bluuebunny/crossref_metadata_2025_split huggingface dataset:
Analysis of development of Norwegian household solar energy ecosystem
Authors: Meng Qian , Yin Huilin , Johannessen Marius Rohde , Berntzen Lasse 
Published: July 2023

Abstract
Solar energy for self-production is one of the tools for improving energy efficiency in buildings to achieve EU’s climate and energy goals, while solar energy has a very small share and is increasing slowly in Norway. This paper analyses the four main reasons why solar power has an insignificant role: hydropower with much lower cost, low energy output in winter due to less sunlight, unclear personal willingness to adopt solar photovoltaics (PV) on their houses and current fixed PV panels with low energy efficiency. Based on this analysis, we propose to use a tilting PV system for the current buildings to improve the efficiency and performance of utilization of the solar radiation. In three cities Oslo, Stavanger and Trondheim, economic return for the investment in PV panels is also calculated with payback period (PBP) analysis based on the electricity prices in 2022. It shows that it is profitable with the payback period of over 10 years while the solar panels’ life span is over 30 years. Further research questions are also discussed.
Fatigue life analysis of offshore wind turbine tower under combined action of wind and wave
Authors: Xie Ya , Dai Bing , Huang Zhonghua 
Published: July 2023

Abstract
In order to obtain the fatigue life of an 8 MW offshore wind turbine tower, the fatigue damage characteristics of tower under combined action of wind and wave were analyzed. The calculation method of fatigue damage degree of the tower under different working conditions in unit cycle time is given. Based on the linear extension theory of fatigue damage, the annual fatigue damage degree of the tower under different working conditions was calculated, and the fatigue life of the tower was obtained. The calculation results show that the fatigue life of the tower is 31.2 years when the ideal S-N curve is adopted, which is longer than the design life of 25 years. The influences of average stress, roughness and structure size on S-N curve are analyzed. When Goodman method is selected for average stress correction, roughness coefficient is 0.473, and dimension correction coefficient is 0.639, the fatigue life of the tower is 26.7 years, decreasing by 14%. The fatigue life of the tower under different roughness is calculated. The calculated results show that the fatigue life of the tower decreases with the decrease of the roughness coefficient. When the roughness coefficient is 0.287, the fatigue life of the tower is about 25 years.
Using network pharmacology to fabricate crosslinked hyaluronan–chondroitin sulphate-resveratrol composite hydrogels for cartilage regeneration
Authors: Zhang Yushen , Wang Lei , Shi Yubo , Cheng Debin , Zhu Dongze , Mi Zhenzhou , Dang Jingyi , Zhang Zhao , Liu Xincheng , Fan Hongbin 
Published: July 2023

Abstract
Cartilage tissue engineering provides a new approach for the treatment of cartilage damage. The combination of drug system with a tissue scaffold could be highly beneficial. Resveratrol (RES) is a potent anti-inflammatory agent, but its target genes and molecular mechanism of cartilage repair remain to be further studied. We used systems biology and network pharmacology methods to explore the mechanism of RES for chondrocyte and macrophages. Meanwhile, crosslinked hyaluronan–chondroitin sulphate-RES hydrogels (cHA-CS-RES) were constructed based on the target prediction results. By in vitro and in vivo experiments, we investigated its anti-inflammatory and pro-chondrogenesis. The results showed there were 12 hub genes potentially interacting in the RES-chondrocyte-macrophage network. In vitro experiments were used to further verify the validity of the predicted hub genes. The composite hydrogels were successfully fabricated, and maintenance of the characteristic was further confirmed. In vitro study, cHA-CS-RES showed high cell viability, anti-inflammatory and pro-chondrogenesis abilities. In vivo study of cartilage defects confirmed that the cHA-CS-RES groups were significantly better than the control group. Network pharmacology was used to predict and screen the target proteins of RES critical to cartilage tissue engineering. Moreover, cHA-CS-RES composite hydrogel showed good cartilage repair effects, anti-inflammatory and pro-chondrogenesis abilities.
Groundwater-dependent ecosystems at risk – global hotspot analysis and implications
Authors: Link Andreas , El-Hokayem Léonard , Usman Muhammad , Conrad Christopher , Reinecke Robert , Berger Markus , Wada Yoshihide , Coroama Vlad , Finkbeiner Matthias 
Published: July 2023

Abstract
Many land-based ecosystems are dependent on groundwater and could be threatened by human groundwater abstraction. One key challenge for the description of associated impacts is the initial localisation of groundwater-dependent ecosystems (GDEs). This usually requires a mixture of extensive site-specific data collection and the use of geospatial datasets and remote sensing techniques. To date, no study has succeeded in identifying different types of GDEs in parallel worldwide. The main objective of this work is to perform a global screening analysis to identify GDE potentials rather than GDE locations. In addition, potential risks to GDEs from groundwater abstraction shall be identified. We defined nine key indicators that capture GDE potentials and associated risks on a global grid of 0.5° spatial resolution. Groundwater-dependent streams, wetlands and vegetation were covered, and a GDE index was formulated incorporating the following three aspects: the extent of groundwater use per GDE type, GDE diversity and GDE presence by land cover. The results show that GDE potentials are widely distributed across the globe, but with different distribution patterns depending on the type of ecosystem. The highest overall potential for GDEs is found in tropical regions, followed by arid and temperate climates. The GDE potentials were validated against regional studies, which showed a trend of increasing matching characteristics towards higher GDE potentials, but also inconsistencies upon closer analysis. Thus, the results can be used as first-order estimates only, which would need to be explored in the context of more site-specific analyses. Identified risks to GDEs from groundwater abstraction are more geographically limited and concentrated in the US and Mexico, the Iberian Peninsula and the Maghreb, as well as Central, South and East Asia. The derived findings on GDEs and associated risks can be useful for prioritising future research and can be integrated into sustainability-related tools such as the water footprint.
Lagrangian reduction of forced discrete mechanical systems
Authors: Caruso Matías I , Fernández Javier , Tori Cora , Zuccalli Marcela 
Published: July 2023

Abstract
In this paper we propose a process of Lagrangian reduction and reconstruction for symmetric discrete-time mechanical systems acted on by external forces, where the symmetry group action on the configuration manifold turns it into a principal bundle. We analyze the evolution of momentum maps and Poisson structures under different conditions.
Overgroups of subsystem subgroups in exceptional groups: inside a sandwich
Authors: Gvozdevsky P. 
Published: July 2023

This paper supplements a previous paper by the author (Overgroups of subsystem subgroups in exceptional groups: a

2

A
1

2A_1

-proof, (2020)), where the overgroup lattice of the elementary subsystem subgroup

E
(
Δ
,
R
)

E(\Delta ,R)

of the Chevalley group

G
(
Φ
,
R
)

G(\Phi ,R)

for a sufficiently large root subsystem

Δ
\Delta

was studied. Currently, the subject-matter is the relationship between the elementary subgroup

E
^

(
σ
)

\widehat {E}(\sigma )

given by a net of ideals

σ
\sigma

of the ring

R
R

, and the stabilizer

S
(
σ
)

S(\sigma )

of the corresponding Lie subalgebra of the Chevalley algebra. In particular, it is proved that under a certain condition the subgroup

E
^

(
σ
)

\widehat {E}(\sigma )

is normal in

S
(
σ
)

S(\sigma )

, and some properties of the corresponding quotient group are established.
Symbol length of classes in Milnor 𝐾-groups
Authors: Chapman A. 
Published: July 2023

Given a field

F
F

, a positive integer

m
m

and an integer

n
≥
2

n\geq 2

, it is proved that the symbol length of classes in Milnor’s

K
K

-groups

K
n

F

/

2
m

K
n

F

K_n F/2^m K_n F

that are equivalent to single symbols under the embedding into

K
n

F

/

2

m
+
1

K
n

F

K_n F/2^{m+1} K_n F

is at most

2

n
−
1

2^{n-1}

under the assumption that

F
⊇

μ

2

m
+
1

F \supseteq \mu _{2^{m+1}}

. Since

K
2

F

/

2
m

K
2

F
≅

2
m

B
r
(
F
)

K_2 F/2^m K_2 F \cong {_{2^m}Br(F)}

for

n
=
2

n=2

, this coincides with the upper bound of

2
2

(proved by Tignol in 1983) for the symbol length of central simple algebras of exponent

2
m

2^m

that are Brauer equivalent to a single symbol algebra of degree

2

m
+
1

2^{m+1}

. The cases where the embedding into

K
n

F

/

2

m
+
1

K
n

F

K_n F/2^{m+1} K_n F

is of symbol length

2
2

,

3
3

, and

4
4

(the last when

n
=
2

n=2

) are also considered. The paper finishes with the study of the symbol length for classes in

K
3

/

3
m

K
3

F

K_3/3^m K_3 F

whose embedding into

K
3

F

/

3

m
+
1

K
3

F

K_3 F/3^{m+1} K_3 F

is one symbol when

F
⊇

μ

3

m
+
1

F \supseteq \mu _{3^{m+1}}

.
Optimization of an Information Leaflet to Influence Medication Beliefs in Women With Breast Cancer: A Randomized Factorial Experiment
Authors: Green Sophie M C , Hall Louise H , French David P , Rousseau Nikki , Parbutt Catherine , Walwyn Rebecca , Smith Samuel G 
Published: July 2023

Abstract

Background
Adherence to adjuvant endocrine therapy (AET) is low in women with breast cancer. Negative beliefs about the necessity of AET and high concerns are barriers to adherence.

Purpose
To use the multiphase optimization strategy to optimize the content of an information leaflet intervention, to change AET beliefs.

Methods
We conducted an online screening experiment using a 25 factorial design to optimize the leaflet. The leaflet had five components, each with two levels: (i) diagrams about AET mechanisms (on/off); (ii) infographics displaying AET benefits (enhanced/basic); (iii) AET side effects (enhanced/basic); (iv) answers to AET concerns (on/off); (v) breast cancer survivor (patient) input: quotes and photographs (on/off). Healthy adult women (n = 1,604), recruited via a market research company, were randomized to 1 of 32 experimental conditions, which determined the levels of components received. Participants completed the Beliefs about Medicines Questionnaire before and after viewing the leaflet.

Results
There was a significant main effect of patient input on beliefs about medication (β = 0.063, p &lt; .001). There was one significant synergistic two-way interaction between diagrams and benefits (β = 0.047, p = .006), and one antagonistic two-way interaction between diagrams and side effects (β = −0.029, p = .093). There was a synergistic three-way interaction between diagrams, concerns, and patient input (β = 0.029, p = .085), and an antagonistic four-way interaction between diagrams, benefits, side effects, and concerns (β = −0.038, p = .024). In a stepped approach, we screened in four components and screened out the side effects component.

Conclusions
The optimized leaflet did not contain enhanced AET side effect information. Factorial experiments are efficient and effective for refining the content of information leaflet interventions.
CAMEL NANOBODY-BASED B7-H3 CAR-T CELLS WITH HIGH EFFICACY AGAINST SOLID TUMORS
Authors: Li Dan , Wang Ruixue , Liang Tianyuzhou , Ren Hua , Park Chaelee , Tai Chin-Hsien , Ni Weiming , Zhou Jing , Mackay Sean , Edmondson Elijah , Khan Javed , Croix Brad St , Ho Mitchell 
Published: July 2023

Abstract

Background and significance
Chimeric antigen receptor (CAR)-T cell therapy shows promising potency for treating patients with hematological malignancies. However, follow-up data indicate that only 30% to 50% of these patients experience long-term disease control. In solid tumors, the B7-H3 transmembrane protein is an emerging target that harbors in its ectodomain two distinct epitope motifs - IgC and IgV. Here, we developed nanobody-based CAR-T cell strategy targeting B7-H3 and investigated its anti-tumor efficacy in xenograft mouse models.

Methods
We isolated anti-B7-H3 VHHs from our large dromedary camel VHH nanobody libraries with great diversity (&gt; 1012 total) by phage display technology. The binding of isolated VHHs was validated by ELISA, flow cytometry, and Octet. A B7-H3 peptide library was synthesized to predict the epitope of select VHHs. Anti-tumor effect of B7-H3 CAR-T cells was determined via cell luciferase-based cell killing assay as well as xenograft mouse models. Two tumor models, human neuroblastoma and pancreatic adenocarcinoma, were used in the present study. Single-cell transcriptome RNA sequencing coupled with single T-cell functional proteomics analysis was used to analyze the functionality of nanobody-based B7-H3 CAR-T cells.

Results
We analyzed the isoforms of B7-H3 at the RNA and protein levels and validated that only 4IgB7-H3 is a therapeutic target as the dominant isoform in tumors. Targeting 4Ig isoform, we obtained a panel of high-affinity nanobodies cross-reactive to human, mouse, rat, and monkey. Furthermore, we demonstrated that CAR-T cells based on the nanobodies had potent antitumor activity against tumors with rigorous T cell signaling and significant tumor infiltration. Mechanistically, we uncovered the top-upregulated genes that might be critical for the persistence of polyfunctional CAR-T cells in the tumor microenvironment.

Conclusions
Our results provide a novel nanobody-based B7-H3 CAR-T product for use in solid tumor therapy.
OVERCOMING TECHNICAL CHALLENGES OF BISPECIFIC AND MULTI-SPECIFIC ANTIBODIES USING NOVEL TECHNOLOGY PLATFORMS
Authors: Xu Jianqing , Wang Shuang , Fan Xinzhao , Wang George , Gu Jijie , Nie Siwei 
Published: July 2023

Abstract

Background
Bispecific antibodies (bsAbs) and multispecific antibodies (msAbs) are a growing class of next generation biotherapeutics. However, multiple challenges, such as chain mispairing and developability issues are often associated with these complex modalities.

Methods
WuXi Biologics has established bsAb and msAb engineering and development platforms. By replacing CH1/CL domains of one antibody Fab by corresponding T cell receptor (TCR) Cβ/Cα domains, WuXiBody® bsAb technology can ensure the correct heavy-light chain pairing. WuXi Biologics has developed the SDArBody™ platform, which utilizes single domain antibodies (VHH) as building blocks to facilitate the exploration of more complex biologics, such as msAbs.

Results
as shown in case studies, the WuXiBody® technology is able to assemble regular mAbs in a ‘plug-and-play’ manner, and that the SDArBody® can be utilized to identify VHH leads and then assemble into msAbs. Both platforms can generate highly functional bsAb and msAb with good developability.

Conclusions
The establishment of WuXiBody® and SDArBody® platforms could greatly meet the needs of biologics developers in pursuit of different biology and therapeutic approaches through bsAbs and msAbs.
A NOVEL IMMUNOSTIMULATORY PD-L1/OX40 TETRAVALENT BISPECIFIC ANTIBODY FOR CANCER IMMUNOTHERAPY
Authors: Li Baocun , Wu Xuan , Gong Shiyong , Lv Zhou , Zhang Nianying , Zhang Yu , Naren Gaowa , Wu Danqing , Wu Jianfu , Liu Fan , Zhang Rui , Wu Chengbin 
Published: July 2023

Abstract
Single agent immune checkpoint therapy has shown substantial and durable clinical activity in many tumor types; however, only a fraction of the patients could benefit from this approach. To improve beyond the anti-PD-1/PD-L1 treatment options, bispecific antibodies (BsAb) that combines PD-L1 blockade and conditional co-stimulatory receptor activation simultaneously in one molecule have been developed and demonstrated superior anti-tumor activity in pre-clinical models. However, many of these PD-L1 based BsAb faced challenge in clinical development due to insufficient activity or unexpected toxicity. Here, we demonstrated that OX40 might be a more suitable partner for PD-L1 based BsAb design than other agonistic targets (CD27 and 4-1BB, etc.) currently in clinical studies. A novel Fc silenced tetravalent PD-L1/OX40 (EMB-09) BsAb targeting optimal OX40 binding epitope has been developed based on EpimAb’s proprietary FIT-Ig® technology. Results showed that EMB-09 maintained the parental mAb binding characteristic and retained the functional properties of each parental mAb including OX40 agonistic as well as PD-L1/PD1 inhibitory pathways. In addition, EMB-09 induced OX40 activation only in the context of PD-L1 engagement. Concurrent PD-L1/PD-1 blockade and OX40 co-stimulation by EMB-09 led to synergistic activation of T cell in vitro and exerted superior anti-tumor activity in mouse tumor models compared to anti-PD-L1 mAb. The underlining mechanism was extensively analyzed, which indicated an increased CD8+ tumor-infiltrating T-cells (TIL) as well as enhanced CD8 TIL activation status upon EMB-09 treatment. Additionally, EMB-09 was well tolerated in cynomolgus monkeys at high dose levels with a favorable safety and PK profile in a GLP-TOX study. In conclusion, as a PD-L1/OX40 BsAb with a novel biology mechanism, EMB-09 demonstrated a markedly improved anti-tumor activity compared to anti-PD-L1 mAb. The first-in-human clinal study of EMB-09 has been initiated (NCT05263180).
DISCOVERY OF NOVEL ANTI-SERUM ALBUMIN VHH AS A BUILDING BLOCK FOR PK PROLONGATION
Authors: Chen Yunying , Lin Xin , Qin Yi , Wu Donghui , Gu Jijie , Nie Siwei 
Published: July 2023

Abstract

Background
The serum half-life of endogenous albumin is approximately 19 days in humans and 1.5-2.5 days in rodents. This extended half-life in vivo is primarily due to effective recycling upon internalization mediated by the neonatal Fc receptor (FcRn). Many protein therapeutics smaller than 60 kD have short serum half-life, which can be extended by fusing the proteins of interest with an anti-albumin antibody. The fusion proteins then take advantage of FcRn-mediated recycling.
Single domain antibody (VHH) molecules (around 15 kD), derived from camelid heavy-chain-only IgG, are attracting increased attention globally in the field of antibody-based therapies due to several features including small size, high stability, low immunogenicity, good tissue penetration and cost effectiveness in manufacturing.

Methods
an anti-human/cynomolgus monkey/murine/canine/feline serum albumin VHH lead was discovered from a proprietary, large native phage-displayed VHH library, which was then humanized, and affinity matured. The optimized VHH was fused to bispecific and trispecific antibodies for in vivo PK studies.

Results
An anti-human serum albumin VHH Ab was discovered, and it also bound to cyno and mouse serum albumin with high affinity without affecting the interaction of HSA with FcRn. The VHH showed good developability and, once fused to protein therapeutics, long half-life and anti-tumor activity in rodents.

Conclusions
a novel VHH against serum albumin of different species was discovered from native VHH libraries, and it can be easily assembled into bispecific Abs and multispecific Abs to prolong the molecules’ PK profile.
APPLICATION OF EXCHABODY TECHNOLOGY FOR PAIRING VHHS TO ACHIEVE SYNERGISTIC EFFECTS
Authors: Luo Yi , Zhan Xiaoxiao , Shen Yilong , Sheng Ziyang , Zhu Yin , Huang Mingyue 
Published: July 2023

Abstract

Objective
Single-domain antibodies, such as VHH and nanobody, have shown potential for use in therapy and diagnostics. One application of VHHs is the tethering of two fragments to different epitopes on the same target, which is difficult to achieve with conventional antibodies. Synergistic heterologous VHH dimers have higher affinity, better specificity, and broad applications in developing high-affinity monoclonal antibodies, bispecific antibodies, ADCs, and CAR-Ts. However, finding the best pair of VHHs for these applications requires combinational screening, which is traditionally a time-consuming and costly process.
The objective of this study is to develop a technology that can quickly screen and pair two synergistic VHHs without the need to express tandem VHH dimers.

Methods
The researchers developed proprietary tags and specific dockers that, when stabilized on a solid station, can capture any VHHs that the dockers recognize and pull them together to form a non-covalent dimer. This platform is called ExchaBody technology, and the VHH dimers formed this way are ExchaBodies. The researchers used this technology to conduct a bi-epitope screening campaign, where VHHs were first expressed as monomers with tags and then binned and grouped into different categories. VHHs were then paired with all reasonable combinations using ExchaBody technology, and these ExchaBodies were evaluated for their combined activities.

Results
ExchaBody technology was able to link any two VHHs together within one hour, and the resulting ExchaBodies had bivalent or bifunctional VHH activities. The bi-epitope VHH screening campaign, which would have taken months to complete using traditional methods, was finished within two weeks using ExchaBody technology, saving time and cost. The researchers were able to construct two lead molecules, a bi-specific VHH-Fc fusion protein and a tri-valent VHH molecule, using ExchaBody technology. These lead molecules were found to be superior to their counterparts on the market based on affinity and functional assays.

Conclusion
ExchaBody technology is a bispecific VHH screening and pairing platform that can quickly and cost-effectively create non-covalent, bispecific VHHs (ExchaBodies) without the need to express them. ExchaBodies possess the binding and cellular activities of a covalently linked, bispecific, tandem VHH dimer. This technology has broad applications in developing high-affinity monoclonal antibodies, bispecific antibodies, ADCs, and CAR-Ts.
‘Our Practice Has a Superiority:’ Debt Enforcement, Bills of Exchange, and Credit in Eighteenth-Century Glasgow
Authors: Harris Hunter 
Published: July 2023

Abstract
This article explores the relationship between the Scots law of bills of exchange, debt enforcement procedures, and credit in the eighteenth century. Compared to England, Scots law’s procedures for recovering debts on obligations were faster, cheaper, and more efficient. These legal provisions are under-appreciated in the current literature on bills of exchange. Scots law’s superiority meant that the provision of medium-value credit in urban economies often occurred through written obligations. Using a new archival data set of nearly 300 bills of exchange from Glasgow, this article demonstrates how Glaswegians used those instruments. It finds that elements of the law of obligations traditionally stressed in the literature, namely negotiability, do little to explain the use of credit instruments in Glasgow. Instead, it was Scots law’s quick recovery procedures that account for their patterns of use. The data shows that inland bills did not commonly pass from hand to hand but instead were held as proofs of debt that could quickly be enforced. The advantage of Scots law in this area did not go unnoticed by contemporaries, and unsuccessful attempts at legal reform in the Victorian era sought to introduce the Scottish rules to the English system. This article joins a growing literature in turning scholarly focus away from the negotiable properties of bills, and shows the importance of expedited enforcement procedures for understanding the Scots credit system. It suggests that paying closer attention to procedural law and differences between jurisdictions can advance research agendas on the relationship between law and economic development.