implementation of research-based policies in OBHRM and other management subfields.
Summary Idiopathic intracranial hypertension is a disorder characterised by raised intracranial pressure that predominantly affects young, obese women. Pathogenesis has not been fully elucidated, but ...several causal factors have been proposed. Symptoms can include headaches, visual loss, pulsatile tinnitus, and back and neck pain, but the clinical presentation is highly variable. Although few studies have been done to support evidence-based management, several recent advances have the potential to enhance understanding of the causes of the disease and to guide treatment decisions. Investigators of the Idiopathic Intracranial Hypertension Treatment Trial (IIHTT) reported beneficial effects of acetazolamide in patients with mild visual loss. Studies have also established weight loss as an effective disease-modifying treatment, and further clinical trials to investigate new treatments are underway. The incidence of idiopathic intracranial hypertension is expected to increase as rates of obesity increase; efforts to reduce diagnostic delays and identify new, effective approaches to treatment will be key to meeting the needs of a growing number of patients.
The human gut contains trillions of commensal bacteria, and similar to pathogenic bacteria, the gut microbes and their products can be recognized by toll-like receptors (TLRs). It is well ...acknowledged that the interaction between gut microbiota and the local TLRs help to maintain the homeostasis of intestinal immunity. High-fat intake or obesity can weaken gut integrity leading to the penetration of gut microbiota or their bacterial products into the circulation, leading to the activation of TLRs on immune cells and subsequently low-grade systemic inflammation in host. Metabolic cells including hepatocytes and adipocytes also express TLRs. Although they are able to produce and secrete inflammatory molecules, the effectiveness remains low compared with the immune cells embedded in the liver and adipose tissue. The interaction of TLRs in these metabolic cells or organs with gut microbiota remains unclear, but a few studies have suggested that the functions of these TLRs are related to metabolism. Alteration of the gut microbiota is associated with body weight change and adiposity in human, and the interaction between the commensal gut microbiota and TLRs may possibly involve both metabolic and immunological regulation. In this review, we will summarize the current findings on the relationship between TLRs and gut microbiota with a focus on metabolic regulation and discuss how such interaction participates in host metabolism.
Wind and solar power are troubled by large fluctuations in delivery due to changing weather. The surplus electricity can be used in a Solid Oxide Electrolyser Cell (SOEC) to split
CO
2
+
H
2
O
into
...CO
+
H
2
(
+
O
2
)
which can be catalyzed into various types of synthetic fuel using a suitable catalyst.
H
2
O
electrolysis with a new SOEC resulted in a record breaking current density of
-
3.6
A
/
cm
2
at a cell voltage of 1.48
V. Assuming the surplus electricity to cost 3.6
US$/GJ, the
H
2
production price is estimated to 5
US$/GJ equivalent to 30
US$/barrel crude oil or to 0.6
US$/gge (gallon of gasoline equivalent).
Metal hydrides are known as a potential efficient, low-risk option for high-density hydrogen storage since the late 1970s. In this paper, the present status and the future perspectives of the use of ...metal hydrides for hydrogen storage are discussed. Since the early 1990s, interstitial metal hydrides are known as base materials for Ni – metal hydride rechargeable batteries. For hydrogen storage, metal hydride systems have been developed in the 2010s 1 for use in emergency or backup power units, i. e. for stationary applications.
With the development and completion of the first submarines of the U212 A series by HDW (now Thyssen Krupp Marine Systems) in 2003 and its export class U214 in 2004, the use of metal hydrides for hydrogen storage in mobile applications has been established, with new application fields coming into focus.
In the last decades, a huge number of new intermetallic and partially covalent hydrogen absorbing compounds has been identified and partly more, partly less extensively characterized.
In addition, based on the thermodynamic properties of metal hydrides, this class of materials gives the opportunity to develop a new hydrogen compression technology. They allow the direct conversion from thermal energy into the compression of hydrogen gas without the need of any moving parts. Such compressors have been developed and are nowadays commercially available for pressures up to 200 bar. Metal hydride based compressors for higher pressures are under development. Moreover, storage systems consisting of the combination of metal hydrides and high-pressure vessels have been proposed as a realistic solution for on-board hydrogen storage on fuel cell vehicles.
In the frame of the “Hydrogen Storage Systems for Mobile and Stationary Applications” Group in the International Energy Agency (IEA) Hydrogen Task 32 “Hydrogen-based energy storage”, different compounds have been and will be scaled-up in the near future and tested in the range of 500 g to several hundred kg for use in hydrogen storage applications.
•Latest developments in the application of hydride technology.•Investigations on both stationary and mobile applications.•Special attention to metal hydride compressors.•Heat storage and H2 compression especially noted in the Outlook.
The new empirical rules for protein pKa predictions implemented in the PROPKA3.0 software package (Olsson et al. J. Chem. Theory Comput.2010, 7, 525-537) have been extended to the prediction of pKa ...shifts of active site residues and ionizable ligand groups in protein-ligand complexes. We present new algorithms that allow pKa shifts due to inductive (i.e., covalently coupled) intraligand interactions, as well as noncovalently coupled interligand interactions in multiligand complexes, to be included in the prediction. The number of different ligand chemical groups that are automatically recognized has been increased to 18, and the general implementation has been changed so that new functional groups can be added easily by the user, aided by a new and more general protonation scheme. Except for a few cases, the new algorithms in PROPKA3.1 are found to yield results similar to or better than those obtained with PROPKA2.0 (Bas et al. Proteins: Struct., Funct., Bioinf.2008, 73, 765-783). Finally, we present a novel algorithm that identifies noncovalently coupled ionizable groups, where pKa prediction may be especially difficult. This is a general improvement to PROPKA and is applied to proteins with and without ligands.
The mechanical properties of a cell determine many aspects of its behavior, and these mechanics are largely determined by the cytoskeleton. Although the contribution of actin filaments and ...microtubules to the mechanics of cells has been investigated in great detail, relatively little is known about the contribution of the third major cytoskeletal component, intermediate filaments (IFs). To determine the role of vimentin IF (VIF) in modulating intracellular and cortical mechanics, we carried out studies using mouse embryonic fibroblasts (mEFs) derived from wild-type or vimentin−/− mice. The VIFs contribute little to cortical stiffness but are critical for regulating intracellular mechanics. Active microrheology measurements using optical tweezers in living cells reveal that the presence of VIFs doubles the value of the cytoplasmic shear modulus to ∼10 Pa. The higher levels of cytoplasmic stiffness appear to stabilize organelles in the cell, as measured by tracking endogenous vesicle movement. These studies show that VIFs both increase the mechanical integrity of cells and localize intracellular components.
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