Miracle-dz/UniFAR-FTUs huggingface dataset:
Dynamics of Dissolved and Particulate Polyunsaturated Aldehydes in Mesocosms Inoculated with Different Densities of the Diatom Skeletonema marinoi

A survey of the production of polyunsaturated aldehydes (PUA) of manipulated plankton communities is presented here. PUA are phytoplankton-derived metabolites that are proposed to play an important role in chemically mediated plankton interactions. Blooms of different intensities of the diatom Skeletonema marinoi were generated in eight mesocosms filled with water from the surrounding fjord by adding different amounts of a starting culture and nutrients. This set-up allowed us to follow PUA production of the plankton community over the entire induced bloom development, and to compare it with the natural levels of PUA. We found that S. marinoi is a major source for the particulate PUA 2,4-heptadienal and 2,4-octadienal (defined as PUA released upon wounding of the diatom cells) during the entire bloom development. Just before, and during, the decline of the induced diatom blooms, these PUA were also detected in up to 1 nM concentrations dissolved in the water. In addition, we detected high levels of the PUA 2,4-decadienal that was not produced by the diatom S. marinoi. Particulate decadienal correlated well with the cell counts of the prymnesiophyte Phaeocystis sp. that also developed in the fertilized mesocosms. Particulate decadienal levels were often even higher than those of diatom-derived PUA, indicating that PUA sources other than diatoms should be considered when it comes to the evaluation of the impact of these metabolites.
Indentation variability of natural nanocomposite materials

Small-scale depth-sensing indentation (nanoindentation) is a popular technique for measuring the mechanical properties of a wide range of materials. Contact mechanics solutions used in data analysis are based on the indentation of a homogeneous half-space, but the experiments are frequently conducted on mineralized biological tissues—biocomposite materials with nanometer-scale features—such as bone and dentin. The current study examines the experimental indentation response of bone across orders of magnitude in contact dimension length-scale, from nanometers to micrometers. Scaling arguments are used to establish the need for nanoscale simulations of mineralized tissue indentation. A finite element model of an inhomogeneous contact problem is developed and used to interpret experimental indentation data on bone and dentin. Both experimental data and modeling results demonstrate a convergence in apparent elastic modulus at increasing contact length-scales. Models results are used to estimate a feature size associated with inhomogeneity of the indentation response; for experiments conducted here the characteristic feature size is found to be substantially larger for bone than for dentin, and in both cases larger than for individual nanometer-scale mineral platelets.
Treatment of multiple myeloma with the immunostimulatory SLAMF7 antibody elotuzumab

Elotuzumab is a humanized monoclonal antibody targeting the extracellular domain of signaling lymphocytic activation molecule F7 (SLAMF7) highly expressed in multiple myeloma cells. Upon binding to myeloma cells, elotuzumab exerts its cytotoxic effects through antibody-dependent cellular cytotoxicity, the antibody-induced selective lysis of tumor cells by activated natural killer (NK) cells. Furthermore, elotuzumab has been shown to directly induce NK-cell activation by binding to SLAMF7 expressed on NK cells and to indirectly modulate T-cell function by promoting the secretion of cytokines from NK cells. In combination with lenalidomide and low-dose dexamethasone, elotuzumab has shown remarkable effects in patients with relapsed or refractory multiple myeloma. In these patients, the risk of disease progression or death was significantly reduced by 30% on elotuzumab. Currently, elotuzumab is being evaluated in various myeloma patient populations and combination regimens. This review discusses the use of elotuzumab as an antimultiple myeloma agent and provides an update on the results of recent clinical trials evaluating the safety and efficacy of elotuzumab for the treatment of multiple myeloma.
Role of the Epstein-Barr Virus Rta Protein in Activation of Distinct Classes of Viral Lytic Cycle Genes

ABSTRACT Initiation of the Epstein-Barr virus (EBV) lytic cycle is controlled by two immediate-early genes, BZLF1 and BRLF1. In certain epithelial and B-cell lines, their protein products, ZEBRA and Rta, stimulate their own expression, reciprocally stimulate each other’s expression, and activate downstream viral targets. It has been difficult to examine the individual roles of these two transactivators in EBV-infected lymphocytes, as they are expressed simultaneously upon induction of the lytic cycle. Here we show that the Burkitt lymphoma cell line Raji represents an experimental system that allows the study of Rta’s role in the lytic cycle of EBV in the absence and presence of ZEBRA. When expressed in Raji cells, exogenous Rta does not activate endogenous BZLF1 expression, yet Rta remains competent to transactivate certain downstream viral targets. Some genes, such as BaRF1, BMLF1, and a late gene, BLRF2, are maximally activated by Rta itself in the absence of detectable ZEBRA. The use of the Z(S186A) mutant form of ZEBRA, whose transactivation function is manifest only by coexpression of Rta, allows identification of a second class of lytic cycle genes, such as BMRF1 and BHRF1, that are activated in synergy by Rta and ZEBRA. It has already been documented that of the two activators, only ZEBRA stimulates the BRLF1 gene in Raji cells. Thus, there is a third class of viral genes activated by ZEBRA but not Rta. Moreover, ZEBRA exhibits an inhibitory effect on Rta’s capacity to stimulate the late gene, BLRF2. Consequently ZEBRA may function to repress Rta’s potential to activate some late genes. Raji cells thus allow delineation of the combinatorial roles of Rta and ZEBRA in control of several distinct classes of lytic cycle genes.
Assessing the Cost of Helping: The Roles of Body Condition and Oxidative Balance in the Seychelles Warbler (Acrocephalus sechellensis)

In cooperatively breeding species, helping close relatives may provide important fitness benefits. However, helping can be energetically expensive and may result in increased generation of reactive oxygen species. Consequently, an oxidant/antioxidant imbalance can lead to higher oxidative stress susceptibility. Given the potential costs of helping, it may be that only individuals with a sufficiently good body condition and/or stable oxidative balance can afford to help. Knowledge about relationships between social status and oxidative balance in cooperatively breeding systems is still limited. Studying these relationships is important for understanding the costs of helping and physiological pressures of reproduction. Here we evaluate the relationship between helping behaviour, body condition and oxidative balance in a wild population of the cooperatively breeding Seychelles warbler (Acrocephalus sechellensis). In this species, some subordinate individuals help dominant birds with the rearing of young, while others refrain from any assistance. We assessed body condition and oxidative parameters of birds of different social status caught during different breeding stages. We found that, prior to breeding, female subordinates that did not subsequently help (non-helpers) had significantly lower body condition and higher ROMs (reactive oxygen metabolites) than helpers and dominants. During the later stages of breeding, body condition was low in dominants and helpers, but high in non-helpers. Differences in oxidative balance between individuals of different social status were found only during nest care: Dominant males occupied with guarding behaviours tended to have relatively high oxidative stress susceptibility. Furthermore, dominant and helper females showed elevated antioxidant capacity (measured as OXY) in the weeks just prior to egg-laying, possibly representing a change in their reproductive physiology. The results imply that an individuals' oxidative balance may be influenced by factors related to reproduction, which can differ with sex and—within cooperative breeding systems—social status.
Stress urinary incontinence in women with a history of gestational diabetes mellitus.

OBJECTIVE Stress urinary incontinence may serve as a barrier to lifestyle modification among women at high risk for diabetes, but the prevalence of stress urinary incontinence among women with histories of gestational diabetes mellitus (hGDM) is unknown. The purpose of this study was to examine the prevalence of stress incontinence among women with hGDM and to examine its association with their current physical activity. METHODS We surveyed women with hGDM within the past 5 years who were currently enrolled in a managed care plan (n = 228). In a cross-sectional analysis, self-reported weekly or more frequent stress incontinence was the primary independent variable and measures of physical activity and body mass index (BMI) were the outcomes of interest. We constructed multivariable models that adjusted for participant characteristics associated with the measure of incontinence or outcomes in bivariate analyses. RESULTS Of the 228 women with hGDM, 49% reported weekly or more frequent incontinence during pregnancy, and 28% reported that incontinence affected their activities during pregnancy. Fifty percent reported weekly or more frequent incontinence after delivery, with 27% reporting interference of incontinence with activity. Less than a third of women reported optimal physical activity, and 42% were obese. After adjustment for characteristics associated with measures of activity and incontinence, there was minimal association between levels of activity and stress urinary incontinence; similarly, there was no association between BMI and measures of stress incontinence. CONCLUSIONS Stress urinary incontinence is common among women with hGDM but does not appear to be associated with physical activity levels or BMI.
Statistical and molecular dynamics studies of buried waters in globular proteins

Buried solvent molecules are common in the core of globular proteins and contribute to structural stability. Folding necessitates the burial of polar backbone atoms in the protein core, whose hydrogen‐bonding capacities should be satisfied on average. Whereas the residues in α‐helices and β‐sheets form systematic main‐chain hydrogen bonds, the residues in turns, coils and loops often contain polar atoms that fail to form intramolecular hydrogen bonds. The statistical analysis of 842 high resolution protein structures shows that well‐resolved, internal water molecules preferentially reside near residues without α‐helical and β‐sheet secondary structures. These buried waters most often form primary hydrogen bonds to main‐chain atoms not involved in intramolecular hydrogen bonds, providing strong evidence that hydrating main‐chain atoms is a key structural role of buried water molecules. Additionally, the average B‐factor of protein atoms hydrogen‐bonded to waters is smaller than that of protein atoms forming intramolecular hydrogen bonds, and the average B‐factor of water molecules involved in primary hydrogen bonds with main‐chain atoms is smaller than the average B‐factor of water molecules involved in secondary hydrogen bonds to protein atoms that form concurrent intramolecular hydrogen bonds. To study the structural coupling between internal waters and buried polar atoms in detail we simulated the dynamics of wild‐type FKBP12, in which a buried water, Wat137, forms one side‐chain and multiple main‐chain hydrogen bonds. We mutated E60, whose side‐chain hydrogen bonds with Wat137, to Q, N, S or A, to modulate the multiplicity and geometry of hydrogen bonds to the water. Mutating E60 to a residue that is unable to form a hydrogen bond with Wat137 results in reorientation of the water molecule and leads to a structural readjustment of residues that are both near and distant to the water. We predict that the E60A mutation will result in a significantly reduced affinity of FKBP12 for its ligand FK506. The propensity of internal waters to hydrogen bond to buried polar atoms suggests that ordered water molecules may constitute fundamental structural components of proteins, particularly in regions where α‐helical or β‐sheet secondary structure is not present. Proteins 2005. © 2005 Wiley‐Liss, Inc.
Comparison of serum zinc concentrations and body antioxidant status between young women with premenstrual syndrome and normal controls: A case-control study

Background: Premenstrual syndrome (PMS) is one of the important health problems with high incidence in young women. The exact cause of this syndrome is not clear and some theories have been declared from hormonal factors to nutritional disorders. Objective: We investigated the correlation between serum zinc and antioxidant status with PMS. Materials and Methods: In this case-control study, forty eight young girls were selected from a total sample of 110 students residing at university dormitories including PMS (n=23) and healthy (n=25) groups based on PMS questionnaire. Dietary intake questionnaire and blood samples were collected from all participants. Serum total antioxidant capacity (TAC) and zinc concentrations were also measured. Results: Serum TAC and zinc concentrations were lower in PMS patients compared with healthy groups (p<0.01 and p<0.05, respectively). Healthy controls consumed lower servings of hydrogenated oils (p<0.05). There were significant differences in terms of muscle mass between the PMS and healthy groups (p<0.05). Both serum TAC and zinc levels were negatively correlated to PMS scores (r=-0.39, p<0.05 and r= -0.36; p<0.05, respectively). Conclusion: This study shows that higher TAC and zinc serum levels are associated with lower risk of PMS. PMS cases have more hydrogenated oils than their normal counterparts.
Genotyping of Francisella tularensis Strains by Pulsed-Field Gel Electrophoresis, Amplified Fragment Length Polymorphism Fingerprinting, and 16S rRNA Gene Sequencing

ABSTRACT We evaluated three molecular methods for identification of Francisella strains: pulsed-field gel electrophoresis (PFGE), amplified fragment length polymorphism (AFLP) analysis, and 16S rRNA gene sequencing. The analysis was performed with 54 Francisella tularensis subsp. holarctica, 5 F. tularensis subsp. tularensis, 2 F. tularensis subsp. novicida, and 1 F. philomiragia strains. On the basis of the combination of results obtained by PFGE with the restriction enzymes XhoI and BamHI, PFGE revealed seven pulsotypes, which allowed us to discriminate the strains to the subspecies level and which even allowed us to discriminate among some isolates of F. tularensis subsp. holarctica. The AFLP analysis technique produced some degree of discrimination among F. tularensis subsp. holarctica strains (one primary cluster with three major subclusters and minor variations within subclusters) when EcoRI-C and MseI-A, EcoRI-T and MseI-T, EcoRI-A and MseI-C, and EcoRI-0 and MseI-CA were used as primers. The degree of similarity among the strains was about 94%. The percent similarities of the AFLP profiles of this subspecies compared to those of F. tularensis subsp. tularensis, F. tularensis subsp. novicida, and F. philomiragia were less than 90%, about 72%, and less than 24%, respectively, thus permitting easy differentiation of this subspecies. 16S rRNA gene sequencing revealed 100% similarity for all F. tularensis subsp. holarctica isolates compared in this study. These results suggest that although limited genetic heterogeneity among F. tularensis subsp. holarctica isolates was observed, PFGE and AFLP analysis appear to be promising tools for the diagnosis of infections caused by different subspecies of F. tularensis and suitable techniques for the differentiation of individual strains.
FNS Parameter Selection and Upper Limb Characterzation

The design of a controller for functional neuromuscular stimulation requires characterization of the plant, i. e. , the neuromuscular system involved. The present paper is concerned with the modeling and identification of the elbow flexion/extension and wrist pronation/supination systems. These movements can be performed successfully by the surface stimulation of the biceps, triceps, and pronator teres. The scatter in the plant parameters between subjects and for a given subject as a function of time, electrode placement, etc., is outlined. The nonlinear muscle gain is approximated by a threshold below which the torque is zero, followed by a linear region. A least squares identification technique using a pseudorandom binary sequence input returned best fit for a third-order model for both the elbow and wrist dynamics. The dependence of the complex poles on the input signal bandwidth and level of coactivation is examined. The differences in parameters between the wrist and elbow systems are calculated. The results are used to establish design requirements for an appropriate controller.
Selective Impairment of the Auditory-Verbal Short-Term Memory due to a Lesion of the Superior Temporal Gyrus

115 tion: an increase in its volume and slowing down of its circulation that can lead to subdural effusions or hematomas due to extravasation from the dilated venous system [1, 2]. The presence of subdural hematomas in sinus thrombosis, although possible, is rare. The diagnosis of IH requires a CSF pressure measured by lumbar tapping of less than 60 mm H2O. In our case, it could not be carried out due to the risk of cerebral herniation because of the VST. So, we cannot confirm the presence of IH, but the clinical presentation, evolution and MRI findings strongly suggest this diagnosis. The cause of IH could be a CSF leakage due to the strong sustained exercise the patient had practiced the previous month. Other etiologies of IH, like dehydration, diabetic coma, hyperventilation, meningoencephalitis, uremia or systemic infections, were rejected [4, 8]. Chisholm and Campbell [9] reported a superior sagittal sinus thrombosis initially mistaken for an IH syndrome due to the postural headache that the patient suffered. This happened in a young woman in the puerperal period (a risk factor for thrombosis) and without reference to image findings suggesting IH. So, it was understood as a sinus thrombosis that clinically evoked an IH syndrome. However, we interpret our case differently. Based on the physiopathology of IH, we think it could be possible that IH may cause an extreme ingurgitation and stasis of the dural venous system leading to thrombosis. To our knowledge, there is no other reported case prompting the idea of an association between IH and VST. Thus, we consider that VST could complicate an initially trivial IH syndrome. The description of similar cases would increase the knowledge of this association and the physiopathology of both entities.
Healthcare resource use in advanced prostate cancer patients treated with docetaxel

Abstract Objective: Although the treatment of metastatic castrate-resistant prostate cancer (mCRPC) has improved with newer therapies, there is little understanding how these therapies have impacted resource use and associated expenditures; available estimates are dated. The current study examined contemporary healthcare utilization and associated costs for mCRPC patients and how these measures changed over time. Methods: This retrospective cohort analysis used medical and pharmaceutical insurance claims data from a large non-payer-owned integrated claims database of US commercial insurers. Amongst all patients with a prostate cancer diagnosis (n = 256,464), those with ≥ 1 docetaxel claim (docetaxel cohort, n = 3642) were identified as mCRPC patients. Within the docetaxel cohort, an additional 6-months follow-up cohort (n = 2862) was identified, i.e., patients with at least 6 months of follow-up after the first docetaxel claim. Resource utilization and costs were identified for all-cause hospitalizations, emergency room (ER) visits, physician visits and ambulatory visits, and prostate cancer-related prescription treatments. Results: Significant increases in the mean per-patient-per-month (PPPM) count for the docetaxel cohort were observed for all medical resources measured (hospitalizations and ER, physician, and ambulatory visits) in the post-docetaxel period compared with the pre-docetaxel period (p < 0.0001); similar significant increases were observed for the 6-months follow-up cohort in the last 6 months (prior to lost to follow-up date) compared with the period preceding the last 6 months (p < 0.0408 ambulatory visits, p < 0.0001 all other resources). Total docetaxel cohort costs (mean [standard deviation]) rose from an average PPPM cost of US$2593 (3208) in the pre-docetaxel period to US$5847 (6990) in the post-docetaxel period (p < 0.0001); each of the individual resources measured (hospitalization, all healthcare visits, and prescription costs) demonstrated significant increases (p < 0.0001). Limitations: Retrospective study design. Conclusions: This large database analysis showed a significant increase in use of healthcare resources and associated costs among mCRPC patients following first-line docetaxel treatment.
Schizophrenia outcome measures in the wider international community

Background Outcome of schizophrenia has been described as favourable in low-and middle-income countries. Recently, researchers have questioned these findings Aims To examine the outcome studies carried out in different countries specifically looking atthose from low-and middle-income countries Methods Long-term course and outcome studies in schizophrenia were reviewed Results A wide variety of outcome measures are used. The most frequent are clinical symptoms, hospitalisation and mortality (direct indicators), and social/ occupational functioning, marriage, social support and burden of care (indirect indicators). Areas such as cognitive function, duration of untreated psychosis, quality of life and effect of medication have not been widely studied in low-and middle-income countries Conclusions The outcome of schizophrenia appears to be better in low-and middle-income countries. A host of sociocultural factors have been cited as contributing to this but future research should aim to understand this better outcome. There is a need for more culture-specific instruments to measure outcomes