bluuebunny/crossref_metadata_2025_split huggingface dataset:
Structural basis for the stereospecific inhibition of the dual proline/hydroxyproline catabolic enzyme ALDH4A1 by trans‐4‐hydroxy‐L‐proline
Authors: Bogner Alexandra N. , Stiers Kyle M. , McKay Cole M. , Becker Donald F. , Tanner John J. 
Published: May 2021

AbstractAldehyde dehydrogenase 4A1 (ALDH4A1) catalyzes the final steps of both proline and hydroxyproline catabolism. It is a dual substrate enzyme that catalyzes the NAD+‐dependent oxidations of L‐glutamate‐γ‐semialdehyde to L‐glutamate (proline metabolism), and 4‐hydroxy‐L‐glutamate‐γ‐semialdehyde to 4‐erythro‐hydroxy‐L‐glutamate (hydroxyproline metabolism). Here we investigated the inhibition of mouse ALDH4A1 by the six stereoisomers of proline and 4‐hydroxyproline using steady‐state kinetics and X‐ray crystallography. Trans‐4‐hydroxy‐L‐proline is the strongest of the inhibitors studied, characterized by a competitive inhibition constant of 0.7 mM, followed by L‐proline (1.9 mM). The other compounds are very weak inhibitors (approximately 10 mM or greater). Insight into the selectivity for L‐stereoisomers was obtained by solving crystal structures of ALDH4A1 complexed with trans‐4‐hydroxy‐L‐proline and trans‐4‐hydroxy‐D‐proline. The structures suggest that the 10‐fold greater preference for the L‐stereoisomer is due to a serine residue that hydrogen bonds to the amine group of trans‐4‐hydroxy‐L‐proline. In contrast, the amine group of the D‐stereoisomer lacks a direct interaction with the enzyme due to a different orientation of the pyrrolidine ring. These results suggest that hydroxyproline catabolism is subject to substrate inhibition by trans‐4‐hydroxy‐L‐proline, analogous to the known inhibition of proline catabolism by L‐proline. Also, drugs targeting the first enzyme of hydroxyproline catabolism, by elevating the level of trans‐4‐hydroxy‐L‐proline, may inadvertently impair proline catabolism by the inhibition of ALDH4A1.
Robotic surgery can be safely performed for patients and healthcare workers during COVID‐19 pandemic
Authors: Sparwasser Peter , Brandt Maximillian P. , Haack Maximillian , Dotzauer Robert , Boehm Katharina , Gheith Mohammed Kamal , Mager Rene , Jäger Wolfgang , Ziebart Alexander , Höfner Thomas , Tsaur Igor , Haferkamp Axel , Borgmann Hendrik 
Published: May 2021

AbstractObjectivesTo investigate the safety of robotic surgery during COVID‐19 pandemic concerning new‐acquired COVID‐19 infections for patients and healthcare workers.PatientsWe performed a retrospective single‐centre cohort study of patients undergoing robotic surgery in initial period of COVID‐19 pandemic. Patients and healthcare workers COVID‐19 infection status was assessed by structured telephone follow‐up and/or repeated nasopharyngeal swabs.ResultsAfter 61 robotic surgeries (93,5% cancer surgery), one patient (1.6%) had COVID‐19 infection. Sixty healthcare workers cumulatively exposed to 1187 h of robotic surgery had no infection. One patient with postoperative proof of SARS‐CoV‐2 had complete recovery. After this potentially contagious robotic surgery, eight healthcare workers had no COVID‐19 infection after follow‐up with each three nasopharyngeal swabs.ConclusionsEarly clinical experience of robotic surgery during COVID‐19 pandemic shows that robotic surgery can be safely performed for patients and healthcare workers. Despite our results we recommend elective surgery only for verified COVID‐19 negative patients.
Cleaning house before hosting new guests: A political path dependence model of political connection adaptation in the aftermath of anticorruption shocks
Authors: Jiang Han , Jia Nan , Bai Tao , Bruton Garry D. 
Published: May 2021

AbstractResearch SummaryWe develop a political path dependence model that integrates the network embeddedness perspective and the literature on corporate political strategy to understand how firms adapt their political connections when anticorruption efforts lead to the turnover of government officials. We posit that although firms that have close associations with ousted corrupt officials can benefit from both removing existing political connections (“cleaning house”) and developing new connections with their successors (“hosting new guests”), political path dependence enables firms to do the former but constrains them from doing the latter. These effects are magnified when firms are highly dependent on the government, and when the ousted corrupt officials have great political power. Evidence from anticorruption campaigns in China between 2012 and 2018 lends support for our theoretical predictions.Managerial SummaryIt is common for firms to strive to stay connected with government officials. Of interest is, when political power shifts, can firms “update” their connections by severing ties with politicians who fall out of power and building new ones? Our political path dependent model demonstrates that it may not be a symmetric process. After the downfall and replacements of public officials due to corruption indictments, firms that are more closely associated with ousted, corrupt officials will indeed be more motivated and able to remove existing connections. However, the successors of ousted officials will more likely distance themselves from these firms, thereby undermining the firms' abilities to build new connections with them. Empirical evidence from anticorruption campaigns in China between 2012 and 2018 supports our predictions.
Hierarchically Assembling CoFe Prussian Blue Analogue Nanocubes on CoP Nanosheets as Highly Efficient Electrocatalysts for Overall Water Splitting
Authors: Quan Li , Li Shuohan , Zhao Zhanpeng , Liu Jianqiao , Ran Yue , Cui Jiayi , Lin Wei , Yu Xuelian , Wang Lin , Zhang Yihe , Ye Jinhua 
Published: May 2021

AbstractEfficient and durable electrocatalysts are highly desirable for overall water splitting. Herein, a facile strategy is demonstrated to rationally construct CoFe Prussian blue analogues (PBA)@CoP cube‐on‐sheet hierarchical structure by etching reaction with intermediated CoO to form PBA nanocubes. Benefitting from the heterostructured engineering, the as‐synthesized CoFe PBA@CoP presents remarkable electrocatalytic performance in 1.0 m KOH, only requiring overpotentials of 100 mV for hydrogen evolution reaction (HER) and 171 mV for oxygen evolution reaction (OER) to reach the 10 mA cm−2 current density with good stability. Extraordinarily enhanced electrocatalytic performance is ascribed to not only the rapid charge transfer of active species, but also the synergistic effect between each component to achieve tuned electronic structure and abundant electrocatalytic active sites. Especially, the assembled two‐electrode cell using CoFe PBA@CoP as both cathode and anode delivers the current densities of 10 mA cm−2 at a relatively low cell voltage of 1.542 V, outperforming most of low‐cost bifunctional electrocatalysts reported to date. The controllable and versatile strategy will open up an avenue to prepare hybrid films for advanced electrochemical energy storage and conversion.
Patterns of acute decompensation in hospitalized patients with cirrhosis and course of acute‐on‐chronic liver failure
Authors: Balcar Lorenz , Semmler Georg , Pomej Katharina , Simbrunner Benedikt , Bauer David , Hartl Lukas , Jachs Mathias , Paternostro Rafael , Bucsics Theresa , Pinter Matthias , Trauner Michael , Mandorfer Mattias , Reiberger Thomas , Scheiner Bernhard 
Published: May 2021

AbstractIntroductionRecently, based on data from the PREDICT study, the European Foundation for the Study of Chronic Liver Failure (EF‐CLIF) consortium proposed pathophysiological/prognostic groups in hospitalized patients with cirrhosis: stable decompensated cirrhosis (SDC), unstable decompensated cirrhosis (UDC), pre‐acute‐on‐chronic liver failure (pre‐ACLF), and ACLF. We evaluated the outcomes of these subgroups in a real‐life cohort of hospitalized patients with cirrhosis.MethodsPatients with cirrhosis developing first AD between 09/2010 and 12/2017 at the Vienna General Hospital were evaluated for this retrospective analysis.ResultsTwo hundred and ten patients with cirrhosis (aged 57.6 ± 11.8 years) including n = 45 (21.4%) SDC, n = 100 (47.6%) UDC, n = 28 (13.3%) pre‐ACLF, and n = 37 (17.6%) with ACLF were considered. The proposed AD subgroups discriminated between patients with favorable (1‐year mortality: SDC: 6.7% and UDC: 19.6%) and dismal prognosis (90‐day mortality: pre‐ACLF: 42.9%). Interestingly, systemic inflammation gradually increased (e.g., C‐reactive protein, SDC: 0.9 mg/dl, vs. UDC: 2.0 mg/dl vs. pre‐ACLF: 3.2 mg/dl, p < 0.001) while renal function was progressively deteriorating (creatinine levels, SDC: 0.8 mg/dl vs. UDC: 0.9 mg/dl vs. pre‐ACLF: 1.2 mg/dl, p < 0.001) across prognostic subgroups in patients with cirrhosis.DiscussionThe recently proposed pathophysiological/prognostic EF‐CLIF subgroups are also reproduceable in a real‐life cohort of cirrhotic patients. As ACLF is a common and important complication, patients at risk of pre‐ACLF at index AD should be evaluated and if disease proceeds, been treated early and aggressively to avoid excessive mortality.
Chiral massive news: null boundary symmetries in topologically massive gravity
Authors: Adami H. , Sheikh-Jabbari M.M. , Taghiloo V. , Yavartanoo H. , Zwikel C. 
Published: May 2021

Abstract
We study surface charges on a generic null boundary in three dimensional topological massive gravity (TMG). We construct the solution phase space which involves four independent functions over the two dimensional null boundary. One of these functions corresponds to the massive chiral propagating graviton mode of TMG. The other three correspond to three surface charges of the theory, two of which can always be made integrable, while the last one can become integrable only in the absence of the chiral massive graviton flux through the null boundary. As the null boundary symmetry algebra we obtain Heisenberg ⊕ Virasoro algebra with a central charge proportional to the gravitational Chern-Simons term of TMG. We also discuss that the flux of the chiral massive gravitons appears as the (Bondi) news through the null surface.
5d and 4d SCFTs: canonical singularities, trinions and S-dualities
Authors: Closset Cyril , Giacomelli Simone , Schäfer-Nameki Sakura , Wang Yi-Nan 
Published: May 2021

Abstract
Canonical threefold singularities in M-theory and Type IIB string theory give rise to superconformal field theories (SCFTs) in 5d and 4d, respectively. In this paper, we study canonical hypersurface singularities whose resolutions contain residual terminal singularities and/or 3-cycles. We focus on a certain class of ‘trinion’ singularities which exhibit these properties. In Type IIB, they give rise to 4d $$ \mathcal{N} $$
N
= 2 SCFTs that we call $$ {D}_p^b $$

D
p
b

(G)-trinions, which are marginal gaugings of three SCFTs with G flavor symmetry. In order to understand the 5d physics of these trinion singularities in M-theory, we reduce these 4d and 5d SCFTs to 3d $$ \mathcal{N} $$
N
= 4 theories, thus determining the electric and magnetic quivers (or, more generally, quiverines). In M-theory, residual terminal singularities give rise to free sectors of massless hypermultiplets, which often are discretely gauged. These free sectors appear as ‘ugly’ components of the magnetic quiver of the 5d SCFT. The 3-cycles in the crepant resolution also give rise to free hypermultiplets, but their physics is more subtle, and their presence renders the magnetic quiver ‘bad’. We propose a way to redeem the badness of these quivers using a class $$ \mathcal{S} $$
S
realization. We also discover new S-dualities between different $$ {D}_p^b $$

D
p
b

(G)-trinions. For instance, a certain E8 gauging of the E8 Minahan-Nemeschansky theory is S-dual to an E8-shaped Lagrangian quiver SCFT.
An experimental investigation on Inconel 718 interrupted cutting with ceramic solid end mills
Authors: Parenti Paolo , Puglielli Francesco , Goletti Massimo , Annoni Massimiliano , Monno Michele 
Published: May 2021

AbstractSolid ceramic end mills for machining heat resistant super alloys (HRSA) have the potential to generate higher material removal rates, up to one order of magnitude, with respect to standard carbide tools. The machining operations in aerospace industry, where large removals are required to obtain tiny and slender parts like turbine blades, is a cost-intensive task that can benefit of the adoption of ceramic solid end mills. However, these tools show a quite limited tool life, especially when used with interrupted tool engagement strategies. Moreover, they might induce heat-related problems in the workpiece material surface integrity. This paper investigates the cutting and the tool wear during milling Inconel 718 with solid ø12 mm cutting end tool made by SiAlON. The wear mechanisms are studied together with their effects on process signals as cutting forces and power, measured via external and CNC integrated sensors. The carried experimental campaign allowed to find out that tool clogging and edge chipping were the primary cutting phenomena leading the tool wear. Cutting strategy (downmilling or upmilling) produced different results in terms of tool wear sensitivity and process outputs whereas upmilling configuration showed the best results in terms of cutting signals stability and surface integrity. At the same time, cutting speed was found to increase the cutting power more in upmilling than downmilling cutting. The analysis of the forces and power demonstrated that the typical tool wear mechanisms can be traced by signal monitoring due to their high impact on cutting processes. This fact shows the good potential of signal monitoring for a better tool life evaluation.
On the group of unit-valued polynomial functions
Authors: Al-Maktry Amr Ali 
Published: May 2021

AbstractLet R be a finite commutative ring. The set $${{\mathcal{F}}}(R)$$

F
(
R
)

of polynomial functions on R is a finite commutative ring with pointwise operations. Its group of units $${{\mathcal{F}}}(R)^\times $$

F

(
R
)

×

is just the set of all unit-valued polynomial functions. We investigate polynomial permutations on $$R[x]/(x^2)=R[\alpha ]$$

R

[
x
]

/

(

x
2

)

=
R

[
α
]

, the ring of dual numbers over R, and show that the group $${\mathcal{P}}_{R}(R[\alpha ])$$

P
R

(
R

[
α
]

)

, consisting of those polynomial permutations of $$R[\alpha ]$$

R
[
α
]

represented by polynomials in R[x], is embedded in a semidirect product of $${{\mathcal{F}}}(R)^\times $$

F

(
R
)

×

by the group $${\mathcal{P}}(R)$$

P
(
R
)

of polynomial permutations on R. In particular, when $$R={\mathbb{F}}_q$$

R
=

F
q

, we prove that $${\mathcal{P}}_{{\mathbb{F}}_q}({\mathbb{F}}_q[\alpha ])\cong {\mathcal{P}}({\mathbb{F}}_q) \ltimes _\theta {{\mathcal{F}}}({\mathbb{F}}_q)^\times $$

P

F
q

(

F
q

[
α
]

)

≅
P

(

F
q

)

⋉
θ

F

(

F
q

)

×

. Furthermore, we count unit-valued polynomial functions on the ring of integers modulo $${p^n}$$

p
n

and obtain canonical representations for these functions.
Severe homocysteinemia in two givosiran-treated porphyria patients: is free heme deficiency the culprit?
Authors: Petrides Petro E. , Klein Michael , Schuhmann Elfriede , Torkler Heike , Molitor Brigitte , Loehr Christian , Obermeier Zahra , Beykirch Maria K. 
Published: May 2021

AbstractGivosiran is a novel approach to treat patients with acute intermittent porphyrias (AIP) by silencing of ∂-ALA-synthase 1, the first enzyme of heme biosynthesis in the liver. We included two patients in the Envision study who responded clinically well to this treatment. However, in both patients, therapy had to be discontinued because of severe adverse effects: One patient (A) developed local injection reactions which continued to spread all over her body with increasing number of injections and eventually caused a severe systemic allergic reaction. Patient B was hospitalized because of a fulminant pancreatitis. Searching for possible causes, we also measured the patients plasma homocysteine (Hcy) levels in fluoride-containing collection tubes: by LC–MS/MS unexpectedly, plasma Hcy levels were 100 and 200 in patient A and between 100 and 400 μmol/l in patient B. Searching for germline mutations in 10 genes that are relevant for homocysteine metabolism only revealed hetero- and homozygous polymorphisms in the MTHFR gene. Alternatively, an acquired inhibition of cystathionine-beta-synthase which is important for homocysteine metabolism could explain the plasma homocysteine increase. This enzyme is heme-dependent: when we gave heme arginate to our patients, Hcy levels rapidly dropped. Hence, we conclude that inhibition of ∂-ALA-synthase 1 by givosiran causes a drop of free heme in the hepatocyte and therefore the excessive increase of plasma homocysteine. Hyperhomocysteinemia may contribute to the adverse effects seen in givosiran-treated patients which may be due to protein-N-homocysteinylation.
A Family of Semitoric Systems with Four Focus–Focus Singularities and Two Double Pinched Tori
Authors: De Meulenaere Annelies , Hohloch Sonja 
Published: May 2021

AbstractWe construct a one-parameter family $$F_t=(J, H_t)_{0 \le t \le 1}$$

F
t

=

(
J
,

H
t

)

0
≤
t
≤
1

of integrable systems on a compact 4-dimensional symplectic manifold $$(M, \omega )$$

(
M
,
ω
)

that changes smoothly from a toric system $$F_0$$

F
0

with eight elliptic–elliptic singular points via toric type systems to a semitoric system $$F_t$$

F
t

for $$ t^-< t < t^+$$

t
-

<
t
<

t
+

. These semitoric systems $$F_t$$

F
t

have precisely four elliptic–elliptic and four focus–focus singular points. Moreover, at $$t= \frac{1}{2}$$

t
=

1
2

, the system has precisely two focus–focus fibres each of which contains exactly two focus–focus points, giving these fibres the shape of double pinched tori. We exemplarily parametrise one of these fibres explicitly.
Variation of the cochlear anatomy and cochlea duct length: analysis with a new tablet-based software
Authors: Spiegel Jennifer L. , Polterauer Daniel , Hempel John-Martin , Canis Martin , Spiro Judith E. , Müller Joachim 
Published: May 2021

AbstractPurposeIn cochlear implantation, thorough preoperative planning together with measurement of the cochlear duct length (CDL) assists in choosing the correct electrode length. For measuring the CDL, different techniques have been introduced in the past century along with the then available technology. A tablet-based software offers an easy and intuitive way to visualize and analyze the anatomy of the temporal bone, its proportions and measure the CDL. Therefore, we investigated the calculation technique of the CDL via a tablet-based software on our own cohort retrospectively.MethodsOne hundred and eight preoperative computed tomography scans of the temporal bone (slice thickness < 0.7 mm) of already implanted FLEX28™ and FLEXSOFT™ patients were found eligible for analysis with the OTOPLAN software. Measurements were performed by two trained investigators independently. CDL, angular insertion depth (AID), and cochlear coverage were calculated and compared between groups of electrode types, sex, sides, and age.ResultsMean CDL was 36.2 ± 1.8 mm with significant differences between sex (female: 35.8 ± 0.3 mm; male: 36.5 ± 0.2 mm;p = 0.037), but none concerning side or age. Differences in mean AID (FLEX28: 525.4 ± 46.4°; FLEXSOFT: 615.4 ± 47.6°), and cochlear coverage (FLEX28: 63.9 ± 5.6%; FLEXSOFT: 75.8 ± 4.3%) were significant (p < 0.001).ConclusionA broad range of CDL was observed with significant larger values in male, but no significant differences concerning side or age. Almost every cochlea was measured longer than 31.0 mm. Preoperative assessment aids in prevention of complications (incomplete insertion, kinking, tipfoldover), attempt of atraumatic insertion, and addressing individual necessities (hearing preservation, cochlear malformation). The preferred AID of 720° (two turns of the cochlea) was never reached, opening the discussion for the requirement of longer CI-electrodes versus a debatable audiological benefit for the patient in his/her everyday life.
Impact of different work organizational models on gender differences in exposure to psychosocial and ergonomic hazards at work and in mental and physical health
Authors: Migliore Maria Cristina , Ricceri Fulvio , Lazzarato Fulvio , d’Errico Angelo 
Published: May 2021

AbstractPurposeTo examine differences between genders in exposure to psychosocial and ergonomic factors at work and in work-related health, according to different work organization models.MethodsThe study population included a sample of 9749 (women: 37.1%) and 10,374 (women: 39.9%) employees who participated in the 2010 and 2015 European Working Conditions Surveys, respectively. Multiple Correspondence Analysis was applied to work characteristics reported by workers to estimate principal components, followed by Hierarchical Clustering on principal components to identify clusters of work organization models. Gender differences in exposure to work hazards and health outcomes were assessed through Poisson robust regression. Differences of PRs across organizational models were tested through interaction between gender and type of work organization.ResultsThree organizational models were identified in 2010, including lean production, Tayloristic production, and a “reflexive production” model, whereas in 2015, a “simple” or traditional model was also found. In 2010, women employed in companies adopting the Tayloristic or the lean production models were more likely than men to be exposed to unfavourable psychosocial and physical work factors, and to report musculoskeletal pain, compared to those belonging to reflexive production. In 2015, a significantly higher female/male ratio persisted in lean production for exposure to high job strain and for carrying/moving heavy loads, whereas gender differences in Tayloristic and traditional production were quite similar to those of reflexive production.ConclusionsOur results suggest that employment in workplaces characterized by lower monotony, repetitiveness, and production constraints may contribute to reduce exposure to job strain among working women.
Angiogenesis and chemotherapy resistance: optimizing chemotherapy scheduling using mathematical modeling
Authors: Bodzioch Mariusz , Bajger Piotr , Foryś Urszula 
Published: May 2021

AbstractChemotherapy remains a widely used cancer treatment. Acquired drug resistance may greatly reduce the efficacy of treatment and means to overcome it are a topic of active discussion among researchers. One of the proposed solutions is to shift the therapeutic paradigm from complete eradication of cancer to maintenance, i.e., to treat it as a chronic disease. A concept of metronomic therapy (low chemotherapy doses applied continuously) emerged in early 2000s and was henceforth shown to offer a number of benefits, including targeting endothelial cells and reducing acquired drug resistance. Using mathematical modeling and optimal control techniques, we investigate the hypothesis that lower doses of chemotherapy are beneficial for patients. Our analysis of a mathematical model of tumor growth under angiogenic signaling proposed by Hahnfeldt et al. adapted to heterogeneous tumors treated by combined anti-angiogenic agent and chemotherapy offers insights into the effects of metronomic therapy. Firstly, assuming constant long-term drug delivery, the model suggests that the longest survival time is achieved for intermediate drug doses. Secondly, by formalizing the notion of the therapeutic target being maintenance rather than eradication, we show that in the short term, optimal chemotherapy scheduling consists mainly of a drug applied at a low dose. In conclusion, we suggest that metronomic therapy is an attractive alternative to maximum tolerated dose therapies to be investigated in experimental settings and clinical trials.