Researcher mobility in a non-core region: outcomes for firms and academics in Northern Thailand

Entrepreneurship plays a crucial role in the economic and social development of non-core regions, and the exploration of its driving mechanisms has received considerable academic attention. This article applies the theory of entrepreneurial ecosystem to non-core regions with less generous entrepreneurial environments. Utilizing on-site survey data collected from Xingping County, a non-core region in western China and employing fuzzy-set qualitative comparative analysis (fsQCA) methodology, the study investigates how the interactions between entrepreneurial ecosystem elements promote or inhibit entrepreneurship in non-core regions with ungenerous entrepreneurial environment. The research reveals that entrepreneurship in non-core regions depends on the combined effects of multiple factors, leading to two pathways that generate high entrepreneurial rate: a policy-driven pathway and a human capital-supports-driven pathway. Additionally, the study identifies two pathways that result in low entrepreneurial rate: a supports-inhibitory pathway and a human capital-policy-inhibitory pathway. This research contributes to the theoretical understanding of entrepreneurial geography and provides decision-making foundations for fostering entrepreneurship and local economic development in non-core regions.

The evolutionary conservation of non-core RAG regions suggests significant roles that might involve quantitative or qualitative alterations in RAG activity. Off-target V(D)J recombination contributes to lymphomagenesis and is exacerbated by RAG2’ C-terminus absence in Tp53−/− mice thymic lymphomas. However, the genomic stability effects of non-core regions from both Rag1c/c and Rag2c/c in BCR-ABL1+ B-lymphoblastic leukemia (BCR-ABL1+ B-ALL), the characteristics, and mechanisms of non-core regions in suppressing off-target V(D)J recombination remain unclear. Here, we established three mouse models of BCR-ABL1+ B-ALL in mice expressing full-length RAG (Ragf/f), core RAG1 (Rag1c/c), and core RAG2 (Rag2c/c). The Ragc/c (Rag1c/c and Rag2c/c) leukemia cells exhibited greater malignant tumor characteristics compared to Ragf/f cells. Additionally, Ragc/c cells showed higher frequency of off-target V(D)J recombination and oncogenic mutations than Ragf/f. We also revealed decreased RAG cleavage accuracy in Ragc/c cells and a smaller recombinant size in Rag1c/c cells, which could potentially exacerbate off-target V(D)J recombination in Ragc/c cells. In conclusion, these findings indicate that the non-core RAG regions, particularly the non-core region of RAG1, play a significant role in preserving V(D)J recombination precision and genomic stability in BCR-ABL1+ B-ALL.

The evolutionary conservation of non-core RAG regions suggests significant roles that might involve quantitative or qualitative alterations in RAG activity. Off-target V(D)J recombination contributes to lymphomagenesis and is exacerbated by RAG2' C-terminus absence in Tp53-/- mice thymic lymphomas. However, the genomic stability effects of non-core regions from both Rag1c/c and Rag2c/c in BCR-ABL1+ B-lymphoblastic leukemia (BCR-ABL1+ B-ALL), the characteristics, and mechanisms of non-core regions in suppressing off-target V(D)J recombination remain unclear. Here, we established three mouse models of BCR-ABL1+ B-ALL in mice expressing full-length RAG (Ragf/f), core RAG1 (Rag1c/c), and core RAG2 (Rag2c/c). The Ragc/c (Rag1c/c and Rag2c/c) leukemia cells exhibited greater malignant tumor characteristics compared to Ragf/f cells. Additionally, Ragc/c cells showed higher frequency of off-target V(D)J recombination and oncogenic mutations than Ragf/f. We also revealed decreased RAG cleavage accuracy in Ragc/c cells and a smaller recombinant size in Rag1c/c cells, which could potentially exacerbate off-target V(D)J recombination in Ragc/c cells. In conclusion, these findings indicate that the non-core RAG regions, particularly the non-core region of RAG1, play a significant role in preserving V(D)J recombination precision and genomic stability in BCR-ABL1+ B-ALL.

In open mitosis the nuclear envelope (NE) reassembles at the end of each mitosis. This process involves the reformation of the nuclear pore complex (NPC), the inner and outer nuclear membranes, and the nuclear lamina. In human cells cell cycle-dependent NE subdomains exist, characterized as A-type lamin-rich/NPC-free or B-type lamin-rich/NPC-rich, which are initially formed as core or noncore regions on mitotic chromosomes, respectively. Although postmitotic NE formation has been extensively studied, little is known about the coordination of NPC and NE assembly. Here, we report that the nucleoporin ELYS/Mel28, which is crucial for postmitotic NPC formation, is essential for recruiting the lamin B receptor (LBR) to the chromosomal noncore region. Furthermore, ELYS/Mel28 is responsible for focusing of A-type lamin-binding proteins like emerin, Lap2α and the barrier-to-autointegration factor (BAF) at the chromosomal core region. ELYS/Mel28 biochemically interacts with the LBR in a phosphorylation-dependent manner. Recruitment of the LBR depends on the nucleoporin Nup107, which interacts with ELYS/Mel28 but not on nucleoporin Pom121, suggesting that the specific molecular interactions with ELYS/Mel28 are involved in the NE assembly at the noncore region. The depletion of the LBR affected neither the behavior of emerin nor Lap2α indicating that the recruitment of the LBR to mitotic chromosomes is not involved in formation of the core region. The depletion of ELYS/Mel28 also accelerates the entry into cytokinesis after recruitment of emerin to chromosomes. Our data show that ELYS/Mel28 plays a role in NE subdomain formation in late mitosis.

We explore the regional engagement of universities in non-core regions in a Global South context and uncover how new universities form and institutionalize regional ties. Through case studies of five new universities in India, we identify three routes – personal, organizational and brokered – through which new universities form regional ties, and four logics – incrementalism, social responsibility, legitimation and rationalization – through which these ties become embedded. We unpack and combine each of the routes and logics into a framework that explains how new ties are formed and developed between a new university and its surrounding non-core region.

Frequency preference and spectral tuning are two cardinal features of information processing in the auditory cortex. However, sounds should not only be processed in separate frequency bands because information needs to be integrated to be meaningful. One way to better understand the integration of acoustic information is to examine the functional connectivity across cortical depths, as neurons are already connected differently across laminar layers. Using a tailored receiver array and surface-based cortical depth analysis, we revealed the frequency–preference as well as tuning–width dependent intrinsic functional connectivity (iFC) across cortical depths in the human auditory cortex using functional magnetic resonance imaging (fMRI). We demonstrated feature-dependent iFC in both core and noncore regions at all cortical depths. The selectivity of frequency–preference dependent iFC was higher at deeper depths than at intermediate and superficial depths in the core region. Both the selectivity of frequency–preference and tuning–width dependent iFC were stronger in the core than in the noncore region at deep cortical depths. Taken together, our findings provide evidence for a cortical depth-specific feature-dependent functional connectivity in the human auditory cortex.

In high-power laser systems, fused silica aerosols produced by laser-induced damage to optical components impede further improvement in operation efficiency. To mitigate aerosol threats, low-speed gas knives are an attractive online option. Herein, we investigate the protective mechanism of a low-speed gas knife (<20 m/s) against aerosol invasion on the optical component. First, aerosol particles invaded the surface experimentally in two ways and were detected both in the core and non-core regions, depending on the coverage area of the protection flow. Particle sedimentation percentages can directly reflect the protection capability of the gas knife flow. Since a “midstream defect” is readily apparent, a CFD model was developed to explain the phenomenon from the perspective of velocity distribution. Additionally, the Euler-Lagrange method was used to track airflow particle motions and reappear the protective process. The numerical and experimental results on protection efficiency are closely correlated. The numerical calculation indicates that the “midstream defect” manifested in the core region is possibly attributed to the turbulent dispersion and anisotropic near-wall effects of particles of various diameters, while in the non-core region, the mechanism differs. This work provides a framework for airflow clean designs inside high-power laser systems.

The RAG1/RAG2 endonuclease initiates V(D)J recombination at antigen receptor loci but also binds to thousands of places outside of these loci. RAG2 localizes directly to lysine 4 trimethylated histone 3 (H3K4me3) through a plant homeodomain (PHD) finger. The relative contribution of RAG2-dependent and RAG1-intrinsic mechanisms in determining RAG1 binding patterns is not known. Through analysis of deep RAG1 ChIP-seq data, we provide a quantitative description of the forces underlying genome-wide targeting of RAG1. Surprisingly, sequence-specific DNA binding contributes minimally to RAG1 targeting outside of antigen receptor loci. Instead, RAG1 binding is driven by two distinct modes of interaction with chromatin: the first is driven by H3K4me3, promoter-focused and dependent on the RAG2 PHD, and the second is defined by H3K27Ac, enhancer-focused and dependent on ‘non-core’ portions of RAG1. Based on this and additional chromatin and genomic features, we formulated a predictive model of RAG1 targeting to the genome. RAG1 binding sites predicted by our model correlate well with observed patterns of RAG1-mediated breaks in human pro-B acute lymphoblastic leukemia. Overall, this study provides an integrative model for RAG1 genome-wide binding and off-target activity and reveals a novel role for the RAG1 non-core region in RAG1 targeting.

BackgroundThe repertoire of the antigen-binding receptors originates from the rearrangement of immunoglobulin and T-cell receptor genetic loci in a process known as V(D)J recombination. The initial site-specific DNA cleavage steps of this process are catalyzed by the lymphoid specific proteins RAG1 and RAG2. The majority of studies on RAG1 and RAG2 have focused on the minimal, core regions required for catalytic activity. Though not absolutely required, non-core regions of RAG1 and RAG2 have been shown to influence the efficiency and fidelity of the recombination reaction.ResultsUsing a partial proteolysis approach in combination with bioinformatics analyses, we identified the domain boundaries of a structural domain that is present in the 380-residue N-terminal non-core region of RAG1. We term this domain the Central Non-core Domain (CND; residues 87-217).ConclusionsWe show how the CND alone, and in combination with other regions of non-core RAG1, functions in nuclear localization, zinc coordination, and interactions with nucleic acid. Together, these results demonstrate the multiple roles that the non-core region can play in the function of the full length protein.

The Software Process - What It Is, And HowTo Improve It

BackgroundResearchers have a responsibility to protect all participants, especially vulnerable participants, from harm. Vulnerability is increasingly understood to be context specific, yet limited guidance is available regarding the vulnerability and agency of research participants in different cultural settings. This study aims to explore research participants’ daily vulnerability and agency, and how these interact with participants’ research experiences in their own words. Researchers’ views and responses were also explored.MethodsA qualitative study was conducted around two scrub typhus research studies in northern Thailand. A thematic analysis was carried out on 42 semi-structured interviews with research participants, their families, researchers and key informants.ResultsThe majority of the research participants belonged to a hill tribe ethnic minority group. Common challenges were related to Thai language barriers, travel difficulties, uncertain legal status, unstable employment, lack of education and healthcare. We did not identify new vulnerabilities but we found that the extent of these vulnerabilities might be underestimated or even hidden from researchers in some cases. Despite these challenges people demonstrated agency in their daily lives and were often motivated and supported in this by family members. The majority of perceived research benefits were related to healthcare and gaining knowledge, while attending follow-up visits could be a burden for some.ConclusionsOur approach to research in culturally and socioeconomically diverse settings should be more responsive to participants’ specific vulnerabilities and abilities evidenced in their daily life, rather than attributing vulnerability on the basis of membership of pre-defined ‘vulnerable groups’. Researchers need to be aware and responsive towards the challenges participants face locally in order to minimise the burdens of research participation whilst allowing participants to benefit from research.

Researchers have a responsibility to protect all participants, especially vulnerable participants, from harm. Vulnerability is increasingly understood to be context specific, yet limited guidance is available regarding the vulnerability and agency of research participants in different cultural settings. This study aims to explore research participants' daily vulnerability and agency, and how these interact with participants' research experiences in their own words. Researchers' views and responses were also explored. A qualitative study was conducted around two scrub typhus research studies in northern Thailand. A thematic analysis was carried out on 42 semi-structured interviews with research participants, their families, researchers and key informants. The majority of the research participants belonged to a hill tribe ethnic minority group. Common challenges were related to Thai language barriers, travel difficulties, uncertain legal status, unstable employment, lack of education and healthcare. We did not identify new vulnerabilities but we found that the extent of these vulnerabilities might be underestimated or even hidden from researchers in some cases. Despite these challenges people demonstrated agency in their daily lives and were often motivated and supported in this by family members. The majority of perceived research benefits were related to healthcare and gaining knowledge, while attending follow-up visits could be a burden for some. Our approach to research in culturally and socioeconomically diverse settings should be more responsive to participants' specific vulnerabilities and abilities evidenced in their daily life, rather than attributing vulnerability on the basis of membership of pre-defined 'vulnerable groups'. Researchers need to be aware and responsive towards the challenges participants face locally in order to minimise the burdens of research participation whilst allowing participants to benefit from research.

V(D)J recombination generates functional immunoglobulin and T-cell receptor genes in developing lymphocytes. The recombination-activating gene 1 (RAG1) and RAG2 proteins catalyze site-specific DNA cleavage in this recombination process. Biochemical studies have identified catalytically active regions of each protein, referred to as the core regions. Here, we review our progress in the identification and characterization, in biophysical and biochemical terms, of topologically independent domains within both the non-core and core regions of RAG1. Previous characterizations of a structural domain identified in the non-core region of RAG1 from residues 265-380, referred to as the zinc-binding dimerization domain, are discussed. This domain contains two zinc-binding motifs, a RING finger and a C2H2 zinc finger. Core RAG1 also consists of multiple domains, each of which functions individually in one or more of the essential macromolecular interactions formed by the intact core protein. Two structural domains referred to as the central and the C-terminal domains that include residues 528-760 and 761-979 of RAG1, respectively, have been identified. The interactions of the central and C-terminal domains in core RAG1 with the recombination signal sequence (RSS) have contributed additional insight to a developing model for the RAG1-RSS complex.

Software Quality Assurance and Process Improvement are subjects that are difficult to teach in a software engineering course. Students rarely gain an in-depth understanding of the concepts and ideas inherent in process assessment, let alone practical experience with improving software processes. This paper describes a process assessment and improvement experiment performed by the Real World Lab, an undergraduate Software Engineering Practicum course series at Georgia Tech. We used (he SEI's Capability Maturity Model (CMM) as an assessment vehicle for the RWL processes, in order to evaluate not only the software process used in the RWL, but also the educational strengths of our simulated “real world” industry environment.KeywordsProcess ImprovementConfiguration ManagementGeorgia TechImprove Software ProcessCapability Maturity ModelThese keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

New and affordable point-of-care testing (POCT) solutions are hoped to guide antibiotic prescription and to help limit antimicrobial resistance (AMR)—especially in low- and middle-income countries where resource constraints often prevent extensive diagnostic testing. Anthropological and sociological research has illuminated the role and impact of rapid point-of-care malaria testing. This paper expands our knowledge about the social implications of non-malarial POCT, using the case study of a C-reactive-protein point-of-care testing (CRP POCT) clinical trial with febrile patients at primary-care-level health centres in Chiang Rai province, northern Thailand. We investigate the social role of CRP POCT through its interactions with (a) the healthcare workers who use it, (b) the patients whose routine care is affected by the test, and (c) the existing patient-health system linkages that might resonate or interfere with CRP POCT. We conduct a thematic analysis of data from 58 purposively sampled pre- and post-intervention patients and healthcare workers in August 2016 and May 2017.We find widespread positive attitudes towards the test among patients and healthcare workers. Patients’ views are influenced by an understanding of CRP POCT as a comprehensive blood test that provides specific diagnosis and that corresponds to notions of good care. Healthcare workers use the test to support their negotiations with patients but also to legitimise ethical decisions in an increasingly restrictive antibiotic policy environment. We hypothesise that CRP POCT could entail greater patient adherence to recommended antibiotic treatment, but it could also encourage riskier health behaviour and entail potentially adverse equity implications for patients across generations and socioeconomic strata. Our empirical findings inform the clinical literature on increasingly propagated point-of-care biomarker tests to guide antibiotic prescriptions, and we contribute to the anthropological and sociological literature through a novel conceptualisation of the patient-health system interface as an activity space into which biomarker testing is introduced.