bluuebunny/crossref_metadata_2025 huggingface dataset:
Developing evidence-based patient-focused learning materials to support health behaviour change for people living with psoriatic arthritis
Authors: Hailey Louise , Howells Laura , Bundy Christine , Kirtley Shona , Martin Samantha , O'Sullivan Denis , Steinkoening Ingrid , Stepney Melissa , Coates Laura C
Published: August 2023

Objectives

In psoriatic arthritis (PsA), self-management is important for patient function and quality of life. Behaviour change can be difficult, patients could benefit from high-quality support to initiate change. Our aim was to codesign the project as theory-informed, evidence-based, patient-focused, materials supporting healthy lifestyle changes for patients diagnosed with PsA.

Methods

Development of the materials was overseen by a steering group of patients with PsA, psychologists, rheumatologists, a design team and researchers. First, a literature review was performed to establish the evidence base for behaviours and potential interventions in PsA, including diet, weight, alcohol, smoking, exercise, anxiety, depression and stress. An initial roundtable of patients with PsA prioritised areas and content ideas. Draft materials including a website and downloadable materials were produced. A second roundtable of patients with PsA collected feedback on the draft content and design. A third roundtable was held with patients with PsA and a fourth with clinicians to refine the materials and ensuring that they were evidence based, accessible, interesting, and helpful to initiate and maintain change. A final evaluation survey was performed to review the draft website before launching the final materials.

Results

15 candidate topics were prioritised. A website and set of postcards summarising the topics were developed by the design team and refined following feedback from the roundtable groups.

Conclusion

This project created patient-focused resources to support behaviour change. It addresses common concerns of patients with PsA about how they may optimise their health by providing practical and brief interventions to challenge and support them to make changes.
Phase 3, multicentre, randomised, double-blind, placebo-controlled, parallel-group study of ustekinumab in Japanese patients with active polymyositis and dermatomyositis who have not adequately responded to one or more standard-of-care treatments
Authors: Kawahata Kimito , Ishii Tomonori , Gono Takahisa , Tsuchiya Yumi , Ohashi Hiroki , Yoshizawa Katsunori , Zheng Richuan , Ayabe Maori , Nishikawa Kazuko
Published: August 2023

Objectives

To evaluate the efficacy and safety of ustekinumab (UST) in a multicentre, randomised, double-blind, placebo-controlled trial in adult Japanese patients with active polymyositis (PM) and dermatomyositis (DM).

Methods

Fifty-one Japanese adults diagnosed with active PM/DM who did not respond adequately to one or more standard-of-care treatments were randomised 1:1 to receive UST (n=25) or placebo (n=26). Participants received body weight-range based intravenous administration of UST (6 mg/kg) or placebo at week 0 followed by 90 mg subcutaneous (SC) administration of UST or placebo every 8 weeks from week 8 to week 24. At week 24, placebo group crossed over to receive body weight-range based intravenous administration of UST, and thereafter, all participants received/were to receive SC administration of UST 90 mg every 8 weeks (week 32 through to week 72). The primary efficacy endpoint was the proportion of participants who achieved minimal improvement (≥20) in the International Myositis Assessment and Clinical Studies Total Improvement Score (IMACS TIS) at week 24.

Results

No statistically significant difference was seen in the proportion of participants who achieved minimal improvement (≥20) in IMACS TIS at week 24 between the treatment groups (UST 64.0% vs placebo 61.5%, p=0.94) based on the primary estimand of the primary endpoint analysis.

Conclusions

UST was safe and well tolerated but did not meet the primary efficacy endpoint in adult Japanese participants with active PM/DM based on the primary analysis at week 24 in the study.

Trial registration number

NCT03981744.
Preconception clinical factors related to adverse pregnancy outcomes in patients with systemic lupus erythematosus or primary Sjögren’s syndrome: a retrospective cohort study
Authors: Fierro Juan J. , Prins Jelmer R. , Verstappen Gwenny M. , Bootsma Hendrika , Westra Johanna , de Leeuw Karina
Published: August 2023

Objective

To identify preconception clinical factors associated with adverse pregnancy outcomes (APO) in patients with systemic lupus erythematosus (SLE) or primary Sjögren’s syndrome (pSS).

Methods

A single-centre, retrospective cohort study was conducted, which included pregnant women treated at the University Medical Center Groningen between January 2010 and August 2021 who fulfilled classification criteria for SLE or pSS. Demographic data, relevant comorbidities, disease duration, disease activity before and during pregnancy, APO, laboratory parameters and treatment regimens were recorded. Associations between the presence of APO and preconception characteristics were evaluated.

Results

Our study population included 48 (70%) SLE and 21 (30%) pSS pregnancies concerning 70 fetuses (one twin). Preterm birth (n=9, 19%) was the most frequent APO in SLE pregnancies, while in pSS pregnancies this was miscarriages (n=3, 14%). There were no associations between the presence of APO in SLE pregnancies and clinical parameters, laboratory parameters or medication use prior to conception. In the pSS group, significant associations were found between the presence of APO and body mass index (p=0.010), parity (p=0.046), C4 (p=0.021) and low C4 levels (p=0.002).

Conclusions

No preconception risk factors related to APO were found in SLE pregnancies, whereas preconception complement levels were associated with APO development in patients with pSS.
Characteristic of shape factor on electrically conducting radiating ternary nanofluid over an expanding wedge surface
Authors: Nayak B. , Acharya S. , Mishra S. R.
Published: August 2023

In the present scenario, the production process of various electronic gadgets including industrial products needs a higher cooling system to get its better features. Therefore, this study reveals the radiating ternary nanofluid flow through a wedged stretching surface. The forced convection of an electrically conducting fluid in association with the particle concentration enriches the study. The novelty of the proposed phenomena is due to the consideration of various shapes such as spherical, cylindrical, and platelet shaped solid particles combined with various physical models of electrical and thermal conductivity, viscosity, specific heat, and heat capacitance. The performance of the ternary nanofluid is presented using a carbon nanotube, graphene, and aluminum oxide in the base liquid water. To achieve a system of non-dimensional form of the governing equations, suitable transformations are adopted and further, shooting-based Runge-Kutta fourth-order technique is employed for the solution of this set of equations. Further, the important outcomes are deployed as follows: the combined effect of the nanoparticles and the base liquid augments the fluid velocity as well as the temperature distributions and thermal radiation also overshoots the temperature profile.
Formability and Dimensional Accuracy Enhancement with Controlled Tool Rotational Speed in Stretch Forming Process
Authors: Benmessaoud Radouane
Published: August 2023

We present a new stretch forming method for axisymmetric sheet metal parts production. A test bench is designed, fabricated, and mounted on a drilling machine. The blank is fixed rigidly around its periphery in the apparatus, and the forming tool is mounted on the machine spindle. Thus, the control of tool rotational speed, feed rate, and vertical motion from the upper sheet surface becomes possible. Experimental tests are then conducted to form a reference shape. Rotational speed, feed rate, lubrication effect on the final thickness distribution, and geometric profiles are studied. A new multi-pass forming method is also developed and verified. The feed rate decrease, within the range of 0.11–0.18[Formula: see text]mm/rev, reduces the sheet thinning, while its increase improves the dimensional accuracy. The rotational speed increase, within the range of 112–710[Formula: see text]rpm, reduces the thickness, while its decrease enhances the geometrical accuracy. Mineral oil seems to be more effective than greases, so the thickness drop is reduced and the dimensional accuracy is improved. The use of the multi-pass strategy avoids the sheet cracking at great forming depth. The decrease in step size, within the range of 0.3–1[Formula: see text]mm, reduces the thickness minima, while good dimensional accuracy can be obtained in the range of 0.5–1[Formula: see text]mm.
Computing Arbitrage-Free Yields in Multi-Factor Gaussian Shadow Rate Term Structure Models
Authors: Priebsch Marcel A.
Published: August 2023

This paper develops an approximation to arbitrage-free bond yields in Gaussian shadow rate term structure models. In this class of models, yields are constrained to be above an effective lower bound, thus rendering standard bond pricing methods inapplicable. I propose approximating the nonlinear relationship between yields and state variables using moments of the censored normal distribution. In an empirical application, this approximation technique is accurate to within a fraction of a basis point. As I show, minimizing the yield approximation error is crucial for model estimation as even seemingly small errors can lead to economically meaningful inference biases.
Rebuffing the “Hard to Reach” Narrative: How to Engage Diverse Groups in Participation for Resilience
Authors: McEwen Lindsey , Holmes Andrew , Cornish Flora , Leichenko Robin , Guida Kristen , Burchell Kevin , Sharpe Justin , Everett Glyn , Scott Matt
Published: August 2023

Across three years (2017–2020), the ESRC Seminar series, “Civil Agency, Society and Climate Adaptation to Weather Extremes” (CASCADE-NET) critically examined the changing role of civil society in extreme weather adaptation. One full-day seminar explored “less heard voices” within Civil Society, considering ways of engaging diverse groups in resiliency, knowledge exchange, and capacity building. A small interdisciplinary group from the seminar followed up with a roundtable discussion, conducted online, discussing first who the less-heard voices in society are, and how labels, such as “vulnerable” and “hard to reach”, might need to be reappraised, and concluding that it is often those in power who make themselves “hard to reach” and who fail to listen. The group then discussed how deeper engagement with citizens and communities can be achieved through improved relationships and networks. Finally, the roundtable discussed how the succession of crises affecting the UK (and other settings) could, paradoxically, present an opportune moment to press the case for a more joined-up and inclusive civil society. The concluding section summarizes key insights from the roundtable and identifies opportunities to rethink engagement with “hard to reach” groups. To answer our question of “how to” engage diverse groups, we conclude with the action points to change the orientation of the powerful to (i) be genuinely open to listening to, and acting upon the voices of less heard groups; (ii) listen on the terms of groups who are voicing their experience, rather than force them into pre-arranged consultation formats; (iii) engage early, widely and frequently; (iv) build trust by demonstrating willingness to listen, through actions; (v) tackle historical mistrust, unequal resources, experiences of neglect or exploitation that undermine groups’ interest in engaging with the powerful. A transformation in orientation to community engagement is in order if we are to produce effective, locally attuned, collective action in the face of social shocks.
Infinite collision property for the three-dimensional uniform spanning tree
Authors: Watanabe Satomi
Published: August 2023

Let [Formula: see text] be the three-dimensional uniform spanning tree, whose probability law is denoted by [Formula: see text]. For [Formula: see text]-a.s. realization of [Formula: see text], the recurrence of the simple random walk on [Formula: see text] is proved in Benjamini et al. (2001) [I. Benjamini, R. Lyons, Y. Peres and O. Schramm, Uniform spanning forests, Ann. Probab. 29(1) (2001) 1–65] and it is also demonstrated in Hutchcroft and Peres (2015) [T. Hutchcroft and Y. Peres, Collisions of random walks in reversible random graphs, Electron. Commun. Probab. 20(63) (2015) 1–6] that two independent simple random walks on [Formula: see text] collide infinitely often. In this paper, we will give a quantitative estimate on the number of collisions of two independent simple random walks on [Formula: see text], which provides another proof of the infinite collision property of [Formula: see text].
L(3,2,1)-labeling problem of square of path
Authors: Amanathulla Sk , Khatun Jasminara , Pal Madhumangal
Published: August 2023

There are many problems in graph theory, where labeling of graphs is the only alternative to solve it. Graph labeling widely appeared in frequency assignment, communication network addressing, circuit design, X-ray crystallography, coding theory, missile guidance, signal processing, etc. For any graph [Formula: see text], where V is the node set and [Formula: see text] is the distance between nodes p and q, the [Formula: see text]-labeling of G is a mapping [Formula: see text] such that [Formula: see text] if [Formula: see text], [Formula: see text] if [Formula: see text] and [Formula: see text] if [Formula: see text]. This paper is devoted to [Formula: see text]-labeling of squares of path (SOP) [Formula: see text] and we obtained unique results. This is the first result about [Formula: see text]-labeling of SOP. To the best of our knowledge, no result is available related to [Formula: see text]-labeling of square of any classes of graphs.
Formal Specification and Testing for Reinforcement Learning
Authors: Varshosaz Mahsa , Ghaffari Mohsen , Johnsen Einar Broch , Wąsowski Andrzej
Published: August 2023

The development process for reinforcement learning applications is still exploratory rather than systematic. This exploratory nature reduces reuse of specifications between applications and increases the chances of introducing programming errors. This paper takes a step towards systematizing the development of reinforcement learning applications. We introduce a formal specification of reinforcement learning problems and algorithms, with a particular focus on temporal difference methods and their definitions in backup diagrams. We further develop a test harness for a large class of reinforcement learning applications based on temporal difference learning, including SARSA and Q-learning. The entire development is rooted in functional programming methods; starting with pure specifications and denotational semantics, ending with property-based testing and using compositional interpreters for a domain-specific term language as a test oracle for concrete implementations. We demonstrate the usefulness of this testing method on a number of examples, and evaluate with mutation testing. We show that our test suite is effective in killing mutants (90% mutants killed for 75% of subject agents). More importantly, almost half of all mutants are killed by generic write-once-use-everywhere tests that apply to
any
reinforcement learning problem modeled using our library, without any additional effort from the programmer.
How to Evaluate Blame for Gradual Types, Part 2
Authors: Lazarek Lukas , Greenman Ben , Felleisen Matthias , Dimoulas Christos
Published: August 2023

Equipping an existing programming language with a gradual type system
requires two major steps. The first and most visible one in academia
is to add a notation for types and a type checking apparatus. The second, highly
practical one is to provide a type veneer for the large number of
existing untyped libraries; doing so enables typed components
to import pieces of functionality and get their
uses type-checked, without any changes to the libraries. When programmers create such typed veneers for
libraries, they make mistakes that persist and cause
trouble. The question is whether the academically investigated
run-time checks for gradual type systems assist programmers with
debugging such mistakes. This paper provides a first, surprising
answer to this question via a rational-programmer investigation:
run-time checks alone are typically less helpful than the safety checks of the underlying language.
Combining Natural run-time checks with blame, however, provides
significantly superior debugging hints.
Typing Records, Maps, and Structs
Authors: Castagna Giuseppe
Published: August 2023

Records are finite functions from keys to values. In this work we focus on two main distinct usages of records: structs and maps. The former associate different keys to values of different types, they are accessed by providing nominal keys, and trying to access a non-existent key yields an error. The latter associate all keys to values of the same type, they are accessed by providing expressions that compute a key, and trying to access a non-existent key usually yields some default value such as Null or nil. Here, we propose a type theory that covers both kinds of usage, where record
types
may associate to different types either single keys (as for structs) or sets of keys (as for maps) and where the same record
expression
can be accessed and used both in the struct-like style and in the map-like style we just described. Since we target dynamically-typed languages our type theory includes union and intersection types, characterized by a subtyping relation. We define the subtyping relation for our record types via a semantic interpretation and derive the decomposition rules to decide it, define a backtracking-free subtyping algorithm that we prove to be correct, and provide a canonical representation for record types that is used to define various type operators needed to type record operations such as selection, concatenation, and field deletion.
Reflecting on Random Generation
Authors: Goldstein Harrison , Frohlich Samantha , Wang Meng , Pierce Benjamin C.
Published: August 2023

Expert users of property-based testing often labor to craft random generators that encode detailed knowledge about what it means for a test input to be valid and interesting. Fortunately, the fruits of this labor can also be put to other uses. In the bidirectional programming literature, for example, generators have been repurposed as validity checkers, while Python's Hypothesis library uses the same structures for shrinking and mutating test inputs.

To unify and generalize these uses and many others, we propose reflective generators, a new foundation for random data generators that can "reflect" on an input value to calculate the random choices that could have been made to produce it. Reflective generators combine ideas from two existing abstractions: free generators and partial monadic profunctors. They can be used to implement and enhance the aforementioned shrinking and mutation algorithms, generalizing them to work for any values that can be produced by the generator, not just ones for which a trace of the generator's execution is available. Beyond shrinking and mutation, reflective generators generalize a published algorithm for example-based generation, and they can also be used as checkers, partial value completers, and other kinds of test data producers.
Generic Programming with Extensible Data Types: Or, Making Ad Hoc Extensible Data Types Less Ad Hoc
Authors: Hubers Alex , Morris J. Garrett
Published: August 2023

We present a novel approach to generic programming over extensible data types. Row types capture the
structure of records and variants, and can be used to express record and variant subtyping, record extension, and modular composition of case branches. We extend row typing to capture generic programming over rows themselves, capturing patterns including lifting operations to records and variations from their component types, and the duality between cases blocks over variants and records of labeled functions, without placing specific requirements on the fields or constructors present in the records and variants. We formalize our approach in System R𝜔, an extension of F𝜔 with row types, and give a denotational semantics for (stratified) R𝜔 in Agda.
The Verse Calculus: A Core Calculus for Deterministic Functional Logic Programming
Authors: Augustsson Lennart , Breitner Joachim , Claessen Koen , Jhala Ranjit , Peyton Jones Simon , Shivers Olin , Steele Jr. Guy L. , Sweeney Tim
Published: August 2023

Functional logic languages have a rich literature, but it is tricky
to give them a satisfying semantics. In this paper we describe the
Verse calculus, VC, a new core calculus for deterministic functional
logic programming. Our main contribution is to equip VC with a
small-step rewrite semantics, so that we can reason
about a VC program in the same way as one does with lambda
calculus; that is, by applying successive rewrites to it.
We also show that the rewrite system is confluent for well-behaved terms.
With or Without You: Programming with Effect Exclusion
Authors: Lutze Matthew , Madsen Magnus , Schuster Philipp , Brachthäuser Jonathan Immanuel
Published: August 2023

Type and effect systems have been successfully used to statically reason about effects in many different domains, including region-based memory management, exceptions, and algebraic effects and handlers. Such systems’ soundness is often stated in terms of the absence of effects. Yet, existing systems only admit indirect reasoning about the absence of effects. This is further complicated by effect polymorphism which allows function signatures to abstract over arbitrary, unknown sets of effects.

We present a new type and effect system with effect polymorphism as well as union, intersection, and complement effects. The effect system allows us to express
effect exclusion
as a new class of effect polymorphic functions: those that permit any effects except those in a specific set. This way, we equip programmers with the means to directly reason about the absence of effects. Our type and effect system builds on the Hindley-Milner type system, supports effect polymorphism, and preserves principal types modulo Boolean equivalence. In addition, a suitable extension of Algorithm W with Boolean unification on the algebra of sets enables complete type and effect inference. We formalize these notions in the λ
∁
calculus. We prove the standard progress and preservation theorems as well as a non-standard effect safety theorem: no excluded effect is ever performed.

We implement the type and effect system as an extension of the Flix programming language. We conduct a case study of open source projects identifying 59 program fragments that require effect exclusion for correctness. To demonstrate the usefulness of the proposed type and effect system, we recast these program fragments into our extension of Flix.
A General Fine-Grained Reduction Theory for Effect Handlers
Authors: Sieczkowski Filip , Pyzik Mateusz , Biernacki Dariusz
Published: August 2023

Effect handlers are a modern and increasingly popular approach to structuring computational effects in functional programming languages. However, while their traditional operational semantics is well-suited to implementation tasks, it is less ideal as a reduction theory. We therefore introduce a fine-grained reduction theory for deep effect handlers, inspired by our existing reduction theory for shift0, along with a standard reduction strategy. We relate this strategy to the traditional, non-local operational semantics via a simulation argument, and show that the reduction theory preserves observational equivalence with respect to the classical semantics of handlers, thus allowing its use as a rewriting theory for handler-equipped programming languages -- this rewriting system mostly coincides with previously studied type-based optimisations. In the process, we establish theoretical properties of our reduction theory, including confluence and standardisation theorems, adapting and extending existing techniques. Finally, we demonstrate the utility of our semantics by providing the first normalisation-by-evaluation algorithm for effect handlers, and prove its soundness and completeness. Additionally, we establish non-expressibility of the lift operator, found in some effect-handler calculi, by the other constructs.
Modular Models of Monoids with Operations
Authors: Yang Zhixuan , Wu Nicolas
Published: August 2023

Inspired by algebraic effects and the principle of notions of computations as monoids, we study a categorical framework for equational theories and models of monoids equipped with operations.
The framework covers not only algebraic operations but also scoped and variable-binding operations.
Appealingly, in this framework both theories and models can be modularly composed.
Technically, a general monoid-theory correspondence is shown, saying that the category of theories of algebraic operations is equivalent to the category of monoids.
Moreover, more complex forms of operations can be coreflected into algebraic operations, in a way that preserves initial algebras.
On models, we introduce modular models of a theory, which can interpret
abstract syntax in the presence of other operations.
We show constructions of modular models (i) from monoid transformers, (ii) from free algebras, (iii) by composition, and (iv) in symmetric monoidal categories.
Intrinsically Typed Sessions with Callbacks (Functional Pearl)
Authors: Thiemann Peter
Published: August 2023

All formalizations of session types rely on linear types for soundness as
session-typed communication channels must change their type at every
operation. Embedded language implementations of session types follow
suit. They either rely on clever typing constructions to guarantee
linearity statically, or on run-time checks that approximate
linearity.

We present a new language-embedded implementation of session types,
which is inspired by the inversion-of-control design principle. With
our approach, all application programs are intrinsically session-typed and
unable to break linearity by construction. Our design relies on a tiny
encapsulated library, for which linearity remains a proof
obligation that can be discharged once and for all when the library is built.

We demonstrate that our proposed design extends to a wide range of
features of session type systems: branching, recursion, multichannel
and higher-order sessions, as well as context-free sessions. The
multichannel extension provides an embedded implementation of
session types which guarantees deadlock freedom by construction.

The development reported in this paper is fully backed by
type-checked Agda code.
A Graded Modal Dependent Type Theory with a Universe and Erasure, Formalized
Authors: Abel Andreas , Danielsson Nils Anders , Eriksson Oskar
Published: August 2023

We present a graded modal type theory, a dependent type theory with
grades
that can be used to enforce various properties of the
code.
The theory has Π-types, weak and strong Σ-types, natural numbers, an
empty type, and a universe, and we also extend the theory with a unit
type and graded Σ-types.
The theory is parameterized by a modality, a kind of partially ordered
semiring, whose elements (grades) are used to track the usage of
variables in terms and types.
Different modalities are possible.
We focus mainly on quantitative properties, in particular erasure:
with the erasure modality one can mark function arguments as erasable.

The theory is fully formalized in Agda.
The formalization, which uses a syntactic Kripke logical relation at
its core and is based on earlier work, establishes major
meta-theoretic properties such as subject reduction, consistency,
normalization, and decidability of definitional equality.
We also prove a substitution theorem for grade assignment, and
preservation of grades under reduction.
Furthermore we study an extraction function that translates terms to
an untyped λ-calculus and removes erasable content, in
particular function arguments with the “erasable” grade.
For a certain class of modalities we prove that extraction is sound,
in the sense that programs of natural number type have the same value
before and after extraction.
Soundness of extraction holds also for
open
programs, as
long as all variables in the context are erasable, the context is
consistent, and
erased matches
are not allowed for weak
Σ-types.
The Antihyperglycemic Effect of Crude Liang (Gnetum gnemon var. tenerum) Leaves Powder on Wistar Rats
Authors: Suksanga Anunya , Siripongvutikorn Sunisa , Leelawattana Rattana , Yupanqui Chutha T.
Published: August 2023

Chlorophyll and chlorophyllin (CHL) demonstrated antidiabetic activity by inhibiting gluconeogenesis and increasing glucose uptake in rats’ muscle cells. Liang leaves contain high amounts of chlorophyll and chlorophyllin and may provide an antidiabetic effect. The antidiabetic activity of chlorophyll and CHL contained in Liang leaves, Cu-chlorophyllin (CCL) Liang leaves treated with CuSO4, and untreated crude Liang leaves (CLL) were compared using commercial chlorophyllin (CHL) as a reference. Twelve Wistar male rats were separated into 4 groups (3 rats/group); the first was a normal one (based line group), the second were the diabetic rats treated with CHL, while the third and the fourth were the diabetic rats treated with 0.97 g/kg of CCL and CLL, respectively. Diabetic rats were induced by a high fructose diet, before being taken to administer commercial CHL, CCL, and CLL for 7 days. Nonfasting blood glucose and body weight were checked daily. After euthanasia, organ weight, biochemical, hematological, and histopathological properties were evaluated. CCL treatment showed no antihyperglycemic activity in the rat model but caused some biochemical abnormalities and thrombocytopenia. Commercial CHL gave a higher reduction of nonfasting blood glucose (NFBG) than Liang leaves powder CCL or CLL but also showed some signs of abnormal biochemical parameters. CLL exhibited an antihyperglycemic effect, with higher body weight and increased HDL/LDL ratio and thus could be a promising alternative natural source for diabetes treatment.
Global Existence and Decaying Rates of the Strong Solution for the Boussinesq System
Authors: Wang Lu , Yan Shuokai , Zhang Qinghua
Published: August 2023

This paper focuses on the global existence and time-decay rates of the strong solution for the Boussinesq system with full viscosity in

R

n

for

n
≥
3

. Under the initial assumption of

θ

0

,

u

0

∈

L

n
/
3

×

L

n

with a small norm, and

n
>
3

or

n
=
3

and

θ

0

∈

L

r

0

for some

r

0

>
1

, global existence and uniqueness of the strong solution

θ
,
u

for the Boussinesq system is established. This solution is proven to obey the following estimates:

θ

t

r

≤
C

t

−

3
−
n
/
p

/
2

for

n
/
3
≤
p
<
∞

,

u

t

p

≤
C

t

−

1
−
n
/
q

/
2

for

n
≤
q
≤
∞

,

∇
θ

t

p

≤
C

t

−

3
−
n
/
p

/
2
−
1
/
2

and

∇

2

θ

t

p

=
O

t

−
n

1
/
r
−
1
/
p

/
2
−
1

as

t
⟶
∞

for

r
≤
p
<
n
/
2

, and

∇
u

t

q

≤
C

t

−

1
−
n
/
q

/
2
−
1
/
2

and

∇

2

u

t

q

=
O

t

−
n

1
/
r
−
1
/
q

/
2
−
1

as

t
⟶
∞

for

n
≤
q
<
2
n

, where

r
=
n
/
3

if

n
>
3

and

1
<
r
<
 
min

r

0

,
n
/
2

if

n
=
3

.
Sequential Exposure to IL21 and IL15 During Human Natural Killer Cell Expansion Optimizes Yield and Function
Authors: Zhang Caimei , Kadu Siddhant , Xiao Yansen , Johnson Omar , Kelly Andre , O'Connor Roddy S. , Lai Meizan , Kong Hong , Srivatsa Sriram , Tai Victoria , Greenblatt Eli , Holmes Matthew , Riley James L. , June Carl H. , Sheppard Neil C.
Published: August 2023

Natural killer (NK) cells are frequently expanded for the clinic using irradiated, engineered K562 feeder cells expressing a core transgene set of membrane-bound (mb) IL15 and/or mbIL21 together with 41BBL. Prior comparisons of mbIL15 to mbIL21 for NK expansion lack comparisons of key attributes of the resulting NK cells, including their high-dimensional phenotype, polyfunctionality, the breadth and potency of cytotoxicity, cellular metabolism, and activity in xenograft tumor models. Moreover, despite multiple rounds of K562 stimulation, studies of sequential use of mbIL15- and mbIL21-based feeder cells are absent. We addressed these gaps and found that using mbIL15- versus mbIL21-based feeder cells drove distinct phenotypic and functional profiles. Feeder cells expressing mbIL15 alone drove superior functionality by nearly all measures, whereas those expressing mbIL21 alone drove superior yield. In combination, most attributes resembled those imparted by mbIL21, whereas in sequence, NK yield approximated that imparted by the first cytokine, and the phenotype, transcriptome, and function resembled that driven by the second cytokine, highlighting the plasticity of NK cell differentiation. The sequence mbIL21 followed by mbIL15 was advantageous in achieving significant yields of highly functional NK cells that demonstrated equivalent in vivo activity to those expanded by mbIL15 alone in two of three xenograft models. Our findings define the impact of mbIL15 versus mbIL21 during NK expansion and reveal a previously underappreciated tradeoff between NK yield and function for which sequential use of mbIL21-based followed by mbIL15-based feeder cells may be the optimal approach in many settings.
Irmãos na Terra Prometida: crime, igreja e regularização fundiária em São Paulo
Authors: Prieto Gustavo , Verdi Elisa Favaro
Published: August 2023

A tese que desenvolvemos neste artigo é que crime, igreja, empresas e movimentos sociais operam prolongamentos da violência da urbanização nas periferias de São Paulo. Essa violência é mediada, primeiro, pela propriedade privada como fundamento do habitar na cidade capitalista; segundo, pelo Estado e pelo planejamento urbano como operadores e reprodutores da valorização imobiliária e da segregação socioespacial; terceiro, pelo dano de uma vida cotidiana transpassada pela privação do urbano que se manifesta na proliferação de estratégias do empreendedorismo popular. Nessa mediação, concretiza-se uma hegemonia compartilhada da cotidianidade, articulada pela problemática fundiária no centro das disputas pela ordem. Tal hipótese surge de pesquisa etnográfica realizada desde 2017 em favelas da Zona Leste de São Paulo.
Do local ao global: cidades escritas em Luiz Bacellar e Astrid Cabral
Authors: Moura Fadul
Published: August 2023

O presente ensaio discute a presença da cidade nas poesias de Luiz Bacellar e Astrid Cabral. Procede-se à leitura cerrada de poemas retirados respectivamente de Frauta de barro (1963) e Ponto de cruz (1979) a fim de extrair afinidades e divergências entre os autores. O processo de análise é dividido em duas partes: primeiramente, situa-se o topos com alguns exemplos da história da poesia; em seguida, focalizam-se as imagens fundamentais de cada poema. Ao fim, uma abordagem comparada objetiva desfazer certos exotismos comuns quando se pensa em cidades poéticas de autores considerados amazônicos, ao passo que esses nomes revelam outras formas da relação entre poesia e experiência urbana.
Viagem, paisagem e poesia: os sertões de Guimarães Rosa e Juan Rulfo
Authors: Jorge Luís Antônio
Published: August 2023

Com o intuito de abordar os processos criativos no campo das práticas artísticas – o lugar da poesia na elaboração da linguagem ou a inscrição da dimensão poética no desenvolvimento do que se chama projeto no campo da arquitetura ou ainda, simplesmente, design em termos gerais –, o ensaio elege a literatura como exemplo do fazer artístico e, nela, os retratos da viagem e suas paisagens, como metáforas sobre tais processos criativos. Para isso, comenta dois contos, comparativamente, ambientados em dois sertões: “Cara-de-Bronze”, do escritor brasileiro João Guimarães Rosa, e “Talpa”, do escritor e fotógrafo mexicano Juan Rulfo.
RNA-Binding Proteins Regulate Post-Transcriptional Responses to TGF-β to Coordinate Function and Mesenchymal Activation of Murine Endothelial Cells
Authors: Wardman Rhys , Keles Merve , Pachkiv Ihor , Hemanna Shruthi , Grein Steve , Schwarz Jennifer , Stein Frank , Ola Roxana , Dobreva Gergana , Hentze Matthias W. , Heineke Joerg
Published: August 2023

BACKGROUND:

Endothelial cells (ECs) are primed to respond to various signaling cues. For example, TGF (transforming growth factor)-β has major effects on EC function and phenotype by driving ECs towards a more mesenchymal state (ie, triggering endothelial to mesenchymal activation), a dynamic process associated with cardiovascular diseases. Although transcriptional regulation triggered by TGF-β in ECs is well characterized, post-transcriptional regulatory mechanisms induced by TGF-β remain largely unknown.

METHODS:

Using RNA interactome capture, we identified global TGF-β driven changes in RNA-binding proteins in ECs. We investigated specific changes in the RNA-binding patterns of hnRNP H1 (heterogeneous nuclear ribonucleoprotein H1) and Csde1 (cold shock domain containing E1) using RNA immunoprecipitation and overlapped this with RNA-sequencing data after knockdown of either protein for functional insight. Using a modified proximity ligation assay, we visualized the specific interactions between hnRNP H1 and Csde1 and target RNAs in situ both in vitro and in mouse heart sections.

RESULTS:

Characterization of TGF-β–regulated RBPs (RNA-binding proteins) revealed hnRNP H1 and Csde1 as key regulators of the cellular response to TGF-β at the post-transcriptional level, with loss of either protein-promoting mesenchymal activation in ECs. We found that TGF-β drives an increase in binding of hnRNP H1 to its target RNAs, offsetting mesenchymal activation, but a decrease in Csde1 RNA-binding, facilitating this process. Both, hnRNP H1 and Csde1, dynamically bind and regulate specific subsets of mRNAs related to mesenchymal activation and endothelial function.

CONCLUSIONS:

Together, we show that RBPs play a key role in the endothelial response to TGF-β stimulation at the post-transcriptional level and that the RBPs hnRNP H1 and Csde1 serve to maintain EC function and counteract mesenchymal activation. We propose that TGF-β profoundly modifies RNA-protein interaction entailing feedback and feed-forward control at the post-transcriptional level, to fine-tune mesenchymal activation in ECs.
A Novel Silica Hybrid Nanoparticle with Zwitterion-Functionalized Polymer Chains for Highly Efficient N-Glycan Enrichment
Authors: Pan Yiting , Bai Haihong , Zhang Guocheng , Liu Wei , Wu Yanqi , Chen Hui , Tian Ying , Yang Zhenqi , Feng Duan , Liu Jiaqi , Wu Dan
Published: August 2023

N-Glycosylation is one of the most common and important protein posttranslational modifications. Structural aberrations of the N-glycans branching from glycoproteins are closely related to various disease occurrences and progressions. Therefore, global systematic identification of disease-related
N-glycans not only largely facilitates the understanding of their cellular functions but also promotes the development of new diagnostic and therapeutic biomarkers. However, N-glycans are low in abundance and hydrophilic, thereby hindering high-throughput, and large-scale N-glycan analysis
and N-glycoproteome research. Here, a zwitterion-functionalized polymer brush-grafted silica hybrid hydrophilic material (poly-SBMA-S) was fabricated by in situ growth of polymeric [2-(methacryloyloxy)ethyl]dimethyl(3-sulfopropyl)ammonium hydroxide (SBMA) chains on porous silica particles
through a surface-initiated atom transfer radical polymerization technique, and it was used as a new stationary phase for highly selective N-glycan enrichment. Human plasma demonstrated 64 N-glycans due to the densely packed polyzwitterion chains and the significantly increased coverage of
hydrophilic binding sites, demonstrating the high potential of the new hydrophilic matrix in the profiling and analysis of N-glycans and other hydrophilic targets.
Mitochondrial Enzymes Mediate Cisplatin Resistance in Hypopharyngeal Squamous Cell Carcinoma Cells
Authors: Zhao Xiaotong , Ma Dawei , Ju Guoyuan , Gui Bo , Yao Zhangyu , Zhang Jia , Zhao Yanbin , Liu Fangzhou , Zhang Xiao
Published: August 2023

Cisplatin, a widely used chemotherapeutic drug, faces significant challenges due to drug resistance, which hinders its clinical effectiveness. However, the molecular mechanism underlying cisplatin resistance remains unclear. Previous studies have shown that tumor cells rely on glycolysis
for energy and nutrients due to mitochondrial dysfunction. Yet, limited research has explored changes in energy metabolism after the development of drug resistance in tumor cells. In this study, we investigated the relationship between changes in key enzymes involved in aerobic respiration
in mitochondria and cisplatin resistance. Our findings revealed enhanced synthesis of citrate synthase (CS), succinate dehydrogenase (SD), and cytochrome oxidase (CCO) in drug-resistant cancer cells, with CCO showing the greatest increase. Notably, inhibiting CCO activity reversed drug resistance
in cancer cells. These findings shed light on a new mechanism of cisplatin resistance related to energy metabolism and offer a promising approach to overcoming resistance and improving clinical anticancer effects.
Orthokeratology and Visual Motor Training for Juvenile Myopia
Authors: Chen Yao , Zhang Jingjing , Huang Hui , Su Bo
Published: August 2023

This study aimed to explore the effect of orthokeratology (Ortho-K) combined with visual motor training in juvenile myopia. We included 156 myopia patients, which were randomly divided into the combined (visual motor training+Ortho-K) and Ortho-K (only) groups. Corneal morphological
changes (horizontal keratometry [HK], vertical keratometry [VK], central corneal thickness [CCT], and corneal endothelial cell density), regulatory function (positive and negative relative accommodation [PRA, NRA], regulatory amplitude, and regulatory sensitivity), ocular axis, visual acuity
(naked visual acuity, Diopter), tear film stability (BUT test and SIT test), intraocular pressure, and safety before and after treatment were compared between groups. Moreover, we performed a Spearman correlation analysis on the effects of initial age and diopter on axial growth. After treatment,
HK, VK of cornea, and CCT levels significantly decreased in both groups while no significant changes were found in endothelial cell density. In the combined group, there was a higher improvement in PRA, accommodation amplitude, and accommodation sensitivity, which could delay ocular axis growth
and improve naked eye vision and diopters. Meanwhile, a significant negative correlation was found between patients’ initial age and axial growth. Moreover, BUT and SIT recovery in the combined group were relatively better after wearing Ortho-K. In conclusion, Ortho-K combined with visual
motor training could better correct the vision of juvenile myopia patients and delay ocular axis growth. In addition, the earlier the intervention, the better the effect.
Non-SMC Condensin I Complex Subunit G Promotes the Proliferation, Invasion and Homologous Recombination Repair of Endometrial Cancer Through PI3K/AKT Signaling Pathway
Authors: Ren Zhen , Zheng Chunying , Xiao Xiao , Yang Xue , Li Xiaohan , Cai Haiyi , Fu Chun
Published: August 2023

This study aimed to investigate the role of Non-SMC condensin I complex subunit G (NCAPG) in endometrial cancer (EC) progression and prognosis. The researchers utilized various techniques, including analysis of The Cancer Genome Atlas (TCGA) database, immunohistochemistry, qRT-PCR, Western blotting, and functional assays to assess the impact of NCAPG on EC cells. The TCGA analysis revealed that NCAPG was significantly associated with overall survival and disease-free survival in EC patients. Immunohistochemistry analysis further confirmed a positive correlation between NCAPG expression, histological grade, and myometrial invasion in EC tissues.In vitroexperiments demonstrated that NCAPG promoted EC cell proliferation, invasion, and influenced the G1/S cell cycle transition. Additionally, NCAPG was found to regulate the expression of FANCD2 and RAD51 in the homologous recombination repair pathway, and its knockdown sensitized EC cells to poly (ADP-ribose) polymerase inhibitors. The study also revealed the involvement of the PI3K/AKT signaling pathway in mediating the effects of NCAPG on EC cells’ proliferation, invasion, and homologous recombination repair. In conclusion, NCAPG acts as an oncogene in EC, driving proliferation, invasion, and homologous recombination repair through the PI3K/AKT pathway. NCAPG expression correlates with EC prognosis, revealing its significance as a therapeutic target for advanced cases, illuminating EC progression mechanisms.
Anthropogenic Warming Had a Crucial Role in Triggering the Historic and Destructive Mediterranean Derecho in Summer 2022
Authors: González-Alemán Juan Jesús , Insua-Costa Damián , Bazile Eric , González-Herrero Sergi , Marcello Miglietta Mario , Groenemeijer Pieter , Donat Markus G.
Published: August 2023

A record-breaking marine heatwave and anthropogenic climate change have substantially contributed to the development of an extremely anomalous and vigorous convective windstorm in August 2022 over the Mediterranean Sea.
Physical Links from Atmospheric Circulation Patterns to Barents–Kara Sea Ice Variability from Synoptic to Seasonal Timescales in the Cold Season
Authors: Yu Feng Siew Peter , Wu Yutian , Ting Mingfang , Zheng Cheng , Clancy Robin , Kurtz Nathan T. , Seager Richard
Published: August 2023

Previous findings show that large-scale atmospheric circulation plays an important role in driving Arctic sea ice variability from synoptic to seasonal time scales. While some circulation patterns responsible for Barents–Kara sea ice changes have been identified in previous works, the most important patterns and the role of their persistence remain unclear. Our study uses self-organizing maps to identify nine high-latitude circulation patterns responsible for day-to-day Barents–Kara sea ice changes. Circulation patterns with a high pressure center over the Urals (Scandinavia) and a low pressure center over Iceland (Greenland) are found to be the most important for Barents–Kara sea ice loss. Their opposite-phase counterparts are found to be the most important for sea ice growth. The persistence of these circulation patterns helps explain sea ice variability from synoptic to seasonal time scales. We further use sea ice models forced by observed atmospheric fields (including the surface circulation and temperature) to reproduce observed sea ice variability and diagnose the role of atmosphere-driven thermodynamic and dynamic processes. Results show that thermodynamic and dynamic processes similarly contribute to Barents–Kara sea ice concentration changes on synoptic time scales via circulation. On seasonal time scales, thermodynamic processes seem to play a stronger role than dynamic processes. Overall, our study highlights the importance of large-scale atmospheric circulation, its persistence, and varying physical processes in shaping sea ice variability across multiple time scales, which has implications for seasonal sea ice prediction.

Significance Statement

Understanding what processes lead to Arctic sea ice changes is important due to their significant impacts on the ecosystem, weather, and shipping, and hence our society. A well-known process that causes sea ice changes is atmospheric circulation variability. We further pin down what circulation patterns and underlying mechanisms matter. We identify multiple circulation patterns responsible for sea ice loss and growth to different extents. We find that the circulation can cause sea ice loss by mechanically pushing sea ice northward and bringing warm and moist air to melt sea ice. The two processes are similarly important. Our study advances understanding of the Arctic sea ice variability with important implications for Arctic sea ice prediction.