Miracle-dz/UniFAR-FTUs huggingface dataset:
HUPO Brain Proteome Project: aims and needs in proteomics

Proteome and proteomics have a good chance to be voted as the new decade buzzwords in life sciences. The term ‘proteome’ was introduced in 1994 by the Australian Marc Wilkins, describing all the proteins expressed by a genome in a given cell at a given time. Within just a few years, proteomics became the new hope of the scientific community. Proteomes are highly dynamic as they differ in gender, cell type and tissue. They may also change due to aging, medication and other external influences. The study of proteomes is referred to as ‘proteomics’ and is normally performed via 2D gel electrophoresis (protein separation) and mass spectrometry (protein identification). In a standard approach, the proteomes of two stages (e.g., healthy vs. diseased tissue) are compared in a differential proteome analysis, thereby revealing differentially expressed proteins [1]. Further characterization of such proteins (i.e., protein function or involvement in disease) will hopefully reveal biomarkers for the disease, which may be used for early onset diagnosis, or possibly serve as therapeutic targets [2]. In summary, this is the theory.
Free Energy for the Permeation of Na+ and Cl− Ions and Their Ion-Pair through a Zwitterionic Dimyristoyl Phosphatidylcholine Lipid Bilayer by Umbrella Integration with Harmonic Fourier Beads

Understanding the mechanism of ion permeation across lipid bilayers is key to controlling osmotic pressure and developing new ways of delivering charged, drug-like molecules inside cells. Recent reports suggest ion-pairing as the mechanism to lower the free energy barrier for the ion permeation in disagreement with predictions from the simple electrostatic models. In this paper we quantify the effect of ion-pairing or charge quenching on the permeation of Na+ and Cl− ions across DMPC lipid bilayer by computing the corresponding potentials of mean force (PMFs) using fully atomistic molecular dynamics simulations. We find that the free energy barrier to permeation reduces in the order Na+−Cl− ion-pair (27.6 kcal/mol) > Cl− (23.6 kcal/mol) > Na+ (21.9 kcal/mol). Furthermore, with the help of these PMFs we derive the change in the binding free energy between the Na+ and Cl− with respect to that in water as a function of the bilayer permeation depth. Despite the fact that the bilayer boosts the Na+−Cl− ion binding free energy by as high as 17.9 kcal/mol near its center, ion-pairing between such hydrophilic ions as Na+ and Cl− does not assist their permeation. However, based on a simple thermodynamic cycle, we suggest that ion-pairing between ions of opposite charge and solvent philicity could enhance ion permeation. Comparison of the computed permeation barriers for Na+ and Cl− ions with available experimental data supports this notion. This work establishes general computational methodology to address ion-pairing in fluid anisotropic media and details the ion permeation mechanism on atomic level.
HLA dependent immune escape mechanisms in B-cell lymphomas: Implications for immune checkpoint inhibitor therapy?

ABSTRACT Antigen presentation by tumor cells in the context of Human Leukocyte Antigen (HLA) is generally considered to be a prerequisite for effective immune checkpoint inhibitor therapy. We evaluated cell surface HLA class I, HLA class II and cytoplasmic HLA-DM staining by immunohistochemistry (IHC) in 389 classical Hodgkin lymphomas (cHL), 22 nodular lymphocyte predominant Hodgkin lymphomas (NLPHL), 137 diffuse large B-cell lymphomas (DLBCL), 39 primary central nervous system lymphomas (PCNSL) and 19 testicular lymphomas. We describe a novel mechanism of immune escape in which loss of HLA-DM expression results in aberrant membranous invariant chain peptide (CLIP) expression in HLA class II cell surface positive lymphoma cells, preventing presentation of antigenic peptides. In HLA class II positive cases, HLA-DM expression was lost in 49% of cHL, 0% of NLPHL, 14% of DLBCL, 3% of PCNSL and 0% of testicular lymphomas. Considering HLA class I, HLA class II and HLA-DM together, 88% of cHL, 10% of NLPHL, 62% of DLBCL, 77% of PCNSL and 87% of testicular lymphoma cases had abnormal HLA expression patterns. In conclusion, an HLA expression pattern incompatible with normal antigen presentation is common in cHL, DLBCL, PCNSL and testicular lymphoma. Retention of CLIP in HLA class II caused by loss of HLA-DM is a novel immune escape mechanism, especially prevalent in cHL. Aberrant HLA expression should be taken into account when evaluating efficacy of checkpoint inhibitors in B-cell lymphomas.
The Inner Foreskin of Healthy Males at Risk of HIV Infection Harbors Epithelial CD4+ CCR5+ Cells and Has Features of an Inflamed Epidermal Barrier

Male circumcision provides partial protection against multiple sexually transmitted infections (STIs), including HIV, but the mechanisms are not fully understood. To examine potential vulnerabilities in foreskin epithelial structure, we used Wilcoxon paired tests adjusted using the false discovery rate method to compare inner and outer foreskin samples from 20 healthy, sexually active Peruvian males who have sex with males or transgender females, ages 21–29, at elevated risk of HIV infection. No evidence of epithelial microtrauma was identified, as assessed by keratinocyte activation, fibronectin deposition, or parakeratosis. However, multiple suprabasal tight junction differences were identified: 1) inner foreskin stratum corneum was thinner than outer (p = 0.035); 2) claudin 1 had extended membrane-bound localization throughout inner epidermis stratum spinosum (p = 0.035); 3) membrane-bound claudin 4 was absent from inner foreskin stratum granulosum (p = 0.035); and 4) occludin had increased membrane deposition in inner foreskin stratum granulosum (p = 0.042) versus outer. Together, this suggests subclinical inflammation and paracellular transport modifications to the inner foreskin. A setting of inflammation was further supported by inner foreskin epithelial explant cultures secreting higher levels of GM-CSF (p = 0.029), IP-10 (p = 0.035) and RANTES (p = 0.022) than outer foreskin, and also containing an increased density of CCR5+ and CD4+ CCR5+ cells (p = 0.022). Inner foreskin dermis also secreted more RANTES than outer (p = 0.036), and had increased density of CCR5+ cells (p = 0.022). In conclusion, subclinical changes to the inner foreskin of sexually active males may support an inflammatory state, with availability of target cells for HIV infection and modifications to epidermal barriers, potentially explaining the benefits of circumcision for STI prevention.
Validation of the Test of Functional Health Literacy in Adults in a Danish population.

OBJECTIVE To describe how the original American full-length version of the Test of Functional Health Literacy in Adults (TOFHLA) was translated and adapted for use in the Danish setting and culture. A reliable Danish version of the TOFHLA was created and pretested using patients diagnosed with chronic obstructive pulmonary disease (COPD) as case group. METHODS Forty-two patients with COPD completed the Danish TOFHLA and participated in a face-to-face interview concerning their basic demographics. Statistical analyses were conducted to explore the demographic data provided by the participants and to determine the internal consistency and reliability of the Danish TOFHLA. RESULTS The mean age of sample was 68.7 years (range 34-86). The face validity, internal consistency and item to scale correlations of the Danish TOFHLA were determined and found to fulfil well-established criteria; on this basis, we found the reliability and consistency of the Danish TOFHLA to be satisfying. CONCLUSION The Danish TOFHLA is now ready for application in future research projects, which test levels of functional health literacy in an elderly Danish population at risk of chronic diseases. The evolvement in the measurement of health literacy is still ongoing, as there is a need to refine existing methods. Until recently, there has been a total lack of instruments for assessing health literacy in Scandinavia; it is hoped that this development of the Danish TOFHLA will promote further research within the field of health literacy in Scandinavia and other European countries.
EFFECTS OF FASTING PERIOD AND ENZYME SUPPLEMENTATION ON PERFORMANCE AND SOME PHYSIOLOGICAL RESPONSES OF BROILER CHICKENS

This study was conducted to evaluate the effect of fasting period with or without enzyme supplementation on body weight, body weight gain, feed intake, and feed conversion ratio; carcass traits and blood parameters of broilers. One hundred sixty eight, one day old, Cobb broiler chicks were randomly distributed into eight treatments. Each treatment included three replicates each with 7 birds. Birds were distributed into two basal diet groups. The first diet group was subdivided into 4 treatments (T1, T2, T3, and T4) which were supplemented with enzymatic growth promoters VETA –ZYME PLUS A 250 g/ton. The second diet group was also subdivided into 4 treatment groups (T5, T6, T7 and T8) without supplementation. In the first or the second group, the feed was offered to the birds as following: T1, T5: birds were fed ad libitum, T2 and T6 (feed removed from 12:00 to 18:00 am during a day), T3 and T7 (feed removed from 23.00 to 7:00 during a day) and T4 and T8 (removed feed from 23:00 to 9:00 during a day). The results indicated that feed restriction systems with or without enzyme supplementation did significantly affect feed intake, live body weight, body weight gain, and feed conversion at starter, grower and whole periods. Feed restriction did not significantly affected carcass traits and blood parameters during the whole periods.
Simulating climate change in UK cities using a regional climate model, HadRM3

A regional climate model (RCM) at 25 km resolution, coupled to a simple urban land‐surface scheme has been used to assess the sensitivity of UK urban climates to large‐scale greenhouse gas (GHG) induced climate change, local forcing from urban land use, and anthropogenic heat flux (AHF) resulting from energy use in urban areas. GHG‐induced climate change is similar over both urban and rural land surfaces in the model, suggesting that under a changing climate the relative magnitude of urban heat islands in the UK would remain the same. However, indirect effects from urbanisation or changes in energy consumption within UK cities would contribute to further localized anthropogenic climate change that can be quantified by this model. The presence of the urban heat island also has a significant impact on the frequency of extreme high temperatures both in present and future climates, and will exacerbate the impact of climate change on the urban population.
An automated system for the measurement of nitrogen oxides and ozone concentrations from a passenger aircraft: Instrumentation and first results of the NOXAR project

A fully automated system for measuring NO, NO2, and O3 in the upper troposphere and lower stratosphere from a passenger aircraft is described. Detection limits (1σ) of 23, 45, and 500 pptv were achieved for NO, NO2, and O3, respectively, for a 2 min integration time during flights. Continuous measurements were made during a 1 year period ending May 1996 on a total of 540 flights between Zurich and destinations in the United States and the Far East. The measurements represent about a 10-fold increase in the coverage of presently available NOx measurements in the tropopause region. The measurement hardware, based on commercially available instrumentation and specifically designed to meet the very stringent safety regulations normal in civil aviation, is described, and first results are briefly reported.
LOFAR FACET CALIBRATION

LOFAR, the Low-Frequency Array, is a powerful new radio telescope operating between 10 and 240 MHz. LOFAR allows detailed sensitive high-resolution studies of the low-frequency radio sky. At the same time LOFAR also provides excellent short baseline coverage to map diffuse extended emission. However, producing high-quality deep images is challenging due to the presence of direction-dependent calibration errors, caused by imperfect knowledge of the station beam shapes and the ionosphere. Furthermore, the large data volume and presence of station clock errors present additional difficulties. In this paper we present a new calibration scheme, which we name facet calibration, to obtain deep high-resolution LOFAR High Band Antenna images using the Dutch part of the array. This scheme solves and corrects the direction-dependent errors in a number of facets that cover the observed field of view. Facet calibration provides close to thermal noise limited images for a typical 8 hr observing run at ∼ 5 ″ resolution, meeting the specifications of the LOFAR Tier-1 northern survey.
Efficacy and direct costs of chronic hepatitis C treatment with first generation NS3/4A protease inhibitors in a real life population

Introduction Recent years have brought a significant advance in chronic hepatitis C (CHC) treatment that includes development of direct acting antivirals (DAA). Two of them, boceprevir (BOC) and telaprevir (TVR), were first approved for treatment of patients infected with CHC genotype 1 in combination with pegylated interferon (P) and ribavirin (R). Our aim was to evaluate the efficacy and direct costs of BOC/PR and TVR/PR in a real life population. Material and methods The study included adult patients qualified for the CHC Therapeutic Programme treated with TVR/PR or BOC/PR. Treatment was continued for 24 or 48 weeks. Sustained virological response, treatment discontinuation due to adverse events and lack of virological response rates were compared. Results A total of 243 adult patients with CHC were included. TVR/PR and BOC/PR were administered in respectively 122 and 121 patients. Thirty-two patients (13%) were treatment-naïve, whereas liver cirrhosis/advanced fibrosis was observed in 138 patients (56.7%). Overall, 43.6% of patients achieved a sustained virologic response (SVR). In the BOC/PR group the SVR rate was significantly lower than in the TVR/PR group (33.1% vs. 54.1%; p = 0.00094). Lack of response to therapy was observed in 41.3% and 12.3% of patients receiving BOC and TVR, respectively (p < 0.00001). The direct cost of achieving SVR in one patient was 285 450 PLN with BOC and 185 757 PLN with TVR. Conclusions The very low treatment efficacy may be the result of inclusion criteria that allowed treatment of patients with advanced liver fibrosis/liver cirrhosis or previous treatment failure. Telaprevir seems to be significantly more potent against hepatitis C virus, with similar safety and tolerance.
Flow Cytometric Detection of Activated Platelets in Pregnant Women Prior to the Development of Pre-Eclampsia

Summary Pre-eclampsia is a common complication of pregnancy, in which platelets may have an early pathogenetic role. In this prospective study a whole blood flow cytometric method has been used to detect circulating activated platelets in pregnant women prior to the development of pre-eclampsia. Activated platelets were identified by bound fibrinogen or by CD63 antigen expression. Of 121 healthy primiparous women studied at 28 weeks of pregnancy, 18 (15%) developed clinical pre-eclampsia six to thirteen weeks later. The platelets of these women showed increased fibrinogen binding ex vivo (5.1% platelets positive, compared with 3.4% in those who completed a normal pregnancy, p <0.02), and increased CD63 antigen expression (0.73% positive compared to 0.45%, p = 0.01). In contrast, no differences between the women with different outcomes were detected at 28 weeks in platelet counts, or plasma ß-thromboglobulin levels. These findings confirm that whole blood flow cytometry is a sensitive technique for investigating platelet activation in a clinical setting and support the hypothesis that platelets have a critical role in the pathogenesis of pre-eclampsia
Hiding Sensitive Association Rules with Limited Side Effects

Data mining techniques have been widely used in various applications. However, the misuse of these techniques may lead to the disclosure of sensitive information. Researchers have recently made efforts at hiding sensitive association rules. Nevertheless, undesired side effects, e.g., nonsensitive rules falsely hidden and spurious rules falsely generated, may be produced in the rule hiding process. In this paper, we present a novel approach that strategically modifies a few transactions in the transaction database to decrease the supports or confidences of sensitive rules without producing the side effects. Since the correlation among rules can make it impossible to achieve this goal, in this paper, we propose heuristic methods for increasing the number of hidden sensitive rules and reducing the number of modified entries. The experimental results show the effectiveness of our approach, i.e., undesired side effects are avoided in the rule hiding process. The results also report that in most cases, all the sensitive rules are hidden without spurious rules falsely generated. Moreover, the good scalability of our approach in terms of database size and the influence of the correlation among rules on rule hiding are observed
A tale of two diseases: atherosclerosis and rheumatoid arthritis.

Acute coronary syndromes are responsible for most of the morbidity and mortality caused by coronary atherosclerosis. Both unstable angina and acute myocardial infarction are characterized by coronary thrombosis, usually caused by rupture or fissuring of a coronary plaque. Yet the occurrence of plaque rupture and coronary thrombosis is not related to severity of coronary plaques, and functional factors other than the mere presence of atherosclerotic lesions play an important role.1 2 Recent studies have focused on the inflammatory component of atherosclerosis, trying to highlight the differences between stable and unstable coronary plaques. An increasing body of evidence supports the hypothesis that atherosclerosis shares many similarities with other inflammatory/autoimmune diseases. Indeed, there are surprising similarities in the inflammatory/immunologic response observed in atherosclerosis, in unstable angina, and in rheumatoid arthritis, the prototype of autoimmune disease (Table⇓). However, although our understanding of the molecular and immunological mechanisms of rheumatoid arthritis has greatly progressed, due to the relatively easy access to the diseased tissue (synovium) and to the availability of animal models, the study of the inflammatory and immunological components of atherosclerosis is still in its initial stages. Unfortunately, it is more difficult for cardiologists to follow the evolution of inflammatory response in plaques or make correlations with the clinical course. Furthermore, although mice models of atherosclerosis have been developed in the last few years, there are still no animal models able to reproduce the events occurring in acute coronary syndromes. Thus, the study of the molecular mechanisms of rheumatoid arthritis may give valuable hints for research on the inflammatory/immunological mechanisms of atherosclerosis and acute coronary syndromes. Activation of inflammatory cells (in particular macrophages and mast cells), releasing many collagen-breaking enzymes within atherosclerotic plaques is likely to play an important role in destabilization of plaques.3 Collagen degradation is also an essential …
Periodic oscillations of dark solitons in parabolic potentials

We reformulate the Gross–Pitaevskii equation with an external parabolic potential as a discrete dynamical system, by using the basis of Hermite functions. We consider small amplitude stationary solutions with a single node, called dark solitons, and examine their existence and linear stability. Furthermore, we prove the persistence of a periodic motion in a neighborhood of such solutions. Our results are corroborated by numerical computations elucidating the existence, linear stability and dynamics of the relevant solutions.
Estimation of daily space-time precipitation series for macroscale hydrological modelling

An important problem in modelling macroscale basins, especially for sparsely observed regions, is the lack of precipitation information. Alternatives to using straightforward interpolated surface observations include the utilization of more advanced interpolation techniques and the use of additional precipitation information from atmospheric models. Conventional and geostatistical methods are applied for optimal interpolation and assimilation of observed and model precipitation. Various time-series of daily areal precipitation distributions are produced and compared using not only an internal precipitation validation, but also an objective verification based on stream flow simulations. The Mackenzie River Basin in north-western Canada is used as the study area and hydrological simulations are carried out with the model SLURP. It was found that better interpolation techniques and the use of combined precipitation data can improve the hydrological simulations and that the enhancements are related to the relative size of the simulation units used. © 1998 John Wiley & Sons, Ltd.
Enhancement of Gingival Wound Healing by Local Application of Silver Nanoparticles Periodontal Dressing Following Surgery: A Histological Assessment in Animal Model

Background: The value of periodontal dressing and its effects on periodontal wound healing have been questioned. Besides, the early healing of the gingival and periodontal wounds in oral cavity should be emphasized to promote the treatment outcome. Several studies pointed out a potential positive effect of silver nanoparticles (NPs) on the healing process of skin wounds. The present work aimed to design silver NPs periodontal dressing and then, evaluated its effects on gingival wound healing following operation. Methods: Thirty healthy adolescent female rabbits were used in this study. They had intact teeth and the clinical and radiographic examination revealed no periodontal disease. Silver NPs were added to carbonate methyl cellulose as base with two different concentrations of 25% v/v (Group A) and 50% v/v (Group B). On the basis of simple randomized allocation, gingivectomy was performed at the buccal gingiva of the left and right mandibular incisors and subsequently, untreated wounds in the control area were covered with periodontal pack and periodontal dressings A and B were applied in the test regions. Histological changes were monitored in day 4 and 7 post operation to evaluate the inflammatory and repair stage of healing process. Results: We observed significant difference in the inflammatory and repair parameters of the healing process between surgical sites treated with this periodontal dressing and control group. Besides, wounds treated with silver NPs dressing in general terms had all the hallmarks of relatively complete healing one week post operatively. Conclusion: The results indicated positive potential therapeutic effects for this new formulation of periodontal dressing on acceleration of surgical wound healing that led to improvement of periodontal treatment consequences following operation.