223 research outputs found
On the Approximability and Hardness of the Minimum Connected Dominating Set with Routing Cost Constraint
In the problem of minimum connected dominating set with routing cost
constraint, we are given a graph , and the goal is to find the
smallest connected dominating set of such that, for any two
non-adjacent vertices and in , the number of internal nodes on the
shortest path between and in the subgraph of induced by is at most times that in . For general graphs, the only
known previous approximability result is an -approximation algorithm
() for by Ding et al. For any constant , we
give an -approximation
algorithm. When , we give an -approximation
algorithm. Finally, we prove that, when , unless , for any constant , the problem admits no
polynomial-time -approximation algorithm, improving
upon the bound by Du et al. (albeit under a stronger hardness
assumption)
When LLMs step into the 3D world: a survey and meta-analysis of 3D tasks via multi-modal Large Language Models
As large language models (LLMs) evolve, their integration with 3D spatial data (3D-LLMs) has seen rapid progress, offering
unprecedented capabilities for understanding and interacting with physical spaces. This survey provides a comprehensive overview of
the methodologies enabling LLMs to process, understand, and generate 3D data. Highlighting the unique advantages of LLMs, such as
in-context learning, step-by-step reasoning, open-vocabulary capabilities, and extensive world knowledge, we underscore their
potential to significantly advance spatial comprehension and interaction within embodied Artificial Intelligence (AI) systems. Our
investigation spans various 3D data representations, from point clouds to Neural Radiance Fields (NeRFs). It examines their
integration with LLMs for tasks such as 3D scene understanding, captioning, question-answering, and dialogue, as well as LLM-based
agents for spatial reasoning, planning, and navigation. The paper also includes a brief review of other methods that integrate 3D and
language. The meta-analysis presented in this paper reveals significant progress yet underscores the necessity for novel approaches
to harness the full potential of 3D-LLMs. Hence, with this paper, we aim to chart a course for future research that explores and expands
the capabilities of 3D-LLMs in understanding and interacting with the complex 3D world. To support this survey, we have established a
project page where papers related to our topic are organized and listed: https://github.com/ActiveVisionLab/Awesome-LLM-3D
Subcellular Localization of SUN2 Is Regulated by Lamin A and Rab5
SUN2 is an inner nuclear membrane protein with a conserved Sad1/UNC-84 homology SUN-domain at the C-terminus. Intriguingly, SUN2 has also been reported to interact with Rab5, which localizes in early endosomes. To clarify the dual subcellular localization of SUN2, we investigated its localization in lamin A/C deficient cells rescued with lamin A or lamin C isoform, and in HeLa cells transfected with Rab5 or its mutants. We found that expression of lamin A but not lamin C partly restored the nuclear envelope localization of SUN2. SUN2 was redistributed to endosomes upon overexpression of Rab5, but remained on the nuclear envelope when the SUN domain was deleted. To explore the physiological function of SUN2 in vesicle trafficking and endocytosis, we demonstrated the colocalization of endogenous SUN2 and Rab5. Moreover, overexpression of SUN2 stimulated the uptake of transferrin while suppression of SUN2 expression attenuated the process. These findings support a role of SUN2 in endocytosis
Reduced expression of lamin A/C correlates with poor histological differentiation and prognosis in primary gastric carcinoma
<p>Abstract</p> <p>Background</p> <p>Lamin A/C is very important in DNA replication, RNA dependent transcription and nuclear stabilization. Reduced or absent lamin A/C expression has been found to be a common feature of a variety of different cancers. To investigate the role of lamin A/C in gastric carcinoma (GC) pathogenesis, we analyzed the correlations between the lamin A/C expression level and clinicopathological factors and studied its prognostic role in primary GC.</p> <p>Methods</p> <p>The expression of lamin A/C at mRNA level was detected by the reverse transcription-polymerase chain reaction (RT-PCR) and real time RT-PCR, and western blot was used to examine the protein expression. Lamin A/C expression and its prognostic significance were investigated by performing immunohistochemical analysis on a total of 126 GC clinical tissue samples.</p> <p>Results</p> <p>Both lamin A/C mRNA and protein expression were downregulated in the majority of tumours compared with corresponding normal gastric tissues (<it>p </it>= 0.011 and <it>p </it>= 0.036, respectively). Real time RT-PCR further validated that downregulation of lamin A/C is associated with poor histological differentiation (r = 0.438, <it>p </it>= 0.025). The immunohistochemical staining showed an evident decrease of lamin A/C expression in 55.6% (70/126) GC cases. Importantly, the negative lamin A/C expression correlated strongly with histological classification (r = 0.361, <it>p </it>= 0.034). Survival analysis revealed that patients with lamin A/C downregulation have a poorer prognosis (<it>p </it>= 0.034). In addition, lamin A/C expression was found to be an independent prognostic factor by multivariate analysis.</p> <p>Conclusion</p> <p>Data of this study suggest that lamin A/C is involved in the pathogenesis of GC, and it may serve as a valuable biomarker for assessing the prognosis for primary GC.</p
DNA Immunization with Fusion of CTLA-4 to Hepatitis B Virus (HBV) Core Protein Enhanced Th2 Type Responses and Cleared HBV with an Accelerated Kinetic
BACKGROUND: Typically, DNA immunization via the intramuscular route induces specific, Th1-dominant immune responses. However, plasmids expressing viral proteins fused to cytotoxic T lymphocyte antigen 4 (CTLA-4) primed Th2-biased responses and were able to induced effective protection against viral challenge in the woodchuck model. Thus, we addressed the question in the mouse model how the Th1/Th2 bias of primed immune responses by a DNA vaccine influences hepatitis B virus (HBV) clearance. PRINCIPAL FINDINGS: Plasmids expressing HBV core protein (HBcAg) or HBV e antigen and HBcAg fused to the extracellular domain of CTLA-4 (pCTLA-4-HBc), CD27, and full length CD40L were constructed. Immunizations of these DNA plasmids induced HBcAg-specific antibody and cytotoxic T-cell responses in mice, but with different characteristics regarding the titers and subtypes of specific antibodies and intensity of T-cell responses. The plasmid pHBc expressing HBcAg induced an IgG2a-dominant response while immunizations of pCTLA-4-HBc induced a balanced IgG1/IgG2a response. To assess the protective values of the immune responses of different characteristics, mice were pre-immunized with pCTLA-4-HBc and pHBc, and challenged by hydrodynamic injection (HI) of pAAV/HBV1.2. HBV surface antigen (HBsAg) and DNA in peripheral blood and HBcAg in liver tissue were cleared with significantly accelerated kinetics in both groups. The clearance of HBsAg was completed within 16 days in immunized mice while more than 50% of the control mice are still positive for HBsAg on day 22. Stronger HBcAg-specific T-cell responses were primed by pHBc correlating with a more rapid decline of HBcAg expression in liver tissue, while anti-HBs antibody response developed rapidly in the mice immunized with pCTLA-4-HBc, indicating that the Th1/Th2 bias of vaccine-primed immune responses influences the mode of viral clearance. CONCLUSION: Viral clearance could be efficiently achieved by Th1/Th2-balanced immune response, with a small but significant shift in T-cell and B-cell immune responses
Deletion of the N-terminus of SF2/ASF Permits RS-Domain-Independent Pre-mRNA Splicing
Serine/arginine-rich (SR) proteins are essential splicing factors with one or two RNA-recognition motifs (RRMs) and a C-terminal arginine- and serine-rich (RS) domain. SR proteins bind to exonic splicing enhancers via their RRM(s), and from this position are thought to promote splicing by antagonizing splicing silencers, recruiting other components of the splicing machinery through RS-RS domain interactions, and/or promoting RNA base-pairing through their RS domains. An RS domain tethered at an exonic splicing enhancer can function as a splicing activator, and RS domains play prominent roles in current models of SR protein functions. However, we previously reported that the RS domain of the SR protein SF2/ASF is dispensable for in vitro splicing of some pre-mRNAs. We have now extended these findings via the identification of a short inhibitory domain at the SF2/ASF N-terminus; deletion of this segment permits splicing in the absence of this SR protein's RS domain of an IgM pre-mRNA substrate previously classified as RS-domain-dependent. Deletion of the N-terminal inhibitory domain increases the splicing activity of SF2/ASF lacking its RS domain, and enhances its ability to bind pre-mRNA. Splicing of the IgM pre-mRNA in S100 complementation with SF2/ASF lacking its RS domain still requires an exonic splicing enhancer, suggesting that an SR protein RS domain is not always required for ESE-dependent splicing activation. Our data provide additional evidence that the SF2/ASF RS domain is not strictly required for constitutive splicing in vitro, contrary to prevailing models for how the domains of SR proteins function to promote splicing
Fine mapping of qSTV11KAS, a major QTL for rice stripe disease resistance
Rice stripe disease, caused by rice stripe virus (RSV), is one of the most serious diseases in temperate rice-growing areas. In the present study, we performed quantitative trait locus (QTL) analysis for RSV resistance using 98 backcross inbred lines derived from the cross between the highly resistant variety, Kasalath, and the highly susceptible variety, Nipponbare. Under artificial inoculation in the greenhouse, two QTLs for RSV resistance, designated qSTV7 and qSTV11KAS, were detected on chromosomes 7 and 11 respectively, whereas only one QTL was detected in the same location of chromosome 11 under natural inoculation in the field. The stability of qSTV11KAS was validated using 39 established chromosome segment substitution lines. Fine mapping of qSTV11KAS was carried out using 372 BC3F2:3 recombinants and 399 BC3F3:4 lines selected from 7,018 BC3F2 plants of the cross SL-234/Koshihikari. The qSTV11KAS was localized to a 39.2 kb region containing seven annotated genes. The most likely candidate gene, LOC_Os11g30910, is predicted to encode a sulfotransferase domain-containing protein. The predicted protein encoded by the Kasalath allele differs from Nipponbare by a single amino acid substitution and the deletion of two amino acids within the sulfotransferase domain. Marker-resistance association analysis revealed that the markers L104-155 bp and R48-194 bp were highly correlated with RSV resistance in the 148 landrace varieties. These results provide a basis for the cloning of qSTV11KAS, and the markers may be used for molecular breeding of RSV resistant rice varieties
PDGF-Rα gene expression predicts proliferation, but PDGF-A suppresses transdifferentiation of neonatal mouse lung myofibroblasts
<p>Abstract</p> <p>Background</p> <p>Platelet-derived growth factor A (PDGF-A) signals solely through PDGF-Rα, and is required for fibroblast proliferation and transdifferentiation (fibroblast to myofibroblast conversion) during alveolar development, because <it>pdgfa</it>-null mice lack both myofibroblasts and alveoli. However, these PDGF-A-mediated mechanisms remain incompletely defined. At postnatal days 4 and 12 (P4 and P12), using mouse lung fibroblasts, we examined (a) how PDGF-Rα correlates with ki67 (proliferation marker) or alpha-smooth muscle actin (αSMA, myofibroblast marker) expression, and (b) whether PDGF-A directly affects αSMA or modifies stimulation by transforming growth factor beta (TGFβ).</p> <p>Methods</p> <p>Using flow cytometry we examined PDGF-Rα, αSMA and Ki67 in mice which express green fluorescent protein (GFP) as a marker for PDGF-Rα expression. Using real-time RT-PCR we quantified αSMA mRNA in cultured Mlg neonatal mouse lung fibroblasts after treatment with PDGF-A, and/or TGFβ.</p> <p>Results</p> <p>The intensity of GFP-fluorescence enabled us to distinguish three groups of fibroblasts which exhibited absent, lower, or higher levels of PDGF-Rα. At P4, more of the higher than lower PDGF-Rα + fibroblasts contained Ki67 (Ki67+), and Ki67+ fibroblasts predominated in the αSMA + but not the αSMA- population. By P12, Ki67+ fibroblasts comprised a minority in both the PDGF-Rα + and αSMA+ populations. At P4, most Ki67+ fibroblasts were PDGF-Rα + and αSMA- whereas at P12, most Ki67+ fibroblasts were PDGF-Rα- and αSMA-. More of the PDGF-Rα + than - fibroblasts contained αSMA at both P4 and P12. In the lung, proximate αSMA was more abundant around nuclei in cells expressing high than low levels of PDGF-Rα at both P4 and P12. Nuclear SMAD 2/3 declined from P4 to P12 in PDGF-Rα-, but not in PDGF-Rα + cells. In Mlg fibroblasts, αSMA mRNA increased after exposure to TGFβ, but declined after treatment with PDGF-A.</p> <p>Conclusion</p> <p>During both septal eruption (P4) and elongation (P12), alveolar PDGF-Rα may enhance the propensity of fibroblasts to transdifferentiate rather than directly stimulate αSMA, which preferentially localizes to non-proliferating fibroblasts. In accordance, PDGF-Rα more dominantly influences fibroblast proliferation at P4 than at P12. In the lung, TGFβ may overshadow the antagonistic effects of PDGF-A/PDGF-Rα signaling, enhancing αSMA-abundance in PDGF-Rα-expressing fibroblasts.</p
Myosin Light-Chain Kinase Is Necessary for Membrane Homeostasis in Cochlear Inner Hair Cells
The structural homeostasis of the cochlear hair cell membrane is critical for all aspects of sensory transduction, but the regulation of its maintenance is not well understood. In this report, we analyzed the cochlear hair cells of mice with specific deletion of myosin light chain kinase (MLCK) in inner hair cells. MLCK-deficient mice showed impaired hearing, with a 5- to 14-dB rise in the auditory brainstem response (ABR) thresholds to clicks and tones of different frequencies and a significant decrease in the amplitude of the ABR waves. The mutant inner hair cells produced several ball-like structures around the hair bundles in vivo, indicating impaired membrane stability. Inner hair cells isolated from the knockout mice consistently displayed less resistance to hypoosmotic solution and less membrane F-actin. Myosin light-chain phosphorylation was also reduced in the mutated inner hair cells. Our results suggest that MLCK is necessary for maintaining the membrane stability of inner hair cells
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