Weak Basis Research Articles

Heterogeneity of tumor microenvironment cell groups in inflammatory and adenomatous polyposis coli mutant colorectal cancer based on single cell sequencing.

The prognosis of colorectal cancer (CRC) is known to vary across different etiologies. Inflammatory bowel disease (IBD) is often identified as a factor contributing to poorer outcomes. However, the mechanisms that link IBD to a worse CRC prognosis remain to be elucidated. We aim to reveal the complex tumor microenvironment of inflammatory CRC and provide a weak theoretical basis for the treatment of different subtypes of CRC. We conducted a bioinformatics analysis using single-cell RNA sequencing (scRNA-seq) data from 8,494 individual CRC cells derived from azoxymethane (AOM)/dextran sodium sulfate (DSS) and adenomatous polyposis coli (APC) mutant datasets. The expression of implicated genes in both tumor and adjacent normal tissues was examined via immunohistochemistry and immunofluorescence. CRC from AOM/DSS treatment contained fewer immune cells relative to APC-mutant CRC. However, a macrophage subcluster enriched for inflammatory factors was more prevalent in AOM/DSS datasets. This subcluster exhibited elevated expression of APOE and BNIP3. Immunofluorescence and immunohistochemistry of patient samples confirmed that the expression of APOE and BNIP3 was higher in adjacent normal tissues compared to tumors. Our findings shed light on the heterogeneous microenvironments in IBD and APC-mutant CRC. Furthermore, we identify APOE as a potential biomarker for CRC recurrence.

A stable localized weak strong form radial basis function method for modelling variably saturated groundwater flow induced by pumping and injection

The unsaturated zone profoundly affects groundwater (GW) flow induced by pumping and injection due to the capillary forces. However, current radial basis function (RBF) numerical models for GW pumping and injection mostly ignore the unsaturated zone. To bridge this gap, we developed a new three-dimensional weak strong form RBF model in this study, called CCHE3D-GW-RBF. Flow processes were modelled by the mixed-form Richards equation which was iteratively solved by the modified Picard iteration. Soil-water characteristic curves were represented by the widely applicable formulas, the van Genuchten (1980) model. Differential operators were approximated by the localized Gaussian RBF, and the weighted singular value decomposition method was used to construct stable bases. The injection/pumping wells and the flux boundaries were handled by the weak formulation using Meshless Local Petrov Galerkin method, and the strong-form equation using the collocation RBF method was enforced on the other points. Good agreement was found between the simulation results from our numerical model and the well-accepted solutions in all three verification cases, demonstrating the accuracy and applicability of this model. In addition, a smaller RBF shape parameter was found to produce a more accurate modelling resulting, indicating the necessity of implementing stable bases for RBF models.

Enabling cross border open finance systems in Latin America: is consent enough to develop them?

ABSTRACT Since 2016, digital finances have been disrupted by the introduction of open banking policies, which would facilitate data sharing in this particular industry. The UK and the EU have led this approach through the adoption of legal rules that enabled data sharing between financial institutions, particularly payment services providers, under users’ permission; lately, this has been slowly expanded into other financial services and called open finance. In this respect, certain Latin American countries have followed this, particularly led by industry efforts. In contrast to the EU, where the Digital Single Market facilitates the necessary conditions for sharing data, Latin America is fragmented in this respect. As such, this permission might be a weak basis for enabling a cross-border open finance ecosystem. This contribution will explore a selected cohort of Latin American countries and assess whether it would be feasible the development of a regional open finance system.

Climate change and migration: A review and new framework for analysis

AbstractThis article presents a new interpretive framework for understanding the implications of climate change for migration, and reviews and reflects on existing evidence and research gaps in light of this framework. Most existing climate‐migration research is heavily environment‐centric, even when acknowledging the importance of contextual or intervening factors. In contrast, the framework proposed here considers five different pathways through which climate change is affecting, or might affect, migration: short‐term shocks, long‐term climatic and related changes, environmental “pull” factors, climate adaptation and mitigation measures, and perceptions and narratives. In reviewing the existing evidence relating to each of these pathways, the paper finds among other things that short‐term shocks may simultaneously increase and reduce migration; that the evidence on long‐term trends provides a weak basis for understanding future dynamics; and that more attention needs to be paid to the other three pathways, by researchers and policymakers alike. Overall, the proposed framework and associated evidence review suggest a different and broader understanding of the migration implications of climate change from that outlined in the IPCC's most recent assessment, or in many existing reviews.This article is categorized under:Climate and Development Knowledge and Action in Development

Machine-learning-guided Directed Evolution for AAV Capsid Engineering.

Target gene delivery is crucial to gene therapy. Adeno-associated virus (AAV) has emerged as a primary gene therapy vector due to its broad host range, long-term expression, and low pathogenicity. However, AAV vectors have some limitations, such as immunogenicity and insufficient targeting. Designing or modifying capsids is a potential method of improving the efficacy of gene delivery, but hindered by weak biological basis of AAV, complexity of the capsids, and limitations of current screening methods. Artificial intelligence (AI), especially machine learning (ML), has great potential to accelerate and improve the optimization of capsid properties as well as decrease their development time and manufacturing costs. This review introduces the traditional methods of designing AAV capsids and the general steps of building a sequence-function ML model, highlights the applications of ML in the development workflow, and summarizes its advantages and challenges.

Oral microbiome research - working in partnership with Indigenous Australian communities.

Microbiome research is currently biased towards populations of European descent, with such populations providing a weak basis upon which to understand microbiome-health relationships in under-studied populations, many of whom carry the highest burdens of disease. Most oral microbiome studies to date have been undertaken in industrialized countries. Research involving marginalised populations should be shaped by a number of guiding principles. In the Indigenous Australian context, one useful framework is the Consolidated Criteria for Strengthening Reporting of Health Research involving Indigenous Peoples (CONSIDER) statement. This paper describes how the microbiome research field is having impacts in the Indigenous Australian health space, and describes a particular project involving Indigenous Australians in which the CONSIDER statement is used as the underlying framework.

Appropriate Timing of End-of-Life Care: A Dutch Policy Analysis and Opportunities for Improvement.

The Exceptional Medical Expenses Act (EMEA) guaranteed public financing for the costs of end-of-life care in The Netherlands until 2015. A life expectancy shorter than three months was a prerequisite for a patient to qualify. To estimate survival and its potential predictors using the start date of EMEA funded end-of-life care as time origin, and to calculate the ensuing costs. Retrospective observational study using data retrieved from multiple datasets of the national statistical office Statistics Netherlands (https://www.cbs.nl/en-gb/). Included were all adult patients, who received EMEA funded end-of-life care in hospice units in nursing homes and homes for the elderly in The Netherlands between January 1, 2009, and December 31, 2014. In 40,659 patients (median age 79 years), the distribution of survival was extremely skewed. Median, 95%, and maximum survival times were 15 (95% confidence interval [CI] = 15-15), 219 (210-226), and 2,006 days, respectively. The 90-day and 180-day survival rates were 12.4 (12.1-12.7)% and 6.2 (6.0-6.5)%, respectively. Although age, gender, diagnosis, and start year of end-of-life care were statistically significant independent predictors, clinical significance is limited. End-of-life care was delivered for a total of 1,720,002 days, costing almost 440 million Euros. Fifty-nine percent of the costs was for barely 11% of patients, i.e., those who received end-of-life care for more than 90 days. The use of life expectancy is a weak basis for the appropriate timing of end-of-life care. Further research should evaluate potential tools to improve the timing of end-of-life care, while using available resources efficiently.

Dilemma and Outlet of Personality Right Protection in Sports Event Copyright

Using jurisprudence to analyze the connotation and logical relationship of personality right, explore the practical dilemma of personality right protection in sports event copyright, and then point out the path of personality right protection in sports event copyright. The research shows that the adverse factors of the protection of personality rights mainly lie in the controversial theoretical basis, the lack of attention of the subject of rights, the lack of in-depth academic research and the weak legal basis. Suggestions: On the theoretical basis, we should not only recognize the work attribute of sports events, but also emphasize the dialectical unity of "content" and "form" of works, which are the prerequisite for the protection of personality rights; In the protection of personality right, we should not only improve the awareness of safeguarding rights of the subject of rights, but also establish the concept of the overall situation of the subject of rights, so as to promote the healthy development of the sports event market. The subject of rights cannot ignore the protection of personality right due to the realization of property right; In theoretical research, academia should pay attention to the value status of personality right, strengthen the research on the protection of personality right, and provide scientific legal basis for the protection of personality right; On the basis of legal system, we should not only improve the guiding role of sports law in the protection of personality rights, but also expand the scope of works in the copyright law , so as to build a solid legal foundation for the protection of personality rights.

The status and development strategy of coalbed methane industry in China

To achieve the goals of carbon peaking and carbon neutrality under the backgrounds of poor resource endowments, weak theoretical basis and other factors, the development of the coalbed methane industry of China faces many bottlenecks and challenges. This paper systematically analyzes the coalbed methane resources, key technologies and progress, exploration effect and production performance in China and abroad. The main problems are summarized as low exploration degree, low technical adaptability, low return on investment and small development scale. This study suggests that the coalbed methane industry in China should follow the “two-step” (short-term and long-term) development strategy. The short-term action before 2030, can be divided into two stages: (1) From the present to 2025, to achieve new breakthroughs in theory and technology, and accomplish the target of annual production of 10 billion cubic meters; (2) From 2025 to 2030, to form the technologies suitable for most geological conditions, further expand the industry scale, and achieve an annual output of 30 billion cubic meters, improving the proportion of coalbed methane in the total natural gas production. The long-term action after 2030 is to gradually realize an annual production of 100 billion cubic meters. The strategic countermeasure to achieve the above goals is to adhere to “technology+management dual wheel drive”, realize the synchronous progress of technology and management, and promote the high-quality development of the coalbed methane industry. Technically, the efforts will focus on fine and effective development of coalbed methane in the medium to shallow layers of mature fields, effective development of coalbed methane in new fields, extensive and beneficial development of deep coalbed methane, three-dimensional comingled development of coalbed methane, applying new technologies such as coalbed methane displacement by carbon dioxide, microwave heating and stimulation technology, ultrasonic stimulation, high-temperature heat injection stimulation, rock breaking by high-energy laser. In terms of management, the efforts will focus on coordinative innovation of resource, technology, talent, policy and investment, with technological innovation as the core, to realize an all-round and integrated management and promote the development of coalbed methane industry at a high level.

Reforms and Responses to the Internal Governance Structure of Primary and Secondary School in the Context of High-Quality Development in Mainland China

In the wake of the focus on improving the quality of education in the international community, the development of the cause of education in mainland China has entered the stage of high-quality development. Currently, the construction of internal governance structures for primary and secondary schools in mainland China exhibits three areas of difficulties and problems: In vertical governance structures, the configurations are overly hierarchical, and there is a high cost of communication and coordination, and difficulty forwarding reforms and innovations; in horizontal governance structures, professional organizations do not have high status, there is a low degree of coordination, and efforts for oversight and assurance are inadequate; in integrated network governance structures, there is a weak basis for consensus and low responsiveness, and the degree of coupling needs improvement. In order to adapt to the needs of high-quality development, primary and secondary schools in mainland China must make reforms to and tackle several aspects of their internal governance structures, vertically adhering to the logic of management reform, to improve the rationality of decision-making and promote flattening of vertical structures; horizontally adhering to the logic of intrinsic development, to improve the status, authority and influence of a school’s professional organizations; and integratively abiding by the logic of systems integration, to build deliberative democratic network governance structures on the foundation of a consensus of ideas.

Judicial Activism and Judge-Made Law at the ECtHR

Abstract This paper contributes to an ongoing debate concerning the perceived judicial activism of the European Court of Human Rights (ECtHR). It argues that the output of the Court should be better viewed as the phenomenon of judicial law-making, not unlike in domestic jurisdictions. However, unlike many domestic legal systems, the European Convention on Human Rights framework promotes large quantities of judge-made law. This outcome results from a combination of objective factors that, taken together, enhance the process of judicial law-making by the ECtHR. Those factors include the applied mode of interpretation of the Convention, the approach to its construction, the weak textual basis, the existence of positive obligations, the lack of the doctrine of precedent, the extremely high case law and judicial turnovers, the concurrent legislative inactivity, the existence of the inter-state jurisdiction and the doctrine of autonomous meaning. At the same time, the judicial law-making is only hindered by the doctrine of subsidiarity, the principle of margin of appreciation and the Fourth Instance doctrine. As a consequence of this overwhelming dominance of the factors enhancing the process of judicial law-making over those that hinder it, the ECtHR produces large quantities of judge-made law.

Klimaendringer, følelser og benektelse: en psykoanalytisk pilotstudie

Background and aim: Anthropogenic climate change represents an increasing threat to the stability of human societies and ecosystems. The aim of this pilot study was to examine the relationship between emotional activation and the defense mechanism of denial. Few previous studies have investigated this topic while also exploring unconscious aspects of denial. Method: Three informants were interviewed in depth on two separate occasions (six interviews in total). The in-depth interviews were based on the psychoanalytic research interview as described by Cartwright (2004) and Holloway and Jefferson (2012). Results: The analysis showed that climate change was a highly emotional issue for two of the informants, who made use of denial as a distancing strategy. Conclusion: Denial is a common response to climate change, one that can lead to an absence of action and commitment. The restricted sample and method of the pilot study provided a weak basis for generalization, and further studies should use more stringent research designs. Keywords: climate change, denial, psychoanalytic

Size dependent free vibration analysis of 2D-functionally graded curved nanobeam by meshless method

The free vibration of two-directional functionally graded (2D-FG) thick curved nanobeam with concentrated mass is investigated for various boundary conditions. Hamilton’s principle is employed to develop the governing equations of the 2D-FG curved nanobeam using the first-order shear deformation theory (FSDT). The small scale effect is captured by the nonlocal elasticity theory of Eringen. The nanobeam is functionally graded in the transverse and circumferential directions of the curved nanobeam. The governing equations of the system are obtained as three coupled partial differential equations with non-constant coefficients. An appropriate meshless formulation is developed to discretize the governing equations based on local weak formulation and radial basis function. The presented meshless method is employed to study the free vibration of the one-directional and two-directional functional graded curved nanobeams. Simple-simple, free-free, clamped-clamped, and clamped-free edge conditions are investigated. Moreover, an analytical solution is developed for simple-simple transversely 1D-FG curved nanobeam. In the numerical results, the natural frequencies and mode shapes of shadow and deep curved nanobeam are studied and the influence of effective parameters such as nonlocal parameter, FG power indexes, opening angle, edge conditions, and concentrated mass are investigated. It is seen that shear locking effect is eliminated in present meshless formulation.

What's wrong with osteopathy?

This commentary critically examines the foundational assumptions, practices and claimed distinctiveness upon which osteopathy was built and continues to be structured. Five areas which are considered to be highly problematic for osteopathy, namely its weak theoretical basis, inherent biomedicalism, monointerventionism, default practitioner-centredness and predilection for implausible mechanisms. It is argued that these areas require considerable reflection and action as if not remedied, they constitute a major threat to the development, unity and legitimacy of the osteopathic profession. Ongoing reconceptualisation of underpinning theories, assumptions and associated skills informed by current evidence and knowledge from disciplines outside of the osteopathic domain is necessary for professional maturation. Implications for practice•Osteopathy's weak theoretical basis, biomedicalism, monointerventionism, practitioner-centredness and implausible mechanisms are problematic.•These constitute a major threat to the development, unity and legitimacy of osteopathy.•Ongoing critical reflection, practice reconceptualisation and research are needed for professional maturation.•Osteopaths should draw on theory and evidence from outside the osteopathic domain.

In a split second: Handwriting pauses in typical and struggling writers.

A two-second threshold has been typically used when analyzing the writing processes. However, there is only a weak empirical basis to claim that specific average numbers and durations of pauses may be associated with specific writing processes. We focused on handwriting execution pauses, because immature writers are known to struggle with transcription skills. We aimed to provide an evidence-based account of the average number and duration of handwriting pauses in the mid-Primary grades and to identify process-level markers of writing difficulties. Eighty 3rd and 5th graders, with and without writing difficulties, participated in the study. We examined pauses in a handwriting-only task, to be able to isolate those which could only be attributed to handwriting processes. Letter features were considered, as well as children's handwriting fluency level. The average duration of handwriting pauses was around 400ms, in line with assumptions that transcription pauses would fall under the 2,000ms threshold. We found that 3rd graders made more and longer pauses than 5th graders. Struggling writers made a similar number of pauses across grades than typically-developing children, although they were significantly longer, even after controlling for the effect of handwriting fluency. Our findings provide an evidence-based account of the duration of handwriting pauses. They also suggest that children need fewer and shorter handwriting pauses as they progress in automatizing transcription. However, some young writers struggle with letter formation even after 3 to 5 years of instruction.

Gender Identity Discrimination and Religious Freedom

AbstractIs there a legitimate basis for religious exemptions from laws that prohibit gender identity discrimination on the basis of people’s beliefs? The author argues that much depends upon how gender dysphoria is understood. If it is seen as a problem requiring medical diagnosis and treatment, then arguably there is no religious basis for discrimination, except in a few situations where being a biological male or female is theologically essential to a particular role. Transgender identification, understood as a medical issue, fits within a belief system that God created two sexes of human beings, male and female. Within that belief system one can make room for an understanding that there are those who experience disorders of sex development and those who have such a profound sense of being born in the wrong body that they undertake steps toward medical transition to align their bodies, as far as possible, with the opposite sex. However, recent reinterpretations of what it means to be transgender involve an assertion that it should not be seen as a medical issue, that affirmation of a person’s self-declared gender identity, with or without having hormonal treatment or surgery, is a matter of human rights and that the law should recognize that people may have a gender that, however described, is nonbinary. These views rely on certain beliefs and positions that have a very weak basis in science. They challenge religious beliefs, which accord with mainstream scientific understanding, that human beings are intrinsically a sexually dimorphic species. People of faith need the freedom to reject beliefs that are incompatible with their worldviews. That does not mean that ill-treatment of someone on the basis of their gender identity can ever be justified; but it does support a religious exemption from a legal obligation to accept someone else’s self-declared gender identity. It is one thing to ask me to respect your beliefs about yourself. It is another to ask me to act toward you as if I share your beliefs.

Influence of Dowel Center Spacing on Chamfered-Joint Components Made by Cupressus funebris Wood

The traditional tenon and mortise joint has low processing efficiency and a weak theoretical basis, making the structure easy to deform and damage, reducing the safety, and increasing waste of resources. This study aims to determine the optimum dowel center spacing parameter for chamfered-joint components and the maximum value of the strength of joints loaded into bending strength and tensile strength. In this study, an integrated optimization method combining the single-factor test and one-way ANOVA analysis was proposed to study the influence of the dowel center spacing on the bending strength and the tensile strength of chamfered-joint components made by Cupressus funebris wood. The results revealed that the bending strength of chamfered-joint components decreases linearly with the increase of the dowel center spacing. In addition, the tensile strength of chamferedjoint components increases first and then decreases with the increase of the dowel center spacing, showing parabola change. The relational expression between dowel center spacing, the bending strength, dowel center spacing and the tensile strength were obtained.

동아시아를 횡단한 의고의 계보와 학술사적 전망

How did the critical scholarship doubting the authenticity of ancient texts originate and theorize? In the case of East Asia, one can quickly think of Gu Jiegang 顧頡剛 (1893-1980), the representative of the so-called Doubting Antiquity School. But there must have been a long history advocating the idea preceding Gu Jiegang. Based on the criticism on the discrepancies inherent in the ancient texts such as the Venerated Document (Shangshu) suggested by Wang Chung 王充 (27-96?), Liu Zhiji 劉知幾 (661-721), and Ouyang Xiu 歐陽修 (1007-1072), it was not until the 18th century when the scholarly quest for the cause behind the contradictions indeed began.BR The first step in theorizing the doubting of antiquity was the theory of superseding (kajō 加上) proposed by Tominaga Nakamoto 富永仲基(1715-1746). According to Tominaga, competitions between scholars to overcome previous explanations stimulated them to attribute their narratives to far-earlier sages deliberately. It was Cui Shu 崔述 (1740-1816) who applied a similar idea to history and found a fabricating pattern, in which he hypothesized that later the work, the farther in time the purported knowledge of the past is pushed back and the more complex the historical knowledge. All the same, it was not until the early 20th century when Shiratori Kurakichi 白鳥庫吉 (1865-1942) for the first time initiated the iconoclasm of sage kings such as Yao, Shun and Yu as the premise for establishing the doubting antiquity theory. Refining the relatively weak basis of Shiratori’s argument elaborately, Gu Jiegang completed the approach with the idea of the “accumulated creation of ancient history.”BR However, the sheer accumulation of archaeological discoveries in China during the second half of the 20th century exposed limitations in the idea of fabricated ancient texts promoted by the Doubting Antiquity School. Especially, Li Ling convincingly points out that they oversymplified the complicated long-term process of textual formation in early China. In this regard, studying the canonization process from the stream of textual tradition in the newly unearthed Warring States bamboo slips would provide a new vista to overcome the limitations inherent in the theory of doubting antiquity.

Weak edge triangle free detour number of a graph

For any two vertices u and v in a connected graph G = ( V , E ), a u − v path P is called a u − v triangle free path if no three vertices of P induce a triangle. The triangle free detour distance D △ f ( u , v ) is the length of a longest u − v triangle free path in G . A u − v path of length D △ f ( u , v ) is called a u − v triangle free detour . A set S ⊆ V is called a weak edge triangle free detour set of G if every edge of G has both ends in S or it lies on a triangle free detour joining a pair of vertices of S . The weak edge triangle free detour number w d n △ f ( G ) of G is the minimum order of its weak edge triangle free detour sets and any weak edge triangle free detour set of order w d n △ f ( G ) is a weak edge triangle free detour basis of G . Certain properties of these concepts are studied. The weak edge triangle free detour numbers of certain classes of graphs are determined. Its relationship with the triangle free detour diameter is discussed and it is proved that for any three positive integers a , b and n of integers with 3 ≤ b ≤ n − a + 1 and a ≥ 4, there exists a connected graph G of order n with triangle free detour diameter D △ f = a and w d n △ f ( G )= b . It is also proved that for any three positive integers a , b and c with 3 ≤ a ≤ b and c ≥ b + 2, there exists a connected graph G such that R △ f = a , D △ f = b and w d n △ f ( G )= c .

Severe feather deformation in greater white-fronted goose (Anser alb. albifrons) goslings during hot summer period on Kolguev Island 2016.

In summer 2016, we observed premature feather malformation among goslings of greater white-fronted goose (Anser alb. albifrons), between 7 and 10 weeks of age on family gathering areas on Kolguev Island, Russia, the most important breeding island in the Western Palearctic. Rarely reported in wild birds, to our knowledge, this phenomenon has not been recorded in wild geese of this species, despite continuous ringing and marking of thousands of wild geese across Northern Europe and Arctic Siberia. This feather malformations were documented in 36 unfledged goslings showing weak feather basis, deformed or unevenly grown wing feathers or even dead feather buds. Approximately about one-third of all chicks were affected. Feather malformations like this, causing flightless chicks as a result, have never been noticed in any other of our 12 study years since 2006. The lesion was characterised by soft feather buds, weak or incomplete wing feathers and lack of feather development. No other abnormalities were observed in the goslings, so goslings did not differ in weight or body sizes. Affected fledglings never became airworthy and were killed in large numbers by predators or at latest perished during the Arctic winter. Supplementary InformationThe online version contains supplementary material available at 10.1007/s10344-022-01603-9.