Single-Machine Scheduling to Minimize Total Completion Time and Tardiness with Two Competing Agents

We consider a single-machine two-agent problem where the objective is to minimize a weighted combination of the total completion time and the total tardiness of jobs from the first agent given that no tardy jobs are allowed for the second agent. A branch-andbound algorithm is developed to derive the optimal sequence and two simulated annealing heuristic algorithms are proposed to search for the near-optimal solutions. Computational experiments are also conducted to evaluate the proposed branch-and-bound and simulated annealing algorithms

Phosphorylation at Ser473 regulates heterochromatin protein 1 binding and corepressor function of TIF1beta/KAP1

<p>Abstract</p> <p>Background</p> <p>As an epigenetic regulator, the transcriptional intermediary factor 1β (TIF1β)/KAP1/TRIM28) has been linked to gene expression and chromatin remodeling at specific loci by association with members of the heterochromatin protein 1 (HP1) family and various other chromatin factors. The interaction between TIF1β and HP1 is crucial for heterochromatin formation and maintenance. The HP1-box, PXVXL, of TIF1β is responsible for its interaction with HP1. However, the underlying mechanism of how the interaction is regulated remains poorly understood.</p> <p>Results</p> <p>This work demonstrates that TIF1β is phosphorylated on Ser473, the alteration of which is dynamically associated with cell cycle progression and functionally linked to transcriptional regulation. Phosphorylation of TIF1β/Ser473 coincides with the induction of cell cycle gene <it>cyclin A2 </it>at the S-phase. Interestingly, chromatin immunoprecipitation demonstrated that the promoter of <it>cyclin A2 </it>gene is occupied by TIF1β and that such occupancy is inversely correlated with Ser473 phosphorylation. Additionally, when HP1β was co-expressed with TIF1β/S473A, but not TIF1β/S473E, the colocalization of TIF1β/S473A and HP1β to the promoters of <it>Cdc2 </it>and <it>Cdc25A </it>was enhanced. Non-phosphorylated TIF1β/Ser473 allowed greater TIF1β association with the regulatory regions and the consequent repression of these genes. Consistent with possible inhibition of TIF1β's corepressor function, the phosphorylation of the Ser473 residue, which is located near the HP1-interacting PXVXL motif, compromised the formation of TIF1β-HP1 complex. Finally, we found that the phosphorylation of TIF1β/Ser473 is mediated by the PKCδ pathway and is closely linked to cell proliferation.</p> <p>Conclusion</p> <p>The modulation of HP1β-TIF1β interaction through the phosphorylation/de-phosphorylation of TIF1β/Ser473 may constitute a molecular switch that regulates the expression of particular genes. Higher levels of phosphorylated TIF1β/Ser473 may be associated with the expression of key regulatory genes for cell cycle progression and the proliferation of cells.</p

Structural Elements Regulating AAA+ Protein Quality Control Machines

Members of the ATPases Associated with various cellular Activities (AAA+) superfamily participate in essential and diverse cellular pathways in all kingdoms of life by harnessing the energy of ATP binding and hydrolysis to drive their biological functions. Although most AAA+ proteins share a ring-shaped architecture, AAA+ proteins have evolved distinct structural elements that are fine-tuned to their specific functions. A central question in the field is how ATP binding and hydrolysis are coupled to substrate translocation through the central channel of ring-forming AAA+ proteins. In this mini-review, we will discuss structural elements present in AAA+ proteins involved in protein quality control, drawing similarities to their known role in substrate interaction by AAA+ proteins involved in DNA translocation. Elements to be discussed include the pore loop-1, the Inter-Subunit Signaling (ISS) motif, and the Pre-Sensor I insert (PS-I) motif. Lastly, we will summarize our current understanding on the inter-relationship of those structural elements and propose a model how ATP binding and hydrolysis might be coupled to polypeptide translocation in protein quality control machines

Impact of cognitive behavior therapy on osteoarthritis-associated pain, insomnia, depression, fatigue, and physical function in patients with knee/hip osteoarthritis: A systematic review and meta-analysis of randomized controlled trials

BackgroundThis meta-analysis aimed at evaluating the efficacy of cognitive behavior therapy (CBT) against osteoarthritis-associated symptoms in patients with knee/hip osteoarthritis.MethodsMedline, PubMed, Cochrane Library, and EMBASE databases were searched from inception to July 2022 to identify randomized controlled trials (RCTs) comparing the efficacy of CBT with other treatment approaches in adults with confirmed knee/hip osteoarthritis. The pain intensity (primary outcome) and the secondary outcomes including insomnia severity, sleep efficiency, physical function as well as the severity of depression and fatigue were assessed at two time points (i.e., immediately after treatment and during the follow-up period). The effect size is expressed as standardized mean difference (SMD) with SMDs of &lt; 0.2, 0.2–0.5, and 0.5–0.8, and &gt; 0.8 representing negligible, small, medium, and large effect sizes, respectively.ResultsFifteen RCTs were included for analysis. Immediately after CBT intervention, meta-analysis showed similar treatment effect in pain severity [SMD = –0.46, 95% confidence interval (CI): –0.95 to 0.04, 11 studies, 1557 participants] and other symptoms including depression (SMD = –0.26, 95% CI: –0.58 to 0.06, five studies, 735 participants), fatigue (SMD = –2.44, 95% CI:–6.53 to 1.65, two RCTs, 511 participants), and physical function (SMD = –0.11, 95% CI:–0.25 to 0.02, five RCTs, 720 participants) between CBT and control groups, while there was an improvement in insomnia severity (SMD = –0.65, 95% CI: –1.06 to –0.24, four RCTs, 639 participants, medium treatment effect) and sleep efficiency (SMD = 0.32, 95% CI: 0.04 to 0.59, three RCTs, 352 patients, small treatment effect). During follow-up, CBT improved pain severity (SMD = –0.52, 95% CI: –1.03 to –0.01, eight studies, 1447 participants, medium treatment effect), insomnia (SMD = –0.43, 95% CI: –0.85 to –0.01, three RCTs, 571 participants, small treatment effect), and depression (SMD = –0.39, 95% CI: –0.59 to –0.18, four RCTs, 791 participants, small treatment effect). Nevertheless, sleep efficiency, fatigue, and physical function were not improved in the follow-up period.ConclusionOur results may suggest the durability of CBT-associated treatment benefits, supporting its role as a potential promising alternative or complementary intervention for patients with knee/hip osteoarthritis, especially against pain and insomnia. Future large-scale investigations are warranted to verify our findings.Systematic review registration[https://www.crd.york.ac.uk/prospero/], identifier [CRD42022331165]

Nardosinane-Type Sesquiterpenoids from the Formosan Soft Coral Paralemnalia thyrsoides

Five new nardosinane-type sesquiterpenoids, paralemnolins Q–U (1–5), along with three known compounds (6–8), were isolated from the Formosan soft coral Paralemnalia thyrsoides. The structures of new metabolites were elucidated on the basis of extensive spectroscopic methods, and the absolute configuration of 1 was determined by the application of Mosher’s method on 1. Among these metabolites, 1 and 3 are rarely found nardosinane-type sesquiterpenoids, possessing novel polycyclic structures. Compounds 1, 3, 6 and 7 were found to possess neuroprotective activity

Cost-effective complete genome sequencing using the MinION platform for identification of recombinant enteroviruses

Enteroviruses (EVs) are a group of viruses that cause various human illnesses. While the CODEHOP (COnsensus-DEgenerate Hybrid Oligonucleotide Primer) method can generate VP1 gene fragments for enterovirus genotyping, it is unable to detect recombinant strains. Recent advances in viral genome sequencing using next-generation sequencing technologies have enabled comprehensive analyses. However, the high cost poses a challenge for widespread adoption. To address this issue, this study proposes a cost-effective approach for generating complete enterovirus genome sequences using the Oxford Nanopore MinION sequencer. This protocol not only facilitates the generation of accurate genome sequences for various enterovirus strains but also allows for the differentiation of co-infections from viral isolates. In addition, the method can generate polyprotein sequences as well as peptide sequences of the upstream ORF (uORF) whose expression can impact virus infection. Through the analysis of complete enterovirus genomes, this study successfully identified seven enterovirus A71 isolates obtained during the 2018 enterovirus outbreak in Malaysia and Taiwan as recombinants between enterovirus A71 and coxsackievirus A2. Furthermore, our study has made a significant discovery by establishing a strong correlation between uORF trees and the epidemics of EVA71. This finding highlights the potential of uORF sequences as valuable indicators for monitoring and understanding the spread of EVA71 infections. We also identified notable amino acid changes in the transmembrane domain of the uORF protein within a newly identified lineage. These findings provide crucial insights into the molecular characteristics and evolutionary dynamics of EVA71, offering valuable information for future research and intervention strategies

Nutrient supply in the Southern East China Sea after Typhoon Morakot

Author Posting. © Sears Foundation for Marine Research, 2013. This article is posted here by permission of Sears Foundation for Marine Research for personal use, not for redistribution. The definitive version was published in Journal of Marine Research 71 (2013): 133-149, doi:10.1357/002224013807343425.Recent studies show that typhoons have profound effects on phytoplankton assemblages along their tracks, but it is difficult to quantitatively estimate nutrient supply after a typhoon's passage due to a lack of nutrient information before and after the arrival of a typhoon. During the passage of Typhoon Morakot (July 22 to Aug. 26, 2009), we conducted pre- and post-typhoon field cruises to study nutrient supply in the Southern East China Sea (SECS). The results showed nitrate and phosphate supplies to the water column in the SECS after the typhoon's passage were 5.6 × 1011 g-N/day and 7.8 × 1010 g-P/day which were significantly higher than those before the typhoon occurred (nitrate supply = 1 × 109 g-N/day, phosphate supply = 1.6 × 108 g-P/day). We conclude from this data, and after consulting the available physical data, that the highest nitrate concentration was caused by strong upwelling and/or vertical mixing, and input of nutrient-replete terrestrial waters. The nitrate and phosphate input related to the passage of Typhoon Morakot can account for approximately 86% and 87% of summer nitrate and phosphate supplies to the southern East China Sea.This research was supported by the Top University Program and the National Science Council (NSC101-2116M-110- 001, NSC101-2611-M-110-015-MY3, NSC100-2119-M-110-003, NSC98-2611-M-019-014-MY3, NSC NSC98-2611-M-002-019-MY3) of Taiwan to C.-C. Hung, G.-C.Gong and S. Jan

Corrigendum to “Nutrient supply in the Southern East China Sea after Typhoon Morakot”

Author Posting. © Sears Foundation for Marine Research, 2013. This article is posted here by permission of Sears Foundation for Marine Research for personal use, not for redistribution. The definitive version was published in Journal of Marine Research 71 (2013): 451-452, doi:10.1357/002224013812587609

Clinical characteristics and prognosis of acute bacterial meningitis in elderly patients over 65: a hospital-based study

<p>Abstract</p> <p>Background</p> <p>To examine the clinical characteristics of bacterial meningitis in elderly patients.</p> <p>Methods</p> <p>261 patients with adult bacterial meningitis (ABM), collected during a study period of 11 years (2000-2010), were included for study. Among them, 87 patients aged ≥ 65 years and were classified as the elderly group. The clinical and laboratory characteristics and prognostic factors were analyzed, and a clinical comparison with those of non-elderly ABM patients was also made.</p> <p>Results</p> <p>The 87 elderly ABM patients were composed of 53 males and 34 females, aged 65-87 years old (median = 71 years). Diabetes mellitus (DM) was the most common underlying condition (34%), followed by end stage renal disease (7%), alcoholism (4%) and malignancies (4%). Fever was the most common clinical manifestation (86%), followed by altered consciousness (62%), leukocytosis (53%), hydrocephalus (38%), seizure (30%), bacteremia (21%) and shock (11%). Thirty-nine of these 87 elderly ABM patients had spontaneous infection, while the other 48 had post-neurosurgical infection. Forty-four patients contracted ABM in a community-acquired state, while the other 43, a nosocomial state. The therapeutic results of the 87 elderly ABM patients were that 34 patients expired and 53 patients survived. The comparative results of the clinical and laboratory characteristics between the elderly and non-elderly ABM patients showed that only peripheral blood leukocytosis was significant. Presence of shock and seizure were significant prognostic factors of elderly ABM patients.</p> <p>Conclusions</p> <p>Elderly ABM patients accounted for 34.8% of the overall ABM cases, and this relatively high incidence rate may signify the future burden of ABM in the elderly population in Taiwan. The relative frequency of implicated pathogens of elderly ABM is similar to that of non-elderly ABM. Compared with non-elderly patients, the elderly ABM patients have a significantly lower incidence of peripheral blood leukocytosis. The mortality rate of elderly ABM remains high, and the presence of shock and seizures are important prognostic factors.</p