bluuebunny/crossref_metadata_2025_split huggingface dataset:
Affinity2Vec: drug-target binding affinity prediction through representation learning, graph mining, and machine learning
Authors: Thafar Maha A. , Alshahrani Mona , Albaradei Somayah , Gojobori Takashi , Essack Magbubah , Gao Xin 
Published: March 2022

AbstractDrug-target interaction (DTI) prediction plays a crucial role in drug repositioning and virtual drug screening. Most DTI prediction methods cast the problem as a binary classification task to predict if interactions exist or as a regression task to predict continuous values that indicate a drug's ability to bind to a specific target. The regression-based methods provide insight beyond the binary relationship. However, most of these methods require the three-dimensional (3D) structural information of targets which are still not generally available to the targets. Despite this bottleneck, only a few methods address the drug-target binding affinity (DTBA) problem from a non-structure-based approach to avoid the 3D structure limitations. Here we propose Affinity2Vec, as a novel regression-based method that formulates the entire task as a graph-based problem. To develop this method, we constructed a weighted heterogeneous graph that integrates data from several sources, including drug-drug similarity, target-target similarity, and drug-target binding affinities. Affinity2Vec further combines several computational techniques from feature representation learning, graph mining, and machine learning to generate or extract features, build the model, and predict the binding affinity between the drug and the target with no 3D structural data. We conducted extensive experiments to evaluate and demonstrate the robustness and efficiency of the proposed method on benchmark datasets used in state-of-the-art non-structured-based drug-target binding affinity studies. Affinity2Vec showed superior and competitive results compared to the state-of-the-art methods based on several evaluation metrics, including mean squared error, rm2, concordance index, and area under the precision-recall curve.
Thioredoxin interacting protein protects mice from fasting induced liver steatosis by activating ER stress and its downstream signaling pathways
Authors: Miyahara Hiroyuki , Hasegawa Kosei , Yashiro Masato , Ohara Toshiaki , Fujisawa Masayoshi , Yoshimura Teizo , Matsukawa Akihiro , Tsukahara Hirokazu 
Published: March 2022

AbstractUnder normal conditions, fasting results in decreased protein disulfide isomerase (PDI) activity and accumulation of unfolded proteins, leading to the subsequent activation of the unfolded protein response (UPR)/autophagy signaling pathway to eliminate damaged mitochondria. Fasting also induces upregulation of thioredoxin-interacting protein (TXNIP) expression and mice deficient of this protein (TXNIP-KO mice) was shown to develop severe hypoglycemia, hyperlipidemia and liver steatosis (LS). In the present study, we aimed to determine the role of TXNIP in fasting-induced LS by using male TXNIP-KO mice that developed LS without severe hypoglycemia. In TXNIP-KO mice, fasting induced severe microvesicular LS. Examinations by transmission electron microscopy revealed mitochondria with smaller size and deformities and the presence of few autophagosomes. The expression of β-oxidation-associated genes remained at the same level and the level of LC3-II was low. PDI activity level stayed at the original level and the levels of p-IRE1 and X-box binding protein 1 spliced form (sXBP1) were lower. Interestingly, treatment of TXNIP-KO mice with bacitracin, a PDI inhibitor, restored the level of LC3-II after fasting. These results suggest that TXNIP regulates PDI activity and subsequent activation of the UPR/autophagy pathway and plays a protective role in fasting-induced LS.
Detection and characterization of simvastatin and its metabolites in rat tissues and biological fluids using MALDI high resolution mass spectrometry approach
Authors: Yin Wencui , Al-Wabli Reem I. , Attwa Mohamed W. , Rahman A. F. M. Motiur , Kadi Adnan A. 
Published: March 2022

AbstractSimvastatin (SV) is a hypolipidemic agent, and it is the 2nd most widely prescribed lipid-lowering drug. Here, the detection and characterization of SV and its metabolites was studied in selected organs/tissues (lung, liver, brain, heart and kidney) and biological samples (blood, urine and feces) of rats. MALDI Orbitrap MS was used as a high-resolution mass analyzer. 2,5-Dihydroxybenzoic acid (DHB) and 1,5-diaminonaphthalene (DAN) were used as matrices. Several sample loading methods onto the MALDI plate were attempted and dried droplet method was found to be superior. Two different cell disruption methods, pulverization and homogenization, were also evaluated for the optimum sensitivity in MALDI. Pulverization allowed the detection of more metabolites in all organs except the liver, where homogenization led to the detection of more metabolites. Altogether, 13 metabolites were detected, and one metabolite tentatively identified as a reduced product is being reported for the first time. SV and its metabolites were distributed to all the tissues studied except the brain. Overall, the results implied that the pulverized samples were more uniform and larger in surface area, resulting in their more efficient and complete extraction during sample preparation. As shown in the present study, MALDI Orbitrap MS is a useful tool to study drug and metabolite detection and characterization.
European-wide forest monitoring substantiate the neccessity for a joint conservation strategy to rescue European ash species (Fraxinus spp.)
Authors: George Jan-Peter , Sanders Tanja G. M. , Timmermann Volkmar , Potočić Nenad , Lang Mait 
Published: March 2022

AbstractEuropean ash (Fraxinus excelsior) and narrow-leafed ash (F. angustifolia) are keystone forest tree species with a broad ecological amplitude and significant economic importance. Besides global warming both species are currently under significant threat by an invasive fungal pathogen that has been spreading progressively throughout the continent for almost three decades. Ash dieback caused by the ascomyceteHymenoscyphus fraxineusis capable of damaging ash trees of all age classes and often ultimately leads to the death of a tree after years of progressively developing crown defoliation. While studies at national and regional level already suggested rapid decline of ash populations as a result of ash dieback, a comprehensive survey at European level with harmonized crown assessment data across countries could shed more light into the population decline from a pan-European perspective and could also pave the way for a new conservation strategy beyond national boarders. Here we present data from the ICP Forests Level I crown condition monitoring from 27 countries resulting in > 36,000 observations. We found a substantial increase in defoliation and mortality over time indicating that crown defoliation has almost doubled during the last three decades. Hotspots of mortality are currently situated in southern Scandinavia and north-eastern Europe. Overall survival probability after nearly 30 years of infection has already reached a critical value of 0.51, but with large differences among regions (0.20–0.86). Both a Cox proportional hazard model as well as an Aalen additive regression model strongly suggest that survival of ash is significantly lower in locations with excessive water regime and which experienced more extreme precipitation events during the last two decades. Our results underpin the necessity for fast governmental action and joint rescue efforts beyond national borders since overall mean defoliation will likely reach 50% as early as 2030 as suggested by time series forecasting.
Effect of plasma exchange on COVID-19 associated excess of von Willebrand factor and inflammation in critically ill patients
Authors: Seibert Felix S. , Blazquez-Navarro Arturo , Hölzer Bodo , Doevelaar Adrian A. N. , Nusshag Christian , Merle Uta , Morath Christian , Zgoura Panagiota , Dittmer Rita , Schneppenheim Sonja , Wilhelm Jochen , Babel Nina , Budde Ulrich , Westhoff Timm H. 
Published: March 2022

AbstractUbiquitous microthromboses in the pulmonary vasculature play a crucial role in the pathogenesis of COVID-19 associated acute respiratory distress syndrome (ARDS). Excess of Willebrand factor (vWf) with intravascular multimer formation was identified as a key driver of this finding. Plasma exchange (PLEX) might be a therapeutic option to restore the disbalance between vWf and ADAMTS13. We report the effects of PLEX on vWf, ADAMTS13, inflammatory cytokines and parameters of ventilation. We investigated 25 patients, who were on mechanical ventilation for COVID-19 pneumonia with ARDS at two German university hospitals. All patients received PLEX as an ultima ratio measure for refractory ARDS. VWf antigen (vWf:Ag), ADAMTS13 activity, a cytokine panel mirroring the inflammatory situation and clinical parameters were assessed before and after three to six PLEX therapies with fresh frozen plasma. Before the PLEX sequence there was an excessive release of vWf:Ag (425.4 ± 167.5%) and mildly reduced ADAMTS13 activity (49.7 ± 23.3%). After the PLEX series, there was a significant increase of ADAMTS13 activity to 62.4 ± 17.7% (p = 0.029) and a significant decrease of vWf:Ag to 336.1 ± 138.2% (p = 0.041) resulting in a 63% improvement of the ADAMT13/vWf:Ag ratio from 14.5 ± 10.0 to 23.7 ± 14.6, p = 0.024. Comparison of parameters before and after individual PLEX sessions (n = 35) revealed a mean reduction of vWf from 387.8 ± 165.1 to 213.2 ± 62.3% (p = 0.001) and an increase of ADAMTS13 activity from 60.4 ± 20.1 to 70.5 ± 14.0% (p = 0.001). Parallelly, monocyte chemotactic protein-1 and interleukin-18 decreased significantly (p = 0.034 each). Along the PLEX sequence lactate dehydrogenase (p = 0.001), C-reactive protein (p = 0.001), and positive end expiratory pressure (p = 0.01) significantly decreased accompanied by an improvement of Horovitz index (p = 0.001). PLEX restores the disbalance between ADAMTS13 and vWf:Ag, a driver of immunothrombosis. Moreover, it reduces the inflammatory state and is associated with a benefit of ventilation parameters. These findings render a further rationale to regard PLEX as a therapeutic option in severe COVID-19.
Cascading verification initiated by switching attacks through compromised digital relays
Authors: Yamashita Koji , Yang Zhiyuan , Ten Chee‐Wooi , Kar Soummya , Ginter Andrew 
Published: March 2022

AbstractAttackers are able to enumerate all devices and computers within a compromised substation network. Digital relays deployed in the substation are the devices with IP addresses that can be discovered in the process of trial‐and‐error search. This paper is concerned with studies of cyberattacks manipulating digital relays to disruptively disconnect the associated breakers. The plausible enumeration of such disruptive attack for each relay in a substation is verified with the dynamic simulation studies with the special protection system for frequency, voltage, and rotor angle stability. A pertinent approach with smaller scale contingency analysis results is proposed to reduce the enormous computation burden. The devised enumeration reduction method is evaluated using IEEE test cases. The proposed method provides an extensive enumeration strategy that can be used by utility engineers to identify the pivotal relays in the system and can be further strengthened with security protection.
Strength or Ductility Seismic Design? A case study in Sabah using the Eurocode 8 Malaysian National Annex
Authors: Ngui M.F.T. , Looi D.T.W. 
Published: March 2022

Abstract
This paper shares the experience of a building project which piloted seismic design using Eurocode 8, with the Malaysian National Annex legislated in 2017. The 23-storey reinforced concrete building features geometric irregularity with podium and two towers, located in Kota Kinabalu, the capital city of Sabah, Malaysia. Sabah had experienced a magnitude-6 earthquake in 2015, where the epicentre Ranau was just 50 km away from Kota Kinabalu. Conventional Probabilistic Seismic Hazard Assessment has indicated that Kota Kinabalu has a peak ground acceleration (PGA) on rock of only 0.04g for a 475-year return period, which appears to be counter-intuitive for such a potentially destructive near-field magnitude 6 earthquake. Hence, four possible scenarios are postulated, i.e., PGA of 0.04g, 0.08g and 0.12g designed with ductility class low (DCL), assuming force-based non-dissipative mechanism and 0.12g designed with ductility class medium (DCM), engaging seismic detailing to form plastic hinges. This paper is written to give local engineering practitioners, who have either no prior experience in seismic design or have been using the basic equivalent force method, to develop a better sense of response spectrum seismic analysis, code-based design and choice of strength or ductility seismic design in low-to-moderate seismicity regions.
Effects of RH-WMA Additive on the Design Binder Content (DBC) of Warm Porous Asphalt (WPA)
Authors: Samat M. M. , Ahmad J. , Omar b N. , Mohammad Hanapi N. , Mohd Kamal M. M. 
Published: March 2022

Abstract
Warm mix asphalt (WMA) in a pavement construction is a technology that is beneficial and contributes towards reduction of the global warming issues. In this research, WMA was used to design porous asphalt pavement with addition of organic additive which is known as RH-WMA. A Dutch modified gradation to suit Malaysian quarry practice was used to prepare the WMA. The RH-WMA additive ranges between 2 to 5 percent was added to base binder of penetration 60/70 to determine the design binder content (DBC) of the RH-WMA mix. The DBC was then determined based on the binder drainage and Cantabrian tests. The binder drainage test was used to set an upper limit while the Cantabrian test for abrasion loss was adopted to determine the lower limit of the DBC. The results for Cantabrian test indicate significant contribution of incorporating RH-WMA additive into WMA to minimize abrasion loss as compared to unmodified mixes. The binder drainage test results showed that the mixes incorporating RH-WMA additive exhibited higher drainage in varying degrees depending on the quantity of RH-WMA. The discussion was made based on target binder content, critical binder content, maximum binder content and the maximum retained binder content of the of the resulted mixes obtained from the binder drainage test.
A Review of Eggshell Powder and Fly Ash-Based Geopolymers Concrete
Authors: Moison I.C. , Gungat L. , Asrah H. , Chiew F.H. 
Published: March 2022

Abstract
This is a review of the current research on the development of geopolymer based of eggshell powder (ESP) and fly ash (FA). This paper observes the mechanical properties which are the compressive strength and tensile strength of eggshell powder (ESP) and fly ash (FA) based geopolymer that is formed by an alkali activation method. It is shown that the mechanical properties of alkaline activated geopolymer is significantly affected by its proportion of raw material in concrete; specifically, the fly ash (FA) to eggshell powder (ESP) ratio and the alkali activator ratio. Moreover, it is shown that curing temperature also may be a very influential factor towards the mechanical properties of the concrete. However, more experimental studies are required for eggshell powder (ESP) and fly ash (FA) based geopolymer as there are not many studies yet in this field have been conducted till date.
Quantum computation of phase transition in the massive Schwinger model
Authors: Thompson Shane , Siopsis George 
Published: March 2022

Abstract
As pointed out by Coleman, physical quantities in the Schwinger model depend on a parameter θ that determines the background electric field. There is a phase transition for θ = π only. We develop a momentum space formalism on a lattice and use it to perform a quantum computation of the critical point of this phase transition on the NISQ device IMB Q Lima. After error mitigation, our results give strong indication of the existence of a critical point at m/e ≃ 0.32, where m is the bare fermion mass and e is the coupling strength, in good agreement with the classical numerical result m/e ≃ 0.3335.
Inverse Satake isomorphism and change of weight
Authors: Abe N. , Herzig F. , Vignéras M. F. 
Published: March 2022

Let

G
G

be any connected reductive

p
p

-adic group. Let

K
⊂
G

K\subset G

be any special parahoric subgroup and

V
,

V
′

V,V’

be any two irreducible smooth

F

p

¯

[
K
]

\overline {\mathbb {F}_p}[K]

-modules. The main goal of this article is to compute the image of the Hecke bimodule

End

F

p

¯

[
K
]

⁡
(
c
−
I
n

d
K
G

V
,
c
−
I
n

d
K
G

V
′

)

\operatorname {End}_{\overline {\mathbb {F}_p}[K]}(c-Ind_K^G V, c-Ind_K^G V’)

by the generalized Satake transform and to give an explicit formula for its inverse, using the pro-

p
p

Iwahori Hecke algebra of

G
G

. This immediately implies the “change of weight theorem” in the proof of the classification of mod

p
p

irreducible admissible representations of

G
G

in terms of supersingular ones. A simpler proof of the change of weight theorem, not using the pro-

p
p

Iwahori Hecke algebra or the Lusztig-Kato formula, is given when

G
G

is split and in the appendix when

G
G

is quasi-split, for almost all

K
K

.
Short-term social dynamics following anthropogenic and natural disturbances in a free-living mammal
Authors: Gall Gabriella E C , Evans Julian C , Silk Matthew J , Ortiz-Jimenez Chelsea A , Smith Jennifer E 
Published: March 2022

AbstractAnthropogenic disturbances are widely recognized for their far-reaching consequences on the survival and reproduction of wildlife, but we understand comparatively little about their effects on the social lives of group-living animals. Here we examined these short-term changes in affiliative behavior as part of a long-term study on a human-tolerant and socially flexible population of California ground squirrels (Otospermophilus beecheyi). We used social network analysis to examine short-term changes in affiliative behavior and individual consistency in response to disturbances by humans, domestic dogs, or a natural predator (the coyote). Overall, juveniles were more involved than adults in affiliative interactions, but the short-term directional effects of these acute disturbances on social cohesion varied by disturbance type. Human and dog presence reduced aboveground connectivity, particularly for juveniles, whereas disturbances by coyotes generally promoted it. Beyond these effects, we also detected non-random responses to disturbances, though individuals were not very consistent in their directional response to different disturbance types. Our results demonstrate the flexible changes in social behavior triggered by short-term disturbances imposed by humans and other threats. More generally, our findings elucidate the underappreciated sensitivity of animal social interactions to short-term ecological disturbances, raising key questions about their consequences on the social lives of animals.
“e-breakout”? Weaponised Interdependence and the Strategic Dimensions of China’s Digital Currency
Authors: Lanteigne Marc 
Published: March 2022

Abstract
The government of China has touted the development of a digital version of its currency as a watershed moment in its ongoing financial modernisation processes. The experimental digital renminbi or eCNY is expected to be fully implemented in the next few years, and thus far its initial benefits have been seen primarily on the domestic level. Yet Beijing is also open to the eventual use of the eCNY for international transactions, which in light of the many governments seeking to develop their own central bank digital currencies raises the question of whether or not this e-currency could develop into a global standard. The concept of “weaponised interdependence”, meaning the ability of states to gain bargaining advantages from global networks through the collection of data and to deny others access and benefits, is an ideal method of gauging the potential of the digital renminbi for enhancing Beijing’s power in global financial markets.
Inoculum effects of cefepime/zidebactam (WCK 5222) and ertapenem/zidebactam (WCK 6777) for Enterobacterales in relation to β-lactamase type and enhancer effect, as tested by BSAC agar dilution
Authors: Mushtaq Shazad , Vickers Anna , Chaudhry Aiysha , Woodford Neil , Livermore David M 
Published: March 2022

Abstract

Objectives
Combinations of PBP3-active β-lactams with developmental diazabicyclooctanes (DBOs), e.g. zidebactam, remain active against many MBL producers via an enhancer effect. We explored how this activity is affected by inoculum.

Materials and methods
MICs of zidebactam and its cefepime and ertapenem combinations (WCK 5222 and WCK 6777, respectively) were determined by BSAC agar dilution at inocula from 3–6 × 103 to 3–6 × 105 cfu/spot. Isolates, principally Klebsiella spp., were chosen as having previously tested resistant to zidebactam or its cefepime combination, and by β-lactamase type.

Results
MICs of zidebactam, tested alone, were strongly inoculum dependent regardless of β-lactamase type; MICs of its cefepime and ertapenem combinations likewise were strongly inoculum dependent—rising ≥32-fold across the inoculum range tested—but only for MBL producers. Combination MICs for isolates with non-MBLs, including those with OXA-48 (where the enhancer effect remains critical for ertapenem/zidebactam) were much less inoculum dependent, particularly for cefepime/zidebactam. MBL producers frequently moved between putative ‘susceptible’ (MIC ≤ 8 + 8 mg/L) and ‘resistant’ (MIC &gt; 8 + 8 mg/L) categories according to whether the inoculum was at the high or low end of BSAC’s acceptable (1–4 × 104 cfu/spot) range.

Conclusions
The activity of zidebactam combinations against MBL producers, which strongly depends on the enhancer effect, is inoculum dependent. Animal data suggest consistent in vivo activity even in high-inoculum pneumonia models. Contingent on this being supported by clinical experience, the combination behaviour may be best represented by the MICs obtained at the lower end of BSAC’s inoculum range.
Incomplete degradation products of galactomannan from Sesbania cannabina modulated the cecal microbial community of laying hens
Authors: Tao Yuheng , Wang Ting , Huang Caoxing , Lai Chenhuan , Ling Zhe , Zhou Yanmin , Yong Qiang 
Published: March 2022

Abstract
Galactomannan and its degradation products have been gaining attention based on their possible means for improving the natural defense of the host through modulation of the bacterial population in the gut. Herein, incomplete degradation products of galactomannan (IDPG) was supplemented into the diet of aged laying hens to investigate the efficacy of IDPG on the gut microbiome. Four treatments with six replicates of twelve 68-wk-old laying hens (Hy-Line variety brown) each were fed a basal diet supplemented with 0%, 0.01%, 0.025%, and 0.05% IDPG for 8 wk. Results showed that the propionate concentration significantly increased in laying hens fed a diet supplemented with 0.025% or 0.05% IDPG relative to the control diet (P &lt; 0.05). Moreover, the results of 16S rRNA gene sequencing revealed that there was a notable elevation of microbiome species diversity due to the addition of IDPG, with a noted enrichment to phyla Bacteroidetes at the expense of Firmicutes and Proteobacteria. Metabolic prediction of the cecal microbiome suggested significant improvements to carbohydrate and lipid metabolism and a significant depletion for energy metabolism and infectious diseases. More importantly, a strong positive correlation between levels of genera Bacteroides, Rikenellaceae_RC9_gut_group, and Prevotellaceae_UCG-001 with high production of propionate was found using multivariate analysis. Our study demonstrated that IDPG acted by mainly enriching the phyla Bacteroidetes in the cecum, increasing species diversity, and cecal propionate concentrations. It seems that IDPG can be used as feed additives in laying hen farming due to its capacity to positively modulate the cecal microbiome and aid improve overall health.