Physics Possibilities at a Linear Collider

We review some recent studies about the parameter determination of top quarks, W bosons, Higgs bosons, supersymmetric particles and in the ADD model of extra dimensions at a linear collider.Comment: 16 pages, LaTeX, 9 eps figures, invited plenary talk presented by A. Bartl at the "Workshop on High Energy Physics Phenomenology (WHEPP-8)", Indian Institute of Technology, Mumbai, January 5 - 16, 200

Microtubules gate tau condensation to spatially regulate microtubule functions.

Tau is an abundant microtubule-associated protein in neurons. Tau aggregation into insoluble fibrils is a hallmark of Alzheimer's disease and other types of dementia1, yet the physiological state of tau molecules within cells remains unclear. Using single-molecule imaging, we directly observe that the microtubule lattice regulates reversible tau self-association, leading to localized, dynamic condensation of tau molecules on the microtubule surface. Tau condensates form selectively permissible barriers, spatially regulating the activity of microtubule-severing enzymes and the movement of molecular motors through their boundaries. We propose that reversible self-association of tau molecules, gated by the microtubule lattice, is an important mechanism of the biological functions of tau, and that oligomerization of tau is a common property shared between the physiological and disease-associated forms of the molecule

"You have to get wet to learn how to swim" applied to bridging the gap between research into personnel scheduling and its implementation in practice

Personnel scheduling problems have attracted research interests for several decades. They have been considerably changed over time, accommodating a variety of constraints related to legal and organisation requirements, part-time staff, flexible hours of staff, staff preferences, etc. This led to a myriad of approaches developed for solving personnel scheduling problems including optimisation, meta-heuristics, artificial intelligence, decision-support, and also hybrids of these approaches. However, this still does not imply that this research has a large impact on practice and that state-of-the art models and algorithms are widely in use in organisations. One can find a reasonably large number of software packages that aim to assist in personnel scheduling. A classification of this software based on its purpose will be proposed, accompanied with a discussion about the level of support that this software offers to schedulers. A general conclusion is that the available software, with some exceptions, does not benefit from the wealth of developed models and methods. The remaining of the paper will provide insights into some characteristics of real-world scheduling problems that, in the author’s opinion, have not been given a due attention in the personnel scheduling research community yet and which could contribute to the enhancement of the implementation of research results in practice. Concluding remarks are that in order to bridge the gap that still exists between research into personnel scheduling and practice, we need to engage more with schedulers in practice and also with software developers; one may say we need to get wet if we want to learn how to swim

Defining the role of cellular immune signatures in diagnostic evaluation of suspected tuberculosis

BACKGROUND: Diagnosis of paucibacillary tuberculosis (TB) including extrapulmonary TB is a significant challenge, particularly in high-income, low-incidence settings. Measurement of Mycobacterium tuberculosis (Mtb)-specific cellular immune signatures by flow cytometry discriminates active TB from latent TB infection (LTBI) in case-control studies; however, their diagnostic accuracy and clinical utility in routine clinical practice is unknown. METHODS: Using a nested case-control study design within a prospective multicenter cohort of patients presenting with suspected TB in England, we assessed diagnostic accuracy of signatures in 134 patients who tested interferon-gamma release assay (IGRA)-positive and had final diagnoses of TB or non-TB diseases with coincident LTBI. Cellular signatures were measured using flow cytometry. RESULTS: All signatures performed less well than previously reported. Only signatures incorporating measurement of phenotypic markers on functional Mtb-specific CD4 T cells discriminated active TB from non-TB diseases with LTBI. The signatures measuring HLA-DR+IFNγ + CD4 T cells and CD45RA-CCR7-CD127- IFNγ -IL-2-TNFα + CD4 T cells performed best with 95% positive predictive value (95% confidence interval, 90-97) in the clinically challenging subpopulation of IGRA-positive but acid-fast bacillus (AFB) smear-negative TB suspects. CONCLUSIONS: Two cellular immune signatures could improve and accelerate diagnosis in the challenging group of patients who are IGRA-positive, AFB smear-negative, and have paucibacillary TB

Antimicrobial Resistance Patterns of Pathogens Isolated from Patients with Wound Infection at a Teaching Hospital in Vietnam

Nguyen Van An,1,* Hoang Trung Kien,2,* Le Huy Hoang,3 Nguyen Hung Cuong,1 Hoang Xuan Quang,1 Tuan Dinh Le,4 Ta Ba Thang,5 Tien Tran Viet,6 Luong Cong Thuc,7 Dinh Viet Hung,8 Nguyen Hoang Viet,9 Le Nhat Minh,10,11 Vu Huy Luong,12,13 Vinh Thi Ha Nguyen,13,14 Pham Quynh Hoa,15 Hai Ha Long Le16,17 1Department of Microbiology, Military Hospital 103, Vietnam Military Medical University, Hanoi, Vietnam; 2Department of Immunology, Vietnam Military Medical University, Hanoi, Vietnam; 3Department of Bacteriology, National of Hygiene and Epidemiology, Hanoi, Vietnam; 4Department of Rheumatology and Endocrinology, Military Hospital 103, Vietnam Medical Military University, Hanoi, Vietnam; 5Respiratory Center, Military Hospital 103, Vietnam Military Medical University, Hanoi, Vietnam; 6Department of Infectious Diseases, Military Hospital 103, Vietnam Medical Military University, Hanoi, Vietnam; 7Cardiovascular Center, Military Hospital 103, Vietnam Military Medical University, Hanoi, Vietnam; 8Department of Psychiatry, Military Medical 103, Vietnam Military Medical University, Hanoi, Vietnam; 9Molecular Pathology Department, Faculty of Medical Technology, Hanoi Medical University, Hanoi, Vietnam; 10Antimicrobial Resistance Research Center, National Institute of Infectious Disease, NIID, Tokyo, Japan; 11Tay Nguyen Institute of Science Research, Vietnam Academy of Science and Technology, VAST, Hanoi, Vietnam; 12Department of Laser and Skincare, National Hospital of Dermatology and Venereology, Hanoi, Vietnam; 13Department of Dermatology and Venereology, Hanoi Medical University, Hanoi, Vietnam; 14Department of General Planning, National Hospital of Dermatology and Venereology, Hanoi, Vietnam; 15Department of Microbiology, Mycology and Parasitology, National Hospital of Dermatology and Venereology, Hanoi, Vietnam; 16Department of Clinical Microbiology and Parasitology, Faculty of Medical Technology, Hanoi Medical University, Hanoi, Vietnam; 17Department of Biochemistry, Hematology and Immunology, National Hospital of Dermatology and Venereology, Hanoi, Vietnam*These authors contributed equally to this workCorrespondence: Hai Ha Long Le, Department of Clinical Microbiology and Parasitology, Faculty of Medical Technology, Hanoi Medical University, Hanoi, 100000, Vietnam, Tel +84 978520055, Email [email protected]: At a teaching Hospital in Vietnam, the persistently high incidence of diagnosed wound infection poses ongoing challenges to treatment. This study seeks to explore the causative agents of wound infection and their antimicrobial and multidrug resistance patterns.Methods: A cross-sectional study was conducted at the Department of Microbiology, Military Hospital 103, Vietnam. Data on microorganisms that caused wound infection and their antimicrobial resistance patterns was recorded from hospitalized patients from 2014 to 2021. Using the chi-square test, we analyzed the initial isolation from wound infection specimens collected from individual patients.Results: Over a third (34.9%) of wound infection samples yielded bacterial cultures. Staphylococcus aureus was the most prevalent bacteria, followed by Pseudomonas aeruginosa. Worryingly high resistance rates were observed for several antibiotics, particularly among Gram-negative bacteria. Ampicillin displayed the highest resistance (91.9%), while colistin and ertapenem remained the most effective. In Gram-positive bacteria, glycopeptides like teicoplanin and vancomycin (0% and 3.3% resistance, respectively) were most effective, but their use was limited. Clindamycin and tetracycline showed decreasing effectiveness. Resistance rates differed between surgical and non-surgical wards, highlighting the complex dynamics of antimicrobial resistance within hospitals. Multidrug resistance (MDR) was substantial, with Gram-negative bacteria exhibiting a 63.6% MDR rate. Acinetobacter baumannii showed the highest MDR rate (88.0%).Conclusion: This study investigated wound infection characteristics, antibiotic resistance patterns of common bacteria, and variations by hospital ward. S. aureus was the most prevalent bacteria, and concerning resistance rates were observed, particularly among Gram-negative bacteria. These findings highlight the prevalence of multidrug resistance in wound infections, emphasizing the importance of infection control measures and judicious antibiotic use.Keywords: wound infection, multidrug resistance, antimicrobial resistance, AMR in Vietna

Circadian function in patients with advanced non-small-cell lung cancer

This study aimed to evaluate whether patients with advanced non-small-cell lung cancer experience disrupted rest–activity daily rhythms, poor sleep quality, weakness, and maintain attributes that are linked to circadian function such as fatigue. This report describes the rest–activity patterns of 33 non-small-cell lung cancer patients who participated in a randomised clinical trial evaluating the benefits of melatonin. Data are reported on circadian function, health-related quality of life (QoL), subjective sleep quality, and anxiety/depression levels prior to randomisation and treatment. Actigraphy data, an objective measure of circadian function, demonstrated that patients' rest–activity circadian function differs significantly from control subjects. Our patients reported poor sleep quality and high levels of fatigue. Ferrans and Powers QoL Index instrument found a high level of dissatisfaction with health-related QoL. Data from the European Organization for Research and Treatment for Cancer reported poor capacity to fulfil the activities of daily living. Patients studied in the hospital during or near chemotherapy had significantly more abnormal circadian function than those studied in the ambulatory setting. Our data indicate that measurement of circadian sleep/activity dynamics should be accomplished in the outpatient/home setting for a minimum of 4–7 circadian cycles to assure that they are most representative of the patients' true condition. We conclude that the daily sleep/activity patterns of patients with advanced lung cancer are disturbed. These are accompanied by marked disruption of QoL and function. These data argue for investigating how much of this poor functioning and QoL are actually caused by this circadian disruption, and, whether behavioural, light-based, and or pharmacologic strategies to correct the circadian/sleep activity patterns can improve function and QoL

Molecular alterations as target for therapy in metastatic osteosarcoma: a review of literature

Treating metastatic osteosarcoma (OS) remains a challenge in oncology. Current treatment strategies target the primary tumour rather than metastases and have a limited efficacy in the treatment of metastatic disease. Metastatic cells have specific features that render them less sensitive to therapy and targeting these features might enhance the efficacy of current treatment. A detailed study of the biological characteristics and behaviour of metastatic OS cells may provide a rational basis for innovative treatment strategies. The aim of this review is to give an overview of the biological changes in metastatic OS cells and the preclinical and clinical efforts targeting the different steps in OS metastases and how these contribute to designing a metastasis directed treatment for OS

Identification of a General O-linked Protein Glycosylation System in Acinetobacter baumannii and Its Role in Virulence and Biofilm Formation

Acinetobacter baumannii is an emerging cause of nosocomial infections. The isolation of strains resistant to multiple antibiotics is increasing at alarming rates. Although A. baumannii is considered as one of the more threatening “superbugs” for our healthcare system, little is known about the factors contributing to its pathogenesis. In this work we show that A. baumannii ATCC 17978 possesses an O-glycosylation system responsible for the glycosylation of multiple proteins. 2D-DIGE and mass spectrometry methods identified seven A. baumannii glycoproteins, of yet unknown function. The glycan structure was determined using a combination of MS and NMR techniques and consists of a branched pentasaccharide containing N-acetylgalactosamine, glucose, galactose, N-acetylglucosamine, and a derivative of glucuronic acid. A glycosylation deficient strain was generated by homologous recombination. This strain did not show any growth defects, but exhibited a severely diminished capacity to generate biofilms. Disruption of the glycosylation machinery also resulted in reduced virulence in two infection models, the amoebae Dictyostelium discoideum and the larvae of the insect Galleria mellonella, and reduced in vivo fitness in a mouse model of peritoneal sepsis. Despite A. baumannii genome plasticity, the O-glycosylation machinery appears to be present in all clinical isolates tested as well as in all of the genomes sequenced. This suggests the existence of a strong evolutionary pressure to retain this system. These results together indicate that O-glycosylation in A. baumannii is required for full virulence and therefore represents a novel target for the development of new antibiotics

Decidual-Secreted Factors Alter Invasive Trophoblast Membrane and Secreted Proteins Implying a Role for Decidual Cell Regulation of Placentation

Inadequate or inappropriate implantation and placentation during the establishment of human pregnancy is thought to lead to first trimester miscarriage, placental insufficiency and other obstetric complications. To create the placental blood supply, specialized cells, the ‘extravillous trophoblast’ (EVT) invade through the differentiated uterine endometrium (the decidua) to engraft and remodel uterine spiral arteries. We hypothesized that decidual factors would regulate EVT function by altering the production of EVT membrane and secreted factors. We used a proteomics approach to identify EVT membrane and secreted proteins regulated by decidual cell factors. Human endometrial stromal cells were decidualized in vitro by treatment with estradiol (10−8 M), medroxyprogesterone acetate (10−7 M) and cAMP (0.5 mM) for 14 days. Conditioned media (CM) was collected on day 2 (non-decidualized CM) and 14 (decidualized CM) of treatment. Isolated primary EVT cultured on Matrigel™ were treated with media control, non-decidualized or decidualized CM for 16 h. EVT CM was fractionated for proteins <30 kDa using size-exclusion affinity nanoparticles (SEAN) before trypsin digestion and HPLC-MS/MS. 43 proteins produced by EVT were identified; 14 not previously known to be expressed in the placenta and 12 which had previously been associated with diseases of pregnancy including preeclampsia. Profilin 1, lysosome associated membrane glycoprotein 1 (LAMP1), dipeptidyl peptidase 1 (DPP1/cathepsin C) and annexin A2 expression by interstitial EVT in vivo was validated by immunhistochemistry. Decidual CM regulation in vitro was validated by western blotting: decidualized CM upregulated profilin 1 in EVT CM and non-decidualized CM upregulated annexin A2 in EVT CM and pro-DPP1 in EVT cell lysate. Here, non-decidualized factors induced protease expression by EVT suggesting that non-decidualized factors may induce a pro-inflammatory cascade. Preeclampsia is a pro-inflammatory condition. Overall, we have demonstrated the potential of a proteomics approach to identify novel proteins expressed by EVT and to uncover the mechanisms leading to disease states