The optimization of heat conduction is a critical task with widespread applications, and the approaches are typically categorized into two main categories: thermal conductivity distribution ...optimization (TCDO) and heat source layout optimization (HSLO). While extensive research efforts have been devoted to each of these two categories, standalone TCDO and HSLO limit the design possibilities and may lead to suboptimal solutions. In this work, a collaborative methodology combining TCDO and HSLO is proposed by transforming the collaborative optimization problem into a two-level nested problem. In this approach, TCDO forms the inner subproblem, tackled using the gradient-based method, while HSLO constitutes the outer subproblem addressed through Bayesian optimization (BO). The proposed method is employed to solve two problem cases involving volume-to-point and volume-to-edge boundaries, respectively. The results demonstrate that the present method is capable of achieving collaborative optimization of TCDO and HSLO for both scenarios of continuous and discrete thermal conductivity distributions. Comparing with standalone TCDO and HSLO that reduce the average temperature by ▪ and ▪, respectively, the proposed method achieves a significantly greater reduction of ▪, underscoring its efficacy. We anticipate that the proposed method will serve as a valuable tool for optimizing heat conduction across diverse applications, and its adaptable framework holds promise for addressing broader optimization challenges.
•Thermal conductivity and heat source layout are collaboratively optimized.•A nested optimization framework is proposed for the collaborative optimization.•Collaborative optimization outperforms standalone ones by 38.26 K and 82.55 K.•The proposed method is adaptive and efficient for wider range of problems.
Heat conduction optimization with arbitrary boundary conditions is a challenging problem that lacks a universal optimization criterion. In the present work, the concept of generalized entransy ...dissipation (GED) is proposed through transforming heat conduction optimization problems with arbitrary boundaries into their homogeneous counterparts. It is demonstrated that minimizing GED leads to optimal thermal performance of heat conduction problems with arbitrary boundary conditions. In addition, GED-based continuous optimization problems are convex, guaranteeing the uniqueness and global optimality of the solution and benefitting numerical calculations. Two typical problems with complex boundary conditions are studied by applying the minimum principle of GED, and the results are compared with other optimization objectives. The numerical results show that GED achieves better thermal performance than entropy generation- (EG) and entransy dissipation- (ED) based optimizations. For the optimization of boundary average temperature under the given input heat flux of ▪, GED achieves the best result, where the optimized average temperature is ▪ and ▪ lower compared with EG and ED optimizations, respectively. In general, GED offers a reasonable and easy to implement optimization principle for heat conduction processes with arbitrary boundaries and may provide new insights for heat conduction optimization.
•GED-criterion is proposed for optimizing heat conduction with arbitrary boundaries.•Minimizing GED leads to optimal thermal performance of complex boundary conditions.•Convexity of GED-based continuous optimization guarantees global optimality.•GED outperforms EGMP and EDEP, lowering average temperature by 48.8 and 27.5 K.•GED offers a universal and easy-to-use principle for heat conduction processes.
Objectives
The present study aimed to examine the psychometric properties of the Chinese version of the Career Adapt-Abilities Scale-Short Form (CAAS-SF) among a sample of Chinese elite athletes.
...Methods
A sample of Chinese elite athletes (
n
= 770) was invited to participate in this study. First, the factor structure of the Chinese version of the CAAS-SF was examined, and six measurement models (CFA, H-CFA, B-CFA, ESEM, H-ESEM, and B-ESEM) were constructed and compared. Second, the internal consistency reliability of the Chinese version of the CAAS-SF was examined. Finally, structural equation modeling (SEM) was employed to assess the nomological validity of the Chinese version of the CAAS-SF.
Results
The results showed that the hierarchical ESEM (H-ESEM) model best represented the factor structure of the CAAS-SF among Chinese elite athletes. It suggests that the higher-order factor of career adaptability explains the four distinctive but interrelated specific factors of concern, control, curiosity, and confidence. Cronbach's alpha coefficients (0.84–0.90), composite reliability (0.81–0.96), and coefficient omega hierarchical (0.855–0.94) of the Chinese version of the CAAS-SF were larger than the cutoff values, which suggest satisfactory reliability. The results of the SEM revealed that the higher-order factor of career adaptability was positively associated with career decision self-efficacy (β = 0.676,
p
< 0.001). This result is consistent with previous findings (r = 0.65,
p
< 0.01) and provided support for the nomological validity of the CAAS-SF among Chinese elite athletes.
Conclusion
The findings of the present study indicated that the Chinese version of the CAAS-SF displayed satisfactory reliability and validity and could be used to assess the career adaptability of Chinese elite athletes. In addition, the total score of the CAAS-SF is suggested to be used in future research and practical works.
NEMO is the regulatory subunit of the IκB kinase (IKK) in NF-κB activation, and its CC2-LZ region interacts with Lys63 (K63)-linked polyubiquitin to recruit IKK to receptor signaling complexes. In ...vitro, CC2-LZ also interacts with tandem diubiquitin. Here we report the crystal structure of CC2-LZ with two dimeric coiled coils representing CC2 and LZ, respectively. Surprisingly, mutagenesis and nuclear magnetic resonance experiments reveal that the binding sites for diubiquitins at LZ are composites of both chains and that each ubiquitin in diubiquitins interacts with symmetrical NEMO asymmetrically. For tandem diubiquitin, the first ubiquitin uses the conserved hydrophobic patch and the C-terminal tail, while the second ubiquitin uses an adjacent surface patch. For K63-linked diubiquitin, the proximal ubiquitin uses its conserved hydrophobic patch, while the distal ubiquitin mostly employs the C-terminal arm including the K63 linkage residue. These studies uncover the energetics and geometry for mutual recognition of NEMO and diubiquitins.
The motion of heat can be described by a thermal energy–momentum tensor. A general description of heat conduction in the geometrical language is developed based on a two-phase continuum model within ...the framework of relativistic continuum dynamics, and the momentum balance equation of heat, or the general heat conduction equation (GHCE), is derived by the balance equation of the thermal energy–momentum tensor. We demonstrate that the low-speed limit of the GHCE coincides the former version of GHCE of the thermomass theory that is based on the energy–mass equivalence and Newtonian dynamics. Numerical solutions of the GHCE are also provided to demonstrate that the GHCE not only overcomes the paradox of instantaneous heat propagation of the Fourier’s law, but also resolves the defect of the CV model that temperatures may drop below absolute zero under some conditions. The present work formulates a general description of the thermal transport processes, and can provide a deeper insight into the heat transfer discipline from the relativistic point of view.
•A general description of heat conduction is formulated in the geometrical language.•The GHCE is derived within the framework of relativistic continuum dynamics.•The low-speed GHCE can be included in the scope of relativistic dynamics.•The GHCE may reduce to other typical heat conduction models.•Numerical studies show that the GHCE overcomes the defect of the CV model.
Lipopolysaccharide-binding protein (LBP) has been reported to associate with metabolic diseases, such as obesity, diabetes, and non-alcoholic fatty liver disease. Since chronic hepatitis C virus ...(HCV) infection is associated with metabolic derangements, the relationship between LBP and HCV deserves additional studies. This study aimed to determine the serum LBP level in subjects with or without HCV infection and investigate the change of its level after anti-viral treatments with or without interferon.
We recruited 120 non-HCV subjects, 42 and 17 HCV-infected subjects respectively treated with peginterferon α-2a/ribavirin and direct-acting antiviral drugs. Basic information, clinical data, serum LBP level and abdominal ultrasonography were collected. All the subjects provided written informed consent before being enrolled approved by the Research Ethics Committee of the National Taiwan University Hospital. Serum LBP level was significantly higher in HCV-infected subjects than non-HCV subjects (31.0 ± 8.8 versus 20.0 ± 6.4 μg/mL; p-value < 0.001). After multivariate analyses, LBP at baseline was independently associated with body mass index, hemoglobin A1c, alanine aminotransferase (ALT) and HCV infection. Moreover, the baseline LBP was only significantly positively associated with ALT and inversely with fatty liver in HCV-infected subjects. The LBP level significantly decreased at sustained virologic response (27.4 ± 6.6 versus 34.6 ± 7.3 μg/mL, p-value < 0.001; 15.9 ± 4.4 versus 22.2 ± 5.7 μg/mL, p-value = 0.001), regardless of interferon-based or -free therapy.
LBP, an endotoxemia associated protein might be used as an inflammatory biomarker of both infectious and non-infectious origins in HCV-infected subjects.
HLX01 (HanliKang
) is a rituximab biosimilar that showed bioequivalence to reference rituximab in untreated CD20-positive diffuse large B-cell lymphoma (DLBCL) in the phase 3 HLX01-NHL03 study. Here, ...we report the 5-year follow-up results from the open-label extension part. Patients were randomised to either rituximab plus cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP) or HLX01 plus CHOP (H-CHOP) every 21 days for up to six cycles. The primary efficacy endpoint was overall survival (OS), and secondary efficacy endpoint was progression-free survival (PFS). Of the 407 patients enrolled in HLX01-NHL03, 316 patients (H-CHOP = 157; R-CHOP = 159) were included in the 5-year follow-up for a median duration of 65.1 (range, 2.2-76.5) months. 96.5% of the patients had an International Prognostic Index (IPI) of 1 or 2, and 17.7% had bone marrow involvement. The 5-year OS rates were 81.0% (95% CI: 74.9-87.5%) and 75.4% (95% CI: 68.9-82.6%)( HR: 0.75, 95% CI 0.47-1.20; p = 0.23) while 5-year PFS rates were 77.7% (95% CI: 71.4-84.6%) and 73.0% (95% CI: 66.3-80.3%) (HR: 0.84, 95% CI 0.54-1.30; p = 0.43) in the H-CHOP and R-CHOP groups, respectively. Treatment outcomes did not differ between groups regardless of IPI score and were consistent with the primary analysis. H-CHOP and R-CHOP provided no significant difference in 5-year OS or PFS in previously untreated patients with low or low-intermediate risk DLBCL.
QL1706 (PSB205) is a single bifunctional MabPair (a novel technical platform) product consisting of two engineered monoclonal antibodies (anti-PD-1 IgG4 and anti-CTLA-4 IgG1), with a shorter ...elimination half-life (t
) for CTLA-4. We report results from a phase I/Ib study of QL1706 in patients with advanced solid tumors who failed standard therapies.
In the phase I study, QL1706 was administered intravenously once every 3 weeks at one of five doses ranging from 0.3 to 10 mg/kg, and the maximum tolerated dose, recommended phase 2 dose (RP2D), safety, pharmacokinetics (PK), and pharmacodynamics (PD) of QL1706 were investigated. In the phase Ib study, QL1706 was administered at the RP2D intravenously every 3 weeks, and the preliminary efficacies in non-small cell lung cancer (NSCLC), nasopharyngeal carcinoma (NPC), cervical cancer (CC), and other solid tumors were evaluated.
Between March 2020 and July 2021, 518 patients with advanced solid tumors were enrolled (phase I, n = 99; phase Ib, n = 419). For all patients, the three most common treatment-related adverse events (TRAEs) were rash (19.7%), hypothyroidism (13.5%), and pruritus (13.3%). The TRAEs and immune-related adverse events (irAEs) of grade ≥ 3 occurred in 16.0% and 8.1% of patients, respectively. In phase I, 2 of 6 patients in the 10mg/kg group experienced dose-limiting toxicities (DLTs) (grade 3 thrombocytopenia and grade 4 immune-mediated nephritis), so the maximum tolerated dose (MTD) was reached at 10 mg/kg. The RP2D was determined to be 5 mg/kg based on comprehensive analysis of tolerability, PK/PD, and efficacy. For all patients who received QL1706 at the RP2D, the objective response rate (ORR) and median duration of response were 16.9% (79/468) and 11.7 months (8.3-not reached NR), respectively; and the ORRs were 14.0% (17/121) in NSCLC, 24.5% (27/110) in NPC, 27.3% (15/55) in CC, 7.4% (2/27) in colorectal cancer, 23.1% (6/26) in small cell lung cancer. For immunotherapy-naive patients, QL1706 exhibited promising antitumor activities, especially in NSCLC, NPC, and CC, with ORRs of 24.2%, 38.7%, and 28.3%, respectively.
QL1706 was well tolerated and demonstrated promising antitumor activity in solid tumors, especially in NSCLC, NPC, and CC patients. It is currently being evaluated in randomized phase II (NCT05576272, NCT05179317) and phase III (NCT05446883, NCT05487391) trials. Trial Registration ClinicalTrials.gov Identifier: NCT04296994 and NCT05171790.
Peripheral T cell lymphoma (PTCL) is a rare disease and recent approved drugs for relapsed/refractory (r/r) PTCL provided limited clinical benefit. We conducted this study to evaluate the efficacy ...and safety of geptanolimab (GB226), an anti-PD-1 antibody, in r/r PTCL patients.
We did this single-arm, multicenter phase 2 study across 41 sites in China. Eligible patients with r/r PTCL received geptanolimab 3 mg/kg intravenously every 2 weeks until disease progression or intolerable toxicity. All patients who received at least one dose of geptanolimab and histological confirmed PTCL entered full analysis set (FAS). The primary endpoint was objective response rate (ORR) in FAS assessed by the independent radiological review committee (IRRC) per Lugano 2014 criteria.
Between July 12, 2018, and August 15, 2019, 102 patients were enrolled and received at least one dose of geptanolimab. At the data cutoff date (August 15, 2020), the median follow-up was 4.06 (range 0.30-22.9) months. For 89 patients in FAS, 36 achieved objective response (40.4%, 95% CI 30.2-51.4), of which 13 (14.6%) were complete response and 23 (25.8%) had partial response assessed by IRRC. The median duration of response (DOR) was 11.4 (95% CI 4.8 to not reached) months per IRRC. Patients with PD-L1 expression ≥ 50% derived more benefit from geptanolimab treatment compared to < 50% ones (ORR, 53.3% vs. 25.0%, p = 0.013; median PFS 6.2 vs. 1.5 months, p = 0.002). Grade ≥ 3 treatment-related adverse events occurred in 26 (25.5%) patients, and the most commonly observed were lymphocyte count decreased (n = 4) and platelet count decreased (n = 3). Serious adverse events were observed in 45 (44.1%) patients and 19 (18.6%) were treatment related.
In this study, geptanolimab showed promising activity and manageable safety profile in patients with r/r PTCL. Anti-PD-1 antibody could be a new treatment approach for this patient population.
This clinical trial was registered at the ClinicalTrials.gov (NCT03502629) on April 18, 2018.
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