bluuebunny/crossref_metadata_2025_split huggingface dataset:
Dihydropyrimidines Emerge as Promising Dual‐Acting Inhibitors Targeting Acetylcholinesterase and Monoamine Oxidases for Alzheimer's and Other Neurological Disorders
Authors: Saleem Khan Maria , Islam Talha , Farooq Muhammad Umer , al‐Arifa Najiya , Jalil Saquib , Ali Khan Imtiaz , Hameed Abdul , Asari Asnuzilawati , Rehman Atta ur , Iqbal Jamshed , al‐Rashida Mariya 
Published: February 2025

AbstractThe pathogenesis of Alzheimer's disease (AD) is multifaceted, and more than one factor is deemed responsible for its genesis and progression. Hence, the multi‐target approach seems plausible en route to the development of therapeutics targeting Alzheimer's in particular, and other neurological disorders, in general. Among the major factors responsible for AD are acetylcholinesterase and monoamine oxidase enzymes. Acetylcholine is an important neurotransmitter that plays a role in processing memory and learning. Deficiency of this neurotransmitter is observed in patients of AD; this is largely attributed to increased expression of the enzyme acetylcholinesterase (AChE) that is responsible for breakdown of acetylcholine neurotransmitter. Hence, inhibitors of AChE can prevent excessive breakdown of this important neurotransmitter. Monoamine oxidases in the brain are responsible for hydrolyzing important neurotransmitters such as serotonin and dopamine (among others), abnormally rapid hydrolysis of these neurotransmitters via over‐activation of monoamine oxidases is associated with several neurodegenerative disorders including anxiety and Parkinson's disease. Herein, we synthesized a focused library of 1,4‐dihydropyrimidines (40 compounds) using a deep eutectic solvent and evaluated their potential to inhibit cholinesterase (AChE and BChE) and monoamine oxidase (MAO A and MAO B) enzymes. Several selective and highly potent inhibitors were identified; in silico molecular docking and molecular dynamics simulation studies helped to rationalize the binding site interactions and establish useful structure activity relationship. In silico ADME prediction data identified a few inhibitors that could cross the blood‐brain barrier, one such compound was selected for the in vivo estimation of LD50 value and toxicity studies using mice, skin allergy test was also carried out. All in vivo tests and LD50 data established the safety profile of the compound. The results are encouraging enough to further pursue the development of DHPMs as promising multi‐target directed ligands against neurodegenerative disorders.
Metal/Peroxide‐Free [5 + 1] Cyclization of 2‐Vinylanilines with tert‐Butyl Nitrite to Access Diverse Cinnolines
Authors: Liu Huaqing , Yan Qinqin , Liu Zexuan , Zeng Yanzhao , Li Lijun , Li Zejiang 
Published: February 2025

AbstractAn efficient metal/peroxide‐free [5 + 1] cyclization of 2‐vinylanilines with TBN was realized to access various cinnolines with high yields. In addition, benzo[e]pyrrolo[2,1‐c][1,2,4]triazines could also be obtained by using 2‐(1H‐pyrrol‐1‐yl)anilines as the raw materials. This cascade system selected common/low‐cost tert‐butyl nitrite as the N1 source, which performed broad substrate scopes/simple operation/mild conditions/available scaled up to 1 mmol.
Mask‐Free Direct Printing of Highly Customizable, Conformable, Robust, and Recyclable Microelectrodes for Advanced Curvy Electronics
Authors: Kong Xiangyi , Liu Youyou , Wang Jianping , Yue Liancong , Gong Min , Lin Xiang , Gao Fengxian , Zhang Liang , Wang Dongrui 
Published: February 2025

AbstractHighly conformal and mechanically robust curvy electronics that seamlessly adapt to sophisticated and unpredictable 3D geometries provide breakthrough solutions in advanced fields such as health monitoring, wireless energy transmission, and human‐computer interface. Nevertheless, existing material choices along with manufacturing techniques substantially impede these electronics from achieving their full potential. This study presents a mask‐free and straightforward direct writing and transfer (DW&T) technique that employs a polytetrafluoroethylene film as a temporary substrate, utilizing the phase transition of printed electrodes between hydrogel and dry states to enable cost‐effective fabrication of conformally adhering conductive microelectrode patterns on nearly all 3D surfaces. The resultant microelectrodes demonstrate extensively adjustable feature dimensions (linewidth 50–400 µm; height 0.07–2.3 µm; pitch 20 µm in minimum) and possess distinct electrical and optical characteristics, in addition to exhibiting significant stability under severe bending and stretching strains and recyclability. To demonstrate the capabilities of the DW&T, imperceptible and customizable substrate‐free electronic skin (e‐skin) on human skin is developed. The e‐skin maintains ultraconformal and seamless contact with the skin, does not impede the natural sensations and physiological changes of its hosts, and achieves high‐fidelity recording of diverse electrophysiological signals.
Formation of CdTeS Prenucleation Clusters at Elevated Temperatures and Transformation to Magic‐Size Clusters at Room Temperature
Authors: Yu Jiali , Wang Zhe , Wang Shasha , Zhang Chunchun , Luan Chaoran , Sapelkin Andrei , Chen Xiaoqin , Yu Kui 
Published: February 2025

AbstractThe synthesis of colloidal semiconductor magic‐size clusters (MSCs) of ternary II‐VI metal chalcogenide (ME1E2) remains challenging. Using CdTeS as a model system, it is shown that CdTeS MSC‐381 (displaying sharp optical absorption peaking at 381 nm) develops at room temperature from prenucleation‐stage samples of reactions of Cd(OAc)2/OLA (cadmium acetate in oleylamine), TeTOP (tri‐n‐octylphosphine telluride), and S (sulfur). It is proposed that the three precursors experience physical co‐self‐assembly followed by the formation of Te−Cd−S covalent bonds inside each assembly. Chemical self‐assembly results in the occurrence of prenucleation clusters (PNCs), which are the precursor compound (PC‐381) of MSC‐381. High feed concentrations and Cd‐to‐E molar ratios promote the co‐self‐assembly, which is participated more by the precursor molecule of Te than by that of S. With compelling evidence for the formation of ternary PNCs at elevated temperatures and for the PC‐to‐MSC transformation at room temperature, these findings suggest that chemical self‐assembly occurs generally in reactions.
Survey of attitudes toward clinical research among Japanese traditional (Kampo) medicine specialists and certified doctors affiliated with the Japan Society for Oriental Medicine
Authors: Nogami Tatsuya , Uneda Kazushi , Yoshino Tetsuhiro , Ito Hidenori , Imoto Seiya , Tahara Eiichi , Sunagawa Masataka , Takayama Shin , Yakubo Shuji , Mitani Kazuo 
Published: February 2025

AbstractAimThis study aims to assess the motivation, capability, and working environment of Japanese traditional (Kampo) medicine (JTM) specialists and certified physicians affiliated with the Japan Society for Oriental Medicine regarding clinical research. Their awareness and perception of COVID‐19 studies and their interest in clinical research based on traditional JTM diagnostic concepts are explored.MethodsAn online survey was conducted between May 20 and June 30, 2024, using Google Forms, targeting 2146 Japan Society for Oriental Medicine‐certified JTM specialists and physicians. The survey covered their awareness of and participation in COVID‐19 research, barriers to research, and educational needs for clinical researcher training.ResultsIn total, 570 participants (26.6%) responded, 44.1% of whom had more than 15 years of certification experience. Approximately 50% were unaware of the COVID‐19 studies, and participation rates were low. The most common barriers to conducting clinical research included lack of time (58.1%), funding (54.8%), and research personnel (51.1%). In terms of educational needs, 74.3% of respondents expressed a need for statistical analysis training, and nearly 90% felt clinical research education should occur within 10 years of obtaining their medical licenses.ConclusionThis study reveals gaps in awareness and participation in clinical research among JTM specialists. Many respondents expressed willingness to engage in research; however, barriers such as limited time, funding, and personnel remain critical challenges. Furthermore, the need for specialized educational programs was strongly emphasized. Addressing these issues is essential for promoting clinical research in JTM.
Effective treatment of late‐onset urinary incontinence with a slow‐release GnRH analogue implant in an entire male dog with bilateral ectopic ureters
Authors: Hanson Jeanette M. , Ball Elisabeth , Gombert Alexis 
Published: February 2025

AbstractA 2‐year‐old, mixed breed dog of predominantly labrador retriever genotype and phenotype, entire male presented with a 6‐month history of urinary incontinence. The dog had a continuous urine dripping without straining. The urine bladder was small. No neurological abnormalities were found. Haematology, biochemistry, urinalysis and plain abdominal radiographs, including the urethra, were without remarkable findings. On abdominal ultrasonography, caudally displaced ureters were detected. Contrast‐enhanced computed tomography subsequently confirmed bilateral ectopic ureters entering the prostatic urethra. As the dog had remained urinary continent until the onset of sexual maturity, it was hypothesised that the dog would regain continence if it returned to a sexually inactive state. A slow‐release gonadotropin‐releasing hormone analogue (deslorelin) implant was administered subcutaneously in the neck. The incontinence started to decrease after 4 weeks, and the dog was completely continent after 6–7 weeks. Continence was maintained with repeat dosing of gonadotropin‐releasing hormone implants.
A simple experiment to trace stemflow infiltration: Advantages and challenges of using stable isotopes of hydrogen and oxygen and electrical resistivity tomography
Authors: Zuecco G. , Marchina C. , Censini M. , Todini‐Zicavo D. , Cassiani G. , Borga M. 
Published: February 2025

AbstractStemflow is a key process in forested catchments due to its control on soil water content and nutrients’ transport. However, there are still few studies focusing on stemflow infiltration and relying on direct observations that are minimally invasive and repeatable. In this study, we exploited the usefulness of stable isotopes of hydrogen and oxygen, as well as of time‐lapse electrical resistivity tomography (ERT) to investigate water fluxes in the soil. Specifically, we aimed to examine the effectiveness of both isotopes and ERT to trace stemflow infiltration for a beech tree in a steep hillslope in the Italian pre‐Alps, to quantify stemflow infiltration area based on the two methodologies and to provide recommendations for future research. Results showed that both approaches identified an infiltration along the maximum slope gradient with most of the water staying in the upper 45 cm of soil. The analysis of electrical resistivity variations enabled to evaluate the temporal dynamics of stemflow infiltration and to estimate an average stemflow infiltration area of 0.64 m2, which was larger than values found by previous studies based on dye tracers. This high estimate may be due to multiple factors, from the soil conditions to methodological uncertainties. Conversely, the estimation of stemflow infiltration area based on isotopes was affected by the sampling area. Hence, future research based on isotopic tracers needs to consider methods providing a direct field evidence of stemflow infiltration (e.g., dye tracers) or a quick inspection of raw data (e.g., ERT) to inform the sampling design.
Reducing Wind Energy Forecast Error With a Hybrid Ensemble Prediction Method
Authors: Rutherford Justin , Nyhan Marguerite , Gavin Leahy Paul 
Published: February 2025

ABSTRACTWhen wind energy is traded in ex‐ante time frames for Day‐Ahead electricity markets, accurate wind forecasts are needed to secure positions up to 36 h after the market gate closes to bidders. Wind energy is traded in discrete quantities; however, it is generated from an intermittent and variable resource. Deterministic forecasts are preferred for energy trading as they are compatible with providing a defined forecast quantity. However, deterministic forecasts cannot capture the stochastic nature of the underlying power source and are therefore suboptimal. Ensemble‐based forecasts have the potential to reduce forecast error by accounting for uncertainties not captured in deterministic models. However, ensemble forecasts are not always available at wind turbine hub heights. Therefore, a method is needed to apply ensemble information at turbine hub heights for energy forecasting purposes. This paper presents a novel machine learning‐based method that translates the perturbations from a localised Numerical Weather Prediction model's 10‐m wind speed output to an ensemble energy forecast at 100 m. The extrapolated ensemble‐based forecast has improved the forecast accuracy by up to 9% when compared to the deterministic output, in addition to providing useful information on the forecast uncertainty. The findings have important implications for future energy trading, transmission system operation and meteorological forecasting.
PROBs and perverse sheaves I: symmetric products
Authors: Kapranov Mikhail , Schechtman Vadim 
Published: February 2025

Abstract
Algebraic structures involving both multiplications and comultiplications (such as, e.g., bialgebras or Hopf algebras) can be encoded using PROPs (categories with PROducts and Permutations) of Adams and MacLane. To encode such structures on objects of a braided monoidal category, we need PROBs (braided analogs of PROPs). Colored PROBs correspond to multi-sorted structures. In particular, we have a colored PROB

$$\mathfrak {B}$$

B

governing

$$\mathbb {Z}_{\ge 0}$$

Z

≥
0

-graded bialgebras in braided categories. As a category,

$$\mathfrak {B}$$

B

splits into blocks

$$\mathfrak {B}_n$$

B
n

according to the grading. We relate

$$\mathfrak {B}_n$$

B
n

with the category

$$\mathfrak {P}_n$$

P
n

of perverse sheaves on the symmetric product

$${\operatorname {Sym}}^n(\mathbb {C})$$

Sym

n

(
C
)

smooth with respect to the natural stratification by multiplicities. More precisely, we show that

$$\mathfrak {P}_n$$

P
n

is equivalent to the category of functors

$$\mathfrak {B}_n\rightarrow \operatorname {Vect}$$

B
n

→
Vect

. This gives a natural quiver description of

$$\mathfrak {P}_n$$

P
n

.
Generalised killing spinors on three-dimensional Lie groups
Authors: Artacho Diego 
Published: February 2025

Abstract
We present a complete classification of invariant generalised Killing spinors on three-dimensional Lie groups. We show that, in this context, the existence of a non-trivial invariant generalised Killing spinor implies that all invariant spinors are generalised Killing with the same endomorphism. Notably, this classification is independent of the choice of left-invariant metric. To illustrate the computational methods underlying this classification, we also provide the first known examples of homogeneous manifolds admitting invariant generalised Killing spinors with n distinct eigenvalues for each

$$n > 4$$

n
>
4

.
Expression of synaptic proteins and development of dendritic spines in fetal and postnatal neocortex of the pig, the European wild boar Sus scrofa
Authors: Sobierajski Eric , Czubay Katrin , Schmidt Marc-André R. , Wiedenski Sebastian , Rettschlag Sarah , Beemelmans Christa , Beemelmans Christoph , Wahle Petra 
Published: February 2025

Abstract
Synapse formation is a critical step in neuronal development. Current knowledge is largely based on altricial rodents where synapse formation and maturation proceed largely postnatally. In precocially born mammals such as guinea pig presynapse and spine formation start well before birth. Here, we analysed the developmental expression of proteins associated with synapse formation and maturation together with the development of basal dendritic spines of pyramidal neurons of visual and somatosensory cortex of the pig, an emerging translational model for human neurodegenerative disorders. A total of 23 selected proteins was quantified with Western blots. Most were detectable from midgestation embryonal day (E) 65 onwards. About half reached the expression level seen at postnatal day (P) 90 pig already two weeks before birth (gestation 114 days) in somatosensory, albeit not yet in visual cortex. For instance, major molecular components of synaptic plasticity such as GluN2B, CamKIIα, α-actinin-2, synaptopodin and T286 phosphorylated CamKIIα were expressed at E100 in somatosensory cortex. Dendritic spine type quantification with DiI-labeled material revealed an increase of total dendritic protrusions from E70 onwards. The increase was steepest in somatosensory cortex which had, at E110, a proportion of mushroom spines equal to the proportion present at P90. Together, matching the ungulate life history, a rapid development of functional synaptic connectivity in prenatal somatosensory cortex serves the somatomotor abilities essentially required by the newborn nest-fledgling.
Vom Einzelkorn über den Fluss zum Stauraum – Beitrag der numerischen Modellierung zu Sedimentforschung und -management
Authors: Tritthart Michael , Habersack Helmut , Hauer Christoph 
Published: February 2025

Zusammenfassung
Der Artikel beleuchtet die Rolle der numerischen Modellierung im Rahmen der Arbeiten des CD-Labors „Sedimentforschung und -management“. Es werden numerische Modelle und deren Anwendung zur Untersuchung des Sedimenttransports, der Morphodynamik und der ökologischen Funktionen von Gewässern vorgestellt. Die Anwendung der Modellwerkzeuge zur Grundlagenforschung ermöglicht die Entschlüsselung der Mechanismen des Bewegungsbeginns von Sedimentkörnern und des Transports von Schwebstoffen im Wasserkörper. Die angewandte Forschung zeigt, dass sowohl Buhnen als auch Kiesinseln signifikante Auswirkungen auf die Hydrodynamik und Morphodynamik von Fließgewässern haben. Buhnen tragen zur Erreichung eines morphologischen Gleichgewichts und zur Sohlstabilisierung bei, während Kiesinseln multifunktionale Vorteile bieten, darunter die Verbesserung der Habitatverfügbarkeit und die Regulierung des Niederwassers. Die Ergebnisse unterstreichen darüber hinaus die Bedeutung der Wahl geeigneter Modellmaßstäbe, um Skaleneffekte zu minimieren und die Genauigkeit der Modellierungen zu erhöhen. Die gewonnenen Erkenntnisse tragen zu einer breiteren Wissensbasis von ökologischen Wasserbaumaßnahmen in Fließgewässern und Stauräumen bei und können bei zukünftigen Planungen berücksichtigt werden.
Effects of GDF6 on active protein synthesis by cells of degenerated intervertebral disc
Authors: Tam Vivian , Chopra Neha , Sima Stone , Chen Peikai , Sharma Rakesh , Chan Danny , Diwan Ashish 
Published: February 2025

Abstract

Introduction
Intervertebral disc degeneration (IVD) is a leading cause of low back pain, a prevalent musculoskeletal condition. IVD degeneration is characterized by the degradation of nucleus pulposus (NP), annulus fibrosus (AF), and cartilage endplates (EP). Growth Differentiation Factor 6 (GDF6), part of the bone morphogenetic protein family, has demonstrated potential in maintaining disc integrity. However, its precise role in cellular protein synthesis during IVD degeneration remains unclear.

Methods
This study employed Stable Isotope Labeling by Amino Acids in Cell Culture (SILAC) to investigate the effects of GDF6 on protein synthesis in NP, AF, and EP cells isolated from degenerated human IVDs. Cells were cultured in SILAC media with and without GDF6 treatment. The proteomic profiles were analyzed via mass spectrometry, comparing newly synthesized “heavy” proteins with pre-existing “light” proteins.

Results
GDF6 treatment altered protein synthesis in degenerated IVD cells. In NP cells, GDF6 reduced the synthesis of matrisome proteins, including collagens and proteoglycans, while promoting proteins associated with ECM stability, such as LOX, PCOLCE and HAPLN1/3. AF cells demonstrated an upregulation of ECM-stabilizing proteins like POSTN and FMOD. EP cells showed minimal changes, but GDF6 enhanced the synthesis of collagen type II, suggesting improved ECM integrity. Secretome analysis revealed that GDF6 modulated extracellular signalling by promoting ECM-stabilizing proteins and reducing inflammatory markers.

Conclusion
GDF6 exerts compartment-specific effects on protein synthesis in degenerated IVDs, promoting ECM stability, reducing fibrosis, and potentially preserving hydration. These findings support the potential of GDF6 as a therapeutic agent in treating IVD degeneration, particularly in NP-targeted therapies. Future studies should optimize GDF6 dosing and delivery to maximize its regenerative potential.
Three weight Koopman semigroups on Lebesgue spaces
Authors: Miana Pedro J. , Poblete Verónica 
Published: February 2025

Abstract
In this paper, we consider three different semiflows

$$(\phi _t)_{t\ge 0}, \, (\psi _t)_{t\ge 0}$$

(

ϕ
t

)

t
≥
0

,

(

ψ
t

)

t
≥
0

and

$$(\varphi _t)_{t\ge 0}$$

(

φ
t

)

t
≥
0

on the real half-line given by

$$\begin{aligned} \phi _t(r):=e^{-t}r+1-e^{-t},\ \psi _t(r):= \frac{e^t r}{1+r(e^t-1)}, \ \varphi _t(r):= \frac{(1 + e^t)r -1 + e^t}{(-1 + e^t) r + 1 + e^t}, \end{aligned}$$

ϕ
t

(
r
)

:
=

e

-
t

r
+
1
-

e

-
t

,

ψ
t

(
r
)

:
=

e
t

r

1
+
r
(

e
t

-
1
)

,

φ
t

(
r
)

:
=

(
1
+

e
t

)

r
-
1
+

e
t

(
-
1
+

e
t

)

r
+
1
+

e
t

,

for

$$r, t\ge 0$$

r
,
t
≥
0

. These semiflows induce three weight Koopman semigroups,

$$(T^\gamma _{t, p})_{t>0},$$

(

T

t
,
p

γ

)

t
>
0

,

$$ \, (S^\gamma _{t,p})_{t>0}$$

(

S

t
,
p

γ

)

t
>
0

and

$$(R^\gamma _{t,p})_{t>0}$$

(

R

t
,
p

γ

)

t
>
0

on the fractional Lebesgue spaces

$${\mathcal {T}}_p^{(\alpha )}(t^\alpha )$$

T
p

(
α
)

(

t
α

)

, closed subspaces of

$$L^p({\mathbb {R}}^+)$$

L
p

(

R

+

)

for some

$$\alpha $$

α

and

$$\gamma \ge 0$$

γ
≥
0

. We describe spectrum sets, point spectrums and resolvent operators of their infinitesimal generators. Three Cesàro-like operators, defined using the Chen fractional integral,

$$\begin{aligned} {\mathcal {C}}_{\mu , \nu }f(r):= & \frac{1}{\vert r-1\vert ^{\mu +\nu -1}} \int _{\Gamma _{1,r}}\vert s-1\vert ^{\mu -1} \vert r-s\vert ^{\nu -1} f(s)ds, \quad r>0,\\ {{\mathfrak {C}}}_{\mu , \nu }^\gamma f(r):= & \frac{r^\mu }{\vert r-1\vert ^{\mu +\nu +\gamma -1}} \int _{\Gamma _{1,r}}\frac{\vert s-1\vert ^{\mu +\gamma -1}}{s^{\mu +\nu }} \vert r-s\vert ^{\nu -1} f(s)ds,\ r>0, \\ \textbf{C}^\gamma _{\mu , \nu }f(r):= & \displaystyle 2^\nu \frac{|r + 1|^{\mu - \gamma }}{\ |r-1|^{\mu + \nu - 1}} \int _{\Gamma _{1,r}} \frac{|s - 1|^{\mu - 1}}{\ |s + 1|^{\mu + \nu - \gamma } } \, | r - s|^{\nu - 1} f(s) ds, \ r>0, \\ \end{aligned}$$

C

μ
,
ν

f

(
r
)

:
=

1

|
r
-
1
|

μ
+
ν
-
1

∫

Γ

1
,
r

|
s
-
1
|

μ
-
1

|
r
-
s
|

ν
-
1

f

(
s
)

d
s
,

r
>
0
,

C

μ
,
ν

γ

f

(
r
)

:
=

r
μ

|
r
-
1
|

μ
+
ν
+
γ
-
1

∫

Γ

1
,
r

|
s
-
1
|

μ
+
γ
-
1

s

μ
+
ν

|
r
-
s
|

ν
-
1

f

(
s
)

d
s
,

r
>
0
,

C

μ
,
ν

γ

f

(
r
)

:
=

2
ν

|
r
+
1
|

μ
-
γ

|
r
-
1
|

μ
+
ν
-
1

∫

Γ

1
,
r

|
s
-
1
|

μ
-
1

|
s
+
1
|

μ
+
ν
-
γ

|
r
-
s
|

ν
-
1

f

(
s
)

d
s
,

r
>
0
,

(for certain

$$\mu , \nu , \gamma \in {\mathbb {R}}$$

μ
,
ν
,
γ
∈
R

and

$$\Gamma _{1,r}:=(1,r)$$

Γ

1
,
r

:
=

(
1
,
r
)

when

$$r>1$$

r
>
1

and

$$\Gamma _{1,r}:=(r,1)$$

Γ

1
,
r

:
=

(
r
,
1
)

in the case

$$0<r<1$$

0
<
r
<
1

) are subordinated to these

$$C_0$$

C
0

-semigroups. These representations allow to obtain their norms and spectrum sets.