Quantum dynamics in strong fluctuating fields

A large number of multifaceted quantum transport processes in molecular systems and physical nanosystems can be treated in terms of quantum relaxation processes which couple to one or several fluctuating environments. A thermal equilibrium environment can conveniently be modelled by a thermal bath of harmonic oscillators. An archetype situation provides a two-state dissipative quantum dynamics, commonly known under the label of a spin-boson dynamics. An interesting and nontrivial physical situation emerges, however, when the quantum dynamics evolves far away from thermal equilibrium. This occurs, for example, when a charge transferring medium possesses nonequilibrium degrees of freedom, or when a strong time-dependent control field is applied externally. Accordingly, certain parameters of underlying quantum subsystem acquire stochastic character. Herein, we review the general theoretical framework which is based on the method of projector operators, yielding the quantum master equations for systems that are exposed to strong external fields. This allows one to investigate on a common basis the influence of nonequilibrium fluctuations and periodic electrical fields on quantum transport processes. Most importantly, such strong fluctuating fields induce a whole variety of nonlinear and nonequilibrium phenomena. A characteristic feature of such dynamics is the absence of thermal (quantum) detailed balance.Comment: review article, Advances in Physics (2005), in pres

Analysis Results of the Regional Registry of Patients with Diffuse Large B-cell Lymphoma: Risk Factors and Chemo-Immunotherapy Issues

Background & Aims. At least one third of patients with diffuse large B-cell lymphoma (DLBCL) are resistant to first-line therapy. R-CHOP chemo-immunotherapy does not yield acceptable results in high-risk patients. Effectiveness of options based either on increasing the dose intensity or on including auto-HSCT into the first-line therapy was not supported by the results of controlled studies. With this background the present study focuses on options, issues and failures of first-line on the basis of long-term follow-up of DLBCL patient population in the Volgograd Region. Materials & Methods. From 2004 to 2017 the population-based registry of the Hematology Department in the Volgograd Regional Clinical Oncology Dispensary included all 492 primary DLBCL patients: 235 (48 %) men and 257 (52 %) women aged 18 to 88 years. Mean and median age was 59 and 61 years, respectively. CHOP therapy was administered to 206 (42 %) patients, and 223 (45 %) patients received R-CHOP. Other regimens including NHL-BFM-90 and R-DA-EPOCH were used only in 63 (13 %) patients. Second- and third-line therapies were administered to 145 (30 %) and 54 (11 %) patients, respectively. Value of the International Prognostic Index (IPI) and immunomorphologic characteristics was determined by multivariate Cox regression analysis. Pharmacoeconomic aspect of first-line therapy failures was analyzed using Markov model. Results. Improvement of DLBCL therapy effects with the use of R-CHOP chemo-immunotherapy is particularly obvious in the groups with favorable and intermediate prognosis with 5-year overall survival (OS) of 90 % and 69 %, respectively. R-CHOP results are not considered to be satisfactory in the high-risk group: 5-year OS was 38 %. Pharmacoeconomic analysis proves the advantage of chemo-immunotherapy strategy in comparison with the period before rituximab era in terms of the life years gained (LYG) and the incremental cost-effectiveness ratio (ICER). With respect to immunotherapy effects the most significant immunomorphologic parameter is bcl-2 tumor cell expression. In the group of patients with bcl-2 > 50 % 5-year OS was 61 % with median of 88 months, event-free survival (EFS) was 52 % with median of 62 months. In the group without bcl-2 expression above the threshold 5-year OS and EFS were 88 % and 75 %, respectively, medians were not achieved. With c-myc and bcl-2 coexpression EFS and OS appeared to be even worse: 5-year EFS was 29 % with median of 6 months, and 5-year OS was 31 % with median of 15 months. Conclusion. The analysis of actual practice demonstrates the need for new options of first-line therapy for DLBCL high-risk patients and also for introducing new discriminating prognostic factors which include the IPI-independent ones

Use of cDNA Tiling Arrays for Identifying Protein Interactions Selected by In Vitro Display Technologies

In vitro display technologies such as mRNA display are powerful screening tools for protein interaction analysis, but the final cloning and sequencing processes represent a bottleneck, resulting in many false negatives. Here we describe an application of tiling array technology to identify specifically binding proteins selected with the in vitro virus (IVV) mRNA display technology. We constructed transcription-factor tiling (TFT) arrays containing ∼1,600 open reading frame sequences of known and predicted mouse transcription-regulatory factors (334,372 oligonucleotides, 50-mer in length) to analyze cDNA fragments from mRNA-display screening for Jun-associated proteins. The use of the TFT arrays greatly increased the coverage of known Jun-interactors to 28% (from 14% with the cloning and sequencing approach), without reducing the accuracy (∼75%). This method could detect even targets with extremely low expression levels (less than a single mRNA copy per cell in whole brain tissue). This highly sensitive and reliable method should be useful for high-throughput protein interaction analysis on a genome-wide scale

Measuring Resilience in Adult Women Using the 10-Items Connor-Davidson Resilience Scale (CD-RISC). Role of Trauma Exposure and Anxiety Disorders

International audiencePURPOSE: Resilience is the ability of individuals to adapt positively in the face of trauma. Little is known, however, about lifetime factors affecting resilience. METHODS: We assessed the effects of psychiatric disorder and lifetime trauma history on the resilience self-evaluation using the Connor-Davidson Resilience Scale (CD-RISC-10) in a high-risk-women sample. Two hundred and thirty eight community-dwelling women, including 122 participants in a study of breast cancer survivors and 116 participants without previous history of cancer completed the CD-RISC-10. Lifetime psychiatric symptoms were assessed retrospectively using two standardized psychiatric examinations (Mini International Neuropsychiatric Interview and Watson's Post-Traumatic Stress Disorder Inventory). RESULTS: Multivariate logistic regression adjusted for age, education, trauma history, cancer, current psychiatric diagnoses, and psychoactive treatment indicated a negative association between current psychiatric disorder and high resilience compared to low resilience level (OR = 0.44, 95% CI [0.21-0.93]). This was related to anxiety and not mood disorder. A positive and independent association with a trauma history was also observed (OR = 3.18, 95% CI [1.44-7.01]). CONCLUSION: Self-evaluation of resilience is influenced by both current anxiety disorder and trauma history. The independent positive association between resilience and trauma exposure may indicate a "vaccination" effect. This finding need to be taken into account in future studies evaluating resilience in general or clinical populations

The 2024 Outline of Fungi and fungus-like taxa

With the simultaneous growth in interest from the mycological community to discover fungal species and classify them, there is also an important need to assemble all taxonomic information onto common platforms. Fungal classification is facing a rapidly evolving landscape and organizing genera into an appropriate taxonomic hierarchy is central to better structure a unified classification scheme and avoid incorrect taxonomic inferences. With this in mind, the Outlines of Fungi and fungus-like taxa (2020, 2022) were published as an open-source taxonomic scheme to assist mycologists to better understand the taxonomic position of species within the Fungal Kingdom as well as to improve the accuracy and consistency of our taxonomic language. In this paper, the third contribution to the series of Outline of Fungi and fungus-like taxa prepared by the Global Consortium for the Classification of Fungi and fungus-like taxa is published. The former is updated considering our previous reviews and the taxonomic changes based on recent taxonomic work. In addition, it is more comprehensive and derives more input and consensus from a larger number of mycologists worldwide. Apart from listing the position of a particular genus in a taxonomic level, nearly 1000 notes are provided for newly established genera and higher taxa introduced since 2022. The notes section emphasizes on recent findings with corresponding references, discusses background information to support the current taxonomic status and some controversial taxonomic issues are also highlighted. To elicit maximum taxonomic information, notes/taxa are linked to recognized databases such as Index Fungorum, Faces of Fungi, MycoBank and GenBank, Species Fungorum and others. A new feature includes links to Fungalpedia, offering notes in the Compendium of Fungi and fungus-like Organisms. When specific notes are not provided, links are available to webpages and relevant publications for genera or higher taxa to ease data accessibility. Following the recent synonymization of Caulochytriomycota under Chytridiomycota, with Caulochytriomycetes now classified as a class within the latter, based on formally described and currently accepted data, the Fungi comprises 19 Phyla, 83 classes, 1,220 families, 10,685 genera and ca 140,000 species. Of the genera, 39.5% are monotypic and this begs the question whether mycologists split genera unnecessarily or are we going to find other species in these genera as more parts of the world are surveyed? They are 433 speciose genera with more than 50 species. The document also highlights discussion of some important topics including number of genera categorized as incertae sedis status in higher level fungal classification. The number of species at the higher taxonomic level has always been a contentious issue especially when mycologists consider either a lumping or a splitting approach and herein we provide figures. Herein a summary of updates in the outline of Basidiomycota is provided with discussion on whether there are too many genera of Boletales, Ceratobasidiaceae, and speciose genera such as Colletotrichum. Specific case studies deal with Cortinarius, early diverging fungi, Glomeromycota, a diverse early divergent lineage of symbiotic fungi, Eurotiomycetes, marine fungi, Myxomycetes, Phyllosticta, Hymenochaetaceae and Polyporaceae and the longstanding practice of misapplying intercontinental conspecificity. The outline will aid to better stabilize fungal taxonomy and serves as a necessary tool for mycologists and other scientists interested in the classification of the Fungi

Assay for ubiquitin ligase activity: High-throughput screen for inhibitors of HDM2

An assay for the autoubiquitination activity of the E3 ligase HDM2 (Mdm2) was developed and adapted to a high-throughput format to identify inhibitors of this activity. The assay can also be used to measure the activity of other E3s and may be useful in finding both inhibitors and activators of a wide range of different ubiquitin ligase

Inhibitors of ubiquitin-activating enzyme (E1), a new class of potential cancer therapeutics

The conjugation of proteins with ubiquitin plays numerous regulatory roles through both proteasomal-dependent and nonproteasomal-dependent functions. Alterations in ubiquitylation are observed in a wide range of pathologic conditions, including numerous malignancies. For this reason, there is great interest in targeting the ubiquitin-proteasome system in cancer. Several classes of proteasome inhibitors, which block degradation of ubiquitylated proteins, are widely used in research, and one, Bortezomib, is now in clinical use. Despite the well-defined and central role of the ubiquitin-activating enzyme (E1), no cell permeable inhibitors of El have been identified. Such inhibitors should, in principle, block all functions of ubiquitylation. We now report 4[4-(5-nitro-furan-2-ylmethylene)-3,5-dioxo-pyrazolidin-1-yl]-benzoic acid ethyl ester (PYR-41) as the first such inhibitor. Unexpectedly, in addition to blocking ubiquitylation, PYR-41 increased total sumoylation in cells. The molecular basis for this is unknown; however, increased sumoylation was also observed in cells harboring temperature-sensitive El. Functionally, PYR-41 attenuates cytokine-mediated nuclear factor-kappa B activation. This correlates with inhibition of nonproteasomal (Lys-63) ubiquitylation of TRAF6, which is essential to I kappa B kinase activation. PYR-41 also prevents the downstream ubiquitylation and proteasomal degradation of I kappa B alpha. Furthermore, PYR-41 inhibits degradation of p53 and activates the transcriptional activity of this tumor suppressor. Consistent with this, it differentially kills transformed p53-expressing cells. Thus, PYR-41 and related pyrazones provide proof of principle for the capacity to differentially kill transformed cells, suggesting the potential for E I inhibitors as therapeutics in cancer. These inhibitors can also be valuable tools for studying ubiquitylation